702. Advances in transcranial ultrasonic stimulation (TUS) for non-invasive deep brain neuromodulation in humans

Abstract

Abstract Background Transcranial ultrasonic stimulation (TUS) is an emerging technique that comes with the promise of non-invasive deep brain neuromodulation at unprecedented spatial precision, which may revolutionize the treatment of neurological and psychiatric disease. Aims & Objectives However, two major challenges currently constitute roadblocks for a wider adoption in basic research and clinical application: Firstly, the human skull bone causes significant reflection, aberration, and attenuation of the ultrasound beam, often hampering precise targeting and sufficient target exposure. Secondly, the large parameter space of TUS protocols and the known state-dependency of neuromodulatory effects challenges the development of effective neuromodulation protocols, in particular given the constraints by peripheral co-stimulation confounds and safety limits. Method To improve targeting precision (i.e., on- vs off-target exposure), we (i) develop an open-source tool for quickly optimizing transducer positioning before running detailed acoustic simulations, (ii) optimize and empirically validate MR-bone imaging sequences to obtain high quality bone density information for acoustic simulations without the ionizing radiation of CT scans, and (iii) establish MR-guided robotized transducer navigation. To validate the effectiveness of neuromodulation protocols and provide empirical proof of neural target engagement, we combine TUS concurrently with fMRI, EEG, and TMS. Results The PlanTUS software (plan-tus.org) now enables the individual optimization of TUS transducer positions. MR, CT, and microCT images were recorded in N = 25 ex-vivo human skulls to optimize MR-based pseudo-CT generation. Robot-navigated TUS now enables us to combine TUS-EEG and closed-loop EEG-triggered TUS, stimulating the cholinergic basal forebrain during wakefulness and the thalamus during sleep. Within the CITRUS project (project-citrus.eu), we developed a novel TUS-MR device, integrating a 256-channel phased-array TUS system for 3D-beam steering and cross-beam approaches with a custom-tailored MR-receiver coil for accelerated functional imaging of TUS effects with maximal sensitivity. Discussion & Conclusions In my talk I will provide an introduction into both the fundamentals and the practical aspects of TUS application, discuss the promises and pitfalls of a combined application with EEG, fMRI, and TMS, and provide examples from ongoing TUS research in our lab.