ANGI-01. CORRELATION BETWEEN HISTOLOGICAL AND MRI MEASURES OF INFILTRATION IN A PRECLINICAL GLIOBLASTOMA MODEL. (5th November 2018)

• Record Type: Journal Article
• Authors: Thompson, Gerard; Vallatos, Antoine; Al-Mubarak, Haitham; Gilmour, Lesley; Birch, Joanna; Gallagher, Lindsay; Mullin, James; Waldman, Adam; Holmes, William; Chalmers, Anthony
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi28
• Page End: vi28
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.103
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: Maximal safe cytoreductive surgery is the therapeutic ideal in GBM. Occult, non-enhancing, infiltrative disease ultimately drives treatment failure. Diffusion-weighted imaging (DWI) assessment of tumor margins through apparent diffusion coefficient (ADC) transition coefficients shows promise in non-invasive molecular subtyping and relating potentially-invasive behavior to survival. ADC non-specificity limits biomarker interpretation. We aimed to explore histological tumor cell burden relationship to ADC measurements at the macroscopic margin in a GBM model. METHODS: G7 GBM orthotopic xenografts were implanted into nude mice. T2-, and diffusion-weighted images were acquired at 7T. Brains were extracted and fresh-frozen to minimise fixation artefacts and preserve morphology. Cryosections were stained with human leucocyte antigen (HLA) marker specific for human-derived GBM cells. Confocal HLA photomicrographs (10x) and high resolution T2w MRI were linearly co-registered and resampled to match DWI. Macroscopic tumour margin was visually delineated using the low ADC/high-T2w-signal region. Linear profiles perpendicular to these boundary voxels produced serial, centrifugal, spatially-congruent measurements of ADC and HLA across the infiltrating edge over 0.7mm. Spearman's rho was calculated in each subject for every profile. RESULTS: 5 mice were suitable for analysis. In 72% of tumor boundaries (n=562), there was a statistically significant (p<0.05) inverse correlation (<-0.8) between ADC and HLA. Areas with insignificant/positive correlation represented distinct physical boundaries such as pia/ependyma or artefact. DISCUSSION: Characterizing microinvasive disease which ultimately leads to treatment failure in maximally-resected GBM is challenging. Research dwells on the enhancing disease which is excised. Margin assessment provides an opportunity to characterize tumor behavior at the crucial interface between dividing bulk tumor and the parenchymal infiltration which predicates recurrence. The spatially-consistent inverse correlation between tumor margin HLA and ADC values for almost all profiles at the tumor-parenchyma interface indicates that ADC transition profiles relate to tumor infiltration as previously hypothesised, with lower ADC related to higher tumor burden.