17 March – 19 March 2014 Four Seasons Hotel, Sydney, Australia

Congress organiser:

11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 3

Dr Babak Kateb

at the Baltimore Convention Center to treat cancers (brain, breast, last year with near 370 speakers over prostate, lung, liver, and head and 3 days. We have now successfully neck), invented new nano-drugs to accredited our programs across treat brain diseases and pioneered multiple disciplines thanks to American policies that could support such game- Association of Neurological Surgeons changing approach. (AANS), International Society for I congratulate the Honorable Prime Magnetic Resonance Imaging in Medicine (ISMRM) and American Minister Abbott and the Congressman College of Radiation Oncology (ACRO). Fattah for their Pioneer in Healthcare Policy Award. They have been the The Foundation and the Society force behind the sound policies that Let me congratulate Dr. Kuldip Sidhu published the first inaugural impacted the care and well-being of (the 11th President of SBMT) for his textbook of Nanoneuroscience and millions of Americans and Australians. visionary leadership and for organizing Nanoneurosurgery last year and now I also congratulate the pioneering a world class scientific meeting this working on two additional textbooks work done by Dr. Kuldip Sidhu in year. I also thank Glenn Cross and scheduled to be released in 2015. the field of stem cell research and Kirsty Grimwade from AusBiotech The Society has established a new applaud the humanitarian work of Dr. for coordinating such a magnificent publication in collaboration with Charlie Teo. I also congratulate Sharn convention. We could not have PloSOne (world’s largest open access McNeill for her Beacon and Courage done this without the support of Dr. publisher) called NeuroMapping and Dedication Award. We all learn Alfredo Martinez-Coll and without the & Therapeutics. The collection from Sharn’s unwavering, courageous generous contributions and support is now accepting papers online fight against ALS that gives hope and of Brain Mapping Foundation, UNSW, at PlosOne-NeuroMapping and strength to the leaders in scientific/ Government of New South Wells, Therapeutics. We also teamed up medical research and people in the the US State Department, the US with our publishing partners, Taylor ALS community. department of Commerce, the U.S. and Francis and PLosOne, at the Department of Defense, Medtronic, Society for Neuroscience (SFN) in Let’s celebrate our past achievements Stryker, GE Healthcare, NeuroNexus, order to introduce the SBMT to SFN’s but don’t lose the sight for the future. Rouge Research Inc., Neurologica, membership. However, we still have many works Integra, Synapse Biomedical Inc., to be done. Although we made Shining4Sharn Foundation and the Our record of accomplishment some progress, we are still lacking members of the Society. in the past 11 years has in effective treatments for majority It is amazing how far we have been stellar including 11 of common neurological diseases, such as ALS, autism, brain cancer, come in the last 11 years. I am successful world congresses, very proud to oversee the progress Alzheimer’s, Parkinson’s, and traumatic two satellite conferences, 1 brain injuries to name a few. We have of our organization in the last 11 textbook, 3 special issues years. It is amazing how SBMT and to work together and start defeating of Neuroimage, 1 brand these diseases that are killing and Brian Mapping Foundation (BMF) new journal publication with has impacted the way the clinical disabling millions of people and cost PlosOne, 1 congressional translational neuroscience is practiced world economy in trillions of dollars. through our conventions, policy report language and involvement in many initiatives I hope you will enjoy this remarkable advocacies such as our involvement scientific meeting and hope to see worldwide including President in the BRAIN initiative and the G20 you in 12th annual World Brain World Brain Mapping and Therapeutics Obama’s BRAIN initiative. Mapping Congress at the Los Angeles Initiative. Convention Center in California (March SBMT/IBMISPS started as a small We have successfully brought together 6-8th, 2015). diverse scientific, medical, and summit of near 20 scientists, Respectfully yours, physicians, and engineers 11 years engineering communities to tackle ago. We went from a small conference complex neurological disorders such Dr. Babak Kateb as brain cancer, brain and spinal cord room to a larger hotel space to Founding Chairman of the Board of trauma, ALS, Alzheimer’s disease, and a conference center in France, SBMT, President of Brain Mapping Parkinson’s disease. UCLA, Harvard, and UCSF. Our first Foundation, Director of National Center international convention was held in SBMT members have pioneered in for NanoBioElectronics (NASA/JPL), the Metro Toronto Convention Centre the field by introducing a new retinal Research Scientist, Department of in 2012, followed by a successful 2013 imaging to diagnose 1`Alzheimer’s Neurosurgery, Cedars-Sinai Medical w]World b]Brain Mapping Congress disease, introduce microwave device Center. 4 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

A/Prof Kuldip Sidhu

It has been a great journey over the neurosciences and prioritise resource last two years as a team to accept allocation for research towards this responsibility and to host the neurodegenerative diseases and SBMT World Congress in Sydney. other neuropsychiatric ailments. This has been made possible only We presented this proposal to because of tremendous support first the honorable PM Abbott and the from SBMT HQ particularly through honorable President Obama as well as Dr Babak Kateb, Founding Chairman the US Congressional Neuroscience of the board and CEO of SBMT caucus. and president of Brain mapping Foundation based in California, AusEvents a division of AusBiotech, The hosting of the meeting the most professional agency of SBMT here in Sydney, On behalf of the Society for Brain managing this meeting, the high the first one in Australasia Mapping and Therapeutics (SBMT) profile program committee for bringing signifies its vision and policy and its executive board including this excellent state-of-the-art program to open out to the world the local chapter, it is my great to you. Our great sponsors, NSW pleasure as a president to extend and engage top brains Health, Medtronic, GE Healthcare, to find solution to ever our warm welcome to you all to Brain Sciences, UNSW and others Sydney, Australia for the 11th Annual supporting various sessions. My heart increasing burden of the World Congress of the SBMT 2014 goes out to all those colleagues and neurodegenerative disease – Bringing Together Engineering, Art, friends and associations particularly and other related ailments of Science and Medicine. Australia as a multicultural society is also the home the Australasian society of stem cell the brain and promote new for multidisciplinary neuroscience research, NSW stem cell network, frontiers of science in this research and has a worldwide UNSW, NSW Health Department area. Therefore, neurological and many others who promoted this recognition. research should not be views congress through their networks. Brain Sciences UNSW Sydney only as scientific discovery provides a strong platform for such The SBMT under the leadership of but rather as an economical meetings to facilitate collaborative Dr Kateb is playing a very significant necessity. research and access to relevant role worldwide to promote the technologies and expertise. It cause of clinical translational encompasses an inter-disciplinary neurosciences, strategically liaising I sincerely hope that you enjoy the approach drawing together with both the government agencies ambience of this world class scientific researchers with diverse backgrounds and philanthropic institutions which event and our hospitality in Sydney, like engineering, science and can make a difference in this field. the most beautiful, model harbour city, medicine from the various schools, Last year we made presentations the state capital of New South Wales. hospitals and Institutes nationally and to the White House in Washington It offers spectacular beauty, landscape internationally with a collective interest DC under the auspices of Brain and variety of tourist attractions. The in various aspects of the function and Mapping Foundation and The US Four Seasons Hotel, the venue is structure of the brain in both a normal Congressional neurosciences caucus superb for this meeting ensuring your and dysfunction state. Similarly the that lead to the release of 100 million comforts. I look forward to future Melbourne Brain Centre, Queensland collaboration through SBMT with all Brain Institute at Brisbane, Brain dollars ‘BRAIN Initiative’ from the of you and hope together we can and Mind Institute in Sydney, The president Obama. We prepared and Australian Neuro-muscular Research submitted a white paper on this rapidly find solutions for devastating Institute in Perth, Australian Brain initiative and currently we are working neurological disorders. together with various agencies like Bank Network, the Australian Society A/Prof Kuldip Sidhu for Medical Research, the corporate NIH, DOD, NSF, NASA developing and disease related foundation strategies how to make the best of President & co-convener memberships, are other icons in this initiative. This year I proposed to 11th Annual World Congress of SBMT Australia creating specific niche in Dr. Kateb that we submit a proposal Centre for Healthy Brain Ageing neurosciences. to the G20 Summit for the cause of UNSW Medicine Sydney 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 5

A/Prof Kuldip Sidhu (Co-convener) Stem Cells Specialist, UNSW Medicine, Sydney NSW Dr Alfredo Martinez-Coll Senior Business A/Prof Charlie Teo Development Manager (Co-convener) NewSouth Innovations Director, Centre for UNSW Sydney NSW Minimally Invasive Neurosurgery Prince of Wales Private Hospital, Sydney NSW

Dr Babak Kateb SBMT Chairman & CEO (Ex-officio) Maxine Dunitz Neurosurgical Institute CA USA Glenn Cross COO AusBiotech, Melbourne VIC Kirsty Grimwade Events Manager, AusBiotech, Melbourne VIC 6 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Professor George Paxinos Professor Gary F Egan NHMRC Australia Fellow Professor & Foundation Neuroscience Research Professor John Justin Director, Monash Australia, Sydney NSW Gooding Biomedical Imaging, Monash University Director of the Australian Centre for NanoMedicine Deputy Director, National Head, Biosensors and Imaging Facility, Australia Biointerfaces Research Program, School of Chemistry, University of New South Wales, Sydney NSW Professor Perry Bartlett Director, Queensland Brain Institute University of Queensland, Brisbane

A/Prof Caroline Gargett Deputy Director, The Ritchie Centre Monash Institute of Medical Research Mr Glenn Cross Clayton, Victoria Chief Operating Officer AusBiotech, Melbourne VIC Professor Perminder Sachdev Director, Neuropsychiatry Institute UNSW Medicine, Sydney A/Prof Megan Munsie Stem Cell Australia, Melbourne VIC 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 7

Major Partner: Health and medical research play OHMR is responsible for the delivery a vital role in the continued growth of a range of programs and policies NSW Ministry of Health: and better health of our community including: Office for Health and and economy. From increased life • Medical Research Support Program expectancy and new treatments • Medical Devices Fund Medical Research for disease, and technologies that (OHMR) change the way we live and work, to • Biobanking addressing environmental challenges - • Bioinformatics scientific research and the knowledge • Research Hubs it generates affects us all. • Clinical trials As a part of the NSW Ministry of • Clinical research networks Health, the Office for Health and • Research ethics and governance Medical Research (OHMR) plays a crucial role in supporting the State’s For more information please email leading health and medical research [email protected] efforts. OHMR works with the health and medical research communities, Web: www.health.nsw.gov.au\ohmr the higher education sector and business to promote growth and innovation in research to achieve better health and environmental and economic outcomes for the people of NSW.

Gold Partner: At Medtronic, we’re committed to symptoms throughout the patient’s Innovating for life by pushing the life. Today, we’re improving the lives Medtronic boundaries of medical technology and of millions of people worldwide each changing the way the world treats year across numerous conditions - chronic disease. Driven by our deep including heart disease, diabetes, understanding of the human body neurological disorders, spinal and our collaboration with physicians, conditions, and vascular diseases. we’re transforming technology to But it isn’t enough. So we’re treat patients across the entire care innovating beyond products. We’re continuum. Our innovations help breaking down barriers, challenging physicians diagnose diseases earlier, assumptions, and looking beyond the treat patients with the least amount of status quo - to continually find more disruption possible, and help alleviate ways to help people live better, longer. 8 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Session Partner: GE Healthcare provides Healthymagination is GE’s $6 billion transformational medical technologies commitment to bring high-quality GE Healthcare and services that are shaping health care at lower cost to more a new age of patient care. Our people around the world through our broad expertise in medical imaging advanced technologies and research and information technologies, and development capabilities. medical diagnostics, patient Just as ecomagination applies monitoring systems, drug discovery, our scale and innovation toward biopharmaceutical manufacturing tackling environmental challenges, technologies and performance healthymagination offers dramatic solutions services deliver better care new investments toward achieving to more people around the world at a sustainable health lower cost.

Session Partner: Session Partner: Neurologica Brain Sciences UNSW 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 9

Exhibitors: Stryker is a leading medical satisfying lives. We are committed to technology company and together enhancing quality of care, operational Stryker with our customers, we are driven to effectiveness and patient satisfaction. make healthcare better. Stryker offers innovative reconstructive, medical, surgical, neurotechnology, spine and robotic arm assisted technologies to help people lead more active,

Medtronic At Medtronic, we’re committed to symptoms throughout the patient’s Innovating for life by pushing the life. Today, we’re improving the lives boundaries of medical technology and of millions of people worldwide each changing the way the world treats year across numerous conditions - chronic disease. Driven by our deep including heart disease, diabetes, understanding of the human body neurological disorders, spinal and our collaboration with physicians, conditions, and vascular diseases. we’re transforming technology to But it isn’t enough. So we’re treat patients across the entire care innovating beyond products. We’re continuum. Our innovations help breaking down barriers, challenging physicians diagnose diseases earlier, assumptions, and looking beyond the treat patients with the least amount of status quo - to continually find more disruption possible, and help alleviate ways to help people live better, longer.

Rogue Research Rogue Research has brought the advantages of modern frameless neuronavigation to the neuroscience research world. Our product, Brainsight, allows you to use the principles of frameless stereotaxy to perform a variety of neurosurgical procedures with accuracy, simplicity and improved subject comfort when compared to stereotactic frames.

Integra Integra is a world leader in medical peripheral nerve protection and technology, is dedicated to limiting repair, and wound repair. Integra is uncertainty for surgeons, so they a leader in neurosurgery, offering a can concentrate on providing the broad portfolio of implants, devices, best patient care. Integra offers instruments and systems used in innovative solutions in orthopaedic neurosurgery, neuromonitoring, extremity surgery, neurosurgery, and neurotrauma, and related critical care. reconstructive and general surgery. Founded in 1989 Integra is Integra’s orthopaedic products headquartered in Plainsboro, include devices and implants for New Jersey and has over 3,500 foot and ankle, hand and wrist, employees worldwide. shoulder and elbow, tendon and 10 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

The IVY Ballroom 1/330 George Street Sydney

Pre Dinner drinks from 7.00pm Dress: Black Tie Dr. Lucien Maurice Levy (Age 67) Award Winners: Award 1: Dr Lucien Levy passed away December 19, 2013, peacefully at his home in Columbia, Maryland. Pioneer in Healthcare Policy Award Lucien was a great supporter of SBMT and was PM Tony Abbott and US Congressman an important member of its board. Chaka Fattah He played a significant role in SBMT brain initiative proposal that was submitted to the White House, the Award 2: US congress and NIH. The whole Humanitarian Award Winner scientific community is sending Charlie Teo condolence messages.

‘He was our beloved colleague and member of this Award 3: distinguished board’ said Dr Babak Kateb, CEO, SBMT. Pioneer in Medicine Award Winner Lucien’s Doctor of Medicine degree was from Kuldip Sidhu the Johns Hopkins University in 1981 and after fellowship in neuroimaging he attained a full position of Professor of Radiology at The George Washington University since 1999. He served as a Senior Editor Award 3: of AJNR since 2007 and was an Associate Editor of Beacon of Courage and dedication Radiology since 2009 and he was passionate about it. His breadth of knowledge was spectacular, and Award as Editor Emeritus of AJNR, Dr Robert Quencer Sharn McNeill once said, “One could learn more from reading Lucien’s evaluations than from the actual articles he was reviewing.” Lucien was a great teacher and researcher and attracted fellows for mentorship from throughout the world. He was a decorated person with many accolades. Lucien will be remembered for his wit and humor. He brought smiles from all of those, whom he mentored, even on the most mundane of subjects. He was very unassuming, quiet, and private man. He will be missed immensely by his colleagues, his family, his trainees, and all those who encountered him. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 11

MONDAY 17 MARCH 2014

7.00am – 5.00pm Delegate Registration

Grand ballroom 1

8.35 – 8.40am Conference Welcome Kuldip Sidhu, President of SBMT

8.40 – 8.55am Conference Welcome PM Envoy, Australian Government

8.55 – 9.10am Babak Kateb Founder, Chairman, CEO of SBMT & President of Brain Mapping Foundation

9.10 – 9.25am Keynote Address Consul General Hugo Llorens, Embassy of the United States of America

9.25 – 9.40am Keynote Address Kirsty Duncan, Member of Canadian Parliament Video Address

9.40 – 9.50am Keynote address Congressman Chaka Fattah, Senior Member of the House Appropriations Committee Video Address

9.50 – 9.55am Program Overview Charlie Teo, Director, Centre for Minimally Invasive Neurosurgery

9.55 – 10.00am Announcement of 2015 World Brain Mapping in LA, Shouleh Nikzad, SBMT President Elect

10.00 – 10.15am Conference Opening Address The Hon. Jillian Skinner MP

10.15 – 10.30am Morning Tea Networking Break with exhibitors – Grand Foyer

10.30 – 11.00am Plenary session 1 Neurology and neurophysiology Chair: Peter Schofield Prof Trevor Kilpatrick, Director, Melbourne Neuroscience Institute, University of Melbourne 11.00 -11.30am Plenary session 2 The central role of RNA in cognitive function Chair: Peter Schofield Prof John Mattick AO, Executive Director, Garvan Institute of Medical Research Sydney 11.30 – 12.00pm Plenary session 2A Chair: Peter Schofield Prof Peter Burger, Professor of Pathology, Oncology, and Neurosurgery, The Johns Hopkins Hospital

12.00 – 1.30pm Lunch Break with exhibitors – Grand Foyer

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1.30 – 2.45pm Grand ballroom 1

Breakout Session 1 Pluripotent Stem Cells & Neural Lineages Chair: Martin Pera, Kuldip Sidhu 1. Martin Pera (Keynote) 2. Alice Pebay Role of Lysophosphatidic acid in neural stem cells and in traumatic brain injury 3. Henry Chung Whole transciptome analysis of Alzheimer’s disease specific human induced pluripotent stem cells 4. Lezanne Ooi Altered Neuronal Function In Networks Derived From Induced Pluripotent Stem Cells From Alzheimer’s Disease Patients

Gallery

Supported by: Breakout Session 2a CME Symposium Neuro-oncology Chair: Michael Back Kerrie McDonald 1. Charlie Teo (Keynote) Maximising technology in the Surgical Treatment of Gliomas 2. Michael Back Radiation Therapy Dose Painting utilizing FET and FDG PET in the management of high grade glioma 3. Jeff Rosenfeld Targeting calcitonin receptor expressed by brain tumour initiating cells of gliobastoma multiforme 4. Kerrie McDonald 5. Surasak Phuphanich Immunotherapy for Brain Cancer: Vaccine, PD1/PDL1 Antibody

Residential Suite

Supported By: Breakout Session 2b Functional Neurosurgery Chair: Ray Cook, 1. Ray Cook (Keynote) 2. Colleen Loo Non Invasive Therapeutic Brain Stimulation :ECT, TMS, tDCS 3. Raymond Schwartz The relationship between vascular risk factors, small-vessel disease and Parkinson disease: a clinico- pathological study 4. Socrates Dokos Modelling Direct Brain Activation in Electroconvulsive Therapy 5. Takeshi Shimizu Functional connectivity specific to central post stroke pain and alterations after repetitive transcranial magnetic stimulation

2.45 – 4.00pm Breakout Session 3 ACRO CME Symposium Supported by: Neuro-radiation oncology and stereotactic radio-surgery Chair: Anatoly Rosenfeld and Jim Welsh 1. Jim Welsh (Keynote) Proposed New Boron Neutron Capture Therapy Program at Fermilab 2. Anatoly Rosenfeld Advanced quality assurance in Stereotactic Radiosurgery for error free treatment 3. Stephanie Weiss

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2.45 – 4.00pm Breakout Session 4 (Cont.) Neuro-trauma and Neuropsychiatry Chair: Michael Roy, Skye McDonald Supported by: 1. Jeffrey Chung (Keynote) Post Traumatic Epilepsy: Present and Future 2. Skye McDonald 3. Michael Roy Identification of Predictors of Post-Deployment PTSD and postconcussive syndrome in Combat Veterans 4. Stuart Grieve Structural MRI and Diffusion Tensor Imaging evidence of network abnormalities in Major Depressive Disorder - data from the iSPOT-D trial 5. Michele R. Aizenberg 6. Mayuresh Korgaonkar Functional Imaging markers of treatment prediction in depression: data from the International Study to Predict Optimized Treatment in Depression (iSPOT-D).

Supported by: Breakout Session 5 Translational Neuroscience Chair: Gary Housley 1. Gary Housley (Keynote) Neurotrophin-based neural repair and protection 2. Renee Morris Gene therapy for spinal repair 3. Matthias Klugmann Gene therapy for leukodystrophies 4. Andrew Moorhouse The KCC2 chloride transporter as a target for epilepsy 5. John Power Molecular targets for addiction and memory disorders

4.00 – 4.30pm Afternoon Tea Networking Break with exhibitors – Grand Foyer

4.30 – 5.45pm Breakout Session 6 Adult Stem Cells & Personalised medicine Chair: Bob Williamson, Mirella Dottori 1. Bob Williamson (Keynote) Stem Cells and Personalised Medicine 2. Vicky Yamamoto Small molecule based approaches for personalized medicine and adult stem cell therapy 3. James Bourne Does Functional Neurogenesis Occur in the Injured Neocortex of the Nonhuman Primate? 4. Mirella Dottori Functional characterization of Friedreich Ataxia iPS-derived neuronal progenitors and their integration in the adult brain 5. Yashar Kalani exRNAs as biomarkers of neurological disease

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Keith Black Breakout Session 7 Supported by: Neurology and Neurophysiology Chair: Matthew Kiernan S 1. Keith Black (Keynote) 2. Mourad Tayebi 3. Ian Hickie Delayed sleep offset and other markers of circadian rhythm disruption are common in young people with emerging mood disorders 4. Steve Vucic Cortical dysfunction in Motor Neurone Disease 5. Trevor Kilpatrick Genomics of multiple sclerosis

Breakout Session 8 Molecular Imaging Chair: Roger Ordidge and Gary Egan 1. Kishore Bhakoo (Keynote) 2. David Reutens 3. Roger Ordidge Sodium selenate as a therapy for traumatic brain injury: a pre-clinical MRI study

5.35 – 6.00pm Plenary Session 3 Regenerative medicine and stem cells Martin Pera, Stem Cell Science, University of Melbourne

7.00 – 7.30pm Pre-Dinner Drinks at the IVY, 1/330 George St, Sydney

7.30 – 10.00pm Gala Dinner

TUESDAY 18 MARCH 2014

9.00am – 5.00pm Delegate Registration

Grand ballroom 1

10.00 – 10.30am Plenary Session 4 Neurosurgery Prof Jeffrey Rosenfeld AM, OBE, Monash University Improving the outcome from severe traumatic brain injury: how much further can we go?

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10.30 – 11.00am Morning Tea and Networking with Exhibitors

11.00am – Grand ballroom 1 12.15pm

Oral Poster Presentations Chair: Kuldip Sidhu 1. Cecelia Gzell Small increases in enhancement on MRI may predict survival post radiotherapy in patients with glioblastoma 2. Timur Gureyev Quantitative analysis of the EEG source localization problem 3. Andrew Tosolini The Motor End Plates (MEPs) Are A Conduit To Increase Adenoviral Transduction Of Motor Neurons, Dorsal Root Ganglia (DRG) And Myofibres 4. Terry Peters Correlation of quantitative MRI and histology of surgical specimens in drug-resistant focal epilepsy 5. Michael Lerch X-Tream: A Unique Realtime QA System for Submillimeter X-Ray Radiosurgery 6. Terry Peters A pipeline for histology to in-vivo registration of surgically resected specimens in focal epilepsy

Gallery

Breakout Session 9a NanoBioElectronics Chair: Babak Kateb 1. Jeff Rosenfeld (Keynote) The development of bionic vision at Monash University 2. Shouleh Nikzad Advanced Technology for Planetary, Astrophysics, and Medical Applications 3. Justin Gooding Nanobioelectronic Interfaces that Facilitate Efficient Electron Transfer to Biomolecules 4. Uttam Sinha

Studio

Breakout session 9c Emerging application of synchroton radiation in Neuroscience Chair: Pantaleo Romanelli 1. Alberto Bravin Synchrotron-generated microbeams: overview and state of the art 2. Jeffrey Crosbie Microbeam radiation therapy: the state of the art in cancer treatment 3. Pantaleo Romanelli Brain modulation using synchrotron-generated microbeams 4. Paola Coan Brain microimaging using synchrotron radiation

12.15 – 1.30pm Lunch and Networking with Exhibitors

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1.30 – 2.45pm Grand ballroom 1

Breakout Session 10 Sport and Concussion Chair: Geoffrey Ling & Babak Kateb 1. Michael Roy (Keynote) Linking TBI with PTSD in Combat Veterans: Lessons Learned from the Predictors Study 2. Dan Perl 3. Pantaleo Romanelli A Fully-Integrated Externally Rechargeable Wireless System for Long-Term Electrocorticography and Cortical Stimulation 4. Daryl Kipke 5. Geoffrey Ling 6. James Ecklund Building a Community Concussion Program

Gallery

Breakout Session 11 Stem cell technology and tissue engineering Chair: John Whitelock & Jean Paul Allain 1. Ernst Wolvetang (Keynote) Human induced pluripotent cells is tools to study neurological diseases 2. RA Green Conductive hydrogel electrode coatings for optimal neural interfacing 3. John Whitelock

Studio

Breakout Session 12 Brain Networks Chair: Perminder Sachdev 1. Michael Breakspear (Keynote) Brain Connectomics 2. Alex Fornito Mapping context-dependent changes in brain functional networks using event-related graph analysis 3. Michael Valenzuela Plastic Network Responses in Aged Brains to Lifestyle-based Intervention 4. Wei Wen Structural topological organisation of the elderly brain 5. Gilles Guillemin Mapping of the tryptophan metabolism in physiological and pathological conditions

2.45 – 3.30pm Afternoon Tea and Networking with Exhibitors

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3.30 - 4.45pm Breakout Session 13 Neuroimaging genetics Chair: Perminder Sachdev & Peter Schofield 1. Margaret Wright The ENIGMA Projects: identifying genetic loci for brain structure and function 2. Karen Mather Heritability and genetic correlations of cortical and subcortical structures in a cohort of community-dwelling older adults 3. Peter Schofield Neuroimaging and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease 4. Mayuresh Korgaonkar Heritability of neural structure and connectivity changes across the adult lifespan – results from the TWIN-E study. 5. Philip Liu Brain Mapping and Therapy Monitored by Genetic Imaging; A Preclinical Platform

Breakout Session 14 Commercial and Community Considerations in Personalised Medicines Chair: Megan Munsie & Caroline Gargett 1. Ben Borson (Keynote) Commercialization and Protection of Intellectual Assets in Brain Disorders 2. Alfredo Martinez-Coll 3. Megan Munsie 4. Glenn Cross 5. Bob Williamson

Breakout Session 15 Stem Cells & Clinical Translation Chair: Uli Schmidt & Michael Morris 1. Uli Schmidt (Keynote) Huntington’s disease-affected human embryonic stem cells as a model of mitochondrial dysfunction and metabolic disturbances 2. Michael Morris Amino acids act as growth factors to stimulate embryo development up to and including early neurogenesis 3. Mirella Dottori Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system 4. Amanda Capes-Davis Spontaneous transformation of stem cells in vitro: Believe it or not

4.45 – 5.45pm SBMT Board meeting 2014 By invite only

4.45 - 5.45pm Networking Drinks with Exhibitors

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WEDNESDAY 19 MARCH 2014

8.00am – 5.00pm Delegate Registration

Grand ballroom 1

9.00 – 9.30am Plenary Session 5 New frontiers in brain science Geoffrey Ling, Neurologist, Defence Advanced Research Projects Agency (DARPA) USA

9.30 – 10.00am Plenary Session 6 New structural maps of the Brain Jacopo Annese, Director, The Brain Observatory, USA

10.00 – 10.30am Morning Tea and Networking with Exhibitors

10.30 – 11.45am Grand ballroom 1

Breakout Session 18

Gallery

Supported by: Breakout Session 17 Brain Neuromodulation in the Treatment of Epilepsy, Parkinson’s and ALS Chair: Evgeny Tsimerinov 1. Evgeny Tsimerinov (Keynote) Brain Neuro Modulation in Treatment of Parkinson’s, Tremor and Dystonia 2. Tony DeSalles Future Applications of Brain Neuro Modulation in Treatment of Parkinson’s and Neurodegenerative Disorders 3. Lilit Mnatsakanian Advances in Technology in the Treatment of Epilepsy 4. Reese Terry The Brain-Vagus-Heart Connections: Therapeutic Investigations 5. Ashraf Elsayegh Use of Diaphragmatic Pacing System in ALS and Spinal Cord Injury 6. Evgeny Tsimerinov Modern Technologies of Neuro and Brain Modulations in Treatment of ALS

Studio

Breakout Session 16 Neural Stem Cells and Regeneration Chair: Rasul Chudary & Ann Turnley 1. Brent A Reynolds (Keynote) Building Better Brains: From Theory to Reality 2. Rasul Chaudary Promise of Embryonic and Adults Stem Cells for Neural Regeneration

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10.30 – 11.45am 3. Quenten Schwarz (Cont.) Understanding the origin of neurodevelopmental disorders 4. Ann Turnley What will it take to make endogenous adult neural stem cells repair the adult nervous system?

11.45 – 1.00pm Breakout Session 19 Electrodes and Electrochemistry in Brain Mapping Chair: Justin Gooding 1. Evgeny Tsemerinov (Keynote) Modern Brain NeuroModulation in Neurologic Disorders 2. Greg Suaning Electrodes in the supra-choroidal space for visual prosthesis – effecting focused cortical activation 4. Alex Harris A Method for the Systematic in vitro and in vivo Evaluation of Neural Recording Electrodes 5. Justin Gooding Electrodes that resist protein fouling when used in biological fluids: Applications for biosensing, cell biology and implantable electrodes

Breakout Session 20 Brain ‘All Omics’ Chair: Howard Federoff 1. Howard Federoff (Keynote) 2. Brett Stringer The Establishment and Characterisation of Patient-Derived Cell line and Mouse Models for Studying Glioblastoma 3. Brandon Wainwright An integrative functional genomics approach to defining key gene networks in medulloblastoma 4. Bryan Day EphA3 Maintain Tumour-Initiating Cells and is a Therapeutic Target in Brain Cancer 5. Jan Fullerton Enrichment of polygenic risk alleles in a longitudinal cohort at high-risk of bipolar disorder

Supported by: Breakout Session 20a Clinical Neurology and Neurointerventions Chair: George Paxinos & Perminder Sachdev 1.i Bryce V ssel (Keynote) 2. Wieslaw Nowinski CAD systems for ischemic and hemorrhagic strokes 3. Eric Bailey Ambulance based CT and its Impact on Thrombolytic Therapy for Acute Ischemic Stroke 4. Penelope McNulty/ Christine Shiner Investigating neuroplasticity post-stroke: contrasting bilateral differences in magnetoencephalography, transcranial magnetic stimulation and functional motor assessments 5. Yih Yian Sitoh Neuroimaging in Psychiatry 6. Paul Fitzgerald Enhanced neuroimaging based targeting to improve response to rTMS treatment in depression

1.00 – 2.00pm Lunch and Networking with Exhibitors

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2.00 – 3.15pm Grand ballroom 1

Oral Poster Presentations Chair: Glenn Cross 7. Solventa Krackauskaite Accuracy, precision, sensitivity and specificity of non-invasive ICP absolute value measurements 8. Jun-Young Lee Alzheimer disease progress and cognitive reserve 9. Abigale Besemer Impact of PET and MRI Threshold-Based Tumor Volume Segmentation on Targeted Radionuclide Therapy Dosimetry using CLR1404 10. Li Li & Yifan Zhang Metabolic alterations in the frontal white matter of patients with Major Depressive Disorder with treatment of SSRIs :A proton magnetic resonance spectroscopy study 11. Avinash Waghmare A Novel Application of High Frequency Magnetic Stimulation: Enhancing Putative Mirror Neuron Activity 12. NA 13. NA 14. Taskin Duman Internal Carotis Artery Thrombosis in Acute Ischemic Stroke 15. PhuaHwee Tang Arterial Spin Labelling Method of assessing cerebral perfusion compared against PET imaging in children with focal epilepsy

Gallery

Breakout Session 21a Intra-operative Brain Mapping TBC

Studio

Breakout Session 22 New Frontiers in Brain Sciences (Nanobiotechnology, bioengineering and biomaterials) Chair: Babak Kateb & Jean Paul Allain 1. Jeff Sutton (Keynote) Brain Alterations in Spaceflight 2. Kuldip Sidhu Brain in the Petri dish – disease modelling 3. Jean Paul Allain Development of magnetic bacterial nano-cellulose (MBNC) for regenerative neuroendovascular therapeutics 4. Vicky Yamamoto TBC

3.15 – 4.00pm Afternoon Tea and Networking with Exhibitors

Grand ballroom 1

4.00 - 4.30pm Plenary lecture 7 Prof Warwick Anderson, Chief Executive Officer, National Health & Medical Research Council NHMRC Funding and International Collaborations

4.30 – 5.00pm Conference closing remarks by organising chairman and President, Kuldip Sidhu

Information correct as of 7/3/2014 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 21

Seeing the results of research translate into better patient care makes every dollar and every effort invested worthwhile”

Hon Jillian Skinner MP

www.health.nsw.gov.au\ohmr

2014 © NSW Ministry of Health 22 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

March 17-19, 2014 Four Seasons Hotel Sydney, 199 George St, Sydney NSW 2000, Australia

Planning Committee Commercial Interest What I My Role Conflict/ and Speakers received Resolution A/Prof Michael Back, I do not have any relevant None required MBBS, Franzcr, financial relationships with GradDipPsyOnc, MBA any commercial interests.

Valerie Brown, I do not have any relevant None required CPS – planning financial relationships with any commercial interests.

Babak Kateb, MD I do not have any relevant None required financial relationships with any commercial interests.

Dr Kerrie McDonald I do not have any relevant None required financial relationships with any commercial interests.

Surasak Phuphanich MD I do not have any relevant None required FAAN financial relationships with any commercial interests.

Major General, Professor I do not have any relevant None required Jeffrey V. Rosenfeld AM, financial relationships with OBE any commercial interests.

