Pilot Study of Topographic Imaging of the Calf Muscle in Patients With PAD Using 3D Reconstruction of MSOT Images

Study Overview
=================
Brief Summary
-----------------
The aim of this explorative pilot study is to present muscle perfusion of the lower extremity in patients with PAD using the Multispectral Optoacoustic Tomography (MSOT) method to build a 3D reconstruction of the calf muscle. This study aims to show the feasibility of 3D reconstruction of this non-invasive method. Advantages in diagnostics for patients with PAD and three-dimensional tomography representation of the perfusion situation based on muscle oxygenation will be evaluated.

Detailed Description
-----------------
Functional imaging diagnostics is becoming increasingly important due to the steadily growing knowledge of physiological processes in many diseases. Also in peripheral arterial occlusive disease (PAD), new insights into the pathomechanism of the disease are continuously being gained. This also increases the need for new non-invasive imaging methods that are able to visualize the functional level of the disease progression and thus make it possible to diagnose it at an early stage. Recent studies indicate that it may be feasible to use multispectral optoacoustic tomography (MSOT) to visualize hemodynamics as well as the fibrotic muscle remodeling process in PAD. For a better understanding of the distribution pattern , the exploration of a 3D technique is a next necessary step in imaging. This may show a possible existing heterogeneity of these molecules. Holzwarth et al. were already able to gain knowledge about the 3D reconstruction from 2D photoacoustic image slices using an optical pattern and the method's feasibility using phantoms as well as in-vivo measurements of the forearm in healthy volunteers. The aim of this exploratory pilot project is to bring these previous findings together and to image muscle perfusion of the lower extremity in three dimensions using the MSOT method and to verify its feasibility. The advantage of 3D imaging is, beyond the anatomical topography of the muscle, to map a three-dimensional representation of the perfusion situation based on muscle oxygenation. For this purpose, six patients of different symptomatic PAD stages and a healthy control of two volunteers will be included and examined by means of longitudinal MSOT scans in the area of the gastrocnemius muscle. To evaluate the current stage of the disease or to exclude relevant PAD in the healthy control population, non-invasive examination measures commonly used in routine diagnostics of PAD will be applied. In addition to the relevant risk factors/adjacent diseases and the current medication intake, these include the recording of the ankle-brachial index (ABI), color-coded duplex sonographic vascular imaging (CCDS) and a treadmill examination.

Official Title
-----------------
Pilot Study of Topographic Imaging of the Gastrocnemius Muscle in Patients With PAD Using Non-invasive Multispectral Optoacoustic Tomography (MSOT) as a 3D Reconstruction Based on Longitudinal 2D Measurements

Conditions
-----------------
Peripheral Vascular Diseases, Peripheral Arterial Disease

Intervention / Treatment
-----------------
* Device: Multispectral Optoacoustic Tomography (MSOT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with manifest PAD stages II-IV according to Fontaine or healthy volunteers Adult (>18 years) persons who are able to give their consent Exclusion Criteria: Patients with PAD stage I according to Fontaine Healthy volunteers with pre-existing diabetes mellitus, chronic renal failure, or abnormal ABI Underage persons Missing consent form Exclusion due to safety concerns of the study physician (patient with a physical, mental or psychiatric illness which, in the opinion of the study physician, would compromise the safety of the patient or the quality of the data and thus make the patient an unsuitable candidate for the study)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Multispectral Optoacoustic Tomography (MSOT) and B-Mode Ultrasound of the Musculus gastrocnemius of the affected leg in PAD patients or one leg in healthy volunteers (total 1 site) Physical assessment: Color-Coded Duplex Sonography/treadmill examination to determine actual walking distance/Ankle-Brachial-Index/defined walking distance of 150 meters under medical supervision | Device: Multispectral Optoacoustic Tomography (MSOT)<br>* non-invasive transcutaneous imaging of subcellular muscle components<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSOT topogram showing MSOT parameters from 660 up to 1100 nm of the gastrocnemius muscle | MSOT topogram using 3D reconstruction based on longitudinal 2D scans trough an optical pattern showing MSOT parameters from 660 up to 1100 nm of the gastrocnemius muscle | single time point (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acquisition of the quantitative hemoglobin signal (oxygenated/deoxygenated) | This Outcome is measured non-invasively by MSOT, the single wavelengths are spectrally unmixed | single time point (1 day) | 
| Acquisition of the quantitative fibrosis signals (collagen/lipid) | This Outcome is measured non-invasively by MSOT, the single wavelengths are spectrally unmixed | single time point (1 day) | 
| 3D reconstruction of the longitudinal measurements using two different pattern designs | This Outcome is measured non-invasively by MSOT. A foil imprinted with an N is applied and fixed over the calf muscle. Three longitudinal 2D measurements are made or repeated until a promising result is obtained. The same procedure is repeated with a foil imprinted with a trident. | single time point (1 day) | 
| Acquisition of static 2D MSOT measurements before and after gait exposure | This Outcome is measured non-invasively by MSOT. An initial measurement is taken at rest. Subsequently, the patient will complete a defined walking distance of 150 meters under medical supervision. Afterwards, the medial head of the gastrocnemius muscle is measured again. | single time point (1 day) | 
| Validation of the accuracy of the MSOT 3D reconstruction using an overlay from MRA | This Outcome is only realized in participants who received an magnetic resonance angiography regardless of study participation | single time point (1 day) | 
| Acquisition of the flow profile of the common femoral artery and popliteal artery using CCDS | This Outcome is measured non-invasively by standardized vascular sonography | single time point (1 day) | 
| Acquisition of the Ankle-Brachial-Index | This Outcome is measured non-invasively by standardized clinical assessment according to the according to the recommendation from the S3 guideline for PAD of the German Association for Angiology (Deutsche Gesellschaft für Angiologie) dated November 30, 2015 | single time point (1 day) | 
| Acquisition of the current walking distance standardized by treadmill examination | This Outcome is measured by a standardized treadmill examination (excluding PAD patients in chronic critical stage III or IV according to Fontaine) ideally with 3km/h and 12% incline | single time point (1 day) | 
| Acquisition of the PAD stage according to Fontaine and Rutherford | This Outcome is acquired by actual recommendation from national and international guidelines | single time point (1 day) | 
| Recording of relevant patient data from the patient's file | Preexisting disorders, previous performed operations on vessels, current medication, radiological TransAtlantic InterSociety Consensus classification | single time point (1 day) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peripheral Vascular Disease, Peripheral Arterial Disease, Multispectral Optoacoustic Tomography, MSOT, PAD, Claudicatio intermittens, Critical Limb Ischemia, CLI, Diagnostic imaging, Color-Coded Duplex Sonography, CCDS, Non-invasive diagnostic procedure, non-invasive diagnostic, noninvasive diagnostic, 3D imaging, three-dimensional imaging, three-dimensional diagnostic, 3D diagnostic, tattoo tomography, optical pattern