In-office rapid volumetric ablation of uterine fibroids under ultrasound imaging guidance: Preclinical and early clinical experience with the Mirabilis transabdominal HIFU treatment system

Mirabilis Medica, Inc. (Bothell, WA, USA) has developed a high-intensity focused ultrasound (HIFU) system for producing rapid transabdominal volumetric ablation of uterine fibroids in an office-based setting. The Mirabilis HIFU Treatment System utilizes integrated ultrasound imaging guidance and short treatment times under 15 minutes. Treatment with the Mirabilis system is generally well tolerated using only oral analgesia without anesthesia or sedation. This paper summarizes certain technical aspects of the Mirabilis HIFU technology, the preclinical development process, and the results of the first in-human clinical study using the Mirabilis system. During preclinical studies, an in vivo transcutaneous porcine lower extremity model was used in a total of 180 adult swine to develop the HIFU treatment regimen parameters. Additionally, 108 excised human uteri with fibroids obtained from scheduled hysterectomies were treated in an ex vivo experimental setup and evaluated. These preclinical activities resulted in a HIFU treatment technique referred to as Mirabilis Shell Ablation, which enables rapid volumetric fibroid ablation by directing the HIFU energy to the outer perimeter of the target volume (the ‘shell’) without insonating its core. This method results in efficient fibroid treatment through a synergistic combination of direct tissue ablation, cooperative heating effects, and indirect ischemic necrosis in the interior of the volume. After refining this technique and performing safety testing in the in vivo porcine model, a clinical pilot study was conducted to assess the initial safety and performance of the Mirabilis HIFU Treatment System for transabdominal treatment of uterine fibroids in eligible women who were scheduled to undergo hysterectomy following treatment with the device. A total of 37 women meeting certain eligibility criteria were treated at two clinical sites in Mexico. Twenty-nine (29) of these 37 women received only prophylactic sublingual analgesics (tramadol and/or ketorolac) prior to treatment, and 19 out of 37 also underwent post-treatment gadolinium-enhanced magnetic resonance imaging (MRI) to assess the HIFU-mediated non-perfused volumes (NPVs) created within their fibroid(s). All subjects then received their scheduled hysterectomies as planned between 0 and 155 days after HIFU treatment, and the excised uteri were assessed by a pathologist using a viability staining procedure to measure the dimensions of the ablated volumes. Subj