Imaging fetal anatomy.

Due to advancements in ultrasound techniques, the focus of antenatal ultrasound screening is moving towards the first trimester of pregnancy. The early first trimester however remains in part, a 'black box', due to the size of the developing embryo and the limitations of contemporary scanning techniques. Therefore there is a need for images of early anatomical developmental to improve our understanding of this area. By using new imaging techniques, we can not only obtain better images to further our knowledge of early embryonic development, but clear images of embryonic and fetal development can also be used in training for e.g. sonographers and fetal surgeons, or to educate parents expecting a child with a fetal anomaly. The aim of this review is to provide an overview of the past, present and future techniques used to capture images of the developing human embryo and fetus and provide the reader newest insights in upcoming and promising imaging techniques. The reader is taken from the earliest drawings of da Vinci, along the advancements in the fields of in utero ultrasound and MR imaging techniques towards high-resolution ex utero imaging using Micro-CT and ultra-high field MRI. Finally, a future perspective is given about the use of artificial intelligence in ultrasound and new potential imaging techniques such as synchrotron radiation-based CT to increase our knowledge regarding human development.

Technical note: Temperature estimation accuracy based on colourimetry of embalmed human and fresh non-human burned bone.

Estimation of the exposure temperature of skeletal remains can be done by means of colourimetry and a previously published decision model for the colourimetric data, resulting in clusters that represent a range of exposure temperature. The method was based on thermally altered freshly burned human skeletal remains. However, in practice the origin or pre-burning condition of (possibly fragmentary) burned remains can be unknown. Further, in order to use the colourimetric analysis, and accompanying decision model, it is important to have a reference or test set. Fresh human material is not available for this purpose in all countries. Hence, the classification accuracy of the decision model was tested for, in some countries more readily available substitutes for fresh bone; embalmed human bone and non-human bone. The model yielded high accuracies for these sample materials, making it possible to create a reference or test set from fresh non-human and embalmed human bone as substitute for human, and also to use the decision model for these deviating samples in practice.

A multidisciplinary approach to forensic biological profiling on a single tooth and nail sample.

INTRODUCTION: Analysis of a single tooth and nail can provide valuable forensic information, including year of birth, year of death, age, sex, DNA-profile, geographic residence during childhood and at time of death and drug exposure. The aim is to minimize the amount of used bodily material and to validate the applicability of a multidisciplinary sampling protocol. METHODS: A nail of the big toe, a tooth and blood of seven deceased individuals were collected postmortem. Collected materials were sampled and segmented in accordance with the multidisciplinary sampling protocol. DNA analysis was conducted on the pulp of the tooth, isotope analysis (Sr, Pb, O and C) on the enamel and 14C-, toxicological and tooth cementum annulation analysis on root segments. DNA-, isotope (Sr, Pb, O and C) -, toxicological-, and 14C -analysis were conducted on toenail segments. The acquired DNA profiles were compared with profiles acquired from blood. RESULTS: Material from seven deceased persons was analysed. 45 out of 56 analyses on dental samples were successful, constituting a success rate of 80%. Additionally, 27 out of 35 analyses were successful on nail samples, yielding a success rate of 77%. DNA-, toxicological and 14C- analyses performed better in nail than in tooth. Isotope analyses performed better in tooth than in nail. A profile with personal characteristics was constructed and matched for 62% of parameters with collected medical information. CONCLUSION: The performed sampling protocol for simultaneous multidisciplinary forensic analysis on a single tooth and nail sample provided applicable results and valuable information.

History and highlights of the teratological collection in the Narrenturm, Vienna (Austria).

The collection of the Narrenturm in Vienna houses and maintains more than 50,000 objects including approximately 1200 teratological specimens; making it one of the biggest collections of specimens from human origin in Europe. The existence of this magnificent collection-representing an important resource for dysmorphology research, mostly awaiting contemporary diagnoses-is not widely known in the scientific community. Here, we show that the Narrenturm harbors a wealth of specimens with (exceptionally) rare congenital anomalies. These museums can be seen as physical repositories of human malformation, covering hundreds of years of dedicated collecting and preserving, thereby creating unique settings that can be used to expand our knowledge of developmental conditions that have to be preserved for future generations of scientists.

Temperature-specific spectral shift of luminescing thermally altered human remains.

