Abstract
Non-invasive monitoring of electrophysiological neural activities in real-time—that would enable quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. We present in vivo proof-of-concept results of transcranial photoacoustic (PA) imaging of chemoconvulsant seizure activity in the rat brain. The framework involves use of a fluorescence quenching-based near-infrared voltage-sensitive dye (VSD) delivered through the blood-brain barrier (BBB), opened by pharmacological modulation of adenosine receptor signaling. Using normalized time-frequency analysis on temporal PA sequences, the neural activity in the seizure group was distinguished from those of the control groups. Electroencephalogram (EEG) recording confirmed the changes of severity and frequency of brain activities, induced by chemoconvulsant seizures of the rat brain. The findings demonstrate that PA imaging of fluorescence quenching-based VSD is a promising tool for in vivo recording of deep brain activities in the rat brain, thus excluding the use of invasive craniotomy.
Significance statement Non-invasive monitoring of electrophysiological brain activities in real-time (order of milliseconds) is a challenging task of neuroimaging. The approach makes possible quantification of neural functions without need for invasive craniotomy. Existing imaging modalities do not have sufficient transcranial sensitivity with the necessary temporal and spatial resolutions. Here, we present in vivo proof-of-concept results for real-time transcranial photoacoustic imaging of near-infrared voltage-sensitive dye (VSD) signals. The imaging successfully detected the perturbation caused by chemoconvulsant seizures in rat brain. We introduce this novel method to the neuroscientific investigation of rodent brains, with the promise of rapid translation into primate and human brains.