30/10/2020

Biomedical Engineering Medical : Nuclear Imaging, Optical Imaging and more

Alena-Kathrin Golla née Schnurr

Schedule

Day Date Time Lecturer Topic Tuesday 03.11.2020 13:00-14:30 Licht Biosensors & Physiological Signals I Tuesday 10.11.2020 13:00-14:30 Licht Biosensors & Physiological Signals II Thursday 12.11.2020 13:00-14:30 Tönnes Bioelectrical Signals: EEG & ECG Tuesday 17.11.2020 13:00-14:30 Reichert : MRI Thursday 19.11.2020 13:00-14:30 Tönnes Medical Imaging: CT, Xray & US Tuesday 24.11.2020 13:00-14:30 Golla Medical Imaging: Other Thursday 26.11.2020 13:00-14:30 Andoh Blood Flow & Pressure I Tuesday 01.12.2020 13:00-14:30 Andoh Blood Flow & Pressure II Thursday 03.12.2020 13:00-14:30 Golla Machine Learning I Tuesday 08.12.2020 13:00-14:30 Golla Machine Learning II Thursday 10.12.2020 13:00-14:30 Golla 3D Printing Tuesday 22.12.2020 13:00-14:30 All Recap - Exam Preparations Golla, Tuesday 26.01.2021 10:00-12:00 Exam Tönnes Golla, Wednesday 03.02.2021 08:30-10:00 Repeat Exam Tönnes

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Materials

Slides are available from our website: https://www.umm.uni-heidelberg.de/inst/cbtm/ckm/lehre/

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Lecturer: Alena-Kathrin Golla née Schnurr

PhD Student: Medical Image Analysis with Deep Learning

Computer Assisted Clinical Medical Faculty Mannheim Heidelberg University [email protected] Phone:+49 (0) 621 383 4603

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Overview

 Nuclear Imaging

 Single- emission computed (SPECT)

 Positron emission tomography (PET)  Optical Imaging

 Microscopy

 Photography

 Endoscopy

 Optical tomography (OCT)  Magnetic Particle Imaging

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Nuclear Imaging

Small amounts of radioactive agents are introduced into the patient’s body. This radiopharmaceutical accumulates in areas with increased metabolism. The emitted radiation is detected by gamma cameras.

Scintigraphy SPECT PET

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Nuclear Imaging

• 1896: Henri Becquerel discovered mysterious "rays" from uranium

• 1897: Pierre and Marie Curie named the mysterious rays "radioactivity"

• 1934: artificially produced radionuclides by Frédéric Joliot-Curie and Irène Joliot-Curie in Paris, France

• 1950: rectilinear scanner by Benedict Cassen

• 1957: gamma camera by Hal Anger in Berkeley, USA

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Nuclear Imaging

• 1962: David Kuhl introduced emission reconstruction tomography, the basis for SPECT and PET

• 1973: Edward J. Hoffman,Michel Ter-Pogossian and Michael E. Phelps invented the PET scanner

• 1976: Ronald Jaszczak developed the first dedicated head SPECT camera, John Keyes developed the first general SPECT camera

• 1998: first PET/CT prototype by David Townsend in Pittsburgh, USA

• 2008: first simultaneous MRI/PET scanner by Siemens

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Scintigraphy

Gamma Camera

From https://en.wikipedia.org/wiki/File:Gamma_camera_cross_section.PNG and https://en.wikipedia.org/wiki/File:Gamma_Camera_Cross_Section_detail.png

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Scintigraphy

Collimator: by high energy are filtered so that only those traveling orthogonal to the detector are allowed through.

