Introduction to Modern Imaging Physics and Techniques used in Clinical Neurology
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1 Introduction to Modern Imaging Physics and Techniques used in Clinical Neurology Benjamin M. Ellingson, Ph.D., M.S. Associate Professor of Radiology, Biomedical Physics, Bioengineering, and Psychiatry UCLA Neuro-Oncology Program Director, UCLA Brain Tumor Imaging Laboratory (BTIL) Depts. of Radiological Sciences and Psychiatry David Geffen School of Medicine at UCLA CTSI: Modern Imaging Techniques in Clinical Neuroscience Research April 2016
2 Overview Brief History of Neuroimaging Technology Basic Anatomic MRI T2-Weighted MRI T2-Weighted FLAIR Pre- and Post-Contrast T1-Weighted MRI Advanced MRI Techniques Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI) Perfusion MRI (DSC and ASL) Functional MRI MR Spectroscopy Basic PET Imaging
3 Brief History of Neuroimaging Technology
4 Pneumoencephalogram s Brain soft tissue is not opaque on x-ray Walter Dandy, 1918 Injecting filtered air into ventricular system outlines the ventricles and surface of brain Great advance in neuroimaging - but very dangerous
5 Cerebral Angiography 1930 s - Present Egas Moniz, 1927 Injection of positive contrast (iodine) to highlight blood vessels Still used today for certain procedures
6 Computed Tomography (CT) 1970 s - Present William Olendorf (1961), Godfrey Hounsfield (1973), and Allan Cormack (1973) Collects x-rays at various angles around the body, then reconstructs it in 2D (computed axial tomography, CAT) Repeated for multiple slices X-Ray Detectors Patient X-Ray Source
7 Positron Emission Tomography (PET) Present Developed by Edward Hoffman and Michael Phelps (Wash U, later to UCLA) Uses biochemicals labeled with anti-matter to image metabolism and/or follow molecular probes
8 Positron Emission Tomography (PET) Present First human PET scanner was developed by Edward Hoffman and Michael Phelps (Wash U, later to UCLA) Uses biochemicals labeled with anti-matter to image metabolism and/or follow molecular probes MRI 18 F-FDOPA PET
9 Magnetic Resonance Imaging (MRI) Present MRI uses strong magnetic fields and radio waves to image water protons in the body Magnetic fields cause protons on water molecules to absorb RF energy at a certain frequencies (FM - determined by the Larmor Equation & Gyromagnetic Ratio)
10 Magnetic Resonance Imaging (MRI) Present Different tissues then release this RF energy differently (relaxation) depending on local magnetic environment The rates at which RF energy are released/dissipate are T1 and T2
11 Magnetic Resonance Imaging (MRI) Present Damadian,Science, NMR characteristics differ between normal tissue and cancer
12 Magnetic Resonance Imaging (MRI) Paul Lauterbur & Sir Peter Mansfield (Nobel Prize) first MRI images Lauterbur Mansfield
13 Magnetic Resonance Imaging (MRI) Paul Lauterbur & Sir Peter Mansfield (Nobel Prize) first MRI images Damadian - First Human Scan Achieved Currently used routinely First MRI Scanner First MR scan, 1977
14 Why MRI? No radiation (only magnetic fields and radio waves) Better soft tissue contrast More detailed anatomy of the brain Multiple ways to acquire images (flexibility) Physiologic imaging CT Scan MRI Scan
15 Basic Clinical Neuroimaging Protocol T2-Weighted MRI T2-Weighted FLAIR MRI Pre- and Post-Contrast T1-Weighted MRI
16 Basic Clinical Neuroimaging Protocol T2-Weighted MRI Related to rotational mobility of water molecules Darker the Image on T2-Weighted MRI
17 Basic Clinical Neuroimaging Protocol T2-Weighted MRI Related to rotational mobility of water molecules Mobile water = Long T2 = Bright on T2w T2-Weighted MRI
18 Basic Clinical Neuroimaging Protocol T2-Weighted MRI Sensitive to general pathology (non-specific) Edema& Tumor?&
19 Basic Clinical Neuroimaging Protocol T2-Weighted FLAIR MRI Fluid Attenuated Inversion Recovery = FLAIR Uses a RF pulse to null signals from CSF Results in T2-weighting, but dark CSF T2-Weighted MRI FLAIR
