Abstract Focused ultrasound (FUS) is an early-stage, noninvasive technology with great therapeutic potential in oncology and other diseases. FUS offers either an alternative or complementary strategy to existing cancer treatment approaches such as surgery, radiation, drug delivery, and immunotherapy (immuno-oncology, or “IO”). Most recently, IO specifically has demonstrated enormous potential to have a “game-changing” impact in our fight against cancer, however the fraction of responders to IO monotherapy remains low (<25%). It is becoming increasingly clear that adjuvant treatments that modulate the tumor microenvironment, such as FUS, which has shown to be an immunomodulator, will be critical to continue the progress made by IO. Unfortunately, despite empirically observed improvements in treatment outcomes, the mechanisms of action of FUS are largely unknown and data remain unclear how to best make use of this highly impactful technology. Therefore, preclinical research with robust mechanistic hypothesis testing is desperately needed. However, tools to enable preclinical research are greatly lacking in standardization, ease-of-use, accessibility, and throughput. Our customer discovery process has identified the lack of availability of image-guided FUS delivery hardware for small animals as a critical pain point in the field. To address this need, SonoVol Inc. will build upon Phase I success by developing a turnkey image-guided therapy platform (“TherUS”) to remove the challenges associated with studying FUS treatment strategies. TherUS will offer two core functions: treatment modalities to deliver immune-modulation energy to tissue, and imaging modalities to guide and monitor those treatments in 3D. Unlike other solutions, the new TherUS will ensure accurate and repeatable dose delivery irrespective of user expertise in a cost-effective and high-throughput manner leveraging SonoVol’s robotic, hands-free technology. TherUS will accelerate clinical translation of novel cancer therapies by lowering the technological barriers which limit widespread access, putting the technology directly in the hands of the broader market of cancer biologists and immunologists to develop cutting-edge anticancer treatment strategies. The proposed work will proceed via three stages. First, we will improve the robotic gantry that controls ultrasound transducer positioning to facilitate multi-modal guidance, treatment, and real-time monitoring (e.g. thermometry). Second, we will develop software to facilitate treatment planning and confirmation of dose delivery, including registration algorithms for alignment to previous treatment timepoints. Lastly, we will conduct several in vivo studies designed to verify and validate the integrated device. TherUS technology represents an innovative combination of a widefield 3D robotic ultrasound, photoacoustic, and bioluminescence imaging system and bi-modal therapies (focused ultrasound and laser) with real-time dose delivery feedback. Furthermore, the technology can be applied in the future to many other applications, including wound healing, neuro, and gene therapy, increasing the potential market and scientific impacts.

Project Narrative Focused ultrasound (FUS) is a promising new technology that allows physicians to treat cancer without a single incision. While preliminary data has been encouraging, FUS has only been approved for a few specific indications and preclinical FUS research has numerous challenges, including: limited access to the technology, inability to accurately measure doses, and reproducibility. We propose to build and validate a novel turnkey robotic FUS platform to accelerate clinical translation of FUS therapies. This device will enable users to conduct high-quality, reproducible experiments, widening the accessibility of the technology to non-imaging experts including cancer biologists and immunotherapy researchers and drug developers.