Minimally-invasive monitoring of electrophysiological neural activities in real-time —that enables 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. In this paper, we present proof-of-concept in vivo functional PA (fPA) imaging of chemoconvulsant rat seizure model with intact scalp using a fluorescence quenching-based cyanine voltage-sensitive dye (VSD) characterized by a lipid vesicle model mimicking different levels of membrane potential variation. The framework also involves use of a near-infrared 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 fPA 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 need of invasive craniotomy.

Transcranial recording of electrophysiological neural activity in the rodent brain in vivo using functional photoacoustic imaging of near-infrared voltage-sensitive dye