Diffusion Measure Changes of Substantia Nigra Subregions and the Ventral Tegmental Area in Newly Diagnosed Parkinson’s Disease

Historically, studies have extensively examined the basal ganglia in Parkinson’s disease for specific characteristics that can be observed with medical imaging. One particular methodology used for detecting changes that occur in Parkinson’s disease brains is diffusion tensor imaging, which yields diffusion indices such as fractional anisotropy and radial diffusivity that have been shown to correlate with axonal damage. In this study, we compare the diffusion measures of basal ganglia structures (with substantia nigra divided into subregions, pars compacta, and pars reticula), as well as the diffusion measures of the diffusion tracts that pass through each pair of basal ganglia structures to see if significant differences in diffusion measures can be observed in structures or tracts in newly diagnosed Parkinson’s disease patients. Additionally, we include the ventral tegmental area, a structure connected to various basal ganglia structures affected by dopaminergic neuronal loss and have historically shown significant alterations in Parkinson’s disease, in our analysis. We found significant fractional anisotropy differences in the putamen, and in the diffusion tracts that pass through pairs of both substantia nigra subregions, subthalamic nucleus, parabrachial pigmental nucleus, ventral tegmental area. Additionally, we found significant radial diffusivity differences in diffusion tracts that pass through the parabrachial nucleus, putamen, both substantia nigra subregions, and globus pallidus externa. We were able to find significant diffusion measure differences in structures and diffusion tracts, potentially due to compensatory mechanisms in response to dopaminergic neuronal loss that occurs in newly diagnosed Parkinson’s disease patients.

Generation of Mouse Basal Ganglia Diffusion Tractography Using 9.4T MRI

Over the years, diffusion tractography has seen increasing use for comparing minute differences in connectivity of brain structures in neurodegenerative diseases and treatments. Studies on connectivity between basal ganglia has been a focal point for studying the effects of diseases such as Parkinson's and Alzheimer's, as well as the effects of treatments such as deep brain stimulation. Additionally, in previous studies, diffusion tractography was utilized in disease mouse models to identify white matter alterations, as well as biomarkers that occur in the progression of disease. However, despite the extensive use of mouse models to study model diseases, the structural connectivity of the mouse basal ganglia has been inadequately explored. In this study, we present the methodology of segmenting the basal ganglia of a mouse brain, then generating diffusion tractography between the segmented basal ganglia structures. Additionally, we compare the relative levels of connectivity of connecting fibers between each basal ganglia structure, as well as visualize the shapes of each connection. We believe that our results and future studies utilizing diffusion tractography will be beneficial for properly assessing some of the connectivity changes that are found in the basal ganglia of various mouse models.