Computational Approach to 3D Modeling of the Lymph  Node Geometry

Kislitsyn, Alexey Alexeevich; Savinkov, Rostislav; Onder, Lucas; Bocharov, Gennady

doi:10.3390/computation3020222

Cited by 32 publications

(27 citation statements)

References 29 publications

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“…The only available systematic modeling work goes back to the work of Reddy [12]. In our previous studies, we addressed a number of basic issues related to computational modeling of lymph nodes [22] and the flow processes through the conduit network of a lymph node [23,24]. In the present study, we make use of the available anatomical model of the human lymphatic system (from the project PlasticBoy project [20]), which can be obtained through http://www.plasticboy.co.…”

Section: Discussionmentioning

confidence: 99%

Developing Computational Geometry and Network Graph Models of Human Lymphatic System

et al. 2017

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Abstract:The lymphatic system is a body-wide network of lymphatic vessels and lymphoid organs. The complexity of the structural and functional organization of the lymphatic system implies the necessity of using computational modeling approaches to unravel the mechanisms of its regulation in quantitative terms. Although it is a vital part of the circulatory and immune systems, the lymphatic system remains poorly investigated as a mathematical modeling object. Modeling of the lymphatic vessel network needs to be established using a systematic approach in order to advance the model-driven research of this important physiological system. In our study, we elucidate key general features underlying the 3D structural organization of the lymphatic system in order to develop computational geometry and network graph models of the human lymphatic system based on available anatomical data (from the PlasticBoy project), which provides an estimate of the structure of the lymphatic system, and to analyze the topological properties of the resulting models.

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Section: Discussionmentioning

confidence: 99%

Developing Computational Geometry and Network Graph Models of Human Lymphatic System

et al. 2017

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“…The FRC length is chosen to align with experimental data, e.g. [22]. The number of vertices, and radius of the LN, are chosen as large as possible within constraints of computational complexity for the agent-based model, while both maintaining a reasonable edge length [41].…”

Section: B the Steady State Of The Heterogeneous Population Modelmentioning

confidence: 99%

T cell and reticular network co-dependence in HIV infection

Donovan

Lythe

2016

Journal of Theoretical Biology

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Fibroblastic reticular cells (FRC) are arranged on a network in the T cell zone of lymph nodes, forming a scaffold for T cell migration, and providing survival factors, especially interleukin-7 (IL-7). Conversely, CD4 + T cells are the major producers of lymphotoxin-β (LT-β), necessary for the construction and maintenance of the FRC network. This interdependence creates the possibility of a vicious cycle, perpetuating loss of both FRC and T cells. Furthermore, evidence that HIV infection is responsible for collagenation of the network suggests that long term loss of network function might be responsible for the attenuated recovery in T cell count seen in HIV patients undergoing antiretroviral therapy (ART). We present computational and mathematical models of this interaction mechanism and subsequent naive CD4 + T-cell depletion in which (1) collagen deposition impedes access of naive T cells to IL-7 on the FRC and loss of IL-7 production by loss of FRC network itself, leading to the depletion of naive T cells through increased apoptosis; and (2) depletion of naive T cells as the source of LT-β on which the FRC depend for survival, leads to loss of the network, thereby amplifying and perpetuating the cycle of depletion of both naive T cells and stromal cells. Our computational model explicitly includes an FRC network and its cytokine exchange with a heterogeneous T-cell population. We also derive lumped models, in terms of partial differential equations and reduced to ordinary differential equations, that provide additional insight into the mechanisms at work. The central conclusions are that 1) damage to the reticular network, caused by HIV infection, is a plausible mechanism for attenuated recovery post-ART; 2) within this, the production of T cell survival factors by FRCs may be the key ratelimiting step; and 3) the methods of model reduction and analysis presented are useful for both immunological studies and other contexts in which agent-based models are severely limited by computational cost.

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“…Increasing computer processing capabilities has made it feasible to design and generate a paradigmatic LN model based on real organ geometry [4]. Such a systems biology approach has allowed us to develop a generalized 3D solid model of the LN, which consists of the following idealized structures: SCS, B cell follicles, trabecular and medullar lymphatic sinuses, blood vasculature and HEVs, the T cell zone and FRC network.…”

Section: Major Structural Elements Of a Paradigmatic Lymph Nodementioning

confidence: 99%

“…We initialize cells as thin (d ∼ 1.0 µm) cylinders along the graph of reticular network topology (constructed in [4]), forming the conduit system (Figure 1a). Protrusions of different cells are connected at the middles of the corresponding edges.…”

Section: Of 22mentioning

confidence: 99%

“…This implies that the development of computational models of the LN structure and function requires (i) an idealization of the structure, (ii) the implementation of a modular approach, and (iii) the analysis of the performance of specific functional LN units in health and disease. The elements of the above framework can be found in [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Critical Issues in Modelling Lymph Node Physiology

Grebennikov

Loon

Onder

et al. 2016

Preprint

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Abstract:In this study we discuss critical issues in modelling the structure and function of lymph nodes (LNs), with emphasis on how LN physiology is related to its multi-scale structural organization. In addition to macroscopic domains such as B-cell follicles and the T cell zone, there are vascular networks which play a key role in the delivery of information to the inner parts of the LN, i.e., the conduit and blood microvascular networks. We propose object-oriented computational algorithms to model the 3D geometry of the fibroblastic reticular cell (FRC) network and the microvasculature. Assuming that a conduit cylinder is densely packed with collagen fibers, the computational flow study predicted that the diffusion should be a dominating process in mass transport than convective flow. The geometry models are used to analyze the lymph flow properties through the conduit network in unperturbedand damaged states of the LN. The analysis predicts that elimination of up to 60 − 90 % of edges is required to stop the lymph flux. This result suggests a high degree of functional robustness of the network.

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Computational Approach to 3D Modeling of the Lymph Node Geometry

Cited by 32 publications

References 29 publications

Developing Computational Geometry and Network Graph Models of Human Lymphatic System

Developing Computational Geometry and Network Graph Models of Human Lymphatic System

T cell and reticular network co-dependence in HIV infection

Critical Issues in Modelling Lymph Node Physiology

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