Augmentation of Limb Perfusion With Contrast Ultrasound

Study Overview
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Brief Summary
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Our laboratory has discovered that ultrasound (US) imaging together with clinically approved microbubble ultrasound contrast agents can augment limb tissue perfusion. These observations have been made in mice with and without peripheral artery disease (PAD), and also in humans where high power contrast enhanced ultrasound (CEU) was used to measure perfusion but was found also to augment perfusion by almost 2-fold. The latter human studies were performed with ultrasound protocols designed for perfusion imaging and not for flow augmentation. In this study, we will measure the degree to which limb perfusion is augmented with specific therapeutic CEU settings that are still within the FDA-approved limits with regards to US power and contrast dosing.

Official Title
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Augmentation of Limb Perfusion With Contrast Ultrasound

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Device: Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 y.o. For PAD subjects: known history of unilateral or bilateral PAD diagnosed by reduced ankle-brachial index or angiography and a Rutherford symptom class of 4-6. Exclusion Criteria: Major medical illness other than PAD affecting the limb (muscle disease, blood diseases that influence flow or rheology, severe heart failure [NYHA class IV or LVEF <30%]). Pregnant or lactating females Hypersensitivity to any ultrasound contrast agent Known atrial septal defect or large right to left shunt. Hemodynamic instability (hypotension with systolic BP <90 mm Hg, need for vasopressors) Evidence for ongoing myocardial ischemia For normal controls, any known structural non-arrhythmic cardiovascular disease (coronary artery disease, heart failure, moderate or greater valve disease).

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 99 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy subjects<br>Low-power contrast ultrasound perfusion imaging and measurement of ABI and TBI will be performed before and after a 15 min high-power ultrasound cavitation therapy with intermittent ultrasound and intravenous infusion of microbubbles. | Device: Ultrasound<br>* Ultrasound exposure of Definity microbubbles infused over 10 min. Ultrasound administered at 1.3 MHz, mechanical index of 1.3, and pulsing interval of 10 s.<br>* Other names: Contrast ultrasound;|
| Experimental: Peripheral Artery Disease<br>Low-power contrast ultrasound perfusion imaging and measurement of ABI and TBI will be performed before and after a 15 min high-power ultrasound cavitation therapy with intermittent ultrasound and intravenous infusion of microbubbles. | Device: Ultrasound<br>* Ultrasound exposure of Definity microbubbles infused over 10 min. Ultrasound administered at 1.3 MHz, mechanical index of 1.3, and pulsing interval of 10 s.<br>* Other names: Contrast ultrasound;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood flow at 10 min | Change in blood flow in calf skeletal muscle | 10 min post-therapeutic ultrasound cavitation. | 
| Change in blood flow at 60 min | Change in blood flow in calf skeletal muscle | 60 min post-therapeutic ultrasound cavitation |