20 Basic Clinical Neuroimaging Protocol T2-Weighted FLAIR MRI Sensitive (but not specific) to pathology Edema?' Tumor?'
21 Basic Clinical Neuroimaging Protocol Pre-Contrast T1-Weighted MRI Also related to water mobility Short T1 = Bright on T1-Weighted MRI Blood products = shorten T1 on pre-contrast (bright) Pre-Contrast T1-Weighted MRI Blood Products
22 Basic Clinical Neuroimaging Protocol Post-Contrast T1-Weighted MRI Tumor vasculature causes contrast agent to leak into the brain Contrast agents shorten T1 (bright on T1w)
23 Basic Clinical Neuroimaging Protocol Post-Contrast T1-Weighted MRI Tumor vasculature causes contrast agent to leak into the brain Contrast agents shorten T1 (bright on T1w) Pre-Contrast T1-Weighted Post-Contrast T1-Weighted Gadolinium Contrast Injected into Veins
24 Basic Clinical Neuroimaging Protocol T2 vs. FLAIR T2-Weighted FLAIR Edema Tumor Dark Ventricles
25 Basic Clinical Neuroimaging Protocol T1 vs. T2 Pre-Contrast T1-Weighted T2-Weighted Edema Tumor
26 Basic Clinical Neuroimaging Protocol Pre and Post-Contrast T1 Pre-Contrast T1-Weighted T2-Weighted Edema Tumor
27 Basic Clinical Neuroimaging Protocol High-Resolution 3D T1-Weighted Images Used for brain morphometry (e.g. cortical thickness, tumor volume, etc.) Wang, PLoS One, 2013
28 Advanced MRI T1 and T2 characteristics do not tell us everything Physiologic Imaging - Tells us about function Cell Density and Proliferation Metabolism Signaling Perfusion
29 Advanced MRI Routine Advanced MRI at UCLA: Diffusion MRI - Microstructure & location/density of axon tracts Perfusion MRI - Vascularity, blood flow Functional MRI - Brain function & reorganization MR Spectroscopy - Brain metabolite concentrations
30 Diffusion MRI
31 Diffusion MRI Restricted Diffusion
32 Diffusion MRI
33 Diffusion MRI Diffusion MRI in Neuro-Oncology Apparent diffusion coefficient (ADC) and tumor cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008; Ellingson, 2010) ADC (or mean diffusion) = cell density ( hypercellularity ) ADC = cell density ( hypocellularity ) ADC Map Edema Necrosis Viable Tumor (Dark)
34 Diffusion MRI
35 Diffusion MRI ADC Before Radiation ADC After Radiation
36 Diffusion MRI Diffusion MRI in Acute Stroke Intracellular water diffusivity is slower than extracellular water diffusivity Ischemia results in swelling of intracellular volume Increased DWI signal, decreased measured ADC Normal Extracellular Ischemia Extracellular Intracellular Intracellular
37 Diffusion MRI Diffusion MRI in Acute Stroke Courtesy of Jeff Alger, UCLA Brain Mapping Center
38 Diffusion MRI Diffusion MRI in Acute Stroke Courtesy of Jeff Alger, UCLA Brain Mapping Center
39 Diffusion Tensor Imaging (DTI) Measure diffusion in many directions ADC perpendicular to white matter tracts is low ADC parallel to white matter tracts is high
40 Diffusion Tensor Imaging Fiber Tractography Create pseudoaxons in the direction of largest ADC d! r(s) ds! r ( s 1 ) =!! ν 1 ( r ( s) )! r ( s 2 )! r s ( ) Fiber Tracking! ν 1! r s ( ) ( )
41 Diffusion Tensor Imaging Fiber Tractography Create pseudoaxons in the direction of largest ADC d! r(s) ds! r ( s 1 ) =!! ν 1 ( r ( s) )! r ( s 2 )! r s ( ) Fiber Tracking! ν 1! r s ( ) ( )
42 Diffusion Tensor Imaging DTI Tractography Used for pre-surgical planning to avoid cutting important parts of the brain
43 Diffusion Tensor Imaging DTI Tractography Deterministic vs. Probabilistic Tractography Deterministic One Streamline per seed voxel Probabilistic A probability distribution (sum of all streamlines from all seed voxels) Courtesy of Anastasia Yendiki, MGH/Harvard, Martinos Center
44 Diffusion Tensor Imaging DTI Tractography Used to understand the strength of connections between brain regions Courtesy of Human Connectome Project Courtesy of McGill University
45 Perfusion MRI Dynamic Susceptibility Contrast (DSC)-MRI Acquire dynamic MR images during injection of contrast Acquired between pre and post-contrast T1-weighted images Pre-Contrast T1-Weighted Dynamic Perfusion MRI Post-Contrast T1-Weighted Gadolinium Contrast Injected into Veins
46 Perfusion MRI Dynamic Susceptibility Contrast (DSC)-MRI Acquire dynamic MR images during injection of contrast Models the first pass of contrast through the vessels
47 Perfusion MRI Dynamic Susceptibility Contrast (DSC)-MRI Add up all contrast that passes through vessels = Blood Volume