Human bone has shown to have luminescent properties that remain throughout the phases of cremation, with the exception of fully carbonized bone, when excited with a narrow band light source. During this research, an alternate light source (420-470nm, peak at 445nm) was used to visualize and investigate latent details relevant for forensic investigations of human remains recovered at fire scenes. As fire is a destructive force, it induces a vast variety of physical and chemical alterations to all components of the bone, making the subsequent analysis and interpretation of burned human remains challenging. A spectral shift in emission bandwidth, from green to red, was previously observed when the exposure temperature increased from 700 to 800 °C. This spectral shift was reproduced on a total of 10 human forearms, divided into 20 segments, by burning at 700 °C and 900 °C in an ashing furnace. The shift of emission bandwidth caused only by an increase in temperature was furthermore investigated by colorimetric analysis, proving the spectral shift to be significant. By easily quantifying the spectral shift, substantiation is provided for the use of this technique in practice to improve the interpretation of heat induced changes of bone.

Microfocus computed tomography for fetal postmortem imaging: an overview.

Over the last few years, fetal postmortem microfocus computed tomography (micro-CT) imaging has increased in popularity for both diagnostic and research purposes. Micro-CT imaging could be a substitute for autopsy, particularly in very early gestation fetuses for whom autopsy can be technically challenging and is often unaccepted by parents. This article provides an overview of the latest research in fetal postmortem micro-CT imaging with a focus on diagnostic accuracy, endovascular staining approaches, placental studies and the reversibility of staining. It also discusses new methods that could prove helpful for micro-CT of larger fetuses. While more research is needed, contrast-enhanced micro-CT has the potential to become a suitable alternative to fetal autopsy. Further research using this novel imaging tool could yield wider applications, such as its practise in imaging rare museum specimens.

Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation.

The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre-test probability, diagnosis left ventricular noncompaction cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post-natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non-invasive imaging. Using macroscopy, histology and low- and high-resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation-negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation-negative when assessed with MRI-based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.

The role of the University of Padua medical school in the study of conjoined twins between 18th and early 19th century.

The Medical School of Padua (Italy) contributed profoundly to the study of teratology. Many famous physicians and professors of medicine, such as Liceti, Vallisneri, Morgagni, and Malacarne, have studied and investigated these anomalies to better understand the causes and to find a potential explanation, often preserving the specimens for future studies. The present study highlights some historical cases of conjoined twins and a conjoined triplet preserved at the Morgagni Museum of Human Anatomy to show the development of medical theories in the teratological field between the 18th and early 19th century. This approach will provide insights into different study methods and ideas of some of the most famous scholars working in Padua at that time. The current article focuses on rare cases, both human and animal, that were encountered by physicians who worked in the Veneto area in the late 18th and early 19th century. Their detailed descriptions are not only of historical but also of contemporary dysmorphological value.

Mechanical or thermal damage: differentiating between underlying mechanisms as a cause of bone fractures.

To investigate the differences between pre- and post-fire fractures, 30 human forearm bones were subjected to either blunt-force impact, burning, or both. Bones, covered in soft tissue and wrapped in clothing, were burned in a reconstructed house fire. The burning context and dynamics led to differential burning, that was equal amongst the three groups. To evaluate the damage to the bones, a data collection sheet was developed based on the current literature on fracture features. To analyze the relation between exposure temperature and fracture class and occurrence, color was measured to estimate the exposure temperature. Observable and measurable changes on bone, and fracture surfaces, were macro- and microscopically analyzed. Many features overlapped between the three groups, and thus are not usable for differentiation. Fractures caused by blunt force impact (post-mortem, pre-fire) showed a rough fracture surface with smoothness in curved/slanted regions near the margin after burning, while heat-induced bone fractures showed a smooth fracture surface. The margins and surface of bone fractures that originated after the fire (indirect heat-induced) were evenly discolored, whereas heat-induced bone fractures showed uneven discoloration of the fracture margin and surface. Although there were generally more heat-induced fractures in the 450-700 °C range, no other distinctive trend was observed between exposure temperature and class of fractures.

The triangular fibrocartilage complex in the human wrist: A scoping review toward uniform and clinically relevant terminology.

