Brain tumor associated edema is a significant cause of patient morbidity and mortality often requiring continual treatment with differing levels of success across patients. Edema is a broad term that can indicate increased local water as well as diffusely infiltrating tumor cells. Edema is visualized as hyperintense regions on T2-weighted (T2W) magnetic resonance imaging (MRI) and is typically associated with blood-brain-barrier (BBB) breakdown and tumor aggressiveness. Understanding the molecular mechanisms driving imaging patterns of “edema” could provide insights into clinical imaging interpretation and treatment. We have an ongoing image-guided biopsy study that allows us to link biopsy molecular markers with locoregional MRI patterns of edema. Further, we previously developed a physics-based mathematical model to estimate spatial edema abundance (i.e., edema map) from T2W MRIs. Our goal was to identify connections between BBB-associated molecular factors and edema abundance in brain tumors. Our cohort included 38 patients (female: 15, male: 23) with 129 image-guided biopsies (female: 62, male: 67). We correlated image-localized edema map values with the mean transcriptional frequency for 57 genes related to BBB permeability. Additionally, we examined correlations separately according to patient reported sex (i.e., male and female) and imaging phenotype (i.e., ENH: enhancing and NE: non-enhancing). We utilized the Pearson correlation coefficient and multiple comparisons corrections with a 5% false discovery rate to determine significant relationships. For the overall cohort, we observed significant positive correlations for the markers HIF1A (p<0.001), and SOX2, which is indicative of proliferative potential, and modeled edema abundance. For NE samples, significant correlations included APOE (p=0.001), HIF1A (p<0.001), PIK3CA (p<0.001), PTCH1 (p<0.001), and SOX2 (p<0.001). Amongst female samples, a significant correlation with PTCH1 (p=0.002) was observed. There were no significant correlations noted for male and enhancing sub-cohorts. HIF1A is associated with hypoxia, while SOX2, PTCH1, and PIK3CA are all associated with cell proliferation. Further, APOE is often associated with severe brain swelling. Significant correlations between molecular markers of BBB and edema map values could lead to clinical biomarkers for edema,tumor aggressiveness, or therapeutic intervention.