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Correlation of tumor characteristics derived from DCE‐MRI and DW‐MRI with histology in murine models of breast cancer
Author(s) -
Barnes Stephanie L.,
Sorace Anna G.,
Loveless Mary E.,
Whisenant Jennifer G.,
Yankeelov Thomas E.
Publication year - 2015
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.3377
Subject(s) - extracellular , nuclear medicine , histology , diffusion mri , correlation , extracellular fluid , effective diffusion coefficient , breast cancer , magnetic resonance imaging , chemistry , pathology , medicine , cancer , radiology , mathematics , biochemistry , geometry
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.