Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy Using Multispectral Optoacoustic Tomography

Study Overview
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Brief Summary
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This pilot study aims to assess subcellular muscle structure in patients with Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) in comparison to healthy volunteers using multispectral optoacoustic tomography (MSOT). During MSOT, a transducer is placed on the skin similar to a conventional sonography and instead of sound, energy is supplied to the tissue by means of light flashes. This leads to a constant change of minimal expansions and contractions (thermoelastic expansion) of individual tissue constituents or molecules. The resulting sound waves can then be detected by the same examination unit.

Detailed Description
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Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) is one of the most common progressive childhood muscle diseases with an incidence of 1 in 3500 male newborns and is associated primarily with decreased life expectancy. From the age of 4-5 years manifest motor problems in everyday life, typical signs of proximal muscle weakness, with lab-chemical increase of the muscle enzyme (creatinine kinase, CK). Within a few years, relevant muscle and tendon shortening leading to joint malpositions and instability, as well as scoliosis and loss of walking around the age of 10 are formed. Supportive therapies can not curatively affect complications and progression of the disease. Pathogenetically, there is a deficiency of dystrophin, a structural protein of the sarcolemma, which is caused by mutations (usually deletions) of the dystrophin gene (Xp21.3-p21.2). The result of dystrophin deficiency is a necrosis of muscle cells that are replaced by connective tissue and adipose tissue. Clinical scores (6-minute walk test, 6MWT) and MRI studies to characterize the degenerative changes of skeletal muscle in the early stages are available for the quantitative assessment of the disease progression as well as therapy effects, the significance of which is controversially discussed. However, the highly sensitive assessment of gene therapy effects (e.g., PTC 124) will become increasingly important in the future. Sensitive, non-invasive methods for the detection of early muscle degeneration and muscle function in the course are of great clinical and scientific importance. The purpose of this first pilot study is to investigate whether the differences in skeletal muscle composition of healthy volunteers and ambulatory patients with early stage DMD can be quantified and characterized using multispectral optoacoustic tomography (MSOT). This could in the future generate a completely new, non-invasive method to develop non-invasive biomarkers of disease progression or therapy response.

Official Title
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Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy as Diagnostic and Progression Marker Using Multispectral Optoacoustic Tomography

Conditions
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Duchenne Muscular Dystrophy, Muscular Dystrophies, Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Device: Multispectral Optoacoustic Tomography


Participation Criteria
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Eligibility Criteria
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DMD-Patients Inclusion Criteria: Histologic or genetically proven DMD Age 3-10 years Exclusion Criteria: - Healthy controls Inclusion Criteria: Male Age 3-10 years Exclusion Criteria: Suspected muscular disease/myopathia missing informed consent

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Muscular Dystrophia<br>Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis | Device: Multispectral Optoacoustic Tomography<br>* Non-invasive transcutaneous imaging of subcellular muscle components<br>|
| Active Comparator: Healthy Volunteer<br>Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis | Device: Multispectral Optoacoustic Tomography<br>* Non-invasive transcutaneous imaging of subcellular muscle components<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular lipid content | Quantitative lipid signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.) | Single time point (1 day) | 
| Muscular collagen content | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.) | Single time point (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular myo-/hemoglobin content | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.) | Single time point (1 day) | 
| Correlation of lipid signal with age/disease duration | Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with individual disease duration/age (in month) | Single time point (1 day) | 
| Correlation of myo-/hemoglobin signal with age/disease duration | Quantitative moo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with individual disease duration/age (in month) | Single time point (1 day) | 
| Correlation of lipid signal with 6MWT | Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity) | Single time point (1 day) | 
| Correlation of lipid signal with MRC | Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale | Single time point (1 day) | 
| Correlation of collagen signal with 6MWT | Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity) | Single time point (1 day) | 
| Correlation of collagen signal with MRC | Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale | Single time point (1 day) | 
| Correlation of myo-/hemoglobin signal with 6MWT | Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity) | Single time point (1 day) | 
| Correlation of myo-/hemoglobin signal with MRC | Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale | Single time point (1 day) | 
| Signal differences left and right muscles | Comparison of quantitative signal levels (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD/healthy controls in right and left body muscular groups (upper and lower body) | Single time point (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Optoacoustics, MSOT, Multispectral Optoacoustic Tomography