The aim of this scoping review was to assess the composition, terminology, and anatomy of the triangular fibrocartilage complex (TFCC) of the wrist and propose unambiguous terminology regarding the individual components. The review was conducted according to the methodological framework by Arksey and O'Malley (International Journal of Social Research Methodology, 2005, 8, 19-32). Electronic databases were searched from inception until September 1, 2021 for original anatomical studies, using MeSH terms and keywords on terminology and anatomy of TFCC components. Studies using gross dissections or macro- or microscopic histology were included. Animal studies, fetal studies and studies with unknown disease status, were excluded. A total of 24 studies were included. The articular disc, the radioulnar ligaments, the meniscus homologue and the extensor carpi ulnaris tendon (sub)sheath were unanimously classified as TFCC components. One study did not include the ulnolunate and ulnotriquetral ligaments and only one study did include the ligamentum subcruentum. The largest disagreement existed regarding the inclusion of the ulnar collateral ligament. Terminological ambiguity was seen in "triangular fibrocartilage," "triangular ligament," "igamentum subcruentum," and the "proximal and distal lamina." Anatomical ambiguity existed especially regarding the radioulnar ligaments, the ulnar attachments of the TFCC and the ulnar collateral ligament. Definitions of the individual TFCC components are redundant, ambiguous, and ill-defined and therefore subject to different interpretations. In order to preclude confusion, consensus regarding terminology is recommended. We proposed a concise definition of the healthy TFCC that can be used as a starting point for future studies and current clinical practice.

A three-dimensional analysis of the development of cranial nerves in human embryos.

To increase our understanding of the etiology of specific neurological disorders (e.g., Duane syndrome, glossoptosis in Pierre Robin sequence), proper knowledge of anatomy and embryology of cranial nerves is necessary. We investigated cranial nerve development, studied histological sections of human embryos, and quantitatively analyzed the 3D reconstructions. A total of 28 sectioned and histologically stained human embryos (Carnegie stage [CS] 10 to 23 [21-60 days of development]) were completely digitalized by manual annotation using Amira software. Two specimens per stage were analyzed. Moreover, quantitative volume measurements were performed to assess relative growth of the cranial nerves. A chronologic overview of the morphologic development of each of the 12 cranial nerves, from neural tube to target organ, was provided. Most cranial nerves start developing at CS 12 to 13 (26-32 days of development) and will reach their target organ in stage 17 to 18 (41-46 days). In comparison to the rest of the developing brain, a trend could be identified in which relative growth of the cranial nerves increases at early stages, peaks at CS 17 and slowly decreases afterwards. The development of cranial nerves in human embryos is presented in a comprehensive 3D fashion. An interactive 3D-PDF is provided to illuminate the development of the cranial nerves in human embryos for educational purposes. This is the first time that volume measurements of cranial nerves in the human embryonic period have been presented.

Gunshot trauma in human long bones: towards practical diagnostic guidance for forensic anthropologists.

In contrast to cranial gunshot trauma, diagnosis and interpretation of gunshot trauma to long bones remains difficult and controversial. The aim of this study is to review the published literature on fracture patterns resulting from gunshot trauma in human long bones, and to use the described characteristics to provide practical guidance for the forensic anthropologist. In order to achieve this, medical and forensic publications on this topic were reviewed. Several types of fractures, such as linear, oblique, comminuted and butterfly fractures, have been observed in either the shaft or the ends of long bones. Indirect fractures that are not caused by bullets striking bone directly but by bullet-induced forces to the surrounding soft tissue have been found as well. Some of these fractures are related to a specific context or mechanism which might help in the forensic reconstruction of events. It is recommended that future research should focus on available medical data to provide more detailed descriptions on fracture patterns for forensic purposes. Experimentation with bone surrogates and computer modelling might also provide better and more realistic reconstructions of gunshot trauma in the future and provide valuable insights for its diagnosis and interpretation in forensic anthropology.

Dutch teratological collections and their artistic portrayals.

Several teratologic collections containing specimens with malformations and syndromes are maintained in a number of Dutch anatomical museums. Technically, these are not works of art or antiquities. However, many have been depicted in illustrations of such high quality that they merit discussion here. We review a selection of specimens and their artistic portrayals which find their origin in four Dutch teratological collections. These museum specimens are more than just intriguing objects for the inquisitive museum visitor. As we will substantiate, these specimens-and their artistic depictions-can be used to find and describe rarely occurring birth defects, provide etiopathogenetic information and are a source of novel diagnosis. Additionally, we briefly discuss the ethical aspects and motivations of exhibiting these specimens, as these collections have to be protected meticulously by the new generation of museum professionals, who eventually determine what kind of past our future will have. It is therefore imperative that these collections of antique specimens are treasured as their importance is easily overlooked.

Phosphorescence of thermally altered human bone.

