Transcranial FUS Therapy and Monitoring using Nonlinear Acoustics

Abstract

Focused ultrasound (FUS) offers a promising, non-invasive method for modulating neural activity and delivering therapies deep within the brain with immense clinical potential. However, progress in developing transcranial ultrasound (TUS) for clinical applications has been hindered by several factors. The complexity of the human skull causes focal aberrations and attenuation, thereby presenting a major obstacle to the precise targeting of ultrasound waves. Although phased arrays can correct for these aberrations, their high cost and continuous reliance on magnetic resonance imaging (MRI) pose significant obstacles for widespread academic research and clinical translation. To address these challenges, this thesis proposes an innovative framework for the design, registration, and clinical application of acoustic holograms. First, we introduce a novel frequency-domain topology optimization method that overcomes the breakdown of traditional phase-only designs in the megahertz regime by accounting for volumetric wave-propagation effects, thereby achieving high-fidelity focusing. Second, we present a non-invasive registration strategy that utilizes the nonlinear parametric array (PA) effect to enable precise lens alignment without requiring any imaging modalities, such as MRI. Finally, we demonstrate the utility of this nonlinear parametric array (PA) effect as a tool for monitoring ventricular dilation as a non-invasive proxy for intracranial pressure changes in hydrocephalus. Collectively, these developments provide a path toward accessible, high-precision transcranial ultrasound systems for research and clinical use. In addition, we demonstrate a novel platform for in vitro focused ultrasound neuromodulation that leverages acoustics to advance therapeutic discovery.