A narrative review on the application of high-intensity focused ultrasound for the treatment of occlusive and thrombotic arterial disease

Objectives: High-intensity focused ultrasound (HIFU) is a noninvasive therapeutic modality with a variety of applications. It is approved for the treatment of essential tremors, ablation of prostate, hepatic, breast, and uterine tumors. Although not approved for use in the treatment of atherosclerotic arterial disease, there is a growing body of evidence investigating applications of HIFU. Currently, percutaneous endovascular techniques are predominant for the treatment of arterial pathology; however, there are no endovascular techniques of HIFU available. This study aims to review the state of current evidence for the application of HIFU in atherosclerotic arterial disease. Methods: All English-language articles evaluating the effect of HIFU on arterial occlusive and thrombotic disease until 2021 were reviewed. Both preclinical and human clinical studies were included. Study parameters such as animal or clinical model and outcomes were reviewed. In addition, details pertaining to settings on the HIFU device used were also reviewed. Results: In preclinical models, atherosclerotic plaque progression was inhibited by HIFU, through decreases in oxidized low-density lipoprotein cholesterol and increases in macrophage apoptosis. Additionally, HIFU promotes angiogenesis in hindlimb ischemic models by the upregulation of angiogenic and antiapoptotic factors, with increased angiogenesis at higher line densities of HIFU. HIFU also promotes thrombolysis and conversely induces platelet activation at low frequencies and higher intensities. Various clinical studies have attempted to translate some of these properties and demonstrated positive clinical outcomes for arterial recanalization after thrombotic stroke, decreased atherosclerotic plaque burden in carotid arteries, increase in tissue perfusion and a decrease in diameter stenosis in patients with atherosclerotic arterial disease. Conclusions: In current preclinical and clinical data, the safety and efficacy of HIFU shows great promise in the treatment of atherosclerotic arterial disease. Future focused studies are warranted to guide the refinement of HIFU settings for more widespread adoption of this technology.