Publications by authors named "Arastoo Vossough"

111 Publications

Advanced Magnetic Resonance Imaging in Pediatric Glioblastomas.

Front Neurol 2021 10;12:733323. Epub 2021 Nov 10.

Division of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

The shortly upcoming 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System is bringing extensive changes in the terminology of diffuse high-grade gliomas (DHGGs). Previously "glioblastoma," as a descriptive entity, could have been applied to classify some tumors from the family of pediatric or adult DHGGs. However, now the term "glioblastoma" has been divested and is no longer applied to tumors in the family of pediatric types of DHGGs. As an entity, glioblastoma remains, however, in the family of adult types of diffuse gliomas under the insignia of "glioblastoma, IDH-wildtype." Of note, glioblastomas still can be detected in children when glioblastoma, IDH-wildtype is found in this population, despite being much more common in adults. Despite the separation from the family of pediatric types of DHGGs, what was previously labeled as "pediatric glioblastomas" still remains with novel labels and as new entities. As a result of advances in molecular biology, most of the previously called "pediatric glioblastomas" are now classified in one of the four family members of pediatric types of DHGGs. In this review, the term glioblastoma is still apocryphally employed mainly due to its historical relevance and the paucity of recent literature dealing with the recently described new entities. Therefore, "glioblastoma" is used here as an umbrella term in the attempt to encompass multiple entities such as astrocytoma, IDH-mutant (grade 4); glioblastoma, IDH-wildtype; diffuse hemispheric glioma, H3 G34-mutant; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; and high grade infant-type hemispheric glioma. Glioblastomas are highly aggressive neoplasms. They may arise anywhere in the developing central nervous system, including the spinal cord. Signs and symptoms are non-specific, typically of short duration, and usually derived from increased intracranial pressure or seizure. Localized symptoms may also occur. The standard of care of "pediatric glioblastomas" is not well-established, typically composed of surgery with maximal safe tumor resection. Subsequent chemoradiation is recommended if the patient is older than 3 years. If younger than 3 years, surgery is followed by chemotherapy. In general, "pediatric glioblastomas" also have a poor prognosis despite surgery and adjuvant therapy. Magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of glioblastomas. In addition to the typical conventional MRI features, i.e., highly heterogeneous invasive masses with indistinct borders, mass effect on surrounding structures, and a variable degree of enhancement, the lesions may show restricted diffusion in the solid components, hemorrhage, and increased perfusion, reflecting increased vascularity and angiogenesis. In addition, magnetic resonance spectroscopy has proven helpful in pre- and postsurgical evaluation. Lastly, we will refer to new MRI techniques, which have already been applied in evaluating adult glioblastomas, with promising results, yet not widely utilized in children.
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http://dx.doi.org/10.3389/fneur.2021.733323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631300PMC
November 2021

Collateral Protection: Do Favorable Collaterals Predict Better Response in Children Who Undergo Thrombectomy for Large Artery Stroke?

Neurology 2021 Nov 18. Epub 2021 Nov 18.

Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1212/WNL.0000000000013082DOI Listing
November 2021

Physiologic Timeline of Cranial-Base Suture and Synchondrosis Closure.

Plast Reconstr Surg 2021 Dec;148(6):973e-982e

From the Division of Plastic Surgery and Department of Radiology, Children's Hospital of Philadelphia; and University of Pennsylvania Perelman School of Medicine.

Background: Fusion of cranial-base sutures/synchondroses presents a clinical conundrum, given their often unclear "normal" timing of closure. This study investigates the physiologic fusion timelines of cranial-base sutures/synchondroses.

Methods: Twenty-three age intervals were analyzed in subjects aged 0 to 18 years. For each age interval, 10 head computed tomographic scans of healthy subjects were assessed. Thirteen cranial-base sutures/synchondroses were evaluated for patency. Partial closure in greater than or equal to 50 percent of subjects and complete bilateral closure in less than 50 percent of subjects defined the fusion "midpoint." Factor analysis identified clusters of related fusion patterns.

Results: Two hundred thirty scans met inclusion criteria. The sutures' fusion midpoints and completion ages, respectively, were as follows: frontoethmoidal, 0 to 2 months and 4 years; frontosphenoidal, 6 to 8 months and 12 years; and sphenoparietal, 6 to 8 months and 4 years. Sphenosquamosal, sphenopetrosal, parietosquamosal, and parietomastoid sutures reached the midpoint at 6 to 8 months, 8 years, 9 to 11 months, and 12 years, respectively, but rarely completed fusion. The occipitomastoid suture partially closed in less than or equal to 30 percent of subjects. The synchondroses' fusion midpoints and completion ages, respectively, were as follows: sphenoethmoidal, 3 to 5 months and 5 years; spheno-occipital, 9 years and 17 years; anterior intraoccipital, 4 years and 10 years; and posterior intraoccipital, 18 to 23 months and 4 years. The petro-occipital synchondrosis reached the midpoint at 11 years and completely fused in less than 50 percent of subjects. Order of fusion of the sutures, but not the synchondroses, followed the anterior-to-posterior direction. Factor analysis suggested three separate fusion patterns.

