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

StructuralFunctional

Molecular

MRI

MR Spectroscopy

MRI Functional Neuroimaging Tools for brain tumors

– Diffusion Weighted & Tensor Imaging

– Perfusion/Permeability Imaging

– MR Spectroscopy

– Susceptibility-weighted Imaging

– Functional MRI

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

Cellularity in brain tumorsDiffusion Weighted Imaging

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.

Low grade →high grade gliomas

Postoperative Diffusion Abnormality

Pre-op Immed post-op

DWI ADC

2-month F/U 4-month F/U

Recurrence?

Anti-VEGF in recurrent GBM

ADC- Tumor cellularity, tumor ischemia, extracellular matrix

Mak HKF et al., Cancer Imaging, 2012

T2W Post Gd

Ktrans DWI ADC

Tumor Infiltration

Diffusion Tensor Imaging

Isotropic diffusion Anisotropic diffusion

Random Directionality

DWI vs DTI

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

DTI - Loss of Anisotropy

DTI and Tumor ImagingT2

From: J. Burdette and Neeraj Chepuri, WFU

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)

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

Endothelial Proliferation and Vascularity

Perfusion Imaging

*blood flow per unit time through thecapillary bed of a tissue

Unit: Milliliter / 100 gram Tissue / Minute

Perfusion*

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

baseline bolus

recirculation

T2*-weighted susceptibility signal time curve

ab

b x 100a

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)

Met Glioma

Glioma vs. Solitary Metastasis

MetsGlioma

Glioma vs. Metastasis: Peritumoral rCBV

0.39

2.34

0.79

1.11

Mets

Glioma

Law M et al. Radiology 2002

Metabolic Activity

MR Spectroscopy

Proton Magnetic Resonance Spectroscopy (1H-MRS)

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

Examples of 1H-MRS (TE=136ms) of different brain tumours.

Howe et al. Magn Reson Med 2003

Special Property of Lactate

Inverted

Recurrent tumour versus radiation necrosis

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

Proton MR Spectroscopy (1H MRS)

Lipid/Lactate

NAACho

Cr

Choline

Normal

Brandao 2013 Magn Reson Imaging Clinics N Am

Citrate at 2.6ppm is significantly more prominent in aggressive pediatric astrocytoma

Bluml et al. Neuro-Oncology 2011

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

↑

NecrosisADCCBVMRS

Tumor necrosis versus PUS

GBM Abscess

T2W

DWIADC

Post Gd

Necrotic tumor (cerebral metastasis)

Mills SJ et al., Cancer Imaging, 2012

T2 Post-contrast T1 rCBV

Delayed Radiation Necrosis

3-month follow up

Radiation Necrosis

Tumor

Hemorrhage Susceptibility Weighted Imaging

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

Functional MRI

Preoperative Brain Mapping

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

Tumour腫瘤

Speech areas

Corticospinal tract皮層脊髓束

Neuronavigation plan- preoperative術前神经导航計劃

Paper marks speech areas over the cortex

Sylvian fissure

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)

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

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

Endothelial Proliferation and Vascularity

Permeability Imaging

T1W Dynamic contrast enhanced (DCE)

transK

epk

evpv

Cp(t)

Ce(t)

Sorensen AG, et al. Cancer Research 2009

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)

Preoperative DTI TractographyHigh-Grade Glioma: Stereotactic Examination

3D SPGR PostGad

T1

3D FSE T2

PyramidalTract

Postoperative MRIHigh-Grade Glioma: Day 2 Post-Op

PostGad T1

FLAIR

DTI Fiber Tractography: Brain ShiftN

imsk

y et

al.

Neu

rosu

rger

y (2

005)

8-15 mm of intra-op brain shift

DSC pMRI derived variables:

1.Relative cerebral blood volume (rCBV)

2.Abnormal recovery (aRec)

Color Overlay of rCBV Map

Glioblastoma multiforme

Low grade astrocytoma

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.

Limitations

• Susceptibility Artifacts–Near brain-bone-air interface• Anterior & middle cranial fossa

–Metal, blood products, Ca++

6 mm

4 mm

T1 effect

Blood-Brain-Barrier Leakage

Nyquist ghost

Glioblastoma multiforme

Low- Grade Glioma

Recent Advances in MR Neuroimagingof Brain Tumors

Diffusion Imaging DWI- tumor necrosis vs pus - cellularity DTI- tumor infiltration, stereotactic surgery

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

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)

GBM with increased rCBV

Multiple Sclerosis plaque

GBM

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

Mathematical Operation: Fourier Transformmation

Astrocytes Track Along WM

Anisotropy:Fractional anisotropy (FA) is different in different directions

Chemical shift is field independent!

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

Postoperative Brain TumorPre-op Immed post-op

4-mo post-op

1-mo post-op