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.
Optogenetics provides a tool for modulating activity of specific cell types by light pulses. Different light delivery mechanisms such as single optical fiber implanted on a skull or patterned illumination can be employed to direct light to a target area. For a highly scattering medium such as brain tissue, light distribution significantly depends on the scattering parameters of the tissue as well as the inherent inhomogeneity of the specimen. For in vivo studies, blood vessels which have considerable absorption coefficient in the visible spectrum play a major role in producing such inhomogeneity. Therefore, detailed information about brain optical properties and network of blood vessels which was ignored in previous studies is necessary to accurately predict light distribution and designing light delivery mechanism during optogenetic experiments to achieve the desired optical stimulation. In this paper, light pattern preservation while considering the impact of blood vessels is investigated in a rat cortex. First, the typical optical properties of rat cortical tissue were extracted by employing double integrated sphere technique, and then, optical coherence tomography was employed to obtain structure of blood vessels on the cortex. By combining the extracted optical properties and the network of blood vessels, a three-dimensional model of a rat cortical tissue was developed. Then, a Monte Carlo simulation code was used to predict light distribution in this model for different light source configurations and wavelengths. The results confirm that presence of vessels can significantly impact the light pattern in the tissue and affect the practical depth of penetration.