1. Introduction to Diffusion-weighted Imaging Joelle Sarlls, Ph.D. NIH MRI Research Facility National Institute of Neurological Disorder and Stroke National Institutes of Health

2. Motivation Magnetic resonance imaging provides information about the spatial distribution of water. Diffusion-weighted MRI (DWI) provides information about the motion of water. DWIs are sensitive to cellular architecture and tissue integrity. DWI can provide quantitative measures that are directly comparable. Diffusion imaging can be used to identify specific white matter tracts Over 1000 publications combining fMRI and DWI –120 since I gave this lecture last years ago

3. Outline What is diffusion? How do we measure diffusion in MRI? How do we extract directional information? What are the practical problems and limitations? Beyond the diffusion tensor

4. Outline

5. Diffusion Diffusion refers to the random translational (Brownian) motion of molecules that results from the thermal energy of theses molecules (for sphere) Stokes-Einstein

6. Gaussian Distribution 1D2D3D Large number of particles that are free to diffuse have a squared displacement of a Gaussian form Einstein, A. Ann Physik (1905) 4: 549-590

7. Diffusion For H 2 O at 37 o C D ≈ 3.0x10 -3 mm 2 /s T dif ≈ 30 ms r ≈ 25 μm If the motion of water is hindered by cell membranes, macromolecules, etc. the displacement will be less and D will appear lower.

8. Outline What is diffusion? How do we measure diffusion in MRI? How do we extract directional information? What are the practical problems and limitations? Beyond the diffusion tensor

9. Image Intensity in MRI Physical property of tissue water –ρproton density –T1relaxation time –T2relaxation time –T2*relaxation time –Ddiffusion coefficient Experimentally controlled parameters –Sequence Spin-echo/gradient echo –TRTime of Repetition –TETime to echo –b-valuediffusion-weighting factor Rotational motion, Magnetic field strength } Concentration of water Translational motion

10. Frequency ω0ω0 0+Z-Z GzGz Gradients make the resonance frequency a function of spatial position ω = γ B = γ B 0 + γ zG z

11. Basic Diffusion-weighting 90° +x S total -x 0 GxGx

12. Phase Twist +Z -Z 0

13. Basic Diffusion-weighting 90° +x S total -x 0 stationary moving GxGx

14. b-value = 1000 s/mm 2 b-value = 0 s/mm 2 Guess the intensity

15. Spin-echo Diffusion Preparation 90°180° RF G diff  Δ G Stejskal, EO and Tanner, JE. J Chem Phys (1965) 42 : 288-292 echo

16. DWI Non-diffusion-weighted signal intensity B-value sec/mm 2 Diffusion Coefficient mm 2 /sec

17. Typical DWI Single-shot “spin-echo” Echo Planar Imaging ParameterValueComment TE50-100msLimited by b-value TR>5sFully relaxed Matrix96 x 962.5 x 2.5 mm Slice Thickness2.5 mmEqual dimensions B-value~1000 s/mm 2 For brain* *Jones D., et al. Mag Res Med (1999) 42 : 515

18. 8 200400650 b (s/mm 2 ) Diffusion map S = S 0 e -bD Calculate Diffusion Parameters

19. b = 0 s/mm 2 I 0 b = 1100 s/mm 2 Gz Dz

20. 8 μm EM of mouse corpus callosum Water Diffusion in Tissue D perp << D par D perpendicular D parallel X Not Free Cell membranes Myelin Organelles Extracellular matrix Anisotropy

21. ADC b = 0 s/mm 2 Gz Gy Gx

22. b = 0 s/mm 2 720 s/mm 2 Diffusion Map 0.75 x 10 -3 mm 2 /s0.43 x 10 -3 mm 2 /s Acute Stroke Warach S., et al. Ann Neurol (1995) 37:231-241

23. Outline What is diffusion? How do we measure diffusion in MRI? How do we extract directional information? What are the practical problems and limitations? Beyond the diffusion tensor

24. 8 μm EM of mouse corpus callosum Water Diffusion in Tissue D perp << D par D perpendicular D parallel X Not Free Cell membranes Myelin Organelles Extracellular matrix Anisotropy

25. Anisotropic Diffusion

26. The Diffusion Tensor x y z Basser, P, et. al. J Magn Reson B (1994) 3 : 247-254

27. b = 0 s/mm 2 GxGyGz GxyGxz Gyz DTI b = 1100 s/mm 2

28. Calculate Diffusion Tensor

29. Diagonalize DT x y z ε3ε3 ε2ε2 ε1ε1 EigenvaluesEigenvectors

30. Quantitative Parameters Fractional Anisotropy 0 ≤ FA ≤ 1 Average Diffusivity x y z ε3ε3 ε2ε2 ε1ε1 <D><D>

31. isotropicanisotropic

32. FA

33. Directional Encoding for DTI z x y ε3ε3 ε2ε2 ε1ε1 Z X Y Pajevic S. and Pierpaoli C., Magn Reson Med (1999) 43 : 526-540