Professor Anatoly B. I do not have any relevant None required Rozenfeld (Rosenfeld) financial relationships with M.Sc., Ph.D. any commercial interests.

Kuldip S. Sidhu PhD I do not have any relevant None required financial relationships with any commercial interests.

A/Pro Charles Teo, AM, Aesculap Honorarium Consultant Reviewed and MBBS, FRACS discussed. No conflict found to exist.

Stephanie E. Weiss, MD I do not have any relevant None required financial relationships with any commercial interests.

James Welsh, MD Bayer/Algeta Honorarium Speaker Reviewed and Colossal Fossils Nothing yet Board member discussed. Determined no Coqui Nothing Board member conflict exists. radiopharmaceuticals Radion Global Nothing (Former) co-founder and chief science officer 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 23

A/Prof Kuldip Sidhu A/Professor Kuldip Sidhu, PhD, BSC developmental biology including stem (Medical) is a stem cell expert at the cells. He shared this paper in Nature UNSW Medicine Faculty of Medicine, University of New Biotechnology with Noble Laureate South Wales, Australia. His post doc (2012), Prof Yamanaka. He has served training is from St Louis MO USA on the International Society of Stem (1979-80) in assisted reproductive Cell Research Sub Committee and technology and he also worked with the NHMRC Cell Therapy Advisory Prof James Thompson, Wisconsin Committee; he is a member of USA (2000) who produced the first the editorial board of International human embryonic stem cells in 1998. Stem Cell Journals, the open stem cell journal and recent patent on His research focus is on neural stem regenerative medicine, International cells derived from both the embryonic journal of neuropsychiatric diseases. and non-embryonic sources for He is on the expert panel on iPSC developing future cell therapies for research for the European Union. He various neurodegenerative diseases, is president of the local chapter and like Alzheimer’s, Parkinson’s and other vice president of the board of Society neuronal diseases. for Brain Mapping and Therapeutics, He has established a state-of-the- USA. He was the chair of the program art facility to study the cell and committee of the 4th annual meeting developmental biology of stem of the Australasian society of stem cell cells. SCL has expertise to culture, research held in Sydney 2011. He has propagate, differentiate, engineer and eight national and five international transplant in animal models the neural active research collaborations and stem cells from various sources like including three with industry. He has human embryonic stem cells, skin- widely travelled around the world and derived neuroprogenitors and human presented invited lectures, chaired mesenchymal stem cells from bone sessions in scientific meetings, marrow. In addition, he has expertise conferences. in the derivation of new human He is recognised by many awards embryonic stem cell lines including e.g. Medallist for outstanding their clonal propagation. His lab was research from Indian National Science first to produce two hESC lines, Academy 1981, Best book prize, Endeavour (E) 1&2 from Australia 1996, Medal for best presentation and E2 is listed on NIH registry USA in an international conference on for distribution. SCL has seriously frontiers of reproductive biology, embarked on iPS Technology and 1989, Best invention prize, Australia, produced over 100 iPSC clones from 2007, Finalist of Eureka prize Alzheimer’s patients for studying 2009, Advanced Innovation Award the disease processes and drug (Finalist), UNSW 2012. He has discovery. produced 9 PhD, 2 MSC, 4 HONS A/Prof Sidhu has produced two students and some of them are books – the latest one (2012) on stem also recognised with Dean’s list and cells, thirteen book chapters, nine McConaghy Prize. review chapters, two international His passion in science is as good as patents, four proprietary items and in Tennis. one hundred and seventy original research papers including abstracts in journal of repute including one in Nature Biotechnology (2011) and all dealing with mammalian cell and 24 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Dr Babak Kateb Babak Kateb, Neuroscientist, electronic nose. He also pioneered Chairman of the Board of SBMT the technique, which allowed NASA SBMT/Cedars Sinai and President of Brain Mapping Multiwall Carbon nanotubes to be Foundation and one of the main used as a nano-drug/siRNA delivery architects of President Obama’s system for brain cancer therapy. He BRAIN initiative at the East room also has significant collaboration with of the White House prior to the Los Alamos National Lab on ultra- announcement of BRAIN initiative low field MRI technology and new by President Obama (April 2ed, generation of smart microscopes. 2013; courtesy of BRAIN MAPPING FOUNDATION) He chairs the publication committee of SBMT, as editor in chief. He Dr Babak Kateb is a neuroscientist has established a new publication with more than 15 years of research with world’s largest open access experience. His research has been publisher: PLoSOne, which is focused on peripheral neuropathy, called PLoSOne_ NeuroMapping stroke, epilepsy, fetal cell transplant & Therapeutics and was the force into the brain, pancreatic islet behind 3 successful IBMISPS- xenotrasplantation, human brain NeuroImage special issues with computer interface and brain high impact factors. He is editor of implants, effect of hypothermia in “The Textbook of Nanoneuroscience traumatic brain injury patients with low and Nanoneurosurgery”, which is Glasgow Coma Score, image guided published by one of the world’s surgery using NASA’s thermal and UV leading medical publishers, Taylor imaging technology, optical imaging & Francis Publisher by 2012. and laser spectroscopy, microwave ablation, stem cell research, This textbook is the first book nanoneurosurgery and virtual reality ever published on the subject of neurosurgical simulation. Nanoneurosurgery. Babak has been serving as the Babak has been one of the key founding chairman of the board of players in President Obama’s BRAIN directors, CEO and Scientific director initiative. He has been deeply involved of Society for Brain Mapping and in global neuroscience legislation Therapeutics (SBMT) as well as and closely collaborating with the US President and Scientific Director Congressional Neuroscience Caucus of the Brain Mapping Foundation as well as members of Canadian and and Director of National Center Australian Parliaments in order to for Nano-Bio-Electronics. He is a advance neuroscience. His initiatives visiting scientist at NASA/JPL and have impacted the way we care about Research Scientist at Department of the wounded warriors and created a Neurosurgery at Cedars Sinai Medical global alliance for nanobioelectronic, center. He is recipient of NASA Tech a consortium that could revolutionize Brief Award for his pioneering work the way neurological disorders are on sniffing cancer cells using NASA’s diagnosed and treated. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 25

Consul General Hugo Llorens arrived in Sydney Officer at the Consulate General in Hugo Llorens October 3, 2013 to become Principal Vancouver, Canada. In Vancouver, Officer at the U.S. Consulate General he created a novel multi-agency “Law Embassy of United States with responsibility for the region Enforcement Hub” that included the of America encompassing New South Wales, opening of FBI, ATF, U.S. Customs, Queensland and Norfolk Island. Secret Service, and Regional Security offices to work with Canadian Previously, he served as the Assistant counterparts on counterterrorism and Chief of Mission at the U.S. Embassy international crime investigations. in Kabul, Afghanistan from May 2012 to June 2013. In that position, From 1997-1999, Mr. Llorens was he served as the Chief Operating Deputy Director of the Office of Officer of the largest Embassy in Economic Policy in the Bureau of the world with a combined staff of Inter-American Affairs where he 3,000 U.S. local and Third Country helped launch Free Trade Area of the employees representing 19 U.S. Americas negotiations in 1998. As a government agencies. Prior to his 32-year veteran of the U.S. Foreign assignment in Afghanistan, Llorens Service, he has served in economic, was Ambassador-in-Residence and commercial, and consular positions in a faculty advisor at the National War Tegucigalpa, La Paz, Asunción, San College in Fort McNair, Washington Salvador, and Manila. DC. Mr. Llorens received his Master of Llorens served as U.S. Ambassador Science in National Security Studies, to Honduras from September 2008 National War College in 1997; Master to July 2011. Prior to his nomination of Arts in Economics, University of and confirmation as Ambassador, Kent at Canterbury, England in 1980; he served for two years as the and Bachelor of Science in Foreign Deputy Chief of Mission (DCM) at the Service from Georgetown University American Embassy in Madrid, where in 1977. he took up his duties September Mr. Llorens has earned numerous 1, 2006. Ambassador Llorens was awards for distinguished performance, also Deputy Chief of Mission at the including eight Superior Honor and American Embassy in Buenos Aires, five Meritorious Honor Awards. He is Argentina, where he served for three a past recipient of the Cobb Award years from August 2003 until July for excellence in the promotion of 2006. U.S. business, was runner-up for the From 2002-2003, Mr. Llorens was Saltzman Award for distinguished Director of Andean Affairs at the performance in advancing U.S. National Security Council (NSC), international economic interests, and where he was the principal advisor to was nominated for the James Baker the President and National Security Award for superior performance by a Advisor on issues pertaining to Deputy Chief of Mission. He speaks Colombia, Venezuela, Bolivia, Peru, Spanish, Tagalog, and some French. and Ecuador. Prior to the NSC, he served for three years as Principal 26 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Kirsty Duncan Kirsty Duncan is a Canadian medical Eventually, after several years of geographer and current MP for the searching, Duncan learned of Member of Canadian Parliament Liberal Party of Canada in the Toronto seven miners who had died from riding of Etobicoke North. the Spanish flu and were buried in the small town of Longyearbyen, After graduating from Kipling Norway, an area that would contain Collegiate Institute in 1985 as an permafrost. She then began Ontario Scholar, Duncan studied assembling a team of scientists to Geography and Anthropology at accompany her. After several more the University of Toronto. She then years of preparation, which involved entered graduate school at the garnering various permissions to University of Edinburgh in Scotland, perform the exhumations, the ground and completed a Ph.D. in geography survey began in 1998. However, in 1992 the samples were not viable, as the From 1993 to 2000, Duncan taught bodies were not in the permafrost, meteorology, climatology, and climate and the expedition was ultimately change at the University of Windsor. proved a disappointment. In 1992, as she became increasingly In 2003, Duncan wrote a book about aware of the increasing probability her expedition, entitled Hunting the of a global flu crisis, she was led to 1918 Flu: One Scientist’s Search for a investigate the cause of the similar Killer Virus. Published by the University 1918 Spanish flu pandemic, saying, of Toronto Press, it details Duncan’s “I was horrified we didn’t know what process and the expedition itself. caused [Spanish flu], and also knew After the book’s publication, Duncan that if we could find fragments of the began speaking about pandemics, virus, we might be able to find a better which led her to begin teaching flu vaccine” corporate social responsibility at Though at the time she “knew the University of Toronto’s Rotman nothing about influenza”, she began School of Management. In 2008, what she called a “six-month crash Duncan published a second book, course in virology”. Eventually, she Environment and Health: Protecting began searching for possible frozen our Common Future. samples of lung and brain tissue that Duncan was an adjunct professor might contain the virus. Her initial teaching both medical geography at thoughts led her to think of Alaska, as the University of Toronto and global it contains large areas of permafrost, environmental processes at Royal which would leave the viruses intact, Roads University, and served on the but the search proved fruitless. Intergovernmental Panel on Climate Change, an organization that won the 2007 Nobel Prize with Al Gore. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 27

Congressman Chaka Fattah Congressman Chaka Fattah is focused on neuroscience. Currently, a senior member of the House the National Institutes of Health, the Senior Member of the House Appropriations Committee. This Department of Defense, Department Appropriations Committee committee is responsible for setting of Veterans Affairs and National spending priorities for over $1 Science Foundation all fund research trillion in annual discretionary funds. on brain development, cognition, Congressman Fattah is Ranking disease and injury. While specific Member on the Subcommittee research or single-disease-focused on Commerce, Justice, Science projects are critical, the Congressman and related agencies (CJS). The believes that the greatest impact from Subcommittee on CJS oversees close federal funding can be achieved by to $51 billion in discretionary spending broad support and coordination at including the Commerce and Justice the highest levels of government for Departments, NASA. NOAA and the diverse research, addressing all areas National Science Foundation. Fattah of neuroscience. Neuroscience and is also Chair of the Congressional brain disease affect every American Urban Caucus, a bipartisan group family. Whether a relative is afflicted of Members representing America’s by Alzheimer’s, stroke, Parkinson’s, metropolitan centers. These Members Multiple Sclerosis, depression or work collaboratively with other a traumatic brain injury, it is well stakeholders to address the unique understood that the incidence and challenges facing America’s urban national impact of these diseases communities. is huge – and expected to grow tremendously as our population Current Initiatives: ages. It is with this knowledge, and a Fattah Neuroscience Initiative fascination for scientific discovery, that – In November 2011, President Congressman Fattah began this effort Obama signed into law the Fattah to highlight the role of neuroscience Neuroscience Initiative, the first ever research, and this important area of federal inter-agency collaborative science.

A/Prof Charlie Teo Dr Teo is an internationally acclaimed recognised with awards from Rotary neurosurgeon and a pioneer in International, including the Paul Harris Director, Centre for Minimally keyhole minimally invasive techniques. Fellowship (for contribution to World Invasive Neurosurgery He has been invited to many Health), the Brainlab Community Prince of Wales Private Hospital, distinguished universities in over Neurosurgery Award by the Congress Sydney NSW 50 countries as Visiting Professor, of Neurological Surgeons and as a including the Karolinska Institute, finalist in the NSW Australian of the Vanderbilt, Stanford and Johns Year awards in 2003 and 2009. In the Hopkins universities. Dr Teo has 2011 Australia Day awards he was published over 100 articles in peer- named as a Member of the Order of reviewed journals and authored Australia and in 2012 was given the 2 books on keyhole techniques honour of delivering the Australia Day in neurosurgery. He is the past President of ThinkFirst Australasia, Address to the Nation. Charlie is a the Director of the Centre for father to 4 beautiful girls and when not Minimally Invasive Neurosurgery, performing brain surgery is proud to the Australian representative for support his 2 favourite charities, the the Tumor Section of the AANS Cambodian Children’s Trust, which and CNS and the Founder of the runs an orphanage in Battambang, Cure for Life Foundation that has and Voiceless, which funds legislative raised over $8 million for brain reform for the prevention of cruelty to cancer research. Dr Teo has been industrial and farm animals. 28 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Shouleh Nikzad Dr. Shouleh Nikzad is a Senior Dr. Nikzad is the recipient of several Research Scientist at JPL, a position awards including the Lew Allen SBMT President Elect conferred by the Director and the Award of Excellence, NASA Space Office of the Chief Scientist in Act Awards, JPL Instrument Division recognition of her achievements. She Team awards for, and the TAP Team is also a Principal Member of the Staff award for development of high speed and she leads the Advanced Detector UV camera. In 2012, She was elected Arrays, Systems, and Nanoscience as a Fellow of the American Physical Group at JPL. Society. Shouleh is a Senior member of IEEE and has been recognized Dr. Nikzad’s interests in research and featured by the IEEE’s Women span a wide range of fields, including in Engineering (2011) and the SPIE’s materials, devices, astrophysics, Women in Optics (2012) for being a space weather, and medicine. Dr. pioneer and role model. She gave Nikzad’s work in non-equilibrium a keynot address at the Society for techniques to modify surface Women Engineers (SWE) last October and interface bandstructures has in Cal Poly Pomona. pioneered high performance imaging devices. She has initiated, developed Dr. Nikzad is Visiting Faculty at and managed successful and Caltech’s Physics Math, and innovative technology development Astronomy Division and Cedar Sinai programs, including the development Neurosurgery Department. She of advanced UV and visible imagers holds a PhD in Applied Physics from and cameras, broadband UV-NIR Caltech, a MSEE from Caltech and a detector arrays, soft x ray detectors, BS degree in Electrical Engineering solid-state charged and neutral (Electrophysics) from USC. She has particle detectors, human-eye- over 50 peer publications and holds inspired curved focal plane arrays, over 10 US patents. and nanostructure based devices. Dr. Nikzad has been with the SBMT Her work on single photon counting since it’s inception. In the first annual UV imaging has produced world meeting, she organized a “New record sensitivity in UV that enables Horizon” session in which NASA future NASA missions mapping of scientists shared their work with the intergalactic medium, studying nuerosurgeons and neuroscientist primitive bodies as well as Europa which spawned many collaborations. and its moons. Her team also She is the president elect of SBMT holds the record on low energy and will be co organizing the 2015 ion and neutral detection energy SBMT World Congress. threshold after they improved that by an order of magnitude. This work enables compact and low power instruments for Space Weather and mass spectrometry instruments that can be used in a variety of fields including planetary atmospheric studies, life detection, and commercial applications. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 29

The Hon, Jillian Skinner MP Jillian Skinner is the Deputy NSW Jillian has more experience in the Liberal Leader, Minister for Health and health field than any other politician in Minister for Medical Research. Australia, having first been appointed She was first elected as the Member Shadow Minister for Health in 1995. for North Shore in February 1994 and She has also held the Shadow has been re-elected five times. portfolios of Education and Training and Youth Affairs and Arts. Jillian began her career as a journalist in Melbourne, becoming the first Since becoming Minister for Health woman journalist on the Victorian and Minister for Medical Research in Parliamentary Press Gallery. She later March 2011, Jillian has: worked as a journalist in Adelaide, • boosted the workforce (4000 Sydney and South East Asia before additional nurses and 900 extra operating her own editorial, strategic planning and marketing consultancy. doctors) • overseen a $4.7 billion hospital Prior to her election to the NSW building program Parliament, Jillian was the Director of the New South Wales Office of • overseen record health spending Youth Affairs and she has served on to deliver tens of thousands more bodies such as the New South Wales emergency department treatments, Women’s Advisory Council and the hospital admissions and elective New South Wales Youth Advisory surgeries. Council.

Prof Trevor Kilpatrick Trevor Kilpatrick is a Professor of Professor Kilpatrick has been the Neurology and Director of the Centre recipient of the Sunderland Award Melbourne Neuroscience Institute, for Neuroscience Research and the (1994), AMRAD Postdoctoral Award University of Melbourne Melbourne Neuroscience Institute at (1995), inaugural Leonard Cox Award The University of Melbourne; he is the (2000), Bethlehem Griffiths Research leader of the MS Division at the Florey Foundation Award for Medical Institute of Neuroscience and Mental Research (2004), the Australian Health and is a neurologist and Head Museum’s Jamie Callachor Eureka of the MS Unit at the Royal Melbourne Hospital. Prize for Medical Research (2008), the Stephen C. Reingold Research Professor Kilpatrick graduated with Award by the US MS National Multiple a Bachelor of Medicine, Bachelor Sclerosis Society (2010) and most of Surgery from the University of recently, (2013), Professor Kilpatrick Melbourne in 1982 and then went was awarded the Bethlehem Griffiths on to specialise in neurology. He Research Foundation Medal for undertook graduate studies at The University of Melbourne and gained outstanding leadership in medical a Doctor of Philosophy in 1993. research. Appointments at The Salk Institute Professor Kilpatrick has published for Biological Studies (La Jolla, USA), widely including publications in Institute of Neurology (London, Nature, Nature genetics and Nature UK) and The National Hospital and Medicine. His research interests Moorfields Eye Hospital (London, UK) include the neurobiology of multiple followed. He returned to Melbourne as the Viertel Senior Medical Research sclerosis, neural precursor cell Fellow at the Walter & Eliza Hall biology and the study of genetic and Institute for Medical Research and as environmental factors that contribute the Head of the Melbourne Multiple to MS as well as the translation of Sclerosis Research Unit at the Royal basic research discoveries to the Melbourne Hospital. clinic. 30 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Prof John Mattick John Mattick is the Director of the John Mattick has published over 250 Garvan Institute of Medical Research. papers, which have received over Garvan Institute of Medical Research He undertook his undergraduate and 25,000 citations. His honours include graduate training at the University the Honorary Fellowship of the Royal of Sydney and Monash University College of Pathologists of Australasia, in Melbourne. He subsequently the inaugural Gutenberg Professorship worked at Baylor College of Medicine of the University of Strasbourg, the in Houston, the CSIRO Division of International Union of Biochemistry Molecular Biology in Sydney, and the and Molecular Biology Medal, University of Queensland, where he Fellowship of the Australian Academy was the Foundation Director of the of Science, Associate Membership Institute for Molecular Bioscience of the European Molecular Biology and the Australian Genome Research Organization, and the Human Facility. He has also spent research Genome Organisation’s Chen Award periods at the Universities of for Distinguished Achievement Cambridge, Oxford, Cologne and in Human Genetic and Genomic Strasbourg. Research.

Prof Peter Burger Dr Peter Burger MD, Professor Each year he reviews 1,500+ difficult of Pathology, Neurosurgery and brain tumor cases sent to him in Lowy Cancer Centre Oncology, is the Director of Surgical consultation. He served as chairman Neuropathology at Johns Hopkins of the Pediatric Oncology Group Hospital in Baltimore, USA. Over the pathology review committee for brain last 35 years, he has made a wide tumors from 1981-2000, and has range of contributions to the field of also been involved with numerous neuro-oncology and is one of the other brain tumor groups as an expert world’s leading authorities on the neuropathology consultant or medical classification and diagnosis of tumors advisor. of the central nervous system. Dr Burger is the recipient of many He has published over 400 original awards including the Award for papers and review articles. Their Dedication and Distinguished impact is evidenced by the fact that Service, American Association of more than 100 of these have been Neuropathologists in 2009 and the cited at least 50 times, and 38 were Lifetime Achievement Award from the cited 100 times or more. He played a Society for Neuro-Oncology in 2010. key role in generating all three editions Dr Burger is the current Cure For Life of the WHO classification for CNS Foundation Brain Cancer Research tumors, and influences countless Visiting Academic at UNSW. pathologists and others in the field of neuro-oncology, through his many textbooks. An engaging speaker, he has given over 250 invited or honorary lectures around the globe. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 31

Major General, Professor Jeffrey V. Rosenfeld is Professor and million from the NH&MRC. He is a Jeffrey V. Rosenfeld AM, Head, Division of Clinical Sciences member of 8 editorial boards and is a of the Department of Surgery, OBE, reviewer for 27 international journals. Central Clinical School, Monash He is a Principal Investigator within Monash University University, Director, Department of the Monash Bionic Vision Group Neurosurgery at the Alfred Hospital, which aims to develop a bionic vision Adjunct Professor in Surgery at the F. direct to brain implant with a first-in- Edward Hébert School of Medicine, human implant in 2015. He was a Uniformed Services University of The member of the Court of Examiners Health Sciences (USUHS), Bethesda, in Neurosurgery for the Royal MD, USA, Adjunct Professor, Centre Australasian College of Surgeons for Military and Veterans’ Health, University of Queensland and (RACS) for 8 years. He is a Major Honorary Professor in Neurosurgery, General in the Australian Defence University of Papua New Guinea Force (ADF) and was immediate past (PNG). His main research interests Surgeon General, ADF-Reserves are traumatic brain injury and bionic 2009-2011. He has served on 7 vision. He is on of Australia’s ADF Operations including Rwanda, leading academic neurosurgeons East Timor, Bougainville, Solomon and senior military surgeons and Islands and Iraq. He was awarded is internationally recognised for his the United States Air Force (USAF) neurotrauma research and teaching. Commendation Medal and the He was the CIB on the landmark Michael E. DeBakey International Decompressive Craniectomy Study, Military Surgeons’ Award for the first multicentre randomised Excellence in Military Surgery from controlled trial of this procedure which USUHS in 2009. He is an Honorary was published in the New England Fellow for 3 surgical colleges. He Journal of Medicine (NEJM) in 2011. is also Pro-Vice Chancellor (Major He has been an invited Visiting Projects), Monash University, Chair, Professor in 11 countries and an Victorian Neurotrauma Advisory invited speaker for 12 named orations and 65 international meetings. He Council, Honorary Fellow of the has published over 223 peer reviewed Bionics Institute, Victoria, Chair, ADF articles (including Lancet, Lancet Human Research Ethics Committee Neurology and NEJM), 40 book and a member of the Neuroethics chapters and 2 books. He has over Committee, and the Neurotrauma and 3000 citations and has over his career Education Committee of the World been awarded $20.516 million of Federation of Neurosurgical Societies. competitive grant funding including He is President, Graduate Union of $9.9 million from the ARC and $4.973 the University of Melbourne.

Dr Jacopo Annese Jacopo Annese, Ph.D. is the director of The Brain Observatory in The Brain Observatory, USA San Diego and Assistant Professor of Radiology, at the University of California San Diego (UCSD). Dr. Jacopo Annese graduated from the University of Rome (La Sapienza) with a Master degree in Biology and Zoology. He obtained his Masters in Neurological Science from University College London (London, UK) and a Ph.D. in Cognitive Neuroscience from Dartmouth College (NH, USA). 32 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Dr Geoffrey Ling Dr. Geoffrey Ling is the Deputy Dr. Ling received his BA from Director of the Defense Sciences Washington University in Saint Louis, Defence Advanced Research Office at the Defense Advanced Ph.D. in pharmacology from Cornell Projects Agency (DARPA) Research Projects Agency (DARPA) University, and M.D. from Georgetown and attending neuro critical care University. He completed a neurology physician at Johns Hopkins Hospital. residency at Walter Reed and a neuro- He retired from the US Army in intensive care fellowship at Johns 2012 after serving as a military Hopkins. intensive care physician with multiple Dr. Ling is board certified in Neurology deployments to Iraq and Afghanistan. and Neuro Critical Care. He has He formerly served in the Science published over 150 peer-review Division at the White House Office of articles, reviews, and chapters, Science and Technology Policy. including the TBI chapter in Cecil’s Dr. Ling’s DARPA research includes Textbook of Medicine, the VA-DoD Revolutionizing Prosthetics, a Guidelines for Managing mTBI/ program to develop a brain controlled concussion, and the DoD Guidelines prosthetic arm for amputees that has for Prehospital Management of been featured on CBS’s “60 Minutes”, Combat Related Head Injury. and Preventing Violent Explosive Neuro Trauma, an effort to develop new understanding and treatment of blast brain injury.

Prof Warwick Anderson Professor Warwick Anderson is Professor Anderson is a member the Chief Executive Officer (CEO) of the Prime Minister’s Science National Health and Medical of NHMRC, Australia’s major Engineering and Innovation Council, a Research Council governmental funding body for health Board member of the Global Alliance and medical research. Previously, he for Chronic Disease, a member of was Head of School of Biomedical Heads of International (Biomedical) Sciences at Monash University and Research Organizations and of the Deputy Director of the Baker Medical National Lead Clinicians Group. He Research Institute, following research is an Honorary Fellow of the Royal fellowships at the University of Sydney College of Pathologists of Australasia and Harvard Medical School. and an International Fellow of the American Heart Foundation. He was Professor Anderson obtained his PhD made a Member of the Order of from the University of Adelaide. His Australia in 2005. research has focused on renal causes of hypertension, including the roles of renal vascular remodeling, renal innervation and the renin-angiotensin system. He has published over 170 peer review articles. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 33

Plenary session 1 nervous system damage or enhance increasing complexity, reaching Neurology and neurophysiology its repair are currently available. 98.8% in human. The majority of Moreover, the ability of currently these sequences are transcribed, to Prof Trevor Kilpatrick available immunomodulatory therapies produce a plethora of short and long Director, Melbourne Neuroscience used to treat MS, to prevent long- non-protein-coding RNAs (lncRNAs) Institute, University of Melbourne term disability is uncertain. Novel that show specific expression neuroprotective agents have been patterns and subcellular locations. identified in preclinical studies but This is particularly evident in the their development is being hampered brain, where the majority of lncRNAs by the absence of appropriate clinical are expressed in highly restricted platforms by which to test them. patterns in the hippocampus, cortex Therapeutic challenges for I will discuss some of the principal and cerebellum, among others. neurodegenerative disease: therapeutic candidates that could Some lncRNAs are relatively highly the case of multiple sclerosis provide neuroprotection and emerging expressed and associated with methodologies by which to test them. specialized subnuclear organelles, Neurodegenerative diseases I will also discuss the academic and one of which appears to be involved collectively account for a major commercial interactions that will need in activity-dependent splicing percentage of the disability burden to be brokered in order to develop changes in neurons and be linked in our community and one that, effective translational paradigms in to schizophrenia, whereas others if left unchecked, will inexorably this field. are highly cell-specific. Recent increase with time. Over the last evidence suggests that a major twenty years there has been a function of these lncRNAs is to guide revolution in our understanding of chromosomal organization and the pathogenesis of these diseases Plenary session 2 chromatin-modifying complexes to but this has not, as yet, translated The central role of RNA into improved treatment paradigms their sites of action, to supervise the in cognitive function beyond the adoption of symptomatic epigenetic processes that underpin development and cognition. The approaches. In this lecture I will Prof John Mattick AO, former is relatively hard-wired, but the explore the challenges that face Executive Director, Garvan latter appears to be enabled by the us in this arena and will illustrate Institute of Medical Research superimposition of plasticity on these the relevant issues with particular Sydney reference to Multiple Sclerosis (MS) regulatory networks by RNA editing the commonest neurodegenerative and retrotransposon mobilization, disease that affects young Caucasian which have evolved rapidly in adults. Multiple Sclerosis has been mammals and especially primates. traditionally considered to be an autoimmune disease that results from an attack against myelin, It appears that the genetic the layer which surrounds axons. programming of complex organisms Plenary session 2A However, the pathophysiology of MS has been misunderstood, primarily Molecular Markers in CNS is complex, with both demyelination because of the assumption that most Tumour Pathogenesis, and axonal degeneration contributing genetic information is transacted Diagnosis, and Classification to what is essentially an inflammatory by proteins. Surprisingly, humans neurodegenerative disease. possess only about 20,000 protein- Prof Peter Burger Axonal loss is increasingly being coding genes, similar in number and Professor of Pathology, Oncology, accepted as the histopathological functional repertoire to those in simple and Neurosurgery, correlate of neurological disability. nematodes that have only 1,000 The Johns Hopkins Hospital Currently, the underpinnings of cells, including a high proportion neurodegeneration in MS, and how of those involved in the nervous to promote neuroprotection are only system. By contrast, the extent of partly understood. No established intergenic and intronic non-protein- treatments that directly reduce coding sequences increases with 34 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Progress in the molecular Chair: Martin Pera & Kuldip Sidhu human growth and possibly disease characterisation of CNS tumours is onset and progression. opening many doors for improved Following standard procedures, diagnosis and therapy. Correlation we generated human induced of such findings with classical pluripotent stem cells (hiPSCs) from histopathologic features helps define healthy, sporadic AD and familial AD and sub classify known tumour individuals. Vigorous characterization types and aids in identifying new Martin Pera (Keynote) assays were carried out and all entities. Molecular features now cell lines were positive for classic supplement histological diagnoses pluripotent features, including: expression of OCT4, NANOG, SSEA4, in some cases, the “1p/19q” test TRA160; teratoma formation and in for oligodendroglioma being the vitro differentiation into derivatives of best example. Pathways of tumour the three germ layers. origin and evolution are becoming To gain a better understanding of the apparent. Most importantly, efforts Alice Pebay possible disease onset/progression to find therapeutically exploitable mechanisms, we performed a whole molecular targets proceed apace. transcriptome analysis of the hiPSC The extent to which histopathologic lines. Differential gene expressions classification will be bypassed in were performed and subsequent gene favour of purely molecular approaches ontology and pathway enrichment is unclear since pathogenic effects Role of Lysophosphatidic acid in analyses revealed a number of and responsiveness to treatments neural stem cells and in traumatic neuronal and immune system related of specific genetic abnormalities are brain injury terms, which correlates well with contextual; they depend in part on current literature. the tissues or cells from which the Henry Chung The next steps are to differentiate tumours arise. Thus, in the near future, this cohort of hiPSC lines into mature it seems likely that molecular features neurons and examine whether will continue to sub classify classic they develop AD phenotypes entities such as glioblastoma rather such as plaque and neurofibrillary than to establish a primary diagnosis tangle formation and importantly neurodegeneration. independent of histopathological Whole transciptome analysis of study. This may well change, however, 1Centre for Healthy Brain Ageing, UNSW Medicine, Alzheimer’s disease specific human UNSW 2052 especially if molecular inhibitors induced pluripotent stem cells are identified whose effects are Henry Chung1, Perminder Sachdev1, independent of tumour type or cell of Kuldip Sidhu1 Lezanne Ooi origin. The latter two concepts may become less relevant, or irrelevant, in Alzheimer’s disease is the most such a setting. Discovering markers common form of dementia. Despite and therapeutic targets identified extensive research, no immediate by non-invasive techniques such as therapy is available, which is due to our limited understanding of neuroimaging is a subject of great Altered Neuronal Function in the disease. Animal models have interest. Networks Derived from Induced provided great insight, but do not Pluripotent Stem Cells from fully recapitulate the major disease Alzheimer’s Disease Patients hallmarks of human AD, hence Breakout Session 1 alternative models need to be School of Biological Sciences, developed. Human pluripotent stem Illawarra Health and Medical Research Pluripotent Stem Cells cells are one such candidate as they Institute, University of Wollongong, & Neural Lineages mimic the developmental processes of NSW2522, Australia. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 35

