Whole-Fetus HiP-CT: A New Era in postmortem 3D Fetal Imaging

Abstract

We present the first application of Hierarchical Phase-Contrast Tomography (HiP-CT) to complete human fetuses at BM18, the flagship beamline for microtomography on large samples at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Leveraging the advanced capabilities of BM18, six human fetal specimens from the Dutch Fetal Biobank (Amsterdam UMC, ethics approval 2016_285) were scanned at multiple resolutions. This pilot cohort included two specimens at approximately 21 weeks of gestation (one with a cardiac anomaly), two at 16 weeks (one with a cardiac anomaly), and two at 11 weeks (including conjoined twins).

The imaging pipeline comprised rapid post-mortem tissue recovery (2–6 h interval), paraformaldehyde fixation, transfer to 70% ethanol, mounting, degassing in custom vacuum chambers, and transport from Amsterdam UMC to ESRF. Initial whole-body overviews were acquired at 16 or 8 µm isotropic voxel size, followed by targeted scans at 4 and 2 µm, yielding dozens of terabytes of data. Thanks to the high sensitivity brought by the HiP-CT protocols, these multiscale datasets provide unprecedented structural detail and enable exploration of complex anatomical systems including the lymphatic and nervous systems, fascia, and inter-organ relationships. Post-acquisition workflows included advanced segmentation pipelines to support quantitative analysis and AI model training.

To our knowledge, this is the first time the human body has been imaged in its entirety at such high resolution. This pilot study marks a critical expansion of the BM18 HiP-CT pipeline into the fetal domain. These data hold wide-ranging implications for anatomy, developmental biology, congenital anomaly research, and forensic applications. Future steps include cross-institutional collaboration for quantitative analysis and integration with downstream histology and spatial transcriptomics.

We present the first application of Hierarchical Phase-Contrast Tomography (HiP-CT) to complete human fetuses at BM18, the flagship beamline for microtomography on large samples at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Leveraging the advanced capabilities of BM18, six human fetal specimens from the Dutch Fetal Biobank (Amsterdam UMC, ethics approval 2016_285) were scanned at multiple resolutions. This pilot cohort included two specimens at approximately 21 weeks of gestation (one with a cardiac anomaly), two at 16 weeks (one with a cardiac anomaly), and two at 11 weeks (including conjoined twins).

The imaging pipeline comprised rapid post-mortem tissue recovery (2–6 h interval), paraformaldehyde fixation, transfer to 70% ethanol, mounting, degassing in custom vacuum chambers, and transport from Amsterdam UMC to ESRF. Initial whole-body overviews were acquired at 16 or 8 µm isotropic voxel size, followed by targeted scans at 4 and 2 µm, yielding dozens of terabytes of data. Thanks to the high sensitivity brought by the HiP-CT protocols, these multiscale datasets provide unprecedented structural detail and enable exploration of complex anatomical systems including the lymphatic and nervous systems, fascia, and inter-organ relationships. Post-acquisition workflows included advanced segmentation pipelines to support quantitative analysis and AI model training.

To our knowledge, this is the first time the human body has been imaged in its entirety at such high resolution. This pilot study marks a critical expansion of the BM18 HiP-CT pipeline into the fetal domain. These data hold wide-ranging implications for anatomy, developmental biology, congenital anomaly research, and forensic applications. Future steps include cross-institutional collaboration for quantitative analysis and integration with downstream histology and spatial transcriptomics.