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Magnetic resonance imaging perfusion (MRP) techniques can improve the selection of acute ischemic stroke patients for treatment by estimating the salvageable area of decreased perfusion, that is, penumbra. Arterial spin labeling (ASL) is a noncontrast MRP technique that is used to assess cerebral blood flow without the use of intravenous gadolinium contrast. Thus, ASL is of particular interest in stroke imaging. This article will review clinical applications of ASL in stroke such as assessment of the core infarct and penumbra, localization of the vascular occlusion, and collateral status. Given the nonspecific symptoms that patients can present with, differentiating between stroke and a stroke mimic is a diagnostic dilemma. ASL not only helps in differentiating stroke from stroke mimic but also can be used to specify the exact mimic when used in conjunction with the symptomatology and structural imaging. In addition to a case-based overview of clinical applications of the ASL in stroke and stroke mimics in this article, the more commonly used ASL labeling techniques as well as emerging ASL techniques, future developments, and limitations will be reviewed.

Patients with moyamoya arteriopathy are at high risk for developing ischemic stroke in the perioperative period. We sought to evaluate whether preoperative clinical and neuroimaging biomarkers are associated with postoperative stroke and transient ischemic attack in children with moyamoya following revascularization surgery. We performed a retrospective chart review of pediatric patients who underwent revascularization surgery for moyamoya in the last 15 years. Fifty-three patients who underwent 69 surgeries met the inclusion criteria. We recorded clinical predictors of stroke or transient ischemic attack within 7 days following surgery. We used Suzuki stage and Composite Cerebrovascular Stenosis Score to analyze neuroimaging. Significant risk factors for developing postoperative stroke or transient ischemic attack were younger age at surgery ( P = .004) and transient ischemic attack less than 1 month prior to surgery ( P

Lymphatic anomalies comprise a spectrum of disorders ranging from common localized microcystic and macrocystic lymphatic malformations (LMs) to rare complex lymphatic anomalies, including generalized lymphatic anomaly, Kaposiform lymph-angiomatosis, central conducting lymphatic anomaly, and Gorham-Stout disease. Imaging diagnosis of cystic LMs is generally straightforward, but complex lymphatic anomalies, particularly those with multiorgan involvement or diffuse disease, may be more challenging to diagnose. Complex lymphatic anomalies are rare but associated with high morbidity. Imaging plays an important role in their diagnosis, and radiologists may be the first clinicians to suggest the diagnosis. Furthermore, radiologists are regularly involved in management given the frequent need for image-guided interventions. For these reasons, it is crucial for radiologists to be familiar with the spectrum of entities comprising complex lymphatic anomalies and their typical imaging findings. In this article, we review the imaging findings of lymphatic anomalies, including LMs and complex lymphatic anomalies. We discuss characteristic imaging findings, multimodality imaging techniques used for evaluation, pearls and pitfalls in diagnosis, and potential complications. We also review recently discovered genetic changes underlying lymphatic anomaly development and the advent of new molecularly targeted therapies.

To determine the relationship between macular microvascular abnormalities on optical coherence tomography angiography and silent cerebral infarctions (SCIs) on cerebral magnetic resonance imaging in sickle cell disease.Patients (age18 years old) from our previous pediatric sickle cell disease study cohort who had prior optical coherence tomography angiography and brain magnetic resonance imaging were identified. Brain magnetic resonance imaging images were compared with macular optical coherence tomography angiography scans to identify macular vascular density differences between patients with SCI and without SCI.Sixty-eight eyes from 34 patients who underwent optical coherence tomography angiography were evaluated, of whom 28 eyes from 14 patients met the inclusion criteria for this study. Eight patients (57%) with SCI and 6 patients (43%) without SCI were identified. The mean age (17 years in SCI and 16.3 years in non-SCI) was comparable between groups. There was no statistically significant difference in systemic complications. Deep capillary plexus vessel density was lower in the temporal quadrant in patients with SCI (49.3% vs. 53.7%, P = 0.014).Patients with SCI were found to have lower vessel density in the deep capillary plexus compared with those without SCI. This finding suggests that deep capillary plexus vessel density may have utility as an imaging biomarker to predict the presence of SCI.

The cricothyroid membrane (CTM) is the most important anatomic structure when performing emergency front-of-neck access (FONA) procedures. Adolescence is a period of rapid morphologic change in laryngeal structures, including the CTM. We hypothesized that the adolescent CTM would be sufficiently different from pediatric or adult anatomy to merit special consideration in FONA.The aim of the study was to define the procedurally relevant CTM anatomy in an adolescent population.This was a retrospective, multicenter cohort study composed of patients who underwent a diagnostic computed tomography scan during routine clinical care. Inclusion criteria were ages 16 to 19 years and a computed tomography of the neck with or without contrast. The primary outcome was CTM height measured in the midsagittal plane using electronic calipers.One hundred thirty-four imaging studies met inclusion criteria. The average CTM height was strongly associated with age and ranged between 5.4 and 6.2 mm in male adolescents and 4.6 and 5.8 mm in female adolescents. We predicted that standard cuffed endotracheal and tracheostomy tubes recommended for FONA procedures (5.0- and 6.0-mm devices) could potentially fail for most patients in our cohort.The adolescent CTM is smaller than previously recognized. We recommend having a variety of equipment sizes readily available at any site where airway management in adolescents may occur.

