Free-water and free-water corrected fractional anisotropy in primary and premotor corticospinal tracts in chronic stroke

Measures from diffusion MRI have been used to characterize the corticospinal tract in chronic stroke. However, diffusivity can be influenced by partial volume effects from free-water, region of interest placement, and lesion masking. We collected diffusion MRI from a cohort of chronic stroke patients and controls and used a bitensor model to calculate free-water corrected fractional anisotropy (FA T ) and free water (FW) in the primary motor corticospinal tract (M1-CST) and the dorsal premotor corticospinal tract (PMd-CST). Region of interest analyses and whole-tract slice-by-slice analyses were used to assess between-group differences in FA T and FW in each tract. Correlations between FA T and FW and grip strength were also examined. Following lesion masking and correction for multiple comparisons, relative increases in FW were found for the stroke group in large portions of the M1-CST and PMd-CST in the lesioned hemisphere. FW in cortical regions was the strongest predictor of grip strength in the stroke group. Our findings also demonstrated that FA T is sensitive to the direct effects of the lesion itself, thus after controlling for the lesion, differences in FA T in nonlesioned tissue were small and generally similar between hemispheres and groups. Our observations suggest that FW may be a robust biological measurement that can be used to assess microstructure in residual white matter after stroke.