TMOD-16. COMPARING THE EFFECTS OF CIRCUMSCRIBED VERSUS INFILTRATIVE TUMOR GROWTH PATTERNS ON FUNCTIONAL CONNECTIVITY, HEMODYNAMIC PARAMETERS, AND BEHAVIOR IN A MOUSE GLIOMA MODEL

BACKGROUND: Gliomas can cause significant changes in normal brain function leading to behavior deficits. Functional connectivity (fc) disruptions may contribute to these deficits. However, investigating the effects of glioma growth on fc in humans is complicated by heterogeneity in lesion size, type, and location across subjects. In this study, we evaluated the effects of different patterns of growth on fc, hemodynamic parameters, and behavior in a controlled mouse glioma model. METHODS: 5x10(4) glioma cells growing in either a circumscribed (U87 PDE7B H217Q, n=13) or infiltrative (U87 PDE7B WT, n=14) pattern were stereotactically injected into the forepaw somatosensory cortex of adult nude mice. We monitored tumor burden with weekly bioluminescence imaging (BLI). Additionally, we evaluated fc with weekly functional connectivity optical intrinsic signal imaging (fcOIS). Fc was calculated between homotopic brain regions. Furthermore, cerebral blood flow (CBF) and hemodynamic lags were assessed. Lastly, we assessed performance on a somatomotor behavior battery during the 7(th) week post-injection. RESULTS: Mice with infiltrative tumors had more tumor burden then mice with circumscribed tumors. Furthermore, infiltrative tumors disrupted fc and produced hemodynamic lags earlier than circumscribed tumors. However, infiltrative tumors didn’t change CBF, while circumscribed tumors increased CBF near the injection site. Lastly, mice with infiltrative tumors exhibited somatomotor deficits, while mice with circumscribed tumors performed similar to sham mice (n=20). CONCLUSIONS: We were able to detect differences in fc disruptions in mice with gliomas growing in different patterns with fcOIS. Infiltrative tumors produced greater tumor burden and fc disruptions than circumscribed tumors. Additionally, hemodynamic lag was a better indicator of tumor burden than CBF. Lastly, infiltrative tumors induced behavior deficits during this study, while circumscribed tumors did not. A better understanding of how fc disruptions contribute to behavior deficits in glioma patients may lead to better patient risk stratification and improved behavior outcomes.