Publications by authors named "Nicholas Stence"

49 Publications

Imaging of fetal ventriculomegaly.

Pediatr Radiol 2020 12 30;50(13):1948-1958. Epub 2020 Nov 30.

Department of Radiology, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Ave., Box B125, Aurora, CO, 80045, USA.

Fetal ventriculomegaly is the most common central nervous system abnormality detected by prenatal imaging. It has a high association with other anomalies. Etiologies and prognoses for fetal ventriculomegaly range from normal outcomes to significant neurodevelopmental sequelae. In this paper, we review the development, terminology, pathogenesis, imaging and prognosis of fetal ventriculomegaly.
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http://dx.doi.org/10.1007/s00247-020-04880-1DOI Listing
December 2020

Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images.

Sci Rep 2020 10 9;10(1):16885. Epub 2020 Oct 9.

Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, 80045, USA.

Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.
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http://dx.doi.org/10.1038/s41598-020-73278-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547020PMC
October 2020

In Utero Exposure to Maternal Overweight or Obesity is Associated with Altered Offspring Brain Function in Middle Childhood.

Obesity (Silver Spring) 2020 09 8;28(9):1718-1725. Epub 2020 Aug 8.

Department of Psychiatry, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Objective: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy.

Methods: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado.

Results: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all).

Conclusions: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.
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http://dx.doi.org/10.1002/oby.22908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483843PMC
September 2020

Foreign Body Esophageal Perforation Leading to Multifocal Brain Abscesses: A Case Report.

J Emerg Med 2020 Oct 18;59(4):e131-e135. Epub 2020 Jul 18.

Department of Emergency Medicine, Denver Health and Hospital Authority, Denver, Colorado.

Background: Among those aged 5 years or younger, foreign bodies are the fourth most common pediatric exposure reported to the American Association of Poison Control Centers. Although the majority of ingested foreign bodies pass through the gastrointestinal tract without complication, those that do not spontaneously pass can lead to a number of serious complications, such as gastrointestinal obstruction or perforation, which can be complicated by bleeding from aortoesophageal fistula, secondary mediastinitis, peritonitis, esophageal or gastrointestinal fistula formation, and abscesses.

Case Report: We present the case of a 10-month-old child who presented with new-onset focal seizure in the setting of multiple brain abscesses, ultimately found to be due to esophageal perforation from a retained, metallic esophageal foreign body. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Foreign bodies that are retained for longer than 24 h after ingestion have been associated with a higher risk of complications because they are less likely to pass spontaneously through the gastrointestinal tract. Early identification and removal of foreign bodies is necessary to prevent subsequent complications. In patients who have a subacute history of cough, gagging, vomiting, and decreased oral intake with an otherwise unknown cause, foreign-body ingestion or aspiration should be considered. In addition, central nervous system abscess and infection should be considered in patients with concerns about previous foreign body ingestion or aspiration and who are newly presenting with fever, focal neurologic changes, and irritability.
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http://dx.doi.org/10.1016/j.jemermed.2020.06.025DOI Listing
October 2020

Unusual Neuroimaging in a Case of Rapidly Progressive Juvenile-Onset Krabbe Disease.

J Child Neurol 2020 09 2;35(10):649-653. Epub 2020 Jun 2.

Section of Clinical Genetics and Metabolism, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Aurora, CO, USA.

Krabbe disease is a progressive neurologic disorder caused by deficiency of the lysosomal enzyme galactocerebrosidase. The disease commonly has an early-infantile onset, but can have late-infantile, juvenile, or adult-onset phenotypes. Classic computed tomography (CT) and magnetic resonance imaging (MRI) findings in Krabbe have been well described. We report a patient, ultimately diagnosed with juvenile-onset Krabbe, who presented with atypical CT imaging and rapid disease progression. Our patient was a previously healthy and developmentally appropriate female who presented at 3 years 4 months of age with ataxia and motor regression that had progressed over the course of 6 weeks without an identifiable catalyst. CT, performed in the emergency setting, demonstrated extensive white matter hyperdensity. Subsequent MRI showed T2 hyperintensity of the white matter corresponding to the areas of hyperdensity on the CT, as well as enhancement of multiple cranial nerves bilaterally, suggestive of Krabbe disease. Enzymatic testing demonstrated low galactocerebrosidase activity and molecular testing of revealed compound heterozygosity for 2 known pathogenic mutations, consistent with a diagnosis of Krabbe Disease. This included the common 30-kb deletion and a known pathogenic mutation associated with juvenile/adult-onset disease. Our patient's diffuse hyperdensity on CT offers a new radiographic finding to include in the repertoire of Krabbe imaging, and thus aide in the diagnostic evaluation. The rapidity of progression our patient demonstrated is additionally unique and should be considered in the identification of juvenile Krabbe as well as the complicated decision-making process regarding potential treatments.
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http://dx.doi.org/10.1177/0883073820924985DOI Listing
September 2020

Lateral semi-circular canal asymmetry in females with idiopathic scoliosis.

PLoS One 2020 29;15(4):e0232417. Epub 2020 Apr 29.

Department of Orthopaedic Surgery, Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, Colorado, United States of America.

Purpose: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal structural deformity that occurs in otherwise normal individuals. Although curve progression and severity vary amongst individuals, AIS can lead to significant cosmetic and functional deformity. AIS etiology has been determined to be genetic, however, exact genetic and biological processes underlying this disorder remain unknown. Vestibular structure and function have potentially been related to the etiopathogenesis of AIS. Here, we aimed to characterize the anatomy of the semicircular canals (SCC) within the vestibular system through a novel approach utilizing T2-weighted magnetic resonance images (MRI).