Induced pluripotent stem cells (iPSCs) Michael Back therapy (intensity modulated radiation from patients are facilitating research therapy) to areas within the tumour at into neurodegenerative disease different dose levels (integrated boost) pathogenesis. The neuronal iPSC defined by MRI and PET techniques derived models exhibit phenotypes (dose painting). synonymous with their in vivo counterparts and provide a means This presentation will detail the Radiation Therapy Dose Painting to interrogate sporadic diseases, technical aspects of treatment including Alzheimer’s disease. Using utilizing FET and FDG PET in the mapping, dosimetric benefits and a combination of advanced mass management of high grade glioma clinical outcome in the initial 40 spectrometry, gas chromatography Anaplastic oligodendroglial tumours patients with anaplastic glioma and imaging techniques we have are a favourable subsite of high managed under this protocol. identified key changes in lipids and grade glioma that have recently proteins in cells from Alzheimer’s been shown to be associated with disease patients. By promoting the median survival beyond 15 years Prof Jeffrey Rosenfeld AM, OBE, formation of neuronal networks with management by combined Monash University from patient iPSCs we have further modality therapy with limited surgery, interrogated the mechanisms by radiation therapy and chemotherapy. which these changes alter neuronal The more durable survival in this high function in vitro. Using a variety of functioning younger population places techniques we have tracked these a greater emphasis on optimizing changes during differentiation from pluripotent cells into neurons. These therapy with a balance between Targeting calcitonin receptor changes lead to extensive functional tumour control and minimization of expressed by brain tumour initiating effects on neuronal signalling events. late morbidity. Although favourable cells of gliobastoma multiforme prognosis, the tumour is often quite Our data establishes lipids as key Jeffrey V Rosenfeld & Peter J Wookey1 players in differentiation and identifies extensive at initial presentation with major changes in specific lipid species MRI demonstrating widespread T2 The aggressive tumours GBM are in Alzheimer’s disease patient cells. Flair change surrounding the initial T1 generally resistant to conventional dense or enhancing mass. Radiation treatments. A number of potential therapy is the key component of treatments based on antibody management but high dose therapy Breakout Session 2a regimens, stimulation of the immune and large volume standard treatment system and drugs that target tumour- CME Symposium, has been associated with potential specific intracellular pathways have Neuro-oncology late neurocognitive effects that may been tested, and are currently under reach clinical significance in patients trial. However the necessity for Chair: Michael Back with durable survival. new, effective targets remains a & Kerrie McDonald Technological improvements in high priority whilst the outcomes for diagnostic imaging, nuclear medicine patients remain poor. and radiation therapy treatment can • A new target, the calcitonin potentially deliver a more targeted receptor (CTR), has been identified dose of radiation to the tumour by our group, found expressed by and spare normal brain. In these glioma cells in a high proportion of favourable anaplastic oligodendroglial tumour tissue samples of patients Charlie Teo (Keynote) tumours, there may be a less with GBM (>90%, p<0.05)2. aggressive region identified within the tumour by these improved brain • In particular, CTR is expressed by imaging techniques that may be cells with morphology and nucleus managed with lower radiation dose. characteristic of malignant cells Patients can then be managed with some of which express markers Maximising technology in the a novel radiation approach utilizing of brain tumour initiating cells Surgical Treatment of Gliomas improved targeting of radiation (BTICs)2. 36 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

• 40% of high grade glioma cell Surasak Phuphanich Immunosuppression represents lines that represent 4 subtypes of a critical tumor adaptation that BTICs (proneural, neural, classical & contributes to poor outcome by mesenchymal) express CTR protein fostering tumor immunotolerance (QIMR data, unpublished) across all rather than rejection. Emerging data subtypes. implicate enhanced activity of the inhibitory immunoregulatory molecules • Cell death is induced in CTR+ve Immunotherapy for Brain Cancer: programmed death-1 (PD-1) and its BTICs in vitro with picomolar Vaccine, PD1/PDL1 Antibody associated binding partners PD- concentrations of the immunotoxin Glioblastoma is the most common L1 and PD-L2 as pivotal mediators anti-CTR antibody:saporin primary neoplasm of the central of tumor immunoevasion for many conjugate in the presence of an nervous system in adults. Despite cancers including GBM. Indeed, enhancer of endosome release, rigorous therapeutic efforts, recent analyses confirm that PD-L1 namely saponin-1641 (unpublished overall prognosis remains dismal. is expressed by a high percentage of data). Specifically, multimodality therapy GBM cell lines and primary tumors. integrating surgery, radiation therapy These recent, interesting results _ENREF_180 _ENREF_161In addition, and temozolomide chemotherapy suggest testing the immunotoxin for PD-L1 expression correlates with is associated with a median efficacy in a mouse xenograft model glioma grade and is detected on progression-free survival of only 6.9 to be undertaken by collaborators at CD133+ GBM stem cells. We recently 3 months, and a median overall survival QIMR , Brisbane in 2014. evaluated PD-L1 expression in a of 14.6 months (Stupp, et al, 2005). 1. Collaborators include David L Hare (Uni Melb), formalin-fixed, paraffin-embedded Sebastian GB Furness (Monash Uni), Andrew W For recurrent GBM the historical PFS- tissue microarray of 83 GBM tumors Boyd (QIMR), Brett Stringer (QIMR), Bryan Day 6 rate is dismal at ≤ 16% (Prados, (QIMR), Peter Hwang (Monash Uni), Mayank Thakur and noted that 85% express PD-L1 in 2006). Following progression, salvage & Alexander Weng (Charité University, Berlin). over 80% of the tumor cells, including therapies have historically been of 2. Wookey PJ, McLean CA, Hwang P, Furness SGB, approximately 25% that exhibited nominal benefit with PFS-6 rates Nguyen S, Kourakis A, Hare DL, Rosenfeld JV. a membranous staining pattern (D. The expression of calcitonin receptor detected in under 10% noted in recent meta- Reardon, personal communication). malignant cells of the brain tumour glioblastoma analyses. In one of the largest phase multiforme and functional properties in the GBM cell Furthermore, inactivating mutation of line A172. Histopathol 60, 895-910, 2012. Listed by 3 trials for recurrent GBM, enzastaurin the phosphatase and tensin homolog Global Medical Discovery: 25th July 2012. was compared to lomustine (CCNU). (PTEN) tumor suppressor, which 3. Day BW, Stringer BW, Al-Ejeeh F, Ting MJ, Wilson The overall survival (6.6 v 7.1 months) occurs in 40-50% of GBM tumors, J, Ensbey KS, Jamieson PR, Bruce ZC, Lim YC, was disappointing demonstrating Offenhauser C, Charmsaz S, ……, Boyd AW. leads to upregulation of PD-L1 2013. EphA3 maintains tumourigenicity and is CCNU to represent one of the few expression and immunoresistance. a therapeutic target in glioblastoma multiforme. agents with any activity at recurrence Cancer Cell 23:238-248. Targeting PD-1 and PD-L1 has (Wick et al., 2010). The FDA Approval recently generated encouraging of Bevacizumab (Avastin) within evidence of anti-tumor activity among the Neuro-Oncology field has been Kerrie McDonald advanced solid tumor patients. controversial and demonstrated limited efficacy in the upfront setting ICT-107 is an autologous vaccine with a mediocre improvement in consisting of patient dendritic cells overall survival at recurrence(Lai pulsed with six synthetic class I et al., 2011 ). There is a need for peptides from AIM-2, MAGE1, TRP- novel therapeutic strategies for this 2, gp100, Her2/neu and IL-13Rα2. uniformly fatal disease. The rationale for combining MK3475 with ICT-107 is that an adaptive PD-1 signaling mediates immunotherapy regimen combining immunosuppression in glioblastoma PD-1 checkpoint blockade with anti- Profound immunosuppression tumor vaccination may significantly is a hallmark of many complex enhance anti-tumor activity than cancers including glioblastoma. either agent alone.26-30 Specifically, 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 37

inhibition of PD-1 suppression of Breakout Session 2b Raymond Schwartz T-cell activation is expected to enhance tumor antigen-specific T Functional Neurosurgery cell responses. In a recently reported single-arm study, ICT-107 vaccination was associated with median PFS and OS of 16.9 months and 38.4 Chair: Ray Cook Neurological perspective on DBS for months and 5-year survival was neurological conditions 50%, respectively among newly diagnosed GBM patients (Phuphanich et al, 2013). In addition to these Socrates Dokos highly encouraging efficacy data, ICT-107 is the only vaccine that has completed accrual to a randomized, Ray Cook (Keynote) placebo-controlled clinical trial among GBM patients (clinicaltrials. gov NCT01280552). Preliminary Modelling Direct Brain Activation in results of this trial that enrolled 124 Electroconvulsive Therapy patients were reviewed after 67 events and demonstrated that ICT- The efficacy and cognitive outcomes 107 was very well tolerated, and of electroconvulsive therapy (ECT) that PFS increased by 3 months in Colleen Loo have been shown to depend on the ICT-107, per-protocol arm of the variations in treatment technique. study (p=0.01, HR=0.53). A trend of In order to investigate the effects improved OS was also noted on the of electrode montage and stimulus ICT-107 arm, although final results parameters on direct activation are pending further data maturation of the brain during ECT, we have (Immunocellular Therapeutics, DBS and Alzheimer’s disease developed a novel computational unpublished data). Evaluation of pre- approach utilising high resolution ICT-107 vaccine and post- vaccine Non Invasive Therapeutic Brain finite element human head models samples demonstrated increase in Stimulation generated from MRI scans, with anisotropic conductivity and excitable PD-L1 expression in tumor in ¾ post This talk will focus on three vaccine samples and absence of ionic formulations to simulate non invasive brain stimulation neuronal activation in the brain. Our PD-L1 expression in all pre-vaccine techniques, used in the treatment samples. There was also evidence computational approach can be used of neuropsychiatric disorders : of antigen specific cytotoxic T cells to compare the effects of electrode Electroconvulsive therapy (ECT), in post vaccine sample in a patient montage, as well as altered ECT treated with ICT-107 demonstrating Transcranial Magnetic Stimulation stimulus amplitude, pulse width the development of a robust CTL (TMS) and transcranial Direct Current and frequency on the spatial extent of directly activated brain regions. response intratumorally (J Yu, Stimulation (tDCS). Studies have Simulation results indicate that personal communication). These shown that these brain stimulation increases in stimulus frequency, as clinical and immunologic data support treatments can lead to lasting well as decreases in amplitude and the significant immune response changes in brain structure and/ pulse width, lead to overall reductions correlated with clinical outcome using or function. Changes shown after in the spatial extent of activated brain ICT-107 alone and provide a strong brain stimulation include induction of regions as expected. The model rationale for testing the synergy of neurogenesis, alteration in functional represents a powerful approach in PD-1/PD-L1 Antibody and ICT-107 in connectivity and regional cerebral understanding transcranial current combination. metabolism, and enhancement of flow and activation of the brain during neuroplasticity. ECT. 38 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Takeshi Shimizu state fMRI scan. The mean age of demonstrate that the functional CPSP patients was 61.5. All the CPSP connectivity related to primary patients had the neuropathic pain in somatosensory cortex is different in their upper limbs. Then, 12 CPSP CPSP patients and healthy controls. patients among them underwent They also suggest that rTMS sessions 5Hz rTMS over primary motor cortex restore the functional connectivity Functional connectivity specific and resting state fMRI after the rTMS specific to CPSP patients and change to central post stroke pain and sessions. The rTMS was applied the functional connectivity in default alterations after repetitive transcranial through a figure-8 coil connected to mode network (DMN) involving PCC. magnetic stimulation a magnetic stimulator, which provides We speculate that the increased a biphasic pulse. It was consisted of functional connectivity related to Author & Co-authors 500 pulses at 90% intensity of resting primary somatosensory cortex in Takeshi Shimizu Department of motor threshold. 7 CPSP patients CPSP patients may result from Neurosurgery, Osaka University experienced pain reduction more differentiation and interhemispheric Kouichi Hosomi Department of than 10% in VAS. Functional MR data inhibitory interaction. And we also Neurosurgery, Osaka University were acquired with GE (Signa HDX speculate that rTMS may affect the 3T) in the Osaka University Hospital. Tomoyuki Maruo Department of substrates of pain perception. We analyzed the difference of the Neurosurgery, Osaka University functional connectivity between Keywords: Transcranial Magnetic Hui Ming Khoo Department of 9 healthy controls and 14 CPSP Stimulation (primary keyword) Neurosurgery, Osaka University patients and between pre-rTMS Functional brain mapping (fMRI, PET?) Yoshiyuki Watanabe Department of fMRI and post-rTMS fMRI in 7 CPSP Radiology, Osaka University patients who were responders to Toshiyuki Yoshimine Department of rTMS. Functional connectivity maps Breakout Session 3 Neurosurgery, Osaka University were calculated using the statistical software package SPM and conn, ACRO CME Symposium, Youichi Saitoh Department of which is the toolbox running on SPM. Neuro-radiation oncology and Neuromodulation and Neurosurgery, For the group analysis, the images stereotactic radio-surgery Osaka University of the patients who had the lesions Chair: Anatoly Rosenfeld in the right hemisphere were flipped Introduction: It is popularly & Jim Welsh thought that repetitive transcranial by SPM. Voxel level threshold of magnetic stimulation (rTMS) of the uncorrected p < 0.001 and Cluster primary motor cortex can relieve the level threshold of FWE corrected p < neuropathic pain altering the activity of 0.05 were applied. not only the target area of stimulation Results: Compared with healthy but the remote brain regions involved adults, CPSP patients exhibit the in pain sensation as well. In the statistically significant increase of Jim Welsh (Keynote) analysis of neuroimaging series, the functional connectivity between functional connectivity is defined as primary sensory cortex and motor the statistical correlations between cortex and premotor cortex. After spatially remote neurophysiological the rTMS sessions to CPSP patients, events. The aim of this study is to the mean reduction rate of VAS was investigate the functional connectivity 23.6%(±17.2%) and the functional specific to central post-stroke pain connectivity between posterior Proposed New Boron Neutron (CPSP) and the alteration of the cingulate cortex (PCC) and anterior Capture Therapy Program at functional connectivity induced by cingulate cortex (ACC) and the Fermilab rTMS. functional connectivity between PCC James S Welsh1 and prefrontal cortex decreased. Method: 9 healthy adults and 14 The Neutron Therapy Facility (NTF) at CPSP patients underwent the resting Conclusion: Our findings Fermi National Accelerator Laboratory 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 39

treated its first patient using fast Anatoly Rosenfeld (on behalf of while causing little damage to non- neutrons in September 1976. As CMRP) Centre for Medical Radiation cancerous tissue compared to an a fully functional and independent Physics, University of Wollongong, equivalent treatment delivered via clinic, the NTF could be an ideal Australia broad beam synchrotron radiotherapy. The radiation patterns consist of environment to reinitiate investigations Stereotactic Body Radiation Therapy periodic narrow slit beams of 50 into boron neutron capture therapy (SBRT) and Stereotactic Radiosurgery to 600 keV X-rays with extremely and boron neutron capture enhanced (SRS) are new radiation oncology high peak dose rates of the order fast neutron therapy in the USA. modalities which allow the delivery of hundreds to tens of thousands The Fermilab p(66)Be(49) fast neutron of a spatially conformed high dose of Gy/s, for a typical sub-second beam has a mean neutron energy of radiation to the target volume, treatment time. Conventional of 25 MeV. Our team has created i.e. the tumour. This is achieved by dosimetry techniques are not suitable a means of moderating the energy directing radiation beams at the for synchrotron microbeam QA since down to the energies appropriate tumour from multiple angles and they cannot accurately measure for neutron capture therapy. We by delivering several sub-beams or dose with the necessary micron- have been exploring the physical ‘beam segments’ through differently scale resolution due to the extreme characteristics of this modified beam shaped apertures at each treatment brightness of the synchrotron source and using it for in vitro radiobiology angle, which allows an accurate 3D and the enormous dynamic range of “dose painting” of the target volume. experiments. The moderated beam the dose delivered by the microbeam Both techniques involve the delivery energy is enriched neutrons of pattern. Performing direct QA of a single fraction of a high dose of epithermal energy making it potentially dosimetry on a patient in real-time radiation, and therefore the uncertainty suitable for BNCT of deep-seated is impossible; therefore, performing of the dose placement should not tumors without intraoperative accurate pretreatment dose QA in exceed 1 to 2 mm. This requirement exposure. a phantom and developing suitable makes Quality Assurance (QA) in beam quality assurance protocols In parallel with the physics and SBRT and SRS extremely important using CMRP’s newly developed radiobiology advancements, our team and challenging. A suite of detectors high-resolution dosimeter, X-Tream, has been developing and evaluating aimed at performing SBRT, SRS and is of utmost importance. Our results various novel boronated compounds proton therapy pretreatment QA have demonstrate that X-Tream is capable (e.g. glutamine derivatives), which may been developed and implemented of performing fast and accurate offer improved biodistributions over at the Centre for Medical Radiation measurements of the Peak to Valley traditional BNCT agents. Physics. Dubbed Magic Plate and Dose Ratio (PVDR). Its “beam Dose Magnifying Glass, both systems transparency” and fast readout time We propose addressing two primary are capable of measuring the dose allow for real time monitoring of the malignancies in future clinical trials deposition pattern with a very high intensity of the photon microbeams in – glioblastoma multiforme in human spatial and temporal resolution both peaks and valleys and provides a patients and locally advanced (1 mm and 0.1 ms respectively). count of the number of microbeams in bladder cancer in veterinary patients, These devices are currently being the MRT microbeam array, and can be if the final analysis of the modified evaluated in a phantom prior to used to terminate the treatment within beam proves acceptable for clinical their deployment in clinical in vivo 20 us. Results from its deployment at implementation. application. Results of the dosimetric the European Synchrotron Radiation 1 Northern Illinois University pre-treatment QA of static spinal Facility (ESRF) as an important step SBRT and SRT for brain tumours towards the clinical trials on MRT along with the preliminary results of technology will be presented. Anatoly Rosenfeld targeting movable small targets in motion adaptive radiotherapy will be presented. Stephanie Weiss Synchrotron microbeam radiotherapy (MRT) is a new form of spatially

fractionated radiation therapy which Advanced quality assurance in shows great potential as an effective

Stereotactic Radiosurgery for error treatment option for certain cancers free treatment (such as paediatric glioblastoma) 40 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Breakout Session 4 fluid-percussion TBI models in demographically matched control rats, followed by continuous EEG particpants, they were found to Neuro-trauma and monitoring demonstrated the timeline have more variable HRV and SCL Neuropsychiatry of seizure development. Changes at rest. Three TBI particpants were on the molecular level after TBI have excluded due to excessively high been postulated in animal models; HRV. The remainder were significantly however, pharmacologic interventions lower than the control group in HRV. including anti-inflammatory and This normalised somewhat after Chair: Michael Roy anti-epileptic agents did not appear biofeedback. Higher HRV during & Skye McDonald to be promising in preventing biofeedback, and higher SCLs at rest the development of epileptic and during biofeedback, correlated seizures. Better understanding of negatively with trait alexithymia epileptogenesis after TBI is necessary (i.e. emotional awareness) in both for earlier, more targeted interventions the overall sample and separate to prevent of development of post groups. These results suggest that traumatic epilepsy. HRV shows promise as an index of impaired autonomic regulation in Jeffrey Chung (Keynote) severe TBI. Biofeedback training may Skye McDonald help normalise HRV in severe TBI; improved autonomic regulation may ameliorate impairments on emotional self-awareness.

1. School of Psychology, University of New South Post Traumatic Epilepsy: Wales, Australia Present and Future 2. Faculty of Medicine, University of Sydney, Australia Improving emotion regulation *Corresponding author email: [email protected] Traumatic brain injury (TBI) is an and heart rate variability after increasingly prevalent disorder severe traumatic brain injury: and, according to the World Health Biofeedback has potential Michael Roy Organization, it will surpass most Skye McDonald¹*, Jacqueline A. diseases as the major cause for Rushby¹, Alana Fisher¹, Rebekah mortality and disability. About Randall¹ & Robyn Tate2 10 million people world-wide are affected by TBI annually, and in Severe traumatic brain injury (TBI) is the United States, approximately known to impair emotion regulation Identification of Predictors of 1.7 million new cases are reported and arousal. Heart rate variability Post-Deployment PTSD and every year. One of the sequelae (HRV) is an index of autonomic postconcussive syndrome in of TBI is the development of post (dys)regulation, reflecting the Combat Veterans traumatic epileptic, which accounts balance between sympathetic and up to 20% of all epilepsy cases. parasympathetic influences on the Center for Neuroscience and The relative risk of developing post central nervous system. Biofeedback Regenerative Medicine, and traumatic epilepsy is 2.9 in moderate techniques can regulate disrupted Department of Medicine, Uniformed cases and 17.2 in severe cases. As HRV and alleviate symptoms in Services University of the Health high as 50% of patients suffering disorders associated with impaired Sciences, Bethesda, MD, 20814 from penetrating head injury would arousal. The present study aimed to Background: PTSD and TBI are develop post traumatic epilepsy. examine, whether adults with severe the signature wounds of recent While some studies have shown that TBI show: i) HRV dysregulation at wars in Iraq and Afghanistan. There the presence of acute seizure in TBI rest; ii) improved HRV regulation via is often a “honeymoon” period for patient is associated with a higher a biofeedback intervention; as well weeks after return when service incidence of post traumatic epilepsy, as how these relate to aspects of members (SMs) often underreport the mechanism of epileptogenesis emotion regulation. When 30 adults symptoms, yet many subsequently remains elusive. Central and lateral with severe TBI were compared to develop PTSD, and TBI frequently 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 41

leads to postconcussive syndrome anisotropy in the cingulum on DTI, dysfunction in depression? Are there (PCS). However, PTSD and PCS reduced connectivity between the distinctive patterns that identify have similar symptoms and can PCC and MFC on fMRI, and elevated specific “subtypes” of depression? be difficult to distinguish. Effective reexperiencing symptoms of PTSD What pre-treatment aspects of methods for identifying those at high (e.g, flashbacks and nightmares). brain circuitry predict and moderate risk immediately after deployment is Discussion: We identified 3 response to anti-depressants? We important to enable early intervention factors that were associated with have already shown that MDD is to reduce symptoms, promote the development of PTSD after resilience and prevent progression associated with multiple sites of focal deployment. Variation in the DAT gene to full PTSD. Sorting out the two grey matter volume that markedly disorders from each other also may be has also been reported in association exceed the expected rate of loss critical to appropriately direct therapy. with PTSD and depression in other via aging_ENREF_22. We have also The objective of this prospective studies. Variation in S100B, a provided evidence of sub-types in calcium binding protein, has been cohort study is to identify the best depression using DTI3, and have associated with brain injury and predictors of post-deployment PTSD used discriminant analysis of DTI neurodegenerative diseases, and and PCS. data alone to accurately distinguish is thus one potential link between 4 Methods: This is a prospective cohort TBI and subsequent PTSD. The MDD subjects from control subjects . study involving 81 SMs (including 11 amygdala has been associated with Most recently, we have published the with mild combat TBI) representing all hypervigilance and easy startling most comprehensive connectomic military services from across the U.S. in PTSD in other studies, so the analysis of MDD, describing in detail We first conducted a comprehensive associated activity we found on fMRI to key networks that characterise baseline assessment within 2 months fits with that. The links we found MDD5. Finally we ill present predictive post deployment, including fMRI, DTI, between changes on DTI and fMRI, data that demonstrates for the first EEG, ERPs, SNPs, neuroendocrine and PTSD symptoms is suggestive of time that DTI connectivity measures measures and psychophysiology. a relationship between TBI and PTSD, We then performed serial follow-ups can be used to predict remission and which warrants further assessment in non-remission to anti-depressant at 3, 6, and 12 months, and used future studies. univariate and multivariate analyses to medications. determine the strongest predictors of 1. Grieve SM, Korgaonkar MS, Etkin A, Harris A, the development of PTSD and PCS. A/Prof Stuart Grieve Koslow SH, Wisniewski S, Schatzberg AF, Nemeroff Sydney Medical School & Brain CB, Gordon E, Williams LM. Brain imaging Results: In our cohort, 6 developed predictors and the international study to predict PTSD and 1 developed PCS. Dynamics Centre, University of optimized treatment for depression: Study protocol Univariate analysis identified 49 Sydney for a randomized controlled trial. Trials. 2013;14:224 baseline measures which were 2. Grieve SM, Korgaonkar MS, Koslow SH, Gordon associated with PTSD at a p<0.15 E, Williams LM. Widespread reductions in gray level, and two different sophisticated matter volume in depression. NeuroImage. Clinical. multivariate measures (CART 2013;3:332-339 and random forests approaches) 3. Korgaonkar MS, Grieve SM, Koslow SH, Gabrieli each identified 3 factors that were JD, Gordon E, Williams LM. Loss of white matter Structural MRI and Diffusion Tensor associated with PTSD. Two were integrity in major depressive disorder: Evidence Imaging evidence of network single nucleotide polymorphisms for using tract-based spatial statistical analysis abnormalities in Major Depressive of diffusion tensor imaging. Hum Brain Mapp. the dopamine transporter (DAT) and Disorder - data from the iSPOT-D 2011;32:2161-2171 S100B genes, respectively, while the trial final significant factor was connectivity 4. Korgaonkar MS, Cooper NJ, Williams LM, Grieve between the parietal operculum and The iSPOT-D imaging substudy is SM. Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: A the amygdala, as measured on resting a multi-modal MRI study of major whole-brain diffusion tensor imaging tractography state fMRI. We then performed a depressive disorder (MDD) and is the study. Neuroreport. 2012;23:566-571 nested case-control study comparing largest imaging treatment prediction 5. Korgaonkar MS, Fornito A, Williams LM, Grieve 1 those with TBI with age- and ever performed . The study aims SM. Abnormal structural networks characterize sex-matched controls. We found to answer these central questions: major depressive disorder: A connectome analysis. links between reduced fractional Is there a core brain circuitry Biological psychiatry. 2014; in press 42 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Mayuresh Korgaonkar Breakout Session 5 as the physiological function of neurotrophin signalling switches from Translational Neuroscience promoting brain circuit development to maintenance of circuit function and synaptic plasticity. However, potent latent capacity for neural Functional Imaging markers of (re) development is evident by the treatment prediction in depression: propensity of neuronal outgrowth when neurotrophins are delivered data from the International Study Chair: Gary Housley to Predict Optimized Treatment in to the nervous system following Depression (iSPOT-D). injury. The potency of neurotrophins to stimulate neural repair following Major depressive disorder (MDD) is the leading cause of disability and sensori-neural hearing loss exemplifies has an economic impact in the United this. The establishment of the afferent States of $42 billion per year. Typically, innervation of the cochlea occurs via only about 50% of MDD patients a precise spatiotemporal program, respond to antidepressant treatment Gary Housley (Keynote) where promiscuous spiral ganglion and even fewer achieve remission. neurite outgrowth is followed by There are currently no clinically pruning and selective neuronal useful means to predict response to apoptosis; processes inherently tied antidepressant medications. Improved to neurotrophin signalling1. Sensori- methods for objectively predicting neural hearing loss, for example with response to medication could Neurotrophin-based neural repair noise or chemical ototoxicity, causes therefore have an important clinical and protection loss of the neurotrophin source and impact. Brain imaging offers a means consequent auditory nerve atrophy. Department of Physiology & to identify treatment predictors that Cell-based, drug or gene therapy Translational Neuroscience Facility, are grounded in the neurobiology of strategies around the neurotrophin School of Medical Sciences, University the treatment and the pathophysiology translational research platform in the of New South Wales, Sydney, NSW of MDD. The International Study cochlea promote vigorous auditory 2052, Australia. to Predict Optimized Treatment in nerve regeneration, with directional Depression (iSPOT-D) is a multi- Across the breadth of brain and guidance queues reminiscent of the center, parallel model, randomized nervous system injury and disease, developmental programming. Such clinical trial which seeks to identify neurotrophin signalling is moving to control of neural repair provides an factors that predict treatment the vanguard of neurotherapeutics. opportunity to enhance medical response to three commonly Neurotrophins are key molecular bionics neural prosthetic interfaces; prescribed antidepressants. This talk a neurotrophin gene delivery platform will present the functional imaging signals for the developing central, markers of general-medication and peripheral, autonomic and enteric we have developed has established specific responses to antidepressant nervous systems. As examples, proof of principle showing improved medications identified using data from brain-derived neurotrophic factor hearing performance with cochlear the iSPOT-D study. (BDNF), acting via the tyrosine kinase implants. More broadly, neurotrophin- receptor TrkB and downstream induced neural regeneration and phospholipase C signalling, promotes neuromodulation is establishing development of the cerebellar Purkinje a translational base across the cell dendritic arbor, and during spectrum of injury and age-related cochlear in the cochlea, BDNF and neurological disorders. NT3 are necessary for. Expression 1. Barclay M, Ryan AF, Housley GD (2011) Type of neurotrophins and associated Trk I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during receptors is down-regulated with cochlear development. Neural Development 6:33 maturation of the nervous system, doi:10.1186/1749-8104-6-33. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 43

Renee Morris that span across several segments Matthias Klugmann of the cervical spinal cord. Neurons in the uppermost segments of the spinal cord innervate the proximal muscles of the neck and shoulder, while those located in the middle and Gene therapy for spinal repair lower cervical segments supply more Gene therapy for leukodystrophies distal muscles of the upper and lower Department of Anatomy & Department of Physiology & forelimb, respectively. Translational Neuroscience Facility, Translational Neuroscience Facility, School of Medical Sciences, UNSW One can take advantage of the School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, muscle/motor neuron topography Australia, Sydney, NSW 2052, Australia. as well as the retrograde transport Australia. Spinal cord injury (SCI) is a long-term machinery of neurons to shuttle Oligodendrocytes represent a highly health and socio-economic burden neurotrophin genes into motor specialized class of glia in the CNS. worldwide. Although there is no neurons occupying specific spinal They provide electrical insulation cure for SCI, there is evidence that cord segments. In our rat model of of axons by sheathing them in implants of cells genetically modified SCI, we are currently performing membrane extensions (myelin) to secrete neurotrophic factors elicit intramuscular injections of adenoviral enabling fast impulse conduction of axonal elongation and sprouting in the vectors to achieve gradients of axons. Oligodendrocyte dysfunction injured spinal cord1. However, axons gene expression into the cervical results in demyelination and tend to dwell in these neurotrophin- spinal cord. In this minimally invasive secondary axonal degeneration. Acute rich implants rather than to seek out gene therapy scenario, the motor or chronic demyelination underlies the pathology of leukodystrophies, for and reconnect with motor neurons neurons per se become baits for inherited myelin diseases typically caudal to the lesion, a process that is the pre-synaptic injured axons. This caused by single gene mutations. essential for the recovery of function. innovative approach, by encouraging These disorders are incurable and Our research efforts aim to overcome axons to elongate enough to possibly associated with substantial morbidity the limitations associated with these reconnect with motor neurons, has and mortality. This represents a strong cell implants. the potential to overcome the poor rationale for gene therapy. In fact, the outcomes obtained so far with static We have developed a rat model of leukodystrophy Canavan Disease was implants of genetically engineered partial SCI transection at cervical the first neurological disorder ever cells, therefore bringing gene therapy levels. While retaining the ability to on trial using a gene replacement a step closer for human SCI. reach, rats with such transection approach. Gene therapy is based on are no longer capable to rotate the 1. Morris R. Neurotoxicity and neuroprotection in spinal the simple concept of introducing a cord injury. In: Handbook of Neurotoxicity therapeutic gene to dysfunctional cells paw during the grasping action, a (R Kostzewa ed) Springer (in press). motor sequence called the arpeggio with the aim of slowing or reversing 2. Morris R, Tosolini A P, Goldstein J D and I Q 2 disease progression. However, movement . This movement in the Whishaw (2011). Impaired arpeggio movement rat shares extensive similarities with in skilled reaching by rubrospinal tract lesions in sufficient expression levels of the human prehension (e.g. typing on a the rat: a behavioural/anatomical fractionation. J. therapeutic protein require efficient keyboard, operating a hand-controlled Neurotrauma 28:2439-2451. and specific gene delivery systems. wheelchair joystick etc.), the return 3. Tosolini A P and R Morris (2012). Spatial Promising results were obtained characterization of the motor neuron columns recently following lentivirus-mediated of which is most important to supplying the rat forelimb. Neurosci. 200:19-30. quadriplegics. gene therapy to treat children with 4. Tosolini A P, Mohan R and R Morris (2013). metachromatic leukodystrophy, a We have also characterized the Targeting the full length of the motor end plate disease caused by deficiency of the relationship between the spinal cord region in the mouse forelimb increases the uptake of Fluoro-Gold into corresponding spinal cord motor secreted enzyme ARSA. The genetic motor neurons and the forelimb neurons Front. Neurol. 4, 58:1-10 treatment of this disease type can be muscles that they supply3-4. This benefited by cross-correction - the analysis revealed that motor neurons transduction of a small number of are organized into discrete columns host cells followed by release of the 44 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

therapeutic enzyme and subsequent that KCC2 function is rapidly lost in 1. Moorhouse, A.J. and Nabekura, J (2011) Cellular Mechanisms of Neuronal Cl- Homeostasis and its uptake by non-transduced cells. various neuronal injuries, including Modulation by Neuronal Injury. In Inhibitory Synaptic However, leukodystrophies caused by axotomy, ischemia, chronic pain and Plasticity. Contemporary Neuroscience Series. loss of non-secreted proteins, require epilepsy1. The loss of KCC2 renders Springer. Ch. 9, pp. 123-36. a gene delivery system that targets GABA inhibition ineffective or even 2. Wake, H., Watanabe, M., Moorhouse, A.J., et al. sufficient numbers of oligodendrocytes excitatory, which may exacerbate (2007) Early changes in KCC2 phosphorylation in response to neuronal stress results in functional in large CNS areas, ideally through the neuronal injury and maladaptive downregulation. J. Neurosci., 27: 1642-1650. the systemic route of administration. plasticity accompanying this change. 3. Watanabe, M., Wake, H., Moorhouse, A.J. Recent advances in the development We have been investigating the & Nabekura, J. (2009) Clustering of neuronal of recombinant adeno-associated mechanisms and consequences K+-Cl- cotransporters in lipid rafts by tyrosine virus (AAV) vectors – the most of this KCC2 down-regulation in phosphorylation. J Biol Chem., (4) Eto, K., Ishibashi, H., Yoshimura, T et al., (2012) Enhanced GABAergic efficient vehicles for CNS-targeted different neuronal injury models, activity in the mouse primary somatosensory delivery – address both requirements. both in vitro2,3 and in vivo4, recently cortex coupled with reduced potassium-chloride In summary, gene therapy for focussing on epilepsy. Injection of cotransporter function is insufficient to alleviate chronic pain behaviour. J Neurosci. Nov 21; 32(47); leukodystrophies, one of the most mice with the chemoconvulsant p 16552-16559. devastating group of neurological kainic acid or pilocarpine results disorders, has been shown to actually in a severe seizure phenotype, work. The technologies involved might status epilepticus, characterised by John Power be employed to establish effective continuous stage 3-5 behavioural treatments for other demyelinating seizures and high amplitude bursts diseases such as multiple sclerosis. of spikes on electroencephalography (EEG). Using a conditional tetracycline biogenic mouse developed by our Andrew Moorhouse colleagues in Japan, upregulation of KCC2 in adult mice confers a Molecular targets for addiction and marked resistance to seizure activity memory disorders and completely prevents status Department of Physiology & epilepticus. Furthermore, KCC2 Translational Neuroscience Facility, upregulation has no effect on a School of Medical Sciences, University The KCC2 chloride transporter range of mouse behaviours including of New South Wales, Sydney, NSW as a target for epilepsy locomotion in the open field test and 2052, Australia measures of exploration and anxiety in Our memories and the emotions they Department of Physiology & Cellular the elevated plus maze. We have now evoke not only allow us to adapt and Systems Physiology, School of established a robust mouse model to our environment, but also help Medical Sciences, University of New of Temporal Lobe epilepsy in which define our sense of self. Memories South Wales, Sydney, NSW 2052, we can reproduce the symptoms of are thought to be coded by the Australia. frequent focal seizures and temporal coordinated activity of small networks lobe necrosis, and in which changes The correct balance of neuronal of neurons. New memories are formed in GABA signalling seem to contribute excitation and inhibition is critical for by activity dependent changes in to the pathogenesis of seizures. normal brain function and is disrupted the synaptic connections between In summary our results suggest in a myriad of neuronal disorders. neurons leading to the formation of that upregulating KCC2 has little A key determinant of the efficacy new neuronal ensembles. The cellular effect on basal GABA signalling and of neuronal inhibition is KCC2, a processes that underlie the formation transmission in the healthy, normal Potassium Chloride Co-transporter of new neuronal networks involve both brain, but can markedly sustain (SLC12A5, isoform 2) that typically changes at individual synapses and inhibition in the hyperactive brain, extrudes Cl- and thereby maintains changes in the neuronal response to thereby preventing seizures. Targeting a low intracellular Cl- in neurons that synaptic activity. Learning-associated KCC2 and Cl- homeostasis is a facilitates a robust hyperpolarisation excitability changes include the novel approach to maintain neuronal in response to activation of inhibitory reduced activity of a calcium-activated inhibition and potentially mitigate GABAA receptor channels. It has potassium current that limits the against neuronal diseases such as become strikingly clear in recent years generation of action potentials. epilepsy and chronic pain. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 45

