Browsing by Author "Coombe, Dennis"

Now showing 1 - 5 of 5
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    A physiologically-based flow network model for hepatic drug elimination I: regular lattice lobule model
    (2013) Rezania, Vahid; Marsh, Rebeccah; Coombe, Dennis; Tuszynski, Jack A.
    We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.
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    A physiologically-based flow network model for hepatic drug elimination II: variable lattice lobule models
    (2013) Rezania, Vahid; Marsh, Rebeccah; Coombe, Dennis; Tuszynski, Jack A.
    We extend a physiologically-based lattice model for the transport and metabolism of drugs in the liver lobule (liver functional unit) to consider structural and spatial variability. We compare predicted drug concentration levels observed exiting the lobule with their detailed distribution inside the lobule, and indicate the role that structural variation has on these results. Liver zonation and its role on drug metabolism represent another aspect of structural inhomogeneity that we consider here. Since various liver diseases can be thought to produce such structural variations, our analysis gives insight into the role of disease on liver function and performance. These conclusions are based on the dominant role of convection in well-vascularized tissue with a given structure.
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    Building a 3D virtual liver: methods for simulating blood flow and hepatic clearance on 3D structures
    (2016) White, Diana; Coombe, Dennis; Rezania, Vahid; Tuszynski, Jack A.
    In this paper, we develop a spatio-temporal modeling approach to describe blood and drug flow, as well as drug uptake and elimination, on an approximation of the liver. Extending on previously developed computational approaches, we generate an approximation of a liver, which consists of a portal and hepatic vein vasculature structure, embedded in the surrounding liver tissue. The vasculature is generated via constrained constructive optimization, and then converted to a spatial grid of a selected grid size. Estimates for surrounding upscaled lobule tissue properties are then presented appropriate to the same grid size. Simulation of fluid flow and drug metabolism (hepatic clearance) are completed using discretized forms of the relevant convective-diffusive-reactive partial differential equations for these processes. This results in a single stage, uniformly consistent method to simulate equations for blood and drug flow, as well as drug metabolism, on a 3D structure representative of a liver.
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    Liver bioreactor design issues of fluid flow and zonation, fibrosis, and mechanics: a computational perspective
    (2020) Rezania, Vahid; Coombe, Dennis; Tuszynski, Jack A.
    Tissue engineering, with the goal of repairing or replacing damaged tissue and organs, has continued to make dramatic science-based advances since its origins in the late 1980’s and early 1990’s. Such advances are always multi-disciplinary in nature, from basic biology and chemistry through physics and mathematics to various engineering and computer fields. This review will focus its attention on two topics critical for tissue engineering liver development: (a) fluid flow, zonation, and drug screening, and (b) biomechanics, tissue stiffness, and fibrosis, all within the context of 3D structures. First, a general overview of various bioreactor designs developed to investigate fluid transport and tissue biomechanics is given. This includes a mention of computational fluid dynamic methods used to optimize and validate these designs. Thereafter, the perspective provided by computer simulations of flow, reactive transport, and biomechanics responses at the scale of the liver lobule and liver tissue is outlined, in addition to how bioreactor-measured properties can be utilized in these models. Here, the fundamental issues of tortuosity and upscaling are highlighted, as well as the role of disease and fibrosis in these issues. Some idealized simulations of the effects of fibrosis on lobule drug transport and mechanics responses are provided to further illustrate these concepts. This review concludes with an outline of some practical applications of tissue engineering advances and how efficient computational upscaling techniques, such as dual continuum modeling, might be used to quantify the transition of bioreactor results to the full liver scale.
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    Oxygen distribution in the liver lobule: three dimensional computational models
    (2015) Rezania, Vahid; Coombe, Dennis; Tuszynski, Jack A.
    We develop a computational model for the transport and metabolism of drugs as well as oxygen in the functional unit of the liver called the lobule. The functional unit of an organ is the smallest structural unit that can independently serve all of the organ’s functions.