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 (StO 2 ) were measured by laser speckle and spatial frequency domain imaging, respectively. A subset of five patients underwent evaluation by laser Doppler, transcutaneous oximetry (TcPO 2 ), 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 TcPO 2 and by 6% ( p = 0.097) on StO 2 . After all sessions, tissue oxygenation improved by 17% ( p = 0.020) on StO 2 , without significant changes in laser Doppler (+39%, p = 0.41) or TcPO 2 (–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.