Focusing ultrasound through the skull for neuromodulation

项目摘要 这个F31 NRSA项目的目标是开发通过颅骨聚焦超声波的新方法。这些方法 将实现磁共振成像(MRI)引导的经颅聚焦的快速体内重新聚焦 超声(FUS)压力场用于超声神经调节，目前在可实现的范围内有限 颅骨诱导的压力场异常对神经调节的特异性和安全性。 MRI引导下经颅FUS的理想再聚焦方法是安全、快速和有能力的 通过原位测量来补偿任何头骨。经颅FUS的临床应用现状 对患者头骨进行预先的计算机断层扫描(CT)，以得出头骨声学特性图 用于重新聚焦，但这种方法已被证明在一些患者中由于标测不准确而失败 程序，防止这些患者接受治疗。CT扫描也需要辐射剂量。这些方法 在本申请中提出的克服了现有的经颅磁重聚焦方法的局限性 磁共振成像声辐射力成像(MRI ARFI)。核磁共振ARFI扫描间接映射压力 现场通过运动编码梯度与安全、低占空比的超声脉冲同步。经颅 使用MRI ARFI重新聚焦的传统应用是通过观察单个 图像体素经过一些不同的超声波发射，但这需要较长的扫描时间，这已禁止 它在体内的使用。在这个项目中提出的方法在多体素方法中使用mri arfi。 最小二乘优化，以更有效地重新聚焦压力场。在模拟中，我已经证明了 只需一次MRI ARFI采集就有可能实现经颅再聚焦。 这个项目的中心创新是使用基于多体素磁共振ARFI的方法来重新聚焦 核磁共振引导下经颅FUS在不到10分钟内产生压力场。第一个目标是落实 使用水听器和体外实验平台进行多体素重聚焦。第二个目标是优化和 在体外实验中评估多体素重聚焦，并在活体非人类灵长类动物中进一步验证 本课题组为本实验及其他超声神经调节实验建立的动物模型。第一个和 第二个AIMS将使用我们集团为超声定制的128元素经颅FUS系统 非人灵长类动物的神经调节。第三个目标是评估体外多体素重聚焦。 实验使用InSightec ExAblate Neuro，这是一种临床1024元素经颅FUS系统。通过 在不到十分钟的时间内重新聚焦压力场，该项目将从根本上实现高度特定的、非 广泛人群中的侵入性超声神经调节。

Project Summary The goal of this F31 NRSA project is to develop new methods to focus ultrasound through the skull. The methods would enable rapid, in vivo refocusing of magnetic resonance imaging (MRI)-guided transcranial focused ultrasound (FUS) pressure fields for ultrasonic neuromodulation, which is currently limited in the achievable specificity and safety for neuromodulation due to skull-induced aberrations of the pressure field. An ideal refocusing method for MRI-guided transcranial FUS would be safe, rapid, and capable of compensating for any skull with in situ measurements. Current clinical implementations of transcranial FUS use a pretreatment computed tomography (CT) scan of the patient’s skull to derive a map of skull acoustic properties for refocusing, but this method has been shown to fail in some patients due to inaccuracies in the mapping procedure, preventing treatment in those patients. CT scans also require a radiation dose. The methods proposed in this application overcome existing limitations in transcranial refocusing methods using magnetic resonance imaging acoustic radiation force imaging (MRI ARFI). MRI ARFI scans indirectly map the pressure field in situ via motion-encoding gradients synchronized with a safe, low duty cycle ultrasound pulse. Transcranial refocusing with MRI ARFI has conventionally been applied by observing the MRI ARFI-derived signal in a single image voxel after a number of distinct ultrasound emissions, but this requires long scan times that have prohibited its use in vivo. The methods proposed in this project use MRI ARFI in a multi-voxel approach with magnitude least squares optimization to more efficiently refocus the pressure field. In simulations, I have demonstrated that it may be possible to achieve transcranial refocusing with just a single MRI ARFI acquisition. The central innovation in this project is to use a multi-voxel MRI ARFI-based approach for refocusing pressure fields generated by MRI-guided transcranial FUS in less than ten minutes. The first Aim is to implement multi-voxel refocusing using hydrophone and ex vivo experimental platforms. The second Aim is to optimize and evaluate multi-voxel refocusing in ex vivo experiments, with further validation in an in vivo non-human primate animal model developed by our group for this and other ultrasonic neuromodulation experiments. The first and second Aims will use our group’s 128 element transcranial FUS system custom-designed for ultrasonic neuromodulation in non-human primates. The third Aim is to evaluate multi-voxel refocusing in ex vivo experiments using the Insightec ExAblate Neuro, which is a clinical 1024 element transcranial FUS system. By refocusing the pressure field in less than ten minutes, this project will fundamentally enable highly specific, non- invasive ultrasonic neuromodulation in a broad human population.