Microdialysis, microperfusion and convection current-guided distribution of solutes in a brain phantom
Haege, Elijah Rolland
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Glioblastoma multiforme (Glioma) is an extremely aggressive tumor that arises from intrinsic glial cells in the central nervous system (CNS)5. It is the most common primary brain tumor in humans and has a typical survival time of 15-16 months5. Current treatments for gliomas include surgery, radiation, and treatment with temozolomide (TMZ). While these treatments tend to add 2-3 months to a patient’s survival, none have been capable of altering the course of the disease1. One of the shortcomings of novel therapeutics for glioma, is the inability to evaluate in real time how therapeutics are affecting the patient. There is also the problem of the blood brain barrier (BBB), which can be overcome by administering drugs through an intracranial catheter (delivered via CED). The primary obstacle that’s been observed in intracranial drug delivery is the inadequacy of the delivery. This inadequacy is an inability of the drug to diffuse homogenously throughout the tumor. CED also creates a possibility for toxicity due to highly concentrated volumes of drugs delivered; we believe the novel delivery method we are trying to develop, will make this possibility null. The purpose of this study was initially to demonstrate the problem of delivering drugs via diffusion while simultaneously collecting biomarkers to interpret efficacy of the drugs, due to differing molecular weights. The other objective of this study was to demonstrate that it is possible to manipulate both the direction of bulk flow and the rate of diffusion of drugs delivered through a catheter using a gel phantom as a representative of brain tissue. What we found is that by utilizing a two-catheter method with convection and retro-convection enhanced delivery, we could in fact manipulate these parameters and achieve a more even distribution of drug (represented by fluorophores in our experiments). Using these two catheter methods, we will also be able to collect fluids from the tumor to monitor the effect of any treatment in real time.