International Consensus Statement on the Radiological Screening of Contact Children in the Context of Suspected Child Physical Abuse.

Importance: Physical abuse is a common but preventable cause of long-term childhood morbidity and mortality. Despite the strong association between abuse in an index child and abuse in contact children, there is no guidance outlining how to screen the latter, significantly more vulnerable group, for abusive injuries. Consequently, the radiological assessment of contact children is often omitted, or variably performed, allowing occult injuries to go undetected and increasing the risk of further abuse. Objective: To report an evidence-based and consensus-derived set of best practices for the radiological screening of contact children in the context of suspected child physical abuse. Evidence Review: This consensus statement is supported by a systematic review of the literature and the clinical opinion of an internationally recognized group of 26 experts. The modified Delphi consensus process comprised 3 meetings of the International Consensus Group on Contact Screening in Suspected Child Physical Abuse held between February and June 2021. Findings: Contacts are defined as the asymptomatic siblings, cohabiting children, or children under the same care as an index child with suspected child physical abuse. All contact children should undergo a thorough physical examination and a history elicited prior to imaging. Contact children younger than 12 months should have neuroimaging, the preferred modality for which is magnetic resonance imaging, and skeletal survey. Contact children aged 12 to 24 months should undergo skeletal survey. No routine imaging is indicated in asymptomatic children older than 24 months. Follow-up skeletal survey with limited views should be performed if abnormal or equivocal at presentation. Contacts with positive findings should be investigated as an index child. Conclusions and Relevance: This Special Communication reports consensus recommendations for the radiological screening of contact children in the context of suspected child physical abuse, establishing a recognized baseline for the stringent evaluation of these at-risk children and providing clinicians with a more resilient platform from which to advocate for them.

Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.

BACKGROUND: Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. OBJECTIVE: We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types. RESULTS: Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K2=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference. CONCLUSION: Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.

Rate and severity of radiological features of physical abuse in children during the first UK-wide COVID-19 enforced national lockdown.

Rate and severity of radiological features of physical abuse in children during the first UK-wide COVID-19 enforced national lockdown. OBJECTIVE: To assess the number, type and outcome of radiological investigations for children presenting to hospital with suspected physical abuse (SPA; including abusive head trauma) during the first national COVID-19 enforced lockdown compared with the prelockdown period. DESIGN: Multicentre, retrospective, observational, interrupted time series analysis. SETTING: Eight secondary/tertiary paediatric centres between January 2018 and July 2020 inclusive. PARTICIPANTS: 1587 hospital assessed children undergoing radiographic skeletal surveys (SkS) and head CT imaging performed for SPA/child protection concerns. MAIN OUTCOME MEASURES: Incidence and severity of fractures identified on SkS; head injury (composed of incidence rates and ratios of skull fracture, intracranial haemorrhage (ICH) and hypoxic ischaemic injury (HII)) on head CT imaging; and ratio of antemortem and postmortem SkS. RESULTS: 1587 SkS were performed: 1282 (81%) antemortem, 762 (48%) male, and positive findings in 582 (37%). Median patient age was 6 months. There were 1.7 fractures/child prelockdown versus 1.1 fractures/child during lockdown. There was no difference between positive/negative SkS rates, the absolute ratio of antemortem/postmortem SkS or absolute numbers of head injury occurring between January 2018 and February 2020 and the lockdown period April-July 2020. Likewise, prelockdown incidence and rates of skull fracture 30/244 (12%), ICH 28/220 (13%) and HIE 10/205 (5%) were similar to lockdown, 142/1304 (11%), 171/1152 (15%) and 68/1089 (6%), respectively. CONCLUSION: The first UK COVID-19 lockdown did not lead to an increase in either the number of antemortem or postmortem radiological investigations performed for SPA, or the number or severity of fractures and intracranial injuries identified by these investigations.

Fifteen-minute consultation: Fractures in non-ambulant children with cerebral palsy.

OBJECTIVE: To describe a safeguarding decision pathway for the assessment of osteopenic fractures in non-ambulant children with cerebral palsy. METHOD: Literature review and consensus practice of a child safeguarding team, including clinicians and social workers. CONCLUSION: Low-energy fractures of the lower limb in non-ambulant children with cerebral palsy are relatively common and explained by the presence of reduced bone strength, in the absence of any other unexplained injuries or safeguarding concerns.