Methods: Three dimensional, MRI-based models of the SCCs were generated from AIS subjects (n = 20) and healthy control subjects (n = 19). Linear mixed models were used to compare SCC morphological measurements in the two groups. We compared side-to-side differences in the SCC measurements between groups (group*side interaction).

Results: Side-to-side differences in the lateral SCC were different between the two groups [false discovery rate adjusted p-value: 0.0107]. Orientation of right versus left lateral SCC was significantly different in the AIS group compared to the control group [mean side-to-side difference: -4.1°, 95% CI: -6.4° to -1.7°]. Overall, among subjects in the AIS group, the left lateral SCC tended to be oriented in a more horizontal position than subjects in the control group.

Significance: Asymmetry within the SCCs of the vestibular system of individuals with AIS potentially results in abnormal efferent activity to postural muscles. Consequences of this muscular activity during periods of rapid growth, which often coincides with AIS onset and progression, warrant consideration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232417PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190182PMC
July 2020

Fusion patterns of major calvarial sutures on volume-rendered CT reconstructions.

J Neurosurg Pediatr 2020 Feb 7:1-10. Epub 2020 Feb 7.

5Plastic Surgery, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado.

Objective: Recently, the authors investigated the normal course of fusion of minor lateral calvarial sutures on "3D" volume-rendered head CT reconstructions in pediatric trauma patients. While evaluating these reconstructions, they found many more fused sagittal sutures than expected given the currently accepted prevalence of sagittal craniosynostosis. In the present study, using the same set of head CT reconstructions, they investigated the course of fusion of the sagittal as well as the lambdoid, coronal, and metopic sutures.

Methods: They reviewed all volume-rendered head CT reconstructions performed in the period from 2010 through mid-2012 at Children's Hospital Colorado for trauma patients aged 0-21 years. Each sagittal, lambdoid, coronal, or metopic suture was graded as open, partially fused, or fused. The cephalic index (CI) was calculated for subjects with fused and partially fused sagittal sutures.

Results: After exclusions, 331 scans were reviewed. Twenty-one subjects (6%) had fusion or partial fusion of the sagittal suture. Four of the 21 also had fusion of the medial lambdoid and/or coronal sutures. In the 17 subjects (5%) with sagittal suture fusion and no medial fusion of adjacent sutures, the mean CI was 77.6. None of the 21 subjects had been previously diagnosed with craniosynostosis. Other than in the 21 subjects already mentioned, no other sagittal or lambdoid sutures were fused at all. Nor were other coronal sutures fused medially. Coronal sutures were commonly fused inferiorly early during the 2nd decade of life, and fusion progressed superiorly and medially as subjects became older; none were completely fused by 18 years of age. Fusion of the metopic suture was first seen at 3 months of life; fusion was often not complete until after 2 years.

Conclusions: The sagittal and lambdoid sutures do not usually begin to fuse before 18 years of age. However, more sagittal sutures are fused before age 18 than expected given the currently accepted prevalence of craniosynostosis. This finding is of unknown significance, but likely many of them do not need surgery. The coronal suture often begins to fuse inferiorly early in the 2nd decade of life but does not usually complete fusion before 18 years of age. The metopic suture often starts to fuse by 3 months of age, but it may not completely fuse until after 2 years of age.
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http://dx.doi.org/10.3171/2019.11.PEDS1953DOI Listing
February 2020

The utility of magnetic resonance imaging in pediatric trauma patients suspected of having cervical spine injuries.

J Trauma Acute Care Surg 2019 12;87(6):1328-1335

From the Department of Pediatric Surgery (S.C.D.); Department of Pediatric Neurosurgery (K.G., S.G., T.C.H., N.H., A.A., B.R.O., C.C.W., M.H.H.); Department of Radiology (D.M.M., N.V.S.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.

Background: Pediatric cervical spine injuries (CSI) are rare but potentially devastating sequelae of blunt trauma. Existing protocols to evaluate children at risk for CSI frequently incorporate computed topography (CT) and magnetic resonance imaging (MRI); however, the clinical value of performing both remains unclear.

Methods: Single-center retrospective review of pediatric trauma patients who underwent both CT and MRI of the cervical spine between 2001 and 2015. Based on radiographic findings, CT and MRI results were grouped into one of three categories: no injury, stable injury, or unstable injury. Radiographic instability was defined by disruption of two or more contiguous spinal columns while radiographic stability was defined by any other acute cervical spine abnormality on imaging. Clinical instability was defined by the need for surgical intervention (halo or spinal fusion), with the remaining patients, including children discharged in a cervical collar, considered clinically stable.

Results: In total, 221 children met inclusion criteria, with a median age of 9 (interquartile range, 3-14). The Glasgow Coma Scale (GCS) score of the cohort was 9 (interquartile range, 4-15). Thirty-three (14.9%) children had clinically unstable injuries, requiring surgical intervention. Among the 160 (72.4%) children with no injury on CT, MRI identified no injury in 84 (52.5%) cases, a stable injury in 76 (47.5%) cases, and an unstable injury in none. Among the 21 children with stable injuries on CT, MRI findings were concordant in 17 (81.0%) cases. In four (19.0%) cases, a spinal column injury was identified on CT and appeared to be stable, but later deemed unstable on MRI. Forty (18.1%) patients had an unstable injury on CT with 100% MRI concordance.

Conclusion: In pediatric trauma patients suspected of having a CSI, a normal cervical spine CT is sufficient to rule out a clinically significant CSI as no child with a normal cervical CT was found to be radiographically or clinically unstable.

Level Of Evidence: Diagnostic Test, level III.
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http://dx.doi.org/10.1097/TA.0000000000002487DOI Listing
December 2019

Subpial Hemorrhage of the Neonate.

Stroke 2020 01 7;51(1):315-318. Epub 2019 Nov 7.

Department of Radiology (N.V.S., D.M.M.), Children's Hospital Colorado, Aurora.

