Abstract
Many currently employed clinical brain functional imaging technologies rely on indirect measures of activity such as hemodynamics resulting in low temporal and spatial resolutions. To improve upon this, optical systems were developed in conjunction with methods to deliver near-IR voltage-sensitive dye (VSD) to provide activity-dependent optical contrast to establish a clinical tool to facilitate direct monitoring of neuron depolarization through the intact skull. Following the previously developed VSD delivery protocol through the blood-brain barrier, IR-780 perchlorate VSD concentrations in the brain were varied and stimulus-evoked responses were observed. In this paper, a range of optimal VSD tissue concentrations was established that maximized fluorescence fractional change for detection of membrane potential responses to external stimuli through a series of phantom, in vitro, ex vivo, and in vivo experiments in mouse models.
Highlights
It is well-established that neuron activity is the basis for brain function and more generally, organism behavior
Phantom experiments established the voltage-sensitive dye (VSD) concentrationdependent fluorescence in which increased fluorescence was observed with greater concentration up to a maximum fluorescence signal found at 50 μM, followed by decreased fluorescence signal for any higher concentrations (Figure 3A)
We further studied the biological interactions of our cyanine VSD molecules in in vitro primary cortical neuronal (PCN) cultures in different VSD concentrations ranging from 0 to 50 μM
Summary
It is well-established that neuron activity is the basis for brain function and more generally, organism behavior. Many tools have been developed to study the complex nature of how the brain works Some of these techniques rely on bulk physiological effects, such as the blood-oxygen-leveldependent (BOLD) signal which utilizes hemodynamics as an indicator of neuron activity. There have been profound investigations using photoacoustic and ultrasound as alternative modalities, but their contrast remained limited by neurovascular physiology such as oxyhemoglobin saturation and cerebral blood volume or flow (CBV or CBF) (Hu and Wang, 2010; Errico et al, 2015; Kang et al, 2018) Methods such as electroencephalography have been used for direct monitoring of electrical activity, these methods tradeoff spatial resolution (Burle et al, 2015)
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