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Assessing breast cancer angiogenesis in vivo: which susceptibility contrast MRI biomarkers are relevant?

Authors

  • Eugene Kim,

    1. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Jana Cebulla,

    1. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
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  • B. Douglas Ward,

    1. Biophysics Department, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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  • Kevin Rhie,

    1. Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Jiangyang Zhang,

    1. Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Arvind P. Pathak

    Corresponding author
    1. Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    3. Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    • Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 720 Rutland Ave, 217 Traylor Bldg, Baltimore, MD 21205. E-mail: pathak@mri.jhu.edu

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Abstract

Purpose

There is an impending need for noninvasive biomarkers of breast cancer angiogenesis to evaluate the efficacy of new anti-angiogenic therapies in vivo. The purpose of this study was to systematically evaluate the sensitivity of in vivo steady-state susceptibility contrast-MRI biomarkers of angiogenesis in a human breast cancer model.

Methods

Orthotopic MDA-MB-231 human breast cancer xenografts were imaged by steady-state susceptibility contrast-MRI at post-inoculation week 3 and post-inoculation week 5, followed by ex vivo whole tumor 3D micro-CT angiography. “Absolute” (i.e., measures of vascular morphology in appropriate units) and “relative” (i.e., proportional to measures of vascular morphology) MRI biomarkers of tumor blood volume, vessel size, and vessel density were computed and their ability to predict the corresponding micro-CT analogs assessed using cross-validation analysis.

Results

All MRI biomarkers significantly correlated with their micro-CT analogs and were sensitive to the micro-CT-measured decreases in tumor blood volume and vessel density from post-inoculation week 3 to post-inoculation week 5. However, cross-validation analysis revealed there was no significant difference between the predictive accuracy of “absolute” and “relative” biomarkers.

Conclusion

As “relative” biomarkers are more easily computed from steady-state susceptibility contrast-MRI (i.e., without additional MRI measurements) than “absolute” biomarkers, it makes them promising candidates for assessing breast cancer angiogenesis in vivo. Magn Reson Med, 70:1106–1116, 2013. © 2012 Wiley Periodicals, Inc.

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