Toward the next generation in transcranial MR-guided focused ultrasound: Innovations in thermal and acoustic model-based planning and monitoring for improved safety, efficacy and efficiency

经颅脑MRI引导的聚焦超声是一种完全无创的神经介入治疗方法 这项技术在治疗许多神经疾病方面表现出了非凡的前景。的成功之处 聚焦超声在神经介入手术中的应用取决于其能否提供精细聚焦的光束 精确到所需位置，并准确监控由此产生的热量。尽管目前的系统有 取得了一些成功，有强有力的证据表明，患者特定的头骨属性会导致焦点较少 在治疗过程中颅骨的变化会导致进一步的衰减、扩大和移位 焦点。虽然InSightec ExAblate Neuro tcMRgFUS系统已获得FDA批准，可用于治疗必要的 震颤，它不能1)完全监测电离场，2)预测或监测颅骨温度，或3)动态 优化整个过程中所需的光束聚焦和功率级别。这些技术限制 对目前批准的tcMRgFUS程序的安全性、有效性和效率产生不利影响，并限制 原本可以从这项革命性技术中受益的患者数量。 在前期资金的支持下，我们的研究团队为tcMRgFUS引入了重要的技术进步， 包括体积实时磁共振温度成像(MRTI)技术、基于T1的超短回波时间 皮质骨(UTE)温度成像，使用混合角谱的快速超声波束建模 (HAS)方法和特定于tcMRgFUS的射频(RF)线圈。在此背景下，我们的目标是 该提议旨在充分开发和传播迫切需要的能力，以提供下一代 治疗建模、计划、监测、评估和控制。我们将通过三个方面来实现这一点 具体目标：1)开发用于整个大脑和头骨的可靠的体积MRTI监测方法，包括 一种新的单翻转角方法用于颅骨和系统特定射频线圈中基于T1的MRTI以改善MRTI 准确性；2)开发特定于患者的动态经颅超声传播模型 适应头骨内测量的温度变化，动态预测对焦相位和功率 准确完成治疗所需；以及3)证明高级治疗的临床价值 将建模和监控工具整合到开发中的tcMRgFUS可视化工具中，并 在日益复杂的临床前和临床环境中评估这些方法。 这些新的特定于患者的工具与可视化环境相结合将显著提高 TcMRgFUS通过提供完整的、患者特定的资格确定、治疗计划和 全面监测。这将对光束聚焦、定位和跟踪、治疗产生积极影响 准确性和临床工作流程，改善现有的临床适应症，并更好地实现前瞻性- 寻找仍处于转换阶段的应用程序。

Transcranial MRI-guided focused ultrasound (tcMRgFUS) is a completely non-invasive neuro-interventional technique that shows exceptional promise for treating a number of neurological disorders. The success of focused ultrasound in neurointerventional procedures depends on its ability to deliver a finely focused beam exactly to the desired location and accurately monitor the resulting heating. Although current systems have achieved some success there is strong evidence that patient-specific skull attributes cause the focus to be less than ideal and that changes to the skull during treatment cause further attenuation, broadening, and shifting of the focus. While the Insightec Exablate Neuro tcMRgFUS system has received FDA approval to treat essential tremor, it is not able to 1) fully monitor the insonified field, 2) predict or monitor skull heating, or 3) dynamically optimize beam focusing and power levels needed throughout the procedure. These technical limitations adversely affect the safety, efficacy and efficiency of currently approved tcMRgFUS procedures and limit the number of patients that could otherwise benefit from this revolutionary technology. With prior funding, our research team has introduced important technical advancements for tcMRgFUS, including volumetric real-time MR temperature imaging (MRTI) techniques, T1-based ultrashort echo time (UTE) temperature imaging in cortical bone, rapid ultrasound beam modeling using a hybrid angular spectrum (HAS) method, and radiofrequency (RF) coils specific for tcMRgFUS. Building on this background, our goal in this proposal is to fully develop and disseminate critically needed capabilities that will provide next generation treatment modeling, planning, monitoring, assessment and control. We will accomplish this through three specific aims: 1) Develop robust volumetric MRTI monitoring methods for entire brain and skull including a novel mono flip angle method for T1-based MRTI in the skull and system-specific RF coils to improve MRTI accuracy; 2) Develop patient-specific, dynamic modeling of transcranial ultrasound propagation that adapts to measured temperature changes in the skull, dynamically predicting focusing phases and power needed for accurate treatment completion; and 3) Demonstrate the clinical value of advanced treatment modeling and monitoring tools by incorporating them into a developing tcMRgFUS visualization tool and evaluating the methods in increasingly complex preclinical and clinical environments. These new patient-specific tools combined with the visualization environment will significantly advance tcMRgFUS treatments by providing complete, patient-specific eligibility determination, treatment planning and comprehensive monitoring. This will positively impact beam focusing, localization and tracking, treatment accuracy, and clinical workflow, improving existing clinical indications as well as better enabling forward- looking applications that are still in the translational phase.