Calf Muscle Perfusion in Patients With Intermittent Claudication by 3D-reconstruction of MSOT (MSOT_IC_3D)

Study Overview
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Brief Summary
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The aim of the proposed study is to define independent parameters for the diagnostic assessment of the perfusion situation of the calf muscle based on 3D-reconstruction of multispectral optoacoustic tomography (MSOT) in a cross-sectional collective of patients with PAD in Fontaine stage II and a healthy control group.

Detailed Description
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This is a monocentric, prospective cross-sectional study which aims to compare the 3D-reconstructed optoacoustic signals in calf muscle after a exercise in patients with PAD in Fontaine stage II and a healthy control group in order to define MSOT thresholds. MSOT data will be correlated with CCDS, ABI, maximum walking distance in 6MWT, subjectively perceived absolute walking distance in everyday life, PAD-related life quality (VASCUQOL-6) and TASC II classification in angiographic imaging (only in case angiographic imaging is available and independent from this study). Patients with intermittent claudication will be recruited during the consulting hours of the Department of Vascular Surgery, University Hospital Erlangen. Healthy volunteers will be acquired via posters in the clinic. Following detailed information about the study and after providing written consent, relevant clinical data will be collected from the electronical patient file, if available. In addition, a thorough anamnesis interview for relevant data and CCDS would be performed. Afterwards, the 3D-reconstructed parameters will be recorded by means of longitudinal MSOT scans before and after a heel raise exercise until the occurrence of claudication pain in the calf muscle. For patients with PAD, the more affected leg is examined. In healthy volunteers, either leg is examined. ABI would be measured before and after 6MWT. All data will be adequately pseudonymized in compliance with data protection regulations before they are used for statistical analysis. The duration of the study for participants will be max. 90 minutes. The angiographic imaging will be reviewed and analyzed (if available, independently from this study and the interval between MSOT measurement being lesser than 12 months). The complete study including the validation of the data by an independent study group is expected to be finished within one year.

Official Title
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Cross-sectional Study of Calf Muscle Perfusion Via 3D Reconstruction of Multispectral Optoacoustic Tomography in Patients With Peripheral Arterial Disease After Exercise.

Conditions
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Diagnostic Imaging, Peripheral Arterial Disease, Intermittent Claudication

Intervention / Treatment
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* Diagnostic Test: MSOT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with PAD in Fontaine stage II or Rutherford category 1-3 or healthy volunteers Adults (>18 years) who are able to give their consent Exclusion Criteria: Patients with PAD in Fontaine stage I, III and IV or Rutherford category 0, 4, 5 and 6 or healthy volunteers with diabetes mellitus, chronic renal failure, claudication symptoms, abnormal ABI or non-palpable foot pulses People with age under 18 Absence of written consent Safety concerns of the study physician (person with physical, mental or psychiatric conditions which, by the judgement of the study physician, would compromise the person's safety or the quality of the data, thereby rendering the person an ineligible candidate for the study

