Correlation of tumor characteristics derived from DCE‐MRI and DW‐MRI with histology in murine models of breast cancer

The purpose of this work was to determine the relationship between the apparent diffusion coefficient (ADC, from diffusion‐weighted (DW) MRI), the extravascular, extracellular volume fraction ( v e , from dynamic contrast‐enhanced (DCE) MRI), and histological measurement of the extracellular space fraction. Athymic nude mice were injected with either human epidermal growth factor receptor 2 positive (HER2+) BT474 ( n = 15) or triple negative MDA‐MB‐231 ( n = 20) breast cancer cells, treated with either Herceptin ( n = 8), Abraxane (low dose n = 7, high dose n = 6), or saline ( n = 7 for each cell line), and imaged using DW‐ and DCE‐MRI before, during, and after treatment. After the final imaging acquisition, the tissue was resected and evaluated by histological analysis. H&E‐stained central slices were scanned using a digital brightfield microscope and evaluated with thresholding techniques to calculate the extracellular space. For both BT474 and MDA‐MB‐231, the median ADC of the central slice exhibited a significantly positive correlation with the corresponding central slice extracellular space as measured by H&E ( p = 0.03, p < 0.01, respectively). Median v e calculated from the central slice showed differing results between the two cell lines. For BT474, a significant correlation between v e and extracellular space was calculated ( p = 0.02), while MDA‐MB‐231 tumors did not demonstrate a significant correlation ( p = 0.64). Additionally, there was no correlation discovered between ADC and v e with either whole tumor analysis or central slice analysis ( p > 0.05). While ADC correlates well with the histologically determined fraction of extracellular space, these data add to the growing body of literature that suggests that v e derived from DCE‐MRI is not a reliable biomarker of extracellular space for a range of physiological conditions. Copyright © 2015 John Wiley & Sons, Ltd.