DCE-MRI in Glioma, Infiltration Zone and Healthy Brain to Assess Angiogenesis: A Biopsy Study

Abstract

Purpose To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma. Methods 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters. Results All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. Ktrans, kep and ve were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in Ktrans (p = 0.007) and ve (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones. Conclusion The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.

Focused ultrasound for the treatment of glioblastoma

“…The modified Response Assessment Neuro Oncology (RANO) criteria is used to evaluate for tumor growth versus pseudo progression and is especially helpful for longitudinal follow-up during adaptive clinical trials to mitigate false negative and false positive results [37]. Other advanced techniques to quantify vascular permeability with focused ultrasound studies include DCE MRI [38] and contrastenhanced (CE) T1 digital subtraction maps [39]. Dynamic susceptibility contrast (DSC) MRI also allows for quantification of blood volume, flow, and vessel size [40,41].…”

Exploratory Analysis of Serial 18F-fluciclovine PET-CT and Multiparametric MRI during Chemoradiation for Glioblastoma

“…High-grade gliomas (such as GBM) are characterised by disorganised vasculature, immature endothelial cells and increased permeability, with the margins associated with increased microvessel density (MVD) and neovascularization [ 28 ]. Studies of the tissue surrounding the enhancing portion of GBM have shown correlations between DCE-MRI parameters and expression of hypoxia-related proteins such as vascular endothelial growth factor-A (VEGF-A), suggesting that the DCE-MRI changes could be detecting regions of tissue hypoxia [ 12 , 13 , 29 ]. The finding of discordant DCE-MRI and 18 F-fluciclovine PET volumes outside of the Gd-T1 hyperintense regions raises the question of whether the two approaches could be used in a complementary fashion, potentially highlighting regions of increased glioma cellular density and areas of increased tissue hypoxia and therefore highlight different tumour niches.…”

“…Dynamic contrast-enhanced perfusion-weighted imaging (DCE) MRI has also been used to investigate vascular changes in glioblastoma (GBM), and studies have shown a correlation with tumour infiltrating beyond the enhancing margin and with markers of tissue hypoxia and neoangiogenesis [ 2 , 12 , 13 ]. In addition, some DCE-MRI quantitative biomarkers such as interstitial volume (v e ) may correlate with overall survival (OS) and tumour-associated microvascular proliferation [ 12 ].…”

Classification of Benign and Malignant Features of Glioma and Prediction of Early Metastasis and Recurrence Based on Enhanced MRI Imaging

“…Recent studies have proved that magnetic resonance imaging is of great value in the metabolic and physiological processes of gliomas, such as DWI [20]. DTI [21], MRS [22,23], DSC MRI [24,25], and DCE MRI have achieved good results in the evaluation of glioma grading [26,27]. In addition, the evaluation of tumor heterogeneity through imaging is of great benefit to guide the clinic, especially in the individualized treatment of gliomas.…”