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

Abstract

IntroductionAccurate 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.MethodsWe 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.ResultsA 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).ConclusionThis 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.

A multi-sequence and habitat-based MRI radiomics signature for preoperative prediction of MGMT promoter methylation in astrocytomas with prognostic implication

“…Thus when incorporating these factors into the radiomics signature, there was no additional positive effect on the improvement of the prediction performance, but rather an increased complexity of the prediction model. Additionally, even though it was reported that ADC values were correlated with MGMT promoter methylation and prognosis in GBM [22,32,33], our results indicated that radiomic features extracted from T1-CE and T2-FLAIR sequences performed better than those extracted from the ADC sequence. A potential reason for this observation is the relatively poor imaging resolution of ADC, which limited the stability and robustness of the derived radiomics features.…”

Imaging Correlates of Adult Glioma Genotypes

“…Also, in the latter study no effect on overall survival of MGMT status was seen, contrary to expectations. Rundle-Thiele et al (95) demonstrated that these discrepancies also may be attributed to differences in methodology. In the same patient population, they used both a minimum ADC region of interest and a histogram analysis and found a trend toward higher mean minimum ADC ratio and significantly lower ADC L in methylated tumors.…”

Clinically Relevant Imaging Features forMGMTPromoter Methylation in Multiple Glioblastoma Studies: A Systematic Review and Meta-Analysis

“…25 One study was prospective in design. 26 Twenty studies were retrospective, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]27,28,[30][31][32] and 1 study did not explicitly state the design. 29 Study enrollment was consecutive in 3 studies 16,18,25 and not explicit in the remaining studies.…”

“…29 Study enrollment was consecutive in 3 studies 16,18,25 and not explicit in the remaining studies. Fifteen of 22 studies used methylation-specific polymerase chain reaction as a reference standard to detect MGMT methylation, 11,[14][15][16][19][20][21][22][23][24]27,28,[30][31][32] with the other studies using DNA methylation analysis, 18 pyrosequencing, 13 immunohistochemical staining, 29 or multiplex ligation-dependent probe amplification, 26 with the method not being stated in 3 studies. 12,17,25…”

“…Ten studies used 3T scanners, 12,13,15,16,[18][19][20][21]23,25 5 studies used 1.5T scanners, 22,24,[29][30][31] 3 studies used 1.5T and 3T scanners, 17,27,28 and 4 studies did not state the scanner strength. 11,14,26,32 A variety of different MR imaging techniques was used to predict MGMT promoter methylation: conventional MR imaging in 11 studies, 11,13,14,17,[26][27][28][29][30][31][32] DWI in 4 studies, 19,20,22,24 CT/DWI/DTI/DSC in 1 study, 25 DWI/DSC/SWI in 1 study, 18 DCE/DTI in 1 study, 21 DWI/arterial spin-labeling in 1 study, 12 DSC in 1 study, 23 DCE in 1 study, 16 and amide proton transfer in 1 study. 15 Five studies used radiomics approaches from machine learning-based classification.…”