Diffusion Tensor Processing and Visualization Ross Whitaker University of Utah National Alliance for Medical Image Computing Acknowledgments Contributors: • A. Alexander • G. Kindlmann • L. O’Donnell • J. Fallon National Alliance for Medical Image Computing (NIH U54EB005149) Diffusion in Biological Tissue • Motion of water through tissue • Sometimes faster in some directions than others Kleenex newspaper • Anisotropy: diffusion rate depends on direction isotropic anisotropic G. Kindlmann The Physics of Diffusion • Density of substance changes (evolves) over time according to a differential equation (PDE) Change Derivatives in (gradients) in density Diffusion – space matrix, tensor (2x2 or 3x3) Solutions of the Diffusion Equation • Simple assumptions – Small dot of a substance (point) – D constant everywhere in space • Solution is a multivariate Gaussian – Normal distribution – D plays the role of the covariance matrix\ QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. • This relationship is not a coincidence – Probabilistic models of diffusion (random walk) D Is A Special Kind of Matrix • The universe of matrices Matrices Square Skew symmetric Nonsquare D is a “square, symmetric, positivedefinite matrix” Symmetric (SPD) Positive Properties of SPD • Bilinear forms and quadratics Quadratic equation – implicit equation for ellipse (ellipsoid in 3D) • Eigen Decomposition – Lambda – shape information, independent of orientation – R – orientation, independent of shape – Lambda’s > 0 Eigen Directions and Values (Principle Directions) v3 v1 l2 l1 l1 l3 l2 v1 v2 v2 Tensors From Diffusion-Weighted Images • Big assumption – At the scale of DW-MRI measurements – Diffusion of water in tissue is approximated by Gaussian • Solution to heat equation with constant diffusion tensor • Stejskal-Tanner equation – Relationship between the DW images and Physical constants Strength of gradient D kth DW Image Base image Gradient direction Duration of gradient pulse Read-out time Tensors From Diffusion-Weighted Images • Stejskal-Tanner equation – Relationship between the DW images and D Physical constants Strength of gradient Duration of gradient pulse Read-out time kth DW Image Base image Gradient direction Tensors From Diffusion-Weighted Images • Solving S-T for D – Take log of both sides – Linear system for elements of D – Six gradient directions (3 in 2D) uniquely specify D – More gradient directions overconstrain D • Solve least-squares 2D » (constrain lambda>0) S-T Equation Shape Measures on Tensors • Represent or visualization shape • Quanitfy meaningful aspect of shape • Shape vs size Different sizes/orientations Different shapes Measuring the Size of A Tensor • Length – (l1 + l2 + l3)/3 – (l12 + l22 + l32)1/2 • Area – (l1 l2 + l1 l3 + l2 l3) • Volume – (l1 l2 l3) Sometimes used. Generally used. Also called: Also called: “Root sum of squares” “Mean diffusivity” “Diffusion norm” “Trace” “Frobenius norm” l3 Shape Other Than Size Barycentric shape space l1 l2 l1 >= l2 >= l3 (CS,CL,CP) Westin, 1997 G. Reducing Shape to One Number Fractional Anisotropy Properties: Normalized variance of eigenvalues Difference from sphere FA (not quite) FA As An Indicator for White Matter • Visualization – ignore tissue that is not WM • Registration – Align WM bundles • Tractography – terminate tracts as they exit WM • Analysis – Axon density/degeneration – Myelin • Big question – What physiological/anatomical property does FA measure? Various Measures of Anisotropy A1 VF RA FA A. Alexander Visualizing Tensors: Direction and Shape • Color mapping • Glyphs Coloring by Principal Diffusion Direction • Principal eigenvector, linear anisotropy determine color e1 Coronal Axial R=| e1.x | G=| e1.y | B= | e1.z | Sagittal Pierpaoli, 1997 G. Issues With Coloring by Direction • Set transparency according to FA (highlighttracts) • Coordinate system dependent • Primary colors dominate – Perception: saturated colors tend to look more intense – Which direction is “cyan”? Visualization with Glyphs • Density and placement based on FA or detected features • Place ellipsoids at regular intervals Backdrop: FA Color: RGB(e1) G. Glyphs: ellipsoids Problem: Visual ambiguity Worst case scenario: ellipsoids one viewpoint: another viewpoint: Glyphs: cuboids Problem: missing symmetry Superquadrics Barr 1981 Superquadric Glyphs for Visualizing DTI Kindlmann 2004 Worst case scenario, revisited Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Backdrop: FA Color: RGB(e1) Going Beyond Voxels: Tractography • Method for visualization/analysis • Integrate vector field associated with grid of principle directions • Requires – Seed point(s) – Stopping criteria • FA too low • Directions not aligned (curvature too high) • Leave region of interest/volume DTI Tractography Seed point(s) Move marker in discrete steps and find next direction Direction of principle eigen value Tractography J. Fallon Whole-Brian White Matter Architecture L. O’Donnell 2006 Atlas Generation Analysis High-Dimensional Saved structure information Atlas Automatic Segmentation Path of Interest D. Tuch and Others A Find the path(s) between A and B that is most consistent with the data B The Problem with Tractography How Can It Work? • Integrals of uncertain quantities are prone to error – Problem can be aggravated by nonlinearities • Related problems – Open loop in controls (tracking) – Dead reckoning in robotics Wrong turn Nonlinear: bad information about where to go Mathematics and Tensors • Certain basic operations we need to do on tensors – – – – – Interpolation Filtering Differences Averaging Statistics • Danger – Tensor operations done element by element • Mathematically unsound • Nonintuitive Averaging Tensors • What should be the average of these two tensors? Linear Average Componentwise Arithmetic Operations On Tensor • Don’t preserve size – Length, area, volume • Reduce anisotropy • Extrapolation –> nonpositive, nonsymmetric • Why do we care? – Registration/normalization of tensor images – Smoothing/denoising – Statistics mean/variance What Can We Do? (Open Problem) • Arithmetic directly on the DW images – How to do statics? – Rotational invariance • Operate on logarithms of tensors (Arsigny) – Exponent always positive • Riemannian geometry (Fletcher, Pennec) – Tensors live in a curved space Riemannian Arithmetic Example Riemannian Linear Interpolation Interpolation Low-Level Processing DTI Status • Set of tools in ITK – Linear and nonlinear filtering with Riemannian geometry – Interpolation with Riemannian geometry – Set of tools for processing/interpolation of tensors from DW images • More to come… Questions