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Measuring Diffusion Properties in Tissue: The Diffusion Tensor & Derived Indices

Measuring Diffusion Properties in Tissue: The Diffusion Tensor & Derived Indices. Gwenaëlle Douaud FMRIB, University of Oxford. Historical description of the diffusion tensor. Formalised by Peter Basser and colleagues (1994a; 1994b).  In an isotropic, unconstrained environment:

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Measuring Diffusion Properties in Tissue: The Diffusion Tensor & Derived Indices

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  1. Measuring Diffusion Properties in Tissue: The Diffusion Tensor & Derived Indices Gwenaëlle Douaud FMRIB, University of Oxford ISMRM Weekend course – 5th of May 2012

  2. Historical description of the diffusion tensor • Formalised by Peter Basser and colleagues (1994a; 1994b)  In an isotropic, unconstrained environment: D = scalar  In an anisotropic, constrained environment: D = 33 definite symmetric positive D = “diffusion tensor” ISMRM Weekend course – 5th of May 2012

  3. Historical description of the diffusion tensor 1  In an anisotropic, constrained environment: D = 33 definite symmetric positive D = “diffusion tensor” 2 3 with i  {1,2,3} ISMRM Weekend course – 5th of May 2012

  4. Diffusion tensor indices: Mean Diffusivity • Formalised by Peter Basser and Carlo Pierpaoli (1995; 1996)  Magnitude of diffusion Bammer, 2003 • First clinical application: brain ischemia (Moseley et al., 1990; Warach et al., 1992)  Visible only 3 hours after onset of stroke Warach et al., 1995 ISMRM Weekend course – 5th of May 2012

  5. Diffusion tensor indices: diffusion anisotropy • Formalised by Peter Basser and Carlo Pierpaoli (1995; 1996)  Anisotropy of diffusion Bammer, 2003 RA = “Relative Anisotropy” ISMRM Weekend course – 5th of May 2012

  6. Diffusion tensor indices: diffusion anisotropy • Formal comparison of three anisotropy indices (Papadakis et al., 1999)  FA: mapped diffusion anisotropy with the greatest detail and SNR  VR: provided the strongest CNR, but with  noise contamination, resolution  RA: intermediate between FA and VR ISMRM Weekend course – 5th of May 2012

  7. Diffusion tensor indices: diffusion anisotropy • Further comparison between FA and RA (Hasan et al., 2004) ISMRM Weekend course – 5th of May 2012

  8. Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Developmental study: anatomical and tractography-defined ROI (Lebel et al., 2008) ISMRM Weekend course – 5th of May 2012

  9. Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Developmental study: comparison between ROI and VBD (Snook et al., 2007)  The discrepancies related to: - ROI approach inherently limited - issues with the spatial normalisation for VBD analysis - masking localised changes by averaging all the voxels within a ROI ISMRM Weekend course – 5th of May 2012

  10. Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Increasing sensitivity and interpretability of results compared with voxel-based approaches based purely on non-linear registration: TBSS (Smith et al., 2006) Mean Control Mean Patient TBSS VBD ISMRM Weekend course – 5th of May 2012

  11. Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Large developmental and ageing study using TBSS (Westlye et al., 2010) ISMRM Weekend course – 5th of May 2012

  12. Fractional Anisotropy and Mean Diffusivity: first applications • Development(review in Beaulieu et al., 1999) • Ageing(review in Moseley, 2002) • Cognitive performance (review in Moseley et al., 2002) • White matter diseases (review in Horsfield and Jones, 2002): multiple sclerosis (Horsfield et al., 1998), Alzheimer’s disease (Hanyu et al., 1998), ALS, CJD etc. • Psychiatric diseases (review in Lim and Helpern, 2002): schizophrenia (Buchsbaum et al., 1998), alcoholism (Pfefferbaum et al., 2000) , depression etc. ISMRM Weekend course – 5th of May 2012

  13. Fractional Anisotropy and Mean Diffusivity: Two complementary measures • An intriguing finding in multiple sclerosis (Ciccarelli et al., 2001) Patient White matter Control basal ganglia  Increased FA in the basal ganglia in MS: selective Wallerian degeneration, with the intact connections showing an increase of their coherence? ISMRM Weekend course – 5th of May 2012

  14. Fractional Anisotropy and Mean Diffusivity: Two complementary measures • Same findings seen in the basal ganglia in Huntington’s disease (Douaud et al., 2009) ISMRM Weekend course – 5th of May 2012

  15. Using the information from the PDD (Schwartzmann et al., 2005) 1 2 3 Douaud et al., 2009 ISMRM Weekend course – 5th of May 2012

  16. Decrease of the dispersion of the PDD in Huntington’s disease (Douaud et al., 2009) ISMRM Weekend course – 5th of May 2012

  17. Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • No difference in the white matter of mild cognitive impairment (MCI) patients using MD or FA (Douaud et al., 2011)  Mode of anisotropy (MO): 3rd moment of the tensor, introduced by Basser (1997), formalised by Ennis and Kindlamnn (2006). -1 Planar, disc-like 1~ 2: e.g., areas of crossing fibres +1 Linear, cigar-like 2~ 3: e.g., areas of one predominating fibre population ISMRM Weekend course – 5th of May 2012

