MRI analysis to map interstitial flow in the brain tumor microenvironment
Autor: | Kathryn M. Kingsmore, Scott T. Acton, Andrea Vaccari, Daniel Abler, Sophia X. Cui, Jennifer M. Munson, Frederick H. Epstein, Russell C. Rockne |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
lcsh:Medical technology lcsh:Biotechnology Biomedical Engineering Biophysics Brain tumor Bioengineering Invited Articles Imaging phantom Biomaterials 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Nuclear magnetic resonance In vivo lcsh:TP248.13-248.65 Glioma medicine Fluid dynamics Evans Blue medicine.diagnostic_test Magnetic resonance imaging medicine.disease 3. Good health 030104 developmental biology lcsh:R855-855.5 chemistry Flow velocity 030220 oncology & carcinogenesis Special Topic: Bioengineering of Cancer |
Zdroj: | APL Bioengineering APL Bioengineering, Vol 2, Iss 3, Pp 031905-031905-15 (2018) |
ISSN: | 2473-2877 |
Popis: | Glioblastoma (GBM), a highly aggressive form of brain tumor, is a disease marked by extensive invasion into the surrounding brain. Interstitial fluid flow (IFF), or the movement of fluid within the spaces between cells, has been linked to increased invasion of GBM cells. Better characterization of IFF could elucidate underlying mechanisms driving this invasion in vivo. Here, we develop a technique to non-invasively measure interstitial flow velocities in the glioma microenvironment of mice using dynamic contrast-enhanced magnetic resonance imaging (MRI), a common clinical technique. Using our in vitro model as a phantom “tumor” system and in silico models of velocity vector fields, we show we can measure average velocities and accurately reconstruct velocity directions. With our combined MR and analysis method, we show that velocity magnitudes are similar across four human GBM cell line xenograft models and the direction of fluid flow is heterogeneous within and around the tumors, and not always in the outward direction. These values were not linked to the tumor size. Finally, we compare our flow velocity magnitudes and the direction of flow to a classical marker of vessel leakage and bulk fluid drainage, Evans blue. With these data, we validate its use as a marker of high and low IFF rates and IFF in the outward direction from the tumor border in implanted glioma models. These methods show, for the first time, the nature of interstitial fluid flow in models of glioma using a technique that is translatable to clinical and preclinical models currently using contrast-enhanced MRI. |
Databáze: | OpenAIRE |
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