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Sample Sizes for PIANO™ Regional Diffusion Measures 

Sample size per arm required to observe 20-80% reduction of regional diffusion MRI metrics change (MD: mean diffusivity; FW: free water) in a treated group compared to an untreated group over a 12-month period.

Sample size per arm required to observe 20-80% reduction of the regional change in diffusion MRI metrics in a treated group compared to an untreated group over either a 6- or 12-month period using PIANO™

Sample size per arm required to observe 20-80% reduction of the regional change in diffusion MRI metrics in a treated group compared to an untreated group over either a 6- or 12-month period using PIANOTM. The sample size estimations are color-coded, where the green hues indicate less than 50 subjects per arm. Sample sizes are represented for specific diffusion MRI metrics (MD: mean diffusivity; FW: free water), but other diffusion MRI metrics were similar.

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The graph of sample size per arm vs. percent reduction in diffusion MRI metric change highlights a number of white matter, cortical, and subcortical regions that require fewer than 50 subjects to detect a 60% or 80% reduction of the observed change in a treated group compared to an untreated group.

The table shows the sample size calculations for both the 6- and 12- month change timepoints for the sample size per arm estimates required to observe 20-80% reductions in diffusion MRI metric change in a treated group compared to an untreated group. Mean diffusivity (MD) was used for white matter and cortical regions, and free water (FW) was used for subcortical regions, but other diffusion MRI metrics were similar. Even as early as 6 months, less than 50 subjects per arm are estimated to be required to observe a 80% slowing of the diffusion MRI changes in the corpus callosum, parietal white matter, and several cortical and subcortical regions using PIANOTM-based analysis. As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained.

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