Simulation study on high spatio-temporal resolution acousto-electrophysiological neuroimaging.

Objective. Acousto-electrophysiological neuroimaging (AENI) is a technique hypothesized to record electrophysiological activity of the brain with millimeter spatial and sub-millisecond temporal resolution. This improvement is obtained by tagging areas with focused ultrasound (fUS). Due to mechanical vibration with respect to the measuring electrodes, the electrical activity of the marked region will be modulated onto the ultrasonic frequency. The region's electrical activity can subsequently be retrieved via demodulation of the measured signal. In this study, the feasibility of this hypothesized technique is tested. Approach. This is done by calculating the forward electroencephalography response under quasi-static assumptions. The head is simplified as a set of concentric spheres. Two sizes are evaluated representing human and mouse brains. Moreover, feasibility is assessed for wet and dry transcranial, and for cortically placed electrodes. The activity sources are modeled by dipoles, with their current intensity profile drawn from a power-law power spectral density. Results. It is shown that mechanical vibration modulates the endogenous activity onto the ultrasonic frequency. The signal strength depends non-linearly on the alignment between dipole orientation, vibration direction and recording point. The strongest signal is measured when these three dependencies are perfectly aligned. The signal strengths are in the pV-range for a dipole moment of 5 nAm and ultrasonic pressures within Food and Drug Administration (FDA)-limits. The endogenous activity can then be accurately reconstructed via demodulation. Two interference types are investigated: vibrational and static. Depending on the vibrational interference, it is shown that millimeter resolution signal detection is possible also for deep brain regions. Subsequently, successful demodulation depends on the static interference, that at MHz-range has to be sub-picovolt. Significance. Our results show that mechanical vibration is a possible underlying mechanism of acousto-electrophyisological neuroimaging. This paper is a first step towards improved understanding of the conditions under which AENI is feasible.