Periodic Reporting for period 2 - CITRUS (Closed-loop Individualized image-guided Transcranial Ultrasonic Stimulation)
Periodo di rendicontazione: 2023-10-01 al 2025-03-31
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.
So far, CITRUS consortium partners have developed a new generation of transcranial ultrasound transducers with 256 elements, each of which is controlled with its own electronic pathway. This allows for outstanding steering capabilities combined with versatile applicability to the scalp. Careful selection of production materials and design concepts have resulted in transducers with excellent magnetic resonance compatibility as demonstrated in extended tests inside the MR scanners. These water-cooled transducers are attached to novel mounting structures that are included in the housing of the MR coil. Each mounting point comprises a ball joint for maximum flexibility in positioning the transducer on the desired scalp position. The MR coil itself contains 16 receive channels that are positioned in a way to maximise sensitivity and parallel imaging capabilities. Two of these elements are realised as flexible coils in order to combine high-sensitivity data acquisition with versatile transducer placement. Reflective trackers are mounted on both transducers, the MR coil arrays and the study participant in order to enable comprehensive neuronavigational control of the whole sonication procedure, both inside and outside the MR scanner. MR-ARFI was successfully implemented in a HASTE sequence design, which results in very short image acquisition times combined with minimised geometric distortions. Sonication control was integrated into the neuronavigation suite to minimise user interaction and improve workflow. All developments are embedded in a comprehensive technical documentation strategy to streamline human studies and facilitate certification procedures according to the EU Medical Device Regulation.
The tailored 16-channel receive array equipped with the novel mounting solution received a merit award at the 2025 meeting of the International Society for Magnetic Resonance in Medicine (ISMRM) for its novelty in the field. A manuscript with the details on design and performance of this coil array is currently in preparation. The MR-ARFI HASTE sequence is the first combination of ARFI and HASTE and has been presented at several conferences. The respective manuscript is currently in preparation.