Arterial Spin Labeling and Dynamic Susceptibility Contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma

S Ali Nabavizadeh,Jeffrey B Ware,John Detre,Steven Brem,Whitney Sarchiapone,Scott Levy,Stephen J Bagley,Christos Davatzikos,Samantha Guiry,Arati Desai,Hamed Akbari,Donald M O’Rourke,Timothy Prior,Ronald L Wolf,Maclean Nasrallah

doi:10.1038/s41598-019-45312-x

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a dismal prognosis. Significant challenges in the care of patients with GBM include marked vascular heterogeneity and arteriovenous (AV) shunting, which results in tumor hypoxia and inadequate delivery of systemic treatments to reach tumor cells. In this study, we investigated the utility of different MR perfusion techniques to detect and quantify arteriovenous (AV) shunting and tumor hypoxia in patients with GBM. Macrovascular shunting was present in 33% of subjects, with the degree of shunting ranging from (37–60%) using arterial spin labeling perfusion. Among the dynamic susceptibility contrast-enhanced perfusion curve features, there were a strong negative correlation between hypoxia score, DSC perfusion curve recovery slope (r = −0.72, P = 0.018) and angle (r = −0.73, P = 0.015). The results of this study support the possibility of using arterial spin labeling and pattern analysis of dynamic susceptibility contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma.

Highlights

Glioblastoma (GBM) contains irregular vascular proliferations that are not able to sufficiently oxygenate rapidly growing tumor tissue, resulting in a positive feedback loop of hypoxia and aberrant angiogenesis
Arterial spin Labeling (ASL) perfusion and susceptibility weighted imaging (SWI) have been successfully applied to detect and quantify AV shunting in arteriovenous malformations and arteriovenous fistulas in the brain by multiple investigators, including our group[9,10,11,12]
We investigated the utility of arterial spin Labeling (ASL) perfusion and principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) perfusion images to detect and quantify macrovascular AV shunting, as well as to infer capillary-level hemodynamics at the voxel level in patients with glioblastoma

Summary

Introduction

Glioblastoma (GBM) contains irregular vascular proliferations that are not able to sufficiently oxygenate rapidly growing tumor tissue, resulting in a positive feedback loop of hypoxia and aberrant angiogenesis. The presence of AV shunting in patients with GBM may have important therapeutic implications. Arteriovenous shunting results in poor delivery of oxygen to the tumor and can be associated with tumor hypoxia in GBM3. Arterial spin Labeling (ASL) perfusion and susceptibility weighted imaging (SWI) have been successfully applied to detect and quantify AV shunting in arteriovenous malformations and arteriovenous fistulas in the brain by multiple investigators, including our group[9,10,11,12]. We investigated the utility of ASL perfusion and principal component analysis (PCA) of DSC perfusion images to detect and quantify macrovascular AV shunting, as well as to infer capillary-level hemodynamics at the voxel level in patients with glioblastoma

Methods

Results

Discussion

Conclusion