The proposed approach opens new lines of research with potential applications in understanding the role of different cell types in the cerebrovascular regulatory mechanisms and the study of the adaptive process of angiogenesis in the cerebral cortex. The observation of incoherent responses of vessel diameter, blood flow-rate, and velocity suggests that such detailed information is necessary to obtain an accurate interpretation of the data acquired via hemodynamic based functional imaging techniques.
Objective. The main objective of this research was to study the coupling between neural circuits and the vascular network in the cortex of small rodents from system engineering point of view and generate a mathematical model for the dynamics of neurovascular coupling. The model was adopted to implement closed-loop blood flow control algorithms. Approach. We used a combination of advanced technologies including optogenetics, electrocorticography, and optical coherence tomography to stimulate selected populations of neurons and simultaneously record induced electrocorticography and hemodynamic signals. We adopted system identification methods to analyze the acquired data and investigate the relation between optogenetic neural activation and consequential electrophysiology and blood flow responses. Main results. We showed that the developed model, once trained by the acquired data, could successfully regenerate subtle spatio-temporal features of evoked electrocorticography and cerebral blood flow responses following an onset of optogenetic stimulation. Significance. The long term goal of this research is to open a new line for computational analysis of neurovascular coupling particularly in pathologies where the normal process of blood flow regulation in the central nervous system is disrupted including Alzheimer’s disease.
To assess the performance of two spectral-domain optical coherence tomography-angiography systems in a natural model of hypoperfusion: the hibernating thirteen-lined ground squirrel (13-LGS).Methods: Using a high-speed (130 kHz) OCT-A system (HS-OCT-A) and a commercial OCT (36 kHz; Bioptigen Envisu; BE-OCT-A), we imaged the 13-LGS retina throughout its hibernation cycle. Custom software was used to extract the superior, middle, and deep capillary plexus (SCP, MCP, and DCP, respectively). The retinal vasculature was also imaged with adaptive optics scanning light ophthalmoscopy (AOSLO) during torpor to visualize individual blood cells. Finally, correlative histology with immunolabeled or DiIstained vasculature was performed.Results: During euthermia, vessel density was similar between devices for the SCP and MCP (P = 0.88, 0.72, respectively), with a small difference in the DCP (−1.63 ± 1.54%, P = 0.036). Apparent capillary dropout was observed during torpor, but recovered after forced arousal, and this effect was exaggerated in high-speed OCT-A imaging. Based on cell flux measurements with AOSLO, increasing OCT-A scan duration by ∼1000× would avoid the apparent capillary dropout artifact. High correspondence between OCT-A (during euthermia) and histology enabled lateral scale calibration.
Conclusions:While the HS-OCT-A system provides a more efficient workflow, the shorter interscan interval may render it more susceptible to the apparent capillary dropout artifact. Disambiguation between capillary dropout and transient ischemia can have important implications in the management of retinal disease and warrants additional diagnostics.Translational Relevance: The 13-LGS provides a natural model of hypoperfusion that may prove valuable in modeling the utility of OCT-A in human pathologies associated with altered blood flow.
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