Diffusion model fitting and tractography: A primer

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Diffusion model fitting and tractography: A primer Anastasia Yendiki HMS/MGH/MIT Athinoula A. Martinos Center for Biomedical Imaging 03/18/10 Why n how Diffusion model fitting and tractography 0/18

Why diffusion imaging? White matter (WM) is organized in fiber bundles Identifying these WM pathways is important for: Inferring connections b/w brain regions Understanding effects of neurodegenerative diseases, stroke, aging, development From Gray's Anatomy: IX. Neurology 03/18/10 Why n how Diffusion model fitting and tractography 1/18

Diffusion in brain tissue Differentiate tissues based on the diffusion (random motion) of water molecules within them Gray matter: Diffusion is unrestricted isotropic White matter: Diffusion is restricted anisotropic 03/18/10 Why n how Diffusion model fitting and tractography 2/18

How to describe diffusion At every voxel we want to know: Is this in white matter? If yes, what pathway(s) is it part of? What is the orientation of diffusion? What is the magnitude of diffusion? 03/18/10 Why n how Diffusion model fitting and tractography 3/18

Magnetic resonance imaging can provide diffusion encoding Magnetic field strength is varied by gradients in different directions Image intensity is attenuated depending on water diffusion in each direction Compare with baseline images to infer on diffusion process Diffusion MRI g 4 g 5 Diffusion encoding in direction g 1 g 2 g 3 No diffusion encoding 03/18/10 Why n how Diffusion model fitting and tractography 4/18 g 6

Need to know: Gradient directions True diffusion direction Applied gradient direction Maximum attenuation True diffusion direction Applied gradient direction No attenuation Diffusion-encoding gradient g Diffusion detected Diffusion-encoding gradient g Diffusion not detected To capture all diffusion directions well, gradient directions should cover 3D space uniformly Diffusion-encoding gradient g Diffusion partly detected 03/18/10 Why n how Diffusion model fitting and tractography 5/18

How many gradient directions? Acquiring data with more gradient directions leads to: + More reliable estimation of diffusion measures Increased imaging time Subject discomfort, more susceptible to artifacts due to motion, respiration, etc. Diffusion tensor imaging (DTI): Six directions is the minimum Usually a few 10 s of directions Diffusion spectrum imaging (DSI): Usually a few 100 s of directions 03/18/10 Why n how Diffusion model fitting and tractography 6/18

Need to know: b-value The b-value depends on pulse sequence parameters: b = γ 2 G 2 δ 2 (Δ - δ/3) γ the gyromagnetic ratio G the strength of the diffusion-encoding gradient δ the duration of each diffusion-encoding pulse Δ the interval b/w diffusion-encoding pulses 90 δ 180 acquisition G Δ 03/18/10 Why n how Diffusion model fitting and tractography 7/18

How high b-value? Increasing the b-value leads to: + Increased contrast b/w areas of higher and lower diffusivity Decreased signal-to-noise ratio Less reliable estimation of diffusion measures DTI: b ~ 1000 sec/mm 2 DSI: b ~ 10,000 sec/mm 2 Data can be acquired at multiple b-values for trade-off Repeat acquisition and average to increase signal-tonoise ratio 03/18/10 Why n how Diffusion model fitting and tractography 8/18

Looking at the data A diffusion data set consists of: A set of non-diffusion-weighted a.k.a baseline a.k.a. lowb images (b-value = 0) A set of diffusion-weighted images acquired with different gradient directions g 1, g 2, and b-value >0 The diffusion-weighted images have lower intensity values Baseline image b=0 b 1, g 1 b 2, g 2 b 3, g 3 Diffusionweighted images b 4, g 4 b 5, g 5 b 6, g 6 03/18/10 Why n how Diffusion model fitting and tractography 9/18

Pre-process images Data analysis steps FSL: eddy_correct, rotate_bvecs Fit a diffusion model at every voxel DTK: DSI, Q-ball, or DTI FSL: Ball-and-stick (bedpost) or DTI (dtifit) Reconstruct pathways DTK: Deterministic tractography using DSI, Q-ball, or DTI model FSL: Probabilistic tractography (probtrack) using ball-and-stick model DTK: www.trackvis.org, FSL: www.fmrib.ox.ac.uk/fsl 03/18/10 Why n how Diffusion model fitting and tractography 10/18

Models of diffusion Model Diffusion spectrum: Full distribution of orientation and magnitude Orientation distribution function (ODF): No magnitude info Ball-and-stick: Orientation and magnitude for up to N anisotropic compartments (default N=2) Tensor: Single orientation and magnitude Software DTK (DSI option) DTK (Q-ball option) FSL (bedpost) DTK (DTI option) FSL (dtifit) 03/18/10 Why n how Diffusion model fitting and tractography 11/18

A bit more about the tensor A tensor can be thought of as an ellipsoid It can be defined fully by: 3 eigenvectors e 1, e 2, e 3 (orientations of ellipsoid axes) 3 eigenvalues λ 1, λ 2, λ 3 (lengths of ellipsoid axes) λ 1 e 1 λ 2 e 2 λ 3 e 3 03/18/10 Why n how Diffusion model fitting and tractography 12/18

Tensor: Physical interpretation Eigenvectors express diffusion direction Eigenvalues express diffusion magnitude Isotropic diffusion: λ 1 λ 2 λ 3 Anisotropic diffusion: λ 1 >> λ 2 λ 3 λ 1 e 1 λ 2 e 2 λ 3 e 3 λ 1 e 1 λ 2 e 2 λ 3 e 3 03/18/10 Why n how Diffusion model fitting and tractography 13/18

Tensor: Summary measures Faster diffusion Slower diffusion Mean diffusivity (MD): Mean of the 3 eigenvalues MD(j) = [λ 1 (j)+λ 2 (j)+λ 3 (j)]/3 Anisotropic diffusion Isotropic diffusion Fractional anisotropy (FA): Variance of the 3 eigenvalues, normalized so that 0 (FA) 1 FA(j) 2 = 3 2 [λ 1 (j)-md(j)] 2 + [λ 2 (j)-md(j)] 2 + [λ 3 (j)-md(j)] 2 λ 1 (j) 2 + λ 2 (j) 2 + λ 3 (j) 2 03/18/10 Why n how Diffusion model fitting and tractography 14/18

Tensor: More summary measures Axial diffusivity: Greatest eigenvalue AD(j) = λ 1 (j) Radial diffusivity: Average of 2 lesser eigenvalues RD(j) = [λ 2 (j) + λ 3 (j)]/2 Inter-voxel coherence: Average angle b/w the major eigenvector at some voxel and the major eigenvector at the voxels around it 03/18/10 Why n how Diffusion model fitting and tractography 15/18

Deterministic vs. probabilistic Deterministic methods give you an estimate of model parameters 5 Probabilistic methods give you the uncertainty (probability distribution) of the estimate 5 03/18/10 Why n how Diffusion model fitting and tractography 16/18

Tractography Deterministic: One streamline per seed voxel Probabilistic: Multiple streamline samples per seed voxel (drawn from probability distribution) Sample 1 Sample 2 03/18/10 Why n how Diffusion model fitting and tractography 17/18

Tractography outputs Deterministic: One streamline per seed voxel Probabilistic: A probability distribution (sum of all streamline samples from all seed voxels) 03/18/10 Why n how Diffusion model fitting and tractography 18/18