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MRI evaluation of brain tumors- a review of functional neuroimaging techniques in
clinical practice
Dr. Henry KF MAK
Clinical Assistant Professor &Associate Director of 3T MRI Imaging Unit, University of
Hong KongClinical Instructor, Diagnostic Neuroradiology, University of
Virginia Medical Center,USA
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StructuralFunctional
Molecular
MRI
MR Spectroscopy
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MRI Functional Neuroimaging Tools for brain tumors
– Diffusion Weighted & Tensor Imaging
– Perfusion/Permeability Imaging
– MR Spectroscopy
– Susceptibility-weighted Imaging
– Functional MRI
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Pathologic – Radiologic Correlation
Pathology RadiologyCellularity T2/FLAIR SI,
DWI & ADC
Infiltration T2/FLAIR SI, DTI
Endothelial proliferation and Vascularity
Enhancement, Perfusion and Permeability Imaging
Metabolic Activity MRS
Necrosis Ring Lesion, MRS, DWI & ADC
Hemorrhage T1 and T2 SI, SWI
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Cellularity in brain tumorsDiffusion Weighted Imaging
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Apparent Diffusion Coefficient imaging
• Diffusion of water spins - isotropic • Based on molecular diffusion first described by
Einstein in 1905: Brownian motion
H2O molecule displacement is completely random and Is limited only by the boundaries of the container
Hagmann P, Radiographics 2006.
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Low grade →high grade gliomas
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Postoperative Diffusion Abnormality
Pre-op Immed post-op
DWI ADC
2-month F/U 4-month F/U
Recurrence?
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Anti-VEGF in recurrent GBM
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ADC- Tumor cellularity, tumor ischemia, extracellular matrix
Mak HKF et al., Cancer Imaging, 2012
T2W Post Gd
Ktrans DWI ADC
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Tumor Infiltration
Diffusion Tensor Imaging
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Isotropic diffusion Anisotropic diffusion
Random Directionality
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DWI vs DTI
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3T DTI with Parallel Imaging
centrumsemiovale
superiorlongitudinal
fasciculus
cingulum bundle
corpuscallosum,
body
55-directions, b=1000 s/mm2, with ASSET (R=2)
1.8 mm isotropic spatial resolution
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DTI - Loss of Anisotropy
DTI and Tumor ImagingT2
From: J. Burdette and Neeraj Chepuri, WFU
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MRI ScanHi-Res. Anatomical Scans
DTI Scan (15 minutes)DTI Map Processing
(~10 minutes)
DTI Fiber Tracking(~30 minutes)
Stereotactic Surgical NavigationAnatomical Images Integrated with DTI Fiber Tracks
Presurgical Image Processing
Courtesy of Jeffrey I. Berman, PhD (UCSF)
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shoulder
wrist
Roland Henry PhD, Jeff Berman, PhD (Radiology), Mitch Berger, MD (Neurosurgery)
DTI Fiber Tracking of Motor Fibers Launched from Intra-Operative Cortical Stimulation Seed Points
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Endothelial Proliferation and Vascularity
Perfusion Imaging
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*blood flow per unit time through thecapillary bed of a tissue
Unit: Milliliter / 100 gram Tissue / Minute
Perfusion*
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Dynamic Susceptibility T2*W(DSC) Perfusion MR Imaging
• What it is NOT Absolute measure of tissue
perfusion• What it IS Relative measure of tissue
volume, Rough estimation of
intravascular GD-DTPA• What it CAN BE Surrogate marker of
angiogenesis Predictor of outcome Potential endpoint of
angiogenesis treatment
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baseline bolus
recirculation
T2*-weighted susceptibility signal time curve
ab
b x 100a
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T2* signal intensity time curve
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60
Time
Sig
nal I
nten
sity
0
200
400
600
800
1000
1200
1400
1600
0 10 20 30 40 50 60
Time
Sig
nal I
nten
sity
Lung carcinoma metastasis
Grade IV glioma (glioblastoma multiforme)
Lung carcinoma metastasis
Grade IV glioma
(glioblastoma multiforme)
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Met Glioma
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Glioma vs. Solitary Metastasis
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MetsGlioma
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Glioma vs. Metastasis: Peritumoral rCBV
0.39
2.34
0.79
1.11
Mets
Glioma
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Law M et al. Radiology 2002
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Metabolic Activity
MR Spectroscopy
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Proton Magnetic Resonance Spectroscopy (1H-MRS)
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1H-MRS Metabolites @ 1.5 Tesla
Shift (ppm)
Biologic correlate Surrogate marker
NAA 2.01 Neuronal marker (density & function)
↓↓Tumor proliferation↓Edema
Cr 3.03 Energy buffer & shuttle
↓Tumorproliferation
Cho 3.19 Membrane turnover
↑↑Tumor proliferation
Lac 1.31 Anaerobic metabolism
↑Hypoxia; radioresistance
Lip 0.9-1.2 Necrosis ↑Rapid tissue destruction
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Examples of 1H-MRS (TE=136ms) of different brain tumours.
