Synopsis

Previous studies have shown good correlation between ASL and DSC vascular parameters as predictors of glioma grade, indication an option to omit DSC imaging in light of the recent finding of gadolinium deposition in the brain. However, in general these comparative studies were conducted before the recent update of the World Health Organisation classification of brain tumours. This study shows the potential of voxelwise correlations of vascular parameters obtained with ASL and DSC as predictors of IDH-mutation status in non-enhancing glioma and highlights that IDH-mutation status should be included in comparative studies of ASL and DSC vascular parameters in glioma.

Introduction

Methods

Sixteen patients with non-enhancing glioma and confirmed IDH-mutation status (next generation sequencing, 6 IDH-wildtype and 10 IDH-mutated) are included within this study. Patient characteristics are stated in Table 1. Patients underwent 3T MRI scanning (GE, Milwaukee, WI, USA) with a standardised brain tumour imaging protocol extended with advanced imaging. Image acquisition included 3D sagittal CUBE FLAIR (0.8x0.8 mm² in plane resolution, slice thickness 1.6mm, TR/TE/TI= 6.1ms/2.1ms/1897ms ), 3D spiral pseudocontinuous ASL with time-encoded labelling ( 7 effective label delays from 0.8 to 2 s, reconstruction matrix 128x128x42, resolution 1.9x1.9x3.5 mm³), and 2D DSC imaging (122 TRs, TR/TE 1500m/18.6ms, 15 slices, voxel size: 1.875 x 1.875 x 4 mm³) in which a bolus of 7.5ml of gadolinium-based contrast agent (Gadovist, Bayer, Leverkussen, GE) was injected. A pre-load bolus of equal size was given approximately 5 minutes prior to DSC imaging.

DSC images were motion corrected (mcflirt in FSL, version 5.0.9, Oxford, UK) and linearly registered to the FLAIR images (flirt in FSL). Relative CBV (rCBV) maps were calculated via previously described methods⁵. In addition, relative CBF maps were calculated with verbena in FSL, which uses a Bayesian framework for fitting rCBF⁶. Transit time corrected CBF maps were calculated from the pCASL imaging series, based on previously described methods⁷ and linearly registered to the FLAIR images.

The glioma region of interest (ROI) was determined via manual segmentation of the hyperintense FLAIR region. Normalised histograms were calculated across the ROI to investigate differences in ASL-CBF, DSC-rCBV, and DSC-rCBF between IDH-mutated and IDH-wildtype tumours. Voxel-wise Pearson’s linear correlation coefficients (ρ) within this ROI were calculated between ASL-CBF and DSC-rCBV, and between ASL-CBF and DSC-rCBF.

Results

The normalised histograms (Figure 1) indicate that IDH-wildtype glioma has higher values for ASL-CBF, DSC-rCBV, and DSC-rCBF than IDH-mutated glioma. IDH-wildtype glioma has a significantly lower ρ_{ASL-CBF vs DSC-rCBV} and ρ_{ASL-CBF vs DSC-rCBF} than IDH-mutated glioma (0.14 ± 0.21 and 0.15 ± 0.19 compared to 0.39 ± 0.11 and 0.38 ± 0.11, respectively, two-sample t-tests p < 0.005, Figures 2 & 3).

Discussion

To the best of our knowledge this study is the first to indicate that IDH-mutation status of non-enhancing glioma may affect the correlation between ASL-CBF and DSC-rCBF/rCBV. The decreased correlation between ASL and DSC-based vascular parameters in IDH-wildtype gliomas may be due to the more angiogenic phenotype in these more aggressive tumours, including irregular vasculature such as larger and leaky vessels⁸. This in turn can lead to arteriovenous shunting of blood, which will result in overestimation of perfusion in ASL due to presence of labelled water in the venous vasculature⁹.

This works shows the potential of voxelwise correlations of ASL-CBF and DSC-rCBF/DSC-rCBV as predictor of IDH-mutation status in non-enhancing glioma and highlights that IDH-mutation status should not be neglected when performing comparative studies of ASL and DSC perfusion parameters in glioma. Future work includes expansion of the current patient cohort (part of the ongoing iGENE study) and matching the MRI vascular parameters with their histological counterparts in targeted biopsies of glioma tissue.

Acknowledgements

References

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