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiologic marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency of maximum coherence. The HVx is the correlation coefficient between MAP and THb. The PPI is the percentage of coherent MAP-DHb (difference between oxygenated and deoxygenated hemoglobin, a marker of cerebral blood flow) epochs in a chosen time period. Neonates cooled for HIE were prospectively enrolled in an observational study in two neonatal intensive care units. In analyses adjusted for study site and encephalopathy level, all indices detected relationships between poor autoregulation in the first 6 h after rewarming with a higher injury score on MRI. Only HVx and PPI during hypothermia and the PPI during rewarming identified autoregulatory dysfunction associated with a poor outcome independent of study site and encephalopathy level. Our findings suggest that the accuracy of mathematical autoregulation algorithms in detecting the risk of brain injury or death may depend on temperature and postnatal age. Extending autoregulation monitoring beyond the standard 72 h of therapeutic hypothermia may serve as a method to provide personalized care by assessing the need for and efficacy of future therapies after the hypothermia treatment phase.

BACKGROUND Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO. METHODS We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course. RESULTS All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition. CONCLUSIONS High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO. IMPACT The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

Background Subpial hemorrhages are underrecognized, underreported, and poorly understood. The spectrum of their clinical manifestations and consequences in neonates has not been fully described. Here, we describe the demographic, clinical, and radiographic characteristics of neonates with subpial hemorrhages. Methods We reviewed the medical records and neuroimaging studies of neonates with subpial hemorrhage who were admitted to our neonatal intensive care unit between September 2009 and December 2020. Results Of 114 neonates with intracranial hemorrhage, 31 (27%) had subpial hemorrhage. The majority of neonates in our cohort were male (68%) and born at term (55%). The most common imaging indication was apneas and/or seizures in 58%. Common comorbid conditions included cardiorespiratory failure (42%), hypoxic-ischemic encephalopathy (26%), and coagulopathy (23%). Subpial hemorrhages were multifocal in 45% of neonates, located in the temporal lobe in 45% of neonates, and tended to be larger in neonates with coagulopathy, birth trauma, or hydrocephalus requiring neurosurgical intervention. Subpial hemorrhage was associated with another type of intracranial bleed in 77% of cases and with arterial ischemic stroke in 16% of cases. Of 17 patients with more than one year of follow-up data, 14 (82%) have developmental delay and four (24%) have epilepsy. Of 14 patients with follow-up imaging, 10 (71%) had encephalomalacia subjacent to the subpial hemorrhage. Conclusions This is the largest cohort of neonates with subpial hemorrhages to date. Outcome data are limited by duration of follow-up and may be confounded by comorbid conditions and other concurrent hemorrhages. Further study is needed to define the spectrum of risk factors and expected neurological outcomes.

OBJECTIVE: The objective of the study was to evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. STUDY DESIGN: Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. RESULTS: Sixty-two patients were included. Elevated Tau levels on days 2–3 of TH were associated with death or severe injury on MRI (aOR: 1.06, 95% CI: 1.03–1.09; aOR: 1.04, 95% CI: 1.01–1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP index) on the same day (P = .022). CONCLUSIONS: Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger-scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

BACKGROUND Disruption of brain oxygen delivery and consumption after hypoxic-ischemic injury contributes to neonatal mortality and neurological impairment. Measuring cerebral hemodynamic parameters, including cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ), is clinically important. PURPOSE Phase-contrast (PC), velocity-selective arterial spin labeling (VSASL), and T2 -relaxation-under-phase-contrast (TRUPC) are magnetic resonance imaging (MRI) techniques that have shown promising results in assessing cerebral hemodynamics in humans. We aimed to test their feasibility in quantifying CBF, OEF, and CMRO2 in piglets. STUDY TYPE Prospective. ANIMAL MODEL Ten neonatal piglets subacutely recovered from global hypoxia-ischemia (N = 2), excitotoxic brain injury (N = 6), or sham procedure (N = 2). FIELD STRENGTH/SEQUENCE VSASL, TRUPC, and PC MRI acquired at 3.0 T. ASSESSMENT Regional CBF was measured by VSASL. Global CBF was quantified by both PC and VSASL. TRUPC assessed OEF at the superior sagittal sinus (SSS) and internal cerebral veins (ICVs). CMRO2 was calculated from global CBF and SSS-derived OEF. End-tidal carbon dioxide (EtCO2 ) levels of the piglets were also measured. Brain damage was assessed in tissue sections postmortem by counting damaged neurons. STATISTICAL TESTS Spearman correlations were performed to evaluate associations among CBF (by PC or VSASL), OEF, CMRO2 , EtCO2 , and the pathological neuron counts. Paired t-test was used to compare OEF at SSS with OEF at ICV. RESULTS Global CBF was 32.1 ± 14.9 mL/100 g/minute and 30.9 ± 8.3 mL/100 g/minute for PC and VSASL, respectively, showing a significant correlation (r = 0.82, P