Background and Purpose- Subpial hemorrhage of the neonate is a rare stroke subtype reported in few case series. Birth trauma and coagulopathy are commonly proposed etiologies. We evaluated our subpial hemorrhage of the neonate patient cohort to expand current understanding Methods- Cases of subpial hemorrhage of the neonate were identified by keyword searches of the institutional database. The medical records and magnetic resonance imagings were reviewed. Results- Seventeen cases were identified. Assisted delivery occurred in 12% of cases, and acute coagulation abnormalities occurred in 77%. Subpial hemorrhage of the neonate was located in the temporal lobe in 82%, with cytotoxic edema and medullary vein congestion and thrombosis subjacent to the hemorrhages in 100% and 76% of cases, respectively. Neurological disability was present in 44% of survivors. Three patients had chronic coagulation abnormalities. Conclusions- In our cohort, clinical findings supporting a potential relationship with birth trauma were infrequent. The imaging findings suggest a nonarterial, deep venous pattern of hemorrhagic ischemia.
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http://dx.doi.org/10.1161/STROKEAHA.119.025987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050827PMC
January 2020

Serial Magnetic Resonance Imaging (MRI) in Pyruvate Dehydrogenase Complex Deficiency.

J Child Neurol 2020 02 31;35(2):137-145. Epub 2019 Oct 31.

Section of Genetics, Department of Pediatrics, University of Colorado, School of Medicine, Aurora, CO, USA.

Objectives: To report 2 additional cases of pyruvate dehydrogenase complex deficiency with reversible deep gray matter lesions following initiation of ketogenic diet and to perform a literature review of serial imaging in patients with pyruvate dehydrogenase complex.

Methods: Clinical data on 3 previously unpublished cases of patients with pyruvate dehydrogenase complex deficiency and with serial magnetic resonance imagings (MRIs) before and after institution of ketogenic diet were reported. A systematic literature review was performed to search for published cases of patients with confirmed pyruvate dehydrogenase complex deficiency who underwent serial MRIs.

Results: The 3 subjects in this series demonstrated clinical improvement on ketogenic diet. Two subjects showed reversal of some brain lesions on repeat MRI following initiation of ketogenic diet. Of the 21 published cases with serial MRIs, 13 patients underwent some form of treatment, and of this smaller subset 4 patients had repeat MRIs that showed definitive improvement. In both our described cases and those published in the literature, improvement occurred in lesions in the basal ganglia.

Conclusions: In patients with pyruvate dehydrogenase complex deficiency, basal ganglia lesions on MRI are reversible with treatment in some cases and could serve as a biomarker for measuring response to treatment.
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http://dx.doi.org/10.1177/0883073819881940DOI Listing
February 2020

Feasibility and Accuracy of Fast MRI Versus CT for Traumatic Brain Injury in Young Children.

Pediatrics 2019 10;144(4)

School of Medicine, University of Colorado, Denver, Colorado.

Background: Computed tomography (CT) is commonly used for children when there is concern for traumatic brain injury (TBI) and is a significant source of ionizing radiation. Our objective was to determine the feasibility and accuracy of fast MRI (motion-tolerant MRI sequences performed without sedation) in young children.

Methods: In this prospective cohort study, we attempted fast MRI in children <6 years old who had head CT performed and were seen in the emergency department of a single, level 1 pediatric trauma center. Fast MRI sequences included 3T axial and sagittal T2 single-shot turbo spin echo, axial T1 turbo field echo, axial fluid-attenuated inversion recovery, axial gradient echo, and axial diffusion-weighted single-shot turbo spin echo planar imaging. Feasibility was assessed by completion rate and imaging time. Fast MRI accuracy was measured against CT findings of TBI, including skull fracture, intracranial hemorrhage, or parenchymal injury.

Results: Among 299 participants, fast MRI was available and attempted in 225 (75%) and completed in 223 (99%). Median imaging time was 59 seconds (interquartile range 52-78) for CT and 365 seconds (interquartile range 340-392) for fast MRI. TBI was identified by CT in 111 (50%) participants, including 81 skull fractures, 27 subdural hematomas, 24 subarachnoid hemorrhages, and 35 other injuries. Fast MRI identified TBI in 103 of these (sensitivity 92.8%; 95% confidence interval 86.3-96.8), missing 6 participants with isolated skull fractures and 2 with subarachnoid hemorrhage.

Conclusions: Fast MRI is feasible and accurate relative to CT in clinically stable children with concern for TBI.
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http://dx.doi.org/10.1542/peds.2019-0419DOI Listing
October 2019

Diagnostic accuracy of neuroimaging in pediatric optic chiasm/sellar/suprasellar tumors.

Pediatr Blood Cancer 2019 06 8;66(6):e27680. Epub 2019 Mar 8.

Morgan Adams Foundation Pediatric Brain Tumor Research Foundation, Aurora, Colorado.

Preoperative diagnosis for tumors arising in the optic chiasm/sellar/suprasellar region in children is helpful to determine surgical necessity and approach, given the high operative risk in this area. We evaluated the ability to differentiate tumor type by preoperative neuroimaging. Thirty-eight of 53 tumors were correctly diagnosed by neuroimaging based on final pathologic diagnosis (prediction accuracy 72%). Prediction accuracies were 87% (20/23) for craniopharyngioma, 79% (11/14) for optic pathway glioma, 64% (7/11) for germ cell tumor, and 0% (0/5) for Langerhans cell histiocytosis. Diagnosis of optic chiasm/sellar/suprasellar tumors in children by imaging alone should be considered when biopsy is considered high risk.
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http://dx.doi.org/10.1002/pbc.27680DOI Listing
June 2019

Dual energy head CT to maintain image quality while reducing dose in pediatric patients.

