Abstract B152: MR-based assessment and quantification of cerebral edema in an orthotopic mouse glioma model.

Introduction: Brain edema is a prominent feature of brain cancer and contributes to neurologic dysfunction and impaired quality of life. While corticosteroids are the standard of care, improved treatments that are more efficacious and reduce side effects are sought after. In discovery of novel therapies for edema, animal brain tumor models that show relevant, reproducible and high incidence of tumor and cerebral edema are needed. Additionally, quantitative, non-invasive methods for detecting and measuring brain tumor associated edema are needed to facilitate therapeutic discovery efforts. In this work, an intracranial U251-luc human glioma model was characterized for edema incidence and progression. MRI-based relaxivity and contrast-enhancement protocols for edema detection and delineation from tumor tissue, were tested and characterized in the model. Methods: Female nude mice were implanted intracranially with 1×10∧6 U251-luc (Luc-mCherry) glioma cells. Tumor volume assessment was performed by manual segmentation of T1-weighted, gadolinium-enhanced anatomical brain images based on the assumption of tumor enhancement due to leaky vessels or compromised blood-brain barrier. Edema assessment was performed by manual segmentation of T2-weighted anatomical brain images based on the assumption that enhancing regions include tumor tissue in addition to regions of brain edema. The difference in T2-weighted and T1-weighted volumes was assumed to be edema. T2 maps were also generated over the whole brain to measure T2 values over the respective regions of interest, and confirm the differentiation between tumor tissue and edema. Results: Edema volume was successfully distinguished from contrast enhancing tumor tissue and quantified in orthotopically implanted U251-luc (Luc-mCherry) glioma. Incidence was 100%. Edema progression occurred with increasing tumor volume over time. Regions of edema exhibited greater T2 values compared to tumor tissue regions (that also had greater T2 than normal tissue). This is consistent with edematous tissue water content, compared with tumor tissue and normal brain. These results support the use of intracranial U251-luc (Luc-mCherry) as a reliable model for studying the effects of therapies targeting tumor-related cerebral edema, and the application of MR imaging for quantifying those effects real-time in vivo. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B152. Citation Format: Deanne R. Lister, Deepa Balagurunathan, Meridith Baugher, Erin Trachet, Patrick McConville, Scott Wise, W.R. Leopold. MR-based assessment and quantification of cerebral edema in an orthotopic mouse glioma model. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B152.