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Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging

Nature Biomedical Engineering volume 2, pages 85–94 (2018)Cite this article

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Abstract

Positron emission tomography–computed tomography (PET–CT) is the most sensitive molecular imaging modality, but it does not easily allow for rapid temporal acquisition. Ultrafast ultrasound imaging (UUI)—a recently introduced technology based on ultrasonic holography—leverages frame rates of up to several thousand images per second to quantitatively map, at high resolution, haemodynamic, biomechanical, electrophysiological and structural parameters. Here, we describe a pre-clinical scanner that registers PET–CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. We demonstrate that PET–CT–UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. Combined anatomical, functional and molecular imaging with PET–CT–UUI represents a high-performance and clinically translatable technology for biomedical research.

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Fig. 1: PET–CT–UUI set-up and acquisitions.
Fig. 2: Longitudinal PET–UUI imaging monitors the evolution of metabolism and vascularization during tumour growth in a mouse.
Fig. 3: Phenotyping tumours in mice on the basis of bivariate, FDG–ultrafast-power-Doppler histograms.
Fig. 4: PET–CT–UUI of the beating rat heart in a short-axis view.

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Acknowledgements

This study was supported by France Life Imaging grant ANR-11-INBS-0006. The authors are grateful to O. Clément and A. Tedgui for constant support, and to K. Tzavella, G. Leenders, L. Bao and X. Zhang for help with the image co-registration software. This work was supported in part by LABEX WIFI (Laboratory of Excellence ANR-10-LABX-24) within the French programme 'Investments for the Future' under reference ANR-10-IDEX-0001-02 PSL and by a grant from the Plan Cancer Physicancer programme BIMUPET (C16025KS). In vivo imaging was performed at the Life Imaging Facility of Paris Descartes University (Plateforme Imageries du Vivant), supported by France Life Imaging (grant ANR-11-INBS-0006) and Infrastructures Biologie-Santé. The project also received the support of the Institut National de la Santé et de la Recherche Médicale (Inserm) Technology Research Accelerator in Biomedical Ultrasound.

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Author notes

  1. Jean Provost and Anikitos Garofalakis contributed equally to this work.

  2. Mickael Tanter and Bertrand Tavitian jointly supervised this work.

Authors and Affiliations

  1. Institut Langevin, Ecole Supérieure de Physique et de Chimie Industrielles, Paris Sciences and Letters Research University CNRS UMR 7587 Inserm U979, Inserm Technology Research Accelerator in Biomedical Ultrasound, Paris, France

    Jean Provost, Béatrice Berthon, Mafalda Correia, Mathieu Pernot & Mickael Tanter

  2. Inserm, UMR970, Paris Cardiovascular Research Center, Paris, France

    Anikitos Garofalakis, Joevin Sourdon, Damien Bouda, Thomas Viel, Mailyn Perez-Liva, Charlotte Lussey-Lepoutre, Judith Favier & Bertrand Tavitian

  3. Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Anikitos Garofalakis, Joevin Sourdon, Damien Bouda, Thomas Viel, Mailyn Perez-Liva, Judith Favier & Bertrand Tavitian

  4. Faculté de Médecine, Université Pierre et Marie Curie, Paris, France

    Charlotte Lussey-Lepoutre

  5. Nuclear Medicine Department, Pitié-Salpêtrière Hospital, Paris, France

    Charlotte Lussey-Lepoutre

  6. Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France

    Johanna Chiche

  7. Équipe Contrôle Métabolique des Morts Cellulaires, Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire, Nice, France

    Johanna Chiche

  8. Institute for Research on Cancer and Aging, Université de Nice Sophia Antipolis, Centre Antoine Lacassagne, Nice, France

    Jacques Pouysségur

  9. Department of Medical Biology, Centre Scientifique de Monaco, Monaco, Monaco

    Jacques Pouysségur

  10. Department of Radiology, Georges Pompidou European Hospital, Paris, France

    Bertrand Tavitian

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  1. Jean Provost
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Contributions

J.Pr., A.G., M.T. and B.T. designed the experiments. J.Pr., A.G., J.S., D.B., B.B., T.V. and M.P.-L. performed the experiments. J.Pr., A.G., J.S., D.B., B.B., T.V., M.P.-L., M.C., M.P. and B.T. analysed the data. C.L.-L., J.F. and J.Po. provided original material to perform the experiments. J.Pr., A.G., M.T. and B.T. wrote the paper.

Corresponding authors

Correspondence to Mickael Tanter or Bertrand Tavitian.

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Competing interests

M.T. is a co-founder and shareholder of Supersonic Imagine. All other authors declare no competing financial interests.

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Supplementary information

Videos

Supplementary Video 1

PET–CT–ultrafast Doppler imaging of a xenografted tumour in a mouse

Supplementary Video 2

Evolution of FDG uptake and vasculature during the growth of a subcutaneous tumour in a mouse

Supplementary Video 3

Co-registered FDG uptake and vasculature in tumours with different metabolic pathways, and their corresponding bivariate histograms

Supplementary Video 4

Overlaid ECG-gated PET–UU B-mode cine-loops in two sections 3 mm apart in a rat heart

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Provost, J., Garofalakis, A., Sourdon, J. et al. Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging. Nat Biomed Eng 2, 85–94 (2018). https://doi.org/10.1038/s41551-018-0188-z

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