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ATRX is one of the most frequently mutated genes in high-risk neuroblastoma. ATRX mutations are mutually exclusive with MYCN amplification and mark a recognizable patient subgroup, presenting in older children with chemotherapy-resistant, slowly progressive disease. The mechanisms underlying how ATRX mutations drive high-risk and difficult-to-treat neuroblastoma are still largely elusive. To unravel the role of ATRX in neuroblastoma, we generated isogenic neuroblastoma cell line models with ATRX loss-of-function and ATRX in-frame multi-exon deletions, representing different types of alterations found in patients. RNA-sequencing analysis consistently showed significant upregulation of inflammatory response pathways in the ATRX-altered cell lines. In vivo, ATRX alterations are consistently associated with macrophage infiltration across multiple xenograft models. Furthermore, ATRX alterations also result in upregulation of epithelial-to-mesenchymal transition pathways and a reduction in expression of adrenergic core-regulatory circuit genes. Consistent with this, bioinformatic analysis of previously published neuroblastoma patient data sets revealed that ATRX-altered neuroblastomas display an immunogenic phenotype and higher score of macrophages (with no distinction between M1 and M2 macrophage populations) and dendritic cells, but not lymphocytes. Histopathological assessment of diagnostic samples from patients with ATRX mutant disease confirmed these findings with significantly more macrophage infiltration compared to MYCN-amplified tumors. In conclusion, we show that gene expression and cell-state changes as a result of ATRX alterations associate with a characteristic immune cell infiltration in both in vivo models and patient samples. Together, this provides novel insight into mechanisms underlying the distinct clinical phenotype seen in this group of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Introduction: The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes., Methods: A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors., Results: Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes., Discussion: Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Ltd.)

Approximately 10% of children with cancer harbor a mutation in a predisposition gene. In children with the kidney cancer Wilms tumor, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumor, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA sequencing, and genome-wide methylation, validating our findings in an independent cohort. Tumor development differed in children harboring a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high-risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Our findings indicate that predisposition may preordain Wilms tumorigenesis, suggesting a variant-specific approach to managing children merits consideration. Significance: Tumors that arise in children with a cancer predisposition may develop through the same mutational pathways as sporadic tumors. We examined this question in the childhood kidney cancer, Wilms tumor. We found that certain predispositions dictate the genetic development of tumors, with clinical implications for these children. See related commentary by Brzezinski and Malkin, p. 258., (©2025 American Association for Cancer Research.)

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. This prompts the question whether a conventional postmortem examination should remain the gold standard for the anatomical examination of fetal loss. This report summarizes the "for" and "against" arguments made by two experts during a debate at the 28th International Conference on Prenatal Diagnosis and Therapy. Arguments favoring comprehensive fetal autopsy include the need to obtain the most complete and accurate information about the cause of the stillbirth. Arguments in favor of less invasive post-mortem examinations using other technologies include sufficiency in many instances and a more equitable and cost-effective approach to postmortem examination. While both debaters weighed the balance of these conflicting arguments differently, they agreed that more research in this area is needed., (© 2025 John Wiley & Sons Ltd.)

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature. In keeping with epigenetic alterations being a common driver of many childhood cancers, fragmentomics analysis of cfDNA identified tumour-specific epigenetic states and transcription factor binding sites accessible in chromatin. This study leverages a large and well-annotated genomic dataset of aggressive childhood malignancies, identifies genomic and epigenetic drivers of childhood cancer relapse, and highlights the power and practicality of cfDNA analysis to capture both intra-tumoural heterogeneity and the epigenetic state of cancer cells.

