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，正受到越来越多的关注。 治疗，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 无数的大脑疾病和疾病。大多数已发表的工作都使用核磁共振进行监测 在一些应用中，控制tFUS暴露或其生物效应。虽然这种成像模式已经被证明是 到目前为止，对推进tFUS应用至关重要的是，精确交付本地化的tFUS仍然面临重大挑战 由于波在头骨中传播的不确定性。这可能会成为阻碍 在经颅治疗中广泛安全和有效地使用FUSfi。我们的长期目标是发展一种 使用双模超声监测和传送患者经颅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，从而允许 关于靶处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新聚焦算法来提高安全性和 EFfi治疗脑内靶向结构。我们提供了初步的数据来演示 研究了重新聚焦的可行性，并建议将我们的结果推广到宽带tFUS应用中。这种方法 使成像/治疗脉冲的带宽最大化，以提高定位和加热效率 同时最大限度地减少对头骨的暴露。DMUA方法是唯一能够提供这种能力的方法 由于成像和治疗坐标系之间的固有配准而产生的反馈。此外 对于多波段自适应重聚焦方法，我们提出了发展成像方法来表征其质量 体内和体外靶点及颅骨临界点的tFUS。这包括开发一种 加热率的定量估算方法。这一定量测量将为以下方面提供特殊的fic反馈 评估自适应重新聚焦带来的改善。最后，我们建议测试和验证重新聚焦和 慢性颞叶癫痫大鼠模型体内加热率估计法。

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.