Ultrasound-guided Histotripsy for the Complete and Rapid Ablation of Uterine Fibroids

Uterine fibroids (leiomyomas) are the most common benign tumors in women of reproductive age. The overarching goal of this project was to test the technical feasibility and in vivo efficacy of ultrasound-guided histotripsy for the treatment of uterine fibroids. First, experiments were completed using red blood cell tissue phantoms to compare ablation efficiency at PRFs up to 2.5kHz, with results showing effective ablation at all PRFs. Experiments were then conducted to evaluate our recently developed ultra-high PRF histotripsy pulsing regimes for complete and efficient uterine fibroid disintegration using ex vivo human uterine fibroid samples. Histological analysis from these studies showed effective fibroid ablation with histotripsy at all tested PRFs, with varying degrees of tissue damage observed under different PRF and dose combinations. These studies have established that histotripsy can effectively ablate fibroid tissues with an approximate 10x increase in treatment efficiency compared to our previous pilot studies, opening the door for histotripsy as a clinically relevant non-invasive treatment option for fibroids. A manuscript outlining these results is currently in review with Ultrasound in Medicine and Biology. In the second part of this study, our goal was to test the in vivo safety and efficacy of histotripsy in a rat leiomyoma model. Due to the lack of established animal models for uterine fibroids, our group proposed to develop and test a rodent uterine fibroid model based on the only hormone model we could identify in the literature. Following this 9-month protocol, we unfortunately did not observe fibroid formation in any of the rats, although swelling was present in the uterus, cervix, and ovaries, indicating a potential hormone-induced phenotype. Overall, results suggest that histotripsy has potential as a non-invasive and non-thermal treatment for uterine fibroids with future studies needed in order to study the safety and long-term efficacy of histotripsy fibroid ablation which could not be assessed here due to the lack of fibroid formation in the rodent model.