This book presents applications of geometric optimal control to real life biomedical problems with an emphasis on cancer treatments. A number of mathematical models for both classical and novel cancer treatments are presented as optimal control problems with the goal of constructing optimal protocols. The power of geometric methods is illustrated with fully worked out complete global solutions to these mathematically challenging problems. Elaborate constructions of optimal controls and corresponding system responses provide great examples of applications of the tools of geometric optimal control and the outcomes aid the design of simpler, practically realizable suboptimal protocols. The book blends mathematical rigor with practically important topics in an easily readable tutorial style. Graduate students and researchers in science and engineering, particularly biomathematics and more mathematical aspects of biomedical engineering, would find this book particularly useful.

This monograph is a study of optimal control applied to cancer chemotherapy, the treatment of cancer using drugs that kill cancer cells. The aim is to determine whether current methods for the administration of chemotherapy are optimal, and if alternative regimens should be considered.The research utilizes the mathematical theory of optimal control, an active research area for many mathematicians, scientists, and engineers. It is of multidisciplinary nature, having been applied to areas ranging from engineering to biomedicine. The aim in optimal control is to achieve a given objective at minimum cost. A set of differential equations is used to describe the evolution in time of the process being modelled, and constraints limit the policies that can be used to attain the objective.In this monograph, mathematical models are used to construct optimal drug schedules. These are treatment guidelines specifying which drug to deliver, when, and at what dose. Many current drug schedules have been derived empirically, based upon ?rules of thumb?.The monograph has been structured so that most of the high-level mathematics is introduced in a special appendix. In this way, a scientist can skip the more subtle aspects of the theory and still understand the biomedical applications that follow. However, the text is self-contained so that a deeper understanding of the mathematics of optimal control can be gained from the mathematical appendix.The mathematical models in this book and the associated computer simulations show that low intensity chemotherapy is a better choice of treatment than high intensity chemotherapy, under certain conditions.

This book gives a comprehensive treatment of the fundamental necessary and sufficient conditions for optimality for finite-dimensional, deterministic, optimal control problems. The emphasis is on the geometric aspects of the theory and on illustrating how these methods can be used to solve optimal control problems. It provides tools and techniques that go well beyond standard procedures and can be used to obtain a full understanding of the global structure of solutions for the underlying problem. The text includes a large number and variety of fully worked out examples that range from the classical problem of minimum surfaces of revolution to cancer treatment for novel therapy approaches. All these examples, in one way or the other, illustrate the power of geometric techniques and methods. The versatile text contains material on different levels ranging from the introductory and elementary to the advanced. Parts of the text can be viewed as a comprehensive textbook for both advanced undergraduate and all level graduate courses on optimal control in both mathematics and engineering departments. The text moves smoothly from the more introductory topics to those parts that are in a monograph style were advanced topics are presented. While the presentation is mathematically rigorous, it is carried out in a tutorial style that makes the text accessible to a wide audience of researchers and students from various fields, including the mathematical sciences and engineering. Heinz Schättler is an Associate Professor at Washington University in St. Louis in the Department of Electrical and Systems Engineering, Urszula Ledzewicz is a Distinguished Research Professor at Southern Illinois University Edwardsville in the Department of Mathematics and Statistics.

From economics and business to the biological sciences to physics and engineering, professionals successfully use the powerful mathematical tool of optimal control to make management and strategy decisions. Optimal Control Applied to Biological Models thoroughly develops the mathematical aspects of optimal control theory and provides insight into t

With chapters on free boundaries, constitutive equations, stochastic dynamics, nonlinear diffusion–consumption, structured populations, and applications of optimal control theory, this volume presents the most significant recent results in the field of mathematical oncology. It highlights the work of world-class research teams, and explores how different researchers approach the same problem in various ways. Tumors are complex entities that present numerous challenges to the mathematical modeler. First and foremost, they grow. Thus their spatial mean field description involves a free boundary problem. Second, their interiors should be modeled as nontrivial porous media using constitutive equations. Third, at the end of anti-cancer therapy, a small number of malignant cells remain, making the post-treatment dynamics inherently stochastic. Fourth, the growth parameters of macroscopic tumors are non-constant, as are the parameters of anti-tumor therapies. Changes in these parameters may induce phenomena that are mathematically equivalent to phase transitions. Fifth, tumor vascular growth is random and self-similar. Finally, the drugs used in chemotherapy diffuse and are taken up by the cells in nonlinear ways. Mathematical Oncology 2013 will appeal to graduate students and researchers in biomathematics, computational and theoretical biology, biophysics, and bioengineering.

This book provides a unified framework for various currently available mathematical models that are used to analyze progression and regression in cancer development, and to predict its dynamics with respect to therapeutic interventions. Accurate and reliable model representations of cancer dynamics are milestones in the field of cancer research. Mathematical modeling approaches are becoming increasingly common in cancer research, as these quantitative approaches can help to validate hypotheses concerning cancer dynamics and thus elucidate the complexly interlaced mechanisms involved. Even though the related conceptual and technical information is growing at an exponential rate, the application of said information and realization of useful healthcare devices are lagging behind. In order to remedy this discrepancy, more interdisciplinary research works and course curricula need to be introduced in academic, industrial, and clinical organizations alike. To that end, this book reformulates most of the existing mathematical models as special cases of a general model, allowing readers to easily get an overall idea of cancer dynamics and its modeling. Moreover, the book will help bridge the gap between biologists and engineers, as it brings together cancer dynamics, the main steps involved in mathematical modeling, and control strategies developed for cancer management. This also allows readers in both medical and engineering fields to compare and contrast all the therapy-based models developed to date using a single source, and to identify unexplored research directions.

Composed of contributions from an international team of leading researchers, this book pulls together the most recent research results in the field of cancer modeling to provide readers with the most advanced mathematical models of cancer and their applications.Topics included in the book cover oncogenetic trees, stochastic multistage models of carcinogenesis, effects of ionizing radiation on cell cycle and genomic instability, induction of DNA damage by ionizing radiation and its repair, epigenetic cancer models, bystander effects of radiation, multiple pathway models of human colon cancer, and stochastic models of metastasis. The book also provides some important applications of cancer models to the assessment of cancer risk associated with various hazardous environmental agents, to cancer screening by MRI, and to drug resistance in cancer chemotherapy. An updated statistical design and analysis of xenograft experiments as well as a statistical analysis of cancer occult clinical data are also provided.The book will serve as a useful source of reference for researchers in biomathematics, biostatistics and bioinformatics; for clinical investigators and medical doctors employing quantitative methods to develop procedures for cancer diagnosis, prevention, control and treatment; and for graduate students.