Magnetic resonance imaging of fetal vascular malformations.

Vascular anomalies develop during fetal life and can be detected on prenatal ultrasonography and fetal magnetic resonance imaging. Diagnosis of lymphatic, venous, and arteriovenous malformations, as well as congenital hemangiomas and other congenital vascular tumors, may be challenging. The benign vascular anomalies may be difficult to differentiate from malignancies with a similar appearance. In this manuscript, we present a succinct overview of the congenital vascular anomalies that may present in fetal or neonatal life.

Congenital Vascular Malformations in Children: From Historical Perspective to a Multidisciplinary Approach in the Modern Era-A Comprehensive Review.

Congenital vascular malformations (CVMs) are the result of an aberrant development during embryogenesis. Although these lesions are present at birth, they are not always visible yet. Once symptomatic, patients suffer from pain, bleeding, ulcers, infections or lymphatic leakage, depending on the subtype of vessels involved. Treatment includes conservative management, surgery, sclerotherapy, embolization and pharmacological therapy. The clinical presentation varies widely and treatment can be challenging due to the rarity of the disease and potential difficulties of treatment. This review gives an overview of the historical developments in diagnosis and classification and exposes the key elements of innovations in the past decades on the identification of genetic mutations and personalized treatment. These advances in the field and a multidisciplinary approach are highly valuable in the optimization of clinical care aimed at both curing or stabilizing the CVM and pursuing physical and psychosocial wellbeing.

Pediatric diaphragmatic hernia induced by a rib osteochondroma.

Diaphragmatic hernia in children is uncommon, especially when not congenital. We present a case of an 11-year old boy with a diaphragmatic hernia caused by a rib osteochondroma. The osteochondroma was surgically removed and the laceration in the diaphragm was repaired. This case shows the importance of being familiar with acquired diaphragmatic hernia in children, to recognize and prevent possible complications in an early stage.

Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.

OBJECTIVE: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. MATERIAL AND METHODS: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. RESULTS: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10-3 mm2/s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival. CONCLUSION: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.

Oral sialic acid supplementation in NANS-CDG: Results of a single center, open-label, observational pilot study.

NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0-28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.

Clinical differences in sirolimus treatment with low target levels between children and adults with vascular malformations - A nationwide trial.

The clinical presentation of patients with slow-flow vascular malformations is very heterogeneous. High clinical burden and subsequent reduced health-related quality of life is something they have in common. There is an unmet medical need for these patients for whom regular treatments like surgery and embolization are either insufficient or technically impossible. Sirolimus has been reported to be effective and overall well-tolerated in most patients. However, the main limitation of sirolimus is the reported high toxicity, especially when target levels of 10-15 ng/mL are being used. We report the results of a phase IIB single-arm open-label clinical trial consisting of 68 (67 in the challenge phase and 68 in the rechallenge phase) evaluable patients (children n = 33 and adults n = 35) demonstrating that treatment with low sirolimus target levels (4-10 ng/mL) is effective in 79.1% of the patients. When sirolimus treatment was stopped, the majority of patients experienced a recurrence of symptoms, supporting prolonged or even lifelong treatment requirement. Adults experienced a higher baseline pain score compared with children, having an estimated marginal mean of 6.2 versus 4.1, p < 0.05; however, they showed a similar decrease to children. Furthermore, the pediatric population experienced less often a sirolimus-related grade I-IV adverse event (35.9% vs. 64.1%, p > 0.05) compared with adults. Additionally, response rates were higher in children compared with adults (93.8% vs. 65.7%, p < 0.05), and children responded faster (28 vs. 91 days, p < 0.05). These results suggest benefits of sirolimus in patients with slow-flow vascular malformations and support its initiation as young as possible.

The lymphatic system throughout history: From hieroglyphic translations to state of the art radiological techniques.

