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Abstract

Objectives: The pathomechanisms underlying drug resistance in (focal) epilepsy are poorly understood, but hypothesised to be network-based in nature. Whilst several grey matter structural abnormalities have been linked to drug resistance previously, white matter biomarkers remain elusive despite an abundance of research. Two potential reasons for this disparity are: mapping and contextualising network abnormalities in the white matter is inherently more methodologically complex than in the grey matter, and somewhat relatedly, the downstream effects of white matter abnormalities may differ due to individual variability, complicating estimates of structure-function relationships. We leveraged a novel combination of diffusion weighted imaging (DWI) data acquisition and analysis to investigate individual white matter abnormalities associated with drug resistance in focal epilepsy. Methods: High angular resolution fibre-ball DWI was acquired in 30 people with epilepsy (15 well-controlled, 15 drug-resistant) and 15 healthy controls at the (University of) Liverpool Magnetic Resonance Imaging Centre. We then implemented a modified version of the novel fixel-based analysis pipeline, including estimation of fibre and scalar metrics. We first assessed the utility of fibre-ball imaging data for tractography, then, following group comparisons, identified white matter abnormalities associated with drug-resistance in epilepsy, which were used to seed local and distributed networks. Finally, we compared fibre and scalar metrics in our individual patients against our control-defined normative average, across 72 TractSeg-defined tracts. Results: Evidence for reductions of fibre metrics was found in the posterior of the right cingulum and the right middle longitudinal fascicle of the drug-resistant patients when compared to the controls. Similarly, abnormalities specific to the well-controlled patients were identified in the left-projecting isthmus of the corpus callosum and the left middle longitudinal fascicle. We also report scalar-metric differences alongside potential networks of drug resistance, and present individual tract-based metric profiles. Significance: We first demonstrate the relationship between angular resolution and tractography performance, then further characterise the white matter abnormalities that may underlie drug-resistance networks in focal epilepsy, and expand on previous attempts to synthesise individualised quantitative DWI evaluation. This study and its associated materials demonstrate both the feasibility and value of individualised approaches in epilepsy.

Full preprint coming soon