This excitability change occurs in Breakout Session 6 in countries which are experienced several brain regions involved in in such matters, including the use memory formation, including the Adult Stem Cells & Personalised of matched stem cells for cerebral hippocampus, the amygdala, and the medicine palsy, for eye diseases, for tissue cortex. Interestingly, in hippocampal Chair: Bob Williamson & engineering, and for heart attacks. We neurons, this current increases with Mirella Dottori should remind ethics committees that age and this increase correlates with it is unethical to stop much-needed age-related memory impairments research into diseases for which, observed in humans and other at present, we have no satisfactory animal species1,2. Our results have treatment. We should remember shown that this calcium-activated that advances in clinical care are potassium current reduces the almost always incremental and not integration of synaptic inputs, thus revolutionary, often individual rather limiting the neurons capacity to form Bob Williamson FRS than general, and we should discipline 3 enhanced neuronal connections . University of Melbourne (Keynote) ourselves to abjure wild, sweeping Pharmacological agents, such as claims of the coming impact of stem muscarinic acetylcholine receptor cell science on medicine. agonists, that reduce this specific potassium current in vitro, facilitate hippocampal-dependent learning Vicky Yamamoto in ageing subjects4. It is becoming Stem Cells and Personalised increasingly apparent that the cellular Medicine changes that underlie addiction are strikingly similar to that of memory “Personalised Medicine” infers formation; involving changes in clinically relevant information from both synaptic connectivity and the genotype and phenotype of intrinsic neuronal excitability. Thus, an individual; it is hard to think Small molecule based approaches targeting the specific ion channels of anything more personal than for personalized medicine and adult and cellular mechanisms involved someone’s stem cells. The various stem cell therapy in intrinsic neuronal excitability is medical uses proposed for stem cells Abstract: There is considerable likely to have therapeutic value not each raise questions of feasibility, interest in the development of only for the treatment of cognitive safety and ethics. Cells prepared from personalized medicine for the disorders involving impaired or a patient have obvious immunogenetic treatment of various human diseases inappropriate memory formation such advantages over cells from another including neurological disorders as Alzheimer’s disease and post- individual (whether embryo or adult), and cancer. Adult stem cells offer traumatic stress-disorder, but also but vary from one preparation to enormous potential as therapies for addiction. another. In the case of the newest as they can replace diseased or 1. Power, J.M., Wu, W.W.H., Sametsky, E., Oh, M.M., suggested procedure, using acid to damaged tissues. Reprogrammed Disterhoft, J.F. (2002). Age-Related Enhancement of the sIAHP in Hippocampal CA1 Pyramidal Neurons induce pluripotency, we are not even adult cells are even more attractive in vitro. J. Neurosci. 22:7234-43. sure it works! Risks of rejection, and as a therapy as they can overcome 2. Moyer JR, Jr., Power JM, Thompson LT, Disterhoft of causing cancer, are real, but also any immune rejection. While viral JF (2000) Increased excitability of aged rabbit apply to bone marrow transplants, the transfection methods and using CA1 neurons after trace eyeblink conditioning. J Neurosci 20:5476-5482. one form of stem cell therapy that has growth factors have been commonly already been in common use for thirty used to manipulate stem cell fate, 3. Power, JM, Bocklisch, C, Curby, P and Sah, P. (2011). Location and Function of the Slow years. Stem cell tourism is deplorable, the methods have some limitation, Afterhyperpolarization channels in the Basolateral but it does seem to tell us that most especially for clinical application. Amygdala. J. Neurosci. 31:526-37. patients survive injections of poorly Using small molecule modulators can 4. Oh, M.M., Power, J.M., Thompson, L.T., Moriarty, characterised unmatched cells without circumvent some of the limitation and P., Disterhoft, J.F. (1999) Metrifonate increases neuronal excitability in CA1 pyramidal neurons from serious damage, if also without is becoming an emerging method both young and aging rabbit hippocampus. serious improvement. We should in stem cell biology. Here, we will J. Neurosci. 19(5):1814-1823. encourage, even demand, careful describe the current progress of using clinical trials of stem cell therapies small molecule modulators to control 46 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

stem cell fate and how they can be mechanisms could operate in the function. Furthermore, FRDA iPS- used in clinical application. In addition, human. A rigorous understanding derived neural progenitors are able to we will present how a small molecule of endogenous regenerative differentiate into functional neurons Wnt/beta-catenin inhibitor was used mechanisms in the monkey neocortex and integrate in the nervous system for cancer therapy. could have a transformational when transplanted into the cerebellar influence on our attempts to regions of host adult rodent brain. potentiate CNS regeneration in the These findings are highly significant James Bourne human. We are now undertaking to for developing FRDA therapies using address the fundamental question as patient-derived stem cells. to whether quiescent NPCs exhibit 1. Murdoch Childrens Research Institute, Royal the capacity to generate neurones Children’s Hospital, Australia that functionally integrate and survive 2. Department of Paediatrics, The University of long term in the visual cortex of the Melbourne, Australia. Does Functional Neurogenesis marmoset monkey following an 3. Department of Otolaryngology, The University of Occur in the Injured Neocortex ischemic injury. Melbourne, Australia 4. Department of Anatomy and Neuroscience, The of the Nonhuman Primate? University of Melbourne, Australia Research over the last 15-20 years Mirella Dottori 5. Broad Center for Stem Cell and Regenerative has overturned the dogma that Medicine, University of Southern California, USA the generation of neurones in the 6. Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia mammalian central nervous system 7. Walter and Eliza Hall Institute, Australia (CNS) is restricted to development. 8. Victorian Clinical Genetics Services, Royal Children’s It is now firmly established that Hospital, Australia. new neurones are generated in the Functional characterization of 9. Centre for Neural Engineering, Department of hippocampus and the olfactory Friedreich Ataxia Electrical and Electronic Engineering, The University bulbs throughout adult life. Whether of Melbourne, Australia neurogenesis can be induced in other iPS-derived neuronal progenitors and areas of the adult CNS following their integration in the adult brain. Yashar Kalani injury and in particular whether these Matthew J. Bird1, 2, Karina Needham3, neurones can functionally integrate Ann E. Frazier 1,2, Jorien van Rooijen4, into existing neural circuits remains Jessie Leung4, Shelley Hough4, Mark controversial. Most keenly debated Denham4, Matthew E. Thornton5, is the idea that new neurones could Clare L. Parish6, Bryony Nayagam 3, be generated in the adult neocortex Martin Pera4, 6, 7, David R. Thorburn1,2,8, and contribute to neural repair, an Lachlan H. Thompson 6 and Mirella exRNAs as biomarkers of area normally refractory to adult Dottori 4, 9. neurological disease neurogenesis. Fuelling this debate is the finding that that new neurones Friedreich ataxia (FRDA) is an are generated in the adult neocortex autosomal recessive disease characterised by neurodegeneration of the rodent following specific types Breakout Session 7 and cardiomyopathy that is caused by of cortical injury. Moreover, significant an insufficiency of the mitochondrial Neurology and Neurophysiology synaptic plasticity and neurogenesis protein, frataxin. Our previous studies occurs following CNS injury in higher- described the generation of FRDA order mammals, including monkeys. iPS cell lines that retained genetic The significant finding that characteristics of this disease. Here neurogenesis in the monkey can we extend these studies, showing Chair: Matthew Kiernan be induced following injury of the that neural derivatives of FRDA iPS neocortex, an area that is often cells are able to differentiate into damaged as a result of traumatic functional neurons, which don’t show brain injury and stroke, raises the altered susceptibility to cell death, exciting possibility that similar and have normal mitochondrial 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 47

Keith Black (Keynote) include objective and prolonged 2. Naismith SL, Hermens DF, Ip TKC, Bolitho S, Scott actigraphic-derived assessments E, Rogers NL, Hickie IB (2012) Circadian profiles in young people during the early stages of affective of 24-hour sleep-wake cycles and disorder, Translational Psychiatry, e123. daytime physical activity, early 3. Scott EM, Hermens DF, Naismith SL, Guastella AJ, evening melatonin secretion patterns De Regt T, White D, Lagopoulos J Hickie IB. (2013) and relevant metabolic function Distinguishing young people with emerging bipolar parameters in selected sub-groups. disorders from those with unipolar depression. Journal of Affective Disorder, 144, 208–215. Mourad Tayebi Results: In clinical samples, there is 4. Robillard R, Naismith SL, Rogers NL, Ip TKC, evidence of delayed onset and offset Hermens DF, Scott EM, Hickie IB (2013) Delayed of sleep-wake cycles, reduced day- sleep phase and sleep disturbances in young people with unipolar or bipolar affective disorders, time physical activity and disrupted Journal of Affective Disorders, 145: 260-263. onset of night-time melatonin release 5. Hickie IB, Scott J, Hermens DF, Scott EM, Naismith in up to half of young persons with SL, Guastella AJ, Glozier N, McGorry P. (2013) emerging mood disorders. These Clinical classification in mental health at the cross- features are more pronounced in roads: which direction next? BMC Medicine, 11:125 Ian Hickie those with more severe conditions 6. Hickie IB , Naismith1 SL , Robillard R, Scott and those with a history of mania or EM, Hermens DF. Manipulating the sleep-wake cycle and circadian rhythms to improve clinical hypomania episodes. In twins, sleep- management of major depression. (2013) BMC wake cycle phenotypes are predicted Medicine, 11:79, doi:10.1186/1741-7015 by shared genetic characteristics and appear to have their own longitudinal associations with the ‘atypical’ as Steve Vucic Delayed sleep offset and other distinct from more classical ‘anxious markers of circadian rhythm disruption depression’ illness-type. Additionally, are common in young people with hypomanic-type features are emerging mood disorders extremely common in young people, Background: Episodic bipolar with about one-in-five reporting at and unipolar mood disorders are least one episode of sleep disturbance Cortical dysfunction in Motor Neurone characterized by disruptions in sleep- and activitation prior to age 25 years. Disease wake cycle, patterns of physical Delayed sleep offset activity and circadian rhythms. Conclusion: These phenomena are most evident and disrupted circadian function Trevor Kilpatrick in those who experience recurrent are characteristics of a major mania or ‘atypical’ depressive subgroup of young people with episodes. As 75% of major mental emerging mood disorders. While disorders emerge before age 25 under strong genetic control, these years, the focus on recording the features are exacerbated by other earliest features of these disorders in environmental and illness-related teenagers and young adults factors. These studies provide Genomics of multiple sclerosis unique data concerning relationships Methods: We have investigated between circadian factors and the T.J. Kilpatrick1,2, J. Field2, M. sleep-wake cycle, physical activity and onset and course of depression, Binder2, A. Fox2, H. Butzkueven3 in circadian features in young persons and other comorbidities, in young collaboration with ANZgene and the with emerging mood disorders in persons during the early phases IMSGC two large clinical samples (n=307, of illness. Circadian systems may Multiple sclerosis (MS) is the 30% bipolar-type, mean age = 19 represent a key target for behavioural quintessential complex human years; n=1797, 16% bipolar-type, or pharmacological treatments of disease, with its pathogenesis mean age = 18 years). Additionally, depression independent of other reflecting a breakdown in homeostatic we are investigating phenotypic and illness characteristics. circadian features in a longitudinal interactions between the immune 1. Hickie IB, Rogers NL. (2011) Novel melatonin-based study of adolescent twins (n=2459, therapies: Potential advances in the treatment of and nervous systems; its effective mean age=16 years). Measures major depression. The Lancet, 378(9791): 621-631. interrogation therefore requires a 48 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

systems biology approach. It is clear 1. Melbourne Neuroscience Institute, University of Hyperphosphorylated tau protein has that there is an inherited component Melbourne been implicated in cerebral damage influencing the susceptibility to MS, 2. The Florey Institute of Neuroscience and Mental in a variety of neurodegenerative Health given that the risk for sibs of people disorders, including traumatic brain with MS is approximately 30 fold 3. Department of Medicine, Royal Melbourne Hospital injury (TBI). In this study, we used that of the general population and magnetic resonance imaging (MRI) given that the concordance rate for to assess whether treatment with sodium selenate, a compound monozygotic twins is estimated at up Breakout Session 8 to 30%. It has been known for over 30 that reduces the pathological years that the MHC class II complex Molecular Imaging hyperphosphorylation of tau by increasing the activity of PP2A, would contains susceptibility gene(s) for MS Chair: Roger Ordidge & Gary Egan reduce neurodegeneration in a rat but until recently the field has failed fluid percussion model of TBI. Animals to identify additional loci because were given either a severe lateral fluid of insufficiently powered studies, percussion injury (LFPI), or sham-injury inadequate coverage of the genome and treated with either a continuous and lack of standardisation to enable administration of sodium selenate (1 replication. To identify additional mg/kg/day) or saline (sham group), multiple sclerosis (MS) susceptibility Kishore Bhakoo (Keynote) via a subcutaneous osmotic mini- loci, we and others have been taking pump for a period of three months. advantage of recently developed Anatomical T2-weighted and high technology that enables genome-wide angular resolution and high b-value association scans (GWAS). Utilising diffusion images were acquired at this approach, more than 100 genetic baseline and one week, one month loci, identified on the basis of variable and three months post-injury using a frequencies of commonly inherited 4.7T Bruker MR scanner. Volumetric polymorphisms, have now been found David Reutens and axonal integrity measures to contribute to the susceptibility of including fractional anisotropy, mean MS. However, the specific genes diffusivity and tractography were involved, the degrees to which rare investigated. Results demonstrated genetic variants contribute to disease that continuous sodium selenate susceptibility and how the relevant treatment reduced neurodegeneration genes interact all remain uncertain. after a severe LFPI. These findings We are currently unravelling these were supported by behavioural and Roger Ordidge complexities by adopting a number histological assessments which taken together, suggest that sodium of approaches, including the fine selenate has a neuroprotective effect. mapping of individual loci, as well Therefore, such an approach has as focusing on epigenetics and potential value as a novel treatment expression quantitative trait locus following TBI. (eQTL) analyses. We are also involved in understanding how the environment Study of sodium selenate as a and genetic variation interact to treatment in traumatic brain injury transform predisposition into active using MRI. disease and in the identification of Ordidge, R., Shultz, S.R., Wright, D., the genetic determinants of disease Zheng, P., Johnston, L., Hovens, C., severity as a preamble to enabling O’Brien, T. a pharmacogenomic approach to The University of Melbourne and Royal therapeutic intervention. Melbourne Hospital 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 49

Plenary Session 3 data to humans and flawed trial Prof Jeffrey Rosenfeld AM, OBE, design. There are also a number of Monash University (Keynote) Regenerative medicine confounding intrinsic host factors and stem cells including genomics of mitochondrial DNA, cytokine response, and APO-E alleles which may have a deleterious

effect on patient outcome. Neuro- inflammation may also have long The development of bionic vision at lasting adverse effects. Monash University On the positive side, there are Jeffrey V Rosenfeld Plenary Session 4 some promising therapies such Professor and Head, Division of Clinical Sciences and Department as erythropoietin, progesterone, Neurosurgery of Surgery, Central Clinical School, cyclosporine and statins which are Monash University. Prof Jeffrey Rosenfeld AM, OBE, currently being trialled. CENTER-TBI Director, Department of Neurosurgery, Monash University and TRACK-TBI are large European The Alfred Hospital, Melbourne, and American TBI patient data bases Victoria, Australia 3004 which will better characterize TBI. Comparative effectiveness research Co-authors: Professor Arthur Lowery, Dr Li WH and Dr Jeanette from these datasets will provide an Pritchard (Department of Electrical enhanced evidence base for the Improving the outcome from severe Engineering, Monash University), efficacy of various treatments in Professor Marcello Rosa and traumatic brain injury: how much severe TBI. Enhanced neuroplasticity, Professor Ramesh Rajan (Department further can we go? reduction of neuronal cell death, and of Physiology, Monash University), E There have been many recent the inhibition of inflammation and Harvey (miniFAB™), Harcourt J (Grey advances in the management of gliosis will be important therapeutic Innovation) and the Bionic Vision severe traumatic brain injury (TBI) strategies at a cellular level. Group at Monash University. including improved trauma systems, Improved techniques in physical Aims: The Monash University Bionic prehospital care, and intensive care and mental rehabilitation will likely Vision Program commenced in with multimodality monitoring. Despite improve outcome further. PTSD and April 2010 and aims to develop and this, on average 39% of patients with depression post injury are increasingly implant a human bionic vision device severe TBI die and 60% have an recognized. More attention will need by end 2014. Electrical stimulation of unfavourable outcome. The lowest to be focused on the quality of patient human visual cortex produces light mortality rates for severe TBI are outcome as well as mortality. Further percepts (phosphenes) and we believe around 10 to 20%. The efficacy of improvements in outcome following that with a high enough density of therapeutic hypothermia is uncertain. severe TBI are likely to be imminent. electrodes spread over the primary Prehospital induction of hypothermia occipital cortex (V1) that there would is currently under trial. Decompressive be sufficient resolution of vision via a digital camera/computer interface, craniectomy requires further research Breakout Session 9a that blind individuals would be able to determine when it is likely to be to navigate the environment and read most beneficial. NanoBioElectronics large print. Cortical stimulation is an Disappointingly few discoveries Chair: Babak Kateb alternative to retinal stimulation where in the laboratory have translated the retina is unsuitable due to injury or into treatment for severe traumatic disease. brain injury (TBI) in humans. There Methods: This is a collaborative are many reasons including the project between the Departments heterogeneity and complexity of TBI, of Electrical and Computer Systems misleading extrapolation of animal Engineering, Physiology, Surgery 50 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

and Ophthalmology at Monash need for smaller and more capable and School of Chemistry, University and the Alfred Hospital. instruments for astronomy, in situ UNSW Australia, Sydney, NSW 2052 Commercial partners are miniFAB™ planetary applications, as well as, The heart of the bioelectronics and Grey Innovation. A multi-tiled atmospheric analysis and other device is electron transfer between wireless electrode array has been remote sensing applications. With biomolecules and electrodes. developed and is being tested in applications in many fields including This talk will cover two studies animals. Each tile has 45 insulated astronomy, biology, planetary science, from our laboratory that focus on titanium micro-electrodes which will and Earth obsrevation, ultraviolet achieving efficient electron transfer at penetrate the visual (VI) cortex. There and visible imaging and detection biointerfaces for sensing applications will be > 400 electrodes implanted technologies are crucial for in situ and that have broader applicability in unilaterally. A small unilateral occipital remote sensing. neurosciences and bioelectronics. craniotomy will be performed for criminology. Because many of the access. Robotic vision algorithms features and phenomena under study The first concept is to combine the have been incorporated into the produce faint signals, the importance material of electronics, silicon, with ‘pocket’ computer which will enhance of detectors is common in many fields bioelectronics but modifying oxide the visual percepts. A psychophysics including neuroscience, neurosurgery, free silicon with self-assembled program is being developed for clinical pathology, oncology, criminology, and monolayers that can facilitate electron evaluation of the recipients. semiconductor fabrication industry. transfer to biomolecules. Recently, we have shown that the modification of Results: The progress to date in There is special synergy between in NASA instruments and medical silicon with 1,8-nonadiyne produces computer vision algorithms, system silicon surfaces that are both more component design and experimental instruments. We use this synergy and leverage from the technology resistant to oxidation both during results will be presented. The modification and afterwards. Upon challenges of producing a safe developed for space missions for use in medical fields. In this talk, hydrosilylation of 1,9-nonadiyne effective commercial device which we discuss the general overlap of the surface is rendered with a distal is approved by the regulators will be technological requirements in the alkyne such that the surface can be discussed. medical field and space sciecne. We further modified via ‘click’ chemistry Conclusions: The development will discuss an overview of our UV/ with an azide. Here we show how of a cortical implant for bionic visible/near infrared detector program this interface can be used to achieve vision is achievable. This Monash at JPL as well as our nanotechnology- direct electron transfer to proteins University/private industry commercial based technologies, and their in aqueous solution for the very first partnership is a strong model for applications. We will discuss the time. We also show how this same translational research. recent results and plans of our clinical chemistry could be used to fabricate trial of imaging technology. switchable surfaces for the capture and release of cells or proteins. Keywords: UV Imaging, Shouleh Nikzad Nanotechnology, Neurosurgery The second concept is to use molecular wires to allow efficient electron transfer through a protein Justin Gooding resistant layer on an electrode to a surface bound protein. This

technology is then applied to making Advanced Technology for Planetary, immunosensors that can operate in Astrophysics, and Medical whole blood. An example is given Applications for the detection of glycosylated haemoglobin but this generic Shouleh Nikzad Nanobioelectronic Interfaces that technology could be applied to Jet Propulsion Laboratory Facilitate Efficient Electron Transfer the detection of numerous protein Pasadena, California 91109 to Biomolecules or small molecule biomarkers. In recent years, NASA’s trend toward J. Justin Gooding, Simone Ciampi, less costly and potentially more Guozhen Liu, Abbas Barfidokht frequent missions has created a Australian Centre for NanoMedicine 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 51

Uttam Sinha parcellization and disconnection of which require an invasive procedure the ictal focus. The cortical columns involving all the risks related to open subserving eloquent and non- surgery, microbeam transections eloquent neurological functions are are performed in a non invasive way not injured by MST, allowing the and the size and spacing of the treatment of epileptic foci located over transections can be modified by the sensorimotor or language cortex not amenable to surgical resection. surgeon according to the needs. Microbeam transection placed over a Focal irradiation of an epilepsy focus Breakout session 9c highly challenging target, the primary through SRS provides an attractive Emerging application of non invasive approach, mainly limited motor cortex, are well tolerated. synchroton radiation in by the delay of efficacy (several No sign of motor deficit was found Neuroscience months are required to obtain after prolonged observation and seizure relief) and by side effects periodic rotarod testing. Convulsive Chair: Pantaleo Romanelli such as radio-induced edema and seizures originating from this region radionecrosis. Current LINAC- or disappeared almost immediately after cobalt-based technologies do microbeam transections( Romanelli not allow to deliver high doses to et al. 2013 ). Unilateral and bilateral cortical slices of millimetric size, thus replicating the exquisite cortical hippocampal transection are also well tolerated: no memory damage Pantaleo Romanelli incisions generated by MST. was detected and hippocampal A novel exciting approach combining neurogenesis was preserved. the advantages of SRS and MST has been investigated at the ESRF, The development of new devices where arrays of microplanar beams( delivering submillimetric beams able microbeams) have been used to generate cortical transections might Brain Modulation using synchrotron- to generate cortical transections add a powerful new tool to the clinical generated microbeams equivalent to MST in a non invasive, treatment of epilepsy and, more in Dr Pantaleo Romanelli, Brain bloodless way. Microscopic arrays of general, to modulate cortical functions Radiosurgery,Cyberknife Center, X-ray beams (microbeams) originating CDI, Milan; European Synchrotron from a synchrotron source have in a wide variety of neuropsychiatric Radiation Facility (ESRF), been used to generate neocortical disorders. or hippocampal transections by Grenoble,France. References: delivering very high doses of radiation Multiple subpial transections (MST) Romanelli P, Bravin A. Synchrotron-generated to tissue slices of microscopic microbeam radiosurgery: a novel experimental and stereotactic radiosurgery (SRS) thickness. Neurons,glia and axons approach to modulate brain function. Neurol Res. are emerging techniques to treat along the penetration path are 2011 Oct;33(8):825-31. seizure foci involving eloquent ablated, leaving a path equivalent Romanelli P, Striano P, Barbarisi M, Coppola G, cortex (Romanelli et al 2012). to that of a microsurgical incision. Anschel DJ. Non-resective surgery and radiosurgery MST is a microsurgical procedure The adjacent tissue is exposed to for treatment of drug-resistant epilepsy. Epilepsy Res. 2012 May;99(3):193-201 placing vertical incisions through much lower valley doses (less than the epileptic cortex in order to cut Romanelli P, Fardone E, Battaglia G, Bräuer-Krisch 5 Gy) unable to induce histologically E, Prezado Y, Requardt H, Le Duc G, Nemoz C, the horizontal axons responsible of evident tissue damage (Romanelli et Anschel DJ, Spiga J, Bravin A. Synchrotron-generated the propagation of seizures while al. 2011). In essence, synchrotron- microbeam sensorimotor cortex transections induce preserving the vertical columns acting generated cortical transections seizure control without disruption of neurological functions. PLoS One. 2013;8(1):e53549. as the basic unit of cortical function. provide a microradiosurgical Seizure spread is arrested by the equivalent of MST.Compared to MST, 52 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Figure 1 Ludwig Maximilians University, Educational Objectives: 1 Am Coulombwall, Garching, 1. Introducing the audience to 85748, Germany synchrotron radiation based [email protected] imaging as a powerful pre-clinical The advent of modern neuroimaging concept for high resolution and with computed tomography (CT) and high sensitive investigation methods magnetic resonance (MR) imaging in neuroimaging at cell level. has allowed for a better diagnosis and 2. Providing an overview of the main characterization of brain abnormalities results of synchrotron radiation and diseases. Despite the deep based neuroimaging. insights offered by these imaging methods, their sensitivity and/or 3. Enable the audience to ask spatial resolution are insufficient to questions on the possibilities offered study at the cell level the structures of by the novel synchrotron radiation this very complex tissue. Synchrotron based imaging techniques. Synchrotron-generated sensorimotor cortex radiation (SR) may provide the transection opportunity to overcome many of the limitations affecting current diagnostic Jeffrey Crosbie Figure 2 methods. Pre-clinical imaging on Microbeam radiation therapy: the the micro- and nano-scale with state of the art in cancer treatment multidimensional resolution (spatial, temporal and chemical) is made possible by the high intensity, energy selectivity and collimation of the SR beam. Advanced X-ray based imaging techniques have been developed and used for investigating excised rat and human cerebella without the application of any stain or contrast Alberto Bravin agent. Images clearly depict the hippocampus and cerebellum regions (with white and gray matter) and the substantia nigra structure. Normal and tumor tissues are also effectively Synchrotron-generated hippocampal transections discriminated. Proof of principle studies in “phase contrast” micro- Synchrotron radiation generated CT were performed on irradiated rat microbeams: overview and state of Paola Coan brains, demonstrating the ability of the the art method in visualizing the not only the Alberto Bravin1, P. Romanelli2, fine architecture of the organ but also Gabriele Biella3, Elke Bräuer-Krisch1 the effects of the treatment. on behalf of the Microbeam Radiation This presentation will give a concise Therapy community introduction to the principle imaging Synchrotron radiation facilities Brain microimaging using synchrotron methods used at SR facilities for are large scale laboratories where radiation neuroimaging investigations and a extremely intense and highly short overview of the recent results Prof. Paola Coan, PhD collimated X-ray beams are made produced in pre-clinical research. Department of Clinical Radiology, available to researchers for a wide Ludwig Maximilians University, 15 Keywords: Synchrotron radiation, range of applications, among which D Marchioninistr., Munich, 81377 high spatial resolution, high sensitive biology and medicine are constantly Germany; Department of Physics, imaging increasing of imporance. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 53

These applications are particularly currently orphan of effective medical very nature almost invariably a life- advanced at the European and surgical treatments. Selected threatening event, so it can be hard Synchrotron Radiation Facility (ESRF, pioneering results of these new to determine to what extent the Grenoble, France) where intense research avenues will be presented. symptoms are related to the direct nanometric or homogeneous broad 1. European Synchrotron Radiation Facility, Grenoble, physical impact on the brain versus beams are also used to study, analyze France the psychological trauma, yet sorting and treat pathologies of the central 2. CDI Brain Radiosurgery and ABI Medica, Milano out the relative contributions may be nervous system (CNS). critical to appropriately direct therapy. 3. Institute of Molecular Bioimaging and Physiology, We utilized novel imaging techniques Microbeam Radiation Therapy National Research Council, Segrate, Milano to try to elucidate this issue. (MRT) uses polychromatic arrays of microscopic beams (from 25 to 600 Methods: We performed a nested case-control analysis within a microns) delivered with submillimetric Breakout Session 10 precision to the CNS. Doses up to prospective cohort study involving hundreds of Grays, delivered in a Sport and Concussion 81 SMs, in which we compared 11 fraction of a second, can be very well SMs with mild combat TBI and 11 Chair: Geoffrey Ling and Babak controls matched for age and sex. tolerated by the CNS in mammals Kateb as shown in several preclinical trials. We compared the results of resting The potential application of MRT state functional magnetic resonance in the treatment of cancers of the imaging (fMRI), diffusion tensor CNS is presently under evaluation in imaging (DTI), and PTSD symptoms on the Clinician-Administered PTSD veterinarial trials. Scale (CAPS). MRT has also been applied to Results: Those SMs with a history obtain the radiosurgical equivalent of Michael Roy (Keynote) of mild TBI had reduced fractional multiple subpial transections. Cortical anisotropy (FA) on DTI compared to columns are the basic functional units controls in the white matter adjacent of brain computation. Synchrotron to the left precuneus. We then microbeams can generate cortical demonstrated a significant correlation transections disconnecting between the degree of functional adjacent columns and modulating Linking TBI with PTSD in Combat connectivity between the left posterior abnormal columnar processing. The Veterans: Lessons Learned from the cingulate cortex (PCC/ precuneus and hypothesis was verified in epilectic Predictors Study the left medial frontal cortex (MFC) rats. Microradiosurgical transections on fMRI and the left cingulum FA on induced seizure control while motor Michael J. Roy, MD, MPH; Michelle DTI (the white matter that connects function was not affected. Also the Costanzo, PhD; Suzanne Leaman, these regions), such that 31% of ability of microbeams to generate PhD; Jessica Gill, PhD; Dave Keyser, the variance in connectivity was hippocampal transections has been PhD; Mary Coughlin; Yi-Yu Chou; explained by the FA. In addition, we recently investigated. This original Dzung Pham, PhD. found a significant relationship in turn approach offers an interesting new Center for Neuroscience and between resting state connectivity way to study the hippocampal Regenerative Medicine, Uniformed and the re-experiencing category of function and to develop novel Services University of the Health PTSD symptoms (e.g, flashbacks and treatment avenues for mesiotemporal Sciences, Bethesda, MD, 20814 nightmares), which explained 20% of epilepsy. Background: TBI and PTSD the variance seen in such symptoms More recently, X-ray microbeams have both been identified in large in those with combat TBI. We also have been used to explore the numbers of military service members identified that in our overall cohort, electrophysiological behaviour (SMs) after deployment to Iraq or 2 of 11 (18%) with combat of neurons contained inside the Afghanistan. PTSD and persistent TBI compared with 3 of 70 (4%) microbeam-transected primary symptoms related to TBI, which may without combat TBI developed PTSD sensory cortex in experimental be characterized as postconcussive on serial follow-up within 12 months models of chronic pain, a widespread syndrome (PCS), can be difficult to after return from deployment. invalidating neurological disorder distinguish. Moreover, TBI is by its Discussion: The links we report 54 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

between evidence of structural also be used for BCI (e.g. to drive daily for each electrode and remained impairment on DTI, functional prosthetic limbs or an exoscheleton). consistently at very low levels( connectivity on fMRI, and PTSD Materials and methods: ECOGIW- below 20 KOhm ). Somatosensory symptoms is suggestive of a 16E is a compact low-profile device evoked potentials and direct cortical relationship between TBI and PTSD. integrating an RF antenna and stimulation have been performed This relationship is further supported a flexible thin-film custom-made monthly , showing preserved ability to by our identification of a link between Neuronexus grid with 16 platinum map the sensorimotor cortex and to a single nucleotide polymorphism electrodes.The device has a square remotely evoke movements. (SNP) for the calcium binding protein size of 30 mm with a 11.7 mm height. S100B and the development of PTSD The grid size is 16 by 11,5 mm with Remote cortical stimulation was in our cohort, as SNPs for this protein a thickness of 50 µm.Electrode performed by the delivery of trains have previously been reported in diameter is 1,09 mm. Spacing across of 5 pulses of rectangular shapes at association with brain injury. Links electrodes is 3 mm. The device 1 Hz, with an interstimulus interval between TBI and PTSD warrant includes a microcontroller and the of 100 ms. Stimulus intensity was further assessment in future studies. transceiver module for implantable gradually increased in increments medical applications within MICS of 0.5 mA, starting at 1 mA, up to a band, a triaxial accelerometer, a maximum of 3 mA. During cortical Dan Perl stimulus generator, a sensor of stimulation of the motor cortex, temperature/load current and a movements of distinct portions of the Li-Ion battery (3,6V 350mA/h ISO right arm and hand were consistently 13485). The interface consumes 58mA (16CH @ 500SPS + TX_RF), observed with a stimulation intensity 30mA (16CH @ 500SPS) and 7mA in of 2 mA. The device was explanted standby.A dedicated cage equipped after 6 months. The grid was with RF coils was developed to allow encased within a dural layer and was seamless recharging. easily removed from the cortex. No Pantaleo Romanelli ECOGIW-16E was implanted in a adherence was found between the male macaque monkey (Macaca grid and the cortex. fascicularis, 6.95 kg). Experimental Conclusions: ECOGIW-16E is a fully protocol was approved by the regional implantable, externally rechargeable committee (Cometh Grenoble number 12/136_ Clinatec-NTM-01). The device providing wireless real time ECoG recording and brain mapping DR Pantaleo Romanelli, Scientific animal was anesthesized and secured through direct cortical stimulation. Director,AB Medica,Milano,Italy to a stereotaxic frame. Craniotomy was performed , placing the 16 ECOGIW-16E provides much longer A Fully-Integrated Externally contacts grid over the left sensori- recording times as compared to Rechargeable Wireless System motor cortex.Intraoperative stimulation those offered by current technology. for Long-Term Electrocorticography and motor cortex mapping was Research and clinical applications and Cortical Stimulation performed to confirm the correct grid include BCI and invasive monitoring of Introduction: Current techniques of placement. Dura was overlaid over epilepsy. This fully-integrated system the grid and craniotomy was closed. cortical recording for seizure focus can evolve into a closed-loop system The case was fixed above the skull localization and Brain Computer to abort promptly detected seizure immediately behing the craniotomy Interface( BCI) are limited by the activity in epilepsy patients. need to transfer the signal through opening using titanium plates and connecting wires. We have developed screws.The wound was washed and closed. a fully implantable,externally Daryl Kipke rechargeable wireless system Results: The device placement was (ECOGIW-16E ). This device provides not externally visible due to low-profile a highly innovative medium for the design. ECoG was daily recorded for localization and treatment of focal 6 months, maintaining excellent signal drug-refractory epilepsy but can quality. Impedance was recorded 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 55

