Tractography in the presence of white matter lesions in multiple sclerosis

Accurate anatomical localisation of specific white matter tracts and the quantification of their tract-specific microstructural damage in multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease progression and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithm tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvoution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious streamlines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesion on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass areas with high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the cortico-spinal tracts and arcuate fasciculi were successfully reconstructed in more than 90% of individuals. Comparing tract-specific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we showed that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between r = .52 (p