BACKGROUND: Diffusion MRI is routinely used to evaluate brain injury in neonatal encephalopathy. Though abnormal mean diffusivity (MD) is often attributed to cytotoxic edema, the specific contribution from neuronal pathology is unclear. PURPOSE: To determine whether MD from high-resolution diffusion tensor imaging (DTI) can detect variable degrees of neuronal degeneration and pathology in piglets with brain injury induced by excitotoxicity or global hypoxia-ischemia (HI) with or without overt infarction. STUDY TYPE: Prospective. ANIMAL MODEL: Excitotoxic brain injury was induced in 6 neonatal piglets by intrastriatal stereotaxic injection of the glutamate receptor agonist quinolinic acid (QA). Three piglets underwent global HI or sham procedure. Piglets recovered for 20–96 hours before undergoing MRI (n=9). FIELD STRENGTH/SEQUENCE: 3.0T MRI with DTI, T(1)- and T(2)-weighted imaging. ASSESSMENT: MD, fractional anisotropy (FA), and qualitative T(2) injury were measured in putamen and caudate. The cell bodies of normal neurons, degenerating neurons (excitotoxic necrosis, ischemic necrosis, or necrosis-apoptosis cell death continuum), and injured neurons with equivocal degeneration were counted by histopathology. STATISTICAL TESTS: Spearman correlations were used to compare MD and FA to normal, degenerating, and injured neurons. T(2) injury and neuron counts were evaluated by descriptive analysis. RESULTS: The QA insult generated titratable levels of neuronal pathology. In QA, HI, and sham piglets, lower MD correlated with higher ratios of degenerating-to-total neurons (p0.99). Neuron counts were not related to FA (p>0.30) or to qualitative injury from T(2)-weighted MRI. DATA CONCLUSION: MD is more accurate than FA for detecting neuronal degeneration and loss during acute recovery from neonatal excitotoxic and HI brain injury. MD does not reliably detect non-fulminant, nascent, and potentially reversible neuronal injury.

Background: Cooling delays, temperature outside 33–34°C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAPOPT) might diminish neuroprotection from therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized that longer time to reach temperature

Introduction: Moyamoya arteriopathy (MMA) is a significant risk factor for pediatric stroke. Radiographic signs thought to indicate disease severity guide clinical decision making. We hypothesized that there exists a correlation between age and imaging biomarkers. Methods: We retrospectively identified pediatric MMA patients seen at our center that underwent surgical revascularization. Preoperative MRI/MRA imaging was reviewed by two pediatric neuroradiologists who were blinded to clinical characteristics. The following neuroimaging markers were evaluated by consensus: Suzuki staging, cerebrovascular stenosis score (CVSS), the presence of posterior circulation steno-occlusive lesions, ivy sign, and brush sign. Associations of these features with age were analyzed using simple logistic regression and Spearman correlation analyses. Results: We identified 27 patients undergoing 30 individual revascularization procedures between January 2003 and June 2021. There were 29 images of diagnostic quality for analysis. Median age at imaging was 8.5 years. Younger age was associated with posterior arterial lesions (p=0.028). There was no statistically significant association between age and ivy sign (p=0.205), brush sign (p=0.156), Suzuki stage (p=0.671), or CVSS (0.234). Conclusions: In this cohort of surgical MMA patients, younger children were more likely to have posterior circulation involvement on MRA. While not statistically significant, all analyzed radiographic signs were more prevalent among younger patients. Further studies correlating neuroimaging biomarkers with clinical outcomes in larger cohorts including non-surgical MMA patients are needed.

To determine the association of gestational age (GA) and day of life (DOL) with the circulating serum concentration of six brain injury-associated biomarkers in non-brain injured neonates born between 23 and 41 weeks' GA.In a multicenter prospective observational cohort study, serum CNS-insult, inflammatory and trophic proteins concentrations were measured daily in the first 7 DOL.Overall, 3232 serum samples were analyzed from 745 enrollees, median GA 32.3 weeks. BDNF increased 3.7% and IL-8 increased 8.9% each week of gestation. VEGF, IL-6, and IL-10 showed no relationship with GA. VEGF increased 10.8% and IL-8 18.9%, each DOL. IL-6 decreased by 15.8% each DOL. IL-10 decreased by 81.4% each DOL for DOL 0-3. BDNF did not change with DOL. Only 49.67% of samples had detectable GFAP and 33.15% had detectable NRGN. The odds of having detectable GFAP and NRGN increased by 53% and 11%, respectively, each week after 36 weeks' GA. The odds of having detectable GFAP and NRGN decreased by 15% and 8%, respectively, each DOL.BDNF and IL-8 serum concentrations vary with GA. VEGF and interleukin concentrations are dynamic in the first week of life, suggesting circulating levels should be adjusted for GA and DOL for clinically relevant assessment of brain injury.Normative data of six brain injury-related biomarkers is being proposed. When interpreting serum concentrations of brain injury biomarkers, it is key to adjust for gestational age at birth and day of life during the first week to correctly assess for clinical brain injury in neonates. Variation in levels of some biomarkers may be related to gestational and postnatal age and not necessarily pathology.

