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Öğe Closed-Loop Nonlinear Adaptive Control of Anti-angiogenic Tumor Therapy(Ieee, 2013) Hasırcı, Uğur; Burg, Timothy C.; Groff, Richard E.A nonlinear adaptive backstepping controller for the anti-angiogenic tumor growth control problem is presented. The proposed control algorithm directly aims to drive the tumor volume along a desired trajectory as part of a treatment regimen. Toward this aim, we first present an exact-model knowledge controller that ensures the exponential tracking of a time-varying tumor volume profile, and then, an adaptive controller is shown that provides asymptotic tracking despite model uncertainties. A Lyapunov-based analysis approach is used to determine stability and performance results. Numerical simulation results are presented to demonstrate the performance of the proposed approach. Finally, the requirements of a real-time implementation of an in-vitro model of the overall system are discussed.Öğe Closed-loop nonlinear smooth robust control of anti-angiogenic tumor therapy(2013) Hasırcı, Uğur; Burg, Timothy C.; Groff, Richard E.This paper presents a smooth robust controller for anti-angiogenic treatment of a tumor growth. The proposed control algorithm directly aims to drive the carrying capacity of the vascular support network to a desired trajectory that reduces overall tumor volume. For this aim, we present a closed-loop smooth robust controller that ensures the asymptotic tracking of a time-varying carrying capacity profile, despite the model uncertainties. A Lyapunov-based analysis approach is used to determine stability and performance results. Numerical simulation results are presented to demonstrate the performance and feasibility of the proposed approach. Simulation studies also examine some practical issues regarding the clinical application of the proposed dosing algorithm. Finally, the paper provides some basics for real-time implementation of the overall system. © 2013 AACC American Automatic Control Council.Öğe Nonlinear Adaptive Optimal Controller Design for Anti-Angiogenic Tumor Treatment(Mdpi, 2023) Nath, Nitendra; Kil, İrfan; Hasırcı, Uğur; Groff, Richard E.; Burg, Timothy C.Angiogenesis is an important process in tumor growth as it represents the regime when the tumor recruits blood vessels from the surrounding tissue to support further tumor growth. Anti-angiogenic treatments aim to shrink the tumor by interrupting the vascularization of the tumor; however, the anti-angiogenic agents are costly and the tumor response to these agents is nonlinear. Simple dosing schemes, e.g., a constant dose, may yield higher cost or lower efficacy than an approach that considers the tumor system dynamics. Hence, in this study, the administration of anti-angiogenic treatment is considered as a nonlinear control problem. The main aim of the controller design is to optimize the anti-angiogenic tumor therapy, specifically, to minimize the tumor volume and drug dose. Toward this aim, two nonlinear optimal controllers are presented. The first controller ensures exponential tracking of a desired, optimal tumor volume profile under the assumption that all parameters in the system model are known. The second controller, on the other hand, assumes all the parameters are unknown and provides asymptotic tracking. Both controllers take pharmacokinetics and pharmacodynamics into account, as well as the carrying capacity of the vascular network. Lyapunov based arguments are used to design the controllers, using stability arguments, and numerical simulation results are presented to demonstrate the effectiveness of the proposed method.
