Objective: We aimed to develop new imaging biomarkers allowing objective monitoring of early Multiple System Atrophy (MSA) progression, which could improve outcome definition for future neuroprotective trials.

Background: MSA is rare neurodegenerative condition with severe prognosis and no treatment is currently available to slow down disease progression.

Method: 19 MSA patients were enrolled in a multicentric longitudinal cohort (Gait’N’Park – NCT04653688). MRI for volumetric (T1) and diffusion (DTI) data acquisition was performed at baseline (W0), and repeated after 24 (W24) and 48 weeks (W48). Putamen, cerebellum and pons were segmented from T1 and mean diffusivity (MD) maps were calculated from diffusion sequences. P-values were corrected using FDR method.

Results: We observed significant increase of MD as early as W24 in putamen (+3.07% ; p=0.0359) and pons (+12.5% ; p=0.0123), which was confirmed at W48 in putamen (+14.83% ; p=0.0059), cerebellum (+39.99% ; p=0.0059) and pons (+32.14% ; p=0.0059), whereas slight volume atrophy was only significant in pons at W48 (-16.44% ; p=0.0096) [Table 1. and Figure 1].

Conclusion: Our data suggest that diffusion imaging markers are able to highlight microstructural changes as early as 6 months, with high statistical significance and are more sensitive to change along time than volumetric analysis which shows lower and later changes after one year of follow up. These surrogate imaging biomarkers could enable a more sensitive and earlier assessment of disease progression compared to clinical criteria, thereby increasing the statistical power of future clinical trials on neuroprotection.

Table 1. Volume and MD analysis along time

Figure 1. Volume and MD analysis along time

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prospective-comparison-of-volumetric-and-diffusion-mri-biomarkers-for-multiple-system-atrophy/