Revealing neurovascular coupling at a high spatial and temporal resolution in the living human retina

Neurovascular coupling (NVC) regulates local blood flow in response to neuronal activity, yet its precise characterization at the capillary level has been hindered by the lack of a noninvasive, high-resolution imaging method. Here, we introduce the adaptive optics rolling slit ophthalmoscope, a unique noninvasive, label-free, high-speed, cellular-resolution clinical imaging system for assessing retinal NVC in the living human eye. Using an off-axis phase contrast approach combined with camera-based confocal slit gating, our method provides large field-of-view imaging of arterial and venular walls, enabling the study of vascular dynamics with unprecedented spatiotemporal precision. Our findings highlight that this level of precision is essential for accurately distinguishing NVC-driven vasodilation from spontaneous fluctuations, such as vasomotion and the cardiac cycle. By bridging the gap between fundamental neurovascular research and clinical applications, this approach offers a powerful tool for neuroscience research and early disease detection and monitoring of neurodegenerative and vascular disorders.