Clin Imaging 2019 May - Jun;55:83-88. Epub 2019 Feb 7.

Department of Radiology, Children's Hospital Colorado, 13123 E. 16th Ave., Box 125, Aurora, CO 80045, USA.

Aim: The aim of this study was to use dual energy CT technology to maintain or improve image quality in pediatric head CT while simultaneously reducing radiation dose.

Materials And Methods: In this retrospective study, helical head CTs performed using a standard head CT protocol were compared to studies performed with a dual energy (DE) protocol. Objective comparison was performed by measuring regions of interest in 11 areas of the brain. Subjective rating for image quality using a Likert scale, was performed by three radiologists. Radiation doses were evaluated using CT dose index and dose length product.

Results: Signal-to-noise ratio was, for the most part, not significantly different between the DE and conventional scans. Contrast-to-noise ratio was slightly lower for children over 6 year of age utilizing the dual energy protocol versus the standard protocol. Qualitatively, there was little difference in image quality in patients <6 years old, with the only significant difference in infratentorial noise. However, in patients >6 years of age, infratentorial noise, sharpness and diagnostic acceptability, as well as supratentorial sharpness were all significantly improved by DE CT technique. Radiation exposure as measured by CTDI and DLP was modestly lower with the dual energy protocol in all study populations.

Conclusion: Dual energy CT can be used clinically in pediatric patients to maintain or improve image quality while reducing radiation dose.
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http://dx.doi.org/10.1016/j.clinimag.2019.02.005DOI Listing
November 2019

Brain imaging in classic nonketotic hyperglycinemia: Quantitative analysis and relation to phenotype.

J Inherit Metab Dis 2019 05 20;42(3):438-450. Epub 2019 Mar 20.

Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, Colorado.

Patients with severe nonketotic hyperglycinemia (NKH) have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain magnetic resonance imaging (MRI) between phenotypes have not been reported. In a retrospective cross-sectional study, we reviewed 38 MRI studies from 24 molecularly proven NKH patients, and 2 transient NKH patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. All patients age <3 months had restricted diffusion in the posterior limb of the internal capsule, anterior brainstem, posterior tegmental tracts, and cerebellum, not present in transient NKH. In older infants, the pattern evolved and included generalized diffusion restriction in the supratentorial white matter, which quantitatively peaked between 3 and 12 months. No patient had absent corpus callosum or gyral malformation. The corpus callosum was relatively short in severe compared to attenuated phenotypes, and thin in severe cases only. The corpus callosum growth rate differed by severity; age-matched Z-scores of thickness worsened in severe cases only. Cerebral volume was decreased in the hippocampus, globus pallidus, cerebral cortex, thalamus, and cerebellum. Severe patients had greatest glycine/creatine ratios. In this study, no brain malformations were identified. The growth failure of the corpus callosum is worse in severe NKH, whereas the diffusion restriction pattern, reflecting microspongiosis, does not discriminate by phenotypic severity. NKH is therefore a disorder of brain growth best recognized in the corpus callosum, whereas spongiosis is not prognostic.
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http://dx.doi.org/10.1002/jimd.12072DOI Listing
May 2019

A Review of Neuropathological Features of Familial and Adult Hemophagocytic Lymphohistiocytosis.

J Neuropathol Exp Neurol 2019 03;78(3):197-208

Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.

Hemophagocytic lymphohistiocytosis (HLH) is a hematological disorder that can be due to genetic (primary HLH) causes or excessive activation of the immune system in association with infection, malignancy, rheumatologic disorders, or immune suppression (secondary HLH). Hemophagocytic lymphohistiocytosis remains an under-recognized condition among neuropathologists, especially the secondary forms, where it may be diagnosed only at brain biopsy or autopsy due to confounding comorbidities. The CNS is frequently affected, but neuropathological features are underappreciated. We place our own experience with HLH in context with review of neuropathological features from the literature. A 10-year database search for cases from our pediatric and adult hospitals with re-review of neuropathological features revealed 1 biopsy and 5 autopsies. Literature that reported neuropathological features was tabulated and 8 adult and 12 pediatric cases were identified. Children had predominantly secondary HLH: 5/12 co-associated with Epstein Barr (or dual) viral infections, 3/12 with malignancy. One biopsy showed florid lymphohistiocytic infiltrates and hemophagocytosis and served as first diagnosis; 2/5 CNS autopsies had originally been reported as negative for HLH, but on re-review had subtle lymphohistiocytic infiltrates with hemophagocytosis confined to leptomeninges. In conclusion, the neuropathological features are highly variable in HLH; features such as focal erythrophagocytosis may be histologically subtle in early phases, but should be sought.
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http://dx.doi.org/10.1093/jnen/nlz001DOI Listing
March 2019

Age-associated hippocampal volume changes in childhood arterial ischemic stroke.

Childs Nerv Syst 2019 02 8;35(2):295-300. Epub 2018 Dec 8.

Department of Radiology, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

Purpose: Recent evidence suggests that recovery from secondary neurodegeneration following arterial ischemic stroke (AIS) may be related to age at injury and site of occlusion. We conducted a study of hippocampal volume (HCV) in a cohort of pediatric patients with middle cerebral artery (MCA) territory AIS to determine whether HCV would be preserved in younger children as compared to older children.

Methods: This single-center, HIPAA-compliant retrospective study was approved by the institutional review board. The medical records of 149 children treated for AIS between 2000 and 2016 were reviewed for inclusion criteria: unilateral MCA territory AIS and availability of high-resolution T1-weighted MR imaging at both acute and chronic time periods. Manual segmentation was utilized to measure stroke-side HCV, contralateral HCV, hemispheric volumes, and stroke volume on each scan. To correct for variable brain size, HCV measurements were ratio normalized. Patients were divided into two age-at-stroke groups: younger (30 days-9 years old) and older (> 9-18 years old). Analysis was performed using Fisher's test or Student's t test.

