Hales, PW; Olsen, ØE; Sebire, NJ; Pritchard-Jones, K; Clark, CA; (2015) A multi-Gaussian model for apparent diffusion coefficient histogram analysis of Wilms' tumour subtype and response to chemotherapy. NMR in Biomedicine , 28 (8) pp. 948-957. 10.1002/nbm.3337.

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Abstract

Wilms' tumours (WTs) are large heterogeneous tumours, which typically consist of a mixture of histological cell types, together with regions of chemotherapy-induced regressive change and necrosis. The predominant cell type in a WT is assessed histologically following nephrectomy, and used to assess the tumour subtype and potential risk. The purpose of this study was to develop a mathematical model to identify subregions within WTs with distinct cellular environments in vivo, determined using apparent diffusion coefficient (ADC) values from diffusion-weighted imaging (DWI). We recorded the WT subtype from the histopathology of 32 tumours resected in patients who received DWI prior to surgery after pre-operative chemotherapy had been administered. In 23 of these tumours, DWI data were also available prior to chemotherapy. Histograms of ADC values were analysed using a multi-Gaussian model fitting procedure, which identified 'subpopulations' with distinct cellular environments within the tumour volume. The mean and lower quartile ADC values of the predominant viable tissue subpopulation (ADC1MEAN , ADC1LQ ), together with the same parameters from the entire tumour volume (ADC0MEAN , ADC0LQ ), were tested as predictors of WT subtype. ADC1LQ from the multi-Gaussian model was the most effective parameter for the stratification of WT subtype, with significantly lower values observed in high-risk blastemal-type WTs compared with intermediate-risk stromal, regressive and mixed-type WTs (p < 0.05). No significant difference in ADC1LQ was found between blastemal-type and intermediate-risk epithelial-type WTs. The predominant viable tissue subpopulation in every stromal-type WT underwent a positive shift in ADC1MEAN after chemotherapy. Our results suggest that our multi-Gaussian model is a useful tool for differentiating distinct cellular regions within WTs, which helps to identify the predominant histological cell type in the tumour in vivo. This shows potential for improving the risk-based stratification of patients at an early stage, and for guiding biopsies to target the most malignant part of the tumour. Copyright © 2015 John Wiley & Sons, Ltd.

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