Application of diffusion MRI to cancer, heart and brain connectome imaging

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1 Department of Physics, NTU Application of diffusion MRI to cancer, heart and brain connectome imaging March 11, 2014 Wen-Yih Isaac Tseng MD, PhD Advanced Biomedical MRI Lab Center for Optoelectronic Medicine National Taiwan University College of Medicine

2 Diffusion phenomenon r(r,dt) r(r,2dt) r(r,3dt) r(r,d) = r(r,0) * P(r r, D) where P(r r, D) = probability density function

3 Encoding diffusion with MR d g d g g CPMG Spin-Echo f r 1a r 1b Dr = r - r The spin of each proton is endowed by a phase term Exp(iDf) where Df = 2pq ( r r) and q = ggd/2p

4 Diffusion signal and PDF Paul T. Callaghan Principle of nuclear magnetic resonance microscopy 1991 Given r(r,d) = r(r,0) * P(r r, D) where the phase term for each spin exp(idf) = exp(i2pq ( r r)) S S g) r ) P r r', D) exp igdg r' r) r r' q) r r) P r r', D) exp i2pq r' r) r r' ) dr' dr ) dr' dr D ) 2 S ( q ) r( r ) dr P ( R, D)exp( i Df) dr S exp f 0 r R

5 Diffusion-weighted EPI sequence Sequence Diffusion-weighted T2 Regular T2 image ln(s/s 0 ) S S0 g d Diffusion Module (q) Imaging Module (k) S S 2 δ ( (γ gd ) (Δ )D) 3 0 exp S0 exp ( bd) 5

6 Diffusion contrast varies with gradient directions Gzz Gxx Gyy 6

7 Diffusion-weighted imaging In 1990, Moseley et al demonstrated in an animal stroke model that the ADC decreased by approximately 30%-50% within 30 minutes after onset of focal ischemia. 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). Conventional T2WI DW-EPI 7

8 Diffusion anisotropy D = 1.2 x 10-3 mm 2 /s D = 0.4 x 10-3 mm 2 /s - Douek et al., JCAT 1991

9 Tensor model for diffusion isotropic anisotropic Courtesy: G. Kindlmann λ 1 = λ 2 = λ 3 λ 1 > λ 2 λ 3 λ 1 λ 2 > λ 3 Eigenvectors define alignment of axes 9

10 Diffusion tensor imaging (DTI) Garrido et al. (Circ Res 1994) and Basser et al. (Biophys J 1994) Diffusion-sensitive gradients [1 1 0] [1-1 0] [0 1 1] [0-1 1] [1 0 1] [-1 0 1] S( q) ln( ) S 0 TE q( t') 0 T ~ Dq( t') dt' ~ bd D ~ Dxx Dyx Dzx Dxy Dyy Dzy Dxz Dyz Dzz

11 Tensor invariants Apparent diffusion coefficient (ADC) ADC Fractional anisotropy (FA) FA trace) trace) trace) 1 Principal direction of diffusion tensor 1 st eigenvector (ev1) ADC FA colored ev1

12 First engenvector map

13 Detection of prostate cancer by ADC Chen et al. JMRI 2010

14 ADC correlates with Gleason scores Chen et al. JMRI 2010

15 Tseng et al. Radiology 216:128-39;2000

16 Myocardial fiber archiecture whole ventricle fibers Inner heart (Yellow) outer heart (Blue) Short-axis view posterior + L S I R

17 Motion of inner heart system partial fibers of inner heart view from base posterior = F Spiral-like Spiral fibers at Apex and Base might contribute to LV torsion Longitudinal fibers in the LV inner wall might contribute to longitudinal shortening F

18 Motion of outer heart system view from base F c posterior Force of contraction F c Circumferential fibers connecting LV and RV might contribute to radial contraction of LV wall Fc

19 Wendell JS Krieg, 1963

20 Diffusion MRI Conventional MRI Wedeen, MGH-NMR

21 Diffusion spectrum imaging 6D (q and k) Space Imaging S( k, q) ρ( r)exp( i 2π k r) P( r, R)exp( i 2π q R) drdr tissue I(x) E(q) P(r) = FT(E) ODF(u) = r 2 Pdr tensor Probability density function Orientation distribution function Wedeen, MGH-NMR

22 DSI acquisition scheme 3D q-space S(q) DSI Diffusion weighted image Fourier Transform P(r) P 2 () r r dr Orientational Distribution Function (ODF)

23 How can we assess white matter integrity from local diffusion information? ODF Orientation map Tractography Tractography was used to generate connection paths between points in the brain based on local diffusion direction 23

24 Male 49Y Bilateral left upper quadrianopsia Medial compression of the right lateral geniculate nucleus

25 The Geometric Structure of the Brain Fiber Pathways Wedeen et al. Science 2012;335: The 3D grid structure in an owl monkey brain Close-up view of the grid structure in the caudal brain

26 Fiber grid pattern: also found in human brain 26

27 Quantify fiber integrity GFA = SD (ODF)/RMS (ODF) ODF Generalized fractional anisotropy Calculated from the ODF Degree of myelination Directional coherence Axonal diameter and density GFA mapping 27

28 Mean Path Algorithm Arcuate Fasciculus (Right Side) Calculate the followings as Mean Path Step 1: Select ROI Step 3: Find the Orientation and the Center of Next Step Step 2: Find the Initial Orientation the and Center Chiang WY et al. ISMAR 2007

29 Tract-specific analysis Arcuate Fasciculus IFOF A Cingulum Stria Terminalis CST Uncinate Fasciculus Fornix SLF GFA profiles for each fiber tract

30 Loss of left-greater-than-right asymmetry in autism Lo et al. Psych Res Neuroimaging, 2011

31 Mean Path Algorithm Arcuate Fasciculus (Right Side) Calculate the followings as Mean Path Step 1: Select ROI Step 3: Find the Orientation and the Center of Next Step Step 2: Find the Initial Orientation the and Center Chiang WY et al. ISMAR 2007

32 Tract-specific analysis Arcuate Fasciculus IFOF A Cingulum Stria Terminalis CST Uncinate Fasciculus Fornix SLF GFA profiles for each fiber tract

33 Loss of left-greater-than-right asymmetry in autism Lo et al. Psych Res Neuroimaging, 2011

34 DSI template of 122 normal subjects SPM LDDMM DSI M1 M1 M1 M1 M2 M2 M2 M2 MNI space M M101.. M M101.. Intermediate DSI Template M M101.. M M101.. DSI Template

35 35

36 Association fibers 36

37 Commissural fibers 37

38 Projection fibers 38

39 74 tracts

40 74 Tracts Tracts Tracts An array-based brain connectome Steps 100 Steps Subjects

41 Conclusion Diffusion MRI allows us to probe tissue microstructure at microscopic level It is detects cancerous tissue It reveals ingenious design of fiber architecture of the myocardium It allows us to visualize and analysis connectivity of the wired brain Therefore, diffusion MRI is a potentially power tool in clinical cancer, cardiac and brain imaging

42 Thank you for your attention blog.roodo.com/nashchou/archives/ html

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