Results: The MR imaging of 19 children (9 younger, 10 older) was analyzed. At follow-up, the average stroke-side HCV increased by 10.9% in the younger group and decreased by 6.3% in the older group (P = 0.010); this between-group difference remained significant even when ratio normalized (P = 0.003). The total brain volume-adjusted acute stroke size between groups was not statistically different (P = 0.649).

Conclusions: In children with AIS, younger age is associated with the relative preservation of HCV, which could reflect differences in age-related plasticity.
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http://dx.doi.org/10.1007/s00381-018-4021-5DOI Listing
February 2019

The conus medullaris ratio: A new way to identify tethered cord on MRI.

J Pediatr Surg 2019 Feb 6;54(2):280-284. Epub 2018 Nov 6.

Department of Radiology.

Purpose: Approximately 25% of patients with anorectal malformation have tethered cord. The traditional way of determining conus medullaris level on magnetic resonance imaging (MRI) relies on counting vertebrae, which may be challenging due to vertebral numeric variation, segmentation anomalies, as well as transitional vertebral body anatomy. The purpose of this study was to utilize more reliable anatomic landmarks (foramen magnum, conus termination, and the upper limit of the iliac crest) to establish a consistent ratio that may differentiate patients with normal and low-lying conus.

Methods: A single institution database search identified two groups of patients: 255 with normal and 85 with abnormal spinal MRI, who underwent tethered cord release. The conus medullaris ratio was calculated in both groups. The ratio was obtained by dividing the distance between the conus level and the iliac crest by the distance between the foramen magnum and the conus level (IRB # 16-2330).

Results: The mean ratio was significantly higher in the non-tethered group compared to the tethered patients (0.184 [sd 0.03] versus 0.118 [sd 0.09]; P < .0001). The ratio proved to be a good discriminator between normal and abnormal patients, with area under the curve (AUC) equal to 0.749, meaning that at random, there is a 75% chance that the tethered cord patient will have a lower ratio than the non-tethered cord patient.

Conclusion: "The Conus Medullaris Ratio" is a good predictor of low-lying conus level on MRI and offers an easy alternative to counting vertebral body levels, particularly in patients with variant or abnormal vertebral body anatomy.

Level Of Evidence: II, Study of Diagnostic Test.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.10.081DOI Listing
February 2019

Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History.

Stroke 2018 11;49(11):2590-2596

Division of Neuroradiology, Department of Radiology, Stanford University, CA (B.J., M.W.).

Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.
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http://dx.doi.org/10.1161/STROKEAHA.118.021556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334774PMC
November 2018

Infection of the spheno-occipital synchondrosis: A morbid complication following adenoidectomy.

Int J Pediatr Otorhinolaryngol 2018 Aug 28;111:59-62. Epub 2018 May 28.

Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Pediatric Otolaryngology, Children's Hospital Colorado, Aurora, CO, USA. Electronic address:

Two 2-year-old males presented post-operatively following adenoidectomy with persistent fever and neck stiffness. After multiple office visits, both patients were admitted and found to have a widened spheno-occipital synchondrosis and other imaging findings indicative of skull base osteomyelitis. Treatment with antibiotics allowed for recovery with good long-term outcomes. Infection involving the spheno-occiptal synchondrosis is rare and its circuitous presentation of these two children no doubt led to delayed diagnosis.
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http://dx.doi.org/10.1016/j.ijporl.2018.05.012DOI Listing
August 2018

Significance of FDG-PET Hypermetabolism in Children with Intractable Focal Epilepsy.

Pediatr Neurosurg 2018 19;53(3):153-162. Epub 2018 Apr 19.

Department of Neurology, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado, USA.

Background: Interictal 18F-fluorodeoxyglucose-positron emission topography (FDG-PET) hypometabolism is routinely used in the presurgical workup of children with medically intractable epilepsy (MIE). FDG-PET hypermetabolism, however, is rarely seen, and the significance of this finding in the epilepsy workup is not well established.

Methods: We performed a retrospective study of patients who underwent FDG-PET during the presurgical workup of MIE over a 4-year period, between 1 January 2010 and 31 December 2013, at the Children's Hospital Colorado, CO, USA.

Results: Focal FDG-PET hypermetabolism was identified in 7 (2.2%) of 317 patients. The median age was 124 months, all cases with catastrophic epilepsy. Surface electroencephalography (EEG) performed concomitantly with FDG injections revealed ictal EEG discharges in 2 patients, frequent interictal epileptiform discharges (IEDs) in 3, occasional IEDs in 1, and no IEDs in 1. All 7 patients underwent functional hemispherectomies. Histopathology revealed type 1 focal cortical dysplasia in all patients. Six (86%) were completely seizure-free (Engel class I) and 1 had extremely infrequent seizures (Engel class II) (mean follow-up, 47.4 months).

Conclusion: While a rare finding, interictal PET hypermetabolism does occur, may help identify epileptogenic zones, and assessment to reveal it should be made by concomitant use of surface EEG during PET scans.
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http://dx.doi.org/10.1159/000487088DOI Listing
September 2018

Occult head injury is common in children with concern for physical abuse.

Pediatr Radiol 2018 08 13;48(8):1123-1129. Epub 2018 Apr 13.

University of Colorado School of Medicine, Aurora, CO, USA.

Background: Studies evaluating small patient cohorts have found a high, but variable, rate of occult head injury in children <2 years old with concern for physical abuse. The American College of Radiology (ACR) recommends clinicians have a low threshold to obtain neuroimaging in these patients.