A comprehensive lymphatic system is indispensable for a well-functioning body; it is integral to the immune system and is also interrelated with the digestive system and fluid homeostasis. The main difficulty in examining the lymphatic system is its fine-meshed structure. This remains a challenge, leaving patients with uninterpreted symptoms and a dearth of potential therapies. We review the history of the lymphatic system up to the present with the aim of improving current knowledge. Several findings described throughout history have made fundamental contributions to elucidating the lymphatic system. The first contributions were made by the ancient Egyptians and the ancient Greeks. Vesalius obtained new insights by dissecting corpses. Thereafter, Ruysch (1638-1731) gained an understanding of lymphatic flow. In 1784, Mascagni published his illustration of the whole lymphatic network. The introduction of radiological lymphography revolutionized knowledge of the lymphatic system. Pedal lymphangiography was first described by Monteiro (1931) and Kinmonth (1952). Lymphoscintigraphy (nuclear medicine), magnetic resonance imaging, and near-infrared fluorescence lymphography further improved visualization of the lymphatic system. The innovative dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) transformed understanding of the central lymphatic system, enabling central lymphatic flow disorders in patients to be diagnosed and even allowing for therapeutic planning. From the perspective of the history of lymph visualization, DCMRL has ample potential for identifying specific causes of debilitating symptoms in patients with central lymphatic system abnormalities and even allows for therapeutic planning.

Current and emerging artificial intelligence applications in chest imaging: a pediatric perspective.

Artificial intelligence (AI) applications for chest radiography and chest CT are among the most developed applications in radiology. More than 40 certified AI products are available for chest radiography or chest CT. These AI products cover a wide range of abnormalities, including pneumonia, pneumothorax and lung cancer. Most applications are aimed at detecting disease, complemented by products that characterize or quantify tissue. At present, none of the thoracic AI products is specifically designed for the pediatric population. However, some products developed to detect tuberculosis in adults are also applicable to children. Software is under development to detect early changes of cystic fibrosis on chest CT, which could be an interesting application for pediatric radiology. In this review, we give an overview of current AI products in thoracic radiology and cover recent literature about AI in chest radiography, with a focus on pediatric radiology. We also discuss possible pediatric applications.

NANS-CDG: Delineation of the Genetic, Biochemical, and Clinical Spectrum.

Background: NANS-CDG is a recently described congenital disorder of glycosylation caused by biallelic genetic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. Sialic acid at the end of glycoconjugates plays a key role in biological processes such as brain and skeletal development. Here, we present an observational cohort study to delineate the genetic, biochemical, and clinical phenotype and assess possible correlations. Methods: Medical and laboratory records were reviewed with retrospective extraction and analysis of genetic, biochemical, and clinical data (2016-2020). Results: Nine NANS-CDG patients (nine families, six countries) referred to the Radboudumc CDG Center of Expertise were included. Phenotyping confirmed the hallmark features including intellectual developmental disorder (IDD) (n = 9/9; 100%), facial dysmorphisms (n = 9/9; 100%), neurologic impairment (n = 9/9; 100%), short stature (n = 8/9; 89%), skeletal dysplasia (n = 8/9; 89%), and short limbs (n = 8/9; 89%). Newly identified features include ophthalmological abnormalities (n = 6/9; 67%), an abnormal septum pellucidum (n = 6/9; 67%), (progressive) cerebral atrophy and ventricular dilatation (n = 5/9; 56%), gastrointestinal dysfunction (n = 5/9; 56%), thrombocytopenia (n = 5/9; 56%), and hypo-low-density lipoprotein cholesterol (n = 4/9; 44%). Biochemically, elevated urinary excretion of N-acetylmannosamine (ManNAc) is pathognomonic, the concentrations of which show a significant correlation with clinical severity. Genotypically, eight novel NANS variants were identified. Three severely affected patients harbored identical compound heterozygous pathogenic variants, one of whom was initiated on experimental prenatal and postnatal treatment with oral sialic acid. This patient showed markedly better psychomotor development than the other two genotypically identical males. Conclusions: ManNAc screening should be considered in all patients with IDD, short stature with short limbs, facial dysmorphisms, neurologic impairment, and an abnormal septum pellucidum +/- congenital and neurodegenerative lesions on brain imaging, to establish a precise diagnosis and contribute to prognostication. Personalized management includes accurate genetic counseling and access to proper supports and tailored care for gastrointestinal symptoms, thrombocytopenia, and epilepsy, as well as rehabilitation services for cognitive and physical impairments. Motivated by the short-term positive effects of experimental treatment with oral sialic, we have initiated this intervention with protocolized follow-up of neurologic, systemic, and growth outcomes in four patients. Research is ongoing to unravel pathophysiology and identify novel therapeutic targets.

Lymphatic malformations adjacent to the airway in neonates: Risk factors for outcome.