Bone has photoluminescent characteristics that can aid the analysis of thermally altered human skeletal remains as part of the forensic anthropological investigation. Photoluminescence stands collectively for fluorescence and phosphorescence. Because the difference in lifetime between fluorescence and phosphorescence is usually in the range of nano- to microseconds, it is only possible to visually determine whether bone phosphoresces when the lifetime is long enough to be observed. For this study, a distinction was made between long-decay and short-decay phosphorescence. So far, it was unknown whether (thermally altered) human bone emits long-decay phosphorescence after being illuminated and, thus, whether phosphorescence contributes to the observed photoluminescence. If so, whether the observable phosphorescence is dependent on temperature, exposure duration, surrounding medium, bone type, skeletal element, and excitation light and could aid the temperature estimation of heated bone fragments. In this study, bone samples were subjected to heat in the range of from room temperature to 900 °C for various durations in either air or adipose as surrounding medium. In addition, different skeletal elements of a human cadaver were recollected after cremation in a crematorium. Both sample collections were illuminated with light of different bandwidths and visually inspected for phosphorescence and photoluminescence. The samples were scored by means of a scoring index for the intensity of long-decay phosphorescence and photographically documented. The results show that thermally altered human bone fragments do phosphoresce. The observed phosphorescence is more dependent on temperature than on exposure duration, surrounding medium or skeletal element. Of the used wavelength bands, ultraviolet light provided the most temperature-related information, showing changes in both phosphorescence intensity and emission spectrum. Long-decay phosphorescence and fluorescence with short-decay phosphorescence coincide; however, there are also temperature-dependent differences. It is therefore concluded that phosphorescence contributes to the observable photoluminescence and that the visibly observable phosphorescent characteristics can aid the temperature estimation of cremated human skeletal fragments.

The triangular fibrocartilage complex on high-resolution 3 T MRI in healthy adolescents: the thin line between asymptomatic findings and pathology.

OBJECTIVE: The objective of the study is to provide a reference for morphology, homogeneity, and signal intensity of triangular fibrocartilage complex (TFCC) and TFCC-related MRI features in adolescents. MATERIALS AND METHODS: Prospectively collected data on asymptomatic participants aged 12-18 years, between June 2015 and November 2017, were retrospectively analyzed. A radiograph was performed in all participants to determine skeletal age and ulnar variance. A 3-T MRI followed to assess TFCC components and TFCC-related features. A standardized scoring form, based on MRI definitions used in literature on adults, was used for individual assessment of all participants by four observers. Results per item were expressed as frequencies (percentages) of observations by all observers for all participants combined (n = 92). Inter-observer agreement was determined by the unweighted Fleiss' kappa with 95% confidence intervals (95% CI). RESULTS: The cohort consisted of 23 asymptomatic adolescents (12 girls and 11 boys). Median age was 13.5 years (range 12.0-17.0). Median ulnar variance was -0.7 mm (range - 2.7-1.4). Median triangular fibrocartilage (TFC) thickness was 1.4 mm (range 0.1-2.9). Diffuse increased TFC signal intensity not reaching the articular surface was observed in 30 (33%) observations and a vertical linear increased signal intensity with TFC discontinuation in 19 (20%) observations. Discontinuation between the volar radioulnar ligament and the TFC in the sagittal plane was seen in 23 (25%) observations. The extensor carpi ulnaris was completely dislocated in 10 (11%) observations, more frequent in supinated wrists (p = 0.031). Inter-observer agreement ranged from poor to fair for scoring items on the individual TFCC components. CONCLUSION: MRI findings, whether normal variation or asymptomatic abnormality, can be observed in TFCC and TFCC-related features of asymptomatic adolescents. The rather low inter-observer agreement underscores the challenges in interpreting these small structures on MRI. This should be taken into consideration when interpreting clinical MRIs and deciding upon arthroscopy.

Characterizing the coalescence area of conjoined twins to elucidate congenital disorders in singletons.

