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Hierarchical Phase-Contrast Tomography Imaging: Applicability in biomedical research

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Objectives Hierarchical Phase-Contrast Tomography (HiP-CT) enables non-destructive, multi-scale imaging of whole human organs. We describe how HiP-CT is utilized for biomedical research within the Human Organ Atlas Hub through three case studies: mapping the enteric nervous system (ENS) of the human colon, analysing myocardial and AV conduction architecture in Tetralogy of Fallot (TOF), and characterizing ductal organization in breast carcinoma. The challenges we faced with this novel biomedical data are discussed. Methods Whole-organ and region-of-interest scans of three types of human organs were acquired at the European Synchrotron Radiation Facility (ESRF) with isotropic voxel sizes ranging from 20 µm to 0.8 µm. For the colon, voxel binning and RootPainter were employed to tackle data size to segment the ENS. For the heart, voxel-wise myocyte orientation mapping was calculated in terabyte-scale datasets with a high-performance computational framework (Cardiotensor). Breast carcinoma samples were correlated with histopathology for structure validation. Results HiP-CT revealed the large-scale organization of the ENS in the colon, enabling visualisation of the 3D structures of the ENS across the colon In TOF hearts, analysis uncovered abnormal myocardial structure and heterogeneous conduction system morphology. In breast carcinoma, HiP-CT resolved the full hierarchy of ductal structures and vascular relationships within tumour and peritumoral regions. Conclusions HiP-CT provides unprecedented, hierarchical insight into intact human organ structure, bridging the gap between histology and radiology. Advances in knowledge HiP-CT establishes a new ex vivo radiological modality capable of linking microscale pathology to whole-organ context, advancing translational research in neurogastroenterology, cardiology, and oncology

Authors 26

  1. Daniël Docter corresponding

    Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis · Amsterdam Gastroenterology Endocrinology Metabolism · Amsterdam Reproduction Development

    Affiliation as printed

    Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands

    Amsterdam Reproduction and Development research institute, Amsterdam, The Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynecology, Meibergdreef 9, Amsterdam, the Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Pediatric Surgery, Emma’s children hospital, Meibergdreef 9, Amsterdam, the Netherlands

  2. European Synchrotron Radiation Facility · University College London

    Affiliation as printed

    Department of Mechanical Engineering, University College London, London, UK

    ESRF – The European Synchrotron, Grenoble, France

  3. University College London

    Affiliation as printed

    Division of Medicine, University College London, London, UK

    Institute of Cardiovascular Science, University College London, London, UK

  4. Universitätsklinikum Aachen

    Affiliation as printed

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

  5. Universitätsklinikum Aachen · KU Leuven

    Affiliation as printed

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

    Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium

  6. University of Copenhagen

    Affiliation as printed

    Department of Computer Science, University of Copenhagen, Universitetsparker1, DK-2100 Copenhagen, Denmark

  7. European Synchrotron Radiation Facility

    Affiliation as printed

    ESRF – The European Synchrotron, Grenoble, France

  8. European Synchrotron Radiation Facility

    Affiliation as printed

    ESRF – The European Synchrotron, Grenoble, France

  9. European Synchrotron Radiation Facility

    Affiliation as printed

    ESRF – The European Synchrotron, Grenoble, France

  10. Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis · Amsterdam Gastroenterology Endocrinology Metabolism · Amsterdam Reproduction Development

    Affiliation as printed

    Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands

    Amsterdam Reproduction and Development research institute, Amsterdam, The Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Pediatric Surgery, Emma’s children hospital, Meibergdreef 9, Amsterdam, the Netherlands

  11. Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development

    Affiliation as printed

    Amsterdam Reproduction and Development research institute, Amsterdam, The Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynecology, Meibergdreef 9, Amsterdam, the Netherlands

  12. Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development

    Affiliation as printed

    Amsterdam Reproduction and Development research institute, Amsterdam, The Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynecology, Meibergdreef 9, Amsterdam, the Netherlands

  13. Amsterdam UMC Location University of Amsterdam

    Affiliation as printed

    Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynecology, Meibergdreef 9, Amsterdam, the Netherlands

  14. Inserm · Université Grenoble Alpes

    Affiliation as printed

    Univ. Grenoble Alpes, Department of Anatomy (LADAF), CIC INSERM 1406, Grenoble, France

  15. University College London

    Affiliation as printed

    Centre for Advanced Research Computing, UCL, London, United Kingdom

    Department of Mechanical Engineering, University College London, London, UK

  16. Helios Universitätsklinikum Wuppertal · Universitätsklinikum Aachen

    Affiliation as printed

    Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, Wuppertal, Germany

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

  17. Universitätsklinikum Aachen

    Affiliation as printed

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

  18. Universitätsklinikum Aachen · German Center for Lung Research

    Affiliation as printed

    Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

  19. University College London

    Affiliation as printed

    Satsuma Lab, UCL Hawkes Institute, University College London, London, UK

    UCL Respiratory, University College London, London, UK

  20. Amsterdam University Medical Centers · University of Amsterdam

    Affiliation as printed

    Amsterdam UMC, University of Amsterdam, Department of Medical Biology, Meibergdreef 9, Amsterdam, the Netherlands

  21. University of Antwerp

    Affiliation as printed

    Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), University of Antwerp, Wilrijkn, Belgium

  22. University College London

    Affiliation as printed

    Division of Medicine, University College London, London, UK

    Institute of Cardiovascular Science, University College London, London, UK

  23. University College London

    Affiliation as printed

    Department of Mechanical Engineering, University College London, London, UK

  24. European Synchrotron Radiation Facility

    Affiliation as printed

    ESRF – The European Synchrotron, Grenoble, France

  25. University College London

    Affiliation as printed

    Department of Mechanical Engineering, University College London, London, UK

  26. Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development

    Affiliation as printed

    Amsterdam Reproduction and Development research institute, Amsterdam, The Netherlands

    Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynecology, Meibergdreef 9, Amsterdam, the Netherlands

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References 27