MRI – MUSCLE IMAGING: P.297Which muscle segmentation approach to use for obtaining the highest discriminate power in natural history neuromuscular diseases using quantitative NMRI?

Abstract

The degree of fatty infiltration, as measured using water-fat NMR imaging separation techniques (such as Dixon) is now a widely accepted muscle imaging biomarker and an often proposed outcome measure in many neuromuscular disease longitudinal studies. The question remains which is the specific muscle (group) to evaluate during the study period. We aimed to compare different segmentation approaches (global vs individual muscles) in a variety of neuromuscular disorders: immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), GNE myopathy (GNEM), Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy types 2B and 2I, Pompe disease (GSD2) and spinal muscular atrophy (SMA). We used the standardized response mean (SRM) of the fat fraction (FF) change after 1 year to assess the sensitivity of the different approaches. In 109 patients (21 IMNM, 21 IBM, 10 GNEM, 20 DMD, 12 LGMD2B, 7 LGMD2I, 13 GSD2, 5 SMA) two NMR scans were obtained with one year between them; on a clinical 3T Siemens system. A fat-water separation 3-point Dixon NMR sequence (TE1/TE2/TE3= 2.75/3.95/5.15 ms; TR = 10 ms) was performed in 5 slices at the level of the thigh as well as at the level of the leg. Regions of interest were drawn in individual muscles, muscle groups and in the whole segment. Global segmentation gave a satisfactory SRM (≥0.8) in thigh for IMNM, IBM, GNEM, LGMD2B and DMD. In leg, this was the case for IMNM, GNEM, LGMD2B and DMD. In some diseases, higher SRMs were found in individual muscles or muscle groups (including for LGMD2I and SMA). We can conclude that global segmentation is in some cases at least as sensitive as individual muscle or muscle group segmentation, implying that individual muscle segmentation is not always mandatory. A significant increase in FF does not automatically imply a high SRM, which means that the best muscle candidates to detect a treatment effect are not systematically the ones experiencing the most and severe and fastest disease progression. Generalization of the concept is premature. Additionally, the extent of intermuscular fat needs to be further investigated as changes in the nutritional status will likely bias the evaluation of muscular FF. Also other NMR outcome measures might be interesting to look into in such as water T2 and muscle cross-sectional area.