Microstructure of Brain Nuclei in Early Parkinson’s Disease: Longitudinal Diffusion Kurtosis Imaging

Abstract

Background: Diffusion kurtosis imaging provides in vivo measurement of microstructural tissue characteristics and could help guide management of Parkinson’s disease. Objective: To investigate longitudinal diffusion kurtosis imaging changes on magnetic resonance imaging in the deep grey nuclei in people with early Parkinson’s disease over two years, and whether they correlate with disease progression. Methods: We conducted a longitudinal case-control study of early Parkinson’s disease. 262 people (Parkinson’s disease: n = 185, aged 67.5±9.1 years; 43% female; healthy controls: n = 77, aged 66.6±8.1 years; 53% female) underwent diffusion kurtosis imaging and clinical assessment at baseline and two-year timepoints. We automatically segmented five nuclei, comparing the mean kurtosis and other diffusion kurtosis imaging indices between groups and over time using repeated-measures analysis of variance, and Pearson correlation with the two-year change in Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III. Results: At baseline, mean kurtosis was higher in Parkinson’s disease than controls in the substantia nigra, putamen, thalamus and globus pallidus when adjusting for age, sex, and levodopa equivalent daily dose (p < 0.027). These differences grew over two years, with mean kurtosis increasing for the Parkinson’s disease group while remaining stable for the control group; evident in significant “group ×time” interaction effects for the putamen, thalamus and globus pallidus ( η p 2 = 0.08–0.11, p < 0.015). However, we did not detect significant correlations between increasing mean kurtosis and declining motor function in the Parkinson’s disease group. Conclusion: Diffusion kurtosis imaging of specific grey matter structures shows abnormal microstructure in PD at baseline and abnormal progression in PD over two years.

Serial deep gray nuclear DTI changes in Parkinson’s disease over twelve years

“…Again, this was the best technology available when data collection first began, ( Chan et al, 2007 ) and remains the most accessible diffusion modeling, which we had applied consistently throughout the three timepoints to ensure comparability of data across the protracted study period. Future studies should leverage on higher-order diffusion MRI acquisitions and more sophisticated diffusion modeling to correct for the free-water fraction, such as the bi-tensor diffusion model ( Ofori et al, 2015 ) or diffusion kurtosis imaging ( Welton et al, 2023 ). These would better characterize the structural complexity and heterogeneities within the putamen and thalamus.…”