Investigational Use of Neuromuscular Ultrasound

Study Description: Currently there are a limited number of biomarkers that can provide quantitative, reliable information about nerve and muscle function and structure in patients with neuromuscular diseases. This protocol aims to investigate and define specific ultrasound imaging techniques of nerves and muscles that may be useful as biomarkers in clinical trials. For nerve studies, we aim to evaluate the use of high resolution ultrasound probes for B-mode imaging including cross sectional area, diameter and nerve fascicle counts. Additional imaging modalities will be evaluated including shear wave elastography and low flow microvascular imaging. Ultrasound modalities for muscle imaging will include B-mode imaging, muscle thickness, echo-intensity and or shear wave imaging and low flow microvascular imaging. The hypothesis for incorporating these ultrasound imaging modalities into neuromuscular evaluations is these techniques can provide unique quantitative, reproducible data about the structure of nerves and muscles. This information can be used to compare patients with controls and measure change in these modalities in neuromuscular disease states and determine if these measure can serve as a reliable biomarker in neuromuscular diseases. Objectives: Primary Objectives: 1. To acquire normative values for B-mode imaging of nerves (fascicle count) and muscles (quantitative echotexture measurement) and shear wave elastography data on muscle and nerve stiffness/speed of sound in a population of healthy volunteers. 2. To collect normal values of M-mode diaphragm imaging during quiet and deep breathing and voluntary sniff testing in a population of health controls to establish normal values. Secondary Objectives: 1. To determine the reproducibility of specialized techniques involving ultrasound of muscle and nerve: shear wave elastography in muscles and nerves, nerve fascicle counts 2. To determine the presence or absence of low flow microvascular flow within nerves of a population of healthy volunteers Exploratory Objectives: 1. To compare shear wave elastography values (kPa, meters/second) with standard nerve conduction values; amplitude and nerve conduction velocities in healthy controls and participants with neuromuscular diseases. 2. To compare shear wave elastography values with muscle thickness, echotexture and Heckmatt Scale values 3. To compare shear wave elastography values (kPa, meters/second), nerve fascicle count and microvascular flow between volunteers with participants with neuromuscular disorders 4. To compare B-mode quantitative measures of muscle in healthy controls and participants with neuromuscular diseases. 5. To compare M-mode imaging values of diaphragm (excursion of movement) during quiet and deep breathing and voluntary sniff tests in healthy controls and patients with neuromuscular diseases. 6. To quantitate the low flow microvascularity in nerves and muscles in healthy volunteers Endpoints: Primary Endpoint: 1. Normative values for muscle and nerve shear wave elastography in a population of normal volunteers 2. Normative values for nerve fascicular count in a population of normal volunteers 3. Normative values for M-mode imaging of the diaphragm in a population of healthy controls. Secondary Endpoints: 1. Reproducibility of muscle and nerve shear wave elastography (meters/sec or kPa) 2. Reproducibility of nerve fascicle counts 3. Presence of low flow microvascularity in nerves in healthy volunteers Exploratory Endpoint: 1. Compare and correlate amplitude and conduction velocity obtained from standard nerve conduction studies with shear wave elastography values obtained from nerves 2. Compare shear wave elastography values with muscle thickness, echotexture and Heckmatt Scale values 3. Compare shear wave elastography, fascicle counts, and presence of microvascular flow between healthy volunteers and patients with neuromuscular disorders. 4. Compare M-imaging of diaphragm between healthy volunteers and people with neuromuscular disorders 5. Quantitate the low flow microvascularity in nerves and muscles in healthy volunteers Study Population: For healthy control volunteers: n=100, over age 18, male and female, in general good health For people with neuromuscular disorders: n= 50, over age 18, male and female, diagnosed with a known or suspected neuromuscular disorder such as; motor neuron disorder, muscle disorder (myopathy, dystrophy, metabolic) or peripheral neuropathy. Description of Sites/Facilities Enrolling Participants: Single site, Clinical Center, Building 10, NIH, Bethesda, MD Study Duration: 5 years Participant Duration: A single visit is 4 hours or less. Many participants will only have one visit. Up to 5 visits is allowed to evaluate for repeated measures and a limited amount of follow-up assessment for changes in measures over time in patients with disease states or controls.

- INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Healthy Volunteers-Adults 1. Healthy adults, male or female, aged 18 years old or older, 2. In good general health as evidenced by medical history, medical conditions under control such as hypertension acceptable. 3. Stated willingness to comply with all study procedures and availability for the duration of the study. 4. Ability of subject to understand and the willingness to sign a written informed consent document. 2. Participants with neuromuscular disorders 1. Adults, male or female, aged 18 years old or older, 2. Diagnosed with a neuromuscular disorder or have signs and symptoms of nerve or muscle disorder or neuromuscular diaphragm dysfunction. 3. Stated willingness to comply with all study procedures and availability for the duration of the study. 4. Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: 1. Healthy Volunteers-Adults History of stroke, muscle disorders, peripheral neuropathy, or spine surgery 2. Participants with neuromuscular disorders No clinical evidence of a neuromuscular disorder on clinical evaluation.

Study Location
Maryland