Howe et al. Magn Reson Med 2003
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Special Property of Lactate
Inverted
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Recurrent tumour versus radiation necrosis
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1H-MRS (TE=288ms) in a GBM patient in the splenium of the corpus callosum before and after superselective intra-arterial cerebral infusion of bevacizumab, showing reduction of Cho/NAA ratio posttreatment.
Jeon et al. AJNR 2012
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Proton MR Spectroscopy (1H MRS)
Lipid/Lactate
NAACho
Cr
Choline
Normal
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Brandao 2013 Magn Reson Imaging Clinics N Am
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Citrate at 2.6ppm is significantly more prominent in aggressive pediatric astrocytoma
Bluml et al. Neuro-Oncology 2011
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FunctionChange in
tumourN-acetyl-aspartate
(NAA)Neuronal marker ↓
Creatine (Cr) Cerebral metabolism marker ↓
Choline (Cho) Reflect membrane synthesis and degradation ↑
Myo-inositol (mI) Glial marker ↑Lactate (Lac) Sign of impaired energy
metabolism ↑Citrate Intermediate in
tricarboxylic acid cycle, malignant process marker
↑
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NecrosisADCCBVMRS
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Tumor necrosis versus PUS
GBM Abscess
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T2W
DWIADC
Post Gd
Necrotic tumor (cerebral metastasis)
Mills SJ et al., Cancer Imaging, 2012
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T2 Post-contrast T1 rCBV
Delayed Radiation Necrosis
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3-month follow up
Radiation Necrosis
Tumor
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Hemorrhage Susceptibility Weighted Imaging
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Susceptibility Weighted Imaging
• SWI is a fully velocity-compensated 3-D gradient-echo sequence.
• Consists of magnitude and phase images.
• Phase mask improves contrast by making low phase areas darker.
Sehgal et al., 2005
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Functional MRI
Preoperative Brain Mapping
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A right-handed patient with left temporal lobe tumor
speech functional activation just posterior to the tumour
Comparison of fMRI and intra-operative cortical stimulation for speech function mapping-A case study. XLZhu, Neursurgery Henry Mak, Neuroradiology
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Tumour腫瘤
Speech areas
Corticospinal tract皮層脊髓束
Neuronavigation plan- preoperative術前神经导航計劃
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Paper marks speech areas over the cortex
Sylvian fissure
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The navigation pointer is pointing at The speech area mapped out by cortical stimulation
Navigation (green cross) is exactly
over the fMRI speech area (pink circle)
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Pathologic – Radiologic Correlation
Pathology RadiologyCellularity T2/FLAIR SI,
DWI & ADC
Infiltration T2/FLAIR SI, DTI
Endothelial proliferation and Vascularity
Enhancement, Perfusion and Permeability Imaging
Metabolic Activity MRS
Necrosis Ring Lesion, MRS, DWI & ADC
Hemorrhage T1 and T2 SI, SWI
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Pathologic – Radiologic CorrelationPathology Radiology
Cellularity T2 SI, DWI & ADC
Endothelial proliferation and Vascularity
Enhancement, Perfusion and Permeability Imaging
Necrosis Ring Lesion, MRS, DWI & ADC
Hemorrhage T1 and T2 SI, SWI
Labeling Indices MRS, Th 201 and FDG
Infiltration T1 and T2 SI, DTI
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Endothelial Proliferation and Vascularity
Permeability Imaging
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T1W Dynamic contrast enhanced (DCE)
transK
epk
evpv
Cp(t)
Ce(t)
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Sorensen AG, et al. Cancer Research 2009