The integration of artificial intelligence (AI) into healthcare is becoming increasingly mainstream. Leveraging digital technologies, such as AI and deep learning, impacts researchers, clinicians, and industry due to promising performance and clinical potential. Digital pathology is now a proven technology, enabling generation of high-resolution digital images from glass slides (whole slide images; WSI). WSIs facilitates AI-based image analysis to aid pathologists in diagnostic tasks, improve workflow efficiency, and address workforce shortages. Example applications include tumor segmentation, disease classification, detection, quantitation and grading, rare object identification, and outcome prediction. While advancements have occurred, integration of WSI-AI into clinical laboratories faces challenges, including concerns regarding evidence quality, regulatory adaptations, clinical evaluation, and safety considerations. In pediatric and developmental histopathology, adoption of AI could improve diagnostic efficiency, automate routine tasks, and address specific diagnostic challenges unique to the specialty, such as standardizing placental pathology and developmental autopsy findings, as well as mitigating staffing shortages in the subspeciality. Additionally, AI-based tools have potential to mitigate medicolegal implications by enhancing reproducibility and objectivity in diagnostic evaluations. An overview of recent developments and challenges in applying AI to pediatric and developmental pathology, focusing on machine learning methods applied to WSIs of pediatric pathology specimens is presented., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy has been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily for limited volumes., Methods: We used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on the microarchitecture of its structural components. We scanned 15 human thymi (9 foetal and 6 postnatal) with synchrotron radiation, and repeated scans using a conventional laboratory x-ray system. We used histology, immunofluorescence and flow cytometry to validate the x-ray findings., Results: Application to human thymi at pre- and post-natal stages allowed reliable tracking and quantification of the evolution of parameters such as size and distribution of Hassall's Bodies and medulla-to-cortex ratio, whose changes reflect adaptation of thymic activity. We show that Hassall's bodies can occupy 25% of the medulla volume, indicating they should be considered a third thymic compartment with possible implications on their role. Moreover, we demonstrate compatible results can be obtained with standard laboratory-based x-ray equipment, making this research tool accessible to a wider community., Conclusions: Our study allows overcoming the resolution and/or volumetric limitations of existing approaches for the study of thymic disfunction in congenital and acquired disorders affecting the adaptive immune system., (© 2024. The Author(s).)

Aim: To evaluate the impact of a new, less-invasive micro-computed tomography (CT) service on autopsy service provision. We recorded parental consent, type of autopsy performed, autopsy reporting times and time taken for the body to be released from the mortuary., Materials and Methods: A retrospective, single-centre case series was conducted for all perinatal deaths since the introduction of our micro-CT service in 2016, with a detailed review of records extracted from 2019 and 2021. Fetal demographics (gestational age, weight), type of autopsy conducted, and the time taken from receiving the body to releasing the body and issuing a final report were recorded., Results: Micro-CT imaging uptake increased to over two hundred cases/year by 2021. Overall, invasive autopsies reduced from (45.8%, 196/428; 2019) to (32.1%, 125/390; 2021) with an equivalent rise in less-invasive autopsy from 54.2% (232/428;2019) to 67.9% (265/390;2019). Offering a micro-CT service resulted in an increase in consent to imaging-based autopsies from (76.9%, 329/428;2019) to (87.2%, 340/390;2021). Micro-CT has become the most common post-mortem imaging performed in our institution at 54.4% (212/251;2021), although the body preparation time from the tissue staining required has increased the time to provide an autopsy report to 17 days and release of the body to 18 days., Conclusion: Our study shows that introducing a micro-CT post-mortem imaging service was associated with reduced use of conventional invasive procedures, despite a slight increase in turnaround times. Understanding these factors and continued improvements in micro-CT service delivery will help make this accessible to a wider population in the future., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objective: We investigated sudden unexpected death in infancy (SUDI) autopsy data from 1996 to 2015 inclusive, comparing findings from infants with and without pre-existing medical conditions., Design: Large, retrospective single-centre autopsy series., Setting: Tertiary paediatric hospital, London, UK., Methods: Non-identifiable autopsy findings were extracted from an existing research database for infants older than 7 days up to and including 365 days old who died suddenly and unexpectedly (SUDI; n=1739). Cases were classified into SUDI with pre-existing condition (SUDI-PEC) (n=233) versus SUDI without PEC (SUDI non-PEC) (n=929), where PEC indicates a potentially life-limiting pre-existing medical condition. Findings were compared between groups including evaluation of type of PEC and whether the deaths were medically explained (infectious or non-infectious) or apparently unexplained., Results: Median age of death was greater in SUDI-PEC compared with SUDI non-PEC (129 days vs 67 days) with similar male to female ratio (1.4:1). A greater proportion of deaths were classified as medically explained in SUDI-PEC versus SUDI non-PEC (73% vs 30%). Of the explained SUDI, a greater proportion of deaths were non-infectious for SUDI-PEC than SUDI non-PEC (66% vs 32%). SUDI-PEC (infectious) infants were most likely to have respiratory infection (64%), with susceptible PEC, including neurological, prematurity with a PEC, and syndromes or other anomalies., Conclusion: SUDI-PEC deaths occur later in infancy and are likely to have their death attributed to their PEC, even in the absence of specific positive autopsy findings. Future research should aim to further define this cohort to help inform SUDI postmortem guidelines, paediatric clinical practice to reduce infant death, and to reduce the risk of overattribution of deaths in the context of a PEC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Three cats were presented for unusual collapsing episodes. Echocardiography revealed a hypertrophic cardiomyopathy (HCM) phenotype in each cat. Continuous electrocardiographic monitoring showed that the clinical signs coincided with periods of severe ST-segment elevation in each cat. The first cat was treated with amlodipine and diltiazem but did not improve and was euthanized due to poor quality of life. Postmortem examination revealed cardiac lymphoma without obstructive coronary disease. The second cat was thought to have cardiac lymphoma, based on pericardial effusion cytology, and was euthanized before starting therapy. The third cat was diagnosed with HCM and left ventricular outflow tract obstruction and was treated with atenolol and diltiazem. This treatment reduced the frequency of episodic clinical signs, but the cat subsequently developed congestive heart failure and was euthanized. This case series describes clinical signs associated with severe ST elevation in cats with an HCM phenotype, and their outcomes. Continuous electrocardiographic monitoring was necessary to detect transient ST elevation in each case., Competing Interests: Conflict of Interest Statement The authors do not have any conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: The purpose of this project was to determine if physician participation in simulation affects students' perceptions of nurse/physician communication and collaboration. Fifty-five students participated in six groups. Three groups had a physician present and involved during their eight-hour pediatric simulation; the others continued with current practice, which involved phone contact with an individual posing as a physician. There was a statistically significant difference in two items on the Nurse Attitudes About Communicating and Collaborating With Physicians tool when pre- and post-simulation means were compared. Findings are consistent with previous research, indicating simulation-based learning can improve students' perceptions of nurse-physician collaboration., Competing Interests: The author has declared no conflict of interest., (Copyright © 2024 National League for Nursing.)

