Safety and feasibility of arterial wall targeting with robot-assisted high intensity focused ultrasound: a preclinical study

Abstract

Purpose: High-intensity focused ultrasound (HIFU) is a potential noninvasive thermal ablation method for the treatment of peripheral artery disease. Dual-mode ultrasound arrays (DMUA) offer the possibility of simultaneous imaging and treatment. In this study, safety and feasibility of femoral artery robotassisted HIFU/DMUA therapy was assessed. Methods: In 18 pigs ($50kg), angiography and diagnostic ultrasound were used to visualize diameter and blood flow of the external femoral arteries (EFA). HIFU/DMUA-therapy was unilaterally applied to the EFA dorsal wall using a 3.5 MHz, 64-element transducer, closed-loop-control was used to automatically adjust energy delivery to control thermal lesion formation. A continuous lesion of at least 25 mm was created by delivering 6-8 HIFU shots per imaging plane perpendicular to the artery spaced 1 mm apart. Directly after HIFU/DMUA-therapy and after 0, 3 or 14 days follow up, diameter and blood flow were measured and the skin was macroscopically examined for thermal damage. The tissue was removed for histological analysis. Results: No complications were observed. The most frequently observed treatment effect was formation of scar tissue, predominantly in the adventitia and the surrounding tissue. No damage to the endothelium or excessive damage of the surrounding tissue was observed. There was no significant decrease in the mean arterial diameter after HIFU/DMUA-therapy. Conclusion: HIFU/DMUA therapy successfully targeted the vessel walls of healthy porcine arteries, without causing endothelial damage or other vascular complications. Therefore, this therapy can be safely applied to healthy arterial walls in animals. Future studies should focus on safety and dose-finding in atherosclerotic diseased arteries.

Influence of High-Intensity Focused Ultrasound (HIFU) Ablation on Arteries: Ex Vivo Studies

“…Meanwhile, if a major blood vessel or artery is ruptured and the hemorrhage cannot be controlled, it is especially critical in closed procedures and may be life-threatening. Thus, this risk requires extensive investigation to better understand and improve the efficacy and safety of HIFU treatment [ 6 , 7 , 8 ]. In the published literature, there are discrepancies in such adverse effects observed in clinics.…”

Safety and feasibility study of non-invasive robot-assisted high-intensity focused ultrasound therapy for the treatment of atherosclerotic plaques in the femoral artery: protocol for a pilot study

“…The effect of this thermal therapy on atherosclerotic plaque is unknown but in the animal studies some swelling at the targeted vascular wall was observed. 21 39 …”

“…Preclinical research with this experimental setup has demonstrated that the endothelium remains intact at the appropriate HIFU intensities, and no rise of temperature in the vessel wall leading to thrombosis occurred. 21 The closed-loop feedback control is also a precaution to prevent overexposure and excessive tissue heating. The endothelial cells of the vessel wall are naturally cooled by the blood flow, thus reducing the chance of plaque rupture.…”

“…The intensity of the shots is depending on the HIFU amplitude and tissue attenuation and absorption but is generally around 6.25 kW/cm 2 . 21 After the HIFU procedure the number of shots and the efficacy of the shots will be determined. The efficacy will be analysed based on the echogenicity change during the shot.…”

“…High-intensity focused ultrasound (HIFU) enables noninvasive tissue ablation 16–18. Dual-mode ultrasound arrays (DMUA) offers the possibility of simultaneous HIFU targeting and ultrasound (US) imaging, thereby allowing inherent registration between imaging and treatment location 19–21. HIFU/DMUA therapy can be used for transcutaneous noninvasive ablation of targets with submillimeter precision and accuracy 17 19–24.…”