Abstract

Diffusional kurtosis imaging (DKI) is an advanced diffusion MRI (dMRI) technique that can quantify several diffusion measures that are highly sensitive to microstructural changes in brain. Previously, we found enhanced sensitivity of DKI-derived diffusion metrics following acute stroke in the lesion core and peri-lesional area that correlated with infiltration of activated glia. Studies have demonstrated that skilled motor training after ischemic damage affecting the sensorimotor cortex (SMC) induces functional motor recovery and neural plasticity in the remaining motor cortex. In the current study, we investigated the relationship between dMRI measures and rehabilitation-induced forelimb functional recovery. Adult male rats (3-4 months old) were trained on a skilled reaching task and given an endothelin-1 (ET-1) induced unilateral ischemic stroke over the SMC. Animals then received 21 days of impaired forelimb rehabilitative training (RT) on a reaching task or no rehabilitative training (No-RT). All animals underwent MRI scans prior to injury, 5 days post-injury, and after 21 days of RT or No-RT procedures, using a 7T Bruker Biospec MRI scanner to acquire dMRI images. Diffusivity and diffusional kurtosis metrics were calculated with in-house software. Multi-slice regions-of-interest were drawn in the lesion core, peri-lesional remaining motor cortex and in the forelimb region of the SMC in the non-infarcted hemisphere. All animals had lesion-induced motor deficits following ET-1 strokes and RT improved reaching forelimb function compared to No-RT. Peri-lesional diffusional kurtosis measures remained significantly different between the lesion and non-lesion SMC at four weeks post-injury, at which time diffusivity differences were no longer detected. Fractional anisotropy of the corpus callosum, inclusive of areas with SMC interhemispheric connections was higher following RT versus No-RT. These data indicate that the kurtosis of peri-lesional motor cortex remains sensitive to chronic ischemic effects, unlike diffusivity measures, and that skilled motor RT likely alters white matter connectivity between the two hemispheres.

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