Stimulated phase contrast motor unit MRI to assess recovery of fatigued muscle as a novel therapeutic response biomarker

Motivation: Current biomarkers for serial functional muscle assessments (eg., for therapeutic response assessment) are limited by sensitivity, spatial resolution, and coverage. Goal(s): We aimed to utilise the high spatial resolution offered by recently developed phase contrast motor unit MRI (PC-MUMRI) techniques to identify potential biomarkers. Approach: We prospectively trialled a novel PC-MUMRI fatigue and recovery paradigm before and after a 12-week exercise intervention in seven participants with genetic mitochondrial disorders. Results: Time-to-half-maximum of PC-MUMRI recovery reduced from a mean of 254 (+/- 109) seconds to 137 (+/- 41) seconds following the intervention. This was not statistically significant (p = 0.074). Impact: We have developed and tested a novel therapeutic response biomarker for muscle-based intervention based on measuring recovery of stimulated muscle twitch velocities following fatigue. This may address problems with spatial resolution, sensitivity, or coverage associated with previously reported biomarkers.