Validating a low-cost laser speckle contrast imaging system as a quantitative tool for assessing retinal vascular function

Dwani D Patel,Daniel M Lipinski

doi:10.1038/s41598-020-64204-z

Dwani D Patel, Daniel M Lipinski

Open Access

https://doi.org/10.1038/s41598-020-64204-z

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Abstract

The ability to monitor progression of retinal vascular diseases like diabetic retinopathy in small animal models is often complicated by their failure to develop the end-stage complications which characterize the human phenotypes in disease. Interestingly, as micro-vascular dysfunction typically precedes the onset of retinal vascular and even some neurodegenerative diseases, the ability to visualize and quantify hemodynamic changes (e.g. decreased flow or occlusion) in retinal vessels may serve as a useful diagnostic indicator of disease progression and as a therapeutic outcome measure in response to treatment. Nevertheless, the ability to precisely and accurately quantify retinal hemodynamics remains an unmet challenge in ophthalmic research. Herein we demonstrate the ability to modify a commercial fundus camera into a low-cost laser speckle contrast imaging (LSCI) system for contrast-free and non-invasive quantification of relative changes to retinal hemodynamics over a wide field-of-view in a rodent model.

Highlights

The ability to monitor progression of retinal vascular diseases like diabetic retinopathy in small animal models is often complicated by their failure to develop the end-stage complications which characterize the human phenotypes in disease
The development of imaging techniques to accurately and reproducibly measure early, pre-symptomatic changes in vascular function would be of substantial benefit as both a diagnostic and screening tool for identifying novel biomarkers of disease progression – enabling the effectiveness of novel therapeutics to be assessed in vivo using small animal models that do not develop end-stage proliferative disease
While a few laser speckle contrast imaging (LSCI) instruments are available for purchase and use in humans and animal models, here we examined whether it was possible to modify a commercial fundus camera found in many ophthalmic research laboratories into a LSCI system for rodent retinal imaging

Summary

Introduction

The ability to monitor progression of retinal vascular diseases like diabetic retinopathy in small animal models is often complicated by their failure to develop the end-stage complications which characterize the human phenotypes in disease. While large animal models such as canines and non-human primates do develop end-stage vascular complications that accurately recapitulate the human phenotype in diseases like diabetes and age-related macular degeneration, their use is severely limited by high maintenance costs and the long time frame required for pathologies to develop[7,8]. The development of imaging techniques to accurately and reproducibly measure early, pre-symptomatic changes in vascular function would be of substantial benefit as both a diagnostic and screening tool for identifying novel biomarkers of disease progression – enabling the effectiveness of novel therapeutics to be assessed in vivo using small animal models that do not develop end-stage proliferative disease. In areas of the field-of-view with faster motion, the standard deviation will decrease considerably more than the mean intensity – resulting in a reduction in speckle contrast[14]

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