P.58 MRI muscle segmentation in Duchenne muscular dystrophy (DMD): Stepwise region of interest (ROI) contractions to minimize fat fraction variability

Abstract

MRI proton density fat fraction (MRI-PDFF) to quantify fatty infiltration is a key efficacy endpoint in DMD and other neuromuscular clinical trials. We have previously shown that fat fraction variability can be reduced by contracting the ROI to eliminate noise from non-muscle tissue due to small segmentation errors. Multiple muscles are of interest due to progressive involvement in DMD, and the ideal contraction may vary depending on the muscle size or location. We tested a strategy for optimizing the segmentation of muscles of varying sizes and depths, designed to minimize the variability of fat fraction measurements while maximizing the volume of the contracted ROI. The vastus lateralis (VL) and soleus muscle bellies were segmented by two technologists from T1-weighted images and the center 3 slices were computed for the MRI-PDFF ROI (VL: N=13; soleus: N=14). Uniform axial contractions between 0 mm to 2 mm (in steps of 0.2 mm) were applied to the ROI and the resulting segmentations were registered to PDFF maps to obtain the fat fraction at every step. The minimal detectable change (MDC) for each contracted ROI was computed from the appropriate intraclass correlation coefficient (2-way or 1-way, random-effects, single-rating, absolute agreement) and pooled standard deviation. The Dice coefficient was used to record how much of the original volume is represented at each contraction. The variability approached a minimum as the Dice coefficient neared 0.9 for both muscles. The fat fraction MDC was reduced by 75% in the VL when a 1.2 mm contraction was applied (MDC=1.0%; Dice 0.91) and by 29% in the soleus when a 1.0 mm contraction was applied (MDC=1.3%; Dice 0.90). Further contracting the muscles had minimal effects on MDC. Therefore, we conclude that an axial contraction of the central ROI that represents 90% of the segmented muscle area is optimal for maximizing the interrogated muscle volume and the ability to demonstrate efficacy of disease-modifying therapeutics.