Towards precision non-invasive neuromodulation: modelling and evaluation of transcranial focused ultrasound systems

Transcranial focused ultrasound (tFUS) is being investigated as a non-invasive neuromodulation approach with the potential to reach deep brain structures with greater spatial selectivity than many established non-invasive techniques. A growing literature suggests that ultrasound can influence neural systems across multiple biological scales, from ion-channel and synaptic effects in cellular preparations to functional and behavioural responses in animals and humans. However, the interpretation of such effects depends critically on knowing the acoustic field delivered to the intended neural target. This remains challenging because the skull can attenuate, refract and distort the transmitted acoustic field, complicating both treatment planning and the interpretation of neuromodulatory outcomes. This thesis examines the physical and methodological basis of transcranial focused ultrasound delivery. It first establishes a framework for acoustic source characterisation and intracranial field measurement. Using this framework, the thesis shows that intracranial delivery depends not only on frequency and skull morphology, but also on transducer-skull spacing. Building on these experimental observations, an analytical model is developed for rapid estimation of transcranial insertion loss. Multiple skull-modelling strategies in k-Wave are then benchmarked against measurements, showing that modelling choices can affect predicted pressure transmission and focal displacement. Finally, a preliminary in-vivo feasibility study demonstrates that tFUS delivery can be integrated with rat hippocampal electrophysiology while preserving interpretable electrophysiological recordings.