Sickle cell disease (SCD) is an inherited hemoglobinopathy with an increased risk of neurological complications. Due to anemia and other factors related to the underlying hemoglobinopathy, cerebral blood flow (CBF) increases as compensation; however, the nature of alterations in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in SCD remains controversial, largely attributed to the different calibration models. In addition, limited studies have been done to investigate oxygen metabolism in pediatric patients. Thus, this study used a non-invasive T2-based MR oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, to measure oxygen homeostasis in pediatric patients with SCD using four different calibration models and examined its relationship to hematological measures. It was found that, compared with controls, SCD patients showed an increased CBF, unchanged total oxygen delivery and increased venous blood T2. The results of OEF and CMRO2 were dependent on the calibration models used. When using sickle-specific, hemoglobin S (HbS) level-dependent calibration, there was a decreased OEF and CMRO2, while the bovine model showed an opposite result. OEF and CMRO2 were also associated with hemoglobin and HbS level; the direction of the relationship was again dependent on the model. Future studies with in vivo calibration are needed to provide more accurate information on the T2-Yv relationship.

BACKGROUND Blood-brain barrier (BBB) disruption may lead to endothelium dysfunction and inflammation in sickle cell disease (SCD). However, abnormalities of BBB in SCD, especially in pediatric patients for whom contrast agent administration less than optimal, have not been fully characterized. PURPOSE To examine BBB permeability to water in a group of pediatric SCD participants using a non-invasive magnetic resonance imaging technique. We hypothesized that SCD participants will have increased BBB permeability. STUDY TYPE Prospective cross-sectional. POPULATION Twenty-six pediatric participants (10 ± 1 years, 15F/11M) were enrolled, including 21 SCD participants and 5 sickle cell trait (SCT) participants, who were siblings of SCD patients. FIELD STRENGTH/SEQUENCE 3 T. Water extraction with phase-contrast arterial spin tagging with echo-planer imaging, phase-contrast and T1 -weighted magnetization-prepared rapid acquisition of gradient echo. ASSESSMENT Water extraction fraction (E), BBB permeability-surface area product (PS), cerebral blood flow, hematological measures (hemoglobin, hematocrit, hemoglobin S), neuropsychological scores (including domains of intellectual ability, attention and executive function, academic achievement and adaptive function, and a composite score). Regions of interest were drawn by Z.L. (6 years of experience). STATISTICAL TESTS Wilcoxon rank sum test and chi-square test for group comparison of demographics. Multiple linear regression analysis of PS with diagnostic category (SCD or SCT), hematological measures, and neuropsychological scores. A two-tailed P value of 0.05 or less was considered statistically significant. RESULTS Compared with SCT participants, SCD participants had a significantly higher BBB permeability to water (SCD: 207.0 ± 33.3 mL/100 g/minute, SCT: 171.2 ± 27.2 mL/100 g/minute). SCD participants with typically more severe phenotypes also had a significantly leakier BBB than those with typically milder phenotypes (severe: 217.3 ± 31.7 mL/100 g/minute, mild: 193.3 ± 31.8 mL/100 g/minute). Furthermore, more severe BBB disruption was associated with worse hematological symptoms, including lower hemoglobin concentrations (β = -8.84, 95% confidence interval [CI] [-14.69, -3.00]), lower hematocrits (β = -2.96, 95% CI [-4.84, -1.08]), and higher hemoglobin S fraction (β = 0.77, 95% CI [0.014, 1.53]). DATA CONCLUSION These findings support a potential role for BBB dysfunction in SCD pathogenesis of ischemic injury. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY: Stage 2.

We determined the safety and efficacy of intraoperative magnetic resonance imaging guided surgical reconstruction of bladder exstrophy for the identification of the urogenital diaphragm fibers and the thickened muscular attachments between the posterior urethra, bladder plate and pubic rami.Institutional review board and U.S. Food and Drug Administration approval was obtained for the use of Brainlab (Munich, Germany) intraoperative magnetic resonance imaging guided navigation of the pelvic floor anatomy during closure of classic bladder exstrophy and cloacal exstrophy at our institution. Preoperative pelvic 3-dimensional magnetic resonance imaging was obtained 1 day before closure in patients undergoing pelvic osteotomies. Intraoperative registration was performed after preoperative planning with a pediatric radiologist using 5 anatomical landmarks immediately before initiation of surgery. Accuracy of pelvic anatomy identification was assessed by 2 pediatric urological surgeons and 1 pediatric radiologist.In 43 patients with classic bladder exstrophy and 4 patients with cloacal exstrophy closed at our institution, Brainlab technology was used successfully to navigate and guide the dissection of the pelvic floor intraoperatively. In all patients there was 100% accuracy in the correlation of gross anatomical landmarks with 3-dimensional magnetic resonance imaging identified landmarks intraoperatively, and all patients had successful closure without any major complications.Brainlab intraoperative 3-dimensional magnetic resonance imaging guided pelvic floor navigation and dissection is an effective way to accurately identify pelvic anatomy during classic bladder exstrophy and cloacal exstrophy closure. This technology offers a unique opportunity for surgical skill education in this complex reconstructive operation.

