1. Einstein on Brownian Motion 1905 five important papers DTI Basics – Water Diffusion (DTI – Diffusion Tensor Imaging)

2. Conventional T 2 WI DW-EPI Why USE DTI MRI : Detection of Acute Stroke “Diffusion Weighted Imaging (DWI) has proven to be the most effective means of detecting early strokes” Lehigh Magnetic Imaging Center Sodium ion pumps fail - water goes in cells and can not diffuse – DW image gets bright (note – much later cells burst and stroke area gets very dark)

3. Why USE DTI MRI Why USE DTI MRI Tumor T2 (bright water) DWI (x direction) (T2 (bright water)+(diffusion)) Contrast (T1 + Gadolinium) T2 (bright water)

4. Why DTI MRI (more recently): Fiber Tracking

5. Diffusion Weighted Image X direction David Porter - November 2000 Artifact or Abnormality  Higher diffusion in X direction  lower signal 1 st level of complexity

6. RF Gx Gy Gz - Time (gradient strength) T2T2 + diffusion T2 Image Sequence Excite Measure diffusion Regular T2 image

7. 2nd Level of complexity DWI : 3 Direction courtesy of Dr Sorensen, MGH, Boston David Porter - November 2000  single-shot EPI diffusion-weighted (DW) images with b = 1000s/mm 2 and diffusion gradients applied along three orthogonal directions  Higher diffusion  lower signal D zz D xx D yy Measuring Diffusion in other directions (examples)

8. 3rd level of complexity Diffusion Tensor Imaging Basics Measures water diffusion in at least 6 directions Echo-planar imaging (fast acquisition) Collecting small voxels (1.8 x 1.8 x 3mm), scanning takes about 10 minutes How can we track white matter fibers using DTI

9. Useful for following white matter tracts in healthy brain  Higher diffusion  lower signal water Diffusion ellipsoid White matter fibers

10. IsotropicAnisotropic Adapted from: Beaulieu (2002). NMR in Biomed; 15:435-455  Higher diffusion  lower signal White matter fibers

11. x y z DTI ellipsoid measure 6 directions to describe no diffusion Ellipsoid represents magnitude of diffusion in all directions by distance from center of ellipsoid to its surface.

12. Pierpaoli and Basser, Toward a Quantitative Assessment of Diffusion Anisotropy, Magn. Reson. Med, 36, 893-906 (1996) Ellipsoid Image Tract Information available through DTI

13. Tractography Zhang & Laidlaw: http://csdl.computer.org/comp/proceedings/vis/2004/8788/00/87880028p.pdf.http://csdl.computer.org/comp/proceedings/vis/2004/8788/00/87880028p.pdf Superior view color fiber mapsLateral view color fiber maps

14. Diffusion Tensor Imaging data for cortical spinal tract on right side blue = superior – inferior fibers green = anterior – posterior fibers red = right – left fibers Note tumor is darker mass on left side of axial slice axial sag cor MRISC

15. FA + color (largest diffusion direction) red = right – left green = anterior – posterior blue = superior - inferior

16. Proton spectroscopy (also can do C, O, Ph,.. Nuclei) Looking at protons in other molecules ( not water) (ie NAA, Choline, Creatine, …….) Need > mmol/l of substances high gyromagnetic ratio ( ) Just like spectroscopy used by chemist but includes spatial localization MRS – Magnetic Resonance Spectroscopy

17. Just looking at Proton Spectroscopy Just excite small volume Do water suppression so giant peak disappears Compare remaining peaks Frequency precession

18. MRS – Magnetic Resonance Spectroscopy Frequency of precession amplitude NAA Cr Cho NAA = N-acetyl aspartate, Cr = Creatine, Cho = Choline

19. Multi – Voxel Spectroscopy (aka Chemical Shift Imaging – CSI) Do many voxels at once Can be some disadvantages with signal to noise (S/N) and “voxel bleeding”

20. Evaluate Health of Neurons (NAA level) Normalize with Creatine (fairly constant in brain) Red means High NAA/CR levels

21. Epilepsy Seizures (effects metabolite levels) find location determine onset time

22. Other Nuclei of interest for Spectroscopy

23. 23Na in Rat Brain (low resolution images are sodium 23 images) (high resolution images are hydrogen images) Note: This slide has nothing to do with Spectroscopy. It is a standard imaging slide created with the 23Na nucleus and the hydrogen nucleus. It has been included to show an example of imaging done with a nuclei other than hydrogen.

24. Common Metabolites used in Proton Spectroscopy

25. Important Concepts What energies are used in each modality? How does the energy interact with the tissue? How is the image produced? What is represented in the image? What are important advantages and disadvantages of the major imaging modalities? What are the fundamental differences between the Xray technologies (2D vs 3D, Radiography vs CT vs Fluoroscopy)? What are the two major types of MRI images (T1, T2), and how are they different? How are Angiograms produced (both Xray and MRI)? Why are the advantages of combining imaging modalities?

26. Important Concepts What does DTI, diffusion tensor imaging, measure? What structures that we are interested in effect DTI images? What does the DTI ellipsoid represent? How might DTI be useful for clinical application or research? What are we looking at with proton spectroscopy? What are the three major metabolites we typically measure? What do we “need” to be able to do proton spectroscopy? What might proton spectroscopy be used for?

