The plot highlights a subset of the regions per FTD variant at 12 months in which 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 are illustrated. Of note is the lower sample size requirements in the svPPA group compared to bvFTD. 

The table shows the sample size estimates for both the 6- and 12- month change time points, including the sample size per arm required to observe 20-80% reductions in diffusion MRI metric change in a treated group compared to an untreated group. The table highlights a number of white matter, cortical, and subcortical regions that require fewer than 50 subjects per arm to detect a 60% or 80% reduction of the observed diffusion MRI metric change in a treated group compared to an untreated group across all FTD subvariant groups. For the semantic variant (svPPA) group, nearly all regions displayed require around or fewer than 50 subjects per arm to detect only a 40% reduction of the diffusion MRI changes at 12 months.

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 similarly powered. 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, fewer than 50 subjects per arm are estimated to be required to observe a 60% slowing of the diffusion MRI changes in all subvariants, specifically in the temporal white matter for the non-fluent variant (nfvPPA) group, the frontal white matter and cortex for the behavioral variant (bvFTD) group, to half a dozen of cortical and subcortical regions for the svPPA group. As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained using PIANO™-based diffusion MRI analysis.