Conclusions: The fusion timelines of cranial-base sutures/synchondroses may help providers interpret computed tomographic data of patients with head-shape abnormalities. Future work should elucidate the mechanisms and sequelae of cranial-base suture fusion that deviates from normal timelines.
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http://dx.doi.org/10.1097/PRS.0000000000008570DOI Listing
December 2021

Comparison of Spinal Cord Magnetic Resonance Imaging Features Among Children With Acquired Demyelinating Syndromes.

JAMA Netw Open 2021 Oct 1;4(10):e2128871. Epub 2021 Oct 1.

Division of Child Neurology, Department of Neurology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Importance: The recognition of magnetic resonance imaging (MRI) features associated with distinct causes of myelitis in children is essential to guide investigations and support diagnostic categorization.

Objective: To determine the clinical and MRI features and outcomes associated with spinal cord involvement in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), multiple sclerosis (MS), and seronegative monophasic myelitis.

Design, Setting, And Participants: In this cohort study, participants were recruited between 2004 and 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study, which enrolled youth younger than 18 years presenting within 90 days of an acquired demyelinating syndrome. Of the 430 participants recruited, those with lesions on available spine MRI and anti-MOG testing performed on archived samples obtained close to clinical presentation were selected. Participants with poor-quality images and final diagnoses of nondemyelinating disease, anti-aquaporin 4 antibody positivity, and relapsing seronegative myelitis were excluded. Data analysis was performed from December 2019 to November 2020.

Main Outcomes And Measures: Spinal cord involvement was evaluated on 324 MRI sequences, with reviewers blinded to clinical, serological, and brain MRI findings. Associated clinical features and disability scores at 5 years of follow-up were retrieved. Results were compared between groups.

Results: A total of 107 participants (median [IQR] age at onset, 11.14 [5.59-13.39] years; 55 girls [51%]) were included in the analyses; 40 children had MOGAD, 21 had MS, and 46 had seronegative myelitis. Longitudinally extensive lesions were very common among children with MOGAD (30 of 40 children [75%]), less common among those with seronegative myelitis (20 of 46 children [43%]), and rare in children with MS (1 of 21 children [5%]). Axial gray matter T2-hyperintensity (ie, the H-sign) was observed in 22 of 35 children (63%) with MOGAD, in 14 of 42 children (33%) with seronegative myelitis, and in none of those with MS. The presence of leptomeningeal enhancement was highly suggestive for MOGAD (22 of 32 children [69%] with MOGAD vs 10 of 38 children [26%] with seronegative myelitis and 1 of 15 children [7%] with MS). Children with MOGAD were more likely to have complete lesion resolution on serial images (14 of 21 children [67%]) compared with those with MS (0 of 13 children).

Conclusions And Relevance: These findings suggest that several features may help identify children at presentation who are more likely to have myelitis associated with MOGAD. Prominent involvement of gray matter and leptomeningeal enhancement are common in pediatric MOGAD, although the pathological underpinning of these observations requires further study.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.28871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515204PMC
October 2021

Arterial spin labeling as an ancillary assessment to postoperative conventional angiogram in pediatric moyamoya disease.

J Neurosurg Pediatr 2021 Oct 1:1-8. Epub 2021 Oct 1.

8Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.

Objective: Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA.

Methods: The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children's hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA.

Results: Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization.

Conclusions: Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.
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http://dx.doi.org/10.3171/2021.7.PEDS21302DOI Listing
October 2021

Longitudinally extensive transverse myelitis as a sign of multisystem inflammatory syndrome following COVID-19 infection: A pediatric case report.

J Neuroimmunol 2021 11 28;360:577704. Epub 2021 Aug 28.

Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

COVID-19 infection can cause inflammatory reactions that could involve several organs. In the pediatric population, Multi-System Inflammatory Syndrome in Children (MIS-C) has been reported as one of the consequences of COVID-19. We report a unique pediatric COVID-19 patient with MIS-C, associated with paralysis of the extremities. MRI showed abnormal signal in the cervical spinal cord compatible with transverse myelitis. Methylprednisolone and IVIG were administered, without significant symptom improvement. As a next step, Infliximab was tried for her, and she responded remarkably well to this treatment. Infliximab may be considered as a treatment option in COVID-19 patients with transverse myelitis.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397488PMC
November 2021

Joint Modeling of RNAseq and Radiomics Data for Glioma Molecular Characterization and Prediction.

Front Med (Lausanne) 2021 19;8:705071. Epub 2021 Aug 19.

Vision Lab, Department of Electrical & Computer Engineering, Old Dominion University, Norfolk, VA, United States.

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate (henceforth, ) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. In this study, we propose a novel radiogenomics-NB model for glioma grading and prediction. Our radiogenomics-NB model is developed based on differentially expressed RNAseq and selected radiomics/volumetric features which characterize tumor volume and sub-regions. The NB distribution is fitted to RNAseq counts data, and a log-linear regression model is assumed to link between the estimated NB mean and radiomics. Three radiogenomics-NB molecular mutation models (e.g., mutation, , and mutation) are investigated. Additionally, we explore gender-specific effects on the radiogenomics-NB models. Finally, we compare the performance of the proposed three mutation prediction radiogenomics-NB models with different well-known methods in the literature: Negative Binomial Linear Discriminant Analysis (NBLDA), differentially expressed RNAseq with Random Forest (RF-genomics), radiomics and differentially expressed RNAseq with Random Forest (RF-radiogenomics), and Voom-based count transformation combined with the nearest shrinkage classifier (VoomNSC). Our analysis shows that the proposed radiogenomics-NB model significantly outperforms (ANOVA test, < 0.05) for prediction of and mutations and offers similar performance for prediction of , when compared to the competing models in the literature, respectively.
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http://dx.doi.org/10.3389/fmed.2021.705071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416908PMC
August 2021

Machine Assist for Pediatric Posterior Fossa Tumor Diagnosis: A Multinational Study.

