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

• Published in: NMR in biomedicine 2015-10, Vol.28 (10), p.1345-1356
• Main Authors: Barnes, Stephanie L., Sorace, Anna G., Loveless, Mary E., Whisenant, Jennifer G., Yankeelov, Thomas E.
• Format: Article
• Language: English
• Subjects: Albumin-Bound Paclitaxel - therapeutic use; Animals; Antineoplastic Agents - therapeutic use; apparent diffusion coefficient; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carcinoma - drug therapy; Carcinoma - pathology; Cell Line, Tumor; Contrast Media - pharmacokinetics; Diffusion; Diffusion Magnetic Resonance Imaging; extracellular space; extravascular extracellular space; Female; Gadolinium DTPA - pharmacokinetics; Heterografts; Humans; Magnetic Resonance Imaging - methods; Mice; Mice, Nude; Microscopy; quantitative imaging; Receptor, ErbB-2 - genetics; Trastuzumab - therapeutic use; Triple Negative Breast Neoplasms - pathology
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3377

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 (ve, 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 ve calculated from the central slice showed differing results between the two cell lines. For BT474, a significant correlation between ve 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 ve 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 ve derived from DCE‐MRI is not a reliable biomarker of extracellular space for a range of physiological conditions. Copyright © 2015 John Wiley & Sons, Ltd. This study evaluated the relationship between the apparent diffusion coefficient (ADC, from diffusion weighted MRI)1 the extravascular, extracellular volume fraction (ve1 from dynamic contrast enhanced MRI), and quantitative histology measurements using two breast cancer animal models, BT474 and MDA‐MB‐231. While ADC correlates well with the extravascular space, this data adds to the growing body of literature which suggests that ve is not a reliable biomarker of extra cellular place.