MIRACLE-AD · Multi-modal Imaging for Retinal Analysis at Cellular Levels in Early Alzheimer’s Disease

Neurovascular coupling (NVC) regulates blood flow to meet the metabolic demands of neural activity by delivering oxygen and nutrients. Its dysfunction is a hallmark of several neurological disorders, including Alzheimer’s disease (AD), where early NVC impairment contributes to disease progression. As the retina is the only optically accessible part of the central nervous system, it provides a unique opportunity to investigate NVC at the cellular level. A precise understanding of retinal NVC could uncover key biomarkers for the evaluation of AD progression and the development of new targeted therapies. However, current imaging tools lack the spatial and temporal resolution necessary to capture neural and vascular functions simultaneously.In recent research, I have pioneered two novel imaging modalities for cellular-level retinal imaging: full-field optical coherence tomography (FF-OCT) and adaptive optics rolling slit ophthalmoscopy (AO-RSO). FF-OCT, with its interferometric properties, has the potential to visualize individual neurons involved in NVC. Meanwhile, AO-RSO, the only system capable of high-speed phase contrast imaging across a wide field of view, reveals critical vascular features, such as vessel walls and red blood cells, which are essential for probing vascular responses during NVC.The MIRACLE-AD project aims to combine the strengths of these modalities to develop an innovative tool capable of characterizing neural and vascular activity at micrometer and sub-millisecond scales in both health and early-AD patients. This approach will map neuronal pathways from photoreceptors to ganglion cells following light stimulation and measure vascular responses linked to individual ganglion cell activation. By elucidating the spatiotemporal relationship between neuronal activation and hemodynamic changes, MIRACLE-AD will deepen our understanding of NVC dysfunction in AD and its role in disease pathophysiology.