Scintillation: crystals emit visible following the absorption of radiation

Photomultiplier: captured photons are converted into electrons, these are the multiplied, a strong signal is rated as an event, the number of events is counted

From https://en.wikipedia.org/wiki/File:Gamma_Camera_Cross_Section_detail.png

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Scintigraphy

Intial Scan After Chemotherapy

From https://commons.wikimedia.org/wiki/File:Scyntygrafia.JPG and https://commons.wikimedia.org/wiki/File:99mTc-HMDP_bone_scintigraphy_01.jpg

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Single-photon emission computed tomography (SPECT)

• the gamma camera heads rotate around the patient's body → more detailed, three-dimensional images

• Upon decay SPECT tracer emits a single Gamma photon

• This photon can then be detected by the gamma camera

• 3D is reconstructed from multiple 2D projections

• Spatial resolution: 1cm MIP of SPECT

From https://en.wikipedia.org/wiki/File:Mouse02-spect.gif

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Positron emission tomography (PET)

• PET: multiple rings of detectors around the patient Tracer

• Upon decay PET tracer emits a positron

• Together with electrons from the patient body 푒 푒 the positron forms a positronium

• Upon decay the positronium emits two photons in opposite directions Ps

• Event is only counted if two photons with 180°angle were measured ɣ ɣ → Less background noise than SPECT 180°

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Positron emission tomography (PET)

• positron might move inside the body → systematic error, resolution is limited

• Spatial resolution: 0.5 – 6 mm (depending on tracer)

From https://en.wikipedia.org/wiki/File:PET-MIPS-anim.gif

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Time of Flight PET Convential PET: An event is not associated with a specific position, but a line.

But: If the time temporal resolution of the detector is ɣ Ps ɣ high enough, we can measure the different time of flight of the two photons.

→ directly locate the signal origin on the scan line → better image quality and reduced scan times

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Common PET Tracers

Name Half-life Target

18F-FDG 110 min cancer, heart disease, and epilepsy

18F-FET 110 min brain tumors

18F-FBB 110 min dementia

68Ga-PSMA 68 min prostate cancer

68Ga-DOTATOC 68 min neuroendocrine tumors

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Positron emission tomography (PET)

Advantages Disadvantages

• The body treats the radiotracer • The PET scan exposes patient fluorodeoxyglucose similar to to radiation. However, the glucose. amount is quite small. • The scan only takes about 30 • The radioactive tracer has a minutes. short half life and high cost • The PET scan can reveal cell • Patients should avoid people level metabolic changes who shouldn’t be exposed to occurring in an organ or tissue. radiation, such as pregnant • Less noise than SPECT women, for a few hours after the scan. • Shows no morphology.

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PET-CT

• Combination of PET and CT

→ both scans can be done nearly simultaneously

• PET-CT systems were initially proposed by David Townsend (at the University of Geneva at the time) and Ronald Nutt (at CPS Innovations in Knoxville, TN) with help from colleagues in 1998.

• The first PET-CT prototype for clinical evaluation was funded by the NCI and installed at the University of Pittsburgh Medical Center in 1998.

• The first commercial system reached the market by 2001.

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PET-CT

• result is a fusion scan with combined information from both scanners • Morphology from the CT • Glucose metabolism from PET

→ enables precise localization of

• PET-CTs are nowadays more common than PETs

• CT images are also used for calibration (attenuation correction) of the PET data • Density information can be considered in PET reconstruction

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PET-CT

This is the PET-CT here in the university clinic:

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PET-CT

CT PET Fusion

From https://commons.wikimedia.org/wiki/File:CT-PET_of_metastatic_Cancer_patient.jpg

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PET-MRI

• Combination of PET and MRI

• 1997: Simultaneous PET/MR detection first demonstrated by Marsden and Cherry

• 2009 first integrated sequential PET-MRI by Philips: • MRI and PET scanner installed 3 m apart

• 2011: Siemens Biograph mMR – first simultaneous clinical scanner

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PET-MRI

• Challenges:

• MRI is not density based → MR images cannot be used for attenuation correction

• pseudo CTs can be generated from the MRI

• PET scanner parts have to be made MRI compatible

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PET-MRI

From https://en.wikipedia.org/wiki/File:PET-IRM-cabeza-Keosys.JPG

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Optical Imaging

Medical optical imaging is the use of light as an investigational imaging technique for medical applications.