Listening to music manipulates attention to be more externally focused, which has the potential to improve muscular efficiency. This study aimed to determine the effect of listening to music on muscle activation during an isometric exercise task, and compare this effect to those of other attentional focus conditions. Apparently healthy subjects ( n = ​35; 16 men/19 women) completed an isometric elbow flexion task for 1 ​min in three randomized and counterbalanced conditions: internal focus (INT), external focus with a simple distraction task (EXT), or listening to music (MUS). Muscle activation of the biceps and triceps brachii and heart rate (HR) were recorded throughout the exercise tasks. Ratings of perceived exertion (RPE), affective valence, and motivation were measured at the end of each trial. There was no difference in muscle activation measures among the three conditions. HR during MUS was lower than EXT at 15 ​s ([89.4 ​± ​11.8] beats/min vs. [93.1 ​± ​12.9] beats/min; p  ​= ​0.018) and 30 ​s ([90.6 ​± ​12.4] beats/min vs. [94.2 ​± ​12.5] beats/min; p  ​= ​0.026), and lower than INT at 60 ​s ([93.3 ​± ​13.3] beats/min vs. [96.7 ​± ​12.0] beats/min; p  ​= ​0.016). Overall RPE was higher for INT (13.4 ​± ​2.2) than for MUS ([12.6 ​± ​2.0]; p  ​= ​0.020) and EXT ([11.94 ​± ​2.22]; p  ​< ​0.001). Affective valence was higher for MUS than for INT ([2.7 ​± ​1.4] vs. [2.1 ​± ​1.5]; p  ​= ​0.011). Manipulating attentional focus did not alter muscle activation for a light-intensity isometric muscular endurance task, though MUS was reported as more positive and requiring less exertion to complete than INT. Using music can therefore be recommended during light-intensity isometric exercise based on the psychological benefits observed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Objectives: The aim of this study was to evaluate the length of time required to achieve full iodination using potassium tri-iodide as a contrast agent, prior to human fetal postmortem microfocus computed tomography (micro-CT) imaging., Methods: Prospective assessment of optimal contrast iodination was conducted across 157 human fetuses (postmortem weight range 2-298 g; gestational age range 12-37 weeks), following micro-CT imaging. Simple linear regression was conducted to analyse which fetal demographic factors could produce the most accurate estimate for optimal iodination time., Results: Postmortem body weight ( r 2 = 0.6435) was better correlated with iodination time than gestational age ( r 2 = 0.1384), producing a line of best fit, y = [0.0304 × body weight (g)] - 2.2103. This can be simplified for clinical use whereby immersion time (days) = [0.03 × body weight (g)] - 2.2. Using this formula, for example, a 100-g fetus would take 5.2 days to reach optimal contrast enhancement., Conclusions: The simplified equation can now be used to provide estimation times for fetal contrast preparation time prior to micro-CT imaging and can be used to manage service throughput and parental expectation for return of their fetus., Advances in Knowledge: A simple equation from empirical data can now be used to estimate preparation time for human fetal postmortem micro-CT imaging., Competing Interests: The authors declare that they have no competing financial interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Introduction: Comprehensive imaging using ultrasound and MRI of placenta accreta spectrum (PAS) aims to prevent catastrophic haemorrhage and maternal death. Standard MRI of the placenta is limited by between-slice motion which can be mitigated by super-resolution reconstruction (SRR) MRI. We applied SRR in suspected PAS cases to determine its ability to enhance anatomical placental assessment and predict adverse maternal outcome., Methods: Suspected PAS patients (n = 22) underwent MRI at a gestational age (weeks + days) of (32 +3 ±3 +2 , range (27 +1 -38 +6 )). SRR of the placental-myometrial-bladder interface involving rigid motion correction of acquired MRI slices combined with robust outlier detection to reconstruct an isotropic high-resolution volume, was achieved in twelve. 2D MRI or SRR images alone, and paired data were assessed by four radiologists in three review rounds. All radiologists were blinded to results of the ultrasound, original MR image reports, case outcomes, and PAS diagnosis. A Random Forest Classification model was used to highlight the most predictive pathological MRI markers for major obstetric haemorrhage (MOH), bladder adherence (BA), and placental attachment depth (PAD)., Results: At delivery, four patients had placenta praevia with no abnormal attachment, two were clinically diagnosed with PAS, and six had histopathological PAS confirmation. Pathological MRI markers (T2-dark intraplacental bands, and loss of retroplacental T2-hypointense line) predicting MOH were more visible using SRR imaging (accuracy 0.73), in comparison to 2D MRI or paired imaging. Bladder wall interruption, predicting BA, was only easily detected by paired imaging (accuracy 0.72). Better detection of certain pathological markers predicting PAD was found using 2D MRI (placental bulge and myometrial thinning (accuracy 0.81)), and SRR (loss of retroplacental T2-hypointense line (accuracy 0.82))., Discussion: The addition of SRR to 2D MRI potentially improved anatomical assessment of certain pathological MRI markers of abnormal placentation that predict maternal morbidity which may benefit surgical planning., Competing Interests: Declaration of competing interest None, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection within the epithelialized lung by infecting primary human airway epithelial cells and subsequently injecting neutrophils. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma., (© 2023. Springer Nature Limited.)

