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

Rundle-Thiele, Dayle, Day, Bryan, Stringer, Brett, Fay, Michael, Martin, Jennifer, Jeffree, Rosalind L., Thomas, Paul, Bell, Christopher, Salvado, Olivier, Gal, Yaniv, Coulthard, Alan, Crozier, Stuart and Rose, Stephen (2015) Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method. Journal of Medical Radiation Sciences, 62 2: 92-98. doi:10.1002/jmrs.103


Author Rundle-Thiele, Dayle
Day, Bryan
Stringer, Brett
Fay, Michael
Martin, Jennifer
Jeffree, Rosalind L.
Thomas, Paul
Bell, Christopher
Salvado, Olivier
Gal, Yaniv
Coulthard, Alan
Crozier, Stuart
Rose, Stephen
Title Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method
Journal name Journal of Medical Radiation Sciences   Check publisher's open access policy
ISSN 2051-3909
Publication date 2015-06-01
Sub-type Article (original research)
DOI 10.1002/jmrs.103
Open Access Status DOI
Volume 62
Issue 2
Start page 92
End page 98
Total pages 7
Place of publication Bognor Regis, United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted 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.
Keyword MGMT
ADC
Diffusion MRI
Glioblastoma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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