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| healthy group<br>Multispectral Optoacoustic Tomography (MSOT) of the Musculus triceps surae of one leg in healthy volunteers Physical assessment: Pulse status / Color-Coded Duplex Sonography / Ankle-Brachial Index / 6-minute walk test (6MWT) / Continued heel raises for at least 30s | Diagnostic Test: MSOT<br>* Similar as the conventional sonography, the MSOT transducer head is placed on the skin of the examined person above the target organ. But instead of sound waves, energy is applied to the tissue via laser light, leading to constant changes of minimal expansions and contractions (thermoelastic expansion) of different tissue components or molecules. The same transducer head that releases the laser flashes can also detect the emitted ultrasound waves. In the newly configured device (Acuity Echo, iThera Medical GmbH, Munich, CE-certified), an extended spectrum of laser light can be used, enabling among others the derivation of values corresponding to hemoglobin and its oxygenation levels. As hemoglobin concentration and oxygenation status are markers for perfusion, MSOT-based imaging of these parameters could be a highly sensitive and reliable method to analyze muscle perfusion.<br>* Other names: multispectral optoacoustic tomograph;|
| Patients with PAD in Fontaine stage II<br>Multispectral Optoacoustic Tomography (MSOT) of the Musculus triceps surae of the affected leg in PAD patients in Fontaine stage II (intermittent claudication) Physical assessment: Pulse status / Color-Coded Duplex Sonography / Ankle-Brachial Index / 6-minute walk test (6MWT) / Continued heel raises for at least 30s | Diagnostic Test: MSOT<br>* Similar as the conventional sonography, the MSOT transducer head is placed on the skin of the examined person above the target organ. But instead of sound waves, energy is applied to the tissue via laser light, leading to constant changes of minimal expansions and contractions (thermoelastic expansion) of different tissue components or molecules. The same transducer head that releases the laser flashes can also detect the emitted ultrasound waves. In the newly configured device (Acuity Echo, iThera Medical GmbH, Munich, CE-certified), an extended spectrum of laser light can be used, enabling among others the derivation of values corresponding to hemoglobin and its oxygenation levels. As hemoglobin concentration and oxygenation status are markers for perfusion, MSOT-based imaging of these parameters could be a highly sensitive and reliable method to analyze muscle perfusion.<br>* Other names: multispectral optoacoustic tomograph;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal diagnostic MSOT thresholds | Quantitative oxygenated hemoglobin signal in 3D-reconstruction (in arbitrary units). [This target variable is collected non-invasively using MSOT]. | single time point (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the corresponding 3D-reconstructed MSOT values before and after exercise | Difference of the values before and after exercise for hemoglobin-associated parameters derived by transcutaneous MSOT inpatients in intermittent claudication stage | single time point (1 day) | 
| Reperfusion profiles of hemoglobin-associated 3D-reconstructed MSOT parameters | i.e. the curves of hemoglobin-associated MSOT parameters in the first ten minutes after exercise | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with the CCDS flow profiles and PSVs | hemoglobin-associated MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT in patients with PAD in Fontaine stage II correlated with the flow profiles and PSVs of A. femoralis communis and A. poplitea determined by CCDS | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with the ABI | hemoglobin-associated MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT correlated with the ABI measurements | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with relative (until the first occurrence of pain) and absolute walking distance (until the first stopping due to pain) determined during the 6MWT | hemoglobin-associated MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT correlated with relative (until the first occurrence of pain) and absolute walking distance (until the first stopping due to pain) | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with maximum walking distance in the 6MWT | hemoglobin-associated, 3D-reconstructed MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT correlated with the maximum walking distance in the 6MWT | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with the subjectively perceived maximum walking distance in everyday life | hemoglobin-associated, 3D-reconstructed MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT correlated with the subjectively perceived maximum walking distance in everyday life | single time point (1 day) | 
| Correlation of acquired 3D-reconstructed MSOT parameters with the perceived PAD-specific quality of life (VASCUQOL-6 questionnaire) | hemoglobin-associated, 3D-reconstructed MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT correlated with the perceived PAD-specific quality of life (VASCUQOL-6 questionnaire) | single time point (1 day) | 
| Correlation of the acquired 3D-reconstructed MSOT parameters with the TASC-classification (angiography) | hemoglobin-associated, 3D-reconstructed MSOT parameters (units: arbitrary units (a.u.)) derived by transcutaneous MSOT in patients with PAD in Fontaine stage II correlated with the TASC-classification (angiography) | single time point (1 day) | 
| Confounder analysis | • Correlation of all collected parameters (anamnestic, demographic, physiological) with regard to their characteristics as basic confounders for the MSOT technique | single time point (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Vascular Diseases, Peripheral Arterial Disease, Peripheral Artery Disease, PAD, Intermittent Claudication, Claudicatio intermittens, Color-Coded Duplex Sonography, CCDS, Ankle Brachial Index, ABI, Multispectral Optoacoustic Tomography, MSOT, Heel Raises, 6-minute walk test, 6MWT, Muscle Perfusion, Calf Muscle Perfusion, 3D, three-dimensional