MR-DTI: Non-invasive imaging of neuroanatomy of white matter Guido Gerig

1. MR-DTI:Non-invasive imaging of neuroanatomy of white matter Guido Gerig

2. Acknowledgments Contributors: • Martin Styner • Susumu Mori • Andy Alexander • Gordon Kindlmann • Randy Gollub • National Alliance for Medical Image Computing (NIH U54EB005149)

3. Use of these slides • Slides were borrowed from various researchers, and we are working on getting permissions for distribution. • Slides can be used for own purposes. • Please do not distribute these slides. • Please do no put slides into public download space.

4. T1w T2w

6. 5D 6Mo 14Mo

7. Networking and Brain Connectivity Major Fiber Tracts extracted from DT MRI UNC Computer Science: Network wire cabinets

8. Gray matter DT MRI White matter Diffusion Tensor Imaging (DT MRI) reveals White Matter Structure Courtesy of Susumu Mori, JHU

9. White matter White Matter Structure • Goal: Measure properties associated with the direction of white matter Fibers White Matter Fibers

10. Example: Corticospinal Tract Source: Duke NeuroAnatomy Web Resources (Christine Hulette) B: Superior longitudinal fasciculus C: Superior occipitofrontal fasciculus D: Cingulum E: Inferior longitudinal fasciculus F: Inferior occipitofrontal fasciculus Tractography: Coronal view

11. t1 t2 t3 Diffusion • Random ‘Walk’ of Water Molecules DT-MRI A. Alexander

12. Diffusion • Diffusion: Brownian motion of one material through another • Anisotropy: diffusion rate depends on direction newspaper Kleenex Gordon Kindlimann

13. Biological Restricted Diffusion • Sextra >> Sintra • Diffusion influenced by mean free path • Tortuosity DT-MRI A. Alexander

14. Biological Restricted Diffusion • Cellular degeneration (necrosis)- Diffusion increases DT-MRI A. Alexander

15. Aniostropic Restricted Diffusion • Diffusion has angular dependence DT-MRI A. Alexander

16. How can we measure diffusion without perturbing the system?

18. Main diffusion direction Nodes of Ranvier Myelin sheet Diffusion and white matter • Diffusion MRI measures diffusion of mainly water molecules • Isotropic medium → molecules move with Brownian motion. • In biological tissues diffusion is often anisotropic • In white matter: “Local structure” • Insulating myelin sheet, low probability to cross into axon • Dense axon bundles exhibits strongly directional local structure • Diffusion along fiber bundle is main diffusion direction

19. (An)isotropic diffusion Isotropic diffusion Free diffusion Probability Distribution Anisotropic diffusion Restricted diffusion Probability Distribution Courtesy of Susumu Mori, John Hopkins University Medical School

20. DWI (indirectly) senses the structure of the tissue by measuring water molecule displacement along a chosen direction. r' End diffusion coefficient in the y direction (= Dy) y r Start

21. If the path of the water molecule is affected by restrictions such as cellular material, the measured diffusion coefficient is reduced intracellular space r r' extracellular space

22. If the tissue structures are oriented, the path of the water molecule (and the measured diffusion coefficients) will reflect this. r' diffusion coefficient in the y direction (= Dy) y r diffusion coefficient in the x direction(= Dx) x Dx > Dy

23. Magnetic Resonance Imaging (MRI) • Larmor Frequency • Magnetic Field Gradient, G

24. Diffusion Weighted (DW) MRI • Accumulated Phase

25. DW-MRI II Attenuation!

26. The pixel signal intensity, S, is related to the b-value and the diffusion coefficient, D, through: This equation (Steyskal Tanner Equation) has two unknowns, the signal intensity for b = 0 (S0) and D. Therefore, at least 2 measurements must be made, each at a different b-value to calculate D.

27. Equation for the diffusion attenuation  G    S  2 2 2 ln    G    D = - bD   S 3 0 Signal Intensity D b-value

28. Measuring D for a Given Direction: Simplified model of two b values (b=0 and b=nnnn) intercept = S0 b-value 1000 0 slope = D ln(S)

29. DWI and ADC 1 G/cm 6 G/cm 10 G/cm 13 G/cm Signal Intensity b-value

30. The b-value is the contrast “knob” in a diffusion experiment and is varied in magnitude and in a specified number of directions. Increasing the b-value increases the contrast between slow and fast diffusing water molecules. Images courtesy: Susumu Mori (JHU) Increasing b-value

31. Apparent Diffusion Coefficient (ADC) Map with Different Measurement Direction Gradient direction X Y Z Only the diffusion along a gradient direction can be measured Courtesy of Susumu Mori, John Hopkins University Medical School

32. Diffusion Weighted Images T2W Reference So (b ~ 0 sec/mm2) 12 DW encoding directions Si (b=912 sec/mm2) DT-MRI Alexander Courtesy JE Lee

33. Measurement along Multiple Directions • Diffusion MRI measures along single gradient directions • Diffusion Weighted Images (DWI) • In principle: Arbitrary gradient directions • 6 different directions → Tensor • 12/24 directions → stability • Diffusion Tensor Imaging (DTI) • High angular acquisition • Sampling of orientation diffusion • Higher order representations (fiber crossings) • Qball (D. Tuch, MGH), >256 dirs • Others: Van Wedeen (MIT), Frank (UCSD) Modified from DavidTuch, MGH

34. Image: “IJK” x Gradients: g1 = (1,0,1) g2 = (1,-1,0) … Dxx, Dxy … slow=K y medium=J z fast=I World: e.g. “RAS” superior anterior right DWI: Three Coordinate Systems “Image Orientation” “Measurement Frame”

35. Measured Apparent Diffusivities 12 encoding directions DT-MRI Alexander Courtesy JE Lee

36. What is “Diffusion – Weighted” Imaging? In “Conventional” MRI, image contrast reflects the local relaxation (T1, T2) environment of the water molecules. In “Diffusion-Weighted” Imaging (DWI), image contrast reflects the physical structure of the Tissue (via the local diffusion distribution).

37. Simplification and assumption Orientational Diffusion Fct Diffusion ellipsoid Courtesy of Susumu Mori, John Hopkins University Medical School

38. The Diffusion Tensor DT-MRI Alexander Courtesy JE Lee

39. DWI summary: MRI newspaper Kleenex • Diffusion: Brownian motion of one material through another • Anisotropy: diffusion rate depends on direction • Magnetic gradients create spatial planar waves of proton phase • Destructive interference measures diffusion along gradient direction only

40. DWI crash course: Model Single Tensor Model (Basser 1994) Ai Dxz Dxx Dxy Tensor estimation D A0 Dyy Dyz Dzz gi

41. Anisotropy & Color-coded Orientation Isotropic GM Anisotropic WM Courtesy of Susumu Mori, John Hopkins University Medical School

42. DTI Tensor Visualization Color: FA value ITK: DTIFiberTubeSpatialObject & SpatialObjectViewers (Julien Jomier)

43. Here comes Ross Whitaker