Neurosurgery 2021 Oct;89(5):892-900

Department of Neurosurgery, Great Ormond Street Hospital, London, United Kingdom.

Background: Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis.

Objective: To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP.

Methods: We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score.

Results: Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179.

Conclusion: An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.
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http://dx.doi.org/10.1093/neuros/nyab311DOI Listing
October 2021

Association of Pediatric ASPECTS and NIH Stroke Scale, Hemorrhagic Transformation, and 12-Month Outcome in Children With Acute Ischemic Stroke.

Neurology 2021 Aug 13. Epub 2021 Aug 13.

Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia.

Objective: We aimed to determine whether a modified pediatric Alberta Stroke Program Early CT Score (modASPECTS) is associated with clinical stroke severity, hemorrhagic transformation, and 12-month functional outcomes in children with acute AIS.

Methods: Children (29 days to <18 years) with acute AIS enrolled in two institutional prospective stroke registries at Children's Hospital of Philadelphia and Royal Children's Hospital Melbourne, Australia were retrospectively analyzed to determine whether modASPECTS, in which higher scores are worse, correlated with acute Pediatric NIH Stroke Scale (PedNIHSS) scores (children ≥2 years of age), was associated with hemorrhagic transformation on acute MRI, and correlated with 12-month functional outcome on the Pediatric Stroke Outcome Measure (PSOM).

Results: 131 children were included; 91 were ≥2 years of age. Median days from stroke to MRI was 1 (interquartile range [IQR] 0-1). Median modASPECTS was 4 (IQR 3-7). ModASPECTS correlated with PedNIHSS (rho=0.40, P=0.0001). ModASPECTS was associated with hemorrhagic transformation (OR 1.13 95% CI 1.02-1.25, P=0.018). Among children with follow-up (N=128, median 12.2 months, IQR 9.5-15.4 months), worse outcomes were associated with higher modASPECTS (common OR 1.14, 95%CI 1.04-1.24, P=0.005). The association between modASPECTS and outcome persisted when we adjusted for age at stroke ictus and the presence of tumor or meningitis as stroke risk factors (common OR 1.14, 95%CI 1.03-1.25, P=0.008).

Conclusions: ModASPECTS correlates with PedNIHSS scores, hemorrhagic transformation, and 12-month functional outcome in children with acute AIS. Future pediatric studies should evaluate its usefulness in predicting symptomatic intracranial hemorrhage and outcome after acute revascularization therapies.

Classification Of Evidence: This study provides Class II evidence that the modified pediatric ASPECTS on MRI is associated with stroke severity (as measured by the baseline pediatric NIH Stroke Scale), hemorrhagic transformation, and 12-month outcome in children with acute supratentorial ischemic stroke.
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http://dx.doi.org/10.1212/WNL.0000000000012558DOI Listing
August 2021

Cerebral Blood Flow of the Neonatal Brain after Hypoxic-Ischemic Injury.

Am J Perinatol 2021 Jul 5. Epub 2021 Jul 5.

Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Objective:  Hypoxic-ischemic encephalopathy (HIE) in infants can have long-term adverse neurodevelopmental effects and markedly reduce quality of life. Both the initial hypoperfusion and the subsequent rapid reperfusion can cause deleterious effects in brain tissue. Cerebral blood flow (CBF) assessment in newborns with HIE can help detect abnormalities in brain perfusion to guide therapy and prognosticate patient outcomes.

Study Design:  The review will provide an overview of the pathophysiological implications of CBF derangements in neonatal HIE, current and emerging techniques for CBF quantification, and the potential to utilize CBF as a physiologic target in managing neonates with acute HIE.

Conclusion:  The alterations of CBF in infants during hypoxia-ischemia have been studied by using different neuroimaging techniques, including nitrous oxide and xenon clearance, transcranial Doppler ultrasonography, contrast-enhanced ultrasound, arterial spin labeling MRI, 18F-FDG positron emission tomography, near-infrared spectroscopy (NIRS), functional NIRS, and diffuse correlation spectroscopy. Consensus is lacking regarding the clinical significance of CBF estimations detected by these different modalities. Heterogeneity in the imaging modality used, regional versus global estimations of CBF, time for the scan, and variables impacting brain perfusion and cohort clinical characteristics should be considered when translating the findings described in the literature to routine practice and implementation of therapeutic interventions.

Key Points: · Hypoxic ischemic injury in infants can result in adverse long-term neurologic sequelae.. · Cerebral blood flow is a useful biomarker in neonatal hypoxic-ischemic injury.. · Imaging modality, variables affecting cerebral blood flow, and patient characteristics affect cerebral blood flow assessment..
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http://dx.doi.org/10.1055/s-0041-1731278DOI Listing
July 2021

Benign longitudinal T2-hyperintense signal in the lateral cord in infancy: a cross-sectional study of spinal cord white matter maturation on magnetic resonance imaging.

Pediatr Radiol 2021 Oct 18;51(11):2069-2076. Epub 2021 Jun 18.

Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Longitudinal T2-hyperintense signal is commonly seen in the spinal cord of infants and likely reflects normal unmyelinated white matter tracts, but it can be mistaken for pathology. Autopsy studies have described incomplete myelination of spinal cord in early childhood; however, the maturation timeline of the spinal cord has not been described on imaging.

Objective: The purpose of this study was to retrospectively evaluate the maturation timeline of the spinal cord on MRI to provide a baseline for image interpretation.

Materials And Methods: We retrospectively reviewed axial T2-W images of the spinal cord acquired on 1.5-tesla (T) and 3.0-T MRI in children ages 0-2 years for presence of longitudinal T2-hyperintense signal, and we subjectively graded this signal as 0 (absent) to 3 (pronounced). Further, we reviewed a summary of medical records for confounding pathology in the brain or spine. Cord signal was interpreted as normal in the clinical report by subspecialized pediatric neuroradiologists for all included children.

Results: We reviewed 437 MRI exams from 409 children and included 189 studies in the analysis. Longitudinal T2-hyperintense signal in the lateral cord was seen in 95% (19/20) of subjects <1 month of age and was not seen in subjects ages 21-24 months (0/15). Grade 3 signal was seen in 22% (11/50) of infants ages 0-2 months and was not seen infants older than 5 months.

Conclusion: Characteristic symmetrical longitudinal T2 hyperintensity in the lateral spinal cord is common in infants and should not be mistaken for pathology, and it was not seen in children older than 21 months.
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http://dx.doi.org/10.1007/s00247-021-05115-7DOI Listing
October 2021

Intracranial Traumatic Hematoma Detection in Children Using a Portable Near-infrared Spectroscopy Device.

West J Emerg Med 2021 Mar 24;22(3):782-791. Epub 2021 Mar 24.

Alpert Medical School of Brown University, Departments of Emergency Medicine and Pediatrics, Providence, Rhode Island.

Introduction: We sought to validate a handheld, near-infrared spectroscopy (NIRS) device for detecting intracranial hematomas in children with head injury.

Methods: Eligible patients were those <18 years old who were admitted to the emergency department at three academic children's hospitals with head trauma and who received a clinically indicated head computed tomography (HCT). Measurements were obtained by a blinded operator in bilateral frontal, temporal, parietal, and occipital regions. Qualifying hematomas were a priori determined to be within the brain scanner's detection limits of >3.5 milliliters in volume and <2.5 centimeters from the surface of the brain. The device's measurements were positive if the difference in optical density between hemispheres was >0.2 on three successive scans. We calculated diagnostic performance measures with corresponding exact two-sided 95% Clopper-Pearson confidence intervals (CI). Hypothesis test evaluated whether predictive performance exceeded chance agreement (predictive Youden's index > 0).

Results: A total of 464 patients were enrolled and 344 met inclusion for primary data analysis: 10.5% (36/344) had evidence of a hematoma on HCT, and 4.7% (16/344) had qualifying hematomas. The handheld brain scanner demonstrated a sensitivity of 58.3% (21/36) and specificity of 67.9% (209/308) for hematomas of any size. For qualifying hematomas the scanner was designed to detect, sensitivity was 81% (13/16) and specificity was 67.4% (221/328). Predictive performance exceeded chance agreement with a predictive Youden's index of 0.11 (95% CI, 0.10 - 0.15; P < 0.001) for all hematomas, and 0.09 (95% CI, 0.08 - 0.12; P < 0.001) for qualifying hematomas.

Conclusion: The handheld brain scanner can non-invasively detect a subset of intracranial hematomas in children and may serve an adjunctive role to head-injury neuroimaging decision rules that predict the risk of clinically significant intracranial pathology after head trauma.
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http://dx.doi.org/10.5811/westjem.2020.11.47251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203002PMC
March 2021

Genetic and Clinical Predictors of Ataxia in Pediatric Primary Mitochondrial Disorders.

Cerebellum 2021 May 30. Epub 2021 May 30.

Division of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Evaluation of ataxia in children is challenging in clinical practice. This is particularly true for highly heterogeneous conditions such as primary mitochondrial disorders (PMD). This study aims to explore cerebellar and brain abnormalities identified on MRI as potential predictors of ataxia in patients with PMD and, likewise, to determine the effect of the patient's genetic profile on these predictors as well as determination of the temporal relationship of clinical ataxia with MRI findings. We evaluated clinical, radiological, and genetic characteristics of 111 PMD patients younger than 21 years of age at The Children's Hospital of Philadelphia. Data was extracted from charts. Blinded radiological evaluations were carried out by experienced neuroradiologists. Multivariate logistic regression and generalized equation estimates were used for analysis. Ataxia was identified in 41% of patients. Cerebellar atrophy or putaminal involvement with mitochondrial DNA (mtDNA) mutations (OR 1.18, 95% CI 1.1-1.3, p < 0.001) and nuclear DNA mutation with no atrophy of the cerebellum (OR 1.14, 95% CI 1.0-1.3, p = 0.007) predicted an increased likelihood of having ataxia per year of age. Central tegmental tract predicted the presence of ataxia independent of age and pathogenic variant origin (OR 9.8, 95% CI 2-74, p = 0.009). Ataxia tended to precede the imaging finding of cerebellar atrophy. Cerebellar atrophy and putaminal involvement on MRI of pediatric-onset PMD may predict the presence of ataxia with age in patients with mtDNA mutations. This study provides predicted probabilities of having ataxia per year of age that may help in family counseling and future research of the population.
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http://dx.doi.org/10.1007/s12311-021-01276-1DOI Listing
May 2021

Automatic Segmentation of Bone Selective MR Images for Visualization and Craniometry of the Cranial Vault.