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MRI ScanHi-Res. Anatomical Scans
DTI Scan (15 minutes)DTI Map Processing
(~10 minutes)
DTI Fiber Tracking(~30 minutes)
Stereotactic Surgical NavigationAnatomical Images Integrated with DTI Fiber Tracks
Presurgical Image Processing
Courtesy of Jeffrey I. Berman, PhD (UCSF)
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Preoperative DTI TractographyHigh-Grade Glioma: Stereotactic Examination
3D SPGR PostGad
T1
3D FSE T2
PyramidalTract
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Postoperative MRIHigh-Grade Glioma: Day 2 Post-Op
PostGad T1
FLAIR
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DTI Fiber Tractography: Brain ShiftN
imsk
y et
al.
Neu
rosu
rger
y (2
005)
8-15 mm of intra-op brain shift
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DSC pMRI derived variables:
1.Relative cerebral blood volume (rCBV)
2.Abnormal recovery (aRec)
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Color Overlay of rCBV Map
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Glioblastoma multiforme
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Low grade astrocytoma
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Johnson G et al. Measuring blood volume and vascular transfer constant from dynamic T2*W contrast enhanced MRI. Magn Reson Med 2004; 51: 961-68.
Johnson G et al. Measuring blood volume and vascular transfer constant from dynamic T2*W contrast enhanced MRI. Magn Reson Med 2004; 51: 961-68.
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Limitations
• Susceptibility Artifacts–Near brain-bone-air interface• Anterior & middle cranial fossa
–Metal, blood products, Ca++
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6 mm
4 mm
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T1 effect
Blood-Brain-Barrier Leakage
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Nyquist ghost
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Glioblastoma multiforme
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Low- Grade Glioma
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Recent Advances in MR Neuroimagingof Brain Tumors
Diffusion Imaging DWI- tumor necrosis vs pus - cellularity DTI- tumor infiltration, stereotactic surgery
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Perfusion & Permeability Imaging rCBV- HGG vs LGG; HGG vs mets
(endothelial proliferation & vascularity) BBB permeability (ktrans) - HGG vs LGG rCBV/ ktrans - HGG vs post-irradiation
necrosis
Recent Advances in MR Neuroimagingof Brain Tumors
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Recent Advances in MR Neuroimagingof Brain Tumors
MR Spectroscopy: high Cho, low NAA- tumor, but not specific (neuronal loss and membrane breakdown) high lactate/lipid- HGG vs LGG (anaerobic
metabolism & tumor necrosis) low Cho, low NAA- post-irradiation necrosis
(fibrinoid necrosis)
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GBM with increased rCBV
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Multiple Sclerosis plaque
GBM
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What is MRS?
• MRS and MRI share the same physical principles
• MRS is a method which conveys the chemical composition of the tissue of interest
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Mathematical Operation: Fourier Transformmation
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Astrocytes Track Along WM
Anisotropy:Fractional anisotropy (FA) is different in different directions
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Chemical shift is field independent!
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H2O
NAA
CrPCr
Glu
Cho
Ins
H2O
NAA
CrPCr
Glu
Cho
Ins
CrPCr
CrPCr
NAANAA
6 5 4 3 2 1 0ppm
6 5 4 3 2 1 0ppm
Figure 1. 1H NMR Spectra of Human Brain at 4 Tesla (child): Grey matter (left) and white matter (right)
STEAM, TE = 6 ms, TR = 5 s, NT = 80, VOI = 8 ml
Gray matter White matter
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Postoperative Brain TumorPre-op Immed post-op
4-mo post-op
1-mo post-op