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Human fetal whole-body postmortem microfocus computed tomographic imaging

Abstract

Perinatal autopsy is the standard method for investigating fetal death; however, it requires dissection of the fetus. Human fetal microfocus computed tomography (micro-CT) provides a generally more acceptable and less invasive imaging alternative for bereaved parents to determine the cause of early pregnancy loss compared with conventional autopsy techniques. In this protocol, we describe the four main stages required to image fetuses using micro-CT. Preparation of the fetus includes staining with the contrast agent potassium triiodide and takes 3–19 d, depending on the size of the fetus and the time taken to obtain consent for the procedure. Setup for imaging requires appropriate positioning of the fetus and takes 1 h. The actual imaging takes, on average, 2 h 40 min and involves initial test scans followed by high-definition diagnostic scans. Postimaging, 3 d are required to postprocess the fetus, including removal of the stain, and also to undertake artifact recognition and data transfer. This procedure produces high-resolution isotropic datasets, allowing for radio-pathological interpretations to be made and long-term digital archiving for re-review and data sharing, where required. The protocol can be undertaken following appropriate training, which includes both the use of micro-CT techniques and handling of postmortem tissue.

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Fig. 1: Microcomputed tomographic imaging.
Fig. 2: Key parts of the workflow for human fetal whole-body postmortem microcomputed tomographic imaging.
Fig. 3: Equipment needed.
Fig. 4: Fetal preparation.
Fig. 5: Tissue preparation with I2KI.
Fig. 6: Representative images of a fetus.
Fig. 7: Positioning and image parameters.
Fig. 8: Examples of issues occurring during micro-CT scanning that require optimization of the workflow.

Data availability

Examples of data produced by following this protocol are included in the protocol. Further details of the data presented are not publicly available because the information could compromise research participant privacy/consent.

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Acknowledgements

I.C.S. is funded by an NIHR Clinical Doctoral Research Fellowship (ICA-CDRF-2017-03-53). O.J.A. is funded by a National Institute for Health Research (NIHR) Career Development Fellowship (NIHR-CDF-2017-10-037). S.C.S. is supported by a RCUK/ UKRI Innovation Fellowship and Medical Research Council (MRC) Clinical Research Training Fellowship (grant MR/R002118/1), jointly funded by the Royal College of Radiologists (RCR). O.J.A. and N.J.S. receive funding from the Great Ormond Street Hospital Children’s Charity. This article presents independent research, and the views expressed are those of the author(s) and not necessarily those of the funding bodies or the Department of Health and Social Care. The authors acknowledge the help from our mortuary staff at Great Ormond Street Hospital: L. Ward, J. Parmenter, H. McGarrick, B. Czarny and D. Alvarez for their assistance and I. Haig, O. Larkin and B. Smit (Nikon, Tring, UK) for their technical advice. We also thank the parents who consented to and participate in this research.

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I.C.S., S.C.S. and J.C.H. developed and tested the methodology within the paper and drafted the manuscript. N.J.S. and O.J.A. supervised the work. All authors assessed the results, thereby optimizing the technique. All authors edited the paper and approved the final version.

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Correspondence to Owen J. Arthurs.

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The authors declare no competing interests.

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Peer review information Nature Protocols thanks Jorge Murillo-Gonzalez and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Key references using this protocol

Hutchinson, J. C. et al. Ultrasound Obstet Gynecol 47, 58-64 (2016): https://doi.org/10.1002/uog.15764

Hutchinson, J. C. et al. Am. J. Obstet. Gynecol. 218, 445.e441-445.e412 (2018): https://doi.org/10.1016/j.ajog.2018.01.040

Shelmerdine, S. C. et al. Am. J. Obstet. Gynecol. 224, 103.e1–103.e15 (2021): https://doi.org/10.1016/j.ajog.2020.07.019

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Supplementary Data 1

Postmortem examination consent form and guidance given to the consent taker used at Great Ormond Street Hospital, London, UK. Provided in Microsoft Word and pdf format.

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Simcock, I.C., Shelmerdine, S.C., Hutchinson, J.C. et al. Human fetal whole-body postmortem microfocus computed tomographic imaging. Nat Protoc 16, 2594–2614 (2021). https://doi.org/10.1038/s41596-021-00512-6

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