Background MRI and CT have been extensively used to study fetal anatomy for research and diagnostic purposes, enabling minimally invasive autopsy and giving insight in human fetal development. Novel (contrast-enhanced) microfocus CT (micro-CT) and ultra-high-field (≥ 7.0 T) MRI (UHF-MRI) techniques now enable micron-level resolution that combats the disadvantages of low-field MRI and conventional CT. Thereby, they might be suitable to study fetal anatomy in high detail and, in time, contribute to the postmortem diagnosis of fetal conditions. Objectives (1) To systematically examine the usability of micro-CT and UHF-MRI to study postmortem human fetal anatomy, and (2) to analyze factors that govern success at each step of the specimen preparation and imaging. Method MEDLINE and EMBASE were systematically searched to identify publications on fetal imaging by micro-CT or UHF-MRI. Scanning protocols were summarized and best practices concerning specimen preparation and imaging were enumerated. Results Thirty-two publications reporting on micro-CT and UHF-MRI were included. The majority of the publications focused on imaging organs separately and seven publications focused on whole body imaging, demonstrating the possibility of visualization of small anatomical structures with a resolution well below 100 μm. When imaging soft tissues by micro-CT, the fetus should be stained by immersion in Lugol's staining solution.Conclusion Micro-CT and UHF-MRI are both excellent imaging techniques to provide detailed images of gross anatomy of human fetuses. The present study offers an overview of the current best practices when using micro-CT and/or UHF-MRI to study fetal anatomy for clinical and research purposes. Key Points • Micro-CT and UHF-MRI can both be used to study postmortem human fetal anatomy for clinical and research purposes.• Micro-CT enables high-resolution imaging of fetal specimens in relatively short scanning time. However, tissue staining using a contrast solution is necessary to enable soft-tissue visualization. • UHF-MRI enables high-resolution imaging of fetal specimens, without the necessity of prior staining, but with the drawback of long scanning time.

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) is progressively used in clinical and morphological research to study developmental anatomy. Lugol’s solution (Lugol) has gained interest as an effective contrast agent; however, usage is limited due to extensive soft-tissue shrinkage. The mechanism of Lugol-induced shrinkage and how to prevent it is largely unknown, hampering applications of Lugol in clinical or forensic cases where tissue shrinkage can lead to erroneous diagnostic conclusions. Shrinkage was suggested to be due to an osmotic imbalance between tissue and solution. Pilot experiments pointed to acidification of Lugol, but the relation of acidification and tissue shrinkage was not evaluated. In this study, we analyzed the relation between tissue shrinkage, osmolarity and acidification of the solution during staining. Changes in tissue volume were measured on 2D-segmented magnetic resonance and diceCT images using AMIRA software. Partial correlation and stepwise regression analysis showed that acidification of Lugol is the main cause of tissue shrinkage. To prevent acidification, we developed a buffered Lugol’s solution (B-Lugol) and showed that stabilizing its pH almost completely prevented shrinkage without affecting staining. Changing from Lugol to B-Lugol is a major improvement for clinical and morphological research and only requires a minor adaptation of the staining protocol.

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