Acad Radiol 2021 Apr 23. Epub 2021 Apr 23.

Department of Radiology, University of Pennsylvania, 1 Founders Building, 3400 Spruce Street, Philadelphia, PA 19104-4283; Laboratory for Structural, Physiologic and Functional Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Rationale And Objectives: Solid-state MRI has been shown to provide a radiation-free alternative imaging strategy to CT. However, manual image segmentation to produce bone-selective MR-based 3D renderings is time and labor intensive, thereby acting as a bottleneck in clinical practice. The objective of this study was to evaluate an automatic multi-atlas segmentation pipeline for use on cranial vault images entirely circumventing prior manual intervention, and to assess concordance of craniometric measurements between pipeline produced MRI and CT-based 3D skull renderings.

Materials And Methods: Dual-RF, dual-echo, 3D UTE pulse sequence MR data were obtained at 3T on 30 healthy subjects along with low-dose CT images between December 2018 to January 2020 for this prospective study. The four-point MRI datasets (two RF pulse widths and two echo times) were combined to produce bone-specific images. CT images were thresholded and manually corrected to segment the cranial vault. CT images were then rigidly registered to MRI using mutual information. The corresponding cranial vault segmentations were then transformed to MRI. The "ground truth" segmentations served as reference for the MR images. Subsequently, an automated multi-atlas pipeline was used to segment the bone-selective images. To compare manually and automatically segmented MR images, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) were computed, and craniometric measurements between CT and automated-pipeline MRI-based segmentations were examined via Lin's concordance coefficient (LCC).

Results: Automated segmentation reduced the need for an expert to obtain segmentation. Average DSC was 90.86 ± 1.94%, and average 95th percentile HD was 1.65 ± 0.44 mm between ground truth and automated segmentations. MR-based measurements differed from CT-based measurements by 0.73-1.2 mm on key craniometric measurements. LCC for distances between CT and MR-based landmarks were vertex-basion: 0.906, left-right frontozygomatic suture: 0.780, and glabella-opisthocranium: 0.956 for the three measurements.

Conclusion: Good agreement between CT and automated MR-based 3D cranial vault renderings has been achieved, thereby eliminating the laborious manual segmentation process. Target applications comprise craniofacial surgery as well as imaging of traumatic injuries and masses involving both bone and soft tissue.
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http://dx.doi.org/10.1016/j.acra.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536795PMC
April 2021

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

BMJ Open 2021 04 22;11(4):e043852. Epub 2021 Apr 22.

Department of Biostatistics, University of Washington, Seattle, Washington, USA.

Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.

Methods And Analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans.

Ethics And Dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor.

Trial Registration Number: NCT02811263; Pre-result.
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http://dx.doi.org/10.1136/bmjopen-2020-043852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070884PMC
April 2021

Anatomical Variations, Mimics, and Pitfalls in Imaging of Patients with Epilepsy.

J Neuroimaging 2021 01 13;31(1):20-34. Epub 2020 Dec 13.

Division of Neuroradiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Epilepsy is among one of the most common neurologic disorders. The role of magnetic resonance imaging (MRI) in the diagnosis and management of patients with epilepsy is well established, and most patients with epilepsy are likely to undergo at least one or more MRI examinations in the course of their disease. Recent advances in high-field MRI have enabled high resolution in vivo visualization of small and intricate anatomic structures that are of great importance in the assessment of seizure disorders. Familiarity with normal anatomic variations is essential in the accurate diagnosis and image interpretation, as these variations may be mistaken for epileptogenic foci, leading to unnecessary follow-up imaging, or worse, unnecessary treatment. After a brief overview of normal imaging anatomy of the mesial temporal lobe, this article will review a few important common and uncommon anatomic variations, mimics, and pitfalls that may be encountered in the imaging evaluation of patients with epilepsy.
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http://dx.doi.org/10.1111/jon.12809DOI Listing
January 2021

Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features.

Pediatr Neurol 2021 02 2;115:1-6. Epub 2020 Nov 2.

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address:

Background: Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurological injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurological dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile-onset AGS.

Methods: We conducted a multi-institution review of individuals with AGS who were older than one year at the time of presentation, including medical history, imaging characteristics, and suspected diagnoses at presentation.

Results: Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurological decline (fulminant phase), with a median onset at 1.33 years (range 1.00 to 17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common magnetic resonance imaging finding (40.0%). Calcifications were less common (12.9%).

Conclusions: This is the first study to characterize the presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classical clinical and neuroimaging findings. Signs of early systemic dysfunction before fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children older than one year.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856674PMC
February 2021

Association of MRI Brain Injury With Outcome After Pediatric Out-of-Hospital Cardiac Arrest.

Neurology 2021 02 18;96(5):e719-e731. Epub 2020 Nov 18.

