Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method

Journal of Medical Radiation Sciences

Dayle Rundle-Thiele BSc⁶  Bryan Day PhD⁴  Brett Stringer PhD⁴  Michael Fay FRACP, FRANZCR⁹  Jennifer Martin FRACP, PhD⁷  Rosalind L. Jeffree FRACS⁸  Paul Thomas FRACP²  Christopher Bell BSc⁶  Olivier Salvado PhD³  Yaniv Gal PhD¹  Alan Coulthard FRANZCR⁵  Stuart Crozier PhD¹ 

[1] Centre for Medical Diagnostic Technologies in Queensland, University of Queensland, Brisbane, Queensland, Australia;Queensland PET Service, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia;CSIRO Digital Productivity Flagship, CSIRO, Herston, Queensland, Australia;Brain Cancer Research Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia;Discipline of Medical Imaging, University of Queensland, St Lucia, Queensland, Australia;Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia;Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia;Department of Neurosurgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia;Department of Radiation Oncology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

关键词: ADC;    diffusion MRI;    glioblastoma;    MGMT;   

DOI  :  10.1002/jmrs.103

来源: Wiley

【 摘 要 】

Abstract

Introduction

Accurate knowledge of O⁶-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC.

Methods

We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods.

Results

A strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246).

Conclusion

This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.

【 授权许可】

CC BY-NC   
© 2015 The Authors. Journal of Medical Radiation Sciences published by Wiley Publishing Asia Pty Ltd on behalf of Australian Institute of Radiography and New Zealand Institute of Medical Radiation Technology.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.