ABSTRACT
Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions. The significant development of digital technologies linked to high-resolution NMR exploration, coupled with the possibilities offered by AI, means that we can envisage the creation of digital twins of tumors and their host organs, thus reducing the use of physical sampling.
ABSTRACT
Our aim in this paper is to study a mathematical model for high grade gliomas, taking into account lactates kinetics, as well as chemotherapy and antiangiogenic treatment. In particular, we prove the existence and uniqueness of biologically relevant solutions. We also perform numerical simulations based on different therapeutical situations that can be found in the literature. These simulations are consistent with what is expected in these situations.
Subject(s)
Glioma , Lactic Acid , Humans , Kinetics , Brain/pathology , Glioma/drug therapy , Glioma/pathology , Models, TheoreticalABSTRACT
Interfaces play a key role on diseases development because they dictate the energy inflow of nutrients from the surrounding tissues. What is underestimated by existing mathematical models is the biological fact that cells are able to use different resources through nonlinear mechanisms. Among all nutrients, lactate appears to be a sensitive metabolic when talking about brain tumours or neurodegenerative diseases. Here we present a partial differential model to investigate the lactate exchanges between cells and the vascular network in the brain. By extending an existing kinetic model for lactate neuro-energetics, we first provide analytical proofs of the uniqueness and the derivation of precise bounds on the solutions of the problem including diffusion of lactate in a representative volume element comprising the interface between a capillary and cells. We further perform finite element simulations of the model in two test cases, discussing the relevant physical parameters governing the lactate dynamics.
Subject(s)
Brain Neoplasms , Lactic Acid , Diffusion , Humans , Kinetics , Models, Biological , Models, TheoreticalABSTRACT
The aim of this article is to show how a tumor can modify energy substrates fluxes in the brain to support its own growth. To address this question we use a modeling approach to explain brain nutrient kinetics. In particular we set up a system of 17 equations for oxygen, lactate, glucose concentrations and cells number in the brain. We prove the existence and uniqueness of nonnegative solutions and give bounds on the solutions. We also provide numerical simulations.
Subject(s)
Brain/pathology , Cerebrovascular Circulation/physiology , Energy Metabolism , Glioma/pathology , Models, Neurological , Models, Theoretical , Computer Simulation , Glioma/metabolism , Glucose/metabolism , Humans , Lactic Acid/metabolism , Oxygen/metabolismABSTRACT
The aim of this article is to study the well-posedness and properties of a fast-slow system which is related with brain lactate kinetics. In particular, we prove the existence and uniqueness of nonnegative solutions and obtain linear stability results. We also give numerical simulations with different values of the small parameter ε and compare them with experimental data.
