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Mathematical modeling and optimal control problems in brain tumor targeted drug delivery strategies
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作者 Aziz Belmiloudi 《International Journal of Biomathematics》 2017年第4期235-296,共62页
In this paper, we present a mathematical model that describes tumor-normal cells inter- action dynamics focusing on role of drugs in treatment of brain tumors. The goal is to predict distribution and necessary quantit... In this paper, we present a mathematical model that describes tumor-normal cells inter- action dynamics focusing on role of drugs in treatment of brain tumors. The goal is to predict distribution and necessary quantity of drugs delivered in drug-therapy by using optimal control framework. The model describes interactions of tumor and normal cells using a system of reactions^diffusion equations involving the drug concentration, tumor cells and normal tissues. The control estimates simultaneously blood perfusion rate, reabsorption rate of drug and drug dosage administered, which affect the effects of brain tumor chemotherapy. First, we develop mathematical framework which mod- els the competition between tumor and normal cells under chemotherapy constraints. Then, existence, uniqueness and regularity of solution of state equations are proved as well as stability results. Afterwards, optimal control problems are formulated in order to minimize the drug delivery and tumor cell burden in different situations. We show existence and uniqueness of optimal solution, and we derive necessary conditions for optimality. Finally, to solve numerically optimal control and optimization problems, we propose and investigate an adjoint multiple-relaxation-time lattice Boltzmann method for a general nonlinear coupled anisotropic convection-diffusion system (which includes the developed model for brain tumor targeted drug delivery system). 展开更多
关键词 Optimal control coupled nonlinear reaztion-diffusion equations anisotropicbrain tumor growth diffusion tensor drug delivery chemotherapy real-time monitoringof distribution logistic growth pointwise controllers adjoint system population dyna-mics magnetic resonance imaging (MRI) convection-enhanced delivery (CED) adjointmultiple-relaxation-time lattice Boltzmann method multiscale Chapman-Enskog expan-sion optimization of therapies.
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