Muscle Perfusion in Patients With PAD by Non-invasive MSOT

Cross-sectional Study of Muscle Perfusion in Patients With PAD by Non-invasive Multispectral Optoacoustic Tomography

The aim of the proposed study is to define an independent parameter for the diagnostic assessment of the perfusion situation of the calf muscle based on Multispectral Optoacoustic Tomography (MSOT) in a cross-sectional collective of healthy volunteers and patients with PAD. The gold standard is a previously performed angiography of the pelvic and femoral vessels based on routine diagnostics, this Imaging is not mandatory for healthy Control group (study group 1). An independent validation group (study group 2) will validate the results found in study group 1.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Peripheral Vascular Disease
• Intervention / Treatment: Device: Multispectral Optoacustic Tomography (MSOT)

Detailed Description

Peripheral arterial occlusive disease (PAD) is one of the most common diseases of the elderly with an overall prevalence of about 3-10%. As life expectancy increases, new treatment concepts and new diagnostic procedures are needed. In addition to the possibility of endovascular treatment and open surgery, in some cases there is also the possibility of a conservative therapeutic approach, e.g. with medication.

To date, the only independent non-invasive validation of these treatment options is the measurement of macrocirculation in the form of Color-Coded Vascular Duplex Sonography (CCDS), the Ankle Brachial Index (ABI) or the measurement of walking distance. The S3 guideline for diagnosis, therapy and medical aftercare of PAD published 2015 by the DGA (Deutsche Gesellschaft für Angiologie und Gefäßmedizin [German Society for Angiology and Vascular Medicine]) recommends aftercare in the sense of clinical examinations, especially for patients after vascular surgery. For the validation measures already mentioned, however, there are not infrequent patient groups for which these methods provide only insufficient or unusable results (diabetes mellitus, terminal renal failure). In these cases, independent verification of the success of the therapy performed would have to be performed using angiography (digital subtraction angiography, CT angiography or MR angiography). However, this is not routinely performed in the respective patient populations due to the associated risks (including radiation exposure, contrast agent administration, invasiveness).

Multispectral Optoacoustic Tomography (MSOT) now provides a new non-invasive diagnostic tool that may be able to fill this diagnostic gap.

The aim of this cross-sectional study is to define an independent parameter using the MSOT method, which allows a statement about the current perfusion situation of the lower extremity and correlates with the angiography, which is considered the gold standard. For this purpose, patients of different PAD stages, who already underwent routinely angiographies in advance, will be included. In addition, a control group of healthy volunteers (prior angiography not obligatory) will be examined.

• Study Type: Observational
• Enrollment (Actual): 220

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • University of Erlangen, Vascular Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with

• PAD IIa with indication for angiography
• PAD IIb with indication for angiography
• PAD III with indication for angiography
• PAD IV with indication for angiography

who come in for a routine presentation of the vascular surgery consultation hours.

And healthy volunteers:

• No PAD previously known
• No diabetes mellitus previously known
• No chronic renal insufficiency previously known
• No symptoms in the sense of a Claudicatio intermitten
• ABI with normal value

who are recruted by clinic notices.

Description

Inclusion criteria:

• Patients with manifest PAD stages II - IV according to Fontaine or category 1-6 according to Rutherford
• Adult (>18 years) persons who are able to give their consent
• Patients in whom angiography has been performed as part of routine diagnostics (independent of the study) or in accordance with current guidelines, or has been indicated and the patients has given consent

Exclusion criteria:

• Patients with PAD stage I according to Fontaine or category 0 according to Rutherford
• Underage persons
• Missing consent form
• Patients with manifest PAD in whom angiography is not indicated
• 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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group 1; Multispectral Optoacoustic Tomography (MSOT) and B-Mode Ultrasound of the Musculus triceps surae 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 Optoacustic Tomography (MSOT); non-invasive transcutaneous imaging of subcellular muscle components
Study group 2; Multispectral Optoacoustic Tomography (MSOT) and B-Mode Ultrasound of the Musculus triceps surae 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 Optoacustic Tomography (MSOT); non-invasive transcutaneous imaging of subcellular muscle components