Objectives: Our aim was to determine the prevalence of occult head injury in a large patient cohort with suspected physical abuse using similar selection criteria from previous studies. Additionally, we evaluated proposed risk factors for associations with occult head injury.

Materials And Methods: This was a retrospective, secondary analysis of data collected by an observational study of 20 U.S. child abuse teams that evaluated children who underwent subspecialty evaluation for concern of abuse. We evaluated children <2 years old and excluded those with abnormal mental status, bulging fontanelle, seizure, respiratory arrest, underlying neurological condition, focal neurological deficit or scalp injury.

Results: One thousand one hundred forty-three subjects met inclusion criteria and 62.5% (714) underwent neuroimaging with either head computed tomography or magnetic resonance imaging. We found an occult head injury prevalence of 19.7% (141). Subjects with emesis (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.8), macrocephaly (OR 8.5, 95% CI 3.7-20.2), and loss of consciousness (OR 5.1, 95% CI 1.2-22.9) had higher odds of occult head injury.

Conclusion: Our results show a high prevalence of occult head injury in patients <2 years old with suspected physical abuse. Our data support the ACR recommendation that clinicians should have a low threshold to perform neuroimaging in patients <2 years of age.
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http://dx.doi.org/10.1007/s00247-018-4128-6DOI Listing
August 2018

Seizure Severity Is Correlated With Severity of Hypoxic-Ischemic Injury in Abusive Head Trauma.

Pediatr Neurol 2018 05 12;82:29-35. Epub 2017 Dec 12.

Department of Pediatrics, Division of Child Neurology, University of Colorado Anschuts Medical Campus, Aurora, Colorado.

Background: The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma.

Methods: We studied 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored.

Results: Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r=0.61, P < 0.001). The ratio of restricted diffusion volume to total brain volume (restricted diffusion ratio) was smaller on magnetic resonance imaging done early (median restricted diffusion ratio 0.03, interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03).

Conclusions: Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury.
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http://dx.doi.org/10.1016/j.pediatrneurol.2017.12.003DOI Listing
May 2018

Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

Radiology 2018 Apr 2;287(1):313-322. Epub 2017 Nov 2.

From the Departments of Radiology (D.B.L., M.P.L., S.S.H., C.P.L.), Computer Science (M.C.C.), and Biomedical Informatics (C.P.L.), Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5105; and Department of Radiology, Children's Hospital Colorado, Aurora, Colo (N.V.S.).

Purpose To compare the performance of a deep-learning bone age assessment model based on hand radiographs with that of expert radiologists and that of existing automated models. Materials and Methods The institutional review board approved the study. A total of 14 036 clinical hand radiographs and corresponding reports were obtained from two children's hospitals to train and validate the model. For the first test set, composed of 200 examinations, the mean of bone age estimates from the clinical report and three additional human reviewers was used as the reference standard. Overall model performance was assessed by comparing the root mean square (RMS) and mean absolute difference (MAD) between the model estimates and the reference standard bone ages. Ninety-five percent limits of agreement were calculated in a pairwise fashion for all reviewers and the model. The RMS of a second test set composed of 913 examinations from the publicly available Digital Hand Atlas was compared with published reports of an existing automated model. Results The mean difference between bone age estimates of the model and of the reviewers was 0 years, with a mean RMS and MAD of 0.63 and 0.50 years, respectively. The estimates of the model, the clinical report, and the three reviewers were within the 95% limits of agreement. RMS for the Digital Hand Atlas data set was 0.73 years, compared with 0.61 years of a previously reported model. Conclusion A deep-learning convolutional neural network model can estimate skeletal maturity with accuracy similar to that of an expert radiologist and to that of existing automated models. RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on January 19, 2018.
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http://dx.doi.org/10.1148/radiol.2017170236DOI Listing
April 2018

Frontal and occipital horn ratio is associated with multifocal intraparenchymal hemorrhages in neonatal shunted hydrocephalus.

J Neurosurg Pediatr 2017 Nov 8;20(5):432-438. Epub 2017 Sep 8.

Radiology, and.

OBJECTIVE Placement of a cerebrospinal fluid diversion device (i.e., shunt) is a routine pediatric neurosurgical procedure, often performed in the first weeks of life for treatment of congenital hydrocephalus. In the postoperative period, shunt placement may be complicated by subdural, catheter tract, parenchymal, and intraventricular hemorrhages. The authors observed a subset of infants and neonates who developed multifocal intraparenchymal hemorrhages (MIPH) following shunt placement and sought to determine any predisposing perioperative variables. METHODS A retrospective review of the electronic medical record at a tertiary-care children's hospital was performed for the period 1998-2015. Inclusion criteria consisted of shunt placement, age < 30 days, and available pre- and postoperative brain imaging. The following data were collected and analyzed for each case: ventricular size ratios, laboratory values, clinical presentation, shunt and valve type, and operative timing and approach. RESULTS A total of 121 neonates met the inclusion criteria for the study, and 11 patients (9.1%) had MIPH following shunt placement. The preoperative frontal and occipital horn ratio (FOR) was significantly higher in the patients with MIPH than in those without (0.65 vs 0.57, p < 0.001). The change in FOR (∆FOR) after shunt placement was significantly greater in the MIPH group (0.14 vs 0.08, p = 0.04). Among neonates who developed MIPH, aqueductal stenosis was the most common etiology (45%). The type of shunt valve was associated with incidence of MIPH (p < 0.001). Preoperative clinical parameters, including head circumference, bulging fontanelle, and coagulopathy, were not significantly associated with development of MIPH. CONCLUSIONS MIPH represents an underrecognized complication of neonatal shunted hydrocephalus. Markers of severity of ventriculomegaly (FOR) and ventricular response to CSF diversion (∆FOR) were significantly associated with occurrence of MIPH. Choice of shunt and etiology of hydrocephalus were also significantly associated with MIPH. After adjusting for corrected age, etiology of hydrocephalus, and shunt setting, the authors found that ∆FOR after shunting was still associated with MIPH. A prospective study of MIPH prevention strategies and assessment of possible implications for patient outcomes is needed.
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http://dx.doi.org/10.3171/2017.6.PEDS16481DOI Listing
November 2017

Predicting Progression of Intracranial Arteriopathies in Childhood Stroke With Vessel Wall Imaging.