From the Department of Anesthesiology and Critical Care Medicine (M.P.K., K.G., M.W., R.A.B., A.T.), Department of Pediatrics (M.P.K., D.J.L., R.A.B., A.T.), Health Analytics Unit (J.F., A.M.), and Department of Radiology (A.V.), Children's Hospital of Philadelphia; and Department of Neurology (M.P.K., D.J.L., R.B., R.D.-A.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Objective: To determine the association between the extent of diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) injury on brain MRI and outcomes after pediatric out-of-hospital cardiac arrest (OHCA).

Methods: Diffusion restriction and T2/FLAIR injury were described according to the pediatric MRI modification of the Alberta Stroke Program Early Computed Tomography Score (modsASPECTS) for children from 2005 to 2013 who had an MRI within 14 days of OHCA. The primary outcome was unfavorable neurologic outcome defined as ≥1 change in Pediatric Cerebral Performance Category (PCPC) from baseline resulting in a hospital discharge PCPC score 3, 4, 5, or 6. Patients with unfavorable outcomes were further categorized into alive with PCPC 3-5, dead due to withdrawal of life-sustaining therapies for poor neurologic prognosis (WLST-neuro), or dead by neurologic criteria.

Results: We evaluated MRI scans from 77 patients (median age 2.21 [interquartile range 0.44, 13.07] years) performed 4 (2, 6) days postarrest. Patients with unfavorable outcomes had more extensive diffusion restriction (median 7 [4, 10.3] vs 0 [0, 0] regions, < 0.001) and T2/FLAIR injury (5.5 [2.3, 8.2] vs 0 [0, 0.75] regions, < 0.001) compared to patients with favorable outcomes. Area under the receiver operating characteristic curve for the extent of diffusion restriction and unfavorable outcome was 0.96 (95% confidence interval [CI] 0.91, 0.99) and 0.92 (95% CI 0.85, 0.97) for T2/FLAIR injury. There was no difference in extent of diffusion restriction between patients who were alive with an unfavorable outcome and patients who died from WLST-neuro ( = 0.11).

Conclusions: More extensive diffusion restriction and T2/FLAIR injury on the modsASPECTS score within the first 14 days after pediatric cardiac arrest was associated with unfavorable outcomes at hospital discharge.
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http://dx.doi.org/10.1212/WNL.0000000000011217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884994PMC
February 2021

Primary Mitochondrial Disorders of the Pediatric Central Nervous System: Neuroimaging Findings.

Radiographics 2020 Nov-Dec;40(7):2042-2067

From the Department of Radiology, Division of Neuroradiology (F.G.G., C.A.P.F.A., S.R.T., J.S.M.S., S.A., A.V.), Department of Pathology (A.N.V.), and Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics (B.H., J.P., A.G.), Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104-4399; and Departments of Pediatrics (A.G.) and Radiology (S.A., A.V.), University of Pennsylvania Perelman School of Medicine (A.N.V.), Philadelphia, Pa.

Primary mitochondrial disorders (PMDs) constitute the most common cause of inborn errors of metabolism in children, and they frequently affect the central nervous system. Neuroimaging findings of PMDs are variable, ranging from unremarkable and nonspecific to florid and highly suggestive. An overview of PMDs, including a synopsis of the basic genetic concepts, main clinical symptoms, and neuropathologic features, is presented. In addition, eight of the most common PMDs that have a characteristic imaging phenotype in children are reviewed in detail. . RSNA, 2020.
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http://dx.doi.org/10.1148/rg.2020200052DOI Listing
July 2021

Spinal Cord Infarct Due to Fibrocartilaginous Embolism.

Neuropediatrics 2021 06 27;52(3):224-225. Epub 2020 Oct 27.

Division of Child Neurology, Department of Neurology and Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.

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http://dx.doi.org/10.1055/s-0040-1718918DOI Listing
June 2021

Cerebral Pulsed Arterial Spin Labeling Perfusion Weighted Imaging Predicts Language and Motor Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

Front Pediatr 2020 25;8:576489. Epub 2020 Sep 25.

Children's Hospital of Philadelphia, Philadelphia, PA, United States.

To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion. A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions. Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation ( < 0.05) in predicting language( = 0.48) and motor( = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language( = 0.76), and motor( = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕. Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.
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http://dx.doi.org/10.3389/fped.2020.576489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546822PMC
September 2020

Predicting pediatric optic pathway glioma progression using advanced magnetic resonance image analysis and machine learning.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa090. Epub 2020 Aug 1.

Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Optic pathway gliomas (OPGs) are low-grade tumors of the white matter of the visual system with a highly variable clinical course. The aim of the study was to generate a magnetic resonance imaging (MRI)-based predictive model of OPG tumor progression using advanced image analysis and machine learning techniques.

Methods: We performed a retrospective case-control study of OPG patients managed between 2009 and 2015 at an academic children's hospital. Progression was defined as radiographic tumor growth or vision decline. To generate the model, optic nerves were manually highlighted and optic radiations (ORs) were segmented using diffusion tractography tools. For each patient, intensity distributions were obtained from within the segmented regions on all imaging sequences, including derivatives of diffusion tensor imaging (DTI). A machine learning algorithm determined the combination of features most predictive of progression.

Results: Nineteen OPG patients with progression were matched to 19 OPG patients without progression. The mean time between most recent follow-up and most recently analyzed MRI was 3.5 ± 1.7 years. Eighty-three MRI studies and 532 extracted features were included. The predictive model achieved an accuracy of 86%, sensitivity of 89%, and specificity of 81%. Fractional anisotropy of the ORs was among the most predictive features (area under the curve 0.83, < 0.05).