34. Directional Encoded Color Map

35. FA DECNo sym DEC LinearLine FieldPlanarSpherical

36. Applications of DTI Cerebral Ischemia (Stroke) Brain Cancer and Effects of Radiotherapy Multiple Sclerosis Epilepsy Metabolic Disorders Normal Brain Maturation and Aging Traumatic Brain Injury Alzheimer’s Disease Amyotrophic Lateral Sclerosis Niemann-Pick type C Disease Dementias Connectivity

37. Pediatric DIPG T2-weightedMDFADEC

38. Outline What is diffusion? How do we measure diffusion in MRI? How do we extract directional information? What are the practical problems and limitations? Beyond the diffusion tensor

39. Typical DW SSEPI Low Resolution Distortions - Field inhomogeneities Distortions - Diffusion weighting Insensitive to Bulk motion Time Efficient PROCON

40. CON: Distortions from field inhomogeneities Non-diffusion-weighted SSEPI T2-weighted FSE SSEPI corrected

41. CON: Distortions from DW FA maps DW SSEPI volumes

42. Other Common Problems in DTI Low SNR Incomplete Fat Suppression Bulk movement Cardiac pulsation

43. Low SNR 1.7mm iso1.3mm iso2.5 mm iso

44. Low SNR 1.7mm iso 4.913 mm 3 1.3mm iso 2.197 mm 3 2.5 mm iso 15.625 mm 3

45. Low SNR 1.7mm iso 4.913 mm 3 1.3mm iso 2.197 mm 3 2.5 mm iso 15.625 mm 3

46. Incomplete Fat Suppression b=1100 s/mm 2 MDFA

47. Cardiac Pulsation Diffusion weighting in Z

48. Bulk Movement

49. Outline What is diffusion? How do we measure diffusion in MRI? How do we extract directional information? What are the practical problems and limitations? Beyond the diffusion tensor

50. What isTractography? The use of orientation information from diffusion imaging to reconstruct estimates of white matter pathways in the brain.

51. Limitation to DTI comes from partial volume effects Typical resolution for SSEPI DTI 2.5 x 2.5 x 2.5 mm Cortical projection systems of left cerebral hemisphere

52. Partial Volume Effect DT ellipsoid distribution

53. Sub-millimeter DTI

54. Beyond Standard DTI High Angular Resolution Diffusion Imaging (HARDI) –Multi-tensor models –Non-parametric algorithums DSI, Qball, SD, PAS

55. Non-parametric Algorithms fODFdistributionfODFdistribution

56. b = 0 s/mm 2

57. ACKNOWLEDGEMENTS Peter Bandettini, PhD Carlo Pierpaoli, MD,PhD Ted Trouard, PhD Lindsay Walker, MS Kathy Warren, MD Emilie Steffen Dan Handwerker, PhD THANK YOU

58. Diffusion Profile IsotropicAnisotropic

59. Inherent Motion in Living Systems ei1ei1 ei2ei2 einein kyky kxkx Diffusion-Weighted MRI S n (t) = F[ k x (t), k y n ] e i  n S n (t) = F[ k x (t)+  k x n, k y n +  k y n ] e i  n

60. kyky kxkx PRO: insensitive to bulk motion S(t) = F[ k x (t)+  k x, k y +  k y ] e i 

61. DWI Non-diffusion-weighted signal intensity B-value sec/mm 2 Diffusion Coefficient mm 2 /sec Take two measures of signal and solve for D.

62. Average (Trace) Image

63. Calculated the ADC I ave b-value = 0 ADC map (mm 2 /sec)

64. Trace b = 0 s/mm 2 FA DEC Gx Gy GzGxy Gxz Gyz λ 1 +λ 2 +λ 3

65. Not all processing software is created equal! TORTOISECompetitor

66. Diffusion-Weighted MRI (DWI) Sensitizes MRI image intensity to small, thermally induced random motion of water molecules The motion of water within tissue is extremely sensitive to the microscopic architecture and integrity of the tissue For H 2 O at 37 o C D ≈ 3.0x10 -3 mm 2 /s T dif ≈ 30 ms r ≈ 25 μm Einstein, A. Ann Physik (1905) 4: 549-590

67. Identical anisotropy maintained throughout the entire voxel Anisotropy a small fraction of the voxel. Not experimentally observed Complete anisotropy, but variable orientation. Experimentally isotropic. Limitation to DTI : Spatial resolution