  18. Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • Significant difference in the white matter of MCI patients, with an increase of MO MCI>CON AD>CON AD>CON Douaud et al., 2011 ISMRM Weekend course – 5th of May 2012

  19. Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • Significant increase of MO in MCI and AD also related to selective degeneration in crossing fibres region (here, centrum semiovale)? Douaud et al., 2011 ISMRM Weekend course – 5th of May 2012

  20. Beyond Fractional Anisotropy and Mean Diffusivity: Parallel and Perpendicular Diffusivity • Validated in animal models by Song and colleagues (2002; 2005)  Parallel diffusivity or axial diffusivity: assessing axonal injury = 1  Perpendicular diffusivity or radial diffusivity: assessing myelin injury ISMRM Weekend course – 5th of May 2012

  21. Beyond Fractional Anisotropy and Mean Diffusivity: Parallel and Perpendicular Diffusivity • Validated in humans using the model of callosotomy (Concha et al., 2006)  Axonal degradation  Myelin degradation ISMRM Weekend course – 5th of May 2012

  22. Diffusion tensor indices: in vivo models and histological validation • Basis of diffusion anisotropy in the brain: comprehensive review by Beaulieu (2002) • Anisotropy due to membrane, not myelin • Myelin modulates anisotropy • Axonal cytoskeleton does not contribute to anisotropy ISMRM Weekend course – 5th of May 2012

  23. Diffusion tensor indices: in vivo models and histological validation • Combined in vivo diffusion/histological study: animal model (van Camp et al., 2012) ISMRM Weekend course – 5th of May 2012

  24. Diffusion tensor indices: in vivo models and histological validation • Combined in vivo diffusion/histological study: epilepsy (Concha et al., 2010) ISMRM Weekend course – 5th of May 2012

  25. The depressing slide… • Sensitivity to noise increases with higher order moments: • noise(MD) < noise(FA) < noise (MO) • Crossing-fibres: effects can be averaged out Groeschel et al., ISMRM 2011 ISMRM Weekend course – 5th of May 2012

  26. The depressing slide… • Sensitivity to noise increases with higher order moments: • noise(MD) < noise(FA) < noise (MO) • Crossing-fibres: effects can be averaged out • Crossing-fibres: problematic interpretation of  and  ISMRM Weekend course – 5th of May 2012

  27. The depressing slide… • Sensitivity to noise increases with higher order moments: • noise(MD) < noise(FA) < noise (MO) • Crossing-fibres: effects can be averaged out • Crossing-fibres: problematic interpretation of  and  • Crossing-fibres: not only influence on FA, but also MD (Vos et al., 2012) Vos et al., ISMRM 2011 ISMRM Weekend course – 5th of May 2012

  28. The depressing slide… • Sensitivity to noise increases with higher order moments: • noise(MD) < noise(FA) < noise (MO) • Crossing-fibres: effects can be averaged out • Crossing-fibres: problematic interpretation of  and  • Crossing-fibres: not only influence on FA, but also MD • Effect of partial volume effect on FA, MD etc. (Jones, ISMRM 2011) • Correction for CSF contamination? (Metzler-Baddeley et al., 2012) • Choice of sequence: anisotropic voxels (Vos et al., ISMRM 2011) • Choice of sequence: 12 orientations, 5 b-values: more sensitive to using MD • 30 orientations, 2 b-values: more sensitive to  using FA ISMRM Weekend course – 5th of May 2012

  29. …Take home message • Choice of sequence: isotropic voxels, optimised for specific question • FA and MD complementary to interpret results: higher FA is not necessarily better •  and  give additional information (e.g., Salat et al., 2010) • Do not forget about PVE, noise andcrossing fibres to help interpret results If ambiguous interpretation: MO, dispersion of PDD, Westin indices (Westin et al., 1997) Vos et al., ISMRM 2011 ISMRM Weekend course – 5th of May 2012

  30. …Take home message • Choice of sequence: isotropic voxels, optimised for specific question • FA and MD complementary to interpret results: higher FA is not necessarily better •  and  give additional information (e.g., Salat et al., 2010) • Do not forget about PVE, noise andcrossing fibres to help interpret results If ambiguous interpretation: MO, dispersion of PDD, Westin indices (Westin et al., 1997) • Crossing fibres helps detect subtle differences (Tuch et al., 2005; Douaud et al., 2011) Tuch et al., 2005 ISMRM Weekend course – 5th of May 2012

  31. Special thanks to: • SHFJ, CEA, Orsay • Cyril Poupon • - Yann Cointepas • - Denis Riviere • - Jean-Francois Mangin • FMRIB, University of Oxford • - Karla Miller • - Stamatios Sotiropoulos • - Timothy Behrens • Steve Smith • Peter Jezzard • Saad Jbabdi THANK YOU ISMRM Weekend course – 5th of May 2012

  32. Other diffusion tensor-derived measures • “Westin” indices describing the tensor shape: sphericity, linearity and planarity (Westin et al., 1997) • Inter-voxel measures: lattice index (Pierpaoli) • Fourth moment: kurtosis (Assaf) ISMRM Weekend course – 5th of May 2012

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