optical medical microscopy photography

optical endoscopy coherence tomography

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Microscopy

• Galileo di Vincenzo Bonaiuti de' Galilei (1564 -1642)

• 1610: he used a telescope at close range to magnify the parts of insects • 1624: he had used an compound microscope and send several of them to be presented to influential people • 1625: Giovanni Faber coined the word “microscope” for Galileo's invention

• Cornelis Jacobszoon Drebbel (1572 – 1633)

• Dutch engineer and inventor develops an automatic precision lens-grinding machine • 1622: sold his compound microscopes

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Microscopy

• Antonie Philips van Leeuwenhoek (1632 - 1723)

• the Father of Microbiology • Dutch businessman and self-taught scientist • developed an interest in lens making • created at least 25 single-lens microscopes • first to document microscopic observations of muscle fibers, bacteria, spermatozoa and red blood cells • first person to use a histological stain

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Compound Microscope

From https://commons.wikimedia.org/wiki/File:Parts_of_a_Microscope_(english).png

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Compound Microscope

objective lense: 100x ocular lense: 20x eye

object

eye real image lense

virtual image

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Break

Do you have any questions so far?

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Sample Preparation

There are 4 possible preparation options for samples: 1. Whole-mount: entire sample is small enough to be placed directly onto a microscope slide 2. Squash: cells are intentionally squashed onto a slide to reveal their contents 3. Smear: cells suspended in a fluid (e.g. blood, semen, cerebro-spinal fluid, or a culture of microorganisms) 4. Section: sample is supported in some way so that very thin slices can be cut, mounted on slides, and stained.

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Sample Preparation

• Tissue samples are very delicate and can easily be distorted • For sectioning the sample has to be fixed: • Freezing • Chemical fixation → paraffin sections • Sections are cut using a microtome • thickness of 3 - 5µm (paraffin) • Section is then placed on a slide • cells are colorless → staining • hematoxylin and eosin (H&E) stain • Covering with a glass coverslip • Ready to be examined

From https://en.wikipedia.org/wiki/File:Retina_--_high_mag.jpg

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Bright Field Microscopy

Advantages Disadvantages • Simplicity of setup • can only image dark or strongly • Cheap refracting objects effectively • Widely available • diffraction limits resolution to • Living cells can be seen approximately 0.2 micrometres → limits the practical magnification limit to ~1500x • Out-of-focus light from points outside the focal plane reduces image clarity • Inspecting cells often requires staining and fixation to increase contrast, but this kills the cell.

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Microscopy

A huge selection of optical microscopy techniques are available: • Dark field • Phase contrast • Fluorescence • Super-Resolution microscopy

As well as: • X-ray microscopy • Electron microscopy

From https://commons.wikimedia.org/wiki/File:FluorescentCells.jpg

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Photography

• 1822: first permanent photoetching by French inventor Nicéphore Niépce

• in 1826 or 1827, “View from the Window at Le Gras” • Bitumen based process that required at least 8 hours of exposure

• partnership with Louis Daguerre

• Niépce died in 1833

• 1837: daguerreotype process: • silver-plated surface • sensitized by iodine vapor • developed by mercury vapor • "fixed" with hot saturated salt water • exposure time was measured in minutes instead of hours. From https://en.wikipedia.org/wiki/File:View_from_the_Window_at_Le_Gras_colorized_2020_new.png

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Photography Three advances comprise the corner-stones of modern photography:

1. color photography • First ‘color’ photographs: late 1800s • widespread accessibility: early 1900s.

