Kang, J. U. | Search bioRxiv

bioRxiv2018

Voltage-sensitive dye delivery through the blood brain barrier using adenosine receptor agonist Regadenoson

Optical imaging of brain activity has mostly employed genetically manipulated mice, which cannot be translated to clinical human usage. Observation of brain activity directly is challenging due to difficulty in delivering dyes and other agents through the blood brain barrier (BBB). Using fluorescence imaging, we have demonstrated the feasibility of delivering the near-infrared voltage-sensitive dye (VSD) IR-780 perchlorate to the brain tissue through pharmacological techniques, via an adenosine agonist (Regadenoson). Comparison of VSD fluorescence of mouse brains without and with Regadenoson showed significantly increased residence time of the fluorescence signal in the latter case, indicative of VSD diffusion into the brain tissue. Dose and timing of Regadenoson were varied to optimize BBB permeability for VSD delivery.

bioengineering↗

bioRxiv2017

Transcranial real-time in vivo recording of electrophysiological neural activity in the rodent brain with near-infrared photoacoustic voltage-sensitive dye imaging

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 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. Our normalized time-frequency analysis presented in vivo VSD response in the seizure group significantly distinguishable from those of the control groups at sub-mm spatial resolution. 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 the near-infrared fPA VSD imaging is a promising tool for in vivo recording of brain activities through intact scalp, which would pave a way to its future translation.

neuroscience↗