PURPOSE: To evaluate imaging, treatment, and outcomes in neonates with a lymphatic malformation (LM) adjacent to the airway and to evaluate risk factors that can predict outcome. METHODS: A retrospective case series was conducted of ten patients treated between January 2011 and July 2019. The main outcome measures included airway compromise and clinical response to sclerotherapy ± surgery. Categorical data were compared using the Fisher's exact test. RESULTS: Ex-utero intrapartum therapy was performed in four cases, among whom one died due to sepsis. All patients underwent schlerotherapy, with surgical debulking in two. Four patients showed a good clinical response, and five started experimental systemic treatment. Patients with bilateral disease and patients with an LM with >180° tracheal surrounding were significantly at risk for airway compromise (bilateral: n = 6/6 versus n = 0/4, p = 0.005; >180°: n = 5/5 versus n = 1/5, p = 0.048). The need for LM treatment in the neonatal period was indicative of a poor clinical response ('non-responders' 5/6, 'responders' 0/4; p = 0.048). CONCLUSIONS: This study indicates that bilateral disease and >180° tracheal surrounding are risk factors for airway compromise in neonates with an LM adjacent to the airway. In addition, the need for early treatment seems to be indicative of a poor clinical response.

Pseudolesion in the right parafissural liver parenchyma on CT: The base is found in embryology and collagen content.

BACKGROUND: Computed tomography (CT) images of livers may show a hypo-attenuated structure alongside the falciform ligament, which can be a focal fatty pseudolesion and can mimic a malignancy. The preferred location is on the right parafissural site, ventral in segment IVa/b. The etiology is not clear, nor is it known how the histology of this location develops. These are evaluated in this study. METHODS: 40 adult cadavers with autopsy and / or postmortem CT in a university hospital and a forensic center were included. Liver biopsies were taken at the left side of the falciform ligament as control, and at the right side as the possible precursor of a pseudolesion; these were examined for collagen and fat content. Cadavers with steatotic (>5% fat) or fibrotic (>2% collagen) control samples were excluded. RESULTS: Significantly more collagen was present in the right parafissural liver parenchyma: median 0.68% (IQR: 0.32-1.17%), compared to the left side 0.48% (IQR: 0.21-0.75%) (p 0.008), with equal fat content and CT attenuation values. The etiophysiology goes back to the demise of the umbilical venes in the early embryonic and neonatal period. CONCLUSIONS: The right parafissural area contains more collagen and an equal amount of fat compared to the control left side. This supports the hypothesis of delayed, 'third' inflow: the postnatal change in blood supply from umbilical to portal leaves the downstream parafissural area hypoperfused leading to hypoxia which in turn results in collagen accumulation and the persistence of paraumbilical veins of Sappey.

Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands.

BACKGROUND: Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood. METHODS: For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries. Standardized incidence ratios were calculated using cancer incidence rates from the general Dutch population. Excess relative risks (ERRs) per 100 mGy organ dose were calculated with Poisson regression. All statistical tests were two-sided. RESULTS: Standardized incidence ratios were elevated for all cancer sites. Mean cumulative bone marrow doses were 9.5 mGy at the end of follow-up, and leukemia risk (excluding myelodysplastic syndrome) was not associated with cumulative bone marrow dose (44 cases). Cumulative brain dose was on average 38.5 mGy and was statistically significantly associated with risk for malignant and nonmalignant brain tumors combined (ERR/100 mGy: 0.86, 95% confidence interval = 0.20 to 2.22, P = .002, 84 cases). Excluding tuberous sclerosis complex patients did not substantially change the risk. CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. No association was observed for leukemia. Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.

Fatal Complications after Pediatric Surgical Interventions: Lessons Learned.

Placement of catheters, drains, shunts, and tubes in children can lead to serious or even fatal complications at the moment of placement, such as hemorrhage at insertion, or in the longterm, such as infections and migration into adjacent organs. The clinician should always be aware of these potential complications, especially if the child is unwell. For postmortem diagnostic evaluation, either with a computed tomography scan or an invasive autopsy, all tubes, drains, shunts, and/or catheters should be left in situ. We present three cases with fatal complications after the placement of a chest drain, ventriculoperitoneal shunt, and gastrostomy tube.

Correlation Between Liver Volumetric Computed Tomography Results and Measured Liver Weight: A Tool for Preoperative Planning of Liver Transplant.