2. portable camera • compact cameras developed by Kodak in the 1920s • instant cameras developed by Edwin Land and the Polaroid corporation between 1940 and 1960

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Photography Three advances comprise the corner-stones of modern photography:

3. digital camera • digital camera designed by Steven Sasson in the 1970s • widespread popularity by the late 1990s • integration of digital photography into mobile phones between 2000 and 2010 dramatically advanced photography to its current state of instantaneous accessibility

From https://en.wikipedia.org/wiki/File:Reflex_camera_simple_labels.svg

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Photography in Medicine

• 1840: first documented application • Alfred Francois Donne of the Charite Hospital in Paris photographed sections of bones, teeth, cells from body fluids and cellular debris

• 1849: first appearance of photographs in medical journals

• 1870: The Photographic Review of Medicine and Surgery • A journal dedicated to photographic case studies • published in Philadelphia

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Photography in Medicine

There are four main purposes for medical photography:

1. medical consultation and documentation

2. medical education

3. patient and family education

4. medical publications

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Photography in Dermatology

• Dermatology is a highly visual field • Photography is deeply integrated in clinical practise

• rash and lesion appearance and progression

From https://commons.wikimedia.org/wiki/File:Melanoma_Growth_over_14_Months.jpg

• Patient scan now self-document their skin • Teledermatology is becoming more common

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Photography in Wound Management and Trauma

• wound management • track the progression of wound healing • color changes indicate healing or infection • size can be documented with reference object

From https://commons.wikimedia.org/wiki/File:Wound_Healing.jpg

• documentation of physical abuse • often key evidence for legal proceedings

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Surgical Photography • Intra-operative images are shared with patients to better illustrate the findings • exploratory surgery • resection • pre- and postoperative images document patient progress • plastic and reconstructive surgery • Photographing is a sterile environment requires special care.

From https://commons.wikimedia.org/wiki/File:Radionecrosis_resection.jpg

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Photography in Medicine

Advantages Disadvantages

• Objective depiction • the image produced is often not the same as is seen with the • Fast documentation naked eye • influence of lighting • Cost effective • perspective projection does • Widely available not preserve angles or proportions • Pictures only require small • the three dimensionality amount of storage is not represented • Patient consent and patient confidentiality

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Endoscopy

• 1806: first endoscope was developed in by Philipp Bozzini in Mainz, Germany • 1853: Antonin Jean Desormeaux presents his device for endoscopic surgery to the French Academy of Sciences • First successful endoscopic surgery in a living patient • use of an external gasogene lamp • 1865: Dublin urologist Sir Francis Richard Cruise introduces an improved version of Desmoreaux's endoscope • cystoscopy, hysteroscopy, sigmoidoscopy, urethrotomy and thoracoscopy • use of an external electric lamp • 1908: internal light made possible by smaller bulbs • 1912: first laparoscopy

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Endoscopy

Endoscope: • flexible tube • delivers light to illuminate an organ or tissue • delivers high-resolution images in real time back to the physician • working channel for surgical instruments

working channel camera light tube

From https://commons.wikimedia.org/wiki/File:Insertion_tip_of_endoscope.jpg Alena-Kathrin Golla I Slide 45 I 30.10.2020

Laparoscopic Appendectomy

• incision just below the belly button • inflation of abdominal cavity

with CO2 • insertion of endoscope • two additional working ports for surgical instruments

From https://youtu.be/mbk36SrBkfU

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Laparoscopic Appendectomy

From https://youtu.be/mbk36SrBkfU

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Endoscopy

Advantages Disadvantages • very safe and effective tool in • cannot detect functional disease the diagnosis and therapy • depth of insertion is limited • minimally invasive • perforation of the stomach, • decrease in wound infection duodenum, and colon are highly • shortening in hospital stay unlikely but can occur due to • minimal preparation required excessive force → can be performed quickly • decreased venous return and/or • low morbidity and mortality rates hypoxia may occur if the stomach is overinflated with air • photographic and/or video documentation • requires extensive training for the surgeon

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Optical Coherence Tomography (OCT)

• Basic concept has been simultaneously developed by multiple research groups: • 1990: Adolf Fercher et al. (Vienna, Austria) • 1990: Naohiro Tanno et al. (Yamagata , Japan) • 1991: David Huang et al. (Massachusetts, USA) • coined the term „ Optical Coherence Tomography “

