Precision assessment of transcranial ultrasound neuromodulation effects with hemodynamic, metabolic, thermal and acoustic radiation force imaging

PROJECT SUMMARY / ABSTRACT Transcranial ultrasound stimulation (TUS) holds great promise as a noninvasive tool to focally modu- late activity anywhere in the brain. However, the physiological impact of TUS on the human brain is mostly unknown. A better mechanistic understanding of TUS effects would allow much more precise design of stimulation protocols for TUS, accelerating its use as a novel circuit therapeutic for neuro- psychiatric conditions. The overall objective of the current proposal is to measure the physiological impact of TUS in the human brain in vivo in healthy participants with multimodal complementary neu- roimaging techniques, using the visual system as an ideal test-bed. The expected outcome of com- pleting this project is the quantification of the hemodynamic and neurometabolic effects of TUS, the spatial extent of effects at the target, and brain-wide neural network effects, measured in an early sensory thalamic nucleus and a higher-order associative thalamic nucleus. The proposed Aim uses MR-acoustic radiation force imaging (ARFI) to unambiguously target either the lateral geniculate nu- cleus (LGN, the primary visual relay nucleus of the thalamus) or the pulvinar (the higher-order visual thalamic nucleus), nucleus, and measure hemodynamic, metabolic, and thermal impact of TUS with BOLD, arterial spin labeling (ASL), FDG-PET, and MR-thermometry. Measurements will be made both at resting-state and during visual stimulation. The significance of this work is that, if successful, it validates the use of ARFI for TUS target confirmation, identifies potential TUS biomarkers, quantifies in vivo TUS spatial specificity, and determines the long-range effects of focal thalamic modulation in both a core sensory and higher-order associative nucleus. This causally tests the roles of different thalamic nuclei in thalamocortical visual networks at rest and during vision. Moreover, It accelerates the development of TUS as a safer and more effective circuit-based therapeutic for CNS visual disor- ders including amblyopia, visual hallucinations, dyslexia, and visual agnosias.