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 (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.
Vanderbilt Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
Stephanie L
SL
Barnes
Vanderbilt Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
Anna G
AG
Sorace
Vanderbilt Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Mary E
ME
Loveless
Vanderbilt Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
Jennifer G
JG
Whisenant
Vanderbilt Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA.|Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.|Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Thomas E
TE
Yankeelov
D000068196:Albumin-Bound Paclitaxel / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008853:Microscopy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000068878:Trastuzumab / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000473:pathology
D000068196:Albumin-Bound Paclitaxel; D000970:Antineoplastic Agents; D003287:Contrast Media; D019786:Gadolinium DTPA; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
apparent diffusion coefficient; extracellular space; extravascular extracellular space; quantitative imaging