Stroke 2017 08 5;48(8):2274-2277. Epub 2017 Jul 5.

From the Department of Radiology (N.V.S., D.M.M.) and Departments of Pediatrics and Pediatric Neurology (T.J.B.), Children's Hospital Colorado, Aurora; and Hemophilia and Thrombosis Center (L.L.P., A.L.H., T.J.B.), Department of Anesthesiology (P.S.H., R.J.T.), and Department Neurology (S.P.), University of Colorado Denver, Aurora.

Background And Purpose: Childhood arterial ischemic stroke is frequently associated with an intracranial arteriopathy that often progresses in the first 3 to 6 months post stroke. We hypothesized that children with enhancing arteriopathies on vessel wall imaging (VWI) would have a higher risk of arteriopathy progression than those without enhancement.

Methods: Our institutional radiographic database was searched for cases of childhood stroke with VWI. Inclusion criteria consisted of age ranging from 1 month through 20 years, diagnosis of arterial ischemic stroke, available VWI, and follow-up magnetic resonance angiogram. Imaging was reviewed to systematically describe VWI findings, categorize arteriopathies, steroid therapy, and identify progressive arteriopathies using CACADE definitions.

Results: Sixteen cases of childhood stroke at Children's Hospital Colorado between January 1, 2010 and July 1, 2016 were reviewed. Strong vessel wall enhancement at presentation was associated with progressive arteriopathy in 83% of cases (10/12), when compared with 0% (0/4) without strong enhancement (=0.008).

Conclusions: Our case series demonstrates the potential benefit of VWI in children with stroke because it may identify patients who will have progressive arterial disease.
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http://dx.doi.org/10.1161/STROKEAHA.117.017922DOI Listing
August 2017

Pathways for Neuroimaging of Neonatal Stroke.

Pediatr Neurol 2017 04 26;69:37-48. Epub 2017 Jan 26.

Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachuetts.

Purpose: To provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke.

Methods: The Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype.

Results: In a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2-weighted imaging to assess for myelination, extra-axial blood, and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as the utility of follow up-imaging, is also discussed.
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http://dx.doi.org/10.1016/j.pediatrneurol.2016.12.008DOI Listing
April 2017

The Potential for Advanced Magnetic Resonance Neuroimaging Techniques in Pediatric Stroke Research.

Pediatr Neurol 2017 04 24;69:24-36. Epub 2017 Jan 24.

Department of Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: This article was written to provide clinicians and researchers with an overview of a number of advanced neuroimaging techniques in an effort to promote increased utility and the design of future studies using advanced neuroimaging in childhood stroke. The current capabilities of advanced magnetic resonance imaging techniques provide the opportunity to build on our knowledge of the consequences of stroke on the developing brain. These capabilities include providing information about the physiology, metabolism, structure, and function of the brain that are not routinely evaluated in the clinical setting.

Methods: During the Proceedings of the Stroke Imaging Laboratory for Children Workshop in Toronto in June 2015, a subgroup of clinicians and imaging researchers discussed how the application of advanced neuroimaging techniques could further our understanding of the mechanisms of stroke injury and repair in the pediatric population. This subgroup was established based on their interest and commitment to design collaborative, advanced neuroimaging studies in the pediatric stroke population.

Results: In working toward this goal, we first sought to describe here the magnetic resonance imaging techniques that are currently available for use, and how they have been applied in other stroke populations (e.g., adult and perinatal stroke).

Conclusions: With the continued improvement in advanced neuroimaging techniques, including shorter acquisition times, there is an opportunity to apply these techniques to their full potential in the research setting and learn more about the effects of stroke in the developing brain.
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http://dx.doi.org/10.1016/j.pediatrneurol.2016.12.015DOI Listing
April 2017

Use of magnetic resonance imaging to detect occult spinal dysraphism in infants.

J Neurosurg Pediatr 2017 Feb 2;19(2):217-226. Epub 2016 Dec 2.

Departments of 1 Neurosurgery.

OBJECTIVE Cutaneous stigmata or congenital anomalies often prompt screening for occult spinal dysraphism (OSD) in asymptomatic infants. While a number of studies have examined the results of ultrasonography (US) screening, less is known about the findings when MRI is used as the primary imaging modality. The object of this study was to assess the results of MRI screening for OSD in infants. METHODS The authors undertook a retrospective review of all infants who had undergone MRI of the lumbar spine to screen for OSD over a 6-year period (September 2006-September 2012). All images had been obtained on modern MRI scanners using sequences optimized to detect OSD, which was defined as any fibrolipoma of the filum terminale (FFT), a conus medullaris ending at or below the L2-3 disc space, as well as more complex lesions such as lipomyelomeningocele (LMM). RESULTS Five hundred twenty-two patients with a mean age of 6.2 months at imaging were included in the study. Indications for imaging included isolated dimple in 235 patients (45%), asymmetrically deviated gluteal cleft in 43 (8%), symmetrically deviated (Y-shaped) gluteal cleft in 38 (7%), hemangioma in 28 (5%), other isolated cutaneous stigmata (subcutaneous lipoma, vestigial tail, hairy patch, and dysplastic skin) in 31 (6%), several of the above stigmata in 97 (18%), and congenital anomalies in 50 (10%). Twenty-three percent (122 patients) of the study population had OSD. Lesions in 19% of these 122 patients were complex OSD consisting of LMM, dermal sinus tract extending to the thecal sac, and lipomeningocele. The majority of OSD lesions (99 patients [81%]) were filar abnormalities, a group including FFT and low-lying conus. The rate of OSD ranged from 12% for patients with asymmetrically deviated gluteal crease to 55% for those with other isolated cutaneous stigmata. Isolated midline dimple was the most common indication for imaging. Among this group, 20% (46 of 235) had OSD. There was no difference in the rate of OSD based on dimple location. Those with OSD had a mean dimple position of 15 mm (SD 11.8) above the coccyx. Those without OSD had a mean dimple position of 12.2 mm (SD 19) above the coccyx (p = 0.25). CONCLUSIONS The prevalence of OSD identified with modern high-resolution MRI screening is significantly higher than that reported with US screening, particularly in patients with dimples. The majority of OSD lesions identified are FFT and low conus. The clinical significance of such lesions remains unclear.
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http://dx.doi.org/10.3171/2016.8.PEDS16128DOI Listing
February 2017

