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Item Image Segmentation, Parametric Study, and Supervised Surrogate Modeling of Image-based Computational Fluid Dynamics(2022-05) Islam, Md Mahfuzul; Yu, Huidan (Whitney); Du, Xiaoping; Wagner, DianeWith the recent advancement of computation and imaging technology, Image-based computational fluid dynamics (ICFD) has emerged as a great non-invasive capability to study biomedical flows. These modern technologies increase the potential of computation-aided diagnostics and therapeutics in a patient-specific environment. I studied three components of this image-based computational fluid dynamics process in this work. To ensure accurate medical assessment, realistic computational analysis is needed, for which patient-specific image segmentation of the diseased vessel is of paramount importance. In this work, image segmentation of several human arteries, veins, capillaries, and organs was conducted to use them for further hemodynamic simulations. To accomplish these, several open-source and commercial software packages were implemented. This study incorporates a new computational platform, called InVascular, to quantify the 4D velocity field in image-based pulsatile flows using the Volumetric Lattice Boltzmann Method (VLBM). We also conducted several parametric studies on an idealized case of a 3-D pipe with the dimensions of a human renal artery. We investigated the relationship between stenosis severity and Resistive index (RI). We also explored how pulsatile parameters like heart rate or pulsatile pressure gradient affect RI. As the process of ICFD analysis is based on imaging and other hemodynamic data, it is often time-consuming due to the extensive data processing time. For clinicians to make fast medical decisions regarding their patients, we need rapid and accurate ICFD results. To achieve that, we also developed surrogate models to show the potential of supervised machine learning methods in constructing efficient and precise surrogate models for Hagen-Poiseuille and Womersley flows.Item Retinal Phenotyping of Ferrochelatase Mutant Mice Reveals Protoporphyrin Accumulation and Reduced Neovascular Response(ARVO, 2021-02-01) Sardar Pasha, S. P. B.; Shetty, Trupti; Lambert-Cheatham, Nathan A.; Sishtla, Kamakshi; Mathew, Deepa; Muniyandi, Anbukkarasi; Patwari, Neeta; Bhatwadekar, Ashay D.; Corson, Timothy W.; Ophthalmology, School of MedicinePurpose: Heme depletion, through inhibition of ferrochelatase (FECH), blocks retinal and choroidal neovascularization. Both pharmacologic FECH inhibition and a partial loss-of-function Fech mutation (Fechm1Pas) are associated with decreased neovascularization. However, the ocular physiology of Fechm1Pas mice under basal conditions has not been characterized. Here, we aimed to characterize the retinal phenotype of Fechm1Pas mice. Methods: We monitored retinal vasculature at postnatal day 17, 2 months, and 6 months in Fechm1Pas homozygotes, heterozygotes, and their wild-type littermates. We characterized Fech substrate protoporphyrin (PPIX) fluorescence in the eye (excitation = 403 nm, emission = 628 nm), retinal function by electroretinogram, visual acuity by optomotor reflex, and retinal morphology by optical coherence tomography and histology. We stained vasculature using isolectin B4 and fluorescein angiography. We determined endothelial sprouting of retinal and choroidal tissue ex vivo and bioenergetics of retinal punches using a Seahorse flux analyzer. Results: Fundi, retinal vasculature, venous width, and arterial tortuosity showed no aberrations. However, VEGF-induced retinal and choroidal sprouting was decreased in Fechm1Pas mutants. Homozygous Fechm1Pas mice had pronounced buildup of PPIX in the posterior eye with no damage to visual function, bioenergetics, and integrity of retinal layers. Conclusions: Even with a buildup of PPIX in the retinal vessels in Fechm1Pas homozygotes, the vasculature remains normal. Notably, stimulus-induced ex vivo angiogenesis was decreased in Fechm1Pas mutants, consistent with reduced pathologic angiogenesis seen previously in neovascular animal models. Our findings indicate that Fechm1Pas mice are a useful model for studying the effects of heme deficiency on neovascularization due to Fech blockade.