Ultrasound-guided Intrinsic Threshold Histotripsy for the Non-invasive Ablation of Uterine Fibroids

项目总结

PROJECT SUMMARY The goal of this project is to develop intrinsic threshold histotripsy as a non-thermal focused ultrasound (FUS) technique for the non-invasive ablation of uterine fibroids. Uterine fibroids (leiomyomas) are the most common benign tumors in women of reproductive age, resulting in over 250,000 hospital admissions and 200,000 hysterectomies annually. The gold standard for uterine fibroids is hysterectomy, a surgical procedure that requires extended hospitalization and recovery time, and results in the loss of reproductive function. Thermal FUS has emerged as a non-invasive method for the management and conservation of uterine function. However, complications due to thermal spread, reliance on MRI for image-guidance, slow treatment times, and slow resorption of the fibroids after treatment have limited the widespread use of thermal FUS. This proposal develops intrinsic threshold histotripsy for the ablation of uterine fibroids. While histotripsy has shown the potential to overcome limitations of thermal ablation in many clinical applications, the technique has previously been shown to be less effective in highly fibrous tissues, which has thus far prevented histotripsy from being developed for treating uterine fibroids. Recently, our team completed a proof-of-concept study demonstrating that histotripsy can effectively ablate human uterine fibroids using intrinsic threshold histotripsy techniques. In this project, we will investigate the optimal histotripsy treatment methods for the rapid ablation of uterine fibroids under real-time ultrasound image-guidance. In Aim 1, we will compare the histotripsy cavitation bubble cloud behavior and tissue ablation generated by multi-cycle (shock-scattering histotripsy) and single-cycle (intrinsic threshold histotripsy) methods using a wide range of potential histotripsy pulsing parameters. Experiments will be conducted in mechanically-tunable tissue phantoms that mimic the properties of fibrous tissue as well as ex vivo experiments using excised human uterine fibroids. In Aim 2, we will test in vivo safety and efficacy of intrinsic threshold histotripsy ablation in a small animal model. The successful completion of these aims will demonstrate the safety and efficacy of TEH for the non-invasive treatment of uterine fibroids.