Table I.
Overview of Preclinical data of high-intensity focused ultrasound (HIFU) in occlusive and thrombotic arterial disease
| Author(s) | Year | Model | Device name | Proposed mechanism of action | Available specs | Clinical application |
|---|---|---|---|---|---|---|
| Effect on arterial plaque and arterial wall | ||||||
| Shehata et al30 | 2013 | Swine | Imasonic Dual-Mode US Array (Voray sur l’Ognon, France) | Thermal | Frequency: 3.5 MHz, 64-element phased array transducer with fenestrations, through which 10 MHz transducer is applied Intensity: 4100-5600 W/cm2 Pulse length: 250-2000 ms |
Disruption of atherosclerosis in swine PAD model, accompanied by aggregates of lipid laden macrophages with necrosis. No endothelial damage was noted |
| Nazer et al50 | 2015 | Sprague Dawley rats (PAD) | Duolith SD1 (Storz Medical, Tagerwilen, Switzerland) | Biomechanical | Frequency: 1.054 MHz Intensity: 0.1 mJ/mm2 |
Increase in angiogenesis in hindlimb ischemia model for PAD |
| Lu et al51 | 2016 | Diabetic C57BL./6J mice | Custom transducer (Institute of Acoustics of Tongji University, Shanghai, China) | Biomechanical | Frequency: 1 MHz Intensity: 0.3 W/cm2 |
Increased perfusion in hindlimb ischemia model for PAD accompanied by increased angiogenic factors, antiapoptotic factors, capillary density |
| Wang et al52 | 2017 | ApoE–/– Mice | Custom transducer (Harbin Institute of Technology, Harbin, China) | Biomechanical | Frequency: 1 MHz Intensity: 0.1-0.4 W/cm2 |
Inhibition of atherosclerosis via reduction of LDL oxidation |
| Sun et al53 | 2019 | New Zealand white rabbits, ApoE–/– mice | Custom transducer (Harbin Institute of Technology, Harbin, China) | Biomechanical | Frequency: 1 MHz Intensity: 1.5 W/cm2 (rabbits), 0.8 W/cm2 (mice) |
Decrease in atherosclerosis in femoral arteries through decrease in macrophages and lipids |
| Groen et al54 | 2020 | Swine | HIFU Synthesizer, International Cardio Corporation (Edina, MN) Imasonic Dual-Mode US Array (Voray sur l’Ognon, France) |
Thermal | Frequency: 3.5 MHz, 64-element phased array transducer with fenestrations, through which 10 MHz transducer is applied Intensity: 6250 W/cm2 |
Successful targeting of dorsal wall of the external femoral artery without endothelial damage or complications, accompanied by formation of scar tissue |
| Mason et al55 | 2020 | C57BL/6 mice | EPIQ 7 (Philips Healthcare, Andover, MA) | Biomechanical | Frequency: 1.3 MHz | Increased perfusion in hindlimb ischemia model for PAD via microcavitation-dependent mechanism |
| Yao et al56 | 2020 | New Zealand white rabbits | Custom transducer (Harbin Institute of Technology, Harbin, China) | Biomechanical | Frequency: 1 MHz Intensity: 1.5 W/cm2 (rabbits) |
Decrease in carotid artery atherosclerosis through decreased neointima formation, macrophage content, proliferation SMCs, and collagen |
| Effect on thrombolysis | ||||||
| Francis et al36 | 1995 | Blood samples from adult humans | Custom apparatus made with piezoelectric transducer (manufacturer not specified) | Biomechanical | Frequency: 1 MHz Intensity: 1 W/cm2 |
Enhanced thrombolysis via increased uptake of tPA with application of ultrasound |
| Poliachik et al57 | 1999 | Blood samples from adult humans | Sonic Concepts (Sonic Concepts Inc., Bothell, WA) | Biomechanical | Frequency: 1.1 MHz Intensity: 560-2360 W/cm2 |
Cavitation and hemolysis is greater in samples with contrast agent treated with ultrasound, versus without |
| Birnbaum et al58 | 2001 | Blood samples from adult humans | Sonicator model XL 2020 (Misonix Inc., Farmingdale, NY) | Biomechanical | Frequency: 20 kHz | Ultrasound and nongas-filled particles (HAEMACCEL and HAES) decreased clot burden |
| Hölscher et al59 | 2012 | New Zealand white rabbits | ExAblate 4000 (Insightec Inc., Tirat Carmel, Israel) | Biomechanical | Frequency 220 kHz Intensity: 66-200 W (arterial thrombus model), 100-500 W (venous thrombus model) Pulse length: 100-200 ms (arterial thrombus model), 0.1-100.0 ms (venous thrombus model) |
Mild recanalization in carotid artery stroke thrombosis model, dependent on platelet-activation and cavitation |
| Wright et al60 | 2012 | New Zealand white rabbits | Custom using function generator (model AFG 3102, Tektronix, Beaverton, OR) and amplifier (model A-500, ENI, Rochester, NY) | Biomechanical | Frequency: 1.51 MHz Intensity: 300 W Pulse length: 0.1-10.0 ms |
Increased thrombolysis and partial blood flow restoration in femoral artery clot model, accompanied by cavitation |
| Damianou et al61 | 2014 | New Zealand white rabbits | Custom device with amplifier (JJ&A Instruments, Duvall, WA) and piezoelectric ceramic transducer (Piezo-technologies, Etalon, Lebanon, IN) | Biomechanical | Frequency: 1 MHz Intensity: 10-40 W/cm2 |
Enhanced thrombolysis in rabbit carotid model via increased uptake of tPA with application of ultrasound |
| Miscellaneous effects | ||||||
| Williams et al62 | 1978 | Blood samples from adult humans | Sonacell Multiphone (Rank Stanley Cox (Ware, Hertfordshire) | Biomechanical | Frequency: 0.75, 1.5., 3.0 MHz | Release of β-thromboglobulin in platelets is mediated by ultrasound-induced cavitation and release of other aggregating factors |
| Vaezy et al63 | 1999 | Swine | Sonic Concepts (Sonic Concepts Inc., Woodinville, WA) | Thermal | Frequency: 3.5 MHz Intensity: 2500-3100 W/cm2 |
Control of arterial hemorrhage |
| Zderic et al64 | 2006 | New Zealand white rabbits | Custom made 111F-U applicator with piezo-electric discs (Stavely Sensors Inc., East Hartford, CT) and a solid aluminum coupling cone | Thermal | Frequency: 3.5 MHz Intensity: 3000 ± 100 W/cm2 |
Control of arterial hemorrhage |
| Lei et al65 | 2021 | N/A | N/A (mathematical model) | Thermal | Frequency: 1.1 MHz Power: 15 W at 20 s |
Mathematical model to predict damage of plaque ablation based on wall thickness; thermal effects depend on frequency and power |
LDL, Low-density lipoprotein cholesterol; PAD, peripheral artery disease; tPA, tissue plasminogen activator.