Exploring individual fixel-based white matter abnormalities in epilepsy

Diffusion MRI has provided insight into the widespread structural connectivity changes that characterize epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies to date have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical value, they should be able to detect white matter microstructural changes in individual patients. In this study, we apply an individualized approach to a technique known as fixel-based analysis, to examine fibre-tract-specific abnormalities in individuals with epilepsy. We explore the potential clinical value of this individualized fixel-based approach in epilepsy patients with differing syndromic diagnoses. Diffusion MRI data from 90 neurologically healthy control participants and 10 patients with epilepsy (temporal lobe epilepsy, progressive myoclonus epilepsy, and Dravet Syndrome, malformations of cortical development) were included in this study. Measures of fibre density and cross-section were extracted for all participants across brain white matter fixels, and mean values were computed within select tracts-of-interest. Scanner harmonized and normalized data were then used to compute Z-scores for individual patients with epilepsy. White matter abnormalities were observed in distinct patterns in individual patients with epilepsy, both at the tract and fixel level. For patients with specific epilepsy syndromes, the detected white matter abnormalities were in line with expected syndrome-specific clinical phenotypes. In patients with lesional epilepsies (e.g. hippocampal sclerosis, periventricular nodular heterotopia, and bottom-of-sulcus dysplasia), white matter abnormalities were spatially concordant with lesion location. This proof-of-principle study demonstrates the clinical potential of translating advanced diffusion MRI methodology to individual-patient-level use in epilepsy. This technique could be useful both in aiding diagnosis of specific epilepsy syndromes, and in localizing structural abnormalities, and is readily amenable to other neurological disorders. We have included code and data for this study so that individualized white matter changes can be explored robustly in larger cohorts in future work. In this study, Mito et al., implement an individualized fixel-based analysis approach to explore fibre-tract-specific abnormalities in epilepsy. They show highly individualized patterns of white matter abnormality in each patient in this case series, which reflect the clinical phenotype or lesion location, and thereby demonstrate clinical potential of this technique. Graphical abstract