A distributed optimal control problem for a diffuse interface model, which physical context is that of tumour growth dynamics, is addressed. The system we deal with comprises a Cahn--Hilliard equation for the tumour fraction coupled with a reaction-diffusion for a nutrient species surrounding the tumourous cells. The cost functional to be minimised possesses some objective terms and it also penalises long treatments time, which may affect harm to the patients, and big aggregations of tumourous cells. Hence, the optimisation problem leads to the optimal strategy which reduces the time exposure of the patient to the medication and at the same time allows the doctors to achieve suitable clinical goals.
Phase field models recently gained a lot of interest in the context of tumour growth models. Typically Darcy-type flow models are coupled to Cahn-Hilliard equations. However, often Stokes or Brinkman flows are more appropriate flow models. We introduce and mathematically analyse a new Cahn-Hilliard-Brinkman model for tumour growth allowing for chemotaxis. Outflow boundary conditions are considered in order not to influence tumour growth by artificial boundary conditions. Existence of global-in-time weak solutions is shown in a very general setting.
Mechanical effects have mostly been neglected so far in phase field tumour models that are based on a Cahn-Hilliard approach. In this paper we study a macroscopic mechanical model for tumour growth in which cell-cell adhesion effects are taken into account with the help of a Ginzburg--Landau type energy. In the overall model an equation of Cahn-Hilliard type is coupled to the system of linear elasticity and a reaction-diffusion equation for a nutrient concentration. The highly non-linear coupling between a fourth-order Cahn-Hilliard equation and the quasi-static elasticity system lead to new c…
In this work, we study a model consisting of a Cahn-Hilliard-type equation for the concentration of tumour cells coupled to a reaction-diffusion type equation for the nutrient density and a Brinkman-type equation for the velocity. We equip the system with Neumann boundary for the tumour cell variable and the chemical potential, Robin-type boundary conditions for the nutrient and a "no-friction" boundary condition for the velocity, which allows us to consider solution dependent source terms. Well-posedness of the model as well as existence of strong solutions will be established for a broad cla…
A phase field model for tumour growth is introduced that is based on a Brinkman law for convective velocity fields. The model couples a convective Cahn-Hilliard equation for the evolution of the tumour to a reaction-diffusion-advection equation for a nutrient and to a Brinkman-Stokes type law for the fluid velocity. The model is derived from basic thermodynamical principles, sharp interface limits are derived by matched asymptotics and an existence theory is presented for the case of a mobility which degenerates in one phase leading to a degenerate parabolic equation of fourth order. Finally n…
On a relaxed Cahn-Hilliard tumour growth model with single-well potential and degenerate mobility
Università degli Studi di Milano（米兰大学）；IMATI–C.N.R.（意大利国家研究委员会数学应用研究所）；Politecnico di Milano（米兰理工大学）；Sorbonne Université（索邦大学）；CNRS（法国国家科学研究中心）；Université Paris-Cité（巴黎西岱大学）；Inria（法国国立数字研究院）；Laboratoire “Jacques-Louis Lions”（雅克-路易·利昂斯实验室）
We study the existence of weak solutions to a mixture model for tumour growth that consists of a Cahn--Hilliard--Darcy system coupled with an elliptic reaction-diffusion equation. The Darcy law gives rise to an elliptic equation for the pressure that is coupled to the convective Cahn--Hilliard equation through convective and source terms. Both Dirichlet and Robin boundary conditions are considered for the pressure variable, which allows for the source terms to be dependent on the solution variables.