Geoffrey Ling laws that require removal of players Confounding the development of from the game and assessment an appropriate concussion program by appropriately trained advanced is the weak evidence for many medical providers who must provide practices which are often surrounded written authorization before a player by strongly held opinions regarding can return to play. their effectiveness. A desire to do Diagnosis and Treatment of Mild TBI/ something, even if ineffective, at least Concussion makes all concerned “feel” like they James Ecklund are positively impacting the problem. Geoffrey Ling, MD, PhD We will describe our development of Mild traumatic brain injury (TBI) or a community concussion program concussion is finally being recognized across Northern Virginia, spanning 5 as a serious medical condition. hospitals and several counties. The As a result, organized medicine is organization, process of development actively developing evidence based Building a Community Concussion and care, lessons learned, educational clinical practice guidelines (CPG) Program efforts, and research opportunities will be addressed. to help medical providers meet Concussion has received a significant patient needs. This effort is based amount of attention over the last 5-10 largely on the highly successful years. This increased awareness both “Guidelines for the Management by the medical community and the Breakout Session 11 of Severe Traumatic Brain Injury” public has had a profound effect on created by the Joint Committee Stem cell technology and tissue many sports. NFL football in America engineering of the American Association of has changed the rules to ban certain Neurological Surgeons (AANS) and hits and limit the exposure of athletes Chair: John Whitelock the Congress of Neurosurgery (CNS) to plays that pose higher risks for & Jean Paul Allain in 1996. It is now in its 3rd iteration concussion. During the 2013 season, which was published in 2007. Just the NFL mandated that neurological recently, in 2013, the American trauma experts, predominantly Academy of Neurology published neurosurgeons, be present on each the “Summary of evidence-based sideline for every NFL game. The US guideline update: Evaluation and military has also recognized the risk management of concussion in sports: for concussion and mild head injury Ernst Wolvetang (Keynote) Report of the Guideline Development during combat operations and as a Subcommittee of the American result of blast exposure. They have Academy of Neurology.” In 2009, the developed a robust program firmly US’s Veterans Administration and embedded in regulation to identify, Dept of Defense together published monitor, and treat soldiers with their “Clinical practice guidelines: potential concussion. Fortunately, Management of Concussion/mild this increased vigilance at the very Human induced pluripotent cells is Traumatic Brain Injury.” This was visible national level trickles down tools to study neurological diseases. followed soon after in 2012 with the to youth sports where a public Ernst Wolvetang, Assoc. Prof Stem Canadian “Guidelines for mild TBI and awareness and demand for expert Cell Biology, Group leader Stem Cell persistent symptoms.” All of these concussion care in local communities Engineering Group have similar approaches which are has emerged. Developing a program Australian Institute for Bioengineering removing victims from further risk, to meets the needs of a community and Nanotechnology, University of allowing opportunities for recovery requires a multidisciplinary effort Queensland, Brisbane, St Lucia, QLD, and treating symptoms. Return to that recognizes the many interested 4072, Australia. work or play should be assessed parties and stakeholders. This using provocative evaluation clinical includes multiple medical and social Investigations into the of etiology tools. In the US, 49 states and disciplines, school systems, youth neurodegenerative diseases have the DC have adopted concussion sports leagues, and sports trainers. been frustrated by a lack of access 56 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

to developing human tissues, and Living electrodes: Tissue engineering to directly contact excitable tissue. the limited ability of mouse models the neural interface These studies provide further evidence to recapitulate complex human that conducting polymer hybrids with Conductive hydrogel electrode nervous system diseases, creating hydrophilic polymers can provide soft, coatings for optimal neural interfacing a need for new human cellular bioactive interface with neural tissue model systems. We have adopted Dr Rylie Green for applications such as the cochlear human induced pluripotent stem Graduate School of Biomedical implants, bionic eye devices and deep cells (hIPSC) as our model system Engineering, University of New South brain stimulators. of choice. To reveal pathogenic Wales, Sydney, 2052, Australia mechanisms hIPSC from neurological Conducting polymers (CPs) offer diseases such as Down syndrome John Whitelock (Keynote) advantages over conventional (DS) and Ataxia-Telangiectasia (A- metal electrodes by providing a T) we differentiate integration-free lower strain mismatch with tissue, iPSC into cell types relevant to the and greater capacity for charge disease, such as cortical neurons, injection, while presenting options astrocytes and cerebellar granule for modification with biological cells. We employ CRISPR and TALEN molecules. However, most CPs Mapping the Neural Extracellular based genome editing tools to used in biomedical applications tend Matrix: Potential Biomarkers of probe the gene regulatory networks to be brittle and friable, which has Neurodegenerative Disorders. underlying pathogenesis (such as in limited their applicability in implant DS) as well as for generating disease Mast cells are derived from electrodes. Conducting hydrogel models in isogenic backgrounds haematopoietic progenitors that are (CH) coatings provide an interesting (such as Prader-Willi syndrome). known to migrate to and reside within new approach to tailoring the neural In each case our approach is to connective and mucosal tissues combine cell phenotypic analyses, interface by further decreasing the where they differentiate and respond including calcium reporters, with strain mismatch while encapsulating to various stimuli by releasing pro- transcriptome analysis to identify the CP within a soft, deformable inflammatory mediators including the molecular processes underlying hydrogel matrix. In addition, the histamine, growth factors and pathogenic phenotypes that can use of a hydrogel component proteases. This study demonstrated be identified in vitro. Using this provides the potential for delivery that primary human mast cells as strategy we have identified early of therapeutic agents to promote well as the rat and human mast cell developmental phenotypes and regeneration of diseased neurons. A lines, RBL-2H3 and HMC-1, produce Alzheimers disease-like changes in DS typical CH consists of a biosynthetic the heparan sulfate proteoglycan, neurons, mitochondrial and calcium hydrogel integrated with a CP, such perlecan, with a Mr of 640kDa as handling changes in A-T neurons, as poly(ethylene dioxythiophene) well as smaller molecular weight developmental changes in A-T (PEDOT). The hydrogel is a co- species of 300 and 130kDa. Utilizing cerebellar granule cells and a neuronal polymer of poly(vinyl alcohol) (PVA) domain-specific antibodies coupled activity dependent LncRNA potentially and a modified biological molecule. with N-terminal sequencing it was involved in schizophrenia. Collectively Varying the type of biomolecule has confirmed that both forms contained our research provides evidence that allowed the properties of the CH to the C-terminal module of the protein iPSCs are useful tools for dissecting be tailored such that specific cells will core known as endorepellin, which the mechanisms of complex human interact with the electrode coating. were generated by mast cell-derived neurological diseases and, potentially, Studies have been conducted to proteases. Domain specific RT-PCR for testing of novel therapeutics. establish CH efficacy as an electrode experiments demonstrated that coating and explore in vivo tissue transcripts corresponding to domains responses. Furthermore, the ability I and V, including endorepellin, were Rylie Green to present and deliver biomolecules, present however mRNA transcripts including gene constructs has been corresponding to regions of domain investigated. Finally, this concept has III were not present suggesting that been advanced such that neural cells these cells were capable of producing can be embedded in the CH coating, spliced forms of the protein core. thereby creating a “living electrode”, Fractions from mast cell cultures that 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 57

were enriched for these fragments Alex Fornito Michael Valenzuela were shown to bind endothelial cells via the a2b1 integrin and stimulate the migration of cells in “scratch assays”, both activities of which were inhibited by incubation with either anti-endorepellin or anti-perlecan Mapping context-dependent changes Plastic Network Responses in Aged antibodies. This study shows for the in brain functional networks using Brains to Lifestyle-based Intervention first time that mast cells secrete and event-related graph analysis process the extracellular proteoglycan Associate Professor Michael perlecan into fragments containing Monash Clinical and Imaging Valenzuela the endorepellin C-terminal region Neuroscience, School of Leader, Regenerative Neuroscience that regulate angiogenesis and matrix Psychological Sciences and Monash Group, Brain and Mind Research turnover, which are both key events in Biomedical Imaging, Monash Institute, University of Sydney wound healing. University Aged brains exhibit network and Cognition emerges from complex connectivity degradation that is more and dynamic patterns of coordinated pronounced in dementia. Importantly, Breakout Session 12 activity in spatially distributed neuronal a large part of this is likely to be ensembles. These patterns can Brain Networks environmentally determined. In other be studied by analyzing statistical words, by enriching the brain’s dependencies—also called functional Chair: Perminder Sachdev environment we may be able to connectivity—between activity attenuate, normalise or even reverse recordings measured in distinct many of these network changes. In brain regions. Functional magnetic this presentation, Associate Professor resonance imaging (fMRI) has Michael Valenzuela will provide emerged as a popular and powerful

tool for studying the functional direct evidence from his group’s connectivity of large-scale brain animal research as well as human Michael Breakspear (Keynote) networks, though most published neuroimaging studies that show that literature to date has focused on physical exercise as well as intense examining so-called resting-states mental exercise can have powerful in which subjects lie quietly in the network restorative properties. scanner without performing any Moreover, these positive network explicit task. This work has led to effects are linked to improvement important new insights into brain in overall memory and cognition, Brain Connectomics functional organization, although suggesting these may be key Recent technical and methodological its applicability to understanding mechanisms by which lifestyle-based advances now make a complete cognition is limited because it does interventions can help preserve and description of the “wiring diagram” not consider neural activity during enhance brain function. of the brain a distinct possibility. active task performance. In this talk, However summary statistics are I will describe recently developed required in order to achieve a methods that allow quantification of Wei Wen meaningful description of these task-related modulations of functional connectomic data. To address this connectivity that are scalable to the problem, imaging and systems analysis of whole-brain networks. I will neuroscientists are turning to complex demonstrate how these techniques network theory. In this talk I will can be leveraged to map dynamic reconfigurations of large-scale neural highlight the major challenges and Structural topological organisation breakthroughs in this exciting field. systems in response to changing task of the elderly brain conditions, and to understand how these changes relate to individual Alistair Perry1, Perminder Sachdev1, differences in cognitive performance. Anbupalam Thalamuthu1, Michael 58 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Breakspear2, Wei Wen1 an additional analysis, we were able Gilles Guillemin to demonstrate the continuation of Prior investigations of human brain traditional hemispheric lateralization in structural networks have primarily older age, as well as sex differences focused on healthy young adults in asymmetry in line with previous and clinical samples. We aimed to literature. examine age-related changes in structural topological organisation In a separate study using the Mapping of the tryptophan using diffusion-weighted imaging same sample, we examined the metabolism in physiological and (DWI) scans. To do so, the present correlational relationship between pathological conditions study investigated a cognitively cognition and brain connectivity. healthy sample drawn from the The cognitive domains included Sydney Memory and Ageing Study, processing speed, memory, language, Breakout Session 13 which is a longitudinal study of visuospatial, and executive functions. community-dwelling, non-demented We examined the association of Neuroimaging genetics individuals aged 70 and above. We these cognitive assessments with Chair: Perminder Sachdev also sought to investigate whether both the connectivity of the whole & Peter Schofield both hemispheric asymmetry and sex brain network and individual cortical differences in structural networks are regions. We found that the efficiency present in this older population. of the whole brain network of cortical To investigate structural organisation, fibre connections had an influence on we derived edge-wise calculations, processing speed and visuospatial and also connectivity measures and executive functions. Correlations at the nodal, regional, lobar, core- between connectivity of specific network and global levels. Recent regions and cognitive assessments Margaret Wright investigations of human structural were also observed, e.g., stronger networks have primarily focused on connectivity in regions such as network hubs and more recently, superior frontal gyrus and posterior rich-club organisation. Regions that cingulate cortex were associated have been found to bi-hemispherically with better executive function. participate in rich-clubs of traditional Similar to the relationship between The ENIGMA Projects: identifying parcellation methods include the regional connectivity efficiency and genetic loci for brain structure and precuneus, thalamus, putamen, age, greater processing speed was function hippocampus and superior parts of significantly correlated with better Margaret J. Wright1, Paul M. frontal and parietal cortices. Rich connectivity of nearly all the cortical Thompson2, Nicholas G. Martin1, clubs of high-resolution networks regions. Barbara Franke3, Gunter Schumann4, additionally include the limbic, frontal, We conclude from our data that age Derrek P Hibar2, Sarah E Medland1, temporal, parietal and occipital has an impact on the organisation of Jason L Stein5, Alejandro Arias regions. However, our study revealed the structural brain connectome. The Vasquez3, Miguel E. Renteria1, and that structural connectivity was presence of hemispheric asymmetry The ENIGMA Consortium6 primarily distributed along ventral and sex differences in the older visual pathways, especially within the Introduction: Findings from twin connectome are consistent with the right hemisphere. Notably, there was a and family studies show that a topological organisation reported marked absence of highly connected substantial amount of the variance in the previous literature. Our data sub-cortical and frontal regions in the human brain, as measured by provides further evidence on the in our older sample, suggesting a imaging, is due to genetic factors. relationship beween organization of shift in topological organisation with In order to have sufficient power to the brain network and cognition. age. Lobar level analysis provided identify these genetic variants, and further support for a topological 1. University of New South Wales, Sydney, Australia to take advantage of the scale that shift, as the presence of left frontal 2. QIMR Berghofer Medical Research Institute, consortium approaches can bring, regions in core networks was found Brisbane, Australia in December 2009 we founded the to significantly decrease with age. In Enhancing Neuro Imaging through 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 59

Meta-Analysis (ENIGMA; http:// Discussion: Our findings show 65 years and over. A subsample with enigma.loni.ucla.edu/) Consortium. that with large sample sizes specific neuroimaging data available (N=414) While the primary aim of ENIGMA is SNPs are associated with imaging was used for these analyses. T1-MRI to conduct large-scale GWAS meta- phenotypes for brain structure. Similar scans were used for computation analyses of imaging phenotypes, efforts may soon begin to reveal loci of cortical and subcortical structure this effort has expanded to include for white matter structure as well as measures using either FreeSurfer or prospective meta-analyses of imaging functional connectivity. FSL. Cortical thickness was calculated phenotypes to identify how mental 1. QIMR Berghofer Medical Research Institute, for (i) each voxel and (ii) for 34 different illnesses affect the brain. Brisbane, Australia gyral regions of interest (ROI). Vertex- Methods: The ENIGMA Consortium 2. University of Southern California, Los Angeles, US wise (surface deformation-shape) includes 28 groups from 5 continents 3. Radboud University Medical Centre, Nijmegen, and ROI data was collected for seven The Netherlands with the majority of these groups subcortical structures: thalamus, 4. King’s College London, UK caudate, putamen, pallidum, contributing both MRI and GWAS 5. University of California Los Angeles, US data from either case-control or hippocampus, amygdala, nuclear 6. Full author list is at http://enigma.ini.usc.edu/the- accumbens. Heritability estimates population studies. Currently, data enigma-consortium are available for a total of 29,000 were obtained using variance individuals from 46 cohorts. Each components models for cortical thickness (voxel-wise, ROI) and of the groups in ENIGMA analyse Karen Mather vertex-wise (shape) for the subcortical their own data using standardized surfaces of the 7 brain structures. protocols to harmonise the extraction Genetic correlations between bilateral of the imaging phenotypes, as well subcortical structures and cortical as quality assessment, genetic thickness ROIs were assessed using imputation, and genetic association. bivariate variance components model Association analyses control for age, Heritability and genetic correlations of as implemented in the package age2, sex, 4 MDS components, cortical and subcortical structures in SOLAR. intracranial volume (ICV), and disease a cohort of community-dwelling older status (if applicable). Data are then Results: The mean heritability of adults combined across sites using the the voxel-wise analysis for cortical inverse variance-weighted meta- Wei Wen1, Anbupalam Thalamuthu1, thickness was ~0.5. Cortical thickness analysis framework implemented in Karen A. Mather1, Wanlin Zhu2, Jiyang ROI heritability estimates varied with METAL. Jiang1, Margaret J. Wright3, David low to high values observed. Mean 4 1 heritability for the shape of subcortical ENIGMA’s first project (ENIGMA1) Ames , Perminder S. Sachdev ,OATS structures ranged from 0.23 for the was a genome-wide association Research Team right amygdala to the 0.72 for the left study identifying common variants Introduction: As the population thalamus. To examine lateralisation of associated with hippocampal volume is ageing, a greater understanding genetic influence on the cortex and or intracranial volume. Continuing of the genetic contributions to subcortical structures, ROIs were work is exploring genetic associations human brain structure at older ages used. Genetic correlation analysis with subcortical volumes (ENIGMA2) will assist in the elucidation of the suggested strong bilateral genetic and white matter microstructure pathways associated with normal symmetry in the brain for these (ENIGMA-DTI). and pathological brain ageing. Prior measures. Results: Our GWASMA of seven research suggests brain structures Conclusions: In this study we report subcortical volumes and intracranial have moderate to strong heritability. a comprehensive examination of volume, has identified SNPs at five loci However, few studies have examined heritability for both cortex voxel-wise that surpass the cutoff for genome- the heritability of the shape of and subcortical surface deformation. wide significance (p<5×10(-8)) in the subcortical structures. Nor have To our knowledge, it is one of primary analysis. The strongest effects the genetic correlations between the first to estimate heritability for are found for the putamen and the bilateral hemispheric structures been subcortical shape measures. We hippocampus. Another five loci show considered. also demonstrated strong bilateral suggestive associations (p<1×10(-7)). Methods: The Older Australian Twins genetic symmetry across the right We are currently attempting replication Study recruited twins from the eastern and left hemispheres for cortical and of these SNPs. states of Australia who were aged subcortical ROIs. The information 60 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

from this study will be used to inform The order and magnitude of amyloid accumulation. Finally, before further studies aiming to identify the pathologic processes in Alzheimer’s hypometabolism, a hypermetabolic genetic correlates of brain structure in disease (AD) are not well understood, phase was identified for some cortical older adults. partly because the disease develops regions, including the precuneus 1. University of New South Wales, Sydney, Australia over many years. Autosomal dominant and posterior cingulate. Additional 2. Beijing Normal University, Beijing, China AD has a predictable age at onset and analyses of individuals in which 3. QIMR Berghofer Medical Research Institute, provides an opportunity to determine longitudinal data were available Brisbane, Australia, 4National Ageing Research the sequence and magnitude of suggested that an accelerated Institute, Royal Melbourne Hospital, Victoria, pathologic changes that culminate in appearance of volumetric declines Australia symptomatic disease. approximately coincides with the In this prospective, longitudinal onset of the symptomatic phase of the disease. Peter Schofield study, we analyzed data from 128 participants who underwent baseline Increased concentrations of tau clinical and cognitive assessments, protein in the CSF and an increase brain imaging, and cerebrospinal in brain atrophy were detected 15 fluid (CSF) and blood tests. We used years before expected symptom the participant’s age at baseline onset. Cerebral hypometabolism assessment and the parent’s age and impaired episodic memory were Neuroimaging and Biomarker at the onset of symptoms of AD to observed 10 years before expected Changes in Dominantly Inherited calculate the estimated years from symptom onset. Global cognitive Alzheimer’s Disease expected symptom onset (age of impairment, as measured by the Peter R Schofield1, John C Morris2, the participant minus parent’s age Mini–Mental State Examination and Randall J Bateman2, Tammie LS at symptom onset). We conducted the Clinical Dementia Rating scale, Benzinger2, Anne M Fagan2, Chengjie cross-sectional analyses of baseline was detected 5 years before expected Xiong2, Alison Goate2, Nick C Fox3, data in relation to estimated years symptom onset, and patients met Daniel S Marcus2, Nigel J Cairns2, from expected symptom onset in diagnostic criteria for dementia at an order to determine the relative order Xianyun Xie2, Tyler M Blazey2, David average of 3 years after expected and magnitude of patho-physiological M Holtzman2, Anna Santacruz2, symptom onset. changes. Virginia Buckles2, Angela Oliver2, We found that autosomal dominant Krista Moulder2, Paul S Aisen4, Concentrations of amyloid beta (Aβ)42 AD was associated with a series of Bernardino Ghetti5, William E Klunk6, in the CSF appeared to decline 25 patho-physiological changes over Eric McDade6, Ralph N Martins7, Colin years before expected symptom decades in CSF biochemical markers L Masters8, Richard Mayeux9, John M onset. Aβ deposition, as measured by of AD, brain amyloid deposition, Ringman10, Martin N Rossor3, Reisa positron emission tomography with and brain metabolism as well as A Sperling11, Stephen Salloway12, the use of Pittsburgh compound B, progressive cognitive impairment. Our Clifford R Jack Jr13, Robert A was detected in nearly every cortical results require confirmation with the region 15 years before expected Koeppe14, Yi Su2, Marcus E Raichle2, use of longitudinal data and may not symptom onset. Reduced cortical Abraham Z Snyder2, Beau M Ances2, apply to patients with sporadic AD. glucose metabolism and cortical Jon J Christensen2, Lindsay Ercole2, thinning in the medial and lateral References: Russ C Hornbeck2, Angela M Farrar2, parietal lobe appeared 10 and 5 y, Bateman et al. New England Journal Medicine 2012, 2 2 Patricia Aldea , Mateusz S Jasielec , respectively, before estimated age 367; 795-804. 2 2 Christopher J Owen , Xianyun Xie , of onset. Importantly, however, a Benzinger et al. Proceedings of the National Academy 6 of Sciences USA 2013, 110; E4502-4509. Adam Brinkman9, Chester A Mathis , divergent pattern was observed Paul M Thompson10, Andrew J 1. Neuroscience Research Australia, Sydney, NSW, subcortically. All subcortical gray- Australia Saykin5, Keith A Johnson11, Stephen matter regions exhibited elevated 2. Washington University, St Louis, MO, USA Correia12, Christopher Rowe15, Victor PiB uptake, but despite this, only 3. University College London, London, UK L Villemagne15, Sebastien Ourselin3, the hippocampus showed reduced 4. University California San Diego, San Diego, CA, 3 16 David M Cash , Michael W Weiner , glucose metabolism. Similarly, USA for the Dominantly Inherited Alzheimer atrophy was not observed in the 5. Indiana University, Indianapolis, IN, USA Network (DIAN). caudate and pallidum despite marked 6. University of Pittsburgh, Pittsburgh, PA, USA 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 61

7. Edith Cowan University, Perth, WA, Australia provide a valuable foundation for from AAV- CMV-hG-CSF by gene 8. University of Melbourne, Melbourne, VIC, Australia advancing our understanding of therapy will protect the brain from 9. Columbia University, New York, NY, USA why the brain may be sensitive to ischemia – induced brain injury in 10. University California Los Angeles, Los Angeles, neuropathophysiological processes at a process that is similar to what CA, USA different points of the adult lifespan. we observed recently in therapy 11. Brigham and Women’s Hospital, Harvard University, Boston, MA, USA employing exogenous hG-CSF 12. Butler Hospital, Brown University, Providence, protein, and (2) multimodal magnetic RI, USA Philip Liu resonance imaging (MRI) quantitatively 13. Mayo Clinic, Rochester, MN, USA measures neuroprotection in living 14. University of Michigan, Ann Arbour, MI, USA brains associated with gene delivery 15. Austin Health, Heidelberg, VIC, Australia in bilateral carotid artery occlusion 16. University California San Francisco, San Francisco, (BCAO) of C57black6 mice. CA, USA Methods: Brain damage was induced Brain Mapping and Therapy using bilateral carotid artery occlusion Monitored by Genetic Imaging; (BCAO) for 60 min in C57black6 Mayuresh Korgaonkar A Preclinical Platform mice. We applied longitudinal MRI to monitor brain damage and repair 1 1 Philip K. Liu , Iris Chen , Howard by gliogenesis, microglia activation 2 2 Prentice and Jang-Yen Wu and angiogenesis in living brains Introduction: Cardiac arrest, heart by MRI (Fig 1). We have made AS failure and stroke are the number sODN for hG-CSF to monitor the Heritability of neural structure and one cause of death in developed delivery of hG-CSF cDNA after AAV- connectivity changes across the adult countries. Patients who survive these CMV-hG-CSF vector application lifespan – results from the TWIN-E episodes, regardless of age, gender (post BCAO, 4 x 109 fpu in 2 ul, eye study. or race, are at high risk for developing drops). Our sODNs targeting matrix metalloproteinase-9 (MMP-9), glial How much of the adult brain’s neurological disorders, and there are fibrillary acidic protein (GFAP), c-Fos, heritable structure and connectivity few viable interventions available to FosB, Actin or Nestin mRNA was can be modified by the environment is monitor tissue damage in vivo before linked to superparamagnetic iron presently unknown. Previous studies and after treatment. Granulocyte oxide nanoparticles (SPION, a T2 have established that neural structure, colony-stimulating factor (G-CSF) is a susceptibility agent, 4mg Fe per kg) quantified by grey matter indices, cytokine that stimulates growth and or gadolinium (1 ug), all delivered and neural connectivity, quantified by differentiation of myeloid precursors. In by non-invasive intraperitoneal (i.p.) white matter integrity, are moderately addition, G-CSF has neuroprotective injection. Angiogenesis, gliogenesis, heritable. During development into properties in animal models of neurogenesis, microglia activation adolescence, heritability increases Parkinson disorder, stroke, Alzheimer and BBB leakage are monitored in with maturation. However, it remains demintia and other neurodegenerative vivo and validated by histology using unknown if heritability remains diseases. Protein therapy using electron and optical microscopies and constant over adulthood. This talk G-CSF is attractive because G-CSF is by RT-qPCR ex vivo. will present neuroimaging data from well tolerated after systemic delivery 252 twin pairs aged 18-60 years to and its receptor is expressed in Results: The survival rate of evaluate the moderating effects of neurons. However, its plasma half- C57black6 mice by 60 min BCAO is age on heritability of brain structure life is about 4 hours; moreover, there 5 out of 38 mice in two experiments. and connectivity. Here we show is potential for chronically elevating Gene therapy using AAV-CMV-hG- that both structure and connectivity white blood cells during repeated CSF improves survival rate (2 of 3 have significant regionally specific protein delivery. One alternative is to and 3 of 3 in another two trails). Mice changes in heritability with age. These administer human G-CSF (hG-CSF) treated with AAV-CMV-hG-CSF after data provide a valuable insight into encoded by a viral vector –namely a BCAO show less brain damage by the gene-environment mechanisms replication deficient adeno-associated genetic imaging using SPION-nestin that may underlie the ongoing virus (AAV) in conjunction with direct by MRI. changes in brain development over monitoring of delivery. Our hypotheses Conclusion: The significance of the adult lifespan. The findings also are that (1) the expression of G-CSF this project is in correlating gene 62 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

delivery and the accompanied interventions. Investments are unlikely Glenn Cross neuroprotection. This is the first step to be made unless returns on those in translating longitudinal MRI of brain investments can be realized. Returns repair without biopsy during therapy are made possible through licensing throughout the life time of patients of patented inventions, trade secrets, afflicted with neurodegenerative and other intellectual assets (IP). disorders. Patents provide rights to their owners Acknowledgement: Supported to exclude others from using the Bob Williamson by the Boston Area Diabetes patented invention. Trade secrets may Endocrinology Research Center be taking on a more significant role. [P30DK057521-14 (J Avruch)], A world-wide strategy for protecting DA029889 and EB013768 (PKL), intellectual assets requires knowledge B Welcome Foundation (HP). The of different countries’ policies, MRI system was funded in part by laws, and procedures. Patent laws NIH (S10RR025563) to the Martinos continually evolve, and recent court Center for Biomedical Imaging. decisions relating to diagnosis and Breakout Session 15 1.MGH/HST AA Martinos Center for Biomedical treatment creates ongoing challenges Stem Cells & Clinical Translation Imaging, Department of Radiology, CNY149 (2301) to understanding how intellectual Thirteenth St. Charlestown, MA property laws are interpreted and Chair: Uli Schmidt & Michael 2.Florida Atlantic University, Department of Biomedical Morris Science Boca Raton, FL USA enforced. All countries now use a form of a “first to file” patent regime that severely penalizes inventors for Breakout Session 14 disclosing inventions before filing a patent application. Examples will Commercial and Community illustrate some of the challenges and Considerations in Personalised opportunities available. With properly Uli Schmidt (Keynote) Medicines combining business, technology, and Chair: Megan Munsie the law, commercializing important & Caroline Gargett innovations will result in improved patient care, recognition of innovators’ contributions, and business success, all of which can lead to improvements Huntington’s disease-affected human in health care. embryonic stem cells as a model of mitochondrial dysfunction and Alfredo Martinez-Coll metabolic disturbances Ben Borson (Keynote) Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a glutamine expansion in the huntingtin protein. Research has indicated dysfunction in a myriad of Commercialization and Protection of Megan Munsie systems, including mitochondrial and Intellectual Assets in Brain Disorders ubiquitin/proteasome complexes, Bringing improvements in assessing cytoskeletal transport, cell signalling conditions of the Brain requires and transcriptional regulation. We substantial investment in research, examined the earliest molecular development of devices, and methods pathway malfunctions by conducting for diagnostic and therapeutic a comparative shotgun proteomics 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 63

