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Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain

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Abstract

Purpose

The purpose of this study was to introduce synchrotron radiation X-ray phase computed tomography (SR-PCT) as a new method of visualizing ultrasmall superparamagnetic particles of iron oxide (USPIO) distribution into the brains of mice with neuroinflammation.

Procedures

The sensitivity of the technique was assessed by performing back-to-back SR-PCT and magnetic resonance imaging (MRI) in mice stereotaxically injected with a range of USPIO concentrations. Eight mice with cerebral ischemia were then intravenously injected with USPIOs and imaged back-to-back with MRI and SR-PCT.

Results

SR-PCT proved sensitive enough to detect iron in nanomolar quantities. In stroke-induced animals, SR-PCT showed hyperintense areas in the regions of MR signal loss and immunostaining for macrophages. SR-PCT, moreover, identified brain anatomy as clearly as histology, without the need for sectioning or staining, with an examination time of 44 min per brain at an isotropic spatial resolution of 8 μm.

Conclusion

SR-PCT has potential for cellular imaging in intact brain, with unequaled neuroanatomy.

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Acknowledgments

This work was performed within the framework of the LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon, within the program “Investissements d'Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). This work was supported by the ESRF (project MD-499) by allocation of beam time. The authors would like to thank Sébastien Ballet and Anne Dencausse of Guerbet for providing the USPIOs and performing relaxometry measurements for iron dosage. Part of the experiments was performed on the “Animage” platform of CERMEP-Imagerie du Vivant, Lyon, France. We would like to thank Géraldine LeDuc and Elodie Boller from ESRF for assistance in preparing the experiments and Carole Frindel from Creatis (UMR CNRS 5220 U1044 INSERM) for helping with the movie and 3D images.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Université de Lyon, Lyon 1, France

    M. Marinescu, T. H. Cho, N. Nighoghossian & Y. Berthezène

  2. CNRS, UMR 5220; INSERM, U1044; INSA de Lyon; CREATIS, Lyon, France

    M. Marinescu, M. Langer, A. Durand, C. Olivier, A. Chabrol, H. Rositi, F. Chauveau, T. H. Cho, N. Nighoghossian, Y. Berthezène, F. Peyrin & M. Wiart

  3. Hôpital Neuro-cardiologique, Service de Radiologie, Laboratoire Creatis, UMR CNRS 5220, INSERM U1044–Bat. B13, 28, avenue du Doyen LEPINE, 69677, Bron Cedex, France

    M. Wiart

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  1. M. Marinescu
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  2. M. Langer
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Corresponding author

Correspondence to M. Wiart.

Electronic Supplementary Material

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Movie S1

Slice-by-slice overview of a whole SR-PCT exam. (AVI 29820 kb)

Figure S1

Comparison of three typical images obtained with SR-PCT at different slice positions (a1–c1) with corresponding Cresyl violet-stained slices from Franklin Paxinos Atlas (reproduced with permission) [19] (a2–c2). This atlas was also used to label the data. Arrowhead shows the ischemic lesion. (DOC 2328 kb)

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Marinescu, M., Langer, M., Durand, A. et al. Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain. Mol Imaging Biol 15, 552–559 (2013). https://doi.org/10.1007/s11307-013-0639-6

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