Objective: To assess the impact of maternal Coronavirus disease 2019 (COVID-19) infection on placental histopathological findings in an unselected population and evaluate the potential effect on the fetus, including the possibility of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Design: Retrospective cohort comparative study of placental histopathological findings in patients with COVID-19, compared with controls., Setting: During the COVID-19 pandemic, placentas were studied from women at University College Hospital London who reported and/or tested positive for COVID-19., Population: Of 10 508 deliveries, 369 (3.5%) women had COVID-19 during pregnancy, with placental histopathology available for 244 women., Methods: Retrospective review of maternal and neonatal characteristics, where placental analysis had been performed. This was compared with available, previously published, histopathological findings from placentas of unselected women., Main Outcome Measures: Frequency of placental histopathological findings and relevant clinical outcomes., Results: Histological abnormalities were reported in 117 of 244 (47.95%) cases, with the most common diagnosis being ascending maternal genital tract infection. There was no statistically significant difference in the frequency of most abnormalities compared with controls. There were four cases of COVID-19 placentitis (1.52%, 95% CI 0.04%-3.00%) and one possible congenital infection, with placental findings of acute maternal genital tract infection. The rate of fetal vascular malperfusion (FVM), at 4.5%, was higher compared with controls (p = 0.00044)., Conclusions: In most cases, placentas from pregnant women infected with SARS-CoV-2 virus do not show a significantly increased frequency of pathology. Evidence for transplacental transmission of SARS-CoV-2 is lacking from this cohort. There is a need for further study into the association between FVM, infection and diabetes., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Effective communication is an essential skill for the professional nurse. Previous research demonstrates that nursing students lack skills in written communication, and there is limited time in the nursing curriculum to provide needed instruction. To address this issue, a writing workshop was provided for students at a regional state university., Methods: Nursing faculty developed and led four identical in-person sessions of the workshop over the course of one semester. Before and after each workshop, students completed the same quantitative survey., Results: Data indicate that students' knowledge and confidence of American Psychological Association (APA) format increased significantly as a result of the workshop., Conclusion: A workshop approach is a useful strategy to address the writing needs of nursing students., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Shortwave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ∼0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of patients with neuroblastoma, warranting investigation in future clinical trials., Significance: Multispectral near-infrared I/shortwave infrared fluorescence imaging is a versatile system enabling high tumor-to-background signal for safer and more complete resection of pediatric tumors during surgery., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose : To determine whether swimming while listening to fast (140 bpm) or moderate tempo (120 bpm) music enhances physical performance compared to a non-music condition. Methods : Sixteen healthy university students (21.5 ± 2.3 years) with a minimum of one year of experience swimming front crawl were recruited. All completed four testing sessions. In the first session, a graded exercise treadmill test was performed to establish baseline fitness. The next three visits were at the swimming pool and participants were asked to swim as far as possible in 12-minutes (i.e., Swimming Cooper Test) under each of three randomly assigned conditions: 120 bpm (M120), 140 bpm (M140) and a non-music condition (NM). Results : No significant differences were found between conditions for either heart rate (p > .05) or rating of perceived exertion (p > .05). However, differences were found on distance covered (p = .014) between M120 (305.7 ± 19.7 m) and M140 (321.2 ± 19.4 m; p = .035), and on stroke frequency (p = .009) between M120 (48.4 ± 1.8) and M140 (51.6 ± 1.9; p = .028). Conclusion : These results suggest that distance covered and the frequency of strokes per minute were greater when participants were exposed to fast tempo music (M140) compared to moderate tempo music (M120) and a non-music condition (NM) in a 12-minute swimming test.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children., (© 2023. The Author(s).)

