Monitoring and Delivery of Transcranial Therapy Using Dual-mode Ultrasound

摘要： 经颅聚焦超声（tFUS）作为一种非侵入性工具， 治疗，例如特发性震颤，神经调节，肿瘤消融等。此外，最近的结果表明， tFUS介导的血脑屏障开放的可行性有望将tFUS的治疗应用扩展到 大脑的各种状况和疾病。大多数已发表的工作采用MRI进行监测 以及在某些应用中，控制tFUS暴露或其生物效应。虽然这种成像方式已被证明是 到目前为止，对推进tFUS应用至关重要的是，本地化tFUS的精确交付仍然面临重大挑战 因为通过头骨的波传播的不确定性。这可能会成为一个重大障碍， FUS在经颅治疗中的广泛安全有效使用。长远目标是发展一个 使用双模式超声监测和输送患者经颅FUS治疗的实时系统 （DMUA）系统。DMUA能够在治疗和成像模式下实时操作， 对靶组织以及介入组织和周围组织处的tFUS-组织相互作用的即时反馈， 包括头皮和头骨我们建议开发实时重聚焦算法，以提高安全性和 tFUS治疗脑内靶向结构的有效性。我们提供的初步数据表明， 重新聚焦的可行性，并建议将我们的结果扩展到宽带tFUS应用。这种方法 最大化成像/治疗脉冲的带宽，以提高 同时尽量减少对头骨的暴露。DMUA方法是唯一能够提供这种 由于成像和治疗坐标系之间的固有配准，此外 对于多波段自适应重聚焦方法，我们提出发展成像方法来表征质量 tFUS在颅骨上的靶点和关键点的体内和离体的。这包括发展一个 定量方法来估计加热速率。这种定量测量将为以下方面提供具体反馈： 评估由于自适应重新聚焦而引起的改进。最后，我们建议测试和验证重新聚焦， 升温速率估计法在慢性颞叶癫痫大鼠模型体内的应用。

Abstract: Transcranial focused ultrasound (tFUS) is gaining increased attention as a noninvasive tool for a number of therapies, e.g. essential tremor, neuromodulation, tumor ablation, etc. In addition, recent results demonstrating the feasibility tFUS-mediated blood brain barrier opening promise to extend the therapeutic applications of tFUS to a myriad of conditions and diseases of the brain. The majority of the published work employ MRI for monitoring and, in some applications, control of tFUS exposure or its bioeffects. While this imaging modality has proved to be essential to advancing tFUS applications so far, the precise delivery of localized tFUS still faces major challenges due to the uncertainties of wave propagation through the skull. This could present a major barrier towards the widespread safe and efficacious use of FUS in transcranial therapies. The long-term objective is to develop a real-time system for monitoring and delivering transcranial FUS therapies in patients using dual-mode ultrasound (DMUA) systems. DMUAs are capable of operating in both therapy and imaging modes in real-time allowing for immediate feedback on tFUS-tissue interactions at the target as well as the intervening and surrounding tissues, including the scalp and skull. We propose to develop real-time refocusing algorithms to improve the safety and efficacy of tFUS therapy of targeted structures within the brain. We present preliminary data demonstrating the feasibility of refocusing and propose to extend our results to wideband tFUS application. This approach maximizes the bandwidth of the imaging/therapy pulses to improve the localization and heating efficiency at the target while minimizing exposure to the skull. The DMUA approach is uniquely capable of providing this kind of feedback due to the inherent registration between the imaging and therapeutic coordinate systems. In addition to the multiband adaptive refocusing method, we propose to develop imaging methods to characterize the quality of tFUS in vivo and ex vivo at the target and critical points on the skull. This includes the development of a quantitative method to estimate the heating rate. This quantitative measurement will provide specific feedback for assessing the improvement due to adaptive refocusing. Finally, we propose to test and validate the refocusing and heating rate estimation method in vivo rat model of chronic temporal lobe epilepsy.