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MRI引导聚焦超声（tcMRgFUS）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系统疾病方面显示出了非凡的前景。的成功 神经介入手术中的聚焦超声取决于其传送精细聚焦波束的能力 精确到所需的位置，并准确地监测产生的热量。虽然目前的系统 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导致重点较少， 在治疗过程中颅骨的变化会进一步减弱、增宽和移位， 焦点虽然Insightec Exablate Neuro tcMRgFUS系统已获得FDA批准， 震颤，它不能1）完全监测声穿透场，2）预测或监测颅骨加热，或3）动态 优化整个过程中所需的光束聚焦和功率水平。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 许多患者可以从这项革命性技术中受益。 在先前的资助下，我们的研究团队为tcMRgFUS引入了重要的技术进步， 包括容积实时MR温度成像（MRTI）技术、基于T1的超短回波时间 (UTE)皮质骨中的温度成像，使用混合角谱的快速超声束建模 (HAS)方法，以及对tcMRgFUS具有特异性的射频（RF）线圈。在这一背景下，我们的目标是 这项建议是充分发展和传播急需的能力， 治疗建模、规划、监测、评估和控制。我们将通过三个 具体目标：1）为整个大脑和颅骨开发强大的体积MRI监测方法，包括 一种用于颅骨中基于T1的MRTI的新型单翻转角方法和用于改善MRTI的系统特定RF线圈 准确性; 2）开发经颅超声传播的患者特异性动态建模， 适应测量的颅骨温度变化，动态预测聚焦相位和功率 需要准确的治疗完成;和3）证明先进治疗的临床价值 建模和监测工具，将其纳入开发中的tcMRgFUS可视化工具， 在日益复杂的临床前和临床环境中评估方法。 这些新的患者专用工具与可视化环境相结合， tcMRgFUS治疗，提供完整的、患者特定的合格性确定、治疗计划和 全面监测。这将对光束聚焦、定位和跟踪、治疗 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- 寻找仍处于转化阶段的应用程序。

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.