PIANO™ requires substantially lower sample sizes to assess reduction in observed atrophy compared to other quantitative analysis tools/methods.
Sample Sizes for PIANO™ Regional Atrophy
Sample size calculations for the 12 month change from baseline in regional volumes are illustrated as the sample size per arm required to achieve 20-80% slowing of the observed regional atrophy.
Sample Sizes for PIANO™ Regional Volumes Compared to FreeSurfer
Sample size calculations for the 6 and 12 month change from baseline for PIANO™ regional volumes compared to the FreeSurfer 12 month change in equivalent neuroanatomical regions. The sample size per arm required for a 20-80% slowing of observed brain atrophy are color-coded, where the green hues indicate less than 50 subjects per arm.
The graph of sample size per arm vs. percent reduction in observed atrophy highlights a number of subcortical regions that require fewer than 50 subjects to detect a 60% reduction of the observed brain atrophy.
The table shows the sample size calculations for the 6 and 12 month change from baseline volume. Even as early as 6 months less than 50 subjects per arm are estimated to be required to observe a 60% slowing of the observed brain atrophy in the lateral ventricles, third ventricle, thalamus, and pallidum using PIANO™-based volumetric analysis. As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained.
We used FreeSurfer for comparative purposes because of its relative ubiquitous use by the academic community. Sample size calculations based on the 12 month change from baseline volumes derived from FreeSurfer shows substantially higher sample size requirements for the same regional volumes.
Interestingly, the planimetric measurement of MRPI and MRPI 2.0, which are both widely used biomarkers to identify PSP subjects and show statistically significant atrophy over 6 and 12 months, require 2-3 times the sample size compared to the PIANO™-based brainstem 3D volume assessments.