Incorporating Patient-Specific Technologies for Transcranial Focused Ultrasound Applications

Abstract

Transcranial focused ultrasound (tFUS) is a noninvasive, therapeutic modality that can precisely focus sound through the skull. tFUS is clinically approved for thermal ablation, but there is growing interest in its nonthermal advancements, such as neuromodulation for studying brain circuits and opening the blood-brain barrier to enhance drug delivery. To ensure safe and effective tFUS treatments, knowledge of the focus location and in situ pressure estimates are crucial. However, the skull introduces challenges as sound waves are absorbed and reflected, leading to shifting and degradation of the focus location. Moreover, there is significant intersubject variability in skull characteristics requiring subject-specific information for tFUS planning. This dissertation aims to integrate patient-specific technologies into the workflow of tFUS procedures, to ensure precise targeting and minimizing potential adverse effects.

First, synthetic computed tomography (CT) images generated from a conditional generative adversarial network were acoustically evaluated with real CT images, currently the gold standard to obtain subject-specific skull data. The pseudo-CT images were strongly correlated with ground-truth data for skull metrics, with only minor differences observed in the simulated pressure field. Incorporating synthetic CT image for tFUS planning would eliminate patient exposure to harmful ionizing radiation. Acoustic simulations are often used to estimate thermal and mechanical effects during tFUS experiments. A workflow was established to position a transducer model in tFUS scenarios using optical tracking transformations to perform subject-specific simulations. The accuracy of the simulated workflow revealed that the error could not be reduced beyond the limitations of the optical tracking system. However, a vector correction method was implemented to update the simulation grids and improve spatial alignment with magnetic resonance (MR) measurements. The simulation workflow was applied to tFUS non-human primate neuromodulation experiments that were fully conducted in the MR environment, enabling validation of simulated dosimetry estimates and investigation of thermal analysis during neuromodulation. The validated simulation workflow can be utilized in tFUS planning, aiding in the selection of stimulation parameters for neuromodulation experiments. Overall, the potential of integrating patient-specific technologies, including synthetic CT imaging and acoustic simulations, into the workflow of tFUS procedures provides a foundation for safe and accurate treatment planning.