Added value of magnetic resonance spectroscopy for diagnosing childhood cerebellar tumours.

1 H-magnetic resonance spectroscopy (MRS) provides noninvasive metabolite profiles with the potential to aid the diagnosis of brain tumours. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. The aim of the current study was to evaluate, prospectively, the diagnostic accuracy of a previously established classifier for diagnosing the three major childhood cerebellar tumours, and to determine added value compared with standard reporting of conventional imaging. Single-voxel MRS (1.5 T, PRESS, TE 30 ms, TR 1500 ms, spectral resolution 1 Hz/point) was acquired prospectively on 39 consecutive cerebellar tumours with histopathological diagnoses of pilocytic astrocytoma, ependymoma or medulloblastoma. Spectra were analysed with LCModel and predefined quality control criteria were applied, leaving 33 cases in the analysis. The MRS diagnostic classifier was applied to this dataset. A retrospective analysis was subsequently undertaken by three radiologists, blind to histopathological diagnosis, to determine the change in diagnostic certainty when sequentially viewing conventional imaging, MRS and a decision support tool, based on the classifier. The overall classifier accuracy, evaluated prospectively, was 91%. Incorrectly classified cases, two anaplastic ependymomas, and a rare histological variant of medulloblastoma, were not well represented in the original training set. On retrospective review of conventional MRI, MRS and the classifier result, all radiologists showed a significant increase (Wilcoxon signed rank test, p < 0.001) in their certainty of the correct diagnosis, between viewing the conventional imaging and MRS with the decision support system. It was concluded that MRS can aid the noninvasive diagnosis of posterior fossa tumours in children, and that a decision support classifier helps in MRS interpretation.

Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.

Brain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols.

Sibling screening in suspected abusive head trauma: a proposed guideline.

Abusive head trauma (AHT) is the leading cause of death from child abuse in children younger than 5 years. It is well documented that the infant contacts of children presenting with suspected AHT are at an increased risk of abuse when compared to the general infant population. Despite this association, a paucity of literature stratifies this risk and translates it to the clinic such that this high-risk group is stringently screened for abusive injuries. In this light, the authors propose a standardised screening method for all contact children of the index case and call for further consensus on the subject.

Abusive head trauma: neuroimaging mimics and diagnostic complexities.

Traumatic brain injury is responsible for approximately half of all childhood deaths from infancy to puberty, the majority of which are attributable to abusive head trauma (AHT). Due to the broad way patients present and the lack of a clear mechanism of injury in some cases, neuroimaging plays an integral role in the diagnostic pathway of these children. However, this nonspecific nature also presages the existence of numerous conditions that mimic both the clinical and neuroimaging findings seen in AHT. This propensity for misdiagnosis is compounded by the lack of pathognomonic patterns and clear diagnostic criteria. The repercussions of this are severe and have a profound stigmatic effect. The authors present an exhaustive review of the literature complemented by illustrative cases from their institutions with the aim of providing a framework with which to approach the neuroimaging and diagnosis of AHT.

Classification of paediatric brain tumours by diffusion weighted imaging and machine learning.

To determine if apparent diffusion coefficients (ADC) can discriminate between posterior fossa brain tumours on a multicentre basis. A total of 124 paediatric patients with posterior fossa tumours (including 55 Medulloblastomas, 36 Pilocytic Astrocytomas and 26 Ependymomas) were scanned using diffusion weighted imaging across 12 different hospitals using a total of 18 different scanners. Apparent diffusion coefficient maps were produced and histogram data was extracted from tumour regions of interest. Total histograms and histogram metrics (mean, variance, skew, kurtosis and 10th, 20th and 50th quantiles) were used as data input for classifiers with accuracy determined by tenfold cross validation. Mean ADC values from the tumour regions of interest differed between tumour types, (ANOVA P < 0.001). A cut off value for mean ADC between Ependymomas and Medulloblastomas was found to be of 0.984 × 10-3 mm2 s-1 with sensitivity 80.8% and specificity 80.0%. Overall classification for the ADC histogram metrics were 85% using Naïve Bayes and 84% for Random Forest classifiers. The most commonly occurring posterior fossa paediatric brain tumours can be classified using Apparent Diffusion Coefficient histogram values to a high accuracy on a multicentre basis.

Parenchymal brain injuries in abusive head trauma.

The consequences of abusive head trauma (AHT) can be devastating for both the individual child and for wider society. Death is undoubtedly a very real possibility, but even for those children who survive, there is often very significant morbidity with the potential for gross motor and cognitive impairment, behavioural problems, blindness and epilepsy, which can greatly affect their quality of life. Caring for such children places a vast financial and infrastructural burden on society that frequently extends well into adulthood. While few struggle to have any sympathy for the perpetrator, frequently the infant's father, it should be noted that a single solitary and momentary loss of complete control can have horrific and unforeseen consequences. A number of papers within this edition describe features of AHT and include descriptions of skull fractures and extra-axial haemorrhage, along with mimics of such phenomena. However, in this review we concentrate our attention on the myriad of parenchymal findings that can occur. Such parenchymal injuries include hypoxic-ischaemic damage, clefts, contusion and focal haemorrhage. We offer our perspectives on current thinking on these entities and put them in the context of the immensely important question - how do we recognise abusive head trauma?

Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.

The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.

Diagnostic accuracy and added value of qualitative radiological review of 1H-magnetic resonance spectroscopy in evaluation of childhood brain tumors.

BACKGROUND: 1H-magnetic resonance spectroscopy (MRS) facilitates noninvasive diagnosis of pediatric brain tumors by providing metabolite profiles. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. We aimed to evaluate diagnostic accuracy of MRS for childhood brain tumors and determine added clinical value compared with conventional MRI. METHODS: Children presenting to a tertiary pediatric center with brain lesions from December 2015 through 2017 were included. MRI and single-voxel MRS were acquired on 52 tumors and sequentially interpreted by 3 radiologists, blinded to histopathology. Proportions of correct diagnoses and interrater agreement at each stage were compared. Cases were reviewed to determine added value of qualitative radiological review of MRS through increased certainty of correct diagnosis, reduced number of differentials, or diagnosis following spectroscopist evaluation. Final diagnosis was agreed by the tumor board at study end. RESULTS: Radiologists' principal MRI diagnosis was correct in 69%, increasing to 77% with MRS. MRI + MRS resulted in significantly more additional correct diagnoses than MRI alone (P = .035). There was a significant increase in interrater agreement when correct with MRS (P = .046). Added value following radiologist interpretation of MRS occurred in 73% of cases, increasing to 83% with additional spectroscopist review. First histopathological diagnosis was available a median of 9.5 days following imaging, with 25% of all patients managed without conclusive histopathology. CONCLUSIONS: MRS can improve the accuracy of noninvasive diagnosis of pediatric brain tumors and add value in the diagnostic pathway. Incorporation into practice has the potential to facilitate early diagnosis, guide treatment planning, and improve patient care.

Magnetic Resonance Imaging Quantification of Gastrointestinal Liquid Volumes and Distribution in the Gastrointestinal Tract of Children.

The volume and localization of fluid in the paediatric gastrointestinal tract is crucial to the design of in vitro and in silico models that predict the absorption of oral drugs administered to children. Previous studies have used magnetic resonance imaging (MRI) to quantify fluid volumes and localization in the intestines of adults; this study is the first to undertake similar analysis of pediatric participants. This study quantified the amount and distribution of fluid in fasted and fluid-fed children using MRI data captured during the routine clinical assessment. Data from 32 fasted children (aged 0-16 years) and 23 fluid-fed children (aged 8-16 years) were evaluated. The gastric volume ranged from 0 to 9 mL in the fasted and 19-423 mL in the fluid-fed state. The small intestinal volume was recorded to be 0-51 mL in the fasted and 6-91 mL in the fluid-fed state with an average number of 7.7 and 22.4 fluid pockets, respectively. The data showed significant differences in gastric volumes and the number of fluid pockets in the small intestine for age-matched fasted and fluid-fed children (p < 0.05). Both the number and the volume of pockets reported in children are much lower than those previously reported in adults. This study is the first to report intestinal volumes and localization in children and provides new information to achieve the design of biorelevant in vitro models and real values to update in silico models. The data available from both fluid-fed and fasted children show the extremes of fluid volumes that are present in the gastro-intestinal tract which is useful to understand the variability associated with drug absorption in children.

Evaluation of the added value of 1H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice.

BACKGROUND: Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care. METHODS: Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histopathology, and clinical information were reviewed. Final diagnosis was agreed on by the tumor board at study end. RESULTS: Five cases were excluded for lack of documented MRI diagnosis. The principal MRI diagnosis by pediatric radiologists was correct in 59%, increasing to 73% with addition of MRS. Of the 73%, 19.1% (95% CI, 9.1%-33.3%) were incorrectly diagnosed with MRI alone. MRS led to a significant improvement in correct diagnosis over all tumor types (P = .012). Of diagnoses correctly made with MRI, confidence increased by 37% when adding MRS, with no patients incorrectly re-diagnosed. Indolent lesions were diagnosed noninvasively in 85% of cases, with MRS a major contributor to 91% of these diagnoses. Of all patients, 39% were managed without histopathological diagnosis. MRS contributed to diagnosis in 68% of this group, modifying it in 12%. MRS influenced management in 33% of cases, mainly through avoiding and guiding biopsy and aiding tumor characterization. CONCLUSION: MRS can improve accuracy and confidence in noninvasive diagnosis of pediatric brain lesions in clinical practice. There is potential to improve outcomes through avoiding biopsy of indolent lesions, aiding tumor characterization, and facilitating earlier family discussions and treatment planning.

A homozygous variant disrupting the PIGH start-codon is associated with developmental delay, epilepsy, and microcephaly.

Defective glycosylphosphatidylinositol (GPI)-anchor biogenesis can cause a spectrum of predominantly neurological problems. For eight genes critical to this biological process, disease associations are not yet reported. Scanning exomes from 7,833 parent-child trios and 1,792 singletons from the DDD study for biallelic variants in this gene-set uncovered a rare PIGH variant in a boy with epilepsy, microcephaly, and behavioral difficulties. Although only 2/2 reads harbored this c.1A > T transversion, the presence of ∼25 Mb autozygosity at this locus implied homozygosity, which was confirmed using Sanger sequencing. A similarly-affected sister was also homozygous. FACS analysis of PIGH-deficient CHO cells indicated that cDNAs with c.1A > T could not efficiently restore expression of GPI-APs. Truncation of PIGH protein was consistent with the utilization of an in-frame start-site at codon 63. In summary, we describe siblings harboring a homozygous c.1A > T variant resulting in defective GPI-anchor biogenesis and highlight the importance of exploring low-coverage variants within autozygous regions.

Magnetic resonance imaging based functional imaging in paediatric oncology.

Imaging is central to management of solid tumours in children. Conventional magnetic resonance imaging (MRI) is the standard imaging modality for tumours of the central nervous system (CNS) and limbs and is increasingly used in the abdomen. It provides excellent structural detail, but imparts limited information about tumour type, aggressiveness, metastatic potential or early treatment response. MRI based functional imaging techniques, such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, probe tissue properties to provide clinically important information about metabolites, structure and blood flow. This review describes the role of and evidence behind these functional imaging techniques in paediatric oncology and implications for integrating them into routine clinical practice.

Sonographic Bands of Hypoechogenicity in the Spleen in Children: Zebra Spleen.

OBJECTIVE: Zebra spleen is the normal pattern of splenic enhancement during the arterial phase of CT and MRI and is attributed to different flow rates. The purpose of this study was to describe the appearance and occurrence of bands of hypoechogenicity in the spleen on unenhanced sonograms of children with no splenic abnormalities. MATERIALS AND METHODS: We reviewed 100 abdominal ultrasound studies to evaluate the ultrasound characteristics of the spleen. Demographic data were collected for all patients. RESULTS: Homogeneous echogenicity of the spleen was found in 92 children. Heterogeneous echogenicity was present in eight. Three of the eight had discrete macronodules due to known splenic disease. The other five had bands of hypoechogenicity. These five had no known splenic disease, but one had mild splenomegaly of unknown cause. CONCLUSION: The pattern of hypoechoic bands occurred in 5% of our series. This pattern cannot be explained simply by different flow rates and probably reflects different structural components of the parenchyma. At ultrasound this pattern should be considered a normal finding that may simulate a splenic mass.