27. probably no use

29. Tractography Zhang & Laidlaw: http://csdl.computer.org/comp/proceedings/vis/2004/8788/00/87880028p.pdf.http://csdl.computer.org/comp/proceedings/vis/2004/8788/00/87880028p.pdf Superior view color fiber mapsLateral view color fiber maps

30. G 180 90 G echo TE At the echo time TE, NMR signal is decayed by, - T2 decay (spin-spin diffusion) - diffusive motion For any set of diff. gradient pulses Signal loss : by intra-voxel phase dispersion

31. DTI Scalar Parameters Trace: Magnitude of diffusion in a voxel. –Increases in damaged white matter Fractional Anisotropy (FA): Measure of directionally- restricted diffusion. –Decreases in damaged white matter Rosenbloom M, et al. (July 2004). NIAA pubs; http://www.niaaa.nih.gov/publications/arh27-2/146-152.htm

32. The Diffusion Tensor, D Diffusion is not equal in all directions (anisotropic). Use this to probe brain structure! Represent the diffusion pattern at each point in the brain using an ellipsoid.

33. Diffusion Vector (Colour) Map The three magnitudes of the diffusion ellipsoid can be shown using three colours (RGB). –Red = Left – Right –Green = Ant. – Pos. –Blue = Sup. – Inf. Map of major directions of water movement in the brain.

34. Fibre Tractography In principle, the locations of major white matter fibre tracts in the brain can be mapped using the information in the colour map, by “following the arrows.”

35. without hindrance with hindrance Hindered Diffusion (diffusion ellipsoid) WILSON

36. Information available through DTI – Orientation of λ 1 Useful for following white matter tracts

37. Information available through DTI -- A σ Related to the shape of the ellipsoid Independent of D av (normalized) Zero for a sphere, positive for other shapes Sensitive to myelination and cortical development av 

38. Diffusion Tensor Imaging ( A  ) Normal Adult Brain (A  maps)

39.  Higher diffusion  lower signal Tissue Sample A Tissue Sample B Freely Diffusing Water = Dark Freely Diffusing Water = Dark Larger D Larger D Restricted Diffusion = Bright Restricted Diffusion = Bright Smaller D Smaller D CELL EXTRA-CELLULAR SPACE FREELY DIFFUSING WATER IN EXTRA-CELLULAR SPACE

40. K-space view of the spin echo imaging Kx Ky 123.......n123.......n

41. X Diffusion-Weighting Y Diffusion- Weighting Z Diffusion-Weighting G FE G PE G SS RF Diff. Grad. along different axis SS PE FE

42. DTI (Diffusion Tensor Imaging) DTI (Diffusion Tensor Imaging) courtesy of Dr Sorensen, MGH, Boston David Porter - November 2000  single-shot EPI diffusion-weighted (DW) images with b = 1000s/mm 2 and diffusion gradients applied along three orthogonal directions  Higher diffusion  lower signal

43. Conventional T 2 WI DW-EPI Detection of Acute Stroke “Diffusion Weighted Imaging (DWI) has proven to be the most effective means of detecting early strokes” Lehigh Magnetic Imaging Center Sodium ion pumps fail, water goes in cells and can not diffuse.

44. Tumor T2 (bright water) DWI (x direction) (T2 (bright water)+diffusion) T1 + Gadolinium

45. The Diffusion Tensor, D Diffusion is not equal in all directions (anisotropic). Use this to probe brain structure! Diffusion ellipsoid for each voxel x y z

47. DTI Scalar Parameters Trace: The magnitude of diffusion in a voxel. Fractional Anisotropy (FA): The extent to which diffusion is directionally restricted.

48. Unused slides from Ana516 lecture

49. Pulse Sequence: Gradient-Echo Diffusion Weighting in X direction 90 o Excitation Image Acquisition RF Gx Gy Gz G -G-G EPI (T2) diffusion gradients

50. Gradient Coils

51. RF Gx Gy Gz - Time NO DIFFUISION with DIFFUISION y x protons (Hydrogen) signal loss

52. DIFFUSION MAPS (used to remove spin density, T1, T2, TR, and TE effects) S=S 0 e (-bDxx) Ln(S) = Ln(S 0 ) – bD xx or D xx = (Ln(S 0 ) – Ln(S))/b S 0 ( T2 * EPI) S (T2* EPI + weak Diffusion in X direction) D xx Most Important image weak

53. X Diffusion-Weighting Y Diffusion- Weighting Z Diffusion-Weighting G FE G PE G SS RF A Little More Detail SS PE FE x z y y x z

54. Tract tracing problems (fiber crossing)

55. 90 o Excitation Image Acquisition RF Gx Gy Gz G -G-G Do X, Y, and Z at the same time

56. But what is a diffusion tensor ? It is a mathematical description of the ellipsoid. y x z no diffusion D xx D xy D xz D yx D yy D yz D zx D zy D zz z -xz y-z xz y-z xy-xy

57. What is diffusion “Tensor” (D)? D xx D xy D xz D yx D yy D yz D zx D zy D zz D x’x’ 0 0 0 D y’y’ 0 0 0 D z’z’ S=S 0 exp(-bD) difussion gradient direction vector = (mathematical manipulation) Calculate FA (fractional anisotropy) Fiber track y ellipsoid reference framelab reference frame

58. Information available through DTI av  FA (fractional anisotropy) FA = ((D x’x’ -D av ) 2 + (D y’y’ -D av ) 2 + (D z’z’ -D av ) 2 ) 0.5 (D x’x’ 2 +D y’y’ 2 +D z’z’ 2 ) 0.5 D x’x’ D y’y’ D z’z’ FA = 0 FA = 0.9

59. FA (fractional anisotropy) MAP

60. Apparent Diffusion Coefficient ADC (AKA TRACE) ADC = (D xx + D yy + D zz )/3 Z Diffusion-Weighting X Diffusion-Weighting Y Diffusion Weighting Orientation independent used in clinical stroke, tumor, etc No directional information (ie direction of greatest diffusion)