US-Induced Cavitation of Microbubble Contrast Agents May Increase Skeletal Muscle Perfusion

Optimized ultrasound cavitation of contrast microbubbles may increase skeletal muscle perfusion in peripheral artery disease.

Using optimized acoustic environments, ultrasound (US) cavitation of microbubble contrast agents can increase perfusion in limb skeletal muscle, representing a potential treatment option for patients with peripheral artery disease (PAD), according to study results published in JACC: Cardiovascular Imaging.

The researchers first investigated the ideal acoustic conditions in mice. They performed unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) for ten minutes after intravenous (IV) injection of lipid microbubbles. The researchers varied US according to line density (17-, 37-, 65-lines_ and pulse duration. They used US perfusion imaging to assess microvascular perfusion and in vivo optical imaging to assess in vivo adenosine triphosphate (ATP) release.

In the mice, the researchers found that the US-exposed limb had augmented flow for all conditions. At the lowest line density, there was a stepwise increase in perfusion for longer (40-cycle) compared with shorter (5-cycle) pulse duration. At higher line densities, the results indicated that blood flow consistently increased by three- to four–fold in the US-exposed limb, regardless of pulse duration.

After testing in mice, the researchers used the optimal parameters in healthy individuals and patients with PAD alone. All individuals underwent calf ultrasound alone or in combination with IV microbubble contrast infusion for ten minutes.

High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone, so these were the optimized conditions used in humans. .

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Applying these optimized conditions along with IV contrast resulted in increased >two-fold calf muscle blood flow in both healthy individuals and patients with PAD. US alone had no effect on muscle blood flow.

The study had several limitations. The researchers did not assess spatial extent of perfusion augmentation, test MB dose-response or time-response, or evaluate changes in symptoms.

“Further clinical translation will require modifications in transducer technology, scanning schemes, and possibly contrast agent composition that will permit large-volume therapy and longer-duration of effect,” the researchers wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Mason OR, Davidson BP, Sheeran P, et al. Augmentation of tissue perfusion in patients with peripheral artery disease by microbubble cavitation. [published online August 14, 2019]. JACC Cardiovasc Imaging. doi:10.1016/j.jcmg.2019.06.012