Abstract 2066: Comparison of ADC MRI, T2-weighted MRI and combined T2-weighted/T1-contrast-enhanced/ADC MRI quantification of cerebral edema in an intracranial glioma model
Authors: Lister Deanne , Balagurunathan Deepa , Baugher Meridith , Flecha Athena , Trachet Erin , Wise Scott , Leopold W.R. , McConville Patrick 
Published: May 2015

Abstract
Introduction: Brain edema is a prominent feature of brain cancer and contributes to neurologic dysfunction and impaired quality of life. Efficacious treatments with minimal side effects are sought after in this indication. 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. Multiple MRI scan protocols were used to detect tumor, edema and fluid and quantify the volume of each. Apparent diffusion coefficient (ADC) based quantification was compared with a combined T2-weighted/T1-contrast-enhanced method.
Methods: Female nude mice were implanted intracranially with 1x106 U251-luc (Luc-mCherry) glioma cells. A multi-modal MRI scan approach consisting of T2-weighted (T2w), T1-weighted (T1w) contrast-enhanced and ADC scans were used to detect and delineate tumor, fluid, edema and normal brain tissue. These scans yielded:
V(T2): volume defined by hyper intense T2 - assumed to be volume[tumor + edema + fluid]
V(CE): contrast enhancing volume - assumed to be volume[tumor]
V(ADC_high): volume with ADC &gt; threshold value that delineated fluid - assumed to be volume[fluid]
A combinatorial approach to yield the volume of edema, V(edema) was used with:
V(edema) = V(T2) - V(CE) - V(ADC_high)
This approach was then used to examine the ADC and T2 distributions within each of these volumes to determine the sensitivity of T2 and ADC alone for distinguishing tumor, fluid and edema and quantifying edema volume.
Results: The edema incidence was 100% based on T2w and T1w CE scans in orthotopically implanted U251-luc (Luc-mCherry) gliomas. Edema volume could be quantified using the multi-modal MRI scan protocol. Edema progression occurred with increasing tumor volume over time. Regions of edema exhibited greater T2 and ADC values compared to tumor tissue regions (that also had a greater T2 signal than normal tissue). This is consistent with edematous tissue water content, compared with tumor tissue and normal brain. The use of T2 and ADC alone provided good delineation of fluid from other tissues, and reasonable delineation of edema from tumor (based on the initial compartmentalization analysis). However, the combined T2w/ T1w-CE/ADC protocol was considered more precise.
Conclusion: 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. The application of multi-parametric MRI was an effective method for quantifying cerebral edema longitudinally in vivo.
Citation Format: Deanne Lister, Deepa Balagurunathan, Meridith Baugher, Athena Flecha, Erin Trachet, Scott Wise, W.R. Leopold, Patrick McConville. Comparison of ADC MRI, T2-weighted MRI and combined T2-weighted/T1-contrast-enhanced/ADC MRI quantification of cerebral edema in an intracranial glioma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2066. doi:10.1158/1538-7445.AM2014-2066