We consider a diffuse interface model for tumour growth consisting of a Cahn--Hilliard equation with source terms coupled to a reaction-diffusion equation. The coupled system of partial differential equations models a tumour growing in the presence of a nutrient species and surrounded by healthy tissue. The model also takes into account transport mechanisms such as chemotaxis and active transport. We establish well-posedness results for the tumour model and a variant with a quasi-static nutrient. It will turn out that the presence of the source terms in the Cahn--Hilliard equation leads to new…
We derive a Cahn-Hilliard-Darcy model to describe multiphase tumour growth taking interactions with multiple chemical species into account as well as the simultaneous occurrence of proliferating, quiescent and necrotic regions. Via a coupling of the Cahn-Hilliard-Darcy equations to a system of reaction-diffusion equations a multitude of phenomena such as nutrient diffusion and consumption, angiogenesis, hypoxia, blood vessel growth, and inhibition by toxic agents, which are released for example by the necrotic cells, can be included. A new feature of the modelling approach is that a volume-ave…
Using basic thermodynamic principles we derive a Cahn--Hilliard--Darcy model for tumour growth including nutrient diffusion, chemotaxis, active transport, adhesion, apoptosis and proliferation. The model generalises earlier models and in particular includes active transport mechanisms which ensure thermodynamic consistency. We perform a formally matched asymptotic expansion and develop several sharp interface models. Some of them are classical and some are new which for example include a jump in the nutrient density at the interface. A linear stability analysis for a growing nucleus is perform…
In this work, we consider a diffuse interface model for tumour growth in the presence of a nutrient which is consumed by the tumour. The system of equations consists of a Cahn--Hilliard equation with source terms for the tumour cells and a reaction-diffusion equation for the nutrient. We introduce a fully-discrete finite element approximation of the model and prove stability bounds for the discrete scheme. Moreover, we show that discrete solutions exist and depend continuously on the initial and boundary data. We then pass to the limit in the discretization parameters and prove convergence to …
We study the existence of weak solutions to a Cahn--Hilliard--Darcy system coupled with a convection-reaction-diffusion equation through the fluxes, through the source terms and in Darcy's law. The system of equations arises from a mixture model for tumour growth accounting for transport mechanisms such as chemotaxis and active transport. We prove, via a Galerkin approximation, the existence of global weak solutions in two and three dimensions, along with new regularity results for the velocity field and for the pressure. Due to the coupling with the Darcy system, the time derivatives have low…
Carleman estimates for backward Cahn-Hilliard-reaction-diffusion problems
University of Pavia（帕维亚大学）；New York University Abu Dhabi（纽约大学阿布扎比分校）；University of Milan（米兰大学）；Istituto di Matematica Applicata e Tecnologie Informatiche “Enrico Magenes”, CNR（恩里科·马格内斯应用数学与信息技术研究所，意大利国家研究委员会）；The University of Tokyo（东京大学）
We consider the inverse problem of identifying parameters in a variant of the diffuse interface model for tumour growth model proposed by Garcke, Lam, Sitka and Styles (Math. Models Methods Appl. Sci. 2016). The model contains three constant parameters; namely the tumour growth rate, the chemotaxis parameter and the nutrient consumption rate. We study the inverse problem from the viewpoint of PDE-constrained optimal control theory and establish first order optimality conditions. A chief difficulty in the theoretical analysis lies in proving high order continuous dependence of the strong soluti…
We study a phase field model proposed recently in the context of tumour growth. The model couples a Cahn-Hilliard-Brinkman (CHB) system with a elliptic reaction-diffusion equation for a nutrient. The fluid velocity, governed by the Brinkman law, is not solenodial, as its divergence is a function of the nutrient and the phase field variable, i.e., solution-dependent, and frictionless boundary conditions are prescribed for the velocity to avoid imposing unrealistic constraints on the divergence relation. In this paper we give a first result on the existence of weak and stationary solutions to th…
We study a non-local variant of a diffuse interface model proposed by Hawkins--Darrud et al. (2012) for tumour growth in the presence of a chemical species acting as nutrient. The system consists of a Cahn--Hilliard equation coupled to a reaction-diffusion equation. For non-degenerate mobilities and smooth potentials, we derive well-posedness results, which are the non-local analogue of those obtained in Frigeri et al. (European J. Appl. Math. 2015). Furthermore, we establish existence of weak solutions for the case of degenerate mobilities and singular potentials, which serves to confine the …
