CITRUS: Closed-loop Individualized image-guided Transcranial Ultrasonic Stimulation

我们正在欧洲各地联手推进一项新的非侵入性技术-经颅超声刺激（TUS）-以精确到毫米的精度可逆地调节大脑区域，甚至在大脑深处。因此，我们的目标是为神经和精神疾病建立一种迫切需要的新型治疗选择。TUS结合了侵入性脑深部刺激的精度和范围，需要直接靶向临床相关结构，以及经颅电磁技术的非侵入性和低成本性质，这些技术在焦点和深度方面具有固有的局限性。在神经科学和临床应用中广泛采用TUS的主要障碍是难以将小的超声焦点引导到预期目标上并达到所需的强度，目前没有经验验证靶向成功。我们将开发一种神经导航TUS-MRI系统，该系统具有先进的磁共振成像（MRI）引导的应用规划和闭环应用控制，以实现安全，个性化和有效的高精度TUS。因此，我们将释放TUS的全部潜力，以毫米范围内前所未有的空间精度非侵入性地调节深部脑结构。最终的原型将是一个功能齐全的设备，它集成了新型MR兼容的256元件TUS换能器（用于TUS焦点的高级3D转向），定制的32通道MR接收器线圈（用于最大灵敏度的加速成像）和使用MR声辐射力成像（MR-ARFI）的闭环目标验证。这种具有独特功能的新型设备将首次实现对人脑皮层和皮层下目标的个性化非侵入性高精度刺激。它将改变神经科学研究和神经和精神疾病临床应用的游戏规则，有可能使数百万患者受益。

We are joining forces across Europe to advance a new non-invasive technology – transcranial ultrasound stimulation (TUS) – to reversibly modulate brain regions with exquisite millimetre precision, even deep in the brain. As such, we aim to establish an urgently needed novel treatment option for neurological and psychiatric diseases. TUS combines the precision and reach of invasive deep brain stimulation, required to directly target clinically relevant structures, with the non-invasive and low-cost nature of transcranial electromagnetic techniques that are inherently limited in focus and depth. The main roadblock to widespread adoption of TUS in neuroscientific and clinical applications is the difficulty of steering the small ultrasound focus onto the intended target and reaching the desired intensity, with no empirical validation of targeting success currently available. We will develop a neuronavigated TUS-MRI system with advanced magnetic resonance imaging (MRI)-guided application planning and closed-loop application control to enable safe, individualised, and effective high-precision TUS in humans. Assuch we will unlock the full potential of TUS to non-invasively modulate deep brain structures with unprecedented spatial precision in the millimetre range. The final prototype will be a fully functional device that integrates novel MR-compatible 256-element TUS-transducers (for advanced 3D-steering of the TUS focus) with a custom-tailored 32-channel MRreceiver coil (for accelerated imaging with maximal sensitivity) and closed-loop target validation using MR-acoustic radiation force imaging (MR-ARFI). This novel device with its unique features will enable for the first time the personalized non-invasive high-precision stimulation of cortical and subcortical targets in the human brain. It will be a game changer for both neuroscientific research and clinical application in neurological and psychiatric diseases with the potential to benefit millions of patients.