Glioma is a devastating, invasive form of brain cancer with a 36-month median overall survival. The highest grade tumors, glioblastomas, have an even shorter prognosis of about 15 months. A glioma often requires an intense combination of treatments including surgery, chemotherapy, and radiotherapy, often resulting in very damaging side effects. Due to their sensitive location in the brain, which is often difficult to access because of the skull, gliomas are most often visualized using magnetic resonance imaging (MRI), a non-invasive imaging method. Because high grade gliomas (HGGs) are highly aggressive and recurrence is common, patients diagnosed with these tumors stand to significantly benefit from novel, advanced MRI techniques that can lead to better patient-specific tumor characterization and improved response assessment. Magnetic resonance elastography (MRE) is a MRI-based method that measures the mechanical properties of tissue, and has the potential to significantly enhance the ability to distinguish malignant vs. healthy brain tissue by determining spatial differences in physical stiffness. We investigated whether the addition of MRE to standard clinical glioma MRI protocols would provide a more accurate understanding of the extent of tumor invasion. Using routinely available T2-weighted and contrast enhancing T1-weighted clinical MRI images, the Swanson lab has developed the Proliferation-Invasion (PI) model of brain tumor growth. Using this model, we quantify the relative diffusion (D) and proliferation (�) of tumor cells as D/�. Clinical MRIs were segmented in order to parameterize the model and determine these tumor growth metrics for each patient in our retrospective study. Next, we compare these tumor growth metrics with MRE features of physical stiffness of malignant tissue to determine whether there are correlations with the PI model's kinetic parameters. We hypothesized that MRE stiffness measurements would be associated with the PI model of glioma growth and may provide additional patient-specific tumor characterization information useful for optimally choosing treatment and understanding treatment response. MRE has the potential to be a useful addition to the clinical management of glioma and be integral to further understanding tumor growth and invasiveness.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and is linked to poor survival in affected patients due to its invasive and aggressive nature. The potential role of sexual dimorphism in GBM outcomes has long been overlooked. Notably, males and females differ in tumor behavior across many cancers1, which may be attributable to differences in genetic makeup and physiology, and in GBM there is a difference in incidence rate between males and females. The aim of the study was to investigate sex differences in GBM patients and compare median survival outcomes (OS) and progression-free survival outcomes (PFS) between sexes based on tumor location, laterality, age, tumor volume, and extent of resection. Patients who received standard-of-care (Stupp protocol) consisting of surgical intervention, concomitant chemoradiation, and 6 cycles of adjuvant temozolomide (TMZ) were included in this study to investigate sex differences in tumor characteristics (n = 216; males: n = 129, females: n = 87). Pre-surgical MRIs, specifically T1Gd sequences, were analyzed to determine tumor laterality and location. The patient cohort was divided into two groups indicating the extent of resection (EOR) they received: Gross Total Resection (GTR) and Subtotal Resection (STR). Additionally, the patient cohort was split into three age groups (Group I: 18-29, Group II: 30-49, and Group III: >50). Analyses were done using independent t-test and Cox proportional hazard modeling to determine which variables affect patient survival. The log-rank test was utilized to compare differences in survival rate in Kaplan-Meier analysis.
Overall, our results suggest that female patients receiving standard-of-care may have a better prognosis than male patients. There was a significant difference in OS and PFS in females showing an increase in survival. Additionally, survival was significantly different between sexes following resection, with female patients receiving STR or GTR having longer OS and PFS than males. The difference in median OS between sexes is more pronounced among younger patients. Among five different brain locations, female patients who possess a frontal lobe tumor may live longer than male patients. The apparent difference in OS for patients living >1000 days in the Kaplan-Meier plot warrants further investigation in a larger cohort. Following tumor resection, female patients with a frontal lobe tumor may survive longer in comparison to male patients. Comparing brain hemispheres, patients who possessed a tumor on the left may survive longer. Investigating tumor location and tumor laterality, our results suggests that female patients with a left frontal lobe tumor show a significant survival advantage in comparison to females who possess a right frontal lobe tumor.

Glioblastomas (GBMs) are the most aggressive type of brain tumor. GBMs are known for their aggressive and invasive nature because of their ability to easily grow and spread into the surrounding areas of the brain. The annual incidence rate of GBM is 2 to 3 people per 100,000 people in the United States and Europe, and the median survival for patients with an aggressive GBM is 14.6 months. The standard of care for GBMs follows a protocol of surgery, radiation concurrent with the chemotherapeutic drug, temozolomide (TMZ), followed by the administration of up to 6 cycles of TMZ in an adjuvant setting. The objective of this retrospective study was to compare the clinical responses in a patient cohort from varying amount of adjuvant TMZ cycles. Using patient overall survival, the responses to TMZ cycles were tested within different groupings, and the patient covariates were analyzed. The results from the different analyses indicated that survival success of GBM patients is not solely dependent on the number of TMZ cycles, but that other covariates can also affect survival outcomes.

Tumor associated microglia-and-macrophages (TAMS) may constitute up to 30% of the composition of glioblastoma. Through mechanisms not well understood, TAMS are thought to aid the progression and invasiveness of glioblastoma. In an effort to investigate properties of TAMS in the context of glioblastoma, I utilized data from a PDGF-driven rat model of glioma that highly resembles human glioblastoma. Data was collected from time-lapse microscopy of slice cultures that differentially labels glioma cells and also microglia cells within and outside the tumor microenvironment. Here I show that microglia localize in the tumor and move with greater speed and migration than microglia outside the tumor environment. Following previous studies that show microglia can be characterized by certain movement distributions based on environmental influences, in this study, the majority of microglia movement was characterized by a power law distribution with a characteristic power law exponent lower than outside the tumor region. This indicates that microglia travel at greater distances within the tumor region than outside of it.