Scoliosis is frequently encountered in childhood, with prevalence of 2%. The majority is idiopathic, without vertebral segmentation anomaly, dysraphism, neuromuscular abnormality, skeletal dysplasia, tumor, or infection. As a complement to clinical assessment, radiography is the primary imaging modality used to classify scoliosis and subsequently monitor its progression and response to treatment. MRI is utilized selectively to assess for neural axis abnormalities in those at higher risk, including those with congenital scoliosis, early onset idiopathic scoliosis, and adolescent idiopathic scoliosis with certain risk factors. CT, although not routinely employed in the initial evaluation of scoliosis, may have a select role in characterizing the bone anomalies of congenital scoliosis and in perioperative planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Choosing the appropriate imaging in children with accidental traumatic spine injuries can be challenging because the recommendations based on scientific evidence at this time differ from those applied in adults. This differentiation is due in part to differences in anatomy and physiology of the developing spine. This publication uses scientific evidence and a panel of pediatric experts to summarize best current imaging practices for children with accidental spine trauma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Aim There is controversy regarding the diagnosis and classification of vascular anomalies (VA). As torso and extremities are the second most common body part for presentation of VAs, musculoskeletal (MSK) radiologists play a central role in VA classification. The purpose of this study was to evaluate the awareness and clinical use of the International Society for the Study of Vascular Anomalies (ISSVA) classification by MSK radiologists. Materials and Methods A Web-based survey was designed and electronically sent to Society of Skeletal Radiology (SSR) members, with 3 questions on demographics and 7 questions on ISSVA classification use and knowledge. The Z-test for binomial proportions is used to assess for statistical significance between subgroups. Results The response rate was 12% (130 of 1091), comprised of 64% (83 of 130) academic and 36% (47 of 130) nonacademic MSK radiologists. VAs accounted for only a small (0%-5%) proportion of clinical practice in the majority 92% (119 of 130). Only 17% (22 of 130) of MSK radiologists used the ISSVA classification in practice. Of all respondents, 74% (94 of 127) considered hemangioma a type of vascular malformation (VM). There was no significant difference in the response characteristics between academic and nonacademic radiologists. A greater proportion of MSK radiologists with >5 years’ experience provided responses that were discordant with the ISSVA classification compared with less experienced radiologists (0-5 years) in diagnosing hemangiomas in adult patients (P = 0.02), and using the presence of phleboliths to diagnose hemangiomas (P = 0.004). Conclusion Our survey results indicate a lack of familiarity with the ISSVA classification by the MSK radiology community.

Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO.We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course.All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition.High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO.The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

The specific cytopathology that causes abnormal fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) after neonatal hypoxia-ischemia (HI) is not completely understood. The panoply of cell types in the brain might contribute differentially to changes in DTI metrics. Because glia are the predominant cell type in brain, we hypothesized that changes in FA and MD would signify perturbations in glial microstructure. Using a 3-Tesla clinical scanner, we conducted in vivo DTI MRI in nine neonatal piglets at 20-96 h after excitotoxic brain injury from striatal quinolinic acid injection or global HI. FA and MD from putamen, caudate, and internal capsule in toto were correlated with astrocyte swelling, neuronal excitotoxicity, and white matter injury. Low FA correlated with more swollen astrocytes immunophenotyped by aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), and glutamate transporter-1 (GLT-1). Low FA was also related to the loss of neurons with perineuronal GLT-1+ astrocyte decorations, large myelin swellings, lower myelin density, and oligodendrocyte cell death identified by 2',3'-cyclic nucleotide 3'-phosphodiesterase, bridging integrator-1, and nuclear morphology. MD correlated with degenerating oligodendrocytes and depletion of normal GFAP+ astrocytes but not with astrocyte or myelin swelling. We conclude that FA is associated with cytotoxic edema in astrocytes and oligodendrocyte processes as well as myelin injury at the cellular level. MD can detect glial cell death and loss, but it may not discern subtle pathology in swollen astrocytes, oligodendrocytes, or myelin. This study provides a cytopathologic basis for interpreting DTI in the neonatal brain after HI.

OBJECTIVE. Subpial hemorrhages, typically seen in neonates, are rare but can harm the adjacent brain parenchyma. The purpose of this review is to summarize the anatomy and pathophysiology of subpial hemorrhage and highlight its characteristic neuro-imaging pattern. CONCLUSION. The distinctive neuroimaging pattern of subpial hemorrhage is best appreciated on brain MRI, which shows the morphology over the cortex and injury to adjacent cortex and subcortical white matter. These findings do not occur in subarachnoid and subdural hemorrhages. Recognizing the pattern of subpial hemorrhages should guide prognostic precision, prognostication, and counseling.

Since 2009, the Neurosciences Intensive Care Nursery at Johns Hopkins Children’s Center has provided a multidisciplinary approach toward the care of newborns with neurological disorders. The program’s cornerstone is an interdisciplinary approach that involves the primary neonatology team plus experts from more than 10 specialties who convene at a weekly team conference at which newborns with neurological problems are discussed in detail. This interdisciplinary approach fosters in-depth discussion of clinical issues to optimize the management of neonates with neurological problems as well as the opportunity to generate research ideas and provide education about neonatal neuroscience at all levels (faculty, nurses, and trainees). The purpose of this article is to provide a 10-year reflection of our Neurosciences Intensive Care Nursery with a view toward expanding efforts in the 3 areas of our mission: clinical care, research, and education. We hope that our experience will enhance the spread of neonatal neuroscience education, care, and research as widely as possible.

