Computational modeling and magnetic resonance imaging of microcirculation in the ocular lens

Abstract

The aim of this thesis was to investigate the microcirculation system of the ocular lens, through empirical and computational approaches. A 3D computational model of the lens microcirculation was created in this research project, based on the previous 1D and 2D models (Malcolm 2006). This model was used to predict several lens kinetics related parameters. A broad agreement between the predictions of the 3D computational model and the outcomes of previous models and experimentally-obtained literature data was found in this research. Later, the computational model was used to predict the effect of some perturbation conditions (i.e. high extracellular potassium, low temperatures and aging) on the circulatory fluxes inside the lens. It was found that, compared to the normal conditions, the microcirculation was weakened under the perturbed conditions. It was also noticed that parameters linked to the homeostasis of the lens were affected, hinting at an active role for the microcirculation system in upholding the homeostasis of the ocular lens. To experimentally investigate the microcirculation system, different methods of magnetic resonance imaging (MRI) technique were used in the lens. Using the diffusion tensor imaging (DTI) method, it was discovered that the water fluxes are highly anisotropic in the cortex, becoming more isotropic towards the core of the lens. It was also found from DTI outcomes that the principal eigenvectors in the cortex region were perpendicular to the surface of the lens around the polar and equatorial sections, but elsewhere they were parallel to the surface. To directly trace the movement of solutes and water inside the ocular lens, contrast agent MRI experiments were performed. The results appeared to be indicative of an extracellular barrier inside the ocular lens which stops the large molecules from penetrating the lens. A preferential movement of water into the polar regions of the lens was also detected. Similar perturbation conditions used for the modeling section were used in contrast enhanced MRI experiments to compare the experimental results with the computational predictions. It was found that, under the perturbed conditions, the lens was deviated from its homeostasis, comparable to the modeling predictions. Also, the previously observed preferential movement of the contrast agent into the lens polar regions was diminished under these conditions. In general, the microcirculation system has been studied computationally and empirically, and a convergence between the results of the two approaches has been observed. Further improvements of the model to include new features will be of great value to the international lens community. The non-invasive MRI routines developed in this research could also be improved further towards a non-invasive in vivo study of the microcirculation system, perhaps in a clinical environment.