Purpose: ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway., Experimental Design: We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin, and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX)., Results: Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX, lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth., Conclusions: In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma., (©2023 The Authors; Published by the American Association for Cancer Research.)

Introduction/objectives: Thin and hypokinetic myocardial segments (THyMS) represent adverse ventricular (LV) remodeling in human hypertrophic cardiomyopathy. We describe the echocardiographic features and outcome in cats with THyMS, and in a subpopulation, the echocardiographic phenotype before LV wall thinning was detected (pre-THyMS)., Animals: Eighty client-owned cats., Materials and Methods: Retrospective multicenter study. Clinical records were searched for cats with THyMS, defined as LV segment(s) with end-diastolic wall thickness (LVWT) <3 mm and hypokinesis in the presence of ≥one LV segment(s) with LVWT >4 mm and normal wall motion. When available, echocardiograms pre-THyMS were assessed. Survival time was defined as time from first presentation with THyMS to death., Results: Mean thickest LV wall segment (MaxLVWT) was 6.1 mm (95% CI 5.8-6.4 mm) and thinnest (MinLVWT) was 1.7 mm (95% CI 1.6-1.9 mm). The LV free wall was affected in 74%, apex in 13% and septum in 5%. Most cats (85%) presented with heart failure and/or arterial thromboembolism. Median circulating troponin I concentration was 1.4 ng/mL ([range 0.07-180 ng/mL]). Prior echocardiography results were available for 13/80 cats, a mean of 2.5 years pre-THyMS. In segments subsequently undergoing thinning, initial MaxLVWT measured 6.7 mm (95% CI 5.8-7.7 mm) vs. 1.9 mm (95% CI 1.5-2.4 mm) at last echocardiogram (P<0.0001). Survival data were available for 56/80 cats, median survival time after diagnosing THyMS was 153 days (95% CI 83-223 days). Cardiac histopathology in one cat revealed that THyMS was associated with severe transmural scarring., Conclusions: Cats with THyMS had advanced cardiomyopathy and a poor prognosis., Competing Interests: Conflicts of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study compared the effects of an increasing-intensity (UP) and a decreasing-intensity (DOWN) resistance training protocol on affective responses across six training sessions. Novice participants (Mage 43.5 ± 13.7 years) were randomly assigned to UP (n = 18) or DOWN (n = 17) resistance training groups. Linear mixed-effects models showed that the evolution of affective valence within each training session was significantly moderated by the group (b = -0.45, p ≤ .001), with participants in the UP group reporting a decline in pleasure during each session (b = -0.82) and the DOWN group reporting an improvement (b = 0.97; ps < .001). Remembered pleasure was significantly higher in the DOWN group compared to the UP group (b = 0.57, p = .004). These findings indicate that a pattern of decreasing intensity throughout a resistance exercise session can elicit more positive affective responses and retrospective affective evaluations of resistance training.