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Derivation of optimal diagnostic MSOT thresholds for hemoglobin	Derivation of optimal diagnostic MSOT thresholds for hemoglobin through correlation with TASC classification for angiographic imaging as references for relevant stenosis/ occlusion in patients with PAD	single time point (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular oxygenated/deoxygenated/total hemoglobin and the MSOT-values at a wavelength of 800nm before and after gait exposure	Quantitative oxygenated/deoxygenated/total hemoglobin signal and signal at a wavelength of 800 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with PAD before gait exposure compared to the signals after gait exposure	single time point (1 day)
Correlation of oxygenated/deoxygenated/total hemoglobin content and MSOT-values at a wavelength of 800 nm with the TASC-classification (angiography)	Quantitative oxygenated/deoxygenated/total hemoglobin signal and signal at a wavelength of 800 nm(Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with PAD correlated with the TASC-classification (angiography)	single time point (1 day)
Difference between oxygenated/deoxygenated hemoglobin before and after gait exposure	Difference between quantitative oxygenated hemoglobin amount (Units: arbitrary units (a. u.)) and quantitative deoxygenated hemoglobin amount (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with PAD before gait exposure compared to the amount after gait exposure	single time point (1 day)
Correlation of difference between oxygenated/deoxygenated hemoglobin with the TASC-classification (angiography)	Difference between quantitative oxygenated hemoglobin amount (Units: arbitrary units (a. u.)) and quantitative deoxygenated hemoglobin amount (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with PAD correlated with the TASC-classification (angiography)	single time point (1 day)
Muscular quantitative lipid/collagen signal fraction and the MSOT-values at a wavelength of 930 and 1064 nm	Quantitative lipid/collagen signals and signals at 930 and 1064 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with different clinical and angiographic PAD stages	single time point (1 day)
Correlation of acquired MSOT parameters with the CCDS flow profile and PSV	Quantitative oxygenated/deoxygenated/total hemoglobin content and MSOT-values at a wavelength of 800 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT in patients with PAD correlated with the flow profile and PSV of A. CFA and A. poplitea determined by CCDS	single time point (1 day)
Correlation of acquired MSOT parameters with the ABI	Quantitative oxygenated/deoxygenated/total hemoglobin content and MSOT-values at a wavelength of 800 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT correlated with the ABI	single time point (1 day)
Correlation of acquired MSOT parameters with the walking distance determined by treadmill examination	Quantitative oxygenated/deoxygenated/total hemoglobin content and MSOT-values at a wavelength of 800 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT correlated with the walking distance determined by treadmill examination	single time point (1 day)
Correlation of acquired MSOT parameters with the clinical severity of PAD	Quantitative oxygenated/deoxygenated/total hemoglobin content and MSOT-values at a wavelength of 800 nm (Units: arbitrary units (a. u.)) derived by transcutaneous MSOT correlated with the clinical severity of PAD according to Fontaine and Rutherford	single time point (1 day)

Collaborators and Investigators

• Sponsor: University Hospital Erlangen
• Collaborators: Department of Medicine 1 University Hospital Erlangen, Prof. Dr. Maximilian J. Waldner

Publications and helpful links

General Publications

• Lange S, Diehm C, Darius H, Haberl R, Allenberg JR, Pittrow D, Schuster A, von Stritzky B, Tepohl G, Trampisch HJ. High prevalence of peripheral arterial disease and low treatment rates in elderly primary care patients with diabetes. Exp Clin Endocrinol Diabetes. 2004 Nov;112(10):566-73. doi: 10.1055/s-2004-830408.
• Alpert JS, Larsen OA, Lassen NA. Exercise and intermittent claudication. Blood flow in the calf muscle during walking studied by the xenon-133 clearance method. Circulation. 1969 Mar;39(3):353-9.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): February 18, 2022

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: PAD; Peripheral Vascular Disease; Revascularization; Peripheral Arterial Disease; Multispectral Optoacoustic Tomography; Claudicatio intermittens; Critical limb ischemia; MSOT; CLI; Angiography; Color-Coded Duplex Sonography; CCDS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: MSOT_PAD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No