Ultrasound of nerve and muscle.

Over the last two decades, ultrasound has developed into a useful technology for the evaluation of diseases of nerve and muscle. Since it is currently not used at by the majority of clinicians involved in diagnosis or care of patients with neuromuscular disorders, this review briefly describes the technical aspects of ultrasound and its physical principles. It relates normal muscle anatomy and movement to ultrasound images in the axial and sagittal planes and follows with a discussion of ultrasound findings in chronic muscle disease. These include evident atrophy and the loss of the hypoechoic architecture of normal muscle tissue. It highlights evolving uses of the technique to measure other pathologic changes in disease including altered muscle dynamics. With high-resolution instruments nerve imaging has now become standard, and the relationships of median nerve anatomy and observations of static and dynamic images from ultrasound are reviewed. Changes seen in carpal tunnel syndrome include significant increases in the cross-sectional area of the nerve just proximal to the site of compression, loss of hyperechoic intensities within nerve, and reduced mobility. Preliminary use of the technique for the study of other nerves is reviewed as well. Ultrasound is an ideal tool for the clinical and research investigation of normal and diseased nerve and muscle complementary to existing diagnostic techniques. As the technology continues to evolve, it will likely assume a more significant role in these areas as those most able to exploit its potential, clinical neurophysiologists and neuromuscular clinicians, incorporate its use at the bedside.     

Skeletal muscle imaging in neuromuscular disease

Skeletal muscle imaging is increasingly used as a complement to clinical and electrophysiological examination in neuromuscular disease. Ultrasound and MRI have developed as the modalities of choice, each with strengths and limitations. Characteristic changes of muscle denervation and myopathy are seen on imaging which may delineate the nature of the disease process or help guide muscle biopsy. Identifying patterns of muscle involvement in hereditary myopathies may inform genetic testing. This review discusses skeletal muscle imaging in neuromuscular disease focusing on practical applications of current and emerging ultrasound and MRI techniques.     

Muscle imaging in inherited and acquired muscle diseases

In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.     

Calibrated quantitative ultrasound imaging of skeletal muscle using backscatter analysis

We evaluated the ability of an ultrasound method, which can characterize cardiac muscle pathology and has reliability across different imaging systems, to obtain calibrated quantitative estimates of backscatter of skeletal muscle. Our procedure utilized a tissue-mimicking phantom to establish a linear relationship between ultrasound grayscale and backscatter levels. We studied skeletal muscles of 82 adults: 45 controls and 37 patients with hereditary myopathies. We found that skeletal muscle ultrasound backscatter levels varied with probe orientation, age, and muscle contraction and pathology. Reliability was greater with the probe in longitudinal compared with transverse planes. Backscatter levels were higher in those >40 years of age, in muscle extension than flexion, and in myopathic patients than controls. Calibrated measurements of muscle backscatter have sensitivity and specificity in identifying and reliably measuring levels of skeletal muscle pathology.     

Measurement of muscle contraction with ultrasound imaging

To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine-wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles.     

Electrically silent muscle visible by ultrasound

A 65-year-old woman with multiple chronic cranial neuropathies had spinal accessory innervated muscles that were virtually invisible to electromyography. Ultrasound imaging revealed the extensive atrophy and increased echogenicity that corresponded to the thinness of the muscles and their loss of insertional activity. In patients with severe atrophy of trapezius or sternocleidomastoid muscles, ultrasound may help in identify chronically denervated muscle.     

Neuromuscular ultrasound

High-resolution ultrasound now is capable of imaging muscle and nerve in fine detail. It is sensitive in detecting chronic myopathies and neurogenic atrophy and may be able to detect subtle changes associated with acute denervation. It is particularly well suited to the study of fasciculations and kinesiology. Recent studies show that ultrasound also is capable of imaging most peripheral nerves,including small branches, and of sensitively measuring the swelling that follows chronic compression. This noninvasive technology holds considerable promise for providing anatomic information to complement other tests of nerve and muscle function.     

Quantitative muscle ultrasound versus quantitative magnetic resonance imaging in facioscapulohumeral dystrophy

Introduction: Ultrasound and magnetic resonance imaging (MRI) are non‐invasive methods that can be performed repeatedly and without discomfort. In the assessment of neuromuscular disorders it is unknown if they provide complementary information. In this study we tested this for patients with facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed quantitative muscle ultrasound (QMUS) and quantitative MRI (QMRI) of the legs in 5 men with FSHD. Results: The correlation between QMUS‐determined z‐scores and QMRI‐determined muscle fraction and T1 signal intensity (SI) was very high. QMUS had a wider dynamic range than QMRI, whereas QMRI could detect inhomogeneous distribution of pathology over the length of the muscles. Conclusions: Both QMUS and QMRI are well suited for imaging muscular dystrophy. The wider dynamic range of QMUS can be advantageous in the follow‐up of advanced disease stages, whereas QMRI seems preferable in pathologies such as FSHD that affect deep muscle layers and show inhomogeneous abnormality distributions. Muscle Nerve 50: 968–975, 2014     

Ultrasound imaging and directed needle biopsy in the diagnosis of selective involvement in muscle disease

Four children investigated for neuromuscular disorder by routine ultrasound imaging showed selective involvement within the quadriceps femoris muscle, with involvement of the vasti and sparing of the rectus femoris. This was confirmed by concurrent needle biopsy of the two muscles. Real-time ultrasound imaging is quick, noninvasive, readily accepted by children, and has the advantage over CT scans of being practical for routine outpatient use. Needle biopsy is relatively atraumatic and enables one to select specific superficial and deep muscles for concurrent biopsy.     