Pediatric Brain: Repeated Exposure to Linear Gadolinium-based Contrast Material Is Associated with Increased Signal Intensity at Unenhanced T1-weighted MR Imaging.

Radiology 2017 Jan 28;282(1):222-228. Epub 2016 Jul 28.

From the Department of Radiology, University of Colorado, Aurora, Colo (T.F.F.); and Department of Radiology, University of Colorado Children's Hospital, 13123 E 16th Ave, Box B125, Aurora, CO 80045 (N.V.S., J.A.M., D.M.M.).

Purpose To determine whether repeated exposure of the pediatric brain to a linear gadolinium-based contrast agent (GBCA) is associated with an increase in signal intensity (SI) relative to that in GBCA-naive control subjects at unenhanced T1-weighted magnetic resonance (MR) imaging. Materials and Methods This single-center, retrospective study was approved by the institutional review board and compliant with HIPAA. The authors evaluated 46 pediatric patients who had undergone at least three GBCA-enhanced MR examinations (30 patients for two-group analysis and 16 for pre- and post-GBCA exposure comparisons) and 57 age-matched GBCA-naive control subjects. The SI in the globus pallidus, thalamus, dentate nucleus, and pons was measured at unenhanced T1-weighted MR imaging. Globus pallidus-thalamus and dentate nucleus-pons SI ratios were calculated and compared between groups and relative to total cumulative gadolinium dose, age, sex, and number of and mean time between GBCA-enhanced examinations. Analysis included the Wilcoxon signed rank test, Wilcoxon rank sum test, and Spearman correlation coefficient. Results Patients who underwent multiple GBCA-enhanced examinations had increased SI ratios within the dentate nucleus (mean SI ratio ± standard error of the mean for two-group comparison: 1.007 ± 0.0058 for GBCA-naive group and 1.046 ± 0.0060 for GBCA-exposed group [P < .001]; mean SI ratio for pre- and post-GBCA comparison: 0.995 ± 0.0062 for pre-GBCA group and 1.035 ± 0.0063 for post-GBCA group [P < .001]) but not the globus pallidus (mean SI ratio for two-group comparison: 1.131 ± 0.0070 for GBCA-naive group and 1.014 ± 0.0091 for GBCA-exposed group [P = .21]; mean SI ratio for pre- and post-GBCA comparison: 1.068 ± 0.0094 for pre-GBCA group and 1.093 ± 0.0134 for post-GBCA group [P = .12]). There was a significant correlation between dentate nucleus SI and total cumulative gadolinium dose (r = 0.4; 95% confidence interval [CI]: 0.03, 0.67; P = .03), but not between dentate nucleus SI and patient age (r = 0.23; 95% CI: -0.15, 0.56; P = .22), sex (mean SI ratio: 1.046 ± 0.0072 for boys and 1.045 ± 0.0110 for girls; P = .88), number of contrast-enhanced examinations (r = 0.13; 95% CI: -0.25, 0.48; P = .49), or time between contrast-enhanced examinations (r = -0.06; 95% CI: -0.42, 0.32; P = .75). Conclusion SI in the pediatric brain increases on unenhanced T1-weighted MR images with repeated exposure to a linear GBCA. RSNA, 2016.
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http://dx.doi.org/10.1148/radiol.2016160356DOI Listing
January 2017

Confidence in Assessment of Lumbar Spondylolysis Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited Field of View, Decreased-Dose CT.

Sports Health 2016 Jul 9;8(4):364-71. Epub 2016 Jun 9.

Department of Radiology, Children's Hospital Colorado, Aurora, Colorado.

Background: Limited z-axis-coverage computed tomography (CT) to evaluate for pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is comparable or lower than radiographs, is currently used at our institution. The objective of the study was to determine whether volumetric 3-dimensional fast spin echo magnetic resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation.

Hypothesis: Volumetric 3D MRI can provide equal or greater diagnostic accuracy compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation.

Study Design: Clinical review.

Level Of Evidence: Level 2.

Methods: Three pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited CT examinations in 42 pediatric patients who obtained imaging for low back pain and suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis besides surgery, interobserver agreement and degree of confidence were compared to determine which modality is preferable.

Results: Decreased-dose CT provided a greater level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%, 40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%).

Conclusion: For diagnosing spondylolysis, radiologist agreement and confidence trended toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI sequences compared with 2D MRI alone; however, agreement and confidence remain significantly greater using decreased-dose CT when compared with either MRI acquisition.

Clinical Relevance: Decreased-dose CT of the lumbar spine remains the optimal examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite promising features of rapid acquisition time, increased spatial resolution, and reconstruction capability).
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http://dx.doi.org/10.1177/1941738116653587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922525PMC
July 2016