48 Perfusion MRI Dynamic Susceptibility Contrast (DSC)-MRI Acquire dynamic MR images during injection of contrast Models the first pass of contrast through the vessels Raw Dynamic Data Post-Contrast T1-Weighted Cerebral Blood Volume
49 Perfusion MRI Dynamic Susceptibility Contrast (DSC)-MRI Acquire dynamic MR images during injection of contrast Models the first pass of contrast through the vessels Raw Dynamic Data Post-Contrast T1-Weighted Cerebral Blood Volume
50 Perfusion MRI DSC-MRI in Stroke Copen, Neuroimaging Clin N Am, 2011
51 Perfusion MRI DSC-MRI in Stroke Copen, Neuroimaging Clin N Am, 2011
52 Arterial Spin Labeling (ASL) No Contrast Uses magnetically tagged or labeled blood Courtesy of JJ Wang, UCLA Brain Mapping Center
53 Arterial Spin Labeling (ASL) No Contrast Uses magnetically tagged or labeled blood Zaharchuk, MRM, 1999
54 Arterial Spin Labeling (ASL) No Contrast Uses magnetically tagged or labeled blood Bokkers, Stroke, 2012
55 Functional MRI Changes in brain function cause a change in the amount of oxygen in blood Hemoglobin = molecule that carries oxygen, contains iron (magnetic) Oxyhemoglobin Deoxyhemoglobin
56 Functional MRI Changes in brain function cause a change in the amount of oxygen in blood Hemoglobin = molecule that carries oxygen, contains iron (magnetic) Changes in oxygenation cause a change in MRI 97% Oxygen - 3% Halothane 0% Oxygen - 100% Nitrogen Ogawa, PNAS, 1990
57 Functional MRI Perform a series of tasks - finger tapping, language, etc. Used for surgical planning - avoid important areas of the brain
58 Functional MRI Resting-state fmri - No Tasks Signal fluctuates over time in sync with other areas of the brain networks Fox, Front Syst Neurosci, 2010
59 Functional MRI Resting-state fmri No Tasks Signal fluctuates over time in sync with other areas of the brain networks Xuan, PLoS One, 2012
60 MR Spectroscopy Water protons far outnumber other protons in the body With MR Spectroscopy we can suppress water protons and examine other biochemicals within the brain Courtesy of MGH/Harvard Radiology Courtesy of Hesselink, UCSD
61 MR Spectroscopy Water protons far outnumber other protons in the body With MR Spectroscopy we can suppress water protons and examine other biochemicals within the brain Cho NAA
62 MR Spectroscopic Imaging (MRSI) Fast MRS technique to create an image of metabolites
63 MR Spectroscopic Imaging (MRSI) Fast MRS technique to create an image of metabolites Lipids/Lactate NAA Choline
64 Positron Emission Tomography (PET) Uses biochemicals labeled with anti-matter to image metabolism and/or follow molecular probes
65 Positron Emission Tomography (PET) Uses biochemicals labeled with anti-matter to image metabolism and/or follow molecular probes Fischman et al., Clin Pharmacokinet, 2002
66 Positron Emission Tomography (PET) Brain Tumor Recurrence Pre-Surgical (9/21/10) Post-Surgical (9/24/10) 10/5/10 11/3/10 Recurrence (12/28/10) T1+C FLAIR
67 Positron Emission Tomography (PET) Brain Tumor Recurrence Pre-Tx 1 Month Post-Tx 2 Months Post-Tx 4 Months Post-Tx 6 Months Post-Tx Recurrence 4.5 Years Post-Tx 18 F-FDOPA SUV
68 18 F-FDOPA PET FLAIR FDOPA PET FLAIR FDOPA PET
69 Overview Brief History of Neuroimaging Technology Basic Anatomic MRI T2-Weighted MRI T2-Weighted FLAIR Pre- and Post-Contrast T1-Weighted MRI Advanced MRI Techniques Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI) Perfusion MRI (DSC and ASL) Functional MRI MR Spectroscopy Basic PET Imaging
70 Benjamin M. Ellingson, Ph.D., M.Sc. Associate Professor of Radiology, Biomedical Physics, Psychiatry and Bioengineering UCLA Brain Tumor Imaging Lab (BTIL) Depts. of Radiological Sciences and Psychiatry David Geffen School of Medicine University of California - Los Angeles bellingson@mednet.ucla.edu American Cancer Society Research Scholar Grant NIH/NCI R21CA University of California Cancer Research Grant National Brain Tumor Society Research Grant Siemens Healthcare Research Grant Genentech/Roche Research Grant Art of the Brain Ziering Family Foundation in memory of Sigi Ziering Singleton Family Foundation Clarence Klein Fund for Neuro-Oncology UC Cancer Research Coordinating Committee Grant UCLA Jonsson Comprehensive Cancer Center Grant UCLA Institute for Molecular Medicine Seed Grant UCLA Radiology Exploratory Research Grant
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