Predictive modelling of thrombus formation in diabetic retinal microaneurysms.

He Li,Alireza Yazdani,Konstantina Sampani,Jennifer K Sun,Dimitrios P Papageorgiou,Xiaoning Zheng,George E Karniadakis,Miguel O Bernabeu

doi:10.1098/rsos.201102

Abstract

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). Vision can be reduced at any stage of DR by MAs, which may enlarge, rupture and leak fluid into the neural retina. Recent advances in ophthalmic imaging techniques enable reconstruction of the geometries of MAs and quantification of the corresponding haemodynamic metrics, such as shear rate and wall shear stress, but there is lack of computational models that can predict thrombus formation in individual MAs. In this study, we couple a particle model to a continuum model to simulate the platelet aggregation in MAs with different shapes. Our simulation results show that under a physiologically relevant blood flow rate, thrombosis is more pronounced in saccular-shaped MAs than fusiform-shaped MAs, in agreement with recent clinical findings. Our model predictions of the size and shape of the thrombi in MAs are consistent with experimental observations, suggesting that our model is capable of predicting the formation of thrombus for newly detected MAs. This is the first quantitative study of thrombosis in MAs through simulating platelet aggregation, and our results suggest that computational models can be used to predict initiation and development of intraluminal thrombus in MAs as well as provide insights into their role in the pathophysiology of DR.

Highlights

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR)
Our force coupling method (FCM) simulation results in figure 3a show that after one cardiac cycle, the platelets close to the aneurysm wall become activated and adhered to the wall where the wall shear stress is low
Three-dimensional luminal surfaces of patient-specific MAs have been reconstructed based on the retinal images in order to quantify the haemodynamic metrics inside MAs, such as shear rate and wall shear stress

Summary

Clinical image processing and microaneurysm geometry reconstruction

Four MAs from the eyes of adult study participants with diabetes (type 1 or 2) underwent AOSLO imaging. The magnification factor on AOSLO images was determined by eye axial length measurement or derived from the spherical equivalent of the eye For this exploratory study, we included MAs with high-quality AOSLO images where the two-dimensional MSL images and corresponding perfusion maps provided sufficient details to identify the full extent of MAs’ bodies and their parenting vessels’ boundaries. The segmented MA (figure 1c) or the mask, is used to generate the three-dimensional model for simulation (figure 1d) under the assumption that the MA geometries are rotationally symmetric. More details of this method can be found in [27].

Platelet aggregation model

Platelet aggregation in microaneurysms

Effect of microaneurysm’s shape on intraluminal thrombus formation

Dependence of growth of thrombus on haemodynamic conditions

Discussion