Ein mehrskaliges Modell zur Beschreibung des Medikamententransports in der menschlichen Lunge zur Lungenkrebstherapie
| Autor: | Erbertseder, Karin Maria |
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| Přispěvatelé: | Helmig, Rainer (Prof. Dr.-Ing.) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Popis: | This thesis proposes a multi-scale model for describing cancer-therapeutic transport in the human lung. The developed multi-scale model represents flow, transport and reaction processes: in the pulmonary macrocirculation on the organ scale, in the capillary bed around an alveolus, in the surrounding pulmonary tissue and in the tumor on the tissue scale, and in the tumor cell population and in the single cancer cells on the cells scale. The model concept is specialized for an alveolar cell carcinoma. The therapeutic agent is administered via a bolus injection into the blood stream. The relevant processes occurring on these three scales are described by three different numerical models that are sequentially coupled to each other. On the organ scale, the discrete vascular graph model (VGM) simulates the advection and reaction of the blood-dissolved drug within the non-capillary part of the pulmonary vasculature (arteries, arterioles, venules and veins). To determine the amount of administered therapeutic agent that will reach the cancer cells, the VGM is coupled to the alveolus model: a double-continuum approach for porous media (DCM). The processes occurring in the alveolar capillaries and in the surrounding pulmonary tissue are represented by the DCM. The DCM is also used to describe the tumor regions in the lung. The system of equations of the coupled discrete / continuum model contains terms that account for degradation processes of the therapeutic agent, the reduction of the number of drug molecules by the lymphatic system and the interaction of the drug with the tissue cells. Further, the low-dimensional population model for TRAIL-induced proapoptotic signaling ([PMTS]_s) is sequentially coupled to the alveolus model. In this way, the spatiotemporal distribution of the therapeutic agent in the pulmonary tissue is linked with the biochemical reactions occurring on the cells scale. The low-dimensional population model for TRAIL-induced proapoptotic signaling describes the reactions of a heterogeneous cancer cell population to the administered therapeutic agent and calculates the percentage of cancer cells undergoing cell death. As such, the multi-scale model can predict the spatial and temporal distribution of a drug administered by a continuous bolus injection in the human lung and the reaction of the cancer to the therapeutic agent. The functionality of the developed multi-scale model is demonstrated in example simulations using simplified pulmonary vascular networks. Diese Arbeit stellt ein Mehrskalenmodell zur Beschreibung der Fluss-, Transport- und Reaktionsprozesse in der menschlichen Lunge zur Behandlung von Lungenkrebs vor. Das entwickelte mathematische und numerische Modell verbindet drei unterschiedliche räumliche Skalen und die entsprechenden physikalischen Prozesse jeder Skala miteinander. Das entwickelte Mehrskalenmodell besteht aus den folgenden drei Modellen: dem Vascular Graph Model zur Darstellung der Prozesse in der Makrozirkulation, dem Alveolus Model für die Beschreibung der Prozesse im Kapillarbett um eine Alveole und dem umliegenden Lungengewebe, sowie dem Low-Dimensional Population Model for TRAIL-Induced Proapoptotic Signaling zur Abbildung der Reaktionen der Krebszellen auf das verabreichte Medikament. |
| Databáze: | OpenAIRE |
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