Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Vallatos, A., Al-Mubarak, H.F.I., Birch, J.L., Gallagher, L., Mullin, J.M., Gilmour, L., Holmes, W.M. and Chalmers, A.J. (2019) Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region. Journal of Magnetic Resonance Imaging, 50(2), pp. 529-540. (doi: 10.1002/jmri.26580) (PMID:30569620)

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Abstract

Background: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. Purpose: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type: Animal model. Subjects: Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences: 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment: Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.” Statistical Tests: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results: High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy.

Item Type:Articles
Additional Information:Contract grant sponsor: The Brain Tumour Charity; Contract grant number: 26/160.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gallagher, Mrs Lindsay and Birch, Dr Joanna and Mullin, Mr James and Holmes, Dr William and Vallatos, Dr Antoine and Chalmers, Professor Anthony and Al-mubarak, Haitham Farooq Ibrahim
Authors: Vallatos, A., Al-Mubarak, H.F.I., Birch, J.L., Gallagher, L., Mullin, J.M., Gilmour, L., Holmes, W.M., and Chalmers, A.J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Magnetic Resonance Imaging
Publisher:Wiley
ISSN:1053-1807
ISSN (Online):1522-2586
Published Online:19 December 2018
Copyright Holders:Copyright © 2018 International Society for Magnetic Resonance in Medicine
First Published:First published in Journal of Magnetic Resonance Imaging 50(2):529-540
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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