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J Clin Neurosci. 2018 Sep;55:86-92. doi: 10.1016/j.jocn.2018.06.018. Epub 2018 Jun 20.

Molecular physiology of contrast enhancement in glioblastomas: An analysis of The Cancer Imaging Archive (TCIA).

Author information

1
Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA. Electronic address: treiber@bcm.edu.
2
Department of Neurosurgery, Emory University, Atlanta, GA, USA. Electronic address: tsteed@emory.edu.
3
Department of Neurosurgery, University of California, San Diego, La Jolla, CA, USA. Electronic address: mbrandel@ucsd.edu.
4
Department of Neurosurgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. Electronic address: kunalpatel@mednet.ucla.edu.
5
Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USA. Electronic address: amdale@ucsd.edu.
6
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA. Electronic address: bcarter@mgh.harvard.edu.
7
Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA. Electronic address: ccchen@umn.edu.

Abstract

The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CEi), the intensity heterogeneity in CE (CEh), and volumetric ratio of CE to necrosis (CEr). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CEi was associated with expression of genes that mediate inflammatory responses. High CEh was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CEr was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.

KEYWORDS:

Contrast enhancement; Gene expression; Glioblastoma; MRI; Magnetic resonance imaging

PMID:
29934058
DOI:
10.1016/j.jocn.2018.06.018
[Indexed for MEDLINE]

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