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Diffusion Tensor MR Imaging & White Matter Tracking
Elias R. Melhem, M.D., Ph.D. Professor of Radiology and Neurosurgery Chief, Division of Neuroradiology Hospital of the University of Pennsylvania
Overview
q Definitions:
– Diffusion Tensor Imaging (DTI)
q DTI
– Data Acquisition – Data Processing (Tractography)
q Applications q Advances
Definitions
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Diffusion Principle
Ln(S/S0) = -bD
diffusion coefficient dependent on sensitizing gradients
Tissue differences in the diffusivity of water molecules (slow incoherent motion) can be brought
to the MR sequence
Pulsed Diffusion Gradients
RF SS / FE / PE Pulsed Gradients G δ ∆ echo
b = γ 2G2δ2 (∆ - δ /3)
G δ 90ο 180ο Pulsed Gradients SI SI SI time G
rephasing
X
G
dephasing
The Effect of Bipolar Gradients on the Mxy of Tissues with Random Motion (Brownian)
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G
dephasing
Pulsed Gradients SI SI SI SI time T2 - decay G
rephasing
The Effect of Bipolar Gradients on the Mxy of Tissues with Reduced Random Motion
Isotropic vs. Anisotropic Diffusion
Isotropic Anisotropic Direction of diffusion-sensitizing gradients
b = 560 b = 560
Diffusion Anisotropy: Orientation of Fiber Tracts in White Matter
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Diffusion Tensor Imaging Diffusion Tensor
q In anisotropic media (WM) diffusion can be
characterized by a Tensor
q When the Tensor is determined for every voxel:
Diffusion Tensor Imaging
Basser et al. 1994 J Magn Reson
Diffusion Tensor
Mxx Mxy Mxz Myx Myy Myz Mzx Mzy Mzz
λxx 0 0 λyy 0 0 λzz Diagonalize
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q Eigenvalues: shape of the ellipsoid q Trace (λxx + λyy + λzz): volume of the ellipsoid q Euler angles: direction of the ellipsoid
Diffusion Tensor Diffusion Ellipsoid Map Data Acquisition
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Data Acquisition
DTI: 2D multi-shot or single-shot SE-EPI – Cardiac-gated – Navigator-echo-corrected – TR/TE:5000 – 6000 / 92 – Number of Averages: ~ 4 – FOV:24 x 24 cm2 - Slice thickness: 3mm (no gap) – Matrix:64 x 64 (zero-filled 128) – Diffusion: 6 to 40 directions – Two b-values (0 and 800 s/mm2)
D-WI Using 6 Different Directions
x y z xy xz yz i b=0
Data Processing
Step 1: DTI images realigned using the AIR program Step 2: Elements of the Tensor obtained with multi-variant linear square fitting Step 3: Eigenvalues maps determined by diagnolizing the Tensor Step 4: Principal eigenvectors used for vector maps Step 5: Fractional anisotropy (FA) and Trace calculation Step 6: Tracking Algorithm and Color Maps
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Diffusion Tensor Imaging: Eigen Maps
λxx λyy λzz
Diffusion Tensor MR Imaging
Trace FA Σ (λi – D)2 (λi )2 Σ =
Fractional Anisotropy & Vector Maps
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White Matter Tractography
A C B
* *
Thresholds: FA > 0.6 Angle < 40o
White Matter Tractography: DTI
uncinate fasciculus corpus callosum corticospinal tract anterior thalamic radiation inferior occipitofrontal fasciculus inferior longtudinal fasciculus superior longitudinal fasciculus cingulum
Brain Stem Tractography: DTI
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Applications Stroke Transient Left Sided Weakness:: Relationship of Infarct to Corticospinal Tract
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White Matter Diseases
q Biophysical basis for Diffusion Anisotropy in WM q Biophysical basis for Reduced Diffusivity in
Demyelinating Diseases
Adrenoleukodystrophy (ALD)
q X-linked disorder that affects brain white matter q Most severe phenotype: Cerebral Form q Cerebral form has 3 distinct pathologic:
I- Vasogenic edema and active demyelination II- Inflammatory reaction and disruption of BBB III- Axonal destruction and cavitation
Diffusion Anisotropy: ALD
FA T2-W ADC
Itoh et al. Neurology
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Diffusion Anisotropy: ALD
FA
Average ADCi (SD) FA (SD) NAWM 0.66 (0.12) 0.52 (0.16) Area I 0.84 (0.16) 0.31 (0.12) Area II 1.36 (0.19) 0.22 (0.07) Area III 1.73 (0.15) 0.13 (0.05) Itoh et al. ISMRM 2000
DTI and MR Spectroscopic Imaging
Eichler et al. Radiology in-press
ALD: MR Tractography Using DTI
200 400 600 800 1000 1200 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39
Volume
genu Splenium
Fractional Anisotropy ( ) Volume (mm
3) ( )Slice position ( colonal ) Anterior Posterior
ALD Normal Mori et al. ISMRM 2000
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Decreased ADC??
