Quantification of glioblastoma mass effect by lateral ventricle displacement

Tyler C. Steed,Clark C. Chen,Bob S. Carter,Kunal S. Patel,Anders M. Dale,Michael G. Brandel,Jeffrey M. Treiber

doi:10.1038/s41598-018-21147-w

Abstract

Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were determined. Associations with patient survival and tumor genomics were investigated using data from The Cancer Genome Atlas (TCGA). Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not explained by tumor volume, as defined by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which accounted for both age and Karnofsky’s Performance Scale (KPS) (p = 0.006). Glioblastomas with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes associated with tumor invasion. Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.

Highlights

Glioblastoma is the most common form of adult brain cancer and remains one of the deadliest of human cancers[1]
Using automatic methods of segmentation developed by our laboratory[8,9], we propose a novel radiographic parameter for quantifying mass effect related to glioblastoma, which we termed lateral ventricle displacement (LVd)
LVd was determined for 550 subjects without diagnosis of brain tumor from the Information eXtraction from Images (IXI) cohort as well as 214 The Cancer Imaging Archive (TCIA) glioblastoma subjects

Summary

Introduction

Glioblastoma is the most common form of adult brain cancer and remains one of the deadliest of human cancers[1]. Assessment of glioblastoma tumor burden relies on interpretation of magnetic resonance imaging (MRI) in the context of clinical evaluation[2]. The two MR sequences most commonly used in the clinical setting to assess glioblastoma tumor burden include: contrast enhancement (CE) sequences and fluid-attenuated inversion recovery (FLAIR) sequences[3]. Because the skull encompasses a fixed volume, growth of neoplastic tissue necessarily results in the displacement of normal cerebrum[6]. While CE volume (CEV) and FLAIR hyper-intensity volumes (FHV) are often used as clinical proxy of glioblastoma tumor burden, these variables provide limited information about the mass effect related to glioblastoma. LVd measures the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to the center of mass of the lateral ventricle volume from the standard Montreal Neurological Institute (MNI) template brain (Fig. 1). Elevated LVd in glioblastoma is associated with increased expression of genes related to increased cellular proliferation, while tumors with low levels of LVd expressed genes involved in cell migration and motility

Methods

Results

Conclusion