• 1993: first in vivo OCT images displaying retinal structures

• 1996: first commercially available ophthalmic OCT

• 1997: first endoscopic OCT images

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Optical Coherence Tomography (OCT)

1. Light source for light with low temporal coherence length 2. Beam is split 1. directed at the sample surface 2. directed at a scanning reference mirror. 3. detector captures the interference of light rays reflected back from both arms

From https://commons.wikimedia.org/wiki/File:OCT_B-Scan_Setup.GIF

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Optical Coherence Tomography (OCT)

• Constructive interference is observed as an intensity maximum when the optical paths of both arms are exactly equal.

• By changing the distance of the reference mirror we can scan through the z-axis.

From https://commons.wikimedia.org/wiki/File:OCT_B-Scan_Setup.GIF

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Optical Coherence Tomography (OCT)

• resolution of OCT is much higher than that of other medical imaging methods: • OCT: 5 - 20 μm • CT: 0.5-0.625 mm • MRI: 1-2 mm • resolution is highly anisotropic: much higher axial resolution

• penetration depth is lower than US • OCT: 1 - 3 mm • US: up to 10 cm

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Optical Coherence Tomography (OCT)

• Ophthalmology: • Established and heavily used in clinical practice • high-resolution imaging of the retina and anterior segment • vascular health of the retina via a technique called OCT

• Cardiology: • Intravascular OCT to image coronary arteries in order to visualize vessel wall lumen morphology and microstructure

• Dermatology: • diagnosis of various skin lesions

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Optical Coherence Tomography (OCT)

From https://commons.wikimedia.org/wiki/File:SD-OCT_Optic_Disc_Cross-Sections.png

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Optical Coherence Tomography (OCT)

Advantages Disadvantages • Live sub-surface images at • limited to imaging 1 to 2 mm near-microscopic resolution below the surface in biological • Instant, direct imaging of tissue tissue morphology • no preparation of the sample or subject • no contact • no ionizing radiation

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Magnetic Particle Imaging (MPI)

• 2001: developed by Royal Philips Research lab in Hamburg, Germany

• 2005: Nature publication

• Tomographic imaging using the nonlinear response of magnetic particles, Bernhard Gleich and Jürgen Weizenecker

• 2013: first commercial (pre-clinical) MPI scanner was launched by the joint venture of Bruker and Philips

• 2019: Magnetic Insight introduces the first commercially available MPI system with integrated CT

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Magnetic Particle Imaging (MPI)

• iron oxide nanoparticles tracer

• broken down in the liver, where the iron is stored and used to produce hemoglobin

• very responsive to even weak magnetic fields

• the human body does not contain anything which will create magnetic interference in imaging

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Magnetic Particle Imaging (MPI)

• ferromagnetic material has a nonlinear magnetization • particle magnetization saturates at a certain magnetic field strength.

• modulation field: oscillating magnetic field, • the magnetization M is dependent on the time • M(t) contains a series of harmonic frequencies • selection field: time constant magnetic field • vanishes in the center of the imaging device (the field-free point, FFP) • increases in magnitude towards the edges

• by steering the FFP through the volume of interest, a tomographic image can be generated.

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Magnetic Particle Imaging (MPI)

Advantages Disadvantages • High resolution (~0.4 mm) • No morphology • Fast image results (~20 ms) • Still in preclinical phase • No radiation • safety limits are currently • No iodine being set • No background noise (high contrast)

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Magnetic Particle Imaging (MPI)

• Bernhard Gleich, Jürgen Weizenecker and team - Magnetic Particle Imaging (MPI) https://youtu.be/1mIn3bO6RFA

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Summary

 Nuclear Imaging

 Scintigraphy

 Single-photon emission computed tomography (SPECT)

 Positron emission tomography (PET)  Optical Imaging

 Microscopy

 Photography

 Endoscopy

 Optical coherence tomography (OCT)  Magnetic Particle Imaging (not in the exam)

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