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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral Arterial Disease; Peripheral Vascular Diseases
• Intervention / Treatment: Device: Multispectral Optoacoustic Tomography (MSOT)

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.

• Study Type: Observational
• Enrollment (Actual): 9

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: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with PAD IIa/IIb/III/IV according to Fontaine who come in for a routine presentation of the the vascular surgery consultation hours.

Healthy volunteers with

• no PAD previously known
• no diabetes mellitus previously known
• no chronic renal insufficiency previously known
• no symptoms in the sense of a Claudicatio intermittens
• ABI with normal value who are recruited by clinic notices.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; 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); non-invasive transcutaneous imaging of subcellular muscle components

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)

Collaborators and Investigators

• Sponsor: University Hospital Erlangen
• Collaborators: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany; Division of Computer Assisted Medical Interventions, German Cancer Research Center, Heidelberg, Germany

Publications and helpful links

General Publications

• Signorelli SS, Vanella L, Abraham NG, Scuto S, Marino E, Rocic P. Pathophysiology of chronic peripheral ischemia: new perspectives. Ther Adv Chronic Dis. 2020 Feb 5;11:2040622319894466. doi: 10.1177/2040622319894466. eCollection 2020.
• Karlas A, Kallmayer M, Fasoula NA, Liapis E, Bariotakis M, Kronke M, Anastasopoulou M, Reber J, Eckstein HH, Ntziachristos V. Multispectral optoacoustic tomography of muscle perfusion and oxygenation under arterial and venous occlusion: A human pilot study. J Biophotonics. 2020 Jun;13(6):e201960169. doi: 10.1002/jbio.201960169. Epub 2020 Mar 25.
• Holzwarth N, Schellenberg M, Grohl J, Dreher K, Nolke JH, Seitel A, Tizabi MD, Muller-Stich BP, Maier-Hein L. Tattoo tomography: Freehand 3D photoacoustic image reconstruction with an optical pattern. Int J Comput Assist Radiol Surg. 2021 Jul;16(7):1101-1110. doi: 10.1007/s11548-021-02399-w. Epub 2021 May 16.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 24, 2021
• Primary Completion (ACTUAL): January 31, 2022
• Study Completion (ANTICIPATED): July 31, 2022

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (ACTUAL): November 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Diagnostic imaging; PAD; Peripheral Vascular Disease; Peripheral Arterial Disease; Multispectral Optoacoustic Tomography; Claudicatio intermittens; MSOT; CLI; Color-Coded Duplex Sonography; CCDS; Critical Limb Ischemia; 3D imaging; three-dimensional imaging; Non-invasive diagnostic procedure; non-invasive diagnostic; noninvasive diagnostic; three-dimensional diagnostic; 3D diagnostic; tattoo tomography; optical pattern
• 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_3D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No