Evaluation of Musculoskeletal Microcirculation With Ultrasound

Study Overview
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Brief Summary
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This study aims to validate the use of Dynamic Contrast-Enhanced Ultrasound in measuring the blood supply to the muscles of the leg, and how this changes with exercise and vascular pathology.

Detailed Description
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We propose a model for the use of Dynamic Contrast-Enhanced Ultrasound (DCEU) to directly evaluate the microcirculation of the musculoskeletal system. We believe that this will be a valuable research tool into diseases of the microcirculation, and in the future may also offer a clinical benefit by quantifying and monitoring disease over time and after intervention. It may also allow targeting of therapies towards those patients most at risk of ulcers and peripheral neuropathy, and those that would get the maximum benefit from these therapies.

Official Title
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Evaluation of Musculoskeletal Microcirculation With Ultrasound

Conditions
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Standardised Claudication Treadmill Test

Intervention / Treatment
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* Procedure: Contrast enhanced ultrasound
* Behavioral: Treadmill test
* Procedure: Contrast enhanced ultrasound


Participation Criteria
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Eligibility Criteria
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Group 1 - Healthy subjects Inclusion 18+ years old Exclusion Personal history of diabetes or peripheral arterial disease, current pregnancy, previous surgery to the lower limb, heart attack within 4 weeks, or unstable angina Group 2 - Peripheral arterial disease subjects Inclusion 18+ years old, radiological evidence of peripheral arterial disease (arterial doppler or angiogram), ankle-brachial pressure index (ABPI) 0.5-0.8 Exclusion Personal history of diabetes, current pregnancy, previous amputation, heart attack within 4 weeks, or unstable angina Group 3 - Diabetic subjects Inclusion 18+ years old, with a clinical diagnoses of diabetes (1, 2) Exclusion - ABPI<0.9, previous amputation, current pregnancy or breastfeeding, heart attack within 4 weeks, or unstable angina.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy<br>Healthy volunteers, deemed to have normal metabolic and cardiovascular biology by trial criteria | Procedure: Contrast enhanced ultrasound<br>* Infusion of microbubbles to enhance blood vessels in the leg for ultrasound<br>Behavioral: Treadmill test<br>* Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol<br>Procedure: Contrast enhanced ultrasound<br> <br> |
| Active Comparator: PAD<br>Symptomatic peripheral arterial disease | Procedure: Contrast enhanced ultrasound<br>* Infusion of microbubbles to enhance blood vessels in the leg for ultrasound<br>Behavioral: Treadmill test<br>* Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol<br>Procedure: Contrast enhanced ultrasound<br> <br> |
| Active Comparator: DM<br>Symptomatic diabetic peripheral neuropathy | Procedure: Contrast enhanced ultrasound<br>* Infusion of microbubbles to enhance blood vessels in the leg for ultrasound<br>Behavioral: Treadmill test<br>* Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol<br>Procedure: Contrast enhanced ultrasound<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Threshold of High to Low Frequency Ratio (Threshold HLFR) | Please see published article for in depth method. This ratio is used to classify a given signal as either microbubble or noise. For a pixel containing a micro vessel, as microbubbles occasionally pass this otherwise dark pixel, its temporal signal is expected to have a higher proportion of lower frequency components than white noise. Consequently, the HLFR of the pixel is expected to be smaller than that of noise. A histogram of normalised HLFR shows two expected peaks (one noise, one bubbles). A threshold (Threshold HLFR) is determined to then separate the two peaks. this is done using a double Gaussian model, and where they intercept is deemed the Threshold HLFR. | Baseline, 20 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treadmill test