Despite aggressive treatments, the prognosis of high-risk NB remains poor. Surgical oncology needs innovative intraoperative devices to help surgeons discriminate malignant tissue from necrotic and surrounding healthy tissues. Changes within the tumor vasculature could be used intraoperatively as a diagnostic tool to guide surgical resection. Here, we retrospectively analyzed the mean vascular density (MVD) of different NB subtypes at diagnosis and after induction chemotherapy using scanned histological samples. One patient was prospectively enrolled, and an ex vivo photoacoustic imaging (PAI) scan was performed on two representative sections to assess its capacity to discriminate different tumor regions. We found that post-chemotherapy, viable areas of differentiating NBs and ganglioneuroblastomas are associated with higher MVD compared to poorly differentiated NBs. Early necrotic regions showed higher MVD than late necrotic and viable regions. Finally, calcified areas showed significantly lower MVD than any other histological component. The acquired PAI images showed a good high-resolution ex vivo 3D delineation of NB margins. Overall, these results suggest that a high-definition preclinical imaging device such as PAI could potentially be exploited to guide surgical resection by identifying different vasculature signatures.

Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model., Competing Interests: P.D.C. and L.U. are named inventors of patent application No. PCT/EP2016/071114 and P.D.C. and L.U. are named inventors of UK patent application No. 1708729.7. The remaining authors declare no competing interests., (© 2022.)

Objectives: To determine the feasibility of micro-CT as a high-resolution 3D imaging tool for thyroglossal duct cysts and to evaluate its role augmenting traditional histopathological examination of resected specimens. Methods: A single centre, prospective case series of consecutive children undergoing excision of a thyroglossal duct cyst was performed at a quaternary paediatric referral hospital in the United Kingdom. Consecutive children listed for excision of a thyroglossal duct cyst whose parents agreed to participate were included and there were no exclusion criteria. Results: Surgically excised thyroglossal duct cyst or remnant specimens from five patients (two males, three females) were examined using micro-CT alongside traditional histopathological examination. In all cases, micro-CT imaging was able to demonstrate 3D imaging datasets of the specimens successfully and direct radio-pathological comparisons were made ( Figures 1 - 5 , Supplementary Video 1). Conclusions: The study has shown the feasibility and utility of post-operative micro-CT imaging of thyroglossal duct cysts specimens as a visual aid to traditional histopathological examination. It better informs the pathological specimen sectioning using multi-planar reconstruction and volume rendering tools without tissue destruction. In the complex, often arborised relationship between a thyroglossal duct cyst and the hyoid, micro-CT provides valuable image plane orientation and indicates proximity of the duct to the surgical margins. This is the first case series to explore the use of micro-CT imaging for pediatric thyroglossal duct specimens and it informs future work investigating the generalizability of micro-CT imaging methods for other lesions, particularly those from the head and neck region where precisely defining margins of excision may be challenging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Frauenfelder, Shelmerdine, Simcock, Hall, Hutchinson, Ashworth, Arthurs and Butler.)

Post-mortem imaging has a high acceptance rate amongst parents and healthcare professionals as a non-invasive method for investigating perinatal deaths. Previously viewed as a 'niche' subspecialty, it is becoming increasingly requested, with general radiologists now more frequently asked to oversee and advise on appropriate imaging protocols. Much of the current literature to date has focussed on diagnostic accuracy and clinical experiences of individual centres and their imaging techniques (e.g. post-mortem CT, MRI, ultrasound and micro-CT), and pragmatic, evidence-based guidance for how to approach such referrals in real-world practice is lacking. In this review, we summarise the latest research and provide an approach and flowchart to aid decision-making for perinatal post-mortem imaging. We highlight key aspects of the maternal and antenatal history that radiologists should consider when protocolling studies (e.g. antenatal imaging findings and history), and emphasise important factors that could impact the diagnostic quality of post-mortem imaging examinations (e.g. post-mortem weight and time interval). Considerations regarding when ancillary post-mortem image-guided biopsy tests are beneficial are also addressed, and we provide key references for imaging protocols for a variety of cross-sectional imaging modalities., (© 2021. The Author(s).)