study of HD-affected and unaffected autocrine-like, promoting development Mirella Dottori human embryonic stem cells (hESC), in embryos cultured at low density the earliest non-genetically engineered but not when they are cultured at human cell type available for in vitro high density. Another set of amino research. We also showed a shift acids antagonise these effects, while from mitochondrial dysfunction to other amino acids promote early transcriptional dysregulation and pre-implantation development before Multipotent caudal neural progenitors cytoskeletal abnormalities during becoming toxic to development derived from human pluripotent stem development, by conducting a second thereafter. cells that give rise to lineages of the study of HD-affected and unaffected central and peripheral nervous system hESC terminally differentiated to a ES cells, which are derived from 1, 2 3, culture of neural cells. The ability of the inner cell mass cells of the Mark Denham , Kouichi Hasegawa 4,Trevelyan Menheniott5, Ben Rollo5, hESC to mimic HD pathology offers pre-implantation embryo, are also responsive to development/directed Dongcheng Zhang5, Shelley Hough1, insight into pathology initiation, 5 differentiation by selected amino Samiramis Ighaniyan , Jessie Leung aetiology and progression while 1 5 5 acids. Here we show that LIF, the , David Elliott , Donald F Newgreen , potentially leading to novel therapeutic Martin F Pera1, 6, 7 and Mirella Dottori1,8 targets. ligand responsible for ES-cell self- renewal, together with L-proline The caudal neural plate is a distinct promote neurogenesis of mouse ES region of the embryo that gives rise Michael Morris cells via a series of embryologically to major progenitor lineages of the relevant cell types including epiblast- developing central and peripheral like pluripotent primitive ectoderm, nervous system, including neural germ-layer-like multipotent definitive crest and floor plate cells. We show that dual inhibition of the GSK3b ectoderm and neurectoderm (the first and activin/nodal pathways by cells of the developing neural system). small molecules differentiate human Amino acids act as growth factors to Inhibitor studies and kinome array pluripotent stem cells directly into an stimulate embryo development up to analysis show that L-proline works early OCT4-/SOX2+/PAX6- caudal and including early neurogenesis by (i) rapidly changing the activity of neural progenitor cell (CNP), which signalling pathways already stimulated 1,2 are equivalent to progenitors of the Michael B. Morris , Rachel by LIF and (ii) acutely activating 1,2 3 embryonic caudal neural plate. CNPs Shparberg , Fernando Felquer additional signalling pathways. can efficiently generate neural crest, 3 Nancy Hamra3, Anna C. Lonic , floor plate, roof plate and caudally- 2 1 These results indicate that selected Mariana Todorova , Sukran Ozsoy , specified neuroepithelial cells. Neural 1 1 Mark Zada , Matthew Zada , Sarah amino acids have growth factor-like crest derived from CNPs differentiated Faigenbaum1, Margot L. Day1 properties in early development up to neural crest derivatives and to and including early neurogenesis. We have shown that selected amino demonstrated extensive migratory They point to (i) a cheap and reliable acids act as a novel class of small- properties in vivo. Our studies define a means of improving the culture molecule growth factor, able to novel progenitor derived from human conditions of embryos to be used pluripotent stem cells, which is the cooperate with other growth factors for assisted reproduction and (ii) the precursor to major caudal lineages of and cytokines to promote (i) pre- development of protocols of directed the embryonic neural tube. implantation embryonic development differentiation of ES cells to neural and (ii) the directed differentiation 1. Department of Anatomy and Neurosciences, University of Melbourne, Australia of ES cells across sequential cell types suitable for use in animal models of CNS disease and injury. 2. Danish Research Institute of Translational developmental stages out to early Neuroscience, Aarhus University, Denmark neurogenesis. 1. Bosch Institute and Physiology, School of Medical 3. Institute for Integrated Cell-Material Sciences, Kyoto Sciences, University of Sydney University, Japan In cultured mouse embryos, selected 2. Centre for Developmental and Regenerative 4. InStem, NCBS, India amino acids stimulate development Medicine, Kolling Institute of Medical Research, 5. Murdoch Children’s Research Institute, Australia to the hatching blastocyst stage. Royal North Shore Hospital, Sydney, Australia 6.Walter and Eliza Hall Institute, Australia The mechanism does not appear 3. School of Biomedical Science, University of 7. Florey Institute of Neuroscience and Mental Health, Adelaide, Australia Australia to be a simple metabolic effect nor 8. Centre for Neural Engineering, University of is it an osmolyte effect. Instead, it is Melbourne, Australia 64 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Amanda Capes-Davis cell cultures for obvious quality Plenary Session 5 concerns. Preclinical work does not New frontiers in brain science have the regulatory requirement for quality control laid down as part Geoffrey Ling of Good Manufacturing Practice. Neurologist, Defence Advanced However, basic quality control and Research Projects Agency Spontaneous transformation of stem characterisation is part of Good (DARPA) USA cells in vitro: Believe it or not? Cell Culture Practice and should be performed routinely and integrated 1,2 Amanda Capes-Davis into preclinical cell culture work. Spontaneous transformation of human Essential quality control adult stem cells was first published includes testing for Mycoplasma in 2005. Two studies reported that contamination; and authentication This is an exciting time for human mesenchymal stem cells testing to exclude cross- (MSCs), derived from adipose tissue neuroscience. There is an expanding contamination. For human cell lines, and bone marrow, spontaneously appreciation for the potential that short tandem repeat (STR) profiling overcame senescence to proliferate innovations developed in brain indefinitely in cell culture and form allows comparison to commonly used science will have profound positive tumours in nude mice. The risk of cell lines worldwide. The International implications for patients throughout tumour development was a serious Cell Line Authentication Committee the international community. In concern for scientists and clinicians (ICLAC) maintains a database of cell particular, in April, 2013, President working towards the therapeutic lines that are known to be cross- Obama announced his BRAIN use of MSCs. But subsequent contaminated, in many cases from the initiative. The acronym BRAIN stands publications showed that not all was time the cell line was first established. for Brain Research Advanced through as it seemed on the surface. In 2010, It is advisable to check the database Innovative Neurotechnologies. The MSC cultures in both studies were before beginning work with any new last word, neurotechnologies is key. shown to be cross-contaminated by cell line. It refers to the need for new tools unrelated cancer cell lines. Results For stem cells, in addition to quality that will enable neuroscientists to were therefore artefacts of the cell control, it is important to perform test hypotheses, open new lines of culture process and irrelevant to MSC characterisation and stability testing. investigation and to innovate. To this research. New stem cell lines should be end, the NIH, NSF and DARPA have Spontaneous transformation of assessed for pluripotency, stability been charged by the President to MSCs has now been conclusively of karyotype and phenotypic invest over $100M of uncommitted demonstrated in rodent models, characteristics. Every effort should be 2014 funds to begin his initiative. This where MSCs are prone to made to keep cells at low passage is being matched by a number of chromosomal abnormalities. MSCs by freezing down stocks in a “master private organizations such as the Allen from other species appear to be more bank”, with a second “working bank” Institute, Howard Hughes Medical stable. Spontaneous transformation to provide stocks for day-to-day Institutions, Kavli Foundation and of human MSCs has finally been requirements. the Salk Foundation. DARPA has demonstrated in vitro, following already issued a number of requests authentication testing to exclude These simple measures will help to for proposals through its Broad cross-contamination. However, make ongoing stem cell research Agency Announcement process. transformation of human MSCs more reliable, avoiding the common Specifically, DARPA seeks to develop appears to be a rare event that only problems that affect many cell culture neurotechnologies that will enable occurs after long-term culture. Clinical based projects. study of neuropsyciatric disease, trials suggest that the risk of tumour 1. CellBank Australia, Children’s Medical Research mesoscale neuronal activity (100K-1M development in vivo is low, although Institute, Westmead NSW 2145, www. neurons) and memory. Other requests ongoing vigilance is required. cellbankaustralia.com. will be forthcoming over the next year 2. International Cell Line Authentication Committee, as well. The introduction of the brain What can we learn from this complex iclac.org. story? A great deal of confusion science tools will be both enabling could have been avoided by testing and transformative. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 65

of cellular-level features also show Rasul Chaudary unprecedented detail within the Plenary Session 6 so-called white matter substance, revealing an interwoven system of New structural maps of the axonal fibers. The challenge, presently, Brain is to make sense of the seemingly Jacopo Annese insurmountable complexity with Promise of Embryonic and Adults Director, The Brain Observatory, white and gray matter and produce Stem Cells for Neural Regeneration USA discrete templates that can, in spite of individual variability, be generalized 1,3 Chaudhry G R, 1,3McKee C, for translational applications. In other 1,3 Beeravolu NR, 2,3Dinda S, words, neuroanatomy, in the XXI 3,4Perez-Cruet M. Century has become the virtualization It is projected that one of three and standardization of brain tissue. individuals in the United States could benefit from regenerative medicine New Structural Maps of the Brain therapy in their lifetime. Many of these The study of human brain anatomy Breakout Session 16 individuals suffer from damage of the has undeniably made a comeback in central nervous system, including neuroscience and this is due largely Neural Stem Cells and degeneration of the intervertebral disc to the sophistication of the techniques Regeneration (IVD) and retina upon aging as well and concepts that are applied to as neurodegenerative diseases such the study of neural architecture. Chair: Rasul Chudary & Ann as Parkinson’s, Alzheimer’s and ALS. At a macroscopic scale and in the Turnley De novo regeneration is particularly clinical domain, we have seen a difficult due to the lack of renewing shift of emphasis from mapping the capability of neural cells and tissues. topography and morphology of gray We have successfully accomplished matter compartments to tracing proliferation, differentiation and interconnections of neural parcels integration of neuro-progenitors and via white matter fibers. At the other chondro-progenitors in animal models end of the scale, digital technologies Brent A Reynolds (Keynote) of retinal and IVD degeneration, boost the scope of microscopic and respectively, using embryonic stem nanometric models of brain tissue. cells. Because of moral and ethical We are at the exciting stage where it controversies concerning the use has become conceivable and even of embryonic stem cells, we sought practical to represent and measure alternative sources to regenerate the anatomy of a whole human skeletal and neural tissues of nervous Building Better Brains: From Theory brain at the cellular level; that is, the system. This has led us to isolate adult to Reality meso-scale level. Gray still matters; stem cells from umbilical cord tissue cytological parameters, such as For the better part of the past century and blood which have shown potential neuronal number, size, and cortical it was a well held belief that the adult to differentiate into chondrogenic layer organization are still extremely mammalian brain did not have the and neural cells in vitro. Recently, relevant to the clinical neurosciences. capacity to repair itself. The discovery we have derived a mouse stem cell This knowledge, if formalized at of neural stem cells in the early 1990’s line which can be differentiated into the system level, can also bridge opened the door to the possibility chondro- and neuro- progenitors. The Connectome-era brain maps with of brain repair, however, this hope chondro-progenitors could be further older but still valuable human and and potential has yet to become a differentiated into chondrocytes and comparative data produced by reality. In the lecture we will look at the osteocytes expressing Col II and histological quantitative methods discovery of neural stem cells, explore Col I, respectively. Likewise, Neuro- and stereology. The combination of their potential and look forward to progenitors can be differentiated histology, 3-D reconstruction, and some of the applications of neural into neural cell types expressing algorithms for the automated analysis stem cell based therapies. Nef, TH and RHO. We also isolated 66 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

mesenchymal stem cells (MSCs) in the past 10 years underpin the / ex vivo models and generated from umbilical cord tissues which hypothesis that these disorders arise a suite of monoclonal antibodies were successfully differentiated into from neurodevelopmental deficiencies specific to 14-3-3ζ. These unique chondro- and neuro-progenitors. affecting the hippocampus and tools provide us the opportunity to Human MSCs derived chondro- prefrontal cortex. However, the unravel the molecular interactions progenitors differentiated into vast majority of underlying defects controlling neurodevelopment. Our cells capable of producing remain unknown. Due to this gap in work provides definitive support to glucosaminoglycans (GAG) and knowledge diagnosis is only made the neurodevelopmental origin of expressed Sox9, ACAN and Col on the presentation of debilitating psychiatric illness. Using a cross- II in vitro. Whereas, human neuro- clinical symptoms, including disciplinary approach we are progenitors differentiated into neural positive (psychosis), negative (social addressing several of the outstanding cell types expressing Tuj1. Future withdrawal) and cognitive defects issues in the field. Such findings are studies are focused on determining (working memory). expected to significantly progress our the potential of these progenitors to understanding of neurodevelopment We recently found that the regulatory regenerate and restore function of and neurodevelopmental disorders. protein 14-3-3ζ plays an essential damaged IVD and neural tissues in role in neuronal migration, dendritic vivo. arborization and axonal growth. Using Ann Turnley 1. Department of Biology, Oakland University our unique neurodevelopmental 2. School of Health Sciences mouse model of schizophrenia 3. OU-WB Institute for Stem Cell and Regenerative and related disorders we have Medicine, Oakland University, Rochester, MI, USA, demonstrated that 14-3-3ζ mutant 4. Beaumont Health System, Royal Oak, MI, USA. mice have many of the anatomical and behavioural defects associated What will it take to make endogenous Quenten Schwarz with the human condition. Using this mouse model we are now addressing adult neural stem cells repair the adult which brain defects underpin the nervous system? aetiology of schizophrenia-like It has been known for two decades symptoms. The centrosome / dynein that the adult brain contains niches motor complex controls many of neural stem cells that normally neurodevelopmental processes produce new neurons in the Understanding the origin of that are thought to be disturbed subventricular zone of the lateral neurodevelopmental disorders in neuropsychiatic illness. At the ventricles and the dentate gyrus of the Hayley Ramshaw, Xiangjun Xu, molecular level, we have found hippocampus. Since their discovery Eiman Saleh, Zarina Greenberg, that 14-3-3ζ interacts with and a lot of effort has been spent, with Peter McCarthy, Angel Lopez and maintains phosphorylation of the limited success, to enhance the Quenten Schwarz. core centrosome protein, Ndel1, ability of these neural stem cells to to regulate neuronal migration. Our Centre for Cancer Biology, SA promote repair after injury or disease data also show that 14-3-3ζ interacts of the nervous system. Not only does Pathology, Adelaide, Australia. with DISC1, a known schizophrenia production of neural precursor cells Neurodevelopmental disorders risk factor, raising the possibility of need to be increased to generate such as schizophrenia, autism, distinct functions for 14-3-3ζ / DISC1 sufficient numbers for repair, the epilepsy and intellectual disability interactions in neuronal migration precursor cells need to migrate to the encompass a highly prevalent / synapse / axonal formation. site of damage, differentiate into the group of defects thought to arise These biochemical interactions right sort of neuron or glial cell and, from impaired development of the suggest that 14-3-3ζ interacts with perhaps most importantly, survive brain. Despite a limited range of the DISC1 / Ndel1 complex to and integrate appropriately into the antipsychotic drugs masking clinical promote neurodevelopment. One local neural circuitry. Most newborn symptoms, current medications of our key aims is to understand neurons that are produced die within have significant levels of chronic the biological relevance of these 1 month of their generation and so relapse and associated functional interactions. To address this question do not contribute to regeneration. impairment. Biomedical advances we have established several in vivo Factors that regulate each of these 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 67

steps – proliferation, migration and involuntary sustained or spasmodic 11 major improvement (88%). The differentiation will be discussed, with muscle contractions involving co- improvement was maintained for up a focus on our current work aiming contraction of the agonist and the to 29 months (mean follow-up 13 to promote survival and integration of antagonist. The movements are [SD 9] months). Adverse effects were newborn neurons following traumatic usually slow and sustained, and mild and could be eradicated by brain injury to improve functional they often occur in a repetitive and reduction or cessation of stimulation. outcome and neural repair. patterned manner; however, they can This reversibility and adaptability, be unpredictable and fluctuate. allowing control of side-effects, make thalamicstimulation preferable Scientific approach: Medication to thalamotomy, especially when treatment of all three disorders could Breakout Session 17 treatment of both sides of the brain slow down disease but not improve Brain Neuromodulation in is needed. its outcome. Scientists have been the Treatment of Epilepsy, looking for the brain target and its Thalamic stimulation has been Parkinson’s and ALS modulation to achieve better clinical proposed to treat disabling tremor. result. The aims of this multicentre study were to evaluate the efficacy and Basal ganglia and thalamus the morbidity of thalamic stimulation become the center of interest of in a large number of patients with Chair: Evgeny Tsimerinov scientist and neurologist. Hirotaro parkinsonian or essential tremor. Narabayashi constructed a stereotaxic One hundred and eleven patients apparatus based on drawings of were included in the study and 110 that constructed in the United States were implanted either unilaterally or by Victor Horsley and Robert H. bilaterally. Patients were evaluated Clarke and in 1951 performed the with clinical scales, before and up first stereotactic pallidotomy on an to 12 months after surgery. Upper athetoid child. The next year he and lower limb tremor scores were Evgeny Tsimerinov (Keynote) performed a procaine oil blocking reduced in both groups. Eighty five of the pallidum of a patient with per cent of the electrodes satisfied Parkinson’s disease, successfully the arbitrary criteria of two point abolishing the rigidity and tremor reduction in rest tremor reduction in symptomatic of this disease. the parkinsonian tremor group and The usefulness of high- 89% for postural tremor reduction Brain Neuro Modulation in Treatment frequency stimulation of the in the essential tremor group. In the of Parkinson’s, Tremor and Dystonia ventralintermediatenucleus (Vim) as parkinsonian tremor group, limb Objectives: Parkinson disease (PD) is the first neurosurgical procedure in akinesia and limb rigidity scores were one of the most common neurologic disabling tremor was assessed in 26 moderately but significantly reduced. disorders, affecting approximately patients with Parkinson’s disease and Thalamic stimulation was shown to 1% of individuals older than 60 6 with essential tremor. 7 of these be an effective and relatively safe years and causing progressive patients had already undergone treatment for disabling tremor. This disability that can be slowed, but thalamotomy contralateral to the procedure initially applied in a very not halted, by treatment. Essential stimulated side, and 11 others had limited number of centres has been tremor, the most common movement bilateral Vim stimulation at the same successfully used in 13 participating disorder, is a syndrome of unknown time. Chronic stimulating electrodes centers. etiology characterized by a slowly connected to a pulse generator Multicentre European study of progressive postural and/or kinetic were implanted in the Vim. Tremor thalamic stimulation in essential tremor, usually affecting both upper amplitude at rest, during posture tremor: a six year follow up. extremities. Fundamental debate holding, and during action and exists as to whether essential tremor intention manoeuvres was assessed Sydow O, Thobois S, Alesch F, is a neurodegenerative disease. by means of accelerometry. Of the Speelman JD. SourceDepartment Dystonia (from Greek, meaning altered 43 thalami stimulated, 27 showed of Neurology, Karolinska Hospital, muscle tone) refers to a syndrome of complete relief from tremor and Stockholm, Sweden. 68 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Thalamic stimulation is an efficient Disease Questionnaire (PDQ-39), and use of a computerised minimisation treatment for disabling essential the severity of symptoms without procedure to immediate surgery tremor, as previously shown, but medication, according to the Unified (lesioning or deep brain stimulation follow up has mostly been short term. Parkinson’s Disease Rating Scale, part at the discretion of the local clinician) 37 patients with essential tremor had III (UPDRS-III). Pairwise comparisons and best medical therapy or to best implantation of a thalamic stimulator, showed that neurostimulation, as medical therapy alone. Patients were either unilaterally or bilaterally. The compared with medication alone, analysed in the treatment group results at one year have been reported caused greater improvements from to which they were randomised, earlier. After six years, 19 patients baseline to six months in the PDQ- irrespective of whether they received were available for follow up. The 39 (50 of 78 pairs, P=0.02) and the their allocated treatment. The main instrument for evaluation was UPDRS-III (55 of 78, P<0.001), with primary endpoint was patient self- the essential tremor rating scale. mean improvements of 9.5 and 19.6 reported quality of life on the 39-item The patients were examined with points, respectively. Neurostimulation Parkinson’s disease questionnaire pulse generators turned on and off. resulted in improvements of 24 to (PDQ-39). At 1 year, surgery and best In the majority of patients, the very 38 percent in the PDQ-39 subscales medical therapy improved patient self- good results with stimulation seen for mobility, activities of daily living, reported quality of life more than best at one year were maintained after a emotional well-being, stigma, medical therapy alone in patients with mean of 6.5 years. The reduction in and bodily discomfort. Serious advanced Parkinson’s disease. These tremor scores and improvement in adverse events were more common differences are clinically meaningful, activities of daily living were highly with neurostimulation than with but surgery is not without risk and significant compared with baseline medication alone (13 percent vs. targeting of patients most likely to and with the stimulation turned off. 4 percent, P<0.04) and included a benefit might be warranted. There were few serious adverse fatal intracerebral hemorrhage. The events. Minor side effects related overall frequency of adverse events Bilateral globus pallidus internus to stimulation were common. A few was higher in the medication group (GPi) deep brain stimulation (DBS) device related complications were (64 percent vs. 50 percent, P=0.08). in a patient with severe idiopathic observed and most could be resolved. In this six-month study of patients generalized dystonia resulted in Good reduction in tremor can be under 75 years of age with severe immediate improvement of all maintained for more than six years in motor complications of Parkinson’s aspects of dystonia. During joystick the majority of these severely disabled disease, neurostimulation of the movement, GPi DBS reduced patients. Thalamic stimulation can subthalamic nucleus was more PET activation bilaterally in the be recommended in essential tremor effective than medical management primary motor, lateral premotor, where there is insufficient response to alone. (ClinicalTrials.gov number, supplementary motor, anterior drug treatment. Surgical procedures NCT00196911 [ClinicalTrials.gov].). cingulate, and prefrontal areas and and follow up should be concentrated ipsilaterally in the lentiform nucleus. Surgical intervention for advanced in relatively few centers, which will Altering basal ganglia function with Parkinson’s disease is an option thereby acquire a high degree of GPi DBS reverses the overactivity of if medical therapy fails to control expertise. certain motor cortical areas present in symptoms adequately. We aimed Dystonia. Neurostimulation of the subthalamic to assess whether surgery and nucleus reduces levodopa-related best medical therapy improved In 22 patients with generalized motor complications in advanced self-reported quality of life more Dystonia bilateral DBS showed Parkinson’s disease. We compared than best medical therapy alone in average 55% improvement at this treatment plus medication patients with advanced Parkinson’s 12 months follow up. Significant with medical management. In this disease. The PD SURG trial is an improvement is seen in 40 patients randomized-pairs trial, we enrolled ongoing randomised, open-label with primary Generalized and 156 patients with advanced trial. At 13 neurosurgical centres in Segmental Dystonia at 3 month Parkinson’s disease and severe motor the UK, between November, 2000, follow up. In sham stimulation only symptoms. The primary end points and December, 2006, patients with 15% improvement is seen. 46% were the changes from baseline Parkinson’s disease that was not improvement average is at 6 months. to six months in the quality of life, adequately controlled by medical Up to 80% improvement is at 3 year as assessed by the Parkinson’s therapy were randomly assigned by follow up and thereafter. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 69

Conclusion: Brain Neuro Modulation for the treatment of epilepsy. Its recovery with therapy delayed 6 especially DBS is a safe procedure use has been extended not only in months from the time of the stroke. with predictable AEs knowing different types of epilepsies, but other Rat studies have demonstrated the anatomy and functional topography. 1. conditions, comorbid with epilepsy. ability of VNS therapy to promote AEs are classified and reported in the More studies have become available functional recovery from traumatic long-term mostly as hardware- and offering deep brain stimulation of brain injury and a clinical study has stimulation-related; 2. Bradykinesia the anterior thalamus, responsive been approved. Publicly available and gait difficulties have been neurostimulation, and trigeminal nerve information on these studies will be observed long-term bilateral pallidal stimulation for treatment of refractory presented. epilepsies. The mechanisms of action, DBS, completely reversible when Co-authors: R. Terry1. switching off the stimulation or using and efficacy of new neurostimulation devices are reviewed, and the key 1. Medical Device Consulting, BK Consulting, more dorsally located active contacts; Houston, USA. Three suicides have been reported in advantages and disadvantages are patients with dystonia after DBS, all discussed. of them had depression before DBS; Ashraf Elsayegh Three suicides have been reported in patients with dystonia after DBS, all of Reese Terry them had depression before DBS.

Tony DeSalles Management of Respiratory Failure in ALS The Brain-Vagus-Heart Connections: Therapeutic Investigations I will be discussing briefly the different Implantable vagus nerve stimulation respiratory issues that are a challenge

(VNS) for the control of epilepsy for ALS patients. I will discuss different Future Applications of Brain began 25 years ago in November treatment options including devices Neuro Modulation in Treatment of 1988. More than 70,000 epilepsy that are helpful in reducing day to Parkinson’s and Neurodegenerative patients have been treated worldwide day respiratory struggles. The crux Disorders with VNS therapy. This therapy has of my talk will concentrate on a opened the understanding of the relatively new device (the diaphragm brain-vagus-heart connections, pacemaker). I will discuss indications Lilit Mnatsakanian which have led to investigations into of this device, the workup required, potential new therapies. The heart the actual implantation technique, and responds to seizure activity prior to our experience with the diaphragm EEG changes and these changes pacemaker here in our center. in heart rate are being investigated in clinical studies in Europe and the Evgeny Tsimerinov Advances in Technology in the US as a method of seizure detection Treatment of Epilepsy for activation of VNS therapy. Vagus nerve stimulation is being One-third of people with epilepsy will investigated by several companies fail antiepileptic drug therapy. Epilepsy as a potential method of treating surgery can offer a potential cure congestive heart failure and animal from disabling seizures. However up studies suggest the potential of VNS Modern Technologies of Neuro and to 40 % of patients suffering a drug- to acutely reduce infarct size. Vagus Brain Modulations in Treatment of ALS resistant epilepsy, might not qualify stimulation has been demonstrated Evgeny I. Tsimerinov, MD, PhD for surgical treatment. The field of to reduce the infarct size in rat focal neurostimulation for epilepsy has ischemia and to improve functional Objectives: Amyotrophic Lateral grown dramatically since the vagus recovery. VNS therapy is currently Sclerosis (ALS) is a uniform world- nerve stimulation became available being clinically investigated for stroke wide distributed disorder with 70 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

incidence of 2-3 per 100,000/year. modest but significant slowing of patients is warranted. The results of Overall 1.5 to 2; male to female the deterioration rate. Though the the pilot study might open up a new ratio is 2.1 to 1.8. Time of disease authors cannot be sure whether the therapeutic perspective in ALS based onset is usually 65-74 (male±10.2; effects observed can be attributed on neuromodulation. female±7.4). Prevalence 3-8 per to cTBS, because of the restricted Preliminary data suggest that 100,000, and risk increases with number of patients studied, further repetitive transcranial magnetic age au to 74. It affects upper (UMN) investigation on a larger group of ALS stimulation (rTMS) of the brain may and lower (LMN) motor neurons. It patients is warranted. The results of produce a modest slowing of disease affects UMN in the primary motor the pilot study might open up a new progression in amyotrophic lateral cortex, Brodmann’s area 4 and the therapeutic perspective in ALS based sclerosis (ALS). The present study premotor areas, Brodmann’s area on neuromodulation. 6 (secondary motor complex and was designed to test the hypothesis premotor complex); Betz’s giant Repetitive transcranial magnetic that rTMS given as continuous theta pyramidal neurons are the distinct stimulation (rTMS) of brain can burst stimulation (cTBS), repeated group of neurons in layer 5 and other modulate cortical neurotransmission, monthly for one year, would affect ALS smaller neurons; corticospinal and a novel paradigm of repetitive progression. A double blind, placebo- corticobulbar tracts and reticular stimulation termed continuous controlled trial of patients with ALS formation and limbic system. LMN theta-burst stimulation (cTBS) were randomly allocated to blinded locates in the brainstem and spinal produces a pronounced and real or placebo stimulation. cTBS of cord, anterior horn cell. prolonged suppression of motor the motor cortex was performed for cortex excitability. The aim of this five consecutive days every month for Scientific approach: Repetitive preliminary study was to investigate one year. Primary outcome was the transcranial magnetic stimulation whether cTBS of motor cortex could rate of decline as evaluated with the (rTMS) of brain can modulate cortical have any beneficial effect in patients revised ALS functional rating scale neurotransmission, a novel paradigm with amyotrophic lateral sclerosis (ALSFRS-R). Treatment was well of repetitive stimulation termed (ALS). We performed a double-blind, tolerated. There was no significant continuous theta-burst stimulation placebo-controlled trial. Twenty difference in the ALSFRS-R score (cTBS) produces a pronounced and patients with definite ALS were deterioration between patients treated prolonged suppression of motor randomly allocated to blinded active with real or placebo stimulation. cortex excitability. The aim of this or placebo stimulation. Repetitive ALSFRS-R mean scores declined preliminary study was to investigate stimulation of the motor cortex was from 32.0 (SD 7.1) at study entry to whether cTBS of motor cortex performed for five consecutive days 23.1 (SD 6.3) at 12 months in patients could have any beneficial effect in every month for six consecutive receiving real cTBS and from 31.3 (SD patients with amyotrophic lateral months. 6.9) to 21.2 (SD 6.0) in those receiving sclerosis (ALS). A double-blind, placebo stimulation. Although cTBS The primary outcome was the rate placebo-controlled trial of 20 patients proved a safe procedure, on the of decline as evaluated with the with definite ALS were randomly basis of the present findings a larger ALS functional rating scale. The allocated to blinded active or placebo randomized confirmatory trial seems treatment was well tolerated by the stimulation. Repetitive stimulation of unjustified in ALS patients, at least in patients. Fifteen patients (seven the motor cortex was performed for advanced stage of the disease. five consecutive days every month active and eight sham) completed for six consecutive months. The the study and were included in the From April to July 2002, four primary outcome was the rate of 6-months analysis. Both active and consecutive patients affected by decline as evaluated with the ALS sham patients deteriorated during amyotrophic lateral sclerosis (ALS) functional rating scale. The treatment treatment, however, active patients were surgically treated with bilateral was well tolerated by the patients. showed a modest but significant chronic cortical stimulation. The Fifteen patients (seven active and slowing of the deterioration rate. preoperative diagnostic assessment eight sham) completed the study Though we cannot be sure whether was based on the results of a and were included in the 6-months the effects observed can be attributed neurological examination, integrated analysis. Both active and sham to cTBS, because of the restricted by the ALS functional rating scale, patients deteriorated during treatment, number of patients studied, further electromyography, magnetic however, active patients showed a investigation on a larger group of ALS resonance imaging, and single-photon 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 71

emission computed tomography Inpatient Sample, an administrative as high as 60. Using this protocol, (SPECT). In particular, SPECT database representing 20% of U.S. there were no failures to extubate or provided a remarkable contribution hospitals, 1,600 hospitalizations in 30-day mortalities. The DPS system in terms of its ability to demonstrate patients with ALS were identified and increases the respiratory system specific morphological and metabolic compared with 5,364,728 non-ALS compliance by decreasing posterior ALS lesions of the brain. These hospitalizations. The most common lobe atelectasis and can stimulate preliminary results are surprising, concurrent diagnoses in patients respirations at the end of each case. because they suggest that chronic with ALS were dehydration and Laparoscopic surgery with general cortical stimulation can play a role malnutrition (574 patients, 36%), anesthesia can be safely performed in against ALS and deserve confirmation pneumonia (507 patients, 32%), and patients with ALS undergoing DPS. in larger numbers of patients and for respiratory failure (398 patients, 25%). Conclusion: Concomitant Brain a longer follow-up. We present the Only 38% of patients with ALS were and peripheral nervous system theoretical grounds for these findings, discharged to home without home modulations of UMN and LMN by as well as the diagnostic and surgical health care compared with 73% using modern advanced technologies procedures and results. of patients with non-ALS. Fifteen percent of patients with ALS died should significantly improve survival Humanitarian Device Exemption Post- rate of patients suffering from ALS Approval Study of NeuRx Diaphragm in the hospital compared with 3% Pacing System for Amyotrophic of non-ALS patients. The average Lateral Sclerosis is approved on length of hospital stay and charges 9/28/2011. were greater for patients with ALS Breakout Session 18 than for non-ALS patients (8.4 days Forty four patients treated at Cedars- and $19,810 for ALS patients and Biomaterials and The Brain Sinai Medical Center, Los Angeles, 5.4 days and $11,924 for non-ALS Therapeutics California since December of 2011. patients). Mortality was significantly TBC FVC <45 was not predictive of lack associated with emergency room of response to direct diaphragm admission (versus nonemergency stimulation. 72% of those with low admission; OR = 1.60), increasing FVC and positive direct stimulation age (per year; OR = 1.03), respiratory had bulbar involvement. Both phrenic failure (OR = 3.37), and pneumonia Breakout Session 19 nerve conduction and fluoroscopy (OR = 2.02) Electrodes and Electrochemistry were predictive of intraoperative There is a paucity of literature in Brain Mapping response in the majority of cases concerning general anesthesia and (82%). Both pre-operative studies surgery in patients with amyotrophic Chair: Justin Gooding had false positives. Discordant results lateral sclerosis (ALS or Lou Gehrig’s on phrenic nerve conduction and disease). This report summarizes the fluoroscopy were not explained by largest series of surgical cases in ALS duration between workup and surgery. during multicenter prospective trials Currently planned clinical trials using of the laparoscopic diaphragm pacing minimum phrenic amplitude of 0.1 mV system (DPS) to delay respiratory Evgeny Tsemerinov (Keynote) should expect a nonplacement rate failure. The overall strategy outlined of ~18% due to lack of DNS in the includes the use of rapidly reversible operating room. short-acting analgesic and amnestic As ALS progresses, extensive agents with no neuromuscular supportive care is required, including relaxants. Fifty-one patients were multidisciplinary outpatient care and implanted from March 2005 to March Modern Brain NeuroModulation in hospitalization. The authors studied 2008 at 2 sites. Age at implantation Neurologic Disorders the causes, health care utilization, ranged from 42 to 73 years and the Evgeny I. Tsimerinov, MD, PhD and outcomes for hospitalized percent predicted forced vital capacity patients with ALS. Methods: (FVC) ranged from 20% to 87%. On Objectives: Brain Neuromodulation With use of the 1996 Nationwide preoperative blood gases, PCO2 was with continuous or intermittent 72 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

stimulations is considered a delivery Epilepsy, Depression, and Autism. is an adjunctive therapy in reducing of electrical stimulation through the frequency of seizures in individuals Milestone comes 25 years after the implanted electrodes to the specific 18 years of age or older with partial first DBS implant for Tremor carried area of the brain using an implanted onset seizures who have undergone out in Grenoble, France, Medtronic, pulse generator. The goal is to deliver diagnostic testing that localized no Inc. announced that a patient therapeutic current that modifies a more than 2 epileptogenic foci, are from Kempenhaeghe-Heeze (The disease course and improves patient refractory to two or more antiepileptic Netherlands) is the first patient to be health and quality of life. medications, and currently have enrolled into the MORE (MedtrOnic frequent and disabling seizures Brain and Neural stimulations are used Registry for Epilepsy) Registry which (motor partial seizures, complex in the following Neurologic Disorders: is designed to look at the long-term partial seizures and/or secondarily Epilepsy, Depression, Parkinson, efficacy, quality of life impact and generalized seizures). The RNS® Tremor, Dystonia and ALS. safety of deep brain stimulation System has demonstrated safety (DBS) in patients with refractory Scientific basics and historical and effectiveness in patients who aspects: epilepsy. DBS for epilepsy received average 3 or more disabling seizures CE mark for use in Europe in August • 1938 Bailey and Bremer: VNS in per month over the three most recent 2010. Medtronic DBS Therapy is not cat elicited desynchronized orbital months (with no month with fewer currently approved by the U.S. Food cortex activity than two seizures), and has not and Drug Administration for use in been evaluated in patients with less • 1952 Zanchetti: intermittent VNS the United States for the treatment of frequent seizures. reduced or eliminated interictal refractory epilepsy. Anterior nucleus of epileptic effects chemically induced the Thalamus is a target for DBS. The effectiveness of responsive in focal cortex stimulation is sustained over years Aggression: In the final installment • 1980 Radna and MacLean: VNS in of follow-up. Combining data from to this three-part, essay-editorial on monkey caused marked single-unit all subjects treated with the RNS psychosurgery, we relate the history effects on basal limbic structures System, the responder rate, defined of deep brain stimulation (DBS) in as the percentage of subjects with a • 1985 Zabara: Postulated that VNS humans and glimpse the phenomenal 50% or greater reduction in seizures would antagonize hypersynchronous body of work conducted by Dr. Jose and shown in black, and the median seizure states Delgado at Yale University from the percent reduction in seizures, shown • First Animal Studies (J. Zabara, 1950s to the 1970s. The inception stippled, increases over the first 1 Temple University) of the National Commission for the two years after implant and is then • 1987 Cyberonics founded by Protection of Human Subjects of maintained in the 50% or higher Reese Terry Biomedical and Behavioral Research range even past 6 years for some. (1974-1978) is briefly discussed as • 1988 First Human Implant The numbers of subjects, shown on it pertains to the “determination of (Dr. Kiffin Penry) the x-axis, becomes smaller primarily the Secretary of Health, Education because subjects hadn’t reached that • 1992 First Randomized Active and Welfare regarding the time point as of the data cut-off. Control Study recommendations and guidelines on DBS was approved for a Parkinson’s The VNS Therapy System consists psychosurgery.” The controversial disease in 1997, but it is not an of an implanted pacemaker-like work — namely recording of brain accepted treatment for epilepsy at this generator and nerve stimulation activity, DBS, and amygdalotomy for time. Deep brain stimulation (DBS) electrodes, which deliver intermittent intractable psychomotor seizures in is an effective surgical treatment for stimulation to the patient’s left vagus patients with uncontrolled violence — medication-refractory hypokinetic and nerve that sends signals to the conducted by Drs. Vernon H. Mark hyperkinetic movement disorders, brain. Main mechanism of action is and Frank Ervin is recounted. and it is being explored for a variety increasing of Norepinephrine output Neuropace: New generation of smart of other neurological and psychiatric from the locus coeruleus that causes technology that recognizes specific diseases. Deep brain stimulation has cortical and limbic Neuromodulation. pattern and deliver treatment to the been Food and Drug Administration- VNS has been used in treatment of target in the brain. The RNS® System approved for essential tremor 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 73

