Disorders of the brain, including neurological and psychiatric diseases, affect one in four people. The personal impact can be devastating, and societal costs are enormous. New treatment options are needed with enhanced efficacy and reduced side-effects, costs, and invasiveness. What is needed is a non-invasive brain stimulation (NIBS) technique that can stimulate brain targets with high anatomical precision, unlimited penetration depth, full reversibility, and low risk-profile. In this project, we will thus develop two fully functional prototypes for non-invasive transcranial ultrasound stimulation (TUS)of the human brain. These medical devices integrate novel multi-element ultrasound transducer technology with optical neuronavigation and multi-channel receive magnetic resonance (MR) coil arrays tailored for application in humans. TUS transducers possess advanced 3D steering capabilities that allow for adjusting focus position and shape according to the target location required. MR coil elements are designed to maximise sensitivity while simultaneously allowing for adequate space for manipulating TUS positions as required for the experiments at hand. Version 1 of the prototype will include 16 MR receive elements with integrated TUS mounting device that ensure both easy adjustment and high robustness. For version V2, the number of receive elements will be doubled to increase sensitivity and parallel imaging capabilities even further. In addition to these hardware developments, CITRUS will not only develop a novel approach for obtaining magnetic resonance based bone imaging but also for mapping ultrasound effects in vivo using magnetic resonance acoustic radiation force imaging (MR-ARFI). This will enable swift and reliable validation of both target position and intensity in human studies. In the V2 version, MR-ARFI will be implemented to allow for closed-loop adjustment of TUS focus position to provide for truly validated targeting of deep-brain structures in humans. The two prototypes are tested in proof-of-concept studies combining ultrasound stimulation of clinically relevant deep brain regions with functional magnetic resonance imaging (fMRI) acquisitions.
