Tracking diaphragm movement by using ultrasound to assess its strength

Progressive neuromuscular diseases, such as Duchenne muscular dystrophy, but also the normal ageing process, result in muscle atrophy and remodelling (including infiltration with non-contractile fat and connective tissue). These effects impair the ability of muscle to generate and maintain force and endurance. Symptoms including weakness and fatigue are first noticed in ambulatory muscles but do not spare other skeletal muscles, including the respiratory muscles (diaphragm and intercostal muscles) (Sharma & Goodwin, 2006). Respiratory and bulbar muscle weakness interferes with airway clearance, increases risk of recurrent chest infections, and ultimately leads to respiratory failure. In fact, the prognosis for people with progressive neuromuscular disorders depends primarily on the degree of respiratory muscle involvement. In people, respiratory muscle function is typically assessed indirectly by using pulmonary function indices, such as forced vital capacity, peak expiratory and inspiratory pressures, the fluoroscopic sniff test, or nerve conduction studies and electromyography (Sarwal et al. 2013). Nerve conduction studies and electromyography are challenging and uncomfortable. Pulmonary function tests may be difficult to perform and therefore less reliable in people with significant respiratory muscle weakness. In preclinical rodent models, such as the mdx mouse (a model for human Duchenne muscular dystrophy), the standard method to evaluate respiratory muscle strength is ex vivo measured isometric force developed by a small (a few millimeters in width) diaphragm strip. The limitations of this approach include: (i) the single time point of measurement (mice need to be killed to harvest the diaphragm strips), (ii) the strip may not be representative of the whole diaphragm because fibrosis, a major cause of muscle weakness, is not distributed evenly across that diaphragm, and (iii) muscle force development depends on both intrinsic and extrinsic (e.g. innervation) factors, which are not all accounted for ex vivo. In this issue of The Journal of Physiology, Whitehead et al. (2016) describe a newly developed high-frequency, high resolution ultrasonography method to evaluate diaphragm function in vivo in mice. They first validated diaphragm ultrasonography as a reliable measure of in vivo diaphragm function by measuring diaphragm movement amplitude in 8and 18-month-old wild type (WT) and mdx mice and comparing these measurements with ex vivo specific force measurements. They found that ultrasound imaging reliably detected diaphragm dysfunction in mdx mice both at 8 and 18 months of age and the ultrasound-measured diaphragm amplitude measurements correlated strongly with ex vivo-measured isometric force. They then used the ultrasound method to track (serial measure-