Search

The PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5  GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield.

We are conducting an experiment to search for WIMPs, or weakly-interacting massive particles, in the galactic halo using terrestrial detectors. This generic class of hypothetical particles, whose properties are similar to those predicted by extensions of the standard model of particle physics, could comprise the cold component of non-baryonic dark matter. We describe our experiment, which is based on cooled germanium and silicon detectors in a shielded low-background cryostat. The detectors achieve a high degree of background rejection through the simultaneous measurement of the energy in phonons and ionization. Using exposures on the order of one kilogram-day from initial runs of our experiment, we have achieved (preliminary) upper limits on the WIMP-nucleon cross section that are comparable to much longer runs of other experiments.

Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

Object: The authors evaluated the efficacy of posterior instrumentation for the management of spontaneous spinal infections. Standard surgical management of spontaneous spinal infection is based on debridement of the infected tissue. However, this can be very challenging as most of these patients are medically debilitated and the surgical debridement requires a more aggressive approach to the spine either anteriorly or via an expanded posterior approach. The authors present their results using an alternative treatment method of posterior-only neuro-decompression and stabilization without formal debridement of anterior tissue for treating spontaneous spinal infection., Methods: Fifteen consecutive patients were treated surgically by 2 of the authors. All patients had osteomyelitis and discitis and were treated postoperatively with intravenous antibiotics for at least 6 weeks. The indications for surgery were failed medical management, progressive deformity with ongoing persistent spinal infection, or neurological deficit. Patients with simple epidural abscess without bony instability were treated with laminectomy and were not included in this series. Fourteen patients were treated with posterior-only decompression and long-segment rigid fixation, without formal debridement of the infected area. One patient was treated with staged anterior and posterior surgery due to delay in treatment related to medical comorbidities. The authors examined as their outcome the ambulatory status and recurrence of deep infection requiring additional surgery or medical treatment., Results: Of the initial 15 patients, 10 (66%) had a minimum 2-year follow-up and 14 patients had at least 1 year of followup. There were no recurrent spinal infections. There were 3 unplanned reoperations (1 for loss of fixation, 1 for early superficial wound infection, and 1 for epidural hematoma). Nine (60%) of 15 patients were nonambulatory at presentation. At final followup, 8 of 15 patients were independently ambulatory, 6 required an assistive device, and 1 remained nonambulatory., Conclusions: Long-segment fixation, without formal debridement, resulted in resolution of spinal infection in all cases and in significant neurological recovery in almost all cases. This surgical technique, when combined with aggressive antibiotic therapy and a multidisciplinary team approach, is an effective way of managing serious spinal infections in a challenging patient population.

Aims: Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients., Patients & Methods: We conducted a retrospective chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation., Results: One in 240 patients (0.4%; 95% CI: 0.01-2.00; median total dose: 7375 mg/m(2); interquartile range: 1300) were diagnosed with PJP., Conclusion: There was a <1% rate of PJP for brain tumor patients treated with temozolomide until progression without PJP prophylaxis.

Background and Purpose: Pediatric brain tumors have diverse pathologic features, which poses diagnostic challenges. Although perfusion evaluation of adult tumors is well established, hemodynamic properties are not well characterized in children. Our goal was to apply arterial spin-labeling perfusion for various pathologic types of pediatric brain tumors and evaluate the role of arterial spin-labeling in the prediction of tumor grade., Materials and Methods: Arterial spin-labeling perfusion of 54 children (mean age, 7.5 years; 33 boys and 21 girls) with treatment-naive brain tumors was retrospectively evaluated. The 3D pseudocontinuous spin-echo arterial spin-labeling technique was acquired at 3T MR imaging. Maximal relative tumor blood flow was obtained by use of the ROI method and was compared with tumor histologic features and grade., Results: Tumors consisted of astrocytic (20), embryonal (11), ependymal (3), mixed neuronal-glial (8), choroid plexus (5), craniopharyngioma (4), and other pathologic types (3). The maximal relative tumor blood flow of high-grade tumors (grades III and IV) was significantly higher than that of low-grade tumors (grades I and II) (P < .001). There was a wider relative tumor blood flow range among high-grade tumors (2.14 ± 1.78) compared with low-grade tumors (0.60 ± 0.29) (P < .001). Across the cohort, relative tumor blood flow did not distinguish individual histology; however, among posterior fossa tumors, relative tumor blood flow was significantly higher for medulloblastoma compared with pilocytic astrocytoma (P = .014)., Conclusions: Characteristic arterial spin-labeling perfusion patterns were seen among diverse pathologic types of brain tumors in children. Arterial spin-labeling perfusion can be used to distinguish high-grade and low-grade tumors.