Two decades of advances in muscle imaging in children: from pattern recognition of muscle diseases to quantification and machine learning approaches

Muscle imaging has progressively gained popularity in the neuromuscular field. Together with detailed clinical examination and muscle biopsy, it has become one of the main tools for deep phenotyping and orientation of etiological diagnosis. Even in the current era of powerful new generation sequencing, muscle MRI has arisen as a tool for prioritization of certain genetic entities, supporting the pathogenicity of variants of unknown significance and facilitating diagnosis in cases with an initially inconclusive genetic study. Although the utility of muscle imaging is increasingly clear, it has not reached its full potential in clinical practice. Pattern recognition is known for a number of diseases and will certainly be enhanced by the use of machine learning approaches. For instance, MRI heatmap representations might be confronted with molecular results by obtaining a probabilistic diagnosis based in each disease “MRI fingerprints”. Muscle ultrasound as a screening tool and quantified techniques such as Dixon MRI seem still underdeveloped. In this paper, we aim to appraise the advances in recent years in pediatric muscle imaging and try to define areas of uncertainty and potential advances that might become standardized to be widely used in the future.     

Skeletal muscle ultrasound

Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increases muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity needs to be quantified to correct for age-related increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique, it is possible to detect neuromuscular disorders with predictive values of 90%. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to Electromyography (EMG) and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders.     

Diagnostic advantage of needle muscle biopsy and ultrasound imaging in the detection of focal pathology in a girl with limb girdle dystrophy

Ultrasound imaging of the thigh in a 6-year-old girl with limb girdle muscular dystrophy showed striking focal involvement of the vastus intermedius and vastus lateralis muscles, with sparing and hypertrophy of the rectus femoris muscle. This was confirmed on needle muscle biopsy, using the Bergstrom needle, which showed normal histology in the rectus femoris and severe dystrophic change in the vastus intermedius. In neuromuscular disease, it is important to be aware of the possibility of focal muscle involvement, which can be screened for by ultrasound imaging and more effectively investigated by needle than by open muscle biopsy.     

Skeletal muscle ultrasound

Abstract

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Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increases muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity needs to be quantified to correct for age-related increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique, it is possible to detect neuromuscular disorders with predictive values of 90%. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to Electromyography (EMG) and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders.     

Ultrasound imaging of muscles in Duchenne muscular dystrophy

The ultrasound imaging of quadriceps, gastrocnemius and soleus muscles was performed in 30 patients with Duchenne muscular dystrophy (DMD) and 16 control subjects. In controls, the skeletal muscle itself was scarcely echogenic. However, bone surface and fascia were clearly echogenic. The transverse scan of muscle in all DMD patients showed an increased echogenicity, which made the echo from bone or fascia less intense. The abnormal muscle echo was graded according to Heckmatt et al. From the quantitative aspect, there was a significant correlation between disability scale of DMD patients and abnormal echogenicity of the quadriceps muscle. A similar correlation was also observed between results of manual muscle testing the ultrasound imaging. The soleus muscle was usually less abnormal than the gastrocnemius in the ultrasound imaging. Thus, the ultrasound imaging seemed to provide an important information for the clinical assessment of DMD patients.     

Measurement of intramuscular fat by muscle echo intensity

Introduction: The aim of this study was to compare ultrasound echo intensity (EI) with high‐resolution T₁‐weighted MRI and to establish calibration equations to estimate percent intramuscular fat from EI. Methods: Thirty‐one participants underwent both ultrasound and MRI testing of 4 muscles: rectus femoris (RF); biceps femoris (BF); tibialis anterior (TA); and medial gastrocnemius (MG). Results: Strong correlations were found between MRI percent fat and muscle EI after correcting for subcutaneous fat thickness (r = 0.91 in RF, r = 0.80 in BF, r = 0.80 in TA, r = 0.76 in MG). Three types of calibration equations were established. Conclusions: Muscle ultrasound is a practical and reproducible method that can be used as an imaging technique for examination of percent intramuscular fat. Future ultrasound studies are needed to establish equations for other muscle groups to enhance its use in both research and clinical settings. Muscle Nerve 52 : 963–971, 2015     

