Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

Abstract

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multi-modal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels

“…For arterioles and venules, when measuring RBC velocity responses to flicker stimulation, we have shown that individual capillary RBC velocities vary across capillaries (either increasing or decreasing), differing from arterioles and venules, which show a consistent response. 10 , 24 , 41 Unlike other studies that have found increases in RBC velocity in larger retinal vessels during flicker stimulation, 42 – 44 our capillary measurements in this study showed an increase in RBC velocity in only three out of the five subjects, although from a larger sample we found on average that capillary flow increased by about the same amount as arteriole flow, but the change was not statistically significant, in part due to the variability in capillary measurements. 24 …”

Evaluation of flicker induced hyperemia in the retina and optic nerve head measured by Laser Speckle Flowgraphy

“…As such, studies using multifunction OCT angiography show that this technique allows for the assessment of flicker evoked hemodynamic responses of individual layers of the retina. [17, 18] Alternatively, dual-beam bidirectional Doppler Fourier-domain has been used to quantify flicker evoked hemodynamic changes in both animal and human experiments. [19, 20] However, the latter techniques are currently not commercially available and therefore only limited to specialized research centers.…”

Retinal vascular reactivity in carriers of X-linked inherited retinal disease – a study using optical coherence tomography angiography

“…There are many methods available to elicit a dynamic response in the retinal microvasculature. The handgrip test and hyperoxic conditions have been previously used to induce retinal vasoconstriction ( 27 , 30 , 51 , 52 ), while the flicker test and hypoxia have been reported to illicit a vasodilatory response ( 27 , 30 , 53 ). Currently, these techniques are limited to research use, however they may have clinical applicability with standardization of methods and reporting of test findings.…”