Background and Purpose: 2D gradient-echo imaging is sensitive to T2* lesions (hemorrhages, mineralization, and vascular lesions), and susceptibility-weighted imaging is even more sensitive, but at the cost of additional scan time (SWI: 5-10 minutes; 2D gradient-echo: 2 minutes). The long acquisition time of SWI may pose challenges in motion-prone patients. We hypothesized that 2D SWI/phase unwrapped images processed from 2D gradient-echo imaging could improve T2* lesion detection., Materials and Methods: 2D gradient-echo brain images of 50 consecutive pediatric patients (mean age, 8 years) acquired at 3T were retrospectively processed to generate 2D SWI/phase unwrapped images. The 2D gradient-echo and 2D SWI/phase unwrapped images were compared for various imaging parameters and were scored in a blinded fashion., Results: Of 50 patients, 2D gradient-echo imaging detected T2* lesions in 29 patients and had normal findings in 21 patients. 2D SWI was more sensitive than standard 2D gradient-echo imaging in detecting T2* lesions (P < .0001). 2D SWI/phase unwrapped imaging also improved delineation of normal venous structures and nonpathologic calcifications and helped distinguish calcifications from hemorrhage. A few pitfalls of 2D SWI/phase unwrapped imaging were noted, including worsened motion and dental artifacts and challenges in detecting T2* lesions adjacent to calvaria or robust deoxygenated veins., Conclusions: 2D SWI and associated phase unwrapped images processed from standard 2D gradient-echo images were more sensitive in detecting T2* lesions and delineating normal venous structures and nonpathologic mineralization, and they also helped distinguish calcification at no additional scan time. SWI processing of 2D gradient-echo images may be a useful adjunct in cases in which longer scan times of 3D SWI are difficult to implement.

Background and Purpose: Neurofibromatosis type 1 is associated with increased risk for stroke, cerebral vasculopathy, and neurocognitive deficits, but underlying hemodynamic changes in asymptomatic children remain poorly understood. We hypothesized that children with neurofibromatosis type 1 have decreased cerebral blood flow., Materials and Methods: Arterial spin-labeled CBF was measured in 14 children with neurofibromatosis type 1 (median age, 9.7 years; mean, 10.2 years; range, 22 months to 18 years) and compared with age-matched control subjects on 3T MR imaging. Three-dimensional pseudocontinuous spin-echo arterial spin-labeled technique was used. Measurements were obtained at cortical gray matter of bilateral cerebral hemispheres and centrum semiovale by use of the ROI method. Comparison by Mann-Whitney test was used, with Bonferroni-adjusted P values ≤.004 judged as significant., Results: We identified 7 of 12 areas with significantly diminished arterial spin-labeled CBF in patients with neurofibromatosis type 1 compared with control subjects. These areas included the anterior cingulate gyrus (P = .001), medial frontal cortex (P = .004), centrum semiovale (P = .004), temporo-occipital cortex (P = .002), thalamus (P = .001), posterior cingulate gyrus (P = .002), and occipital cortex (P = .001). Among patients with neurofibromatosis type 1, there were no significant differences in these regions on the basis of the presence of neurofibromatosis type 1 spots or neurocognitive deficits., Conclusions: Reduced cerebral perfusion was seen in children with neurofibromatosis type 1, particularly in the posterior circulation and the vascular borderzones of the middle and posterior cerebral arteries.

