Evaluation of a Multimodal Confocal Therapeutic Focused Ultrasound Apparatus: Bridging Cavitation, Thermal Ablation, and Histotripsy in Preclinical Treatments

Abstract

ObjectivesThe development of versatile and user-friendly preclinical platforms is vital for therapeutic ultrasound research. We introduce a flexible ultrasound-guided focused ultrasound (FUS) platform with two confocal therapeutic transducers, allowing thermal and mechanical modalities, and present its design and, features, with validation of potential applications in preclinical studies. MethodsThe probe's acoustic properties, energy delivery efficiency, and thermal and mechanical modalities are characterized. A computational model predicts thermal effects while optimizing treatment parameters. Ex vivo tissue samples are used to validate system performance, safety, and usability. In vivo experiments on mice with MC38 tumors are presented with immunohistochemistry (IHC) to validate treatment outcomes. ResultsElectroacoustic conversion efficiency levels were 80% and 40% for 1.1 MHz and 3.3 MHz, respectively. Confocal therapy transducers at 1.1 MHz and 3.3 MHz successfully demonstrated cavitation histotripsy and thermal treatments. At 1.1 MHz, for histotripsy, −20 MPa negative peak pressure is achieved, while at 3.3 MHz used for thermal ablation a maximum of 35 MPa is reached for positive peak pressure. Numerical analysis provides thermal treatment planning, aligning with in vitro and in vivo experiments for lesion prediction. Real-time in vivo cavitation monitoring was consistent with in vitro chemical dosimetry, ensuring treatment uniformity. ConclusionThe ultrasound platform induces thermal or mechanical lesions with precise spatial resolution, validated by IHC tissue characterization. Integrated cavitation monitoring enables real-time treatment monitoring. Coupling with thermal simulations provides optimization of thermal treatment parameters. This versatile “all-in-one” therapeutic platform supports multiple treatment modalities including cavitation, thermal ablation, and histotripsy, facilitating direct comparisons to assess their efficacy in diverse therapeutic settings.