Transcranial Acoustoelectric Brain Imaging with Neuronavigation Toward Accurate, High Resolution Maps of Neuronal Currents

Abstract

Non-invasive functional brain imaging modalities like surface EEG and fMRI have provided new insights into neurological dysfunction, but they are both fundamentally limited in their spatial and temporal resolutions, respectively. Clinicians need higher resolution non-invasive electrical brain mapping technology that approaches the scale of neuronal activity to better treat and understand conditions including epilepsy, Alzheimer's, Parkinson's, and depression. Transcranial acoustoelectric brain imaging (tABI) is an emerging high resolution electrical brain mapping modality that non-invasively maps local current densities in the head by combining pulsed and focused transcranial ultrasound (US) with simultaneous electrical recording through the scalp. The ultrasound pulses are electronically steered through the head to create the image and define the field of view. The intensity of this beam is also proportional to the tABI signal, meaning it is important to maximize US transmission through the skull. Thus, there is a clear need to guide and optimize the US beam for the accuracy and sensitivity of tABI. The three main objectives of this dissertation are to: 1) Validate the performance of MR-based neuronavigation for tABI in an ex-vivo human head model to guide US placement and co-register electrical maps (tABI) onto anatomy (MRI), 2) Quantify improvement of the US beam through the human skull using acoustic modeling with optimizations (aberration correction and apodization filtering) based on feedback from the neuronavigation system, and 3) Confirm feasibility and analyze image quality changes of MR-neuronavigated tABI with optimized US in the human head model. The completion of these objectives enables efficient, safe, and accurate localization of pseudo-neuronal currents in a human head model. This system included image registration accuracy of <6.4 mm, improved tABI sensitivity by an average of 47.8%, increased the signal to noise ratio by up to 91.7%, and widened the imaging field of view by up to 75%.This final neuronavigated and aberration corrected system is a vital steppingstone towards clinical translation and using tABI to better understand and treat the brain.