Background and Purpose: RS-EPI has been suggested as an alternative approach to EPI for high-resolution DWI with reduced distortions. To determine whether RS-EPI is a useful approach for routine clinical use, we implemented GRAPPA-accelerated RS-EPI DWI at our pediatric hospital and graded the images alongside standard accelerated (ASSET) EPI DWI used routinely for clinical studies., Materials and Methods: GRAPPA-accelerated RS-EPI DWIs and ASSET EPI DWIs were acquired on 35 pediatric patients using a 3T system in 35 pediatric patients. The images were graded alongside each other by using a 7-point Likert scale as follows: 1, nondiagnostic; 2, poor; 3, acceptable; 4, standard; 5, above average; 6, good; and 7, outstanding., Results: The following were the average scores for EPI and RS-EPI, respectively: resolution, 3.5/5.2; distortion level, 2.9/6.0; SNR, 3.4/4.1; lesion conspicuity, 3.3/5.9; and diagnostic confidence, 3.2/6.0. Overall, the RS-EPI had significantly improved diagnostic confidence and more reliably defined the extent and structure of several lesions. Although ASSET EPI scans had better SNR per scanning time, the higher spatial resolution as well as reduced blurring and distortions on RS-EPI scans helped to better reveal important anatomic details at the cortical-subcortical levels, brain stem, temporal and inferior frontal lobes, skull base, sinonasal cavity, cranial nerves, and orbits., Conclusions: This work shows the importance of both resolution and decreased distortions in the clinics, which can be accomplished by a combination of parallel imaging and alternative k-space trajectories such as RS-EPI.

Summary: HPE is a congenital brain malformation characterized by failure of the prosencephalon to divide into 2 hemispheres. We have identified 7 patients who have a mild subtype of HPE in which the midline fusion was restricted to the septal region or preoptic region of the telencephalon. This subtype, which we call septopreoptic HPE, falls in the spectrum of lobar HPE, but lacks significant frontal neocortical fusion seen in lobar HPE. Other imaging characteristics include thickened or dysplastic fornix, absent or hypoplastic anterior CC, and single unpaired ACA. The SP was fully formed in 4, partially formed in 2, and absent in 1. Mild midline craniofacial malformation, such as SMMCI and CNPAS were found in 86% and 71%, respectively. Patients outside of infancy often manifested language delay, learning disabilities, or behavioral disturbances, while motor function was relatively spared.

We present a case of congenital salivary gland anlage tumor (SGAT) of the nasal septum in a 2-week-old infant who had difficulty breathing through her nose since birth. CT and MR imaging demonstrated a circumscribed mass within the nasal cavity that did not communicate with the intracranial compartment. Differential diagnosis and clinical significance of recognizing this rare lesion are reviewed.

Intracellular pathogens must withstand nitric oxide (NO.) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER) system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP) sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

Objective: To determine if metabolite ratios at near-term age predict outcome in very low birth weight preterm infants at 18 to 24 months adjusted age., Study Design: Thirty-six infants (birth weight

Background and Purpose: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury., Materials and Methods: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods., Results: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region., Conclusions: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

Dissemination of Yersinia pseudotuberculosis within mice after oral inoculation was analyzed. Y. pseudotuberculosis translocated to organs such as the liver and spleen shortly after oral inoculation, but was quickly cleared. In contrast, a second temporally distinct bacterial translocation event resulted in successful hepatosplenic replication of the bacteria. Replicating pools of bacteria could be established in these organs in mouse mutants that lacked Peyer's patches. These animals frequently had sterile mesenteric lymph nodes, a finding consistent with translocation taking place independently of regional lymph node colonization. In further contradiction to accepted models for dissemination of enteropathogens, clonal analysis revealed that bacteria causing disease in the spleen and liver of C57BL/6J mice were derived from populations located outside the intestinal lymph nodes. Replication of bacteria in the intestine before translocation appeared critical for dissemination, as transient selective suppression by streptomycin of bacterial growth in the intestine delayed dissemination of Y. pseudotuberculosis. These results collectively indicate that hepatosplenic colonization appears intimately connected with the ability of Y. pseudotuberculosis to successfully establish replication in the intestinal lumen and does not result from ordered spread leading from the intestine to regional lymph nodes before dissemination.

