Modeling glioma-induced impairments on the glymphatic system

Abstract

Altered glymphatic function is observed for many neurological diseases. Glioma, one of the most common brain cancers, is known to have altered fluid dynamics in terms of edema and blood-brain-barrier breakdown, both features potentially impacting the glymphatic function. To study glioma and its fluid dynamics, we propose a flexible mathematical model, including the tumor, the peri-tumoral edema as well as the healthy tissue. From a mechanical point of view, we consider the brain as a multicompartment porous medium and model both the fluid movement in the brain and the clearance of solutes that are convected but also diffuse in the extra-cellular space. Our results indicate that the impairment on the glymphatic system due to glioma growth is two-fold. First, edema resulting from leakage of fluid from the blood vessels or occlusion of the peri-vascular spaces, considered as an exit route, result in a local high pressure zone, consequently impairing negatively glymphatic clearance. Second, local changes of porosities (volume fraction of certain compartments such as perivascular or extracellular spaces), result in a disruption of the transport of solutes in the brain. Our results indicate that an effect similar to the enhanced permeability and retention is obtained using biologically relevant changes of parameter values of our model. Our mathematical model can be viewed as the first step towards a digital twin for drug or contrast product delivery within the cerebro-spinal fluid directly (e.g. from intrathecal injection) for patients suffering from gliomas.