OBJECTIVES: Before liver transplant, it is necessary to know the size of the organ in advance of the procedure. We studied the correlation between liver volumetric computed tomography results and liver weight. MATERIALS AND METHODS: Postmortem volumetric computed tomography was conducted on cadavers before autopsy, and 3-dimensional liver volume was estimated with semiautomated software. Liver weight was then determined at autopsy. Linear regression and univariate analysis of variance results were used to determine the accuracy of volumetric 3-dimensional computed tomography in estimating liver weight. We also used 2-dimensional liver sizes to design a 2-dimensional formula to estimate liver volume. RESULTS: We found that 3-dimensional volumetric computed tomography was able to accurately estimate liver weight (standard error = 157 g) with a liver density of 0.99 g/mL. Intraobserver and interobserver variabilities were small. The 2-dimensional formula estimated liver weight slightly less accurately (standard error = 212 g). CONCLUSIONS: We conclude that liver weight can be estimated accurately with 3-dimensional volumetric computed tomography; estimates were more precise than with the 2-dimensional formula-based liver volume estimation. Volumetric computed tomography can be an important tool during preoperative workup before transplant surgery.

Liver parenchyma at the site of hypodense parafissural pseudolesion contains increased collagen.

PURPOSE: To identify a histological substrate explaining the hypodense pseudolesion in the liver at the right side of the falciform ligament and the correlation with CT radiodensity. MATERIALS AND METHODS: Tissue specimens were obtained from the right (pseudolesion) and left (control) side of the falciform ligament at the level of the left portal vein, in deceased adults during autopsy. Radiodensity was measured at the same locations at CT. Digital image analysis determined the amount of collagen and fat in histological sections, and the number of portal triads and central veins were counted. Glycogen content was visually assessed by the area percentage of the histological section. RESULTS: Specimens from 17 patients showed a 39% increase in collagen for the site of the pseudolesion compared to the contralateral side (p = 0.08). No significant differences were found for the amount of fat, glycogen, portal triads, or central veins. In one patient a pseudolesion was visible on CT, and this contained 52% more collagen than the control side. CONCLUSION: The pseudolesion at the right parafissural side in the liver contains more collagen compared to the control left side, while there is no difference in fat or glycogen content or number of portal and hepatic veins. Collagen may be the cause of the pseudolesion.

[Herlyn-Werner-Wunderlich syndrome]. / Het Herlyn-Werner-Wunderlich-syndroom.

BACKGROUND: Many patients are admitted to accident and emergency departments with acute abdominal pain. Herlyn-Werner-Wunderlich syndrome (HWWS) is one of the less well-known causes of this. It is characterised by uterine didelphys with an obstructed hemivagina and ipsilateral renal agenesis or dysplasia. CASE DESCRIPTION: A 16-year-old girl presented to the emergency department with progressive abdominal pain and a previous history of renal and anal abnormalities. Acute appendicitis was suspected because of both tenderness on pressure and rebound tenderness, and a raised C-reactive protein level. Abdominal ultrasonography revealed a cystic structure, probably of ovarian or tubal origin. An emergency laparoscopy was performed as ovarian torsion was suspected. This revealed uterine didelphys with an abnormal right horn. Additional abdominal MRI scan diagnostic revealed abnormalities consistent with HWWS. CONCLUSION: Congenital urogenital abnormalities should be included in the differential diagnosis of patients with a previous history of renal or anal abnormalities who present with progressive abdominal pain or dysmenorrhoea.

Magnetic resonance imaging measurement of blood volume flow in peripheral arteries in healthy subjects.

OBJECTIVE: Peripheral arterial disease results in insufficient blood supply to the leg. Assessment of blood flow may provide information about severity of the disease. Magnetic resonance imaging (MRI) has potential use for simple, fast quantitative blood flow measurement. We investigated normal blood flow values for age and sex in the common femoral artery and popliteal artery in 50 healthy volunteers. In addition, we examined reproducibility and determinants of blood flow. METHODS: We performed cardiac-triggered phase-contrast quantitative flow measurements in the common femoral artery and popliteal artery, and MRI of the calves in 50 healthy volunteers (age, 26-80 years). Ten persons underwent MRI three times, to analyze reproducibility. RESULTS: All measurements were technically successful. Mean blood flow was 353 mL/min in the femoral artery and 61.9 mL/min in the popliteal artery. Coefficient of variation of femoral measurements was 16%, and of popliteal measurements was 19%. Femoral blood flow was significantly related to age and sex. Popliteal blood flow was significantly related to calf muscle volume, adjusted for age and sex. CONCLUSION: Normal values for blood flow to the legs are presented. The measurements have reasonable reproducibility. Blood flow to the legs depends on age, sex, and calf muscle volume.