and Parkinson disease and has a since my diagnosis. My diaphragm is and a distant monopolar return. humanitarian device exemption for the one muscle in my body that not Through acute in vivo testing in the Dystonia and obsessive-compulsive only stays the same, but has gotten feline, we have determined that the disorder. stronger. 90% of ALS patients choose effect of the of guard ring electrodes not to go on a ventilator. The pacer is that activation is largely contained Medronic, Inc. and Boston Scientific will help extend the decision while we to within the ring. However, activation are the leaders in this field and offer help find a cure.” June 2008 “I am not thresholds using this approach diversity of electrodes and IPGs for using a vent because of your device!” alone are approximately three times DBS. October 2009 (Augie Neito’s Story). higher with respect to monopolar Direct cortical stimulation with stimulation alone owing to inefficient, Conclusion: Brain Neurostimulation is Medtronic device patients with lateral shunting of the electric fields. the fruit of decades of both technical ALS: From April to July 2002, four By splitting a proportion of the return and scientific advances in the field of consecutive patients affected by current to a distant monopole, the basic neuroscience, neurology and amyotrophic lateral sclerosis (ALS) electric field is directed towards functional neurosurgery. were surgically treated with bilateral the target neurons. The monopolar chronic cortical stimulation. The Advances in Brain NeuroModulation component of the return current preoperative diagnostic assessment open New Era in Human fight against effectively reduces the threshold was based on the results of a Neurodegenerative Disorders and of activation while the guard ring neurological examination, integrated bring us Hope and Believe in Better component maintains the localisation by the ALS functional rating scale, and Healthier Future. of activation. QMP further affords the electromyography, magnetic possibility of delivering stimulation resonance imaging, and single-photon from multiple sites simultaneously with emission computed tomography Greg Suaning a significant reduction in cross-talk (SPECT). In particular, SPECT between stimulating sites relative to provided a remarkable contribution monopolar stimulation alone. in terms of its ability to demonstrate Discussion: The QMP stimulation specific morphological and metabolic paradigm provides the dual benefits ALS lesions of the brain. These of focused activation via guard-ring preliminary results are surprising, Electrodes in the supra-choroidal localisation with reduced stimulation because they suggest that chronic space for visual prosthesis – effecting thresholds of monopolar stimulation. cortical stimulation can play a role focused cortical activation against ALS and deserve confirmation Acknowledgement: This research Professor Gregg Suaning in larger numbers of patients and for was supported by the Australian Graduate School of Biomedical a longer follow-up. We present the Research Council (ARC) through its Engineering, University of New South theoretical grounds for these findings, Special Research Initiative (SRI) in Wales, Sydney, Australia as well as the diagnostic and surgical Bionic Vision Science and Technology procedures and results. Objective: To describe stimulation grant to Bionic Vision Australia (BVA). paradigms to achieve low-threshold Humanitarian Device Exemption Post- activation to effect selective Approval Study of NeuRx Diaphragm stimulation of retinal ganglion cells via Pacing System for Amyotrophic an electrode array implanted within Lateral Sclerosis is approved on the supra-choroidal space. 9/28/2011. Materials and Methods: A Forty four patients with ALS treated stimulation paradigm that we have at Cedars-Sinai Medical Center, Los described as ‘quasi-monopolar’ Angeles, California since December (QMP) divides the return-path of 2011. of stimulation across a ring of The Diaphragmic Pacer has been guard electrodes adjacent to and the single best decision I have made surrounding the stimulating electrode, 74 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Alex Harris Justin Gooding electrochemical biosensors based on immunoreagents. In this talk the application of these surfaces will be demonstrated for detecting antibiotics in biological samples and glycosylated haemoglobin (HbA1c). A Method for the Systematic in vitro Electrodes that resist protein fouling HbA1c is an important 3 month and in vivo Evaluation of Neural when used in biological fluids: biomarker for the effectiveness of Recording Electrodes Applications for biosensing, cell a diabetics treatment strategy. The biology and implantable electrodes second interface is similar to the first Alexander R. Harris interface where oligo(ethylene oxides) J. Justin Gooding, Alicia L. Gui, ARC Centre of Excellence for are used to provide antifouling ability Guozhen Liu, Abbas Barfidokht Electromaterials Science to the electrode surfaces and where Australian Centre for NanoMedicine New materials and designs for nanoparticles form the conducting and School of Chemistry neural implants are typically tested channels, essentially serving as separately, with a demonstration of The University of New South Wales, molecular wires. This interface is also performance but without reference Sydney, 2052 Australia applied to immunosensing for the to other implant characteristics. This [email protected] detection of HbA1c. precludes a rational selection of a The application of electrodes in The final system to be described is particular implant as optimal for a biological media is not only the basis a completely different strategy for given application and the development of many electrochemical biosensors making electrodes with antifouling of new materials based on the most but also an imperative for in vivo layers which is well suited for critical performance parameters. stimulating electrodes. The issue all implantable electrodes. The other Different electrode designs, materials electrodes have when being used in systems described all essentially and coatings affect neural recording biological media is fouling by proteins produce high impedance layers on performance through changes and cells. For stimulating electrodes electrodes and the molecular wire or to electrochemical, chemical and this increases the potentials that nanoparticles are required to provide mechanical properties. Comparison need to be applied to an electrode to conducting channels. With the third of electrodes in vitro is relatively allow it to stimulate the appropriate strategy we use zwitterions to provide biological response. For biosensors simple, however comparison of in the resistance to non-specific protein such fouling typically means poor vivo response is typically complicated and cell adsorption. Because other analytical performance or complete by variations in electrode/neuron antifouling moieties are just small failure of the device. This talk will distance and between animals. This organic molecules this means the present a number of novel strategies talk introduces a protocol for in vitro antifouling layer can just be a few and in vivo testing of neural recording to developing electrodes with antifouling layers. These effectiveness atoms long. Hence antifouling layers electrodes. This method eliminates can be produced which are low or reduces the impact of many of these modification layers in limiting electrode fouling will be demonstrated impedance, and hence perfect for systematic errors present in simpler and their utility in biosensing and as stimulating electrodes. in vivo testing paradigms, especially stimulating electrodes will be shown. variations in electrode/neuron distance and between animal models. Three different electrode modification The result is a strong correlation strategies to allow antifouling layers Breakout Session 20 between the critical in vitro and in vivo to be applied to electrodes will be Brain ‘All Omics’ responses, such as impedance and presented. The first type of electrode signal-to-noise ratio. construct is where oligo(ethylene Chair: Howard Federoff oxide) units provide antifouling and molecular wires are used to provide electrochemical communication. These interfaces are shown to be effective in the development of 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 75

Howard Federoff (Keynote) Brandon Wainwright 3. Institute for Molecular and Cellular Biology, Singapore 4. The Methodist Hospital Research Institute, Houston, USA.

Bryan Day An integrative functional genomics approach to defining key gene Brett Stringer networks in medulloblastoma. Laura Genovesi1, Melissa Davis2, Ching Ging Ng3, Nancy Copeland4, Neil Jenkins4 and Brandon EphA3 Maintain Tumour-Initiating Cells Wainwright1. and is a Therapeutic Target in Brain Cancer The Establishment and Medulloblastoma is the most common Characterisation of Patient-Derived malignant brain tumour of childhood. Bryan W. Day1, Brett W. Stringer1, Cell line and Mouse Models for Recent gene expression studies Fares Al-Ejeh1, Kathleen S. Ensbey1, Studying Glioblastoma have subtyped medulloblastoma Zara C. Bruce1, Paul R. Jamieson1, into four classes of tumor, “WNT”, Yi Chieh Lim1, Po Inglis2, Lindy Jeffree3 Brett W Stringer1, Bryan W Day1, Paul “SHH”, “Group3” and “Group 4”, and Andrew W. Boyd1 R Jamieson1, Kathleen S Ensbey1, each of which has a distinct clinical Zara C Bruce1, Po Inglis2, Rosalind Significant endeavor has been presentation and prognosis. Recent Jeffrey2, Andrew W Boyd1,3 applied to define markers of glioma whole genome sequencing studies stem cells (GSCs) and to identify Glioblastoma (GBM) is the have indicated that the tumours functional therapeutic targets in commonest form of primary brain have relatively stable genomes and glioblastoma (GBM) to halt the growth cancer and also the most lethal. one of the emergent themes is that of this aggressive cancer. This study Despite surgery, radiotherapy and there is a widespread deregulation identifies EphA3 as a functional, chemotherapy, the median survival of chromatin, potentially leading to targetable cell surface GSC marker in with this disease is only 14 months genome wide gene deregulation. At GBM. and the 5-year survival rate less than this point it is difficult to conclude as 10%. Part of the reason for this is to whether genomes studies have We show that the receptor tyrosine that GBM is a very heterogeneous identified strong candidates for new kinase EphA3 is over expressed in disease. Despite this, genome-wide therapeutic targets. We performed a GBM and in particular in the most approaches applied to GBM have functional screen in a mouse model aggressive mesenchymal stem-like identified several unifying themes. for SHH medullobaltoma using subtype. Importantly, EphA3 is highly the Sleeping Beauty transposon expressed on the tumor-initiating GSC Part of our approach to improve the to identify genes that cooperate population and is critically involved outlook for people with GBM has with SHH signalling to result in in maintaining tumor cells in an been to establish patient-derived cell medulloblastoma. We then took these undifferentiated state by modulating lines and xenograft mouse models genes and constructed networks MAPK signaling. EphA3 knock down that better capture the heterogeneity using a conservative protein=protein or depletion induced differentiation of this disease, both at the intra- and interaction approach. Surprisingly, we and reduced the GSC pool leading to inter-tumoural level. This presentation identified a number of networks that delayed orthotopic tumour formation will describe the establishment of all four medulloblastoma subtypes in mice. Specific targeting of EphA3 these resources, our characterisation have in common which have identified positive GSCs in vivo using a pay of them and how they are being used therapeutic targets that could be loaded EphA3 mAb, reduced GBM to evaluate potential therapeutic deployed against medulloblastoma tumour size and significantly increased targets and therapies for this disease. such as CDK4/6. survival while inducing minimal toxicity. 1. QIMR Berghofer Medical Research Institute 1. Institute for Molecular Bioscience, The University of 2. Royal Brisbane and Women’s Hospital Queensland, Australia While debate still surrounds the 3. Department of Medicine, The University of 2. Department of Electrical Engineering and NICTA, cancer stem cell hypothesis in Queensland The University of Melbourne, Australia solid tumors, such as GBM, 76 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

there is agreement that cells in an assessment protocols across five of biomarkers (genetic, epigenetic, undifferentiated state exist within independent sites in the USA and clinical, brain structural and functional) these highly heterogeneous tumors. Australia, at-risk subjects comprising which appear prior to conversion to These cells are thought to be adolescent and young adult (12- bipolar disorder will be conducted as responsible for tumor recurrence 30 years) offspring and siblings of the study progresses. Incorporating following treatment. Here, we patients with bipolar I disorder (n=369) information about polygenic risk, plus demonstrate that in EphA3-expressing and controls in the same age range early changes in brain structure and GBM, EphA3 is crucial in maintaining but without family history of mood function, will aid in the development of undifferentiated, tumor-initiating cells disorder or psychosis (n=229) have effective tools for risk prediction in the by modulation of MAPK signaling. been studied. future. EphA3 is lowly expressed in adult tissues and therefore represents a These individuals will be reviewed 1. Neuroscience Research Australia, Sydney, Australia relatively tumor-specific therapeutic annually for 5-10 years with structured 2. University of New South Wales, Sydney, Australia clinical and neuropsychological 3. Department of Medical and Molecular Genetics, target in GBM. Indiana University, Indianapolis assessments, and peripheral blood We acknowledge NHMRC Australia 4. Departments of Biochemistry and Molecular samples were collected at baseline. funding (App ID: 1023695) Biology, Medical and Molecular Genetics and Structural and functional brain imaging Center for Medical Genomics, Indiana University, Indianapolis data will be collected biannually on 5. Indiana Alzheimer Disease Centre, Indiana Jan Fullerton the Australian participants. Multimodal University, Indianapolis analysis will be conducted to identify 6. Department of Psychiatry, Washington University, molecular, clinical and environmental St Louis, Missouri risk factors which are associated with 7. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan later conversion to bipolar disorder. 8. Child Psychiatry & Public Health; Johns Hopkins

Results: Using a limited panel of University, Baltimore, Maryland Enrichment of polygenic risk alleles the most robust disease-associated 9. Black Dog Institute, Prince of Wales Hospital, Sydney, Australia in a longitudinal cohort at high-risk of SNPs, we show an increased genetic 10. Department of Psychiatry, Institute of Psychiatric bipolar disorder loading of risk alleles in European at- Research, Indiana University School of Medicine, risk individuals compared to European Indianapolis Fullerton JM1,2, Koller DL3, Edenberg controls at a group level (additive HJ4, Foroud T3, Liu H5, Glowinski AL6, allele-frequency-weighted model: GEE McInnis M7, Wilcox HC8, Frankland Wald χ2=4.53, one tailed p=0.017, A2,9, Roberts G2,9, Schofield PR1,2, Breakout Session 20a relative risk of score >0.30=1.28), Mitchell PB2,9, Nurnberger JI10 although the distribution of scores Clinical Neurology and Background: Bipolar disorder is a would not clearly define future Neurointerventions severe mood disorder with complex diagnostic status at an individual Chair: George Paxinos & etiology. Recent data has indicated level. We have preliminary findings Perminder Sachdev the highly polygenic nature of examining the impact of polygenic disease risk with many hundreds score on brain structure at baseline. of risk variants of small effect, but No significant difference in methylation also a small number of risk variants at any individual locus was observed reproducibly associated with bipolar at baseline between at-risk and disorder have been identified. control subjects on a group-wise However the molecular, biological, and basis. Bryce Vissel (Keynote) neuropsychological factors that are Discussion: Further analysis will associated with the onset of bipolar be conducted longitudinally, as disorder are largely unknown, and can participants who were at-risk of only be dissected through longitudinal developing bipolar disorder at baseline studies of high-risk individuals. convert to bipolar disorder diagnoses Methods: Using standardised clinical in subsequent years. Identification 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 77

Wieslaw Nowinski of anatomy and atlas of blood Eric Bailey supply territories. Atlas-assisted analysis provides the complete list of anatomical structures and blood supply territories along with their volume and percentage contributions 1 CAD systems for ischemic and to the infarct and penumbra . Ambulance based CT and its Impact hemorrhagic strokes The ischemic stroke CAD system for on Thrombolytic Therapy for Acute Ischemic Stroke Wieslaw L. Nowinski nonconstrast CT provides automatic Biomedical Imaging Lab, ASTAR, and rapid detection, localization and Author: Dr. Eric M. Bailey, CEO Singapore volume assessment of ischemic NeuroLogica Corporation, Subsidiary infarcts in a single scan. It first Stroke is a leading cause of death of Samsung Electronics, Danvers determines the intensity ranges of Massachusetts, USA. and the major cause of permanent cerebrospinal fluid, white matter disability. It has a great effect on and gray matter. Then, it separates Stroke is a devastating world health public health and causes high cost the brain scan into the left and right issue. In most developed countries for primary treatment, rehabilitation, hemispheres and, by analyzing the it is the 3rd leading cause of death. and chronic care. Despite a critical characteristics of intensity distributions Even more devastating, it is the need, there is no clinically accepted in the hemispheres, it detects, #1 cause of long term disability. and globally used computer-aided localizes and assesses volume of Economically it is a great burden on diagnosis/detection (CAD) system an ischemic infarct without its actual society, but with an age increasing for stroke yet, though there are a segmentation2. population, it is destined to become number of CAD systems in other even worse. Most strokes (80%) fields including mammography, The hemorrhagic stroke CAD are ischemic in nature and may colonoscopy, and chest cancer. system supports the evacuation of benefit from thrombolysis, the only hemorrhage by thrombolytic treatment available acute therapy. However, This talk presents an overview of CAD through a catheter inserted into the systems for stroke: two for acute thrombolysis is a time critical and ventricular system. This system aims potentially dangerous treatment that ischemic stroke (one supporting at progression and quantification atlas-assisted analysis of the diffusion- requires many steps. Brain imaging of blood clot removal. The clot is perfusion mismatch and the other is necessary in order for thrombolysis automatically segmented from CT providing processing of noncontrast to be administered safely. Because time series, its volume measured over CT) and one for hemorrhagic stroke. of the many time delays in transport time, and the process of clot lysis is and diagnostics, thrombolysis is The acute ischemic stroke CAD dynamically displayed and monitored. generally only given to 1-3% of the system supports thrombolysis. This CAD system has been employed total patients. The approach shifts the paradigm in the CLEAR clinical trial, phase 3. in stroke image processing from a This talk is about the author’s idea and These stroke CAD systems facilitate 2D visual inspection of individual ultimate creation of designing a small and speed up analysis of images, scans and maps to an atlas-assisted portable CT scanner to be installed increase confidence of interpreters, quantification and simultaneous in ambulances whereby diagnostics and support decision making. They visualization of multiple 2D and 3D could be performed at the point of are potentially useful in diagnosis and images. It provides rapid, automatic, pickup and thrombolytic treatment research, particularly, for clinical trials. and quantitative image analysis could be performed in situ. Such a and decision making support from References CT system has been designed and anatomy, diffusion, and perfusion 1. Nowinski WL, et al Analysis of ischemic stroke mobile stroke vehicles have been scans. The diffusion-perfusion MR images by means of brain atlases of anatomy installed in Germany, Norway, Russia, mismatch and the size of the infarct and blood supply territories. Academic Radiology and just recently the USA. This paper 2006;13(8):1025-34. versus that of the middle cerebral will show the different vehicles and artery territory are calculated. For 2. Nowinski WL, et al. Automatic detection, localization approaches that have been developed and volume estimation of ischemic infarcts in non- image quantification, two electronic contrast CT scans: method and preliminary results. and present some of the scientific brain atlases are employed: atlas Investigative Radiology 2013;48(9):6 findings that have been achieved. 78 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

On average, the call-to-thrombolytic activation, brain activation and The pattern of beta-band activity was therapy time has decreased by 40 functional movement ability. similar for each patient when tested minutes. This also lengthens the with less-affected side movements. In separate sessions 8 hemiparetic window for available patients thus Motor evoked potentials could be stroke patients 3-45 months possibly extending this therapy to elicited on the more-affected side post-stroke completed a 30% or more of potential stroke at rest in 4 patients with a mean magnetoencephalography scan patients. If this can be achieved on a threshold of 59.0±9.7% stimulator (MEG); magnetic resonance broad scale it will have a tremendous output, and during a 10% voluntary imaging (MRI); transcranial magnetic impact on stroke treatment and contraction in 5 patients at 47.0±2.5% stimulation (TMS) assessment of ultimate cost to society. stimulator output. WMFT-tt mean resting and active motor threshold; times were 71.4, 12.9, and 2.4 s, and motor-function assessments. for patients with low, moderate and Whole-head MEG recordings Penelope McNulty high motor-function, respectively. In consisted of 160 coaxial first-order and Christine Shiner 3 patients with poor motor-function gradiometers with a 50 mm baseline neither a resting TMS motor evoked while patients performed a unilateral potential nor a rebound beta- finger-tapping task. Both sides were resynchronisation was evident on the tested separately. Structural T1- more-affected side, although all had weighted MRI images were acquired motor evoked potentials on the less- for co-registration of MEG data affected side. The duration of both Investigating neuroplasticity post- and TMS threshold motor evoked beta-band phenomena was correlated stroke: contrasting bilateral differences potentials were recorded bilaterally with resting and active motor in magnetoencephalography, from the first dorsal interosseous thresholds and with upper-limb motor- transcranial magnetic stimulation muscle. Functional movement ability function. A longer desynchronisation and functional motor assessments was assessed using the Wolf Motor was correlated with higher thresholds Function Test timed-tasks (WMFT-tt) Penelope A McNulty and and poorer function (p<0.001) while and stratified as low, moderate or high Christine T Shiner a longer resynchronisation correlated based on performance on the Box Neuroscience Research Australia, with lower thresholds and higher and Block and grooved-pegboard Sydney, Australia function (p=0.002). tests of manual dexterity. School of Medical Sciences, These preliminary data suggest University of New South Wales, Two patients were classified with that post-stroke movement-related Sydney, Australia low, three with moderate, and three MEG beta-band activity is related to with high motor-function. Time- Hemiparesis, or a weakness on both corticomotor excitability and frequency MEG analysis revealed the side of the body contralateral motor-function on the more-affected different patterns of movement-related to the lesion is the most common side. In this study cortical beta- beta-band (13-30 Hz) activity that cause of impaired movement ability band activity was bilaterally affected was associated with motor-function after stroke. Other than natural after stroke even in patients with level. On the more-affected side recovery, rehabilitation remains the relatively preserved ipsilesional cortical there was a robust event-related only means of improving functional excitability and less-affected side desynchronisation of activity for movement, principally through motor-function. all patients during movement cortical reorganisation. Many neural execution, with no consistent pattern Keywords: magnetoencephalography, mechanisms contribute to cortical during movement preparation. The transcranial magnetic stimulation, reorganisation but the relative desynchronisation amplitude and functional assessment, stroke, cortical contribution and sequencing of duration was most prominent for low- reorganisation. individual components is not well functioning patients. An event-related understood. Improvements in rebound synchronisation of beta- behaviour and cortical reorganisation activity followed the desynchronisation cannot necessarily be inferred for patients with moderate motor- from each other. In this preliminary function, was prominent for patients multi-modal study we examined with high motor-function, but absent the relationship between muscle for patients with low motor-function. 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 79

Yih Yian Sitoh stimulation to relevant prefrontal brain Breakout Session 21a regions. The objective of this research CME Symposium, Intra- was to enhance the application of operative Brain Mapping rTMS treatment in depression by improving prefrontal stimulation target Chair: George Paxinos sites and localisation. Neuroimaging in Psychiatry Methods: First, we conducted The use of neuroimaging in psychiatric a functional imaging study and a quantitative meta-analysis to explore disorders has increased recently, with most of the work done under the region within the dorsal prefrontal research protocols. In clinical practice, cortex most implicated in the aetiology neuroimaging facilitates the diagnosis of depression. In addition, we George Paxinos of psychiatric disorders and can conducted a randomised controlled detect structural disorders and trial evaluating the relative efficacy of neurodegenerative conditions causing neuro-navigationally targeted rTMS. psychosis. Third we have developed methods

The clinical use of neuroimaging in using near infrared spectroscopy and psychiatry will increase in the near EEG to optimise coil placement in Brain, Behavior and Evolution future, particularly using MRI and prefrontal cortex. Standard atlases using identical molecular imaging techniques. It is Results: Functional imaging studies nomenclature enable scientists to important to appreciate the role and in patients with depression do not navigate seamlessly between the brain limitations of such techniques. provide a clear and well defined target of humans and experimental animals An overview of the more common for rTMS treatment. However, neuro- to test hypotheses inspired by human clinical conditions presenting with navigationally localising treatment considerations and relate data from psychosis and a summary of recent based on dorsolateral prefrontal experimental animals to humans. MRI based research findings in cortex structure does produce a In current atlas construction we make psychiatric disorders is presented. greater antidepressant response use of genes that are responsible than standard methods of rTMS for the segmentation of the brain application. Finally, NIRS and EEG in development (hox genes). Using Paul Fitzgerald methods appear to be able to be evidence from transgenic mice and used to improve aspects of prefrontal birds we are proposing a new plan coil placement. for the organization and function of certain brain regions of mammals. Conclusions: Improvements in the The brainstem, for instance, can no application of rTMS treatment are longer be considered as a container Enhanced neuroimaging based possible using a range of imaging of haphazardly arranged nuclei (as targeting to improve response to tools that can enhance coil placement potatoes in a sac), but instead as rTMS treatment in depression and localisation. Improvements in regions which co-vary (start and end) rTMS application are likely to arise with their neighbours. Objective: Repetitive transcranial from individualisation of treatment The human brain features many more magnetic stimulation (rTMS) is an well- site based on individual patient brain homologies with the brain of monkey established new treatment modality characteristics. for patients with depressive disorders. (eg, virtually all areas of the cortex are However, studies have consistently homologous), of the rat and of the bird indicated that the effect sizes with than previously thought. Areas which standard methods of rTMS application are shown to be homologous are likely are relatively limited. There are a to have similar function as for example are 9/46 of the prefrontal cortex number of issues which may limit which is homologous in human and the effectiveness of rTMS treatment, monkey and is involved in executive including methods of targeting 80 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

processing in working memory in both brain atlases is advantages. References: species. Anatomical and probabilistic functional 1. Nowinski WL. Computerized brain atlases for (electrophysiology- and imaging- surgery of movement disorders. Seminars in Using MR images in mice and non- based) atlases are complementary, Neurosurgery 2001;12(2):183-194. human primates we are attempting as the functional atlas is of a high 2. Nowinski WL. Anatomical and probabilistic to provide 3D volumes of canonical functional atlases in stereotactic and functional spatial resolution, dynamic, composed brains against which transgenic neurosurgery. In: Textbook of Stereotactic from theoretically unlimited number varieties with clinical significance can and Functional Neurosurgery (eds. Lozano A, of brain specimens, and consistent Gildenberg P, Tasker R), 2ed edition. Springer, Berlin be compared. in 3D, whereas the anatomical 2009:395-441. Finally, on the issue of evolution and atlas is deterministic, sparse, static, 3. Nowinski WL, et al. Simulation and assessment of cerebrovascular damage in deep brain stimulation survival, the brain is wonderful, but it based on a few brain specimens using a stereotactic atlas of vasculature and is not omniscient. Both the dazzling and inconsistent in 3D. Conversely, structure derived from multiple 3T and 7T scans. technological success of our species a low parcellated functional atlas is Journal of Neurosurgery 2010;113(6):1234-41. and the worrisome environmental enhanced by a highly parcellated degradation it has produced are anatomical atlas2. reflections of the function of our There are various ways of integration Breakout Session 22 brains. The author concludes: If the of the brain atlas with the surgical New Frontiers in Brain brain were smaller than what it is, it workstation. The atlas module may Sciences (Nanobiotechnology, would not have been able to support contain a single or multiple atlases. language and the development of The atlases may be available in 2D, bioengineering and science and technology which today in a single or all three orthogonal biomaterials) threatens existence; if the brain were orientations, or in 3D. The atlas may Chair: Babak Kateb larger than what it is, it might have be present in various representations & Jean Paul Allain been able to understand the problem (image, contour, polygonal, and possibly even solve it. The brain is volumetric). The key operation is atlas just not the right size. to scan registration and the resulting labeling and delineation of patient’s specific scans. These featured will be

Wieslaw Nowinski illustrated with the existing surgical workstations, such as StealthStation (Medtronic), and iPlan (BrainLAB). Jeff Sutton (Keynote) The insertion of devices into the brain during microrecording and stimulation may potentially cause microbleeds not Stereotactic brain atlases in intra- discernible on standard scans. A small operative imaging change in location of the DBS (deep Early stereotactic human brain atlases brain stimulation) electrode may result Brain Alterations in Spaceflight in print form were constructed in the in a major change to the patient. To 1950s to support human stereotactic address this issue, a stereotactic and Kuldip Sidhu instruments. At the end of the 1990s, functional neurosurgery-aided system the computerized anatomical brain composed of three stereotactic atlases had become prevalent in brain atlases: anatomical, functional, neurosurgical workstations. They are and vascular, will be presented. This system provides simulation useful in pre-operative planning, intra- and assessment of cerebrovascular operative support and post-operative damage in DBS3. It analyzes the track- evaluation1. The intraoperative Brain in the Petri dish – disease brain spatial relationship and allows usefulness of the brain atlas is modelling the DBS electrode to be placed more enhanced when interfaced with the effectively, potentially reducing the K. S. Sidhu, H. Chung and micropositioning device. invasiveness of the DBS procedure P.S. Sachdev Combination of various stereotactic to the patient. Centre for Healthy Brain Ageing, 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 81

Faculty of Medicine, UNSW Sydney, Jean Paul Allain magnetic bacterial nanocelullose Australia (MBNC) was coated with PEG to improve its biocompatibility. All The number of patients with samples were characterized before neurodegenerative diseases is and after magnetization using escalating significantly worldwide scanning electron microscopy (SEM). and that accounts for disease burden of over 13%. Therefore the Development of magnetic bacterial Cytotoxicity and biocompability current focus of research in this nano-cellulose (MBNC) for were evaluated using Porcine aortic area is to understand the underlying regenerative neuroendovascular smooth muscle cells (PASMC). mechanism of disease development in therapeutics Preliminary cellular migration assays demonstrated the behavior between an effort to identify molecular targets 1,2 Prof. Jean Paul Allain , Lisa M. MBNC and cells labeled with for therapeutic intervention. With 3 1,2 Reece , Mónica Echeverry-Rendón , paramagnetic nanoparticles. Human the advent of induced pluripotent Sandra E. Arias1,2, Juan Jose Pavón1,4 stem cell (iPSC) technology it is aortic smooth muscle cells (HASMCs) now possible to recapitulate the University of Antioquia, Colombia were magnetized through passive uptake, in which cells were incubated disease process in the Petri dish with Current treatments for brain with the 6 µg/mL SPION solution. cells derived from patients. These aneurysms involve clipping and Thick pellicles of BNC were grown humanised disease models thus can neuroendovascular coil embolization, as a translucent and sticky material turn the clock back on diseases such including stent-assisted coiling in an composed of micro fibrils that bundle as in Alzheimer’s from number of attempt to occlude the aneurysmal years in patient to few weeks in the defect from the parent artery. Such together to form long intertwined Petri dish. The generation iPS cells treatments are invasive and traumatic, ribbon-shaped fibrils. After completion offer a unique opportunity to develop not suitable in most patients with of the magnetization procedure, the disease-relevant neurons in large increased risks. An alternative method samples exhibited a paramagnetic numbers and assemble them as mini was developed to use scaffold stents behavior. An effective magnetic brain to study the disease process with their inherent thrombogenicity attractive force was observed using from the donating patient. Here, we coupled to stem cell derivatives from a magnet of 6 Gauss. Internalization provide an overview of human stem the arterial wall and the need to create of SPIONs by HASMCs and their cell models of neurodegeneration a local, focal attraction force of cells distribution was revealed using using iPS cells from patients with to the abluminal side of the stent Prussian blue staining for iron oxide Alzheimer’s disease. We report the scaffold for an in situ reconstruction content. Novel nanobiomechanical first generation of feeder-free iPS cells of the tunica media by Tigno and in-situ testing of the BNC and MBNC from Alzheimer’s patient with an early Armonda1. In 2009, Drs. Allain and membranes were conducted in a wet onset of disease using a polycistronic Tigno introduced for the first time, environments to mimic the pulsating lentiviral vector containing four a multi-functional nanostructured hemodynamic conditions near the pluripotent genes, Oct4, Sox2, Klf4 bioactive coating designed to render cerebral aneurysm. Results show and cMyc. These iPS cells have been an assymetric region of the stent that the MBNC and BNC hydrogels analyzed by using the microarray scaffold magnetic and biomimetic. behave as viscoelastic solids with chip and the computation of data is The bioactive coating utilizes bacterial Young’s moduli near 40 MPa. assisting in developing the in vitro nanocellulose (BNC) as a platform 1. Department of Nuclear, Plasma and, Radiological models for this disease and future for both magnetic attraction and cell Engineering regenerative medicine. These iPSC attraction and proliferation. Bacterial 2. Department of Bioengineering, University of Illinois are also differentiated to relevant Nanocellulose was obtained from at Urbana-Champaign, Urbana, IL USA neurons and our phenotype data in a culture of A. xylinum bacteria. 3. Birck Nanotechnology Center, Purdue University, IN, USA these neurons demonstrate disease The magnetization of the BNC was 4. Group of Advanced Biomaterials and Regenerative affects that could be analysed and realized through the reaction of Iron Medicine, Bioengineering Program hence in vitro disease modelling III and Iron II and heating up to 84°C. possible. Ammonium hydroxide was added References: to the mixture in order to precipitate 1. J.P. Allain, J. Tigno and R. Armonda in ed. Kateb out super paramagnetic iron oxide and Heiss, The Textbook of Nanoneurosurgery, nanoparticles (SPION). Subsequently, Taylor & Francis, 2013. 82 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Vicky Yamamoto Tackling dementia is a good example to consider. It already costs the community economically and socially and this is predicted to worsen during the coming decades. Most of people living with dementia will also be living with other chronic diseases such as cardiovascular disease and arthritis. Plenary lecture 7 Research in dementia may be a case par excellence in which researchers Prof Warwick Anderson, Chief and funders will learn how to conduct Executive Officer, National Health and support the research needed. & Medical Research Council The breadth of approaches and topics presented at this meeting indicates the future research approaches needed. Using dementia as an example health challenge, this talk

will explore the complexities of Research into Complex Diseases funding the best research across the – Challenges for Researchers and spectrum from basic to translation to Funders. implementation as the National Health The most pressing and expensive and Medical Research Council seeks health problems faced by countries to deliver on its responsibility to “raise like Australia in the 21st Century are the standard of individual and public complex and multi-factorial. As the health throughout Australia”. population ages, chronic ill-health becomes more common and many Australians will have more than one chronic disease. There is also a socioeconomic overlay to the prevalence of chronic disease and of access to health care. Even when knowledge is gained from research, effective implementation often does not occur; indeed it requires its own forms of research and the involvement of policy and decision makers. Addressing complex, chronic diseases represents a major challenge for researchers to put together the right teams, make use of new methodologies, and work with policy and decision makers. It’s a challenge too for research funding organisations. How is peer review best performed for multidisciplinary teams tackling complex issues? What are the best funding vehicles for this type of research? How are the community’s views and priorities taken into account? 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 83

