Advancing Research through Enhanced Design of Focused Ultrasound Animal Devices

聚焦超声（FUS）可作为无切口手术的一种工具。FUS可以精确地消融不需要的组织而不损害健康组织。在其他好处中，这缩短了恢复时间并降低了并发症的风险。但FUS为先进的微创手术提供了其他机会。低能量水平的FUS可以触发特定的生物机制。例如，低能量的FUS与微泡结合可以打开细胞膜，使分子大小的物体通过。这将改善靶向治疗的纳米药物输送。还有许多其他潜在的应用。然而，需要更多的研究来充分了解这些生物机制是如何起作用的。通过ARTEmis计划，我建议开发增强的动物和细胞设备，研究人员可以使用这些设备来推进我们对FUS生物效应和潜在机制的理解。理想情况下，我们应该开发可以由非超声专家操作的研究设备，以促进跨学科工作，增加研究范围和成功。然而，构建这样的工具并不是一项微不足道的任务，它们的质量可以直接影响它们的可用性和研究结果。该计划扩展了我之前开发FUS成像和治疗系统的经验，重点关注三个特定目标：1)开发用于小型啮齿动物分子递送，消融或轻度热治疗的脑或腹部目标的独立设备。该设备将允许使用物理地标、磁共振成像（MRI）和正电子发射断层扫描（PET）进行定位。2)改进细胞培养物超声暴露装置，用于分子传递。3)设计一种可容纳小型啮齿动物的装置，集成超声成像（包括基于超声的弹性成像）和声发射监测。预期的结果是利用低成本成像丰富从实验中获得的信息。我将应用以用户为中心的设计方法来有效地解决竞争的用户和技术需求。我们不仅可以深入了解FUS的治疗用途，该项目还将帮助我们开发和改进任何研究人员都可以使用的设备，而不需要高级超声专业知识。该计划将利用与研究人员的积极合作，并将在强大的生物医学工程环境中培养学生。该计划将支持2名博士和3名硕士学员以及本科生。在过去的几年里，我看到了跨学科工作的力量和研究设备在推动发现方面的作用。通过为研究人员提供FUS研究平台，它将为应用这项技术创造新的机会。这将为建立一个加拿大范围的网络提供机会，为FUS的生物学机制提供急需的答案，从而促进采用先进的微创手术工具。

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.