Assessment of complementary white matter microstructural changes and grey matter atrophy in the 6-OHDA-induced model of Parkinson's disease.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Magnetic resonance imaging (MRI) offers a non-invasive means to study PD and its progression. This study utilized the unilateral 6-hydroxydopamine (6-OHDA) rat model of parkinsonism to assess whether white matter microstructural integrity measured using advanced free-water diffusion tensor imaging metrics (fw-DTI) and gray matter density using voxel-based morphometry (VBM) can serve as imaging biomarkers of pathological changes following nigrostriatal denervation. By comparing the 6-OHDA-lesioned vs. sham-lesioned rats, we aimed to identify complementary gray matter and white matter changes indicative of disease pathophysiology. Results showed widespread gray matter atrophy and subtle changes in white matter integrity in the 6-OHDA lesioned rats. Gray matter atrophy predominantly affected ipsilateral cortical regions, with some bilateral regions also showing atrophy. Conversely, higher volumes were observed in some regions of the contralateral gray matter in the 6-OHDA model. Furthermore, increased fw-FA and fw-AX were observed in regions including the brainstem, thalamus, superior and inferior colliculus, and fornix. Smaller clusters of decreased fw-FA and fw-AX were found in the corpus callosum. Regions of both increased and decreased diffusivity were noted in fw-RD, primarily in the brainstem, while the f index was elevated in several regions in the 6-OHDA lesioned group, except for a cluster in the contralateral thalamus. In conclusion, this study underscores the significant potential role for gray and white matter imaging biomarkers in delineating disease pathology in parkinsonism.