Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry

Ararat Chakhoyan,Timothy F Cloughesy,Linda M Liau,Kevin Leu,Albert Lai,William Yong,Jingwen Yao,Benjamin M Ellingson,Whitney B Pope,Noriko Salamon,David A Nathanson,Richard G Everson,Phioanh L Nghiemphu,Robert M Prins

doi:10.1038/s41598-018-37564-w

Ararat Chakhoyan, Timothy F Cloughesy + Show 12 more

Open Access

https://doi.org/10.1038/s41598-018-37564-w

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Abstract

To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber.

Highlights

Neovascularization in gliomas plays an important role in response to anti-tumor strategies[1,2]
vessel size index derived from MRI (VSIMRI) maps showed potential hyper-dense and large vessels in the edges of the lesion as demonstrated with targets overlaid on VSI maps and confirmed with CD31 staining
The current study supports the hypothesis that VSI measured using magnetic resonance imaging (MRI) is highly correlated with the actual vessel caliber in underlying tumor tissue within high-grade gliomas

Summary

Introduction

Neovascularization in gliomas plays an important role in response to anti-tumor strategies[1,2]. A single study involving glioma patients confirmed the association between this model and vascular morphometry using CD34 endothelial cell marker expression[22]; despite the high number of patients and biopsy samples in each individual patient, this study reported very few identifiable vessels (~10 per sample) in some glioma patients, likely related to the small biopsy size (1–1.5 mm in diameter) In this current work, we quantified relative cerebral blood volume (rCBV) and VSIMRI using a spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence during DSC perfusion MRI in patients with high-grade gliomas. We hypothesized that Kiselev’s model, which provide several corrections (both diffusion and perfusion components) to estimate vessel size, would be strongly associated with VSIHistology

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