Efficacy of positive contrast imaging techniques for molecular MRI of tumor angiogenesis

Authors

  • M. Wolters,

    1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • M. Oostendorp,

    1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Department of Radiology, Maastricht University Medical Center, Maastricht, the Netherlands
    3. Laboratory of Clinical Chemistry and Haematology, University Medical Centre Utrecht, the Netherlands
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  • B. F. Coolen,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • M. J. Post,

    1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Department of Physiology, Maastricht University Medical Center, Maastricht, the Netherlands
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  • J. M. H. Janssen,

    1. Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands
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  • G. J. Strijkers,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • M. E. Kooi,

    1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Department of Radiology, Maastricht University Medical Center, Maastricht, the Netherlands
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  • K. Nicolay,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • W. H. Backes

    Corresponding author
    1. Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Department of Radiology, Maastricht University Medical Center, Maastricht, the Netherlands
    • W. H. Backes, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands. E-mail: w.backes@mumc.nl

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Abstract

Superparamagnetic iron oxide particles (SPIOs) are promising contrast agents for molecular MRI. To improve the in vivo detection of iron-based contrast media, positive contrast imaging techniques have been developed. Here, the efficacy of two positive contrast techniques, white marker and susceptibility gradient mapping (SGM), were evaluated for molecular MRI of tumor angiogenesis and compared with conventional negative contrast gradient echo (GE) imaging. In vitro, cylindrical phantoms containing varying iron oxide concentrations were used to measure the response of positive contrast techniques. In vivo, tumor bearing mice were used as a model for tumor angiogenesis. Mice were injected with unlabeled SPIOs (n = 5) or SPIOs labeled with cyclic NGR peptide (cNGR) (n = 5), which homes specifically to angiogenic microvessels. Pre- and post-contrast GE and white marker images were acquired. Subsequently, SGM images and R2* maps were calculated. For image analysis, the contrast-to-noise ratio (CNR) and the percentage of enhanced voxels (EVs) in the tumor rim and core were calculated. In vitro, the linear increases in MRI signal response for increasing iron oxide concentration were much stronger for SGM than white marker. In vivo, the CNR of GE, white marker and SGM imaging was 5.7, 1.2 and 6.2, respectively, with equal acquisition times. Significant differences in the percentage of EVs between the tumor rim and core were found using R2* mapping, GE and SGM (p < 0.05). The two contrast agents had significantly different percentages of EVs by R2* mapping and SGM in the rim (p < 0.001). The in vivo efficacy of white marker and SGM was evaluated for molecular MRI relative to GE imaging and R2* mapping. Only SGM, and not white marker, can be used to transfer the negative contrast from targeted SPIOs in a positive contrast signal without loss of CNR. Copyright © 2012 John Wiley & Sons, Ltd.

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