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
Centre for Clinical Research, University of Queensland Brisbane, Queensland, Australia.
Brain Cancer Research Unit, Queensland Institute of Medical Research Brisbane, Queensland, Australia.
J Med Radiat Sci. 2015 Jun;62(2):92-8. doi: 10.1002/jmrs.103. Epub 2015 Apr 16.
Accurate knowledge of O(6)-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.
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.
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).
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.
准确了解胶质母细胞瘤（GBM）患者的O(6)-甲基鸟嘌呤甲基转移酶（MGMT）基因启动子亚型对于治疗至关重要。然而，这项检测并非总能进行。术前扩散磁共振成像（dMRI）可用于通过表观扩散系数（ADC）探究肿瘤生物学特性；然而，其作为预测MGMT状态替代指标的能力结果不一。我们调查了这是否是由于分析ADC所用方法的差异所致。
我们对32例已测定MGMT状态的GBM患者进行了回顾性研究。使用匹配的术前MRI数据计算肿瘤强化区域内的ADC。使用两种已发表的ADC方法检查ADC与MGMT之间的关系。
观察到“最小ADC”测量值与甲基化状态之间有很强的趋势。与未甲基化的MGMT组相比，甲基化组中最小ADC升高的可能性更大（U = 56，P = 0.0561）。相比之下，采用双混合模型直方图方法，直方图中“低ADC”成分的平均测量值显著降低与MGMT启动子甲基化亚型相关（P < 0.0246）。
本研究表明，在同一患者队列中，选择分析ADC测量值的方法对将该指标用作MGMT状态替代标志物的应用有重大影响。因此，为使dMRI数据具有临床实用性，在建立与基因或表观遗传学特征的任何关系之前，需要建立一致的数据分析方法。
