Muscular imaging represents an important diagnostic tool for the identification and quantification of muscular alterations in patients affected by muscular disorders. Although MRI represents the gold standard to investigate the muscular structure, ultrasound (US) is an emerging tool to study muscle diseases. Muscular dystrophies are characterized by a chronic muscle atrophy and weakness due to a progressive fibro-fatty replacement of muscle tissue, resulting in thinning and increase in echo intensity at US study. The aim of this work is to evaluate the applicability of quantitative muscular ultrasonography (QMUS) in the study of muscle involvement in patients affected by facioscapulohumeral muscular dystrophy type 1 (FSHD1). In our study we will recruit a total of 15 patients with genetically determined FSHD type 1 and 15 controls matched by sex, age and BMI. In each subject we will bilaterally analyze, with a linear transducer (7-14 MHz) five different muscles: pectoralis major, deltoid, rectus femoris, tibialis anterior and semimembranosus muscles. In each image QMUS will be performed calculating the mean muscle echo intensity by computer assisted gray-scale analysis, keeping gain, depth, number of focuses and transducer pressure constant. We will then compare median echo intensities to evaluate whether a difference between healthy and affected muscles exists and to see if there is a correlation between echo intensity and clinical severity. Finally, by comparing MRI and US data we want to evaluate how complementary these techniques are in detecting neuromuscular alterations. This pilot study is a pioneer project to apply US tool in the study of FSHD1 and could open new prospective to forthcoming studies for the application of ultrasonography as a useful biomarker of muscle injury in FSHD1 and other muscular dystrophies.
Several studies, mainly conducted on children, have already demonstrated the high sensitivity and sensibility of quantitative muscle ultrasound in detecting a neuromuscular disorder. In adults, no prospective studies investigating the diagnostic value of muscle ultrasound have yet been performed and, with the exception of Janssen et al. work, no study exploiting quantitative muscular ultrasound has ever been undertaken in FSHD1 patients. As aforementioned, in Janssen study only the quadriceps of 5 FSHD men were studied, while we intend to study both upper and lower limbs muscles in a larger sample, comparing data to healthy controls. The development of non-invasive quantitative biomarkers that allow to estimate muscle involvement and evaluate the natural progression of the disease over time is crucial for a better understanding of the disease pathogenesis and to possibly assess the effectiveness of therapeutic approaches. On this matter, muscle MRI in widely being used, since it is very capable of analyzing both superficial and deeper muscles and is able to discriminate between fatty infiltration an edema. However, muscle MRI is a very expensive and time consuming technique, which cannot always be performed (for example in children, pacemaker carriers etc). Therefore, establishing how well muscular US, which is a low-cost, safe, rapid and tolerable technique, is able to detect muscular alterations will help to design easy and applicable protocols for the follow-up and screening of neuromuscular disorders. Muscular US also presents some advantages compared to MRI. Firstly, it can be used to explore those muscles that cannot be investigated with MRI, such as facial muscle, which are greatly involved in FSHD. Moreover, muscle ultrasound is not only capable of visualizing muscle structure, it is also able to identify muscle movements, and can therefore be exploited in dynamic evaluation of muscle contraction. Finally, it can be used to identify the optimal site for muscle biopsy under direct ultrasound guidance, especially in focally affected muscles or when other vital structures, such as blood vessels and nerves, need to be avoided.