MRI Coregistered Rodent Histotripsy Array for Orthotopic Liver Models

Histotripsy has emerged as a promising therapeutic option for liver tumors, recently gaining food and drug administration (FDA) approval for clinical use in October 2023. Preclinical in vivo histotripsy experiments primarily utilize subcutaneous ectopic murine tumor models, which fail to accurately replicate the complex immunosuppressive tumor microenvironment (TME) of liver tumors. In order to address this gap, we present the design, development, and in vivo demonstration of a miniature, electronically steerable magnetic resonance imaging (MRI)-guided histotripsy array tailored for orthotopic murine liver tumor models. This novel system integrates an 89-element phased array within a 7.0-T small animal MRI scanner, enabling precise targeting through enhanced soft tissue contrast and 3-D visualization. The targeting accuracy of the array was validated in tissue-mimicking red blood cell (RBC) phantoms, exhibiting targeting precision of $0.24~\pm ~0.1$ mm. Subsequent in vivo experiments in naïve mice demonstrated successful liver ablations, confirmed by gross morphology and histological analysis. However, the presence of grating lobes led to undesired collateral damage, highlighted by lung hemorrhages, necessitating future adjustments in the array's design. This study illustrates the foundational steps necessary for translating histotripsy experiments from subcutaneous to orthotopic models.