Abstract

BackgroundThe microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification.MethodsData from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples.ResultsSignificant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2–2.5 times higher rCBV values in IDH-wildtype glioblastoma samples.ConclusionsThe proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

Highlights

  • The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for highgrade glioma classification

  • The general purpose of our study is to evaluate the potential use of relative cerebral blood volume (rCBV), calculated with the ONCOhabitats methodology, to detect the presence or absence of microvessels in different regions of Isocitrate dehydrogenase (IDH)- wildtype glioblastoma, and to find differences in vascularity between IDH-wildtype glioblastoma and IDH-mutant astrocytoma

  • IDH‐wildtype glioblastomas From 38 IDH-wildtype glioblastoma, 14 were not included because of incomplete Magnetic Resonance Imaging (MRI) studies (W04, W06, W16, W19, W20, W21, W26, W27, W28, W32, W39, W45, W53, and W54); From the 24 included patients, 3 patients were discarded due to inability to correctly overlay the image of the resected tumor over the MRI (W08, W09, and W11)

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Summary

Introduction

The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for highgrade glioma classification. One of the results of these mechanisms is microvascular proliferation (MVP), which generally occurs in the core of glioblastomas by sprouting new vascular microvessels from pre-existing ones, depending on the presence of hypoxia [3]. These pathologic heterogeneity features, including vascular proliferation, robust angiogenesis and extensive microvasculature heterogeneity could vary depending on IDH-mutation status in high-grade gliomas [6]. The result of MVP is the formation of large-lumen microvessels, usually with a glomeruloid appearance, that represent one of the main histopathologic hallmark of glioblastoma [9]

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