Quantification of retinal blood leakage in fundus fluorescein angiography in a retinal angiogenesis model

Blood leakage from the vessels in the eye is the hallmark of many vascular eye diseases. One of the preclinical mouse models of retinal blood leakage, the very-low-density-lipoprotein receptor deficient mouse (Vldlr^-/-), is used for drug screening and mechanistic studies. Vessel leakage is usually examined using Fundus fluorescein angiography (FFA). However, interpreting FFA images of the Vldlr^-/- model is challenging as no automated and objective techniques exist for this model. A pipeline has been developed for quantifying leakage intensity and area including three tasks: (i) blood leakage identification, (ii) blood vessel segmentation, and (iii) image registration. Morphological operations followed by log-Gabor quadrature filters were used to identify leakage regions. In addition, a novel optic disk detection algorithm based on graph analysis was developed for registering the images at different timepoints. Blood leakage intensity and area measured by the methodology were compared to ground truth quantifications produced by two annotators. The relative difference between the quantifications from the method and those obtained from ground truth images was around 10% ± 6% for leakage intensity and 17% ± 8% for leakage region. The Pearson correlation coefficient between the method results and the ground truth was around 0.98 for leakage intensity and 0.94 for leakage region. Therefore, we presented a computational method for quantifying retinal vascular leakage and vessels using FFA in a preclinical angiogenesis model, the Vldlr^-/- model.