Abstract

Biomechanical forces are known to affect tumor growth and evolution [1]. Likewise, tumor growth drives physical changes in the micro-environment that affect tissue solid and fluid mechanics. Tumor mass effect, resulting from rapid tumor cell proliferation, has been shown to be prognostic for poor outcome in glioblastoma (GBM) patients and to be associated with the expression of gene signatures consistent with proliferative growth phenotype [2]. Similarly, elevated interstitial fluid flow (IFF) has been shown to drive GBM invasion [3]. This study investigates the relationship between tumor mass effect, diffusion, perfusion and IFF in GBM using anatomical (pre- and post-contrast T1 weighted, T2/FLAIR) and quantitative MR imaging (Dynamic Contrast Enhanced (DCE) MRI, and Diffusion Weighted Imaging (DWI)). We use data from 39 patients from the Ivy Glioblastoma Atlas Project (Ivy GAP)[4] which provides matched imaging, ISH, RNA, gene expression and clinical data over the course of treatment. We analyze pre-operative anatomic imaging data to determine the tumor-induced mass effect in each patient using quantitative measures such as ‘Lateral ventricle displacement’ [2]. Perfusion and diffusion measures are derived from pre-operative DCE and DWI imaging. Additionally, we estimate IFF velocities in the tumor region using DCE imaging data in combination with a computational model of fluid flow [5]. We will report the results of quantitative imaging analysis in relation to tumor mass effect and examine correlations with biological tumor characteristics and treatment outcome. We further investigate our findings in patient-derived xenograft models of GBM. References: [1] R.K. Jain et al. Annu. Rev. Biomed. Eng., 2014, 16, 321–346. [2] T.C. Steed et al. Scientific Reports, 2018, 8, 2827. [3] K.M. Kingsmore et al. Integr. Biol., 2016, 8 1246-1260 [4] N. Shah et al. Data from Ivy GAP. The Cancer Imaging Archive 2016. [5] K.M. Kingsmore et al. APL Bioengineering (In press).

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