Glioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) ( N = 184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established ( N = 40 with SOC, N = 19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM ( N = 144 with SOC, N = 111 without SOC). When stratified by sex, the survival benefit of cystic GBM was only preserved in male patients ( N = 303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.

We analyze the wave-speed of the Proliferation Invasion Hypoxia Necrosis Angiogenesis (PIHNA) model that was previously created and applied to simulate the growth and spread of glioblastoma (GBM), a particularly aggressive primary brain tumor. We extend the PIHNA model by allowing for different hypoxic and normoxic cell migration rates and study the impact of these differences on the wave-speed dynamics. Through this analysis, we find key variables that drive the outward growth of the simulated GBM. We find a minimum tumor wave-speed for the model; this depends on the migration and proliferation rates of the normoxic cells and is achieved under certain conditions on the migration rates of the normoxic and hypoxic cells. If the hypoxic cell migration rate is greater than the normoxic cell migration rate above a threshold, the wave-speed increases above the predicted minimum. This increase in wave-speed is explored through an eigenvalue and eigenvector analysis of the linearized PIHNA model, which yields an expression for this threshold. The PIHNA model suggests that an inherently faster-diffusing hypoxic cell population can drive the outward growth of a GBM as a whole, and that this effect is more prominent for faster proliferating tumors that recover relatively slowly from a hypoxic phenotype. The findings presented here act as a first step in enabling patient-specific calibration of the PIHNA model.

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Fluid intelligence (Gf) has been defined as the ability to reason and solve previously unseen problems. Links to Gf have been found in magnetic resonance imaging (MRI) sequences such as functional MRI and diffusion tensor imaging. As part of the Adolescent Brain Cognitive Development Neurocognitive Prediction Challenge 2019, we sought to predict Gf in children aged 9-10 from T1-weighted (T1W) MRIs. The data included atlas-aligned volumetric T1W images, atlas-defined segmented regions, age, and sex for 3739 subjects used for training and internal validation and 415 subjects used for external validation. We trained sex-specific convolutional neural net (CNN) and random forest models to predict Gf. For the convolutional model, skull-stripped volumetric T1W images aligned to the SRI24 brain atlas were used for training. Volumes of segmented atlas regions along with each subject's age were used to train the random forest regressor models. Performance was measured using the mean squared error (MSE) of the predictions. Random forest models achieved lower MSEs than CNNs. Further, the external validation data had a better MSE for females than males (60.68 vs. 80.74), with a combined MSE of 70.83. Our results suggest that predictive models of Gf from volumetric T1W MRI features alone may perform better when trained separately on male and female data. However, the performance of our models indicates that more information is necessary beyond the available data to make accurate predictions of Gf.

Immune therapies have shown promise in a number of cancers, and clinical trials using the anti-PD-L1/PD-1 checkpoint inhibitor in lung cancer have been successful for a number of patients. However, some patients either do not respond to the treatment or have cancer recurrence after an initial response. It is not clear which patients might fall into these categories or what mechanisms are responsible for treatment failure. To explore the different underlying biological mechanisms of resistance, we created a spatially explicit mathematical model with a modular framework. This construction enables different potential mechanisms to be turned on and off in order to adjust specific tumor and tissue interactions to match a specific patient's disease. In parallel, we developed a software suite to identify significant computed tomography (CT) imaging features correlated with outcome using data from an anti-PDL-1 checkpoint inhibitor clinical trial for lung cancer and a tool that extracts these features from both patient CT images and “virtual CT” images created from the cellular density profile of the model. The combination of our two toolkits provides a framework that feeds patient data through an iterative pipeline to identify predictive imaging features associated with outcome, whilst at the same time proposing hypotheses about the underlying resistance mechanisms.