Contemporary studies of long-term outcomes in children supported on extracorporeal membrane oxygenation (ECMO) in the United States are limited. We enrolled 99 ECMO patients between July 2010 and June 2015 in a two-center prospective observational study that included neurologic and neuropsychologic evaluation at 6 and 12 months, using standardized outcome measures. Pre-ECMO, 20 (20%) had a pre-existing neurologic diagnosis, 40 (40%) had cardiac arrest, and 10 of 47 (21%) children with neuroimaging had acute abnormal findings. Of 50 children eligible for follow-up at 6 or 12 months, 40 (80%) returned for at least one visit. At the follow-up visit of longest interval from ECMO, the median Vineland Adaptive Behavior Scales-II (VABS-II) score was 91 (interquartile range [IQR], 81-98), the median Pediatric Stroke Outcome Measure (PSOM) score was 1 (IQR, 0-2), and the median Mullen Scales of Early Learning composite score was 85 (IQR, 72-96). Presence of new neuroimaging abnormalities during ECMO or within 6 weeks post-ECMO was associated with VABS-II score

Sinusitis is common in children that usually resolves spontaneously. Imaging is not part of the standard of care for initial diagnosis, however may be necessary in cases with persistent or chronic sinusitis to guide surgical intervention, or to rule out intracranial and vascular complications of sinusitis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the leading imaging modalities. In this article, appropriateness in use of imaging modalities are discussed under common/clinically relevant scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Headaches in children are not uncommon and have various causes. Proper neuroimaging of these children is very specific to the headache type. Care must be taken to choose and perform the most appropriate initial imaging examination in order to maximize the ability to properly determine the cause with minimum risk to the child. This evidence-based report discusses the different headache types in children and provides appropriate guidelines for imaging these children. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Vascular anomalies can occur anywhere in the body, and the majority present in the pediatric population. Accurate classification is essential for proper clinical evaluation, particularly because multidisciplinary care is often required. The International Society for the Study of Vascular Anomalies classification offers a comprehensive classification for all subspecialties. In this review article, we present a magnetic resonance imaging protocol with exemplary cases of the most common types of vascular anomalies in the pediatric trunk and extremities using the current International Society for the Study of Vascular Anomalies classification.

Fetoscopic endotracheal occlusion (FETO) is a prenatal treatment that may increase survival in severe congenital diaphragmatic hernia (CDH). In the U.S., FETO is offered for isolated severe left-sided CDH in the context of an FDA approved feasibility study. FETO in non-isolated cases of severe CDH is only performed with a compassionate use exemption from US regulatory bodies. Anomalies frequently associated with CDH include congenital cystic lesions of the lung and cardiac defects. We describe two cases of non-isolated severe left-sided CDH that underwent prenatal FETO, survived after birth and underwent postnatal surgical repair. The potential benefit of FETO in this setting is discussed.

Sensitive, specific, and safe bedside evaluation of brain perfusion is key to the early diagnosis, treatment, and improved survival of neonates with hypoxic ischemic injury. Contrast-enhanced ultrasound (US) imaging is a novel imaging technique in which intravenously injected gas-filled microbubbles generate enhanced US echoes from an acoustic impedance mismatch. This article describes contrast-enhanced US imaging in 2 neonates with hypoxic ischemic injury and future directions on developing quantitative contrast-enhanced US techniques for improved characterization of perfusion abnormalities. The importance of studying the temporal evolution of brain perfusion in neonatal hypoxic ischemic injury is also highlighted.

An 8-year-old boy presented with a 2-week history of worsening right-sided headache and left-sided jerking movements. Symptoms were associated with vomiting, photophobia, phonophobia, and diplopia but no loss of consciousness. cEEG demonstrated increased voltage on the right but no evidence of seizures. Brain MRI demonstrated a large right frontoparietal mass (figure 1). The pathologic findings were compatible with DICER1 -associated pleomorphic spindle cell sarcoma (figure 2). Recently described, DICER1 mutation predisposes individuals to development of a subgroup of tumors termed “spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant” although it may present as “primary intracranial sarcoma, DICER1 -mutant.”1,2

