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

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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.