Measuring Diffusion Properties in Tissue The Diffusion Tensor

Historical description of the diffusion tensor • Formalised by Peter Basser and colleagues (1994

Historical description of the diffusion tensor In an anisotropic, constrained environment: D = 3

Diffusion tensor indices: Mean Diffusivity • Formalised by Peter Basser and Carlo Pierpaoli (1995;

Diffusion tensor indices: diffusion anisotropy • Formalised by Peter Basser and Carlo Pierpaoli (1995;

Diffusion tensor indices: diffusion anisotropy • Formal comparison of three anisotropy indices (Papadakis et

Diffusion tensor indices: diffusion anisotropy • Further comparison between FA and RA (Hasan et

Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Developmental study: anatomical and

Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Developmental study: comparison between

Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Increasing sensitivity and interpretability

Fractional Anisotropy and Mean Diffusivity: ROI and voxel-based/TBSS analysis • Large developmental and ageing

Fractional Anisotropy and Mean Diffusivity: first applications • Development (review in Beaulieu et al.

Fractional Anisotropy and Mean Diffusivity: Two complementary measures • An intriguing finding in multiple

Fractional Anisotropy and Mean Diffusivity: Two complementary measures • Same findings seen in the

• Using the information from the PDD (Schwartzmann et al. , 2005) 1

• Decrease of the dispersion of the PDD in Huntington’s disease (Douaud et

Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • No difference in

Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • Significant difference in

Beyond Fractional Anisotropy and Mean Diffusivity: the Mode of anisotropy • Significant increase of

Beyond Fractional Anisotropy and Mean Diffusivity: Parallel and Perpendicular Diffusivity • Validated in animal

Beyond Fractional Anisotropy and Mean Diffusivity: Parallel and Perpendicular Diffusivity • Validated in humans

Diffusion tensor indices: in vivo models and histological validation • Basis of diffusion anisotropy

Diffusion tensor indices: in vivo models and histological validation • Combined in vivo diffusion/histological

The depressing slide… • Sensitivity to noise increases with higher order moments: noise(MD) <

…Take home message • Choice of sequence: isotropic voxels, optimised for specific question •

Special thanks to: SHFJ, CEA, Orsay FMRIB, University of Oxford - Cyril Poupon -

Other diffusion tensor-derived measures • “Westin” indices describing the tensor shape: sphericity, linearity and

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

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

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

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 ISMRM Weekend course – 5 th of May 2012 Warach et al. , 1995 4

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 – 5 th of May 2012 5

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 – 5 th of May 2012 6

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

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 – 5 th of May 2012 8

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 – 5 th of May 2012 9

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) TBSS VBD ISMRM Weekend course – 5 th of May 2012 Mean Control Mean Patient 10

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 – 5 th of May 2012 11

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 – 5 th of May 2012 12

Fractional Anisotropy and Mean Diffusivity: Two complementary measures • An intriguing finding in multiple sclerosis (Ciccarelli et al. , 2001) White matter Patient 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 – 5 th of May 2012 13

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 – 5 th of May 2012 14

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

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

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): 3 rd 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 ISMRM Weekend course – 5 th of May 2012 +1 Linear, cigar-like 2~ 3: e. g. , areas of one predominating fibre population 17

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 Douaud et al. , 2011 ISMRM Weekend course – 5 th of May 2012 18

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 – 5 th of May 2012 19

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 – 5 th of May 2012 20

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

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 – 5 th of May 2012 22

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 – 5 th of May 2012 23

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

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 – 5 th 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 • 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 – 5 th of May 2012 28

…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 and crossing 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 – 5 th 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 and crossing 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 – 5 th of May 2012 30

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

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 – 5 th of May 2012 32