Conclusions: Our findings show that image analysis and machine learning can be applied to OPGs to generate a MRI-based predictive model with high accuracy. As OPGs grow along the visual pathway, the most predictive features relate to white matter changes as detected by DTI, especially within ORs.
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http://dx.doi.org/10.1093/noajnl/vdaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455885PMC
August 2020

Intracranial calcifications in childhood: Part 1.

Pediatr Radiol 2020 09 30;50(10):1424-1447. Epub 2020 Jul 30.

Department of Radiology, Division of Neuroradiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

This article is the first of a two-part series on intracranial calcification in childhood. Intracranial calcification can be either physiological or pathological. Physiological intracranial calcification is not an expected neuroimaging finding in the neonatal or infantile period but occurs, as children grow older, in the pineal gland, habenula, choroid plexus and occasionally the dura mater. Pathological intracranial calcification can be broadly divided into infectious, congenital, endocrine/metabolic, vascular and neoplastic. The main goals in Part 1 are to discuss the chief differences between physiological and pathological intracranial calcification, to discuss the histological characteristics of intracranial calcification and how intracranial calcification can be detected across neuroimaging modalities, to emphasize the importance of age at presentation and intracranial calcification location, and to propose a comprehensive neuroimaging approach toward the differential diagnosis of the causes of intracranial calcification. Finally, in Part 1 the authors discuss the most common causes of infectious intracranial calcification, especially in the neonatal period, and congenital causes of intracranial calcification. Various neuroimaging modalities have distinct utilities and sensitivities in the depiction of intracranial calcification. Age at presentation, intracranial calcification location, and associated neuroimaging findings are useful information to help narrow the differential diagnosis of intracranial calcification. Intracranial calcification can occur in isolation or in association with other neuroimaging features. Intracranial calcification in congenital infections has been associated with clastic changes, hydrocephalus, chorioretinitis, white matter abnormalities, skull changes and malformations of cortical development. Infections are common causes of intracranial calcification, especially neonatal TORCH (toxoplasmosis, other [syphilis, varicella-zoster, parvovirus B19], rubella, cytomegalovirus and herpes) infections.
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http://dx.doi.org/10.1007/s00247-020-04721-1DOI Listing
September 2020

Cerebrovascular Malformations in a Pediatric Hereditary Hemorrhagic Telangiectasia Cohort.

Pediatr Neurol 2020 09 25;110:49-54. Epub 2020 May 25.

Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background: We determined the frequency of cerebrovascular malformations in a pediatric cohort with hereditary hemorrhagic telangiectasia.

Methods: Retrospective cohort study of 54 children diagnosed with hereditary hemorrhagic telangiectasia at a tertiary care center. All neuroimaging was reviewed to assess for number and types of cerebrovascular malformations and for intracerebral hemorrhage and arterial ischemic stroke. Clinical charts were reviewed for clinical manifestations, genetic mutation, and clinically evident intracerebral hemorrhages and arterial ischemic strokes.

Results: Among 54 children with hereditary hemorrhagic telangiectasia with a median age of 3.5 years (interquartile range 0.4 to 7.9 years) at diagnosis, neuroimaging was performed in 52 (96.3%) at a median age of 5.2 years (interquartile range 1.8 to 9 years). Fourteen of 52 imaged children (26.9%) had cerebrovascular malformations. Cerebrovascular malformations included arteriovenous malformations, arteriovenous fistulas, vein of Galen malformations, and developmental venous anomalies. Six of the 14 children with cerebrovascular malformations (42.9%) had multiple malformations. Three children developed new cerebral arteriovenous malformations over time. Six children (11.1%) had clinically evident intracerebral hemorrhage, arterial ischemic stroke, or transient ischemic attack. The three children with intracerebral hemorrhage presented at young ages (4.3 to 7.7 years).

Conclusions: More than a quarter of children with hereditary hemorrhagic telangiectasia who were imaged had cerebrovascular malformations, and overt stroke occurred in more than 10%. Intracerebral hemorrhages can occur in pediatric hereditary hemorrhagic telangiectasia patients at young ages, and new cerebral arteriovenous malformations may develop over time. Early screening with neuroimaging including neurovascular imaging as well as repeat neuroimaging may be warranted in children with hereditary hemorrhagic telangiectasia.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.05.008DOI Listing
September 2020

Intracranial calcifications in childhood: Part 2.

Pediatr Radiol 2020 09 8;50(10):1448-1475. Epub 2020 Jul 8.