Shared anomalies, always located close to the area of coalescence and observable in virtually every type of conjoined twinning, are currently seen as separate anomalies caused by mostly unknown and seemingly unrelated pathways rather than being connected to the twinning mechanism itself. Therefore, most (case) reports about conjoined twins are mere descriptions of (external) dysmorphologies lacking reflections on the possible origin of their concomitant anomalies. As we will demonstrate in this article, shared anomalies are influenced, and in some cases solely and sequentially explained, by interaction aplasia and neo-axial orientation; two embryological mechanisms to which each set of conjoined twins is subjected and are responsible for their ultimate phenotypical fate. In this review, we consider how the ventral, lateral and caudal conjunction types and their intermediates determine the phenotypic presentation of the twins, including patterns of shared malformations and anomalies, which in themselves can be indistinguishable from those encountered in singleton cases. Hence, it can be hypothesized that certain anomalies in singletons originate in a fashion similar to that in conjoined twins.

Development pattern of tracheal cartilage in human embryos.

INTRODUCTION: Congenital tracheal anomalies are associated with high morbidity and mortality. The etiology of congenital tracheal anomalies is not well understood, but often attributed to malformed tracheal cartilage. The development of tracheal cartilage has not been described in detail. In this study, we aimed to investigate the development pattern and timing of normal tracheal cartilage to better understand the etiology of tracheal anomalies. MATERIALS AND METHODS: The development of tracheal cartilage was examined by studying the trachea in histological sections of 14 healthy human embryos from the Carnegie collection. Two specimens for Carnegie Stages 17-23 (42-60 days of embryological development) were studied. RESULTS: At Carnegie Stages 17-19 (42-51 days), a continuous mesenchymal condensation was observed ventral to the tracheal lumen. At Stages 20 and 21 (51-54 days), this pre-tracheal mesenchyme showed sites of increased condensation indicative of future tracheal rings. Furthermore, growth centers were identified both proximally and distally in the trachea. Characteristic horseshoe shaped tracheal rings were apparent at Carnegie Stages 22 and 23 (54-60 days). CONCLUSIONS: In human embryos, tracheal rings arise from growth centers in the ventral mesenchyme at approximately 51-54 days of embryological development. The observation of proximal and distal growth centers suggests a centripetal growth gradient, potentially contributing to occurrence of complete tracheal ring deformity (CTRD). Although this study shows new insights on tracheal cartilage development, the exact origin of congenital tracheal defects has yet to be elucidated.

Bilateral symmetry of the subtalar joint facets and the relationship between the morphology and osteoarthritic changes.

There is a paucity in the literature regarding bilateral symmetry between the facets of the subtalar joint. Often surgeons use the contralateral side as a reference when dealing with a fracture or other joint pathology. Moreover, the presence of osteoarthritic (OA) changes in the subtalar joint is suggested to have a relation with its morphology. In this study, we addressed both these issues. Forty pairs of cadaveric tali and calcanei were analyzed by dissection and measurement. Twenty pairs of asymptomatic calcanei were morphologically analyzed by computer tomography imaging. In the cadaveric feet, the length and width of the facets, the number and interfacet connections, the intersection angle, and the presence of OA changes were registered. In the healthy feet, the orientation and curvature of the posterior facet were analyzed based on cylinder fittings. Bilateral symmetry was tested with paired Student's t tests. Significant associations between morphometric parameters and the presence of OA changes were tested with generalized estimating equation logistic regression models. The morphometric data demonstrated a high degree of bilateral symmetry. The types of tali and calcanei between left and right differed in about one-fifth of the individuals. No significant interactions were found between morphological parameters and the presence of OA changes. Only age had a significant association. There was a high degree of symmetry in the subtalar joints facets. No significant associations were found between OA changes and morphological features, whereas other studies did. Further research is needed to explore this relationship in further detail. Clin. Anat., 33:997-1006, 2020. © 2019 Wiley Periodicals, Inc.

Sinus venosus incorporation: contentious issues and operational criteria for developmental and evolutionary studies.

The sinus venosus is a cardiac chamber upstream of the right atrium that harbours the dominant cardiac pacemaker. During human heart development, the sinus venosus becomes incorporated into the right atrium. However, from the literature it is not possible to deduce the characteristics and importance of this process of incorporation, due to inconsistent terminology and definitions in the description of multiple lines of evidence. We reviewed the literature regarding the incorporation of the sinus venosus and included novel electrophysiological data. Most mammals that have an incorporated sinus venosus show a loss of a functional valve guard of the superior caval vein together with a loss of the electrical sinuatrial delay between the sinus venosus and the right atrium. However, these processes are not necessarily intertwined and in a few species only the sinuatrial delay may be lost. Sinus venosus incorporation can be characterised as the loss of the sinuatrial delay of which the anatomical and molecular underpinnings are not yet understood.

GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrum.

The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty-eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.