Validity and reliability of nerve and muscle ultrasound

Introduction: Nerve and muscle ultrasound has been studied in several conditions, but validity and reliability have not been assessed systematically. Methods: Nerve cross‐sectional area and muscle thickness were measured ultrasonographically at several sites in 4 cadavers, which were then dissected, and actual measurements were obtained. To assess intrarater and interrater reliability, between 3 and 5 ultrasonographers, with varying experience levels, made repeated measurements on healthy volunteers. Results: Correlation coefficients for nerve and muscle validity were >0.968 (P < 0.001), and for intrarater reliability were >0.901 (P < 0.001) for still and real‐time images. Correlation coefficients for interrater reliability were more varied, but for still images they were all significant at the P < 0.001 (0.542–0.998) level, and for real‐time images they were significant at the P < 0.05 level for half the sites (0.243–0.981). Conclusion: Overall, nerve and muscle ultrasound is a valid and reliable diagnostic imaging technique. Muscle Nerve, 2013     

Emerging technologies in neuromuscular ultrasound

Neuromuscular ultrasound is an accepted and valuable element in the evaluation of peripheral nerve and muscle disease. However, ultrasound has several limitations to consider, including operator dependency and lack of a viable contrast agent. Fortunately, new technological advances show promise in resolving these issues. Ultra-high resolution ultrasound enables imaging of the nerve at the fascicular level. Shear wave elastography imaging can provide measures of tissue stiffness that can act as a surrogate measure of nerve and muscle health. Photoacoustic imaging may overcome neuromuscular ultrasound's current lack of contrast agents to detect inflammation and other functional changes within nerve and muscle, while artificial intelligence stands to address operator dependency and improve diagnostic imaging. The basic principles of each of these technologies are discussed along with current research and potential future applications in neuromuscular imaging.     

Skeletal muscle CT scan and ultrasound imaging in two siblings with central core disease

The computed tomography (CT) and ultrasound (US) imaging studies were performed on skeletal muscles of two siblings (5-year-old boy and 10-year-old girl) with central core disease. The appearance of low-density areas in muscles was remarkable at the levels of the 3rd lumbar vertebra (L3), the midthigh and the thickest part of legs. The muscles at the levels of L3 and thigh were more severely affected than those of legs. Especially, paravertebral muscles, m. vastus, m. sartorius, m. gracilis tended to be more severely affected. The muscles of the legs except m. soleus were well preserved. US imaging of the thigh revealed a marked increase of echogenicity of rectus muscle as well as opaque, indistinct changes of fascia and bone. In contrast, the CT finding of the rectus muscle was relatively well preserved.     

Anatomical information is needed in ultrasound imaging of muscle to avoid potentially substantial errors in measurement of muscle geometry

This study validates two‐dimensional (2D) ultrasound measurements of muscle geometry of the human medial gastrocnemius (GM) and investigates effects of probe orientation on errors in these measurements. Ultrasound scans of GM muscle belly were made both on human cadavers (n = 4) and on subjects in vivo (n = 5). For half of the cadavers, ultrasound scans obtained according to commonly applied criteria of probe orientation deviated 15° from the true fascicle plane. This resulted in errors of fascicle length and fascicle angle up to 14% and 23%, respectively. Fascicle‐like structures were detectable over a wide range of probe tilt and rotation angles, but they did not always represent true fascicles. Errors of measurement were either linear or quadratic functions of tilt angle. Similar results were found in vivo. Therefore, we conclude that similar errors are likely to occur for in vivo measurements. For all cadavers, at the distal end of GM, the true fascicle plane was shown to be perpendicular to the distal aponeurosis. Using transverse images of GM to detect the curvature of the deep aponeurosis at the distal end of the muscle belly is a simple strategy to help identify the fascicle plane. For subsequent longitudinal imaging, probe alignment within this plane will help minimize measurement errors of fascicle length, fascicle angle, and muscle thickness. Muscle Nerve, 2009     

Accuracy of muscle fasciculations for the diagnosis of later-onset spinal muscle atrophy

Diagnosis of later-onset spinal muscular atrophy (SMA) can be challenging. This study aimed to evaluate the diagnostic properties of the detection of muscle fasciculations for SMA diagnosis in adolescents and adults with proximal muscle weakness. A cross-sectional diagnostic accuracy study was performed, in which 10 subjects with SMA (5 with type II and 5 with type III) and 9 subjects with genetic muscle diseases were evaluated by physical examination, muscle ultrasound (MUS) and electromyography (EMG). Inter-rater reliability of MUS was higher than physical examination and in a sensitivity analysis of MUS, all SMA subjects and a single patient with genetic muscle disease presented fasciculations in at least 2 different muscle groups, resulting in a sensitivity of 1 (95% CI: 0.69 to 1) and a specificity of 0.89 (95% CI: 0.52 to 1) for SMA diagnosis. Forty-two percent of evaluated subjects did not agree to perform EMG, limiting this method results. Muscle ultrasound presented the best diagnostic accuracy and physical examination combined with MUS seemed to be a good strategy for screening adolescents and adults with proximal muscle weakness for SMA. These results might improve diagnostic guidelines for later-onset SMA, leading to earlier diagnosis, treatment and specific care.