Division of Neuroradiology, Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

This article is the second of a two-part series on intracranial calcification in childhood. In Part 1, the authors discussed the main differences between physiological and pathological intracranial calcification. They also outlined histological intracranial calcification characteristics and how these can be detected across different neuroimaging modalities. Part 1 emphasized the importance of age at presentation and intracranial calcification location and proposed a comprehensive neuroimaging approach toward the differential diagnosis of the causes of intracranial calcification. Pathological intracranial calcification can be divided into infectious, congenital, endocrine/metabolic, vascular, and neoplastic. In Part 2, the chief focus is on discussing endocrine/metabolic, vascular, and neoplastic intracranial calcification etiologies of intracranial calcification. Endocrine/metabolic diseases causing intracranial calcification are mainly from parathyroid and thyroid dysfunction and inborn errors of metabolism, such as mitochondrial disorders (MELAS, or mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Kearns-Sayre; and Cockayne syndromes), interferonopathies (Aicardi-Goutières syndrome), and lysosomal disorders (Krabbe disease). Specific noninfectious causes of intracranial calcification that mimic TORCH (toxoplasmosis, other [syphilis, varicella-zoster, parvovirus B19], rubella, cytomegalovirus, and herpes) infections are known as pseudo-TORCH. Cavernous malformations, arteriovenous malformations, arteriovenous fistulas, and chronic venous hypertension are also known causes of intracranial calcification. Other vascular-related causes of intracranial calcification include early atherosclerosis presentation (children with risk factors such as hyperhomocysteinemia, familial hypercholesterolemia, and others), healed hematoma, radiotherapy treatment, old infarct, and disorders of the microvasculature such as COL4A1- and COL4A2-related diseases. Intracranial calcification is also seen in several pediatric brain tumors. Clinical and familial information such as age at presentation, maternal exposure to teratogens including viruses, and association with chromosomal abnormalities, pathogenic genes, and postnatal infections facilitates narrowing the differential diagnosis of the multiple causes of intracranial calcification.
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http://dx.doi.org/10.1007/s00247-020-04716-yDOI Listing
September 2020

Emerging Roles of PET/MR in the Pediatric Hospital.

PET Clin 2020 Jul;15(3):253-269

Radiology Department, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Section of Oncologic Imaging, Radiology Department, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address:

Add "improving" before "detection"? PET/MR is beneficial particularly in pediatric patients who undergo recurrent imaging, such as those with cancer or chronic inflammatory disease. PET/MR has advantages compared with PET/computed tomography, including decreased radiation exposure and superior characterization of soft tissue. Ongoing challenges include reducing examination duration and costs and detection of pulmonary lesions. Accepted clinical applications of PET/MR in pediatric patients are evaluation of epileptic foci and diagnosis, staging, and follow-up of solid tumors. PET/MR also may have a role in diagnosis and management of infectious and inflammatory conditions relevant to the pediatric population, including osteomyelitis and Crohn disease.
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http://dx.doi.org/10.1016/j.cpet.2020.03.005DOI Listing
July 2020

Focal Cerebral Arteriopathy in a Pediatric Patient with COVID-19.

Radiology 2020 11 2;297(2):E274-E275. Epub 2020 Jun 2.

From the Department of Neurology, Division of Neurology, Razi Hospital of Birjand, Birjand, Iran (S.M.M.M., S.M.T.); Department of Radiology, Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, Pa (F.G.G., A.V.); and Department of Radiology, Division of Neuroradiology, Imam Reza Hospital of Birjand, Birjand, Iran (M.M.).

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http://dx.doi.org/10.1148/radiol.2020202197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587294PMC
November 2020

Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations.

Ann Neurol 2020 08 13;88(2):218-232. Epub 2020 Jun 13.

Division of Neuroradiology, Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

The neurodiagnostic criteria of Leigh syndrome have not yet been clearly redefined based on the expanding of molecular etiologies. We aimed to analyze 20 years of clinical, genetic, and magnetic resonance studies from our Leigh syndrome cohort to provide a detailed description of central nervous system lesions in Leigh syndrome and their biological evolution in view of their genetic and clinical findings. Our study adds new neurodiagnostic insights to the current knowledge of Leigh syndrome, including association with overlapping syndromes, and the correlation of pathogenic genetic variants with neuroimaging phenotypes. ANN NEUROL 2020;88:218-232.
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http://dx.doi.org/10.1002/ana.25789DOI Listing
August 2020

Phenotypic and Imaging Spectrum Associated With WDR45.

Pediatr Neurol 2020 08 11;109:56-62. Epub 2020 Mar 11.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background: Mutations in the X-linked gene WDR45 cause neurodegeneration with brain iron accumulation type 5. Global developmental delay occurs at an early age with slow progression to dystonia, parkinsonism, and dementia due to progressive iron accumulation in the brain.

Methods: We present 17 new cases and reviewed 106 reported cases of neurodegeneration with brain iron accumulation type 5. Detailed information related to developmental history and key time to event measures was collected.

Results: Within this cohort, there were 19 males. Most individuals were molecularly diagnosed by whole-exome testing. Overall 10 novel variants were identified across 11 subjects. All individuals were affected by developmental delay, most prominently in verbal skills. Most individuals experienced a decline in motor and cognitive skills. Although most individuals were affected by seizures, the spectrum ranged from provoked seizures to intractable epilepsy. The imaging findings varied as well, often evolving over time. The classic iron accumulation in the globus pallidus and substantia nigra was noted in half of our cohort and was associated with older age of image acquisition, whereas myelination abnormalities were associated with younger age.

Conclusions: WDR45 mutations lead to a progressive and evolving disorder whose diagnosis is often delayed. Developmental delay and seizures predominate in early childhood, followed by a progressive decline of neurological function. There is variable expressivity in the clinical phenotypes of individuals with WDR45 mutations, suggesting that this gene should be considered in the diagnostic evaluation of children with myelination abnormalities, iron deposition, developmental delay, and epilepsy depending on the age at evaluation.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387198PMC
August 2020
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