The rates of opioid use disorder during pregnancy have more than quadrupled in the last decade, resulting in numerous infants suffering exposure to opioids during the perinatal period, a critical period of central nervous system (CNS) development. Despite increasing use, the characterization and definition of the molecular and cellular mechanisms of the long-term neurodevelopmental impacts of opioid exposure commencing in utero remains incomplete. Thus, in consideration of the looming public health crisis stemming from the multitude of infants with prenatal opioid exposure entering school age, we undertook an investigation of the effects of perinatal methadone exposure in a novel preclinical model. Specifically, we examined the effects of opioids on the developing brain to elucidate mechanisms of putative neural cell injury, to identify diagnostic biomarkers and to guide clinical studies of outcome and follow-up. We hypothesized that methadone would induce a pronounced inflammatory profile in both dams and their pups, and be associated with immune system dysfunction, sustained CNS injury, and altered cognition and executive function into adulthood. This investigation was conducted using a combination of cellular, molecular, biochemical, and clinically translatable biomarker, imaging and cognitive assessment platforms. Data reveal that perinatal methadone exposure increases inflammatory cytokines in the neonatal peripheral circulation, and reprograms and primes the immune system through sustained peripheral immune hyperreactivity. In the brain, perinatal methadone exposure not only increases chemokines and cytokines throughout a crucial developmental period, but also alters microglia morphology consistent with activation, and upregulates TLR4 and MyD88 mRNA. This increase in neuroinflammation coincides with reduced myelin basic protein and altered neurofilament expression, as well as reduced structural coherence and significantly decreased fractional anisotropy on diffusion tensor imaging. In addition to this microstructural brain injury, adult rats exposed to methadone in the perinatal period have significant impairment in associative learning and executive control as assessed using touchscreen technology. Collectively, these data reveal a distinct systemic and neuroinflammatory signature associated with prenatal methadone exposure, suggestive of an altered CNS microenvironment, dysregulated developmental homeostasis, complex concurrent neural injury, and imaging and cognitive findings consistent with clinical literature. Further investigation is required to define appropriate therapies targeted at the neural injury and improve the long-term outcomes for this exceedingly vulnerable patient population.

Background Previously, sonographic evaluation of the intracranial contents was limited to intraoperative use following bone flap removal, with placement of the probe directly on the cortical surface or through a transsulcal tubular retractor. Cranioplasty with sonolucent implants may represent a postoperative window into the brain by allowing ultrasound to serve as a novel bedside imaging modality. The potential sonolucency of various commonly used cranial implant types was examined in this study. Methods A 3-phase study was comprised of cadaveric evaluation of transcranioplasty ultrasound (TCU) with cranioplasty implants of varying materials, intraoperative TCU during right-sided cranioplasty with clear implant made of poly-methyl-methacrylate (PMMA), and bedside TCU on postoperative day 5 after cranioplasty. Results The TCU through clear PMMA, polyether-ether-ketone, and opaque PMMA cranial implants revealed implant sonoluceny, in contrast to autologous bone and porous-polyethylene. Intraoperative ultrasound via the clear PMMA implant in a single patient revealed recognizable ventricular anatomy. Furthermore, postoperative bedside ultrasound in the same patient revealed comparable ventricular anatomy and a small epidural fluid collection corresponding to that visualized on an axial computed tomography scan. Conclusion Sonolucent cranial implants, such as those made of clear PMMA, hold great promise for enhanced diagnostic and therapeutic applications previously limited by cranial bone. Furthermore, as functional cranial implants are manufactured with implantable devices housed within clear PMMA, the possibility of utilizing ultrasound for real-time surveillance of intracranial pathology becomes much more feasible.

The exstrophy-epispadias complex (EEC) represents a group of congenitally acquired malformations involving the musculoskeletal, gastrointestinal, and genitourinary systems. Classic bladder exstrophy (CBE) is the most common and best studied entity within the EEC. In this review, imaging features of CBE anatomy will be presented with surgical correlation. Magnetic resonance imaging (MRI) has emerged as a useful modality for pre- and postnatal assessment of the abdominal wall, pelvic floor, and gastrointestinal and genitourinary systems of children with CBE. The authors’ experience supports use of preoperative MRI, in conjunction with navigational software, as a method for identifying complex CBE anatomy. Imaging facilitates surgical approach and improves visualization of complex anatomy, potentially helping to avoid complications. Continued investigation of imaging guidance in CBE repair is needed as surgical techniques improve.

Background Current methods of transcranial diagnostic ultrasound imaging are limited by the skull's acoustic properties. Craniotomy, craniectomy, and cranioplasty procedures present opportunities to circumvent these limitations by substituting autologous bone with synthetic cranial implants composed of sonolucent biomaterials. Objective This study examined the potential to image the brain using transcranioplasty ultrasound (TCU) through a sonolucent cranial implant. Materials and methods A validated adult brain phantom was imaged using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound without an implant. Next, for experimental comparison, TCU was performed through a sonolucent implant composed of clear polymethyl methacrylate. Results All imaging modalities successfully revealed elements of the brain phantom, including the bilateral ventricular system, the falx cerebri, and a deep hyperdense mass representing a brain tumor or hematoma. In addition, ultrasound images were captured which closely resembled axial images obtained with both CT and MRI. Conclusion The results obtained in this first-ever, preclinical, phantom study suggest TCU is now a viable immediate and long-term diagnostic imaging modality deserving of further clinical investigation.

