Development of a Preclinical Laser Speckle Contrast Imaging Instrument for Assessing Systemic and Retinal Vascular Function in Small Rodents.

Abstract

PurposeTo develop and test a non-contact, contrast-free, retinal laser speckle contrast imaging (LSCI) instrument for use in small rodents to assess vascular anatomy, quantify hemodynamics, and measure physiological changes in response to retinal vascular dysfunction over a wide field of view (FOV).MethodsA custom LSCI instrument capable of wide-field and non-contact imaging in small rodents was constructed. The effect of camera gain, laser power, and exposure duration on speckle contrast variance was standardized before the repeatability of LSCI measurements was determined in vivo. Finally, the ability of LSCI to detect alterations in local and systemic vascular function was evaluated using a laser-induced branch retinal vein occlusion and isoflurane anesthesia model, respectively.ResultsThe LSCI system generates contrast-free maps of retinal blood flow with a 50° FOV at >376 frames per second (fps) and under a short exposure duration (>50 µs) with high reliability (intraclass correlation R = 0.946). LSCI was utilized to characterize retinal vascular anatomy affected by laser injury and longitudinally measure alterations in perfusion and blood flow profile. Under varied doses of isoflurane, LSCI could assess cardiac and systemic vascular function, including heart rate, peripheral resistance, contractility, and pulse propagation.ConclusionsWe present a LSCI system for detecting anatomical and physiological changes in retinal and systemic vascular health and function in small rodents.Translational RelevanceDetecting and quantifying early anatomical and physiological changes in vascular function in animal models of retinal, systemic, and neurodegenerative diseases could strengthen our understanding of disease progression and enable the identification of new prognostic and diagnostic biomarkers for disease management and for assessing treatment efficacies.