q Cytotoxic Edema + Demyelination q Irreversible axonal damage q Predictor of Activity q Predictor of Progression
Acute Demyelination: Multiple Sclerosis Chronic Demyelination: Multiple Sclerosis
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Acute Disseminated Encephalomyelitis
T2 D-WI ADC
Central Pontine Myelinolysis
T2-W SE D-WI ADC
Asphyxia in Premature Infants
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Periventricular Leukomalacia
q Selective vulnerability of the periventricular
white matter in the premature neonate to ischemic, infectious, or metabolic insults
q Volume of lateral ventricles is strongly
related to severity of spastic cerebral palsy
Melhem et al. Radiology
Periventricular WM Restricted Diffusion
Acute Follow up ADC MPRAGE
Periventricular Leukomalacia
Normal PVL
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Periventricular Leukomalacia
Normal PVL
Hoon et al. Neurology
Developmental Brain Anomalies Holoprosencephaly
q Spectrum of complex congenital brain and facial
malformations resulting from defective cleavage of the developing forebrain during the first five weeks of embryonic development
q HPE is divided into four major categories
Alobar Semilobar Lobar Middle hemispheric variant
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Holoprosencephaly
Present Present Present Present Present Lobar (n=2) Present Present Present Present Absent Semilobar (n=5) Present Present Present Fused Absent Alobar (n=2) ICP MCP SCP MLF CPST
Melhem et al. Radiology
Alobar Holoprosencephaly Semilobar Holoprosencephaly
Normal
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Syntelencephaly
FA FA
Focal Cortical Dysplasia Band Heterotopia
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Tumors MR Tractography in Brain Tumors MR Tractography in Brain Tumors
Tumor B more infiltrative than Tumor A
Mori et al. MRM 2002
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Amytrophic Lateral Sclerosis (ALS) ALS
Disease of Lower and often Upper Motor Neurons
q Pre-clinical markers of disease q Markers of disease progression q Ability to identify and quantify upper motor neuron
involvement
ALS
Control ALS with UMN involvement
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Advances
q Faster Acquisitions
– Parallel Imaging (SENSE-SMASH)
q Number and Orientation of Diffusion Gradients q Greater SNR
– High field Scanner – Better receiver coils
q Improvement in Tracking Methods q Spatial Normalization
Faster Acquisitions DTI with SENSE
256x256x60/ SENSE: 2
1.8 minutes per average!
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Number of Direction of Diffusion Gradients
30 Diffusion Directions
Jones 30: 2 averages / direction; 256x256x40 / SENSE: 2
4 minutes per average!
3D Isotropic DTI
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High Resolution Isotropic 3D DTI
Anisotropy Map Vector Map FA
Voxel: 0.8 mm3
Fiber Tracking
Fiber Tracking: Diffusion Spectrum Technique
A B C A B C
Higher Spatial Resolution
kissing fibers
A B C D
Higher Spatial Resolution
A B C D
intertwining fibers
Wiegell et al. Radiology 2000
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Connectivity of Corticospianl Tracts Using Probabilistic Approach Callosal Connectivity Using Probabilistic Approach Spatial Normalization of WM Tracts
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Population Maps of WM Tracts
10 subjects after elastic warping
Acknowledgement
FM Kirby Research Center:
q Susumu Mori, PhD q Xavier Golay, PhD q James Pekar, PhD q Peter van Zijl, PhD q Ryuta Itoh, MD, PhD
University of Pennsylvania:
q Christos Davatzikos, PhD q Harsih Popotani, PhD q Sumei Wang, MD q Ron Wolf, MD, PhD q John Woo, MD
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