PURPOSE: Non-invasive measurement of cerebral venous oxygenation (Y(v)) in neonates is important in the assessment of brain oxygen extraction and consumption, and may be useful in characterizing brain development and neonatal brain diseases. This study aims to develop a rapid method for vessel-specific measurement of Y(v) in neonates. METHODS: We developed a pulse sequence, named accelerated T(2)-relaxation-under-phase-contrast (aTRUPC), which consists of velocity-encoding phase-contrast module to isolate pure blood signal, flow-insensitive T(2)-preparation to quantify blood T(2), and turbo-field-echo (TFE) scheme for rapid image acquisition, which is critical for neonatal MRI. A series of studies were conducted. First, the pulse sequence was optimized in terms of TFE factor, velocity encoding (VENC), and slice thickness for best sensitivity. Second, to account for the influence of TFE acquisition on T(2) quantification, simulation and experiments were conducted to establish the relationship between TFE-T(2) and standard T(2). Finally, the complete aTRUPC sequence was applied on a group of healthy neonates and normative Y(v) values were determined. RESULTS: Optimal parameters of aTRUPC in neonates were found to be a TFE factor of 15, VENC of 5cm/s, and slice thickness of 10mm. TFE-T(2) was on average 3.9% lower than standard T(2). These two measures were strongly correlated (R(2)=0.86), thus their difference can be accounted for by a correction equation, T(2,standard)=1.2002×T(2,TFE)−10.6276. Neonatal Y(v) values in veins draining cortical brain and those draining central brain were 64.8±2.9% and 70.2±3.3%, respectively, with a significant difference (P=0.02). CONCLUSION: aTRUPC MRI has the potential to provide vessel-specific quantification of cerebral Y(v) in neonates.

Background Arteriovenous malformations (AVMs) are high flow vascular anomalies that are difficult to manage given their high recurrence rate. At this time, the optimal treatment of AVMs involves embolization and surgical resection. However, few studies have examined patient outcomes after a delayed surgical resection approach. Methods A retrospective chart review of all patients presenting to a single institution with vascular malformations from 2000 to 2016 was performed. Patients with facial AVMs that underwent operative management were included. Records were reviewed for patient characteristics, lesion natural history, operative timing after embolization ( 72 hours), and outcomes. Results 11 patients fulfilled the inclusion/exclusion criteria. Nine patients were female, with an average age at resection of 29.1 years. Three patients had hemi/mid-facial AVMs, 1 patient had a nasal AVM, 3 patients had labial AVMs, 1 patient had an AVM on the chin, and 1 had a periorbital AVM. Average time between embolization and primary resection was 8.6 days (range 1-24). No complications requiring reoperation occurred in any patient. Average follow-up was 32.6 months, with 2 recurrences at a mean of 47.6 months. Timing of resection, Schobinger stage, and resection completeness did not significantly affect recurrence (P >0.05). Lesion size >6 cm in any dimension was significantly associated with recurrence (P = 0.018). Conclusion Compared to early resection, delayed (>72 h) surgical resection after embolization of facial AVMs is a viable treatment option and results in non-inferior recurrence rates (25 vs 14% respectively over a 40-month period).

Scoliosis is frequently encountered in childhood, with prevalence of 2%. The majority is idiopathic, without vertebral segmentation anomaly, dysraphism, neuromuscular abnormality, skeletal dysplasia, tumor, or infection. As a complement to clinical assessment, radiography is the primary imaging modality used to classify scoliosis and subsequently monitor its progression and response to treatment. MRI is utilized selectively to assess for neural axis abnormalities in those at higher risk, including those with congenital scoliosis, early onset idiopathic scoliosis, and adolescent idiopathic scoliosis with certain risk factors. CT, although not routinely employed in the initial evaluation of scoliosis, may have a select role in characterizing the bone anomalies of congenital scoliosis and in perioperative planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Choosing the appropriate imaging in children with accidental traumatic spine injuries can be challenging because the recommendations based on scientific evidence at this time differ from those applied in adults. This differentiation is due in part to differences in anatomy and physiology of the developing spine. This publication uses scientific evidence and a panel of pediatric experts to summarize best current imaging practices for children with accidental spine trauma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background: Therapeutic hypothermia provides incomplete neuroprotection for neonatal hypoxic-ischemic encephalopathy (HIE). We examined whether hemodynamic goals that support autoregulation are associated with decreased brain injury and whether these relationships are affected by birth asphyxia or vary by anatomic region. Methods: Neonates cooled for HIE received near-infrared spectroscopy autoregulation monitoring to identify the mean arterial blood pressure with optimized autoregulatory function (MAPOPT). Blood pressure deviation from MAPOPT was correlated with brain injury on MRI after adjusting for the effects of arterial carbon dioxide, vasopressors, seizures, and birth asphyxia severity. Results: Blood pressure deviation from MAPOPT related to neurologic injury in several regions independent of birth asphyxia severity. Greater duration and deviation of blood pressure below MAPOPT were associated with greater injury in the paracentral gyri and white matter. Blood pressure within MAPOPT related to lesser injury in the white matter, putamen and globus pallidus, and brain stem. Finally, blood pressures that exceeded MAPOPT were associated with reduced injury in the paracentral gyri. Conclusions: Blood pressure deviation from optimal autoregulatory vasoreactivity was associated with MRI markers of brain injury that, in many regions, were independent of the initial birth asphyxia. Targeting hemodynamic ranges to optimize autoregulation has potential as an adjunctive therapy to hypothermia for HIE.