Development of an ultrasound-based metric of muscle functional capacity for use in patients with neuromuscular disease.

Introduction/aims: Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are progressive neuromuscular disorders characterized by severe muscle weakness and functional decline (Pillen et al., Muscle Nerve 2008; 37(6):679-693). With new therapeutics, objective methods with increased sensitivity are needed to assess muscle function. Ultrasound imaging is a promising approach for assessing muscle fat and fibrosis in neuromuscular disorders. This study builds on prior work by combining ultrasound-based measurements of muscle size, shape, and quality, relating these measures to muscle strength, and proposing a multivariable image-based estimate of muscle function.

Methods: Maximum voluntary elbow flexion torque of 36 participants (SMA, DMD, and healthy controls) was measured by hand-held dynamometry and elbow flexor muscles were imaged using ultrasound. Muscle size (cross-sectional area, maximum Feret diameter or width, and thickness), quality (echogenicity, texture anisotropy index), and cross-sectional shape (diameter ratio) were measured. Multivariable regression was used to select ultrasound measurements that predict elbow flexion torque.

Results: Significant differences were observed in muscle size (decreased), shape (thinned), and quality (decreased) with increased disease severity and compared to healthy participants. CSA (brachioradialis R² = 0.51), maximum Feret diameter (biceps R² = 0.49, brachioradialis R² = 0.58) and echogenicity (brachioradialis R² = 0.61) were most correlated with torque production. Multivariable regression models identified that muscle size (CSA, maximum Feret diameter) and quality (echogenicity) were both essential to predict elbow flexion torque (R² = 0.65).

Discussion: A multivariable approach combining muscle size and quality improves strength predictions over single variable approaches. These methods present a promising avenue for the development of sensitive and functionally relevant biomarkers of neuromuscular disease.