The trouble with apparent diffusion coefficient papers

This issue of Journal of Medical Radiation Sciences includes a study (Rundle-Thiele et al.) that investigates the correlation between magnetic resonance imaging (MRI)-based estimates of water mobility in glioblastoma tumours and expression of the prognostically important gene promoter methylguanine methyltransferase (MGMT). The authors address previous inconsistent reports regarding a correlation between apparent diffusion coefficient (ADC) and the presence of MGMT by consideration of the effect of tumour heterogeneity. Since tissue water mobility is intimately and directly dependent on tissue microstructure, tumour heterogeneity will manifest as intervoxel differences of calculated ADC. The question then is how to correlate such heterogeneous measurements with tumour type markers. For the same clinical data set, different analyses may lead to different conclusions. One approach to this problem is to consider the histogram of intra-tumour voxel ADCs. If the tumour were homogeneous one would expect a normal distribution of voxel ADCs. This is clearly not the case for glioblastoma which shows a bimodal distribution in the measurements reported by Rundle-Thiele et al. The mean of the lower ADC component of the bimodal distribution correlated strongly with presence of MGMT while the minimum ADC in the tumour did not. There are many potential methods of correlating measurements of heterogeneous tissue with properties such as pathologic status. For example, in the prostate the intervoxel ADC entropy in suspicious regions is reported to correlate more strongly with the presence of cancer than a simple mean. This example, and the investigation reported by Rundle-Thiele et al. emphasise the importance of recognising and accounting for tissue heterogeneity when attempting to develop markers for pathology or pathologic type. However, there is a dark undercurrent to the ADC story and the majority of publications describing clinical ADC-based analysis of diffusion-weighted MRI data. Quite separate from the inter-voxel ADC differences there are potential effects on calculated ADC from sub-voxel tissue heterogeneity, measurement technique and analysis method. This is rarely mentioned in the clinical diffusion MRI literature, and in many cases probably not recognised by authors or reviewers. To a significant extent it may be a confused usage of ADC that leads to inconsistent results when independent studies are compared. Unfortunately, the misuse of ADC is now deeply imbedded in the culture of radiology.