Vagus nerve stimulation (VNS) yields promising therapeutic benefits but is often limited by off-target effects. Imaging tools that reveal the fascicular organization within the nerve can be used to better direct stimulation energy to the intended target. Here, we demonstrate polarization-sensitive (PS)-OCT imaging of an intact 7.5 cm ex-vivo porcine vagus nerve. The limited OCT penetration depth was overcome by using a dual-scanning microscope configured to simultaneously acquire B-scans from the upper and lower segments of a nerve sample. Three-dimensional maps of the complex fascicular organization in these nerves were generated.
The combination of optogenetics and optical imaging modalities has become a popular tool for the investigation of neurovascular coupling. Developing a closed-loop hemodynamic control system capable of dynamically following various blood flow patterns could be beneficial to the causal investigation of neurovascular coupling.
To develop this closed-loop hemodynamic control system, we have added a compensator to create a loop consisting of optogenetic stimulation, neural activities, neurovascular coupling, the evoked hemodynamic response, and a blood flow monitoring device to continuously minimize the difference between the recorded blood flow values and desired blood flow patterns.
A Real-time Doppler Optical Coherence Tomography (D-OCT) is employed in this study to monitor the cross-sectional velocity profile of a vessel at a frame rate of 71 frames per second. At the same time, a proportional-derivative compensator is used to continuously adjust the pulse width of a 450nm pulsed laser that delivers 15 Hz photostimulation to the cerebral cortex of Thy1-Channelrhodopsin-2 mice.
For each vessel, time-varying desired patterns and stimulation parameters were chosen according to the effect of pulse width modulation on its hemodynamic response, then proportional and derivative gains were tuned to produce a near-critically damped response.
After parameter optimization, the closed-loop hemodynamic compensator successfully controlled the blood flow in middle cerebral artery branches.
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