Research Scientist Fralin Biomedical Resarch Institute, United States
Introduction: Interstitial fluid flow (IFF) paths have been correlated with specific pathways within the brain. Proximity to key drainage paths can influence bulk movement of fluid and is dependent on cerebral location due to the distinct architecture that exists throughout the brain. Glioblastoma, the most common and deadly primary brain tumor, forms across various vascular landscapes and itself alters the vascular architecture of the brain as it develops. Thus, both the brain and the tumor influence the vascular landscape and the corresponding interstitial fluid flow that occurs within and around the tumor. As glioma invasion has been shown to be sensitive to interstitial fluid flows, there is a need to understand how drainage amidst the complex cerebral architectures drives IFF and, consequently, regional-specific invasion.
Materials and
Methods: We utilize murine GL261 tumor models that span multiple vascular landscapes to understand how cerebral location, and corresponding vascularity, contributes to IFF and invasion. We inject 100,000 cells and allow the tumors to form for 9 days. By using dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), we are able to measure location-specific differences in transport. We measure velocity magnitude, diffusion coefficient, and tumor-originating pathline accumulation and examine these metrics in regions of glioblastoma cell invasion. We then extend our analysis to healthy, non-tumor bearing models to examine baseline, location-specific differences in transport. We measure transport following a variety of injection techniques, focused ultrasound (FUS), cerebral spinal fluid injection (CSF), intraventricular injection, and direct cannula injection.
Results, Conclusions, and Discussions: Upon characterization of tumor growth, ventricular tumors grew the smallest and were the least associated with transport-specific invasive trends. Invasion in grey matter and white matter tumors were associated with elevated velocity magnitudes, and diffusion coefficients. Elevated tumor-originating pathline densities were associated with invasion in grey matter tumors only. FUS measurements resulted in elevated velocity magnitudes and diffusion coefficients, however transport was similar across locations. Our healthy work emphasizes that baseline metrics may be indicative of future tumor-associated transport and vascular densities. Our location-based analyses present a first step in identifying specific outcomes which may be associated with surrounding environments. By having a better understanding of location-specific outcomes, we may be able to better predict therapeutic response and invasive patterns when patients present with tumors within these locations.
Acknowledgements (Optional): Dr. Maosen Wang at Fralin Biomedical Research Institute for MRI support.
