Non-invasive Molecular Imaging of Muscle Structure (MSOT_muscles)

Study Overview
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Brief Summary
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This study aims to determine hemoglobin and collagen levels in muscles before and after exercise, and over time, 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 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. 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 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. MSOT has already been demonstrated to be a potential monitoring tool in different diseases. However, it has not yet been investigated to what extent 1) previous physical activity 2) different measuring ranges at the muscle, 3) longitudinal measurements and 4) intra- and interoperative variability influences the measured results. In particular, molecular changes immediately after the 6-MWT are relevant for studies in patients with DMD. In this first pilot study, the investigators want to investigate in healthy adults, whether increased exercise changes the hemoglobin values, whether the collagen content remains constant and whether repeated measurements at different muscle positions by different investigators provide consistent results over time. This information is indispensable for future studies of children with muscular diseases in order to be able to make statements about disease progression or even therapy response.

Official Title
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Non-invasive Molecular Imaging to Determine Hemoglobin and Collagen Levels in Muscles Before and After Exercise, and Over Time

Conditions
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Muscular Diseases

Intervention / Treatment
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* Device: Multispectral Optoacoustic Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years of age Exclusion Criteria: any reference to a myopathy pregnancy tattoo in the scanning region

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers<br>Multispectral Optoacoustic Tomography (MSOT) of proximal and distal leg muscles (total of 12 sites: left and right, 3 measurement points of Musculus quadriceps, and 3 measurement points of Musculus triceps surae) before and after the 6-Minute-Walk-Test by to independent investigators. Repetition of the same protocol after 14 days. | 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 collagen content | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT. | one time point ( 2 measurements on day 1) | 
| Muscular myo-/hemoglobin content | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT. | one time point ( 2 measurements on day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular oxygenated and deoxygenated myo-/hemoglobin content | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT and after 14 days. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Intraindividual collagen content | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Intraindividual myo-/hemoglobin content | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Intraindividual oxygenated and deoxygenated myo-/hemoglobin content | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Muscular collagen content in men and women | Quantitative collagen signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Muscular myo-/hemoglobin content in men and women | Quantitative myo-/hemoglobin signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Muscular oxygenated and deoxygenated myo-/hemoglobin content in men and women | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Correlation of collagen signal with the 6-MWT | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Correlation of myo-/hemoglobin signal with the 6-MWT | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Correlation of oxygenated and deoxygenated myo-/hemoglobin signal with the 6-MWT | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interrater reliability of collagen content | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interrater reliability of myo-/hemoglobin content | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interrater reliability of oxygenated and deoxygenated myo-/hemoglobin content | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interreader reliability of collagen content | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interreader reliability of myo-/hemoglobin content | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Interreader reliability of oxygenated and deoxygenated myo-/hemoglobin content | Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Muscular collagen content over time period | Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared between day 1 and after 14 days. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 
| Muscular myo-/hemoglobin content over time period | Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared between day 1 and after 14 days. | multiple time points ( 2 measurements on day 1 and 2 measurements on day 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular Diseases, Duchenne muscular disease, MSOT