Noninvasive therapeutic ultrasound to increase perfusion in chronic limb-threatening ischemia: An early feasibility study.

Background: Preclinical studies have demonstrated that therapeutic ultrasound (TUS) increases perfusion in peripheral artery disease (PAD). This pilot study assessed the safety and effectiveness of a noninvasive TUS device in patients with advanced PAD.

Methods: A phased array of TUS transducers was fabricated on a wearable sleeve, designed to sonicate the posterior and anterior tibial arteries (and their collaterals) at the calf level. Twelve patients with PAD (Rutherford classes 3-5) were enrolled in a single-arm study in which they underwent 30-40 daily 90-minute TUS sessions to the diseased limb. Changes in pedal flow and tissue oxygenation (StO₂) were measured by laser speckle and spatial frequency domain imaging, respectively. A subset of five patients underwent evaluation by laser Doppler, transcutaneous oximetry (TcPO₂), and quality of life questionnaires (Vascular Quality of Life Questionnaire [VascuQoL] and the Walking Impairment Questionnaire [WIQ]).

Results: Eleven out of 12 enrolled patients completed the study. During 90-minute TUS sessions pedal flow improved by 180% (p < 0.001) on laser speckle imaging, and 18% (p = 0.12) on laser Doppler. Tissue oxygenation improved by 18% (p = 0.43) on TcPO₂ and by 6% (p = 0.097) on StO₂. After all sessions, tissue oxygenation improved by 17% (p = 0.020) on StO₂, without significant changes in laser Doppler (+39%, p = 0.41) or TcPO₂ (-3%, p = 0.70), which was largely in the normal range (56 ± 15 mmHg) at baseline. VascuQoL improved by 2.4 points (14%, p = 0.080) and WIQ improved by 8.2 points (11%, p = 0.053).

Conclusions: TUS for patients with symptomatic PAD was safe and well tolerated. Most metrics of tissue perfusion and oxygenation improved, but future sham-controlled studies are needed and planned.