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Reproducibility of Contrast-Enhanced Ultrasound in Mice with Controlled Injection

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Abstract

Purpose

Sensitivity of contrast-enhanced ultrasound (CEUS) to microvascular flow modifications can be limited by intra-injection variability (injected dose, rate, volume).

Procedures

To evaluate the effect of injection variability on microvascular flow evaluation, CEUS was compared between controlled and manual injections where enhancement was assessed in vitro within a flow phantom, in normal murine kidney (N = 12) and in murine ectopic tumors (N = 10).

Results

For both in vitro and in vivo measurements in the renal cortex, controlled injections significantly improved reproducibility of functional parameter estimation. Their coefficient of variation (CV) in the renal cortex ranged from 4 to 19 % for controlled injection vs. 5 to 43 % for manual injections. For measurements in tumors, controlled injection only decreased the CV significantly for the mean transit time. In tumors, multiple injections of contrast agent with a 15-min delay between each were shown to strongly modify contrast uptake by facilitating penetration of microbubbles.

Conclusion

Improved reproducibility of CEUS assessments in murine models should provide more robust quantification of flow parameters and more sensitive evaluation of tumor modifications in therapeutic models.

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Acknowledgments

The authors would like to acknowledge Bracco Suisse SA for their help in the implementation of the controlled injection system. The authors also thank the CEF (Centre d’Explorations Fonctionnelles, Cordeliers’ Research Center) for their technical support and help with animals care.

We gratefully acknowledge support from the French research program Plan Cancer 2009–2013 (project NABUCCO) and the Fondation Recheche Médicale (Recherche soutenue par le FRM DBS20131128436). This work was partly funded by the French program “Investissement d’Avenir” run by the “Agence Nationale pour la Recherche”, and grant Infrastructure d’avenir en Biologie Santé—ANR-11-INBS-0006.

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Authors and Affiliations

  1. Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, F-75006, Paris, France

    Alexandre Dizeux, Thomas Payen, Guillaume Barrois, Delphine Le Guillou Buffello & S. Lori Bridal

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  1. Alexandre Dizeux
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  2. Thomas Payen
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  3. Guillaume Barrois
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  4. Delphine Le Guillou Buffello
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  5. S. Lori Bridal
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Corresponding author

Correspondence to Alexandre Dizeux.

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Human and Animal Rights and Informed Consent

All experiments were conducted in accordance with the institutional guidelines and the recommendations for the care and use of laboratory animals established by the French Ministry of Agriculture.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Dizeux, A., Payen, T., Barrois, G. et al. Reproducibility of Contrast-Enhanced Ultrasound in Mice with Controlled Injection. Mol Imaging Biol 18, 651–658 (2016). https://doi.org/10.1007/s11307-016-0952-y

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