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Understanding Haemodynamic Changes Surrounding Epileptic Events in Children

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Understanding Haemodynamic Changes Surrounding Epileptic Events in Children Understanding Haemodynamic Changes Surrounding Epileptic Events in Children Elhum Anahit Shamshiri Thesis submitted for the degree of Doctor of Philosophy of University College London. Developmental Imaging and Biophysics Section University College London 02 March 2017 Declaration I, Elhum Shamshiri, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Elhum Shamshiri Abstract The interrelationship between cerebral haemodynamics and epileptic activity has been the subject of study for over 100 years. The overall goal of this PhD is to use and develop multimodal imaging to better understand this relationship in a paediatric population. This has important implications for the localisation of epileptic activity that can aid pre-surgical evaluation and seizure detection. The benefit of interictal epileptiform discharge (IED) suppression in clinical treatment is under debate, considering little is known about their impact on cognitive function. By applying EEG-fMRI, it was found that transient effects of IEDs were responsible for connectivity differences between patients and controls, showing the widespread impact of IEDs on BOLD signal and suggesting the importance of IED suppression for normal functional connectivity. Haemodynamic changes may occur prior to epileptic event onset. Therefore we evaluated the response function (HRF) to IEDs in paediatric focal epilepsy patients, as an HRF was created from simultaneous EEG-fMRI data and found to be beneficial in the delineation of epileptic foci. However, the underlying neurovascular changes seen in this altered HRF still needed to be explored. Therefore EEG-NIRS was utilised to interpret the mechanistic changes found in BOLD during IEDs. NIRS provides the added information of concentration changes of both –oxy and –deoxy haemoglobin rather than relative changes in deoxyhaemoglobin. To perform these experiments a new optode holder applicable to the clinical environment had to be made and tested for efficacy. The best design was a flexible optode grid, as it required no interference with the standard clinical protocol. Once tested in patients, EEG-NIRS found pre-ictal/pre-IED increases in oxygen saturation and oxyhaemoglobin concentrations, thereby corroborating with prior haemodynamic changes seen in EEG-fMRI. Therefore, by utilizing both EEG-fMRI and EEG-NIRS a greater understanding of the haemodynamic changes surrounding epileptic events in children can be obtained. Acknowledgements I would like to express my sincere gratitude to my supervisors, Doctor David Carmichael for his guidance which helped me throughout my PhD as well as through the writing of this thesis, and Professor Helen Cross for all of the help and support she has given me. I would also like to thank Alan Worley for all the good advice he has given me and always having his door open for a discussion. I would also like to thank my co-workers Tim Tierney, Doctor Maria Centeno, and Suejen Perani for their guidance and encouragement that made working at the Institute of Child Health a rewarding (and fun) experience. From the staff at Great Ormond Street Hospital I would like to thank Charlotte Wilkinson for her help and never-ending patience, which I am very grateful for. I would also like to thank Kelly St Pier for her knowledge and guidance throughout my PhD, and her willingness to teach me about working in the clinical realm. I would also like to thank the telemetry team, including Emma Dean, Rui Silva, and Arjel Lejarde for their support and making my work at the hospital an exciting and inviting place to be. I would also like to thank Dil Hair for his support and encouragement. Furthermore I would like to thank all of the radiographers in the MR department. In particular I would like to thank Jessica Cooper and Tina Banks for all of their help and hard work, as without their patience and support this would not have been possible. From the University College London Medical Physics Department, I would like to thank Doctor Ilias Tachtsidis for his willingness to work with such an interdisciplinary team to apply optical imaging in the clinical realm, and introducing me to the field of Near Infrared Spectroscopy. I would also like to thank my family who have been extremely supportive throughout the entire PhD, even from afar. I would especially like to thank my mother, who has always been there for me and whose strength and intellect I aspire to live up to. Papers and Abstracts Directly arising from this Thesis Papers Shamshiri EA, Tierney TM, Centeno M, St Pier K, Pressler RM, Sharp DJ, Perani S, Cross JH, Carmichael DW (2016): Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy. Hum Brain Mapp 236:221–236. Publications related to the work in this thesis Centeno M., Tierney T.M., Perani S., Shamshiri E.A., St Pier K., Wilkinson C., Konn D., Banks T., Vulliemoz S., Lemieux L., Pressler R.M., Clark C.A., Cross J.H., Carmichael D.W. (2016). Optimising EEG-fMRI for localisation of focal epilepsy in children. PLoS One 11: e0149048. Tierney T.M., Weiss-Croft L.J., Centeno M., Shamshiri E.A., Perani S., Baldeweg T., Clark C.A., Carmichael D.W. (2016). FIACH: A biophysical model for automatic retrospective noise control in fMRI. Neuroimage 124: 1009-10020. Abstracts Shamshiri E., Centeno M., St Pier K., Perani S., Cross J.H., Carmichael D.W. (2014, May). Failure of connectivity modulation during an attentional task in children with epilepsy is not explained fully by interictal activity. Poster presented at the annual meeting of International Society for Magnetic Resonance in Medicine, Milan, Italy. Shamshiri E., Centeno M., Tierney T., St Pier K., Perani S., Cross J.H., Carmichael D.W. (2014, June). An investigation of the role of interictal activity on a natural stimulus in children with epilepsy. Poster presented at the annual meeting of Organization for Human Brain Mapping, Hamburg, Germany. Shamshiri E.A., Centeno M., Tierney T.M., St Pier K., Pressler R., Perani S., Cross J.H., Carmichael D.W. (2014, December). Investigating the role of interictal activity during a natural stimulus presentation in children with epilepsy. Poster presented at the annual meeting of Brain Modes, London, United Kingdom. Shamshiri E.A., Centeno M., Tierney T.M., St Pier K., Pressler R., Perani S., Cross J.H., Carmichael D.W. (2015, May). Investigating the role of interictal activity during a natural stimulus presentation in children with focal epilepsy. Poster presented at the annual meeting of International Society for Magnetic Resonance in Medicine, Toronto, Canada. Shamshiri E.A., Centeno M., Tierney T.M., St Pier K., Pressler R., Perani S., Cross J.H., Carmichael, D.W. (2015, June). Investigating the role of interictal activity during a natural stimulus presentation in children with focal epilepsy. Poster presented at the annual meeting of Organization for Human Brain Mapping, Toronto, Canada. Shamshiri E.A., Centeno M., Tierney T.M., St Pier K., Pressler R., Perani S., Cross J.H., Carmichael, D.W. (2015, September). Assessing the impact of interictal discharges on resting state network connectivity in focal epilepsy using EEG-fMRI and a natural stimulus task. Talk presented at the annual meeting of International Epilepsy Congress, Istanbul, Turkey. Table of Contents Declaration ................................................................................................................... 2 Abstract ........................................................................................................................ 3 Acknowledgements ...................................................................................................... 4 Papers and Abstracts .................................................................................................... 5 Table of Contents ......................................................................................................... 7 Table of Figures ......................................................................................................... 12 Table of Tables ........................................................................................................... 15 Table of Abbreviations ............................................................................................... 16 Chapter 1 General Introduction .............................................................................. 20 1.1 Epilepsy ...................................................................................................... 20 1.1.1 Neurophysiology and Neurochemistry of Cortical Neurons .................. 20 1.2 Vascular and Physiological Relationships ................................................. 27 1.2.1 Vasculature ............................................................................................. 27 1.2.2 Cerebral Autoregulation ......................................................................... 28 1.2.3 Metabolic, Vascular, and Neuronal Coupling ........................................ 29 1.3 Neuroimaging ............................................................................................. 34 1.3.1 Electroencephalography ......................................................................... 34 1.3.2 Magnetic Resonance Imaging ................................................................ 36 1.3.3 Combining EEG and fMRI ...................................................................
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