Chair: Kuldip Sidhu Results: 52 patients were included increase. This suggests that increase in the analysis, with median age at in radiological abnormality of <25% diagnosis of 50 years. Seven patients may predict survival. Further studies 1. Cecelia Gzell were still alive at time of analysis and are required with larger sample sizes Small increases in enhancement the median survival was 18 months to confirm these results. on MRI may predict survival post (95% CI 15-23). Concordance radiotherapy in patients with between the three measurement techniques was an average of 62% glioblastoma 2. Timur Gureyev agreement for RANO and volumetric Introduction: To determine the analysis, 55% for RANO and rim Quantitative analysis of the EEG rate of pseudoprogression (PsP) in analysis, and 86% for volumetric and source localization problem glioblastoma patients (GBM) receiving rim analysis. Introduction: With the proliferation chemoradiotherapy (CRT) using both of computers, in addition to the modified RANO and novel volumetric Pseudoprogression was defined as spectral frequency analysis of analysis techniques. progressive disease (>25% from baseline value or new lesions) at electroencephalography (EEG) Methods: Patients >17 years M+1, M+3, or M+5, with subsequent recordings, the problem of 3D spatial diagnosed with WHO grade IV stable disease or partial response localization of the sources of electrical glioma managed with CRT between (>50% decrease from baseline) by activity inside the brain from surface June 2008 and November 2011 M+12. Using RANO technique we EEG data has attracted increased were included. Patients who had identified four patients (8%) with interest due to its potential importance incomplete set of MRI images for all pseudoprogression. There were for diagnosis and monitoring of study time points were excluded. four patients with volumetric analysis abnormal brain activity in epilepsy, Modified RANO and two different (only one in common with RANO stroke, traumatic brain injury, etc. volumetric calculations (volumetric technique), and two patients (4%) with Source localization in EEG represents versus rim analyses) were performed rim analysis (both in common with the an example of a mathematical on post-operative MRI, and MRIs at volumetric group although none in “inverse problem” which is severely 1 month (M+1), 3 months (M+3), 5 common with RANO). underdetermined and, hence, requires months (M+5), 7 months (M+7), and additional constraints in order to Using the volumetric analysis we 12 months (M+12) post completion provide an accurate solution. In this examined the difference in overall of RT. Overall survival was calculated study we carry out a systematic survival for patients that had a >5% in months post definitive surgery. All evaluation of the localization accuracy increase in enhancement versus <5% patients were treated with intensity of a popular source localization at the time points M+1, M+3, and modulated radiotherapy (IMRT) to method, sLORETA (http://www. M+5. There were 17 patients (33%) 60 Gray and had concurrent and uzh.ch/keyinst/loreta.htm), applied at M+1 with >5%, 28 (54%) at M+3, adjuvant temozolomide chemotherapy specifically to the cases of low-density and 26 patients (50%) at M+5. There (EORTC protocol). EEG headsets. We also compare was no significant difference at M+1 these results with the performance Modified RANO technique involved (19 v 18 months, p=0.548) but at of a new sparsity prior based EEG measurement of the surgical cavity M+3 and M+5 there was a significant source localization technique utilising with surrounding enhancement on improvement in survival for those with Brodmann map (http://en.wikipedia. T1 gadolinium enhanced MRI and <5% increased volume: M+3 23 v 15 org/wiki/Brodmann_area), for different compared subsequent scans with months (p=0.005), and M+5 26 v 15 number of simultaneously active the baseline post-operative scan months (p=0.004). sources and different noise levels. to determine response. Two novel We present a detailed analysis of the volumetric techniques used the ARIA Conclusion: This series of 52 corresponding lead-field matrices Eclipse radiotherapy planning software patients demonstrated low rates which not only sets an upper limit on to calculate the volume (cm3) of of pseudoprogression (4-8%). An the maximum number of simultaneous cavity plus surrounding enhancement increase in the volume of the surgical active sources that could be reliably (volumetric) versus the enhancement cavity and enhancement of >5% at localized in principle, but also provides only (rim). RANO definitions of M+3 and M+5 post completion of RT a basis for an optimal application response were implemented for all was associated with reduced survival of sparsity constraints for a given three techniques. compared with patients who had <5% 84 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

electrode configuration and brain the brain, but performs poorly in the in the innervating spinal cord motor segmentation. presence of multiple simultaneously neurons. active sources. In the latter cases Methods: Experiments are performed Methods: Recombinant adenovirus the proposed sparsity prior source on a realistic model obtained by serotype 5 driven by the CMV reconstruction method based on segmenting the MRI images of a promoter and encoding the reporter the Brodmann map produces head into five usual components, tag-GFP (Ad-GFP) was obtained considerably more accurate results. namely scalp, skull, Cerebrospinal through the UPenn vector core. fluid (CSF), white matter and The above results related to sLORETA Using our recently published MEP gray matter. sLORETA method is method have been included into a map of the mouse forelimb as a evaluated in the cases of a one or paper submitted to Medical Physics guide (Tosolini et al., 2013), Ad- two simultaneously active dipoles, journal; other results have not been a GFP (5.3x1012 pfu/ml) was injected at different levels of noise in the EEG part of any previous publication. along the entire MEP region of data. For the sparsity-prior-based triceps brachii muscle. Mice were Educational objectives: Quantify source reconstruction, multiple virtual subsequently intra-cardially perfused the performance of the EEG source dipoles are clustered according to the and the spinal cord, DRG, ventral localization methods, including Brodmann map into 84 active areas, and dorsal roots as well as targeted sLORETA and a new method based and the Sparse Bayesian Learning myofibres were dissected, sectioned on Brodmann map, for different method (http://ieeexplore.ieee.org/xpl/ and the tissue was analysed under low-density electrode configurations. articleDetails.jsp?arnumber=1315936) epifluorescence. The results are intended as a guide is used to perform the reconstruction. for practical applications of these Results: This analysis showed that The study is carried out considering methods for diagnosis and monitoring targeting the MEPs with Ad-GFP up to six completely or partially of various brain disorders. produced significant expression active areas and with different levels of GFP within spinal cord motor of superimposed noise, for different neurons. Moreover, GFP expression types of low-density electrode setups was also present within ventral roots, with 19, 33 and 71 electrodes. 3. Andrew Tosolini dorsal roots, DRG and triceps brachii Results: We evaluate the width of The Motor End Plates (MEPs) Are myofibres. the reconstructed source distributions A Conduit To Increase Adenoviral Discussion: This study shows that produced by sLORETA, which is Transduction Of Motor Neurons, targeting muscles’ MEP regions around 83mm and 113mm for the two Dorsal Root Ganglia (DRG) And with an adenovirus is an effective considered cases of low-density EEG Myofibres and minimally invasive way to deliver setups with 14 and 19 electrodes, Contact: therapeutic genes into the central respectively. We also quantify the andrew.tosolini @unsw.edu.au and peripheral component of the very large localization error produced neuromuscular junction. These data by sLORETA in the cases involving Introduction: Somatic viral-mediated have implications for gene therapies multiple simultaneously active dipoles. gene therapy has been utilised aiming to overcome lower motor We provide a systematic quantitative to deliver therapeutic genes into neuron dysfunctions such as spinal analysis of the accuracy of localization spinal cord motor neurons. Indeed, cord injury and motor neuron disease. of multiple sources by the new intramuscular injections and the Ref: 1) Tosolini et al., (2013) Front. Brodmann map based source subsequent retrograde transport of Neurol. 4:58. reconstruction method for different the viral vector is a minimally invasive low-density electrode setups. way to transduce the corresponding motor neurons. We have previously Conclusions: Given the severely shown that targeting the entire length 4. Terry Peters underdetermined nature of the of muscles’ MEP region significantly Correlation of quantitative MRI and EEG inverse problem, the state- increases the uptake of a retrograde histology of surgical specimens in of-the-art EEG source localization tracer into motor neurons (Tosolini et drug-resistant focal epilepsy methods have certain limits for their al., 2013). The aim of this study was application. sLORETA is very accurate to determine if targeting the MEP Maged Goubran1, Robert R. when applied to localization of a region with adenovirus would produce Hammond2, Sandrine de Ribaupierre3, single source of electric activity in significant expression of the transgene Terry M. Peters1, and Ali R. Khan1 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 85

Current clinical MRI protocols used preliminary findings suggest that T1 in Methods: The performance of for pre-operative assessment of focal gray matter may act as a predictor of X-Tream was tested at the biomedical epilepsy lack sensitivity, with greater neuronal density and thus in-vivo T1 beamline (ID17) at the European than 30% of patients diagnosed as mapping may provide a non-invasive Synchrotron Radiation Facility (ESRF), MR negative. The histology evaluation tool for estimating neuronal loss in Grenoble, France. All aspects of the of the surgical tissue, nevertheless, neurological disorders. experimental set-up at ESRF (filters etc) were as for full MRT irradiation often reveals gliosis or malformations 1. Imaging Laboratories, Robarts Research Institute, of cortical development undetected London, Ontario, Canada, conditions. A tungsten multislit pre-operatively. Such data have 2. Department of Pathology, Western university, collimator striates the broad X-ray motivated the need for MRI-histology London, Ontario, Canada, beam of height 0.5 mm and width 20 correlation, to validate improved 3. Department of Clinical Neurological Sciences, mm into 49 microbeams. Additionally, pre-operative imaging for localizing Western university, London, Ontario, Canada depth dose measurements epileptogenic foci. Our objective under broad beam conditions for here is to correlate quantitative MRI comparison with an ionisation and histology metrics of surgical 5. Michael Lerch chamber (IC) were carried out at the Illawarra Cancer Care Centre, specimens from temporal lobe X-Tream: A Unique Realtime QA epilepsy (TLE) patients. 10 TLE Wollongong. The X-Tream and IC System for Submillimeter X-Ray patients who were candidates for depth dose profiles of a 6 MV LINAC Radiosurgery epilepsy surgery were recruited for photon field in a 30cm x 30cm solid this study. All patients underwent Contact: [email protected] water phantom were compared. pre-operative imaging (relaxation Introduction: Microbeam radiation Results: The linearity of the response mapping and diffusion-tensor of the system over five orders therapy (MRT), a submillimeter X-ray imaging) on a 3T scanner. Field maps of magnitude is excellent with a radiosurgery technique, utilises of NeuN (representing neuronal conversion factor of 2.51 counts/nA. the dose volume sparing effect by density) and GFAP (representing The measured profile of the 0.5 mm gliosis) immunohistochemistry stains using highly collimated, parallel x 20 mm MRT field by the X-Tream of surgically resected tissue were X-ray microbeams (with width 0.05 System at 20 mm depth in perspex automatically computed. Regions mm and pitch 0.4 mm) to deliver a clearly demonstartes this excellent of interest (ROIs) were subsequently uniform radiation dose to a target. (<0.01 mm) spatial resolution and delineated on 100 µm downsampled A microbeam peak dose of 400 Gy, large operating dynamic range. The histology slices in both brain tissues delivered in <1 sec minimises any deduced PVDR and other important (GM & WM). Using our previously cardiosynchronous related blurring of parameters will be presented. The reported histology to MRI registration the microbeam X-ray paths. response with incident photon energy, PVDR with depth in a PMMA protocol, the histology ROIs were MRT quality assurance (QA) is warped to match corresponding phantom and factors that influence very challenging due to the high regions on in-vivo quantitative maps the measured PVDR will be discussed dose rates (~20,000 Gy/sec) and (T1, T2, FA, MD). Spearman’s rank in the presentation. Comparison with highly striated X-ray radiation field. correlation was employed to test for equivalent Monte Carlo radiation X-Tream is a high speed readout correlation between the MRI metrics: transport simulations will also be system with high resolution (micron- T1, T2, FA & MD, and field fractions of made. scale) silicon detectors for real-time NeuN & GFAP. A negative correlation The depth dose profiles along the beam monitoring, developed at the between NeuN field fraction and the central axis of the 6 MV LINAC Centre for Medical Radiation Physics T1 value in gray matter was found radiation field agree to within 1% using both tests (r= −0.617, p=0.001). (CMRP). The System has the ability to giving confidence to our dosimetry A negative correlation was also found measure the instantaneous dose rate methodology. The instantaneous peak between T1 and FA in white matter, associated at any point with micron radiation dose rate using the LINAC as well as a positive correlation spatial resolution and hence is able is ~6000 Gy/sec which is comprable between WM T1 and MD. This study to deduce the peak dose and valley to that used in MRT. The LINAC is the first to relate in-vivo T1 values dose between microbeams as well photon energy spectrum however is to the proportion of neurons in the as the MRT peak-to-valley dose ratio significantly higher than that used in grey matter for focal epilepsy. These (PVDR). MRT. T

86 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

Conclusions: The new X-Tream ex-vivo on a 9.4T small bore magnet, Chair: Glenn Cross Dosimetry System has been and then processed for histological developed and demonstrates assessment. We divide this process excellent performance characteristics. into two distinct steps through the 7.Solventa Krackauskaite X-Tream is the first, and currently use of an intermediate 3D ex-vivo MRI Accuracy, precision, sensitivity only realtime QA system in the of the specimen, l . The registration ex and specificity of non-invasive ICP world for MRT. We have succesfully detailed in this work relates to absolute value measurements benchmarked the realtime X-ray beam finding the transformations between monitoring capabilities of X-Tream, Accuracy, precision, sensitivity lin and lex, thus connecting images and the feasibility of the on line obtained in-vivo with histological and specificity of non-invasive ICP dosimetry method. It is envisaged slides. These transformations are absolute value measurements. that the X-Tream system will be used obtained in a hierarchical fashion, Solventa Krakauskaite1, Rolandas for real-time, on-line dosimetry and beginning with an initial translation, Zakelis1, Vytautas Petkus1, Laimonas immediately prior to patient treatment. , a landmark-based similarity Bartusis1, Romanas Chomskis1, transformation, , and finally a Aidanas Preiksaitis2, Arminas non-rigid deformation, . To assess Ragauskas1. 6. Terry Peters significant differences between the Contact information: Studentu St. rigid and deformable registrations, we 48-446, LT-51367, Kaunas, Lithuania, A pipeline for histology to in-vivo computed a Wilcoxon matched-pairs registration of surgically resected [email protected], [email protected]. signed-rank test between the mean specimens in focal epilepsy TRE values of both registrations. Our Keywords: non-invasive ICP absolute Maged Goubrana3, Catherine Curriea, mean TRE for rigid and non-rigid value method; two depth transcranial Sandrine de Ribaupierre2,3, Robert R. registrations was (1.46±0.30 mm & Doppler meter; Bland & Altman, Hammondd, Jorge J.Burneo2, Andrew 1.35 ±0.11 mm) and (1.71±0.36 mm regression and ROC analysis. G. Parrent2, Terry M. Peters1,3,5, & 1.41±0.33 mm) for neocortical and Introduction: Intracranial arteries Ali R. Khana5 hippocampal specimens respectively. are the natural pressure sensors. The Our statistical analysis confirmed Histopathological validation of existing ophthalmic artery (OA) is an unique that the deformable registration and emerging MRI image modalities vessel with almost the same anatomy and analysis techniques is a pressing significantly improved the registration of intracranial and extracranial need in the neuroimaging field and accuracy for the neocortex (Pneo segments. Because of that we has significant implications on clinical = 0.0019) and the hippocampus. proposed to use the OA as a natural diagnostics. Accurate registration, or (Php = 0.0011). Our in-vivo MRI „scales“ for aICP measurement and to alignment, between MRI and histology to histology registration pipeline use a two depth transcranial Doppler is required for effective quantitative allows for a quantitative spatially- meter (TCD) as a balance indicator of comparison at a spatially-local scale. local assessment of pathological such ”scales“. This is „re-invention“ Here we present one stage of a novel correlates of MRI by fusing information of non – invasive ABP measurement pipeline for registering in-vivo MRI from both modalities using dense method for aICP value measurement and histology of hippocampal and correspondences. The reported application. registration accuracy is within an temporal lobe neocortical sections Objectives: from epilepsy surgery, namely the acceptable range and demonstrates registration of in-vivo to ex-vivo the potential of this pipeline to enable 1. To validate accuracy, precision, MRI, and assess the accuracy and prediction of pathology from in-vivo sensitivity and specificity of reliability. 10 temporal lobe epilepsy MRI through correlation studies. proposed non-invasive aICP measurement method by patients who were candidates for 1. Imaging Research Laboratories, Robarts Research anterior temporal lobectomy (ATL) Institute, multicenter comparative clinical surgery were recruited for this study. 2. Department of Clinical Neurological Sciences, studies (Bland & Altman, regression All patients underwent pre-operative 3. Biomedical Engineering, and ROC analysis) on wide groups imaging (relaxation mapping and 4. Department of Pathology, of neurological and ICU patients: diffusion-tensor imaging) on a 3T MRI 5. Department of Medical Biophysics, Western • Turku Hospital: TBI patients, scanner. Following surgery the excised University, London, Ontario, Canada invasive “gold standard” neocortical specimens were scanned ventricular or parenchymal 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 87

pressure sensors prospective Conclusions: 8. Jun-Young Lee study. 1. ROC analysis confirms high Alzheimer disease progress and • Republic Vilnius University sensitivity (88%), specificity (93%) cognitive reserve Hospital: TBI patients, ventricular and area under ROC curve (0.96) “gold standard” invasive ICP Hyeun Ju Park of non-invasive ICP measurement sensors prospective study. SMG-SNU Boramae Medical Center method. • Lithuanian Life Science University: In Hye Kim prospective neurological 2. Negligible mean systematic error SMG-SNU Boramae Medical Center patient Phase III study: non – (0.03 mmHg) is a statistically Hee Jung Kim invasive ICP comparing with significant evidence of two – depth SMG-SNU Boramae Medical Center “gold standard” CSF pressure TCD based non-invasive aICP value Yu Kyeong Kim measured via lumbar puncture. measurement method and shows SMG-SNU Boramae Medical Center • Umea Hospital: dynamic infusion that is the only which does not Dae Jong Oh tests on elderly neurological need a patient specific calibration. SMG-SNU Boramae Medical Center patient group (age 65-85) Jun-Young Lee prospective double blinded study. Clinical studies and technology SMG-SNU Boramae Medical Center development were funded by EU FP7 2. To validate linearity study (HUT/ projects: Abstract: Introduction Education is HDT, regression analysis) at Kaunas the surrogate marker for cognitive University of Technology. • Brainsafe II – Development of a reserve. Larger cognitive reserve is Novel Autonomous Non-Invasive Methods: Prospective randomized related to slower cogntive change in Absolute Intracranial Pressure comparative clinical studies of normal elders, but, whether cognitive Measurement Device Based on simultaneous non-invasive aICP reserve has biological influence on and “gold standard” invasive ICP Ultrasound Doppler Technology. Alzheimer disease (AD) progress is not measurements. Data collected from • TBICare – Evidence based well investigated. We thus aimed to 110 patients from clinical centers in Diagnostic and Treatment Planning investigate the effect of education on Lithuania (Vilnius, Kaunas), Sweden Solution for Traumatic Brain Injuries. longitudinal change of AD brain. (Umeå), Finland (Turku). • BrainCare – Scientific research Methods: Twelve AD patients who Healthy volunteers’ study was and development of innovative were educated lower than 3 years and performed with 217 snapshots by evidence based non-invasive brain 10 AD patients who were educated aICP non-invasive measurements in 6 diagnostic and monitoring solutions higher than 9 years were followed up body positions. for neurological and TBI patients. for 3 years with repeated measures Results: Bland & Altman plot of 171 of magnetic resonance imaging and paired non-invasive and invasive US projects: cognitive tests. Repeated ANOVA ICP data points showed that mean • Randomized prospective non- were used to assess whether rates systematic error (accuracy) of non- invasive ICP measurement study of of brain and cognitive change were invasive aICP value measurement patients with idiopathic hypertension modified by education levels. was equal to 0.03 mmHg and syndrome. Study partially supported Results: The decline of cognition was standard deviation of the random by NASA. slower in AD participants with higher error (precision) SD = 2.65 mmHg (CL • NSBRI (NASA) - Research and education. Atrophy of This effect = 0.965) or SD = 2.2 mmHg (CL = Technology Development to Support is remarkable in left prefrontal and 0.95). temporal area. Crew Health and Performance in Healthy volunteers’ study confirms Conclusions: After buffering effect linearity (R=0.995) of non-invasive Space Exploration Missions. against amyloid deposition by aICP value measurement method in 1. Kaunas University of Technology, Telematics cognitive reserve is failed, the rate of the clinically important aICP range Science Centre, Kaunas, Lithuania. 2Vilnius brain atrophy and cognitive change [6.3 - 37.8 mmHg] which is below and University, Faculty of Medicine, Clinics of Neurology may be fast in the course of AD above of critical ICP thresholds 14.7 and Neurosugery, Centre of Neuroangiosurgery, Vilnius, Lithuania. progression. mmHg (neurology) and 20.0 mmHg (neurosurgical intensive care). 88 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

9. Abigale Besemer two SUV threshold levels (1.0 and 1.2) 10. Li Li & Yifan Zhang and two TBR threshold levels (1.6 and Impact of PET and MRI Threshold- Metabolic alterations in the frontal 2.0). Additionally, the tumor was also Based Tumor Volume Segmentation white matter of patients with Major segmented based on a T1 contrast- on Targeted Radionuclide Therapy Depressive Disorder with treatment of enhanced MRI threshold. The Dosimetry using CLR1404 SSRIs: A proton magnetic resonance 124I-CLR1404 activity was converted spectroscopy study Introduction: The treatment of to the 131I-CLR1404 activity by malignant brain tumors, especially accounting for the difference in Introduction: Proton magnetic gliomas, with conventional external decay rates. The 131I-CLR1404 resonance spectroscopy (1H-MRS), beam radiation therapy (EBRT) is cumulated activity distribution was provides a non-invasively detecting unsuccessful in many cases due calculated by numerically integrating Metabolite levels in vivo, which can to the inability to deliver curative the activity at each scan time point, be used to measure biochemical doses to the tumor while limiting on a voxel-by-voxel basis, over the or metabolite concentrations in the toxicity to normal brain tissues. whole patient volume. This was then circumscribed brain regions. Current Targeted Radionuclide Therapy (TRT) used to estimate the therapeutic research has highlighted the role of is emerging as an attractive adjuvant 131I-CLR1404 absorbed dose glial cells in white matters(Schipke treatment in these cases because the deposition for each patient using the C G, et al., 2011). It is assumed selective uptake and retention of the Monte Carlo code Geant4.9.4. that antidepressant treatment of radioactive agent within the tumor has Results: Significant differences in SSRIs not only affects neurons, but the potential to treat the microscopic the shape of the MRI, SUV, and TBR also activates glial cells(Czéh B, Di tumor extent. CLR1404, a small- tumor dose volume histograms (DVHs) Benedetto B.,2013). Seldom article molecule, phospholipid ether analog were observed for each patient. Mean had focus on prefrontal white matter can serve as a “diapeutic” (diagnostic 131I-CLR1404 tumor doses ranged to observe a true drug response with and therapeutic) agent for the from 0.23 to 0.74 mGy/MBq and had SSRIs. The purpose of this study detection and treatment of multiple a standard deviation between 0.05 was aims to observe whether there cancers. Isosteric iodine substitution and 0.13 mGy/MBq. In general, TBR was any effect of antidepressant in CLR1404 creates a molecular tumor volumes were larger (2.3 – 63.9 treatment on the metabolite levels in imaging agent when labeled with cc) than the SUV (0.1 – 34.7 cc) and the ventral prefrontal white matter in I-124 or a targeted radiotherapeutic MRI (0.4 – 11.8 cc) volumes which the depressed patients. agent when labeled with I-131. resulted in lower mean tumor doses Methods: Forty-five patients (mean Phase I and II trials evaluating the in most patients. One patient had age 44 ± 13 years) diagnosed as effectiveness of CLR1404 in patients notably high discordance between MDD according to DSM-IV with with brain tumors are currently the gadolinium enhancement and scores of 18 or greater on the 24- underway. This work investigates the the 124I-CLR1404 avid areas which item Hamilton Depression Rating impact of PET and MRI threshold- resulted in a lower dose in the MRI Scale (HDRS). MRS studies were based tumor segmentation on TRT tumor volume compared to the SUV performed on a 3.0T MR system dosimetry in patients with primary and and TBR volumes. (General Electric, Excite Signa HD metastatic tumors. Conclusions: The tumor volume and 3.0T). single voxel PRESS (spin-echo Methods: In this study, PET/CT interpretation of the 131I-CLR1404 point resolved) spectroscopy with images of five high grade glioma tumor dose is highly sensitive to the chemical-shift selective saturation patients were acquired at 4.5, 24, and imaging modality and threshold level (CHESS) water suppression.The 48 hours post injection of 74 to 185 used for tumor volume segmentation. volume of interest (VOI)was localized MBq of 124I-CLR1404. The initial MRI The large variations in tumor doses at the bilateral ventral prefrontal white and the PET/CT images at each time clearly demonstrate the need for matter regions（voxel size: 2×2×2 mm3 point were fused and used to segment standard protocols for multimodality ）.The analysis of the spectral dataset tumor volumes using different tumor volume segmentation in TRT was performed with the manufacturer- thresholding techniques. Standardized dosimetry. The results gathered from supplied software package program Uptake Values (SUVs) and Tumor- this investigation may help guide of the MR system (GE Advantage to-Background Ratios (TBRs) were combined TRT and EBRT of brain Workstation: AW4.2). calculated from the 48 hour PET. The tumors. Results: The comparison at baseline tumor volume was segmented using revealed significantly lower CHO/ 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY 89

Cr (t=2.36; p=0.02) in right ventral motor evoked potentials (MEP) in the 15. Taskin Duman prefrontal white matter. We also found right first dorsal interosseous (FDI) Internal Carotis Artery Thrombosis In a reduced CHO/Cr (t=1.81,p=0.07) muscle with three stimulus paradigms: Acute Ischemic Stroke in left ventral prefrontal white matter, (a) 120% of resting motor threshold however this difference was not (RMT), (b) stimulus intensity set to Contact: [email protected] statistically significant. After 12 wk evoke MEP of 1-millivolt amplitude Mustafa Kemal University Medical treatment, the HDRS had significantly (MT1) and (c) a short latency paired Faculty Department of Neurology, decreased in the patients (paired t pulse paradigm, administered in HATAY Taskin Duman, Ozcan tests. t =11, p <0.001), indicating random sequence. This was done Demetgul, Esra Okuyucu, Fidan positive treatment response.Bilateral while the subjects observed videos of Surgun, Ismet Melek CHO/Cr values of patients increased (a) inanimate motion of two bouncing significantly compared to pretreatment balls (control condition), (b) two videos Introduction: Cerebrovascular values[left:t =3.17 p =0.006;right:t depicting goal-directed action of the accidents due to carotid artery =2.35 p =0.03]. FDI (action-observation condition). disease are amongst the most The MEP difference between control common causes for death and Conclusion: Our results suggest that and action-observation conditions disability. [1] According to the results alterations in ventral prefrontal white formed the measure of putative MNA. obtained by Framingham Heart matter metabolite levels are likely Study, the frequency of carotid involved in MDD pathophysiology and Results: On two-way RMANOVA, artery narrowing above %50 is %7 may help improve our understanding there was a significant group (true in women between 66-93 years of of this pathophysiology and the crucial versus sham) X occasion (pre- and age, and %9 in men between the role of white matter in MDD. post-HF-rTMS MNA) interaction effect same ages [2]. According to the data for MT1 [F (df) = 12.143 (1,29), p= from the NASCET (North American 0.002] and 120% RMT stimulus [F Symptomatic Carotid Endarterectomy 12.Avinash Waghmare (df)= 7.326 (1,29), p= 0.01] indicating Trial) study, the risk for ischemic SVO greater enhancement of MNA in the in the first year is %11 in carotid artery A Novel Application of High Frequency true HF-rTMS group than the sham narrowing between %70-79. This Magnetic Stimulation: Enhancing group. This effect was not noticed in risk reaches %35 when narrowing is Putative Mirror Neuron Activity the paired pulse stimulus paradigm [F %90 or above [3,4]. In cases of acute Introduction: Social cognition deficits (df) = 1.815 (1,29), p= 0.18]. ischemic stroke, imaging methods in schizophrenia lead to substantial Conclusions: HF-rTMS delivered used in the right time and under the socio-occupational dysfunction at the left inferior frontal gyrus right conditions with the guidence and respond poorly to conventional resulted in significantly greater MNA of clinical tables carries critical medications. Dysfunctional mirror enhancement than sham-rTMS. These importance for the results. neuron activity (MNA) has been findings suggest the potential role Case: A 62 year old, right handed associated with these deficits. We of HF-rTMS as a novel therapeutic male patient applied with sudden examined if a single session of high application to enhance MNA and thus weakness of the left side and frequency repetitive transcranial improve social cognition and disability unconsciousness. In his neurologic magnetic stimulation (HF-rTMS) in patients with major psychiatric examination; somnolance, left central would enhance TMS-measured MNA disorders. facial asymmetry, motor loss of 2/5 at compared to sham-rTMS in healthy the left upper and lower extremities individuals, using a randomized and Babinski positive on the left were controlled study design. 13. NA detected. In the DWI of the patient Methods: 31 consenting, right- whose brain tomography was found handed, healthy individuals were to be normal; hyperintensity in the randomized to receive true (n= 15) or diffusion weighted imaging done sham (n= 16) HF-rTMS administered on the right frontotemporoparietal over the left inferior frontal gyrus. 14.NA area and hypointensity in the ADC Putative MNA before and after mapping. In the Carotid Doppler HF-rTMS, was assessed using USG performed on the patient for investigational-TMS. We recorded 10 etiology images compatible with 90 11TH ANNUAL WORLD CONGRESS OF SBMT BREAKING BOUNDARIES OF SCIENCE, TECHNOLOGY, MEDICINE, ART AND HEALTHCARE POLICY

hypoechoic thrombus filling the 16. PhuaHwee Tang with the same sequence but long TI lumen originating from the right ICA and TR. All four paediatric patients Arterial Spin Labelling Method completely were detected and no had focal epilepsy localized unilaterally of assessing cerebral perfusion vascular flow coding was seen in determined by both PET and EEG. compared against PET imaging in the doppler examination done for children with focal epilepsy ASL images were pre-processed by distal thrombus. For this reason CT FSL (Oxford, UK) and MIPAV (NIH, Angiography was performed on the Contact: [email protected] USA) for motion and inhomogeneity patient and a hypodense, soft, non Introduction: Epilepsy can result in ulcerated plaque formation with a correction. Perfusion Weighted significant childhood morbidity. MRI Imaging (PWI), calculated from the lenght of 1 cm and 3.5 mm causing structural scans show abnormality %90 narrowing at the right ICA perfusion difference images divided by in only about 50% of cases. Current the M0, is proportional to CBF. PWI origin level attracted our attention. ways to determine the epileptic foci No contrast material passage to was registered to the standard space rely on FDG-PET and EEG. Arterial (MNI152 template) through linear and the ICA in the distal was observed. spin labelling (ASL) perfusion MRI is a After consultation it was agreed non-linear registration of the M0 image non-invasive technique for measuring to MPRAGE and SPACE images using that right carotid endarterectomy regional cerebral blood flow (CBF) and and patch plasty operations would FSL. ASL CBF maps were visually may be able to improve the diagnosis compared with PET images. be done on the patient. The patient of epilepsy on MRI. The purpose of who got better neurologically shortly this study was to investigate the use Results: All except 1 had normal after the operation was discharged. of ASL in detecting brain lesions in structural MRI scans. In 3 of the 4 No reasons besides the excessive children with focal epilepsy, and to patients, areas of hypoperfusion on use of cigarettes were found in the compare against FDG-PET. ASL match the areas of hypoperfusion investigation done regarding the seen on PET. In one patient, the ASL Methods: This study was approved etiology. CONCLUSION This case CBF map was normal although PET by the institutional review board and emphasises the critical importance of was abnormal. In 2 patients, there written consent was obtained. Four the earliest possible use of appropriate were artefacts present in the parietal paediatric patients (ages: 13-15) with imaging techniques in determining the lobes (unilateral in one and bilateral in focal epilepsy were scanned on a treatment in the emergency evaluation the other). of acute ischemic stroke. whole-body 3T MR scanner (Siemens MAGNETOM Skyra) with a 32-channel Conclusion: Areas of hypoperfusion phased-array receive-only head coil. on ASL CBF maps match the areas of High-resolution anatomical images hypoperfusion seen on PET imaging were acquired using T1-weighted in most cases in our small cohort 3D MPRAGE and T2 –weighted 3D of patients. However, artefacts are SPACE. FAIR-ASL was acquired present in the ASL CBF maps and using TI=1700ms with background refinement of technique is required suppression and 3D GRASE before it can be used routinely. acquisition. M0 image was acquired

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