Targetable NOTCH1 rearrangements in reninoma.

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.

Use of super resolution reconstruction MRI for surgical planning in Placenta accreta spectrum disorder: Case series.

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.

Lung viral infection modelling in a bioengineered whole-organ.

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.

Routine placental histopathology findings from women testing positive for SARS-CoV-2 during pregnancy: Retrospective cohort comparative study.

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.

Genomic investigations of unexplained acute hepatitis in children.

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 UK1. 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.

Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma.

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.

Dynamic Changes in Microvascular Density Can Predict Viable and Non-Viable Areas in High-Risk Neuroblastoma.

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.

Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.

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.

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model.

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.

A pragmatic evidence-based approach to post-mortem perinatal imaging.

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.

Human fetal whole-body postmortem microfocus computed tomographic imaging.

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.

Structure-function relationships in the feto-placental circulation from in silico interpretation of micro-CT vascular structures.

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.

Ligamentum arteriosum calcification on paediatric postmortem computed tomography.

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.

Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy.

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.

Investigation of optimal sample preparation conditions with potassium triiodide and optimal imaging settings for microfocus computed tomography of excised cat hearts.

OBJECTIVE: To determine optimal sample preparation conditions with potassium triiodide (I2KI) and optimal imaging settings for microfocus CT (micro-CT) of excised cat hearts. SAMPLE: 7 excised hearts (weight range, 10 to 17.6 g) obtained from healthy adult cats after euthanasia by IV injection of pentobarbital sodium. PROCEDURES: Following excision, the hearts were preserved in 10% formaldehyde solution. Six hearts were immersed in 1.25% I2KI solution (n = 3) or 2.5% I2KI solution (3) for a 12-day period. Micro-CT images were acquired at time 0 (prior to iodination) then approximately every 24 and 48 hours thereafter to determine optimal sample preparation conditions (ie, immersion time and concentration of I2KI solution). Identified optimal conditions were then used to prepare the seventh heart for imaging; changes in voltage, current, exposure time, and gain on image quality were evaluated to determine optimal settings (ie, maximal signal-to-noise and contrast-to-noise ratios). Images were obtained at a voxel resolution of 30 µm. A detailed morphological assessment of the main cardiac structures of the seventh heart was then performed. RESULTS: Immersion in 2.5% I2KI solution for 48 hours was optimal for sample preparation. The optimal imaging conditions included a tube voltage of 100 kV, current of 150 µA, and exposure time of 354 milliseconds; scan duration was 12 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided an optimal micro-CT imaging protocol for excised cat hearts prepared with I2KI solution that could serve as a basis for future studies of micro-CT for high resolution 3-D imaging of cat hearts.

Photoacoustic imaging of the human placental vasculature.

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin-to-twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry-Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear-array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS-treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies.

Learning from cases: Analysis of two cases of craniopharyngioma from the 19 th to the 21 st centuries.

This manuscript describes the study of two cases of craniopharyngioma, which have been examined repeatedly over three separate centuries. This includes analysis by Josef Engel in 1839, who sought to uncover the physiological role of the pituitary gland; Jacob Erdheim in 1904, who initially described the disease we now call craniopharyngioma, and recent high resolution MRI and micro-CT imaging and attempted DNA analyses of the tumours. The cases highlight how, rightly or wrongly, our interpretation of data is shaped by the technologies, methodologies and prevailing theories of a given time.

Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.

To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (µ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo µ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1 -weighted signal enhancement in the solid tumor component following Gd-DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1 -weighted images. Ex vivo µ-CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on µ-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient-derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.

Imaging the human placental microcirculation with micro-focus computed tomography: Optimisation of tissue preparation and image acquisition.

Micro-CT provides 3D volume imaging with spatial resolution at the micrometre scale. We investigated the optimal human placenta tissue preparation (contrast agent, perfusion pressure, perfusion location and perfusion vessel) and imaging (energy, target material, exposure time and frames) parameters. Microfil (Flow Tech, Carver, MA) produced better fill than Barium sulphate (84.1%(±11.5%)vs70.4%(±18.02%) p = 0.01). Perfusion via umbilical artery produced better fill than via chorionic vessels (83.8%(±17.7%)vs78.0%(±21.9%), p < 0.05), or via umbilical vein (83.8%(±16.4%)vs69.8%(±20.3%), p < 0.01). Imaging at 50 keV with a molybdenum target produced the best contrast to noise ratio. We propose this method to enable quantification and comparison of the human fetoplacental vascular tree.

Cranial bone structure in children with sagittal craniosynostosis: Relationship with surgical outcomes.

BACKGROUND: While spring-assisted cranioplasty has become a widespread technique to correct scaphocephaly in children with sagittal synostosis, predicting head shape changes induced by the gradual opening of the springs remains challenging. This study aimed to explore the role of cranial bone structure on surgical outcomes. METHODS: Patients with isolated sagittal synostosis undergoing spring-assisted cranioplasty at GOSH (London, UK) were recruited (n = 18, age: 3-8 months). Surgical outcome was assessed by the change in cephalic index measured on 3D head scans acquired before spring insertion and after their removal using a 3D handheld scanner. Parietal bone samples routinely discarded during spring-assisted cranioplasty were collected and scanned using micro-computed tomography. From visual assessment of such scans, bone structure was classified into one- or three-layered, the latter indicating the existence of a diploë cavity. Bone average thickness, volume fraction and surface density were computed and correlated with changes in cephalic index. RESULTS: Cephalic index increased for all patients (p < 0.001), but individual improvement varied. Although the patient age and treatment duration were not significantly correlated with changes in cephalic index, bone structural parameters were. The increase of cephalic index was smaller with increasing bone thickness (Pearson's r = -0.79, p < 0.001) and decreasing bone surface density (r = 0.77, p < 0.001), associated with the three-layered bone structure. CONCLUSIONS: Variation in parietal bone micro-structure was associated with the magnitude of head shape changes induced by spring-assisted cranioplasty. This suggests that bone structure analysis could be a valuable adjunct in designing surgical strategies that yield optimal patient-specific outcomes.