Underlying vasculature and perivasculature direct fluid flow in and around tumors

Project Summary The perivascular system has been implicated in a number of diseases in the brain and is responsible to the conduction of fluid flow and transport throughout the parenchyma. In glioma, both perivascular spaces and heightened interstitial fluid flow have been implicated in driving invasion of tumor cells, a major barrier to treatment. However, the relationship between the perivascular spaces and interstitial flow in the context of cancer development is understudied. Here we propose to develop a computational model and fundamental relationship understanding between these two important forces in glioma invasion. Specifically, we will use advanced MRI techniques to generate dynamic imaging of interstitial transport within normal and tumor bearing brains in mice followed by high-field (17.6T) MRI to generate detailed maps of the perivascular spaces in those same mice, correlating the outcomes. These maps will then be used to build and validate whole brain computational models of the PVS and interstitial flow within the brain in the context of tumor development. Using the model and our in vivo data, we will examine the differences in flow during tumor development in two locations based on density of the PVS. Last, we will test the impact of one of the most common treatments received by glioblastoma patients, dexamethasone, a steroid with anti-inflammatory and anti-edemic effects to determine if and how fluid flow, the PVS, and interstitial transport are altered by this therapy. In all, our work will develop the first whole brain model of fluid flow, with a focus on the parenchyma, validate this model, and apply it to tumors, with an end goal of this model being able to give better insight tumor transport and development.