Background: COVID-19 lockdowns have reduced opportunities for physical activity (PA) and encouraged more sedentary lifestyles. A concomitant of sedentariness is compromised mental health. We investigated the effects of COVID-19 lockdown on PA, sedentary behavior, and mental health across four Western nations (USA, UK, France, and Australia)., Methods: An online survey was administered in the second quarter of 2020 (N = 2541). We measured planned and unplanned dimensions of PA using the Brunel Lifestyle Physical Activity Questionnaire and mental health using the 12-item General Health Questionnaire. Steps per day were recorded only from participants who used an electronic device for this purpose, and sedentary behavior was reported in hours per day (sitting and screen time)., Results: In the USA and Australia samples, there was a significant decline in planned PA from pre- to during lockdown. Among young adults, Australians exhibited the lowest planned PA scores, while in middle-aged groups, the UK recorded the highest. Young adults exhibited the largest reduction in unplanned PA. Across nations, there was a reduction of ~ 2000 steps per day. Large increases in sedentary behavior emerged during lockdown, which were most acute in young adults. Lockdown was associated with a decline in mental health that was more pronounced in women., Conclusions: The findings illustrate the deleterious effects of lockdown on PA, sedentary behavior, and mental health across four Western nations. Australian young and lower middle-aged adults appeared to fare particularly badly in terms of planned PA. The reduction in steps per day is equivalent to the non-expenditure of ~ 100 kcal. Declines in mental health show how harmful lockdowns can be for women in particular.

A well-functioning placenta is critical for healthy fetal development, as the placenta brings fetal blood in close contact with nutrient rich maternal blood, enabling exchange of nutrients and waste between mother and fetus. The feto-placental circulation forms a complex branching structure, providing blood to fetal capillaries, which must receive sufficient blood flow to ensure effective exchange, but at a low enough pressure to prevent damage to placental circulatory structures. The branching structure of the feto-placental circulation is known to be altered in complications such as fetal growth restriction, and the presence of regions of vascular dysfunction (such as hypovascularity or thrombosis) are proposed to elevate risk of placental pathology. Here we present a methodology to combine micro-computed tomography and computational model-based analysis of the branching structure of the feto-placental circulation in ex vivo placentae from normal term pregnancies. We analyse how vascular structure relates to function in this key organ of pregnancy; demonstrating that there is a 'resilience' to placental vascular structure-function relationships. We find that placentae with variable chorionic vascular structures, both with and without a Hyrtl's anastomosis between the umbilical arteries, and those with multiple regions of poorly vascularised tissue are able to function with a normal vascular resistance. Our models also predict that by progressively introducing local heterogeneity in placental vascular structure, large increases in feto-placental vascular resistances are induced. This suggests that localised heterogeneities in placental structure could potentially provide an indicator of increased risk of placental dysfunction., Competing Interests: Conflict of Interest No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Context.—: Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborns are heterogeneous., Objectives.—: To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death., Design.—: A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm., Results.—: Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery., Conclusions.—: A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies., (© 2021 College of American Pathologists.)

Background: Priming is a process in which exposure to a stimulus activates relevant mental representations that are given increased weight in subsequent judgment tasks. Affective primes can influence affective evaluations and associations. Such influence has meaningful implications for the promotion of exercise behavior, yet there is scant research on priming effects in exercise settings., Purpose: The purpose of the present pair of studies was to examine the efficacy of music (M), music video (MV), and music video with affective primes (PRIME) in modulating psychological responses during and immediately following an exercise bout among two distinct populations., Methods: In Study 1, physically active participants completed a brisk walking task on a treadmill under four conditions: M, MV, PRIME, and control. Affective valence and rating of perceived exertion (RPE) were assessed during exercise and remembered/forecasted pleasure was measured immediately following each exercise bout. In Study 2, largely inactive and overweight participants completed a brisk walking task on a treadmill under two conditions: MV and PRIME. Affective valence was assessed during exercise, while exercise enjoyment and remembered/forecasted pleasure were assessed postexercise., Results: In Study 1, PRIME yielded more positively valenced affect, remembered/forecasted pleasure, and lower RPE when compared to the other conditions (MCohen's d for all DVs = 0.91). In Study 2, PRIME elicited more positively valenced affect, greater enjoyment, and enhanced remembered/forecasted pleasure when compared to MV (MCohen's d for all DVs = 0.64)., Conclusions: Subliminal primes embedded in music video can elicit positive changes in psychological responses during and immediately following exercise., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ligamentum arteriosum calcification may be a normal finding in some children, although the frequency has not been well described., Objective: To estimate the frequency of ligamentum arteriosum calcification in children at postmortem imaging., Materials and Methods: We conducted a single-centre retrospective review of paediatric postmortem CT and chest radiographic imaging over a 6-year period (January 2012 to December 2018). Two independent reviewers assessed the presence of calcification on imaging. We calculated descriptive statistical analysis of ligamentum arteriosum calcification frequency and association with age and gender., Results: During the study period, 220 children underwent whole-body postmortem CT and 182 underwent radiographic imaging. The frequency was higher on postmortem CT than plain radiographs (67/220, 30.5% vs. 3/182, 1.6%) and was highest in children ages 1-7 years (53.6-66.7%), with gradual reduction in frequency in older children, and none in children older than 12 years. There was no gender predilection., Conclusion: In the postmortem setting, ligamentum arteriosum calcification is a common finding in children <8 years of age. It can be better identified on postmortem CT than chest radiographs. Radiologists new to reporting postmortem paediatric CT studies should recognise this as a common normal finding to avoid unnecessary further investigations at autopsy.

Background: Noninvasive imaging autopsy alternatives for fetuses weighing <500 grams are limited. Microfocus computed tomography has been reported as a viable option in small case series with the potential to avoid an invasive autopsy. Implementation of postmortem microfocus computed tomography in a large cohort as part of routine clinical service has yet been unreported, and realistic "autopsy prevention rates" are unknown., Objective: This study aimed to describe the range of abnormalities detectable on fetal microfocus computed tomography in a clinical setting and additional findings identified on the antenatal ultrasound and to estimate the invasive autopsy avoidance rate (ie, cases in which imaging was sufficient to deem autopsy unnecessary)., Study Design: A prospective observational case series of all fetuses referred for microfocus computed tomography imaging at a single institution was conducted for 3 years (2016-2019). Imaging was reported by 2 pediatric radiologists before autopsy, with "decision to proceed" based on the specialist perinatal pathologists' judgment and parental consent. Agreement rates between microfocus computed tomography and antenatal ultrasound were evaluated, and where feasible, diagnostic accuracy for microfocus computed tomography was calculated using autopsy as a reference standard., Results: A total of 268 fetuses were included (2-350 grams body weight; 11-24 weeks' gestation), with cause for demise in 122 of 268 (45.5%). Of the 122 fetuses, 64 (52.5%) exhibited fetal anomalies. Although 221 of 268 (82.5%) fetuses had consent for invasive autopsy, only 29 of the 221 (13.1%) underwent this procedure, which implied an autopsy avoidance rate of 192 of 221 (86.9%). Complete agreement was present for all brain, thoracic, and abdominal pathologies, whereas sensitivity and specificity for cardiac anomalies were 66.7% and 91.7%, respectively. Microfocus computed tomography and antenatal ultrasound agreement was found in 219 of 266 cases (81.9%), with partial agreement in 21 of 266 (7.9%) and disagreement in 26 of 266 (10.5%), mostly because of additional cardiac, soft tissue, or genitourinary findings by microfocus computed tomography, which were not seen on the ultrasound., Conclusion: Fetal microfocus computed tomography imaging is a viable and useful tool for imaging early gestational fetuses and can avoid the need for invasive autopsy. Confirmation of antenatal diagnoses is achieved in most cases, and additional anomalies may also be detected., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Objectives: To determine the feasibility and tissue yield of a perinatal incisionless ultrasound-guided biopsy procedure, the INcisionless Targeted Core Tissue (INTACT) technique, in the context of minimally invasive autopsy., Methods: Cases of perinatal death in which the parents consented for minimally invasive autopsy underwent postmortem magnetic resonance imaging and an INTACT biopsy procedure, defined as needle biopsy of organs via the umbilical cord, performed under ultrasound guidance. In each case, three cores of tissue were obtained from seven target organs (both lungs, both kidneys, heart, spleen and liver). Biopsy success was predefined as an adequate volume of the intended target organ for pathological analysis, as judged by a pathologist blinded to the case and biopsy procedure., Results: Thirty fetuses underwent organ sampling. Mean gestational age was 30 weeks (range, 18-40 weeks) and mean delivery-to-biopsy interval was 12 days (range, 6-22 days). The overall biopsy success rate was 153/201 (76.1%) samples, with the success rates in individual organs being highest for the heart and lungs (93% and 91%, respectively) and lowest for the spleen (11%). Excluding splenic samples, the biopsy success rate was 150/173 (86.7%). Histological abnormalities were found in 4/201 (2%) samples, all of which occurred in the lungs and kidneys of a fetus with pulmonary hypoplasia and multicystic kidney disease., Conclusions: Incisionless ultrasound-guided organ biopsy using the INTACT procedure is feasible, with an overall biopsy success rate of over 75%. This novel technique offers the ideal combination of an imaging-led autopsy with organ sampling for parents who decline the conventional invasive approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)