The graph of sample size per arm vs. percent expected diffusion MRI metric change in the treated group compared to natural history highlights a number of white matter tracts and gray matter structures that require fewer than 50 subjects to detect a 40-60% change in the observed diffusion MRI metrics compared to an untreated group. 

The table shows the sample size calculations for the 6 and 12 months change from baseline in diffusion MRI metrics. Radial diffusivity (RD) was used for white matter tracts, and free water (FW) was used for gray matter structures, but other metrics were similar. Infratentorial regions are not well represented due to a lack of consistent MRI coverage in the datasets used for analysis. Even as early as 6 months, less than 50 subjects per arm are estimated to be required to observe a 60% reduction of changes in the caudate, striatum, and cingulate cortex using PIANO™-based analysis. As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained.