Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Radiomic Features Based on MRI Predict Progression-Free Survival in Pediatric Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma.

Purpose: Biopsy-based assessment of H3 K27 M status helps in predicting survival, but biopsy is usually limited to unusual presentations and clinical trials. We aimed to evaluate whether radiomics can serve as prognostic marker to stratify diffuse intrinsic pontine glioma (DIPG) subsets. Methods: In this retrospective study, diagnostic brain MRIs of children with DIPG were analyzed. Radiomic features were extracted from tumor segmentations and data were split into training/testing sets (80:20). A conditional survival forest model was applied to predict progression-free survival (PFS) using training data. The trained model was validated on the test data, and concordances were calculated for PFS. Experiments were repeated 100 times using randomized versions of the respective percentage of the training/test data. Results: A total of 89 patients were identified (48 females, 53.9%). Median age at time of diagnosis was 6.64 years (range: 1-16.9 years) and median PFS was 8 months (range: 1-84 months). Molecular data were available for 26 patients (29.2%) (1 wild type, 3 K27M-H3.1, 22 K27M-H3.3). Radiomic features of FLAIR and nonenhanced T1-weighted sequences were predictive of PFS. The best FLAIR radiomics model yielded a concordance of .87 [95% CI: .86-.88] at 4 months PFS. The best T1-weighted radiomics model yielded a concordance of .82 [95% CI: .8-.84] at 4 months PFS. The best combined FLAIR + T1-weighted radiomics model yielded a concordance of .74 [95% CI: .71-.77] at 3 months PFS. The predominant predictive radiomic feature matrix was gray-level size-zone. Conclusion: MRI-based radiomics may predict progression-free survival in pediatric diffuse midline glioma/diffuse intrinsic pontine glioma.

Abusive head trauma: Canadian and global perspectives.

Canada has come a long way since Dr. C. Henry Kempe first described battered-child syndrome in 1962. The year 1999 was crucial in Canada's battle against shaken baby syndrome/abusive head trauma (SBS/AHT), when the first national conference on the topic was held in Saskatoon. This was followed by the issuance of a national statement and multidisciplinary guidelines, recently updated in 2020. Incidence of AHT in Canada is similar to that found in population-based studies from Switzerland and New Zealand. The mainstay of prevention of AHT in Canada is education of parents and caregivers with respect to their response to infant crying. Population-based data for global incidence of AHT are lacking, largely because of social and cultural differences contributing to poor understanding of AHT as a medico-legal entity. India faces a distinct challenge in the battle against female feticide and infanticide.

Mapping the neuroanatomical impact of very preterm birth across childhood.

Those born very preterm (VPT; <32 weeks gestational age) have an increased risk in developing a wide range of cognitive deficits. In early-to-late childhood, brain structure has been shown to be altered in VPT compared to full-term (FT) children; however, the results are inconsistent. The current study examined subcortical volumes, cortical thickness, and surface area in a large cohort of VPT and FT children aged 4-12 years. Structural magnetic resonance imaging (MRI) was obtained on 120 VPT and 146 FT children who returned up to three times, resulting in 176 VPT and 173 FT unique data points. For each participant, Corticometric Iterative Vertex-based Estimation of Thickness was used to obtain global measurements of total brain, cortical grey and cortical white matter volumes, along with surface-based measurements of cortical thickness and surface area, and Multiple Automatically Generated Templates (MAGeT) brain segmentation tool was used to segment the subcortical structures. To examine group differences and group-age interactions, mixed-effects models were used (controlling for whole-brain volume). We found few differences between the two groups in subcortical volumes. The VPT children showed increased cortical thickness in frontal, occipital and fusiform gyri and inferior pre-post-central areas, while thinning occurred in the midcingulate. Cortical thickness in occipital regions showed more rapid decreases with age in the VPT compared to the FT children. VPT children also showed both regional increases, particularly in the temporal lobe, and decreases in surface area. Our results indicate a delayed maturational trajectory in those born VPT.

Treatment Strategies and Related Outcomes for Brain Arteriovenous Malformations in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE. The objective of this study was to assess the available evidence in the literature regarding treatment outcomes for pediatric patients with brain arteriovenous malformation (bAVM) with the aim of providing practice guidelines for treatment decisions and highlighting research areas that need attention. MATERIALS AND METHODS. Keyword searches for studies published from January 1, 1981, to April 16, 2018, were performed in MEDLINE, Embase, and Web of Science. Predefined inclusion criteria were used to identify studies. Poisson regression analysis for associations between patient and bAVM characteristics and treatment outcomes. RESULTS. We identified 34 articles comprising 2158 children with bAVM who underwent treatment or observation. The mean age of the study cohort was 12.0 ± 1.6 (SD) years, and 48.1% of the patients were female; 64.3% of bAVMs were hemorrhagic at presentation. The mean follow-up was 50.6 ± 32.3 months. Overall, the meta-analysis of pooled data showed an obliteration rate of 69.8% (95% CI, 62.9-75.9%), recurrence rate of 2.2% (95% CI, 1.1-4.3%), and mortality rate of 2.4%. The pooled complication rate was 22.5% (95% CI, 15.7-31.1%) after surgery, 26.4% (95% CI, 15.2-41.9%) after embolization, and 27.1% (95% CI, 18.1-38.4%) after radiosurgery. Mortality was not associated with age, sex, or hemorrhage; however, recurrence after treatment was inversely associated with age. Complication and mortality rates were reduced for multimodal treatments. For patients with bAVM treated with observation only, complication and mortality rates were 35.9% and 23.5%, respectively. CONCLUSION. Multimodality treatments for pediatric bAVM had lower mortality and complication rates than individual treatments. However, there is a lack of evidence for long-term outcomes. The mortality rate was highest in conservatively managed patients (i.e., observation only). Further research directly comparing different treatment modalities for recurrence and complications is warranted. Gathering data prospectively through multiinstitutional registries will be key to provide strong evidence.

Posttransplant Lymphoproliferative Disorder in Children: A 360-degree Perspective.

An earlier incorrect version of this article appeared online. This article was corrected on December 17, 2019.

The role of MRA in pediatric sickle cell disease with normal transcranial Doppler imaging velocities.

PURPOSE: The purpose of this study was to determine the additional information provided by Magnetic Resonance Angiography (MRA) in pediatric sickle cell disease (SCD) patients with normal Transcranial Doppler imaging (TCDI) examinations. METHODS: This cohort study included all pediatric SCD patients over an 18-year period who had no history of stroke and had normal TCDI examinations and subsequently underwent MRA. Routine TCDI inclusive of time-averaged mean of maximum velocities (TAMMV) were assesses and compared with tortuosity on MRA and silent infarct on MRI. RESULTS: 86 children (52.3% female; mean age 8.7 ± 3.5years) were included. There were 77 patients (89.5%) with Hb-SS disease and 9(10.4%) with HB-S beta-thalassemia. All patients had normal TAMMV (<170 cm/s) on TCDI. 76/86 (88.3%) patients also had one or more velocity readings <70 cm/s, albeit none in the middle cerebral arteries. Posterior cerebral arteries had the lowest velocities, <70 cm/s in 51.7% (right) and 60.9% (left). Silent MRI infarcts were seen in 27/86 (31.4%) patients. No new lesions were identified on follow-up MRI. Although mild vascular tortuosity was appreciated in 31/86 (36.0%) of the patients, there were no steno-occlusive lesions in the circle of Willis. CONCLUSIONS: TCDI and MRA are routinely performed for non-invasively evaluating intracranial vascular abnormalities in children with SCD. In SCD children with no history of TIA or stroke, MRA following a normal TCDI examination is unlikely to show vascular abnormality. However, almost a third of these patients show silent infarcts on MRI, unassociated with MRA changes.

Quantitative color-coded digital subtraction neuroangiography for pediatric arteriovenous shunting lesions.

BACKGROUND: Several complex pediatric neurovascular conditions are amenable to endovascular treatment. Given the unique anatomical and physiological challenges in children, there is an ongoing need for tools and techniques that provide accurate information for treatment planning, while minimizing exposure to ionizing radiation and contrast. This is more so for neonates and infants with high-flow arteriovenous (AV) shunts that are challenging to assess using conventional techniques. OBJECTIVE: In this brief report, we describe, through representative cases, the potential role of quantitative color-coded digital subtraction angiography (qDSA) in neuroendovascular procedures in children with high-flow AV shunting lesions. METHODS: Images were obtained using an ArtisQ biplane system (Siemens Healthineers, Erlangen, Germany). Post-processing was performed at a dedicated workstation (Syngo, Siemens) using the iFlow module to generate color-coded maps of individual digital subtraction angiography runs. CONCLUSION: Color-coded qDSA provides real-time quantitative information in high-flow AV shunting neurovascular lesions. This can potentially help direct treatment choices, optimize endovascular treatment protocols, monitor outcomes, and determine treatment end points.

Easing anxiety in preparation for pediatric magnetic resonance imaging: a pilot study using animal-assisted therapy.

BACKGROUND: Children undergoing magnetic resonance imaging (MRI) can experience negative emotions both before and during their scan, causing them to move and often necessitating the use of procedural sedation. Several strategies to improve patient compliance have been attempted. OBJECTIVE: This study was designed to evaluate the effectiveness of a non-pharmacological intervention to reduce anxiety in pediatric patients preparing for MRI using animal-assisted therapy. MATERIALS AND METHODS: An animal intervention pilot study was performed in patients who agreed in advance to interact with a dog. Patients and caregivers filled out questionnaires, including questions designed to capture changes in patient emotion before and after the intervention. MRI diagnostic quality was compared to age- and gender-matched control groups with and without general anesthesia. RESULTS: The intervention in 21 patients comparing pre- and post-scan surveys demonstrated a statistically significant improvement in patient anxiety levels (P<0.01). Diagnostic MRI scans were achieved in 19/21 (90%), with no significant difference in exam quality or times compared against control groups. The majority of caregivers and staff members agreed strongly that patients benefited from the therapy dog's presence. CONCLUSION: The use of animal-assisted therapy in a pilot group in our MRI division resulted in a beneficial effect on patients' emotional status, easing anxiety in preparation for scheduled scans, without impacting MRI quality or duration. Further randomized studies will be needed to demonstrate its significance in reducing sedation rates in children undergoing MRI.

Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm.

Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions.

Ultrasound guidance for difficult lumbar puncture in children: pearls and pitfalls.

Pediatric lumbar puncture can be challenging or unsuccessful for several reasons. At the same time, the excellent sonographic window into the pediatric spine provides a distinct opportunity for ultrasound-guided lumbar puncture. Minimal cerebrospinal fluid and thecal displacement by subdural or epidural hematomas are common after failed clinical attempts. Ultrasound is useful for determining a safe infraconal level for subarachnoid access. Real-time guidance increases not only the success rate but also the safety of diagnostic lumbar puncture and injections for chemotherapy and myelography. In this article, we discuss clinical and technical factors for ultrasound-guided pediatric lumbar puncture.

Longitudinal cerebellar growth following very preterm birth.

PURPOSE: To measure cerebellar growth in a longitudinal cohort of very preterm infants to identify early predictors of subsequent brain growth. Although the cerebellum grows rapidly during late gestation, the rate and variability of growth following premature birth, and the effects of associated injury, are largely unknown. MATERIALS AND METHODS: In all, 105 very-preterm born infants (24-32 weeks GA) were imaged using magnetic resonance imaging (MRI) at birth, term-equivalent, 2, and 4 years of age. Cerebellar and total cerebral volumes were estimated from 1 mm isotropic T1 -weighted scans acquired at 1.5T and 3T, using an atlas-based approach. Linear models were used to analyze cerebellar volume as cross-sectional and longitudinal functions of age, clinical, and radiological correlates. Linear models were also used to test for associations between volume and cognitive outcome. RESULTS: Cerebellar volume increased rapidly with age-at-scan during both the preterm (0.7 mL/wk, P < 0.001) and term periods (1.8 mL/wk, P < 0.001). Infants with grade 3 or 4 germinal matrix hemorrhage (GMH) had smaller cerebellar volumes as a percentage of total brain volume starting at birth and continuing to 4 years of age (-0.43%, -0.57%, -1.09% at preterm, term, and 4 years, respectively, P < 0.01). Irrespective of age-at-scan, early cerebellar volume was predictive of volume at 4 years of age (slope = 1.3, P < 0.001). Cerebellar volumes were not found to predict cognitive outcome at 4 years of age; P < 0.2. CONCLUSION: High-grade GMH and small perinatal cerebellar size is predictive of cerebellar development up to 4 years of age. These findings suggest that it is possible to identify individuals at high risk of reduced cerebellar volumes at an early age. J. Magn. Reson. Imaging 2016;43:1462-1473.

Evaluation of drug release efficiency and antibacterial property of a pH-responsive dextran-based silver nanocomposite hydrogel.

The bioavailability of curcumin (CUR), a highly lipophilic and commonly used anticancer drug, is mainly affected by its poor solubility in aqueous environment and quick metabolism. These challenges can be met by employing delivery systems. Nanocomposite materials have been used as delivery systems to enhance the solubility and dissolution rate of the drug. This study aims to develop dextran-graft-poly(4-acryloylmorpholine) silver nanocomposite using a microwave-assisted method to evaluate its drug-release efficiency and antimicrobial activity. The materials were characterized by FT-IR, FE-SEM, EDS, XRD, HR-TEM, TGA, and BET techniques. Drug loading and release efficiency were evaluated using CUR as the model drug. The swelling and drug release studies were conducted in buffer solutions of pH 1.2 and 7.4. Staphylococcus aureus and Escherichia coli were employed to evaluate the antibacterial activity. The cytotoxicity was assessed by MTT assay against the breast MCF-10. Higher swelling and drug release were observed at pH 1.2 than 7.4. Nanocomposite hydrogel exhibited antibacterial activity against the tested bacterial strains. Cytotoxicity study proved the safety of the developed matrix. The results suggest the developed nanocomposite hydrogel to be a promising polymer matrix for the sustained release of CUR for cancer treatment that requires infectious control.

Axial compression tests on CFRP strengthened CFS plain angle short columns.

A comprehensive test program was performed to experimentally investigate the effect of CFRP strengthening on the axial strength and stability of CFS plain angle short columns subjected to monotonic axial compression. A total of 28 specimens were tested by varying the CFRP strengthening configurations for different column heights. Both uni-directional (CF_UD) and bi-directional (CF_BD) CFRP were considered. The influence of various parameters such as the type of CFRP, fiber orientation, and number of CFRP layers was investigated and discussed in detail. For single layer (ply) of CFRP, CF_UD-0° strengthening configuration resulted in maximum increase of axial capacity by 58.33% and 45.72% (in comparison to bare steel specimens), corresponding to 0.5 m and 1.0 m column lengths respectively. All the bare steel and skin-strengthened specimens failed predominantly due to torsional-flexural buckling mode. Additional layer of CFRP wrapping was found to enhance the axial capacity further and CF_UD-0°/BD was found to possess greater capacity in the case of double layer of CFRP. Adopting cardboard in-fill in addition to CF_UD-0° wrap has prevented the torsional mode of buckling and resulted in a peak increase of axial capacity by 192.55% and 240.61% corresponding to 500 mm and 100 mm long specimens, respectively.

Quantitative MRI in the very preterm brain: assessing tissue organization and myelination using magnetization transfer, diffusion tensor and T1 imaging.

Magnetization transfer ratio (MTR), diffusion tensor imaging (DTI) parameters and T(1) relaxometry values were used to create parametric maps characterizing the tissue microstructure of the neonatal brain in infants born very premature (24-32 gestational weeks) and scanned at preterm and term equivalent age. Group-wise image registration was used to determine anatomical correspondence between individual scans and the pooled parametric data at the preterm and term ages. These parametric maps showed distinct contrasts whose interrelations varied across brain regions and between the preterm and term period. Discrete patterns of regional variation were observed for the different quantitative parameters, providing evidence that MRI is sensitive to multiple independent aspects of brain maturation. MTR values showed a marked change in the pattern of regional variation at term equivalent age compared to the preterm period such that the ordinal ranking of regions by signal contrast changed. This was unlike all other parameters where the regional ranking was preserved at the two time points. Interpreting the data in terms of myelination and structural organization, we report on the concordance with available histological data and demonstrate the value of quantitative MRI for tracking brain maturation over the neonatal period.

2010 McDonald criteria for diagnosing pediatric multiple sclerosis.

OBJECTIVE: The diagnosis of multiple sclerosis (MS) rests on confirmation of central nervous system inflammatory disease that is disseminated in space and time, as evidenced clinically or by magnetic resonance imaging (MRI). The 2010 McDonald criteria simplified MRI requirements, and newly proposed that the criteria are also suitable for the diagnosis of pediatric MS. METHODS: In a national prospective incident cohort study of children with acute demyelination observed for a minimum of 24 months, baseline and serial clinical and MRI examinations were used to retrospectively evaluate the 2010 and 2005 McDonald criteria using clinically relapsing disease as the gold standard. RESULTS: Of 212 eligible participants, 34 experienced 2 or more clinical attacks, 58 met the 2010 criteria, and 42 met 2005 McDonald criteria. The 2010 criteria demonstrated high sensitivity (100%), specificity (86%), positive predictive value (76%), and negative predictive value (100%) for children older than 11 years with non-acute disseminated encephalomyelitis (ADEM) presentations, as did the 2005 McDonald criteria. In younger children with a non-ADEM presentation, PPV of the 2010 criteria was only 55%. None of the 50 children with ADEM met clinical criteria for MS, but 10 met 2010 and 4 met 2005 criteria. INTERPRETATION: Both 2005 and 2010 McDonald criteria identify children with relapsing-remitting MS, although caution is suggested when applying these criteria in younger children. The 2010 McDonald criteria are simple and enable an early diagnosis of MS, but are not suited for application in the context of ADEM-like presentations.

The development of regional functional connectivity in preterm infants into early childhood.

INTRODUCTION: Resting state networks are proposed to reflect the neuronal connectivity that underlies cognitive processes. Consequently, abnormal behaviour of these networks due to disease or altered development may predict poor cognitive outcome. To understand how very preterm birth may affect the development of resting state connectivity, we followed a cohort of very preterm-born infants from birth through to 4 years of age using resting state functional MRI. METHODS: From a larger longitudinal cohort of infants born very preterm (<32 weeks gestational age), 36 at birth, 30 at term, 21 two-year and 22 four-year resting state fMRI datasets were acquired. Using seed-based connectivity analyses with seeds in the anterior cingulate cortex, posterior cingulate cortex, left and right motor-hand regions and left and right temporal lobes, we investigated local and inter-region connectivity as a function of group and age. RESULTS: We found strong local connectivity during the preterm period, which matured into inter-hemispheric and preliminary default-mode network correlations by 4 years of age. This development is comparable to the resting state networks found in term-born infants of equivalent age. CONCLUSION: The results of this study suggest that differences in developmental trajectory between preterm-born and term-born infants are small and, if present, would require a large sample from both populations to be detected.

Prediction of DDoS attacks in agriculture 4.0 with the help of prairie dog optimization algorithm with IDSNet.

Integrating cutting-edge technology with conventional farming practices has been dubbed "smart agriculture" or "the agricultural internet of things." Agriculture 4.0, made possible by the merging of Industry 4.0 and Intelligent Agriculture, is the next generation after industrial farming. Agriculture 4.0 introduces several additional risks, but thousands of IoT devices are left vulnerable after deployment. Security investigators are working in this area to ensure the safety of the agricultural apparatus, which may launch several DDoS attacks to render a service inaccessible and then insert bogus data to convince us that the agricultural apparatus is secure when, in fact, it has been stolen. In this paper, we provide an IDS for DDoS attacks that is built on one-dimensional convolutional neural networks (IDSNet). We employed prairie dog optimization (PDO) to fine-tune the IDSNet training settings. The proposed model's efficiency is compared to those already in use using two newly published real-world traffic datasets, CIC-DDoS attacks.