MR Elastography Analysis of Glioma Stiffness and IDH1-Mutation Status

Abstract

Background and purpose: Our aim was to noninvasively evaluate gliomas with MR elastography to characterize the relationship of tumor stiffness with tumor grade and mutations in the isocitrate dehydrogenase 1 (IDH1) gene.

Materials and methods: Tumor stiffness properties were prospectively quantified in 18 patients (mean age, 42 years; 6 women) with histologically proved gliomas using MR elastography from 2014 to 2016. Images were acquired on a 3T MR imaging unit with a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected contralateral white matter, across tumor grade, and by IDH1-mutation status. The performance of the use of tumor stiffness to predict tumor grade and IDH1 mutation was evaluated with the Wilcoxon rank sum, 1-way ANOVA, and Tukey-Kramer tests.

Results: Gliomas were softer than healthy brain parenchyma, 2.2 kPa compared with 3.3 kPa (P < .001), with grade IV tumors softer than grade II. Tumors with an IDH1 mutation were significantly stiffer than those with wild type IDH1, 2.5 kPa versus 1.6 kPa, respectively (P = .007).

Conclusions: MR elastography demonstrated that not only were gliomas softer than normal brain but the degree of softening was directly correlated with tumor grade and IDH1-mutation status. Noninvasive determination of tumor grade and IDH1 mutation may result in improved stratification of patients for different treatment options and the evaluation of novel therapeutics. This work reports on the emerging field of "mechanogenomics": the identification of genetic features such as IDH1 mutation using intrinsic biomechanical information.

© 2018 by American Journal of Neuroradiology.

Figures

Fig 1.

Brain MRE experimental setup and image processing. A, Brain MRE soft pillow driver placed within the 8-channel MR imaging head coil and positioned beneath the head to induce shear waves in the brain. B, Axial T2 FLAIR image of a glioblastoma, IDH1 wild type (51-year-old man), with tumor denoted by a solid white line, and peritumoral edema, by a black dotted line. MRE shear wave image (C) and elastogram (D) or stiffness map display a soft tumor with a stiffness of 1.1 kPa in the tumor compared with 3.5 kPa in a size-matched region of unaffected white matter on the contralateral hemisphere.

Fig 2.

A, Gliomas are softer than normal brain tissue, compared with size-matched ROIs in the unaffected contralateral white matter (asterisk indicates P < .001). An outlier is indicated by a plus sign, and whiskers on the boxplot indicate the 25th and 75th percentiles. B, Glioma stiffness decreases with increasing tumor grade (double asterisks indicate P < .05).

Fig 3.

A, Comparison of the tumor stiffness (|G*|) between IDH1–R132H (n = 12) and wild type (WT) gliomas (n = 6). Gliomas with wild type IDH1 were significantly softer than gliomas with a mutation in IDH1–R132H (asterisk indicates P = .007). The whiskers on the boxplot indicate the 25th and 75th percentiles. B, Tumor shear stiffness by tumor grade for all patients in this study including IDH1–R132H mutated tumors (white circles) and wild type IDH1 (WT, black circles). The horizontal dotted line at 2.0 kPa separates the IDH1-mutated and wild type gliomas with a sensitivity and specificity of 83% and 100%. There is one secondary IDH1-mutated GBM with a low |G*| = 1.5 kPa, and it may be unique due to the secondary disease subtype.

Fig 4.

Stiffness heterogeneity of gliomas. Noncontrast, axial MRE magnitude images (left column), shear wave images (middle column), and elastograms (right column) for 2 patients with grade III gliomas. Images in the top row are from an oligodendroglioma with an IDH1–R132H mutation with |G*| = 3.3 kPa (a 31-year-old man), while the bottom row is from a diffuse astrocytoma with wild type IDH1 with |G*| = 1.7 kPa (a 44-year-old woman).