Diffusion Magnetic Resonance Imaging Microstructural Abnormalities in Multiple System Atrophy: A Comprehensive Review

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure, ataxia, and/or parkinsonism. Its prominent pathological alterations can be investigated using diffusion magnetic resonance imaging (dMRI), a technique that exploits the characteristics of water random motion inside brain tissue. The aim of this report was to review currently available literature on the application of dMRI in MSA and to describe microstructural abnormalities, diagnostic applications, and pathophysiological correlates. Sixty-four published studies involving microstructural investigation using dMRI in MSA were included. Widespread microstructural abnormalities of white matter were described, especially in the middle cerebellar peduncle, corticospinal tract, and hemispheric fibers. Gray matter degeneration was identified as well, with diffuse involvement of subcortical structures, especially in the putamina. Diagnostic applications of dMRI were mostly explored for the differential diagnosis between MSA parkinsonism and Parkinson's disease. Recently, machine learning algorithms for image processing and disease classification have demonstrated high diagnostic accuracy, showing potential for translation into clinical practice. To a lesser extent, clinical correlates of microstructural abnormalities have also been investigated, and abnormalities related to motor, ocular, and cognitive impairments were described. dMRI in MSA has contributed to in vivo identification of known pathological abnormalities. Translation into clinical practice of the latest advancements for the differential diagnosis between MSA and other forms of parkinsonism seems feasible. Current limitations involve the possibility of correctly diagnosing MSA in the very early stages, when the clinical diagnosis is most uncertain. Furthermore, pathophysiological correlates of microstructural abnormalities remain understudied. (c) 2022 International Parkinson and Movement Disorder Society.

Automated summary

This review summarizes the literature on the application of diffusion magnetic resonance imaging (dMRI) in multiple system atrophy (MSA), focusing on microstructural abnormalities, diagnostic applications, and pathophysiological correlates. The studies included in this review identified widespread microstructural abnormalities in white matter, especially in specific brain regions. Gray matter degeneration and its involvement in subcortical structures were also observed. Diagnostic applications of dMRI, particularly for differentiating MSA parkinsonism from Parkinson's disease, showed promising results with high diagnostic accuracy using machine learning algorithms. Additionally, some studies explored the clinical correlates of microstructural abnormalities, highlighting links with motor, ocular, and cognitive impairments. However, the correct diagnosis of MSA in the early stages and further investigation of the pathophysiological mechanisms underlying microstructural abnormalities are still challenging.