Given that PSP is a rare disease, minimizing the number of participants in clinical trials is critical. The aim of this work was to identify the brain regions that require the lowest sample sizes to detect potential therapeutic effects for PSP clinical trials.
By using both the exploratory voxelwise analysis and regional volumetric measurements of brain atrophy, as well as diffusivity changes we have shown:
- The brain regions-of-interest that require the lowest sample sizes to detect potential therapeutic effects for PSP clinical trials.
- Subcortical regional volumes illustrate the rapid progression of PSP with statistically significant changes in atrophy as early as 6 months from baseline visit.
- Evaluating regional volume changes over time with a neuroimaging processing and analysis pipeline designed for clinical trials can result in lower sample size requirements compared to clinical scoring or the planimetric biomarkers MRPI and MRPI 2.0 when monitoring disease progression.
This work provides a thorough analysis of MRI data from the 4RTNI study. Our results show that progressive, regional brain atrophy and diffusivity changes can be effectively assessed using quantitative analysis of MR images with reasonable sample sizes over a relatively short timeframe. As such, these imaging biomarkers appear to be promising for assessment of the efficacy of disease-modifying therapeutics in PSP clinical trials.