Abstract
Background: Glioblastoma (GBM) is the deadliest and most common brain tumor in adults, with poor survival and response to aggressive therapy. Limited access of drugs to tumor cells is one reason for such grim clinical outcomes. A driving force for therapeutic delivery is interstitial fluid flow (IFF), both within the tumor and in the surrounding brain parenchyma. However, convective and diffusive transport mechanisms are understudied. In this study, we examined the application of a novel image analysis method to measure fluid flow and diffusion in GBM patients. Methods: Here, we applied an imaging methodology that had been previously tested and validated in vitro, in silico, and in preclinical models of disease to archival patient data from the Ivy Glioblastoma Atlas Project (GAP) dataset. The analysis required the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is readily available in the database. The analysis results, which consisted of IFF flow velocity and diffusion coefficients, were then compared to patient outcomes such as survival. Results: We characterized IFF and diffusion patterns in patients. We found strong correlations between flow rates measured within tumors and in the surrounding parenchymal space, where we hypothesized that velocities would be higher. Analyzing overall magnitudes indicated a significant correlation with both age and survival in this patient cohort. Additionally, we found that neither tumor size nor resection significantly altered the velocity magnitude. Lastly, we mapped the flow pathways in patient tumors and found a variability in the degree of directionality that we hypothesize may lead to information concerning treatment, invasive spread, and progression in future studies. Conclusions: An analysis of standard DCE-MRI in patients with GBM offers more information regarding IFF and transport within and around the tumor, shows that IFF is still detected post-resection, and indicates that velocity magnitudes correlate with patient prognosis.
Highlights
Glioblastoma (GBM) is the most lethal form of brain tumor, with a median lifespan post-diagnosis of 12–15 months and a 100% recurrence rate, often within several centimeters of the resection cavity
The patient data were only analyzed if an axial, T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-magnetic resonance imaging (MRI)) that was devoid of motion artifacts was available [24,25]
In The Cancer Imaging Archive patient data were available for DCE-MRI image acquisitions, which took approximately 1200 images over the course of two-to-three minutes
Summary
Glioblastoma (GBM) is the most lethal form of brain tumor, with a median lifespan post-diagnosis of 12–15 months and a 100% recurrence rate, often within several centimeters of the resection cavity. The most recent advancement in GBM therapy was the implementation of concurrent radiotherapy and temozolomide reported by Stupp et al in. The Stupp protocol only led to a slight improvement in outcomes for patients, increasing the overall five-year survival to only 27.2% for primary GBM. Glioblastoma (GBM) is the deadliest and most common brain tumor in adults, with poor survival and response to aggressive therapy. A driving force for therapeutic delivery is interstitial fluid flow (IFF), both within the tumor and in the surrounding brain parenchyma. We examined the application of a novel image analysis method to measure fluid flow and diffusion in GBM patients. Methods: Here, we applied an imaging methodology that had been previously tested and validated in vitro, in silico, and in preclinical models of disease to archival patient data from the Ivy Glioblastoma
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