Advancing Research through Enhanced Design of Focused Ultrasound Animal Devices

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Focused ultrasound (FUS) can be used as a tool for incisionless surgery. FUS can precisely ablate unwanted tissues without damaging healthy tissues. Among other benefits, this reduces recovery time and reduces the risk of complications. But FUS offers other opportunities for advanced, minimally invasive procedures. FUS at low energy levels can trigger specific biological mechanisms. For example, low-energy FUS combined with microbubbles can open cell membranes to allow molecule-sized objects to pass through. This would improve nanodrug delivery for targeted therapies. There are many other potential applications. However, more research is needed to fully understand how these biological mechanisms work. Through the ARTEmis program, I propose to develop enhanced animal and cell devices that researchers can use to advance our understanding of FUS's biological effects and underlying mechanisms. Ideally, we should develop research devices that can be operated by non-ultrasound specialists to foster interdisciplinary work and increase research scope and success. Building such tools is not a trivial task though, and their quality can have a direct effect on their usability and research outcomes. The proposed program expands on my previous experience developing FUS imaging and therapy systems to focus on three specific objectives: 1) Develop a standalone device for brain or abdominal targets for molecule delivery, ablation or mild thermal treatments in small rodents. This device will allow targeting using physical landmarks, magnetic resonance imaging (MRI) and positron emission tomography (PET). 2) Improve a device for ultrasound exposure of cell cultures for molecule delivery. 3) Design a device that accommodates small rodents to integrate ultrasound imaging (including ultrasound-based elasticity imaging) and to monitor acoustic emissions. The expected outcome is to enrich the information obtained from experiments using low-cost imaging. I will apply a user-centred design methodology to effectively address competing user and technical needs. Not only will we gain insights into FUS's therapeutic uses, the program will help us develop and refine devices that any researcher can use without the need for advanced ultrasound expertise. The proposed program will take advantage of active collaborations with researchers and will train students in a robust biomedical engineering environment. The program will support two Ph.D. and three master's trainees, as well as undergraduate students. During these last years, I have seen the power of interdisciplinary work and the role of research devices in advancing discovery. By making research platforms for FUS available to researchers, it will spark new opportunities for applying this technology. This will in turn provide an opportunity to create a Canada-wide network providing much-needed answers to the biological mechanisms of FUS, thus facilitating adoption as a tool for advanced, minimally invasive procedures.