Advancing Research through Enhanced Design of Focused Ultrasound Animal Devices

聚焦超声(FUS)可作为非切开手术的一种工具。FUS可以精确地消融不需要的组织，而不会损害健康组织。除了其他好处外，这还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FUS与微泡相结合可以打开细胞膜，允许分子大小的物体通过。这将改善靶向治疗的纳米片输送。还有许多其他潜在的应用。然而，还需要更多的研究来充分了解这些生物学机制是如何工作的。 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促进我们对FUS的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，扩大研究范围和成功。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。 拟议的计划扩展了我之前开发FUS成像和治疗系统的经验，专注于三个具体目标： 1)开发一种用于脑或腹部靶点的独立设备，用于分子输送、消融或小型啮齿动物的温和热疗。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)进行靶向。 2)改进超声波照射细胞培养物以进行分子传递的设备。 3)设计一种可容纳小型啮齿动物的装置，以整合超声成像(包括基于超声的弹性成像)并监测声发射。预期的结果是利用低成本成像丰富从实验中获得的信息。 我将采用以用户为中心的设计方法，有效地满足相互竞争的用户和技术需求。我们不仅将深入了解FUS的治疗用途，该计划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，而不需要先进的超声波专业知识。 拟议的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训学生。该项目将支持两名博士和三名硕士实习生以及本科生。 在过去的这些年里，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FU的研究平台，将为应用这项技术带来新的机会。这反过来将提供一个机会，以创建一个加拿大范围的网络，为FUS的生物机制提供急需的答案，从而促进将其作为先进的微创程序的工具采用。

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.