White matter degeneration revealed by fiber-specific analysis relates to recovery of hand function after stroke.

Recent developments of higher-order diffusion-weighted imaging models have enabled the estimation of specific white matter fiber populations within a voxel, addressing limitations of traditional imaging markers of white matter integrity. We applied fixel based analysis (FBA) to investigate the evolution of fiber-specific white matter changes in a prospective study of stroke patients and upper limb motor deficit over 1 year after stroke. We studied differences in fiber density and macrostructural changes in fiber cross-section. Motor function was assessed by grip strength. We conducted a whole-brain analysis of fixel metrics and predefined corticospinal tract (CST) region of interest in relation to changes in motor functions. In 30 stroke patients (mean age 62.3 years, SD ±16.9; median NIHSS 4, IQR 2-5), whole-brain FBA revealed progressing loss of fiber density and cross-section in the ipsilesional corticospinal tract and long-range fiber tracts such as the superior longitudinal fascicle and trans-callosal tracts extending towards contralesional white matter tracts. Lower FBA metrics measured at the brainstem section of the CST 1 month after stroke were significantly associated with lower grip strength 3 months (p = .009, adjusted R2  = 0.259) and 1 year (T4: p < .001, adj. R2  = 0.515) after stroke. Compared to FA, FBA metrics showed a comparably strong association with grip strength at later time points. Using FBA, we demonstrate progressive fiber-specific white matter loss after stroke and association with functional motor outcome. Our results promote the application of fiber-specific analysis to detect secondary neurodegeneration after stroke in relation to clinical recovery.