Background and Purpose: Ketone bodies provide important alternate fuel for brain metabolism, and their transport into the brain increases with prolonged fasting. During diabetic ketoacidosis (DKA), serum ketone concentrations markedly increase; however, little is known about whether ketone bodies accumulate in cerebral tissues during DKA. We used proton MR spectroscopy (MRS) to detect cerebral beta-hydroxy butyrate (betaOHB) and acetone/acetocaetate (AcAc) in children with DKA., Methods: Twenty-five children underwent brain MRS: nine within 4 hours of the start of treatment for DKA; 11, at 4-8 hours; and five, at 8-12 hours. MRS was repeated after their recovery from the DKA episode at > or =72 hours after the start of treatment. MRS was evaluated for peaks corresponding to betaOHB (doublet centered on 1.20 ppm) and lactate (doublet centered on 1.33 ppm). Difference spectroscopy was used to identify the AcAc peak at 2.22-2.26 ppm., Results: betaOHB was detected in 13 children (52%), more frequently within 4 hours (eight children, 89%) than after 4 hours (five children, 31%). AcAc was detected in 15 children (60%), more frequently at >4 hours after the start of treatment (12 patients, 75%) than in the first 4 hours (three patients, 33%). Lactate was detected in five children (18%), all within the first 8 hours of treatment., Conclusion: In children, betaOHB and AcAc accumulate in the brain during DKA, and they can be detected on MRS. Care should be taken in interpreting MRS results in patients with DKA to avoid erroneously attributing betaOHB peaks to lactate.

Background and Purpose: Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings., Methods: We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age., Results: Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes., Conclusion: These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.

Original quinolinone derivatives structurally related to diazoxide were synthesized and their effects on insulin secretion from rat pancreatic islets and the contractile activity of rat aortic rings determined. A concentration-dependent decrease of insulin release was induced by 6-chloro-2-methylquinolin-4(1H)-one (HEI 713). The average IC(50) values were 16.9+/-0.8 microM for HEI 713 and 18.4+/-2.2 microM for diazoxide. HEI 713 increased the rate of (86)Rb outflow from perifused pancreatic islets. This effect persisted in the absence of external Ca(2+) but was inhibited by glibenclamide, a K(ATP) channel blocker. Inside-out patch-clamp experiments revealed that HEI 713 increased K(ATP) channel openings. HEI 713 decreased (45)Ca outflow, insulin output and cytosolic free Ca(2+) concentration in pancreatic islets and islet cells incubated in the presence of 16.7 or 20 mM glucose and extracellular Ca(2+). The drug did not affect the K(+)(50 mM)-induced increase in (45)Ca outflow. In aortic rings, the vasorelaxant effects of HEI 713, less potent than diazoxide, were sensitive to glibenclamide and to the extracellular K(+) concentration. The drug elicited a glibenclamide-sensitive increase in (86)Rb outflow from perifused rat aortic rings. Our data describe an original compound which inhibits insulin release with a similar potency to diazoxide but which has fewer vasorelaxant effects. Our results suggest that, in both aortic rings and islet tissue, the biological effects of HEI 713 mainly result from activation of K(ATP) channels ultimately leading to a decrease in Ca(2+) inflow.

Hyperinsulinism of infancy (HI) is a congenital defect in the regulated release of insulin from pancreatic beta-cells. Here we describe stimulus-secretion coupling mechanisms in beta-cells and intact islets of Langerhans isolated from three patients with a novel SUR1 gene defect. 2154+3 A to G SUR1 (GenBank accession number L78207) is the first report of familial HI among nonconsanguineous Caucasians identified in the U.K. Using patch-clamp methodologies, we have shown that this mutation is associated with both a decrease in the number of operational ATP-sensitive K+ channels (KATP channels) in beta-cells and impaired ADP-dependent regulation. There were no apparent defects in the regulation of Ca2+- and voltage-gated K+ channels or delayed rectifier K+ channels. Intact HI beta-cells were spontaneously electrically active and generating Ca2+ action currents that were largely insensitive to diazoxide and somatostatin. As a consequence, when intact HI islets were challenged with glucose and tolbutamide, there was no rise in intracellular free calcium ion concentration ([Ca2+]i) over basal values. Capacitance measurements used to monitor exocytosis in control and HI beta-cells revealed that there were no defects in Ca2+-dependent exocytotic events. Finally, insulin release studies documented that whereas tolbutamide failed to cause insulin secretion as a consequence of impaired [Ca2+]i signaling, glucose readily promoted insulin release. Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells.

Current and advanced structural and functional neuroimaging techniques are presented along with guidelines for utilization and principles of imaging diagnosis in fetal and neonatal central nervous system abnormalities. Pattern of injury, timing issues, and differential diagnosis are addressed with emphasis on neurovascular disease. Ultrasonography and computed tomography provide relatively rapid and important screening information regarding gross macrostructural abnormalities. However, current and advanced MRI techniques often provide more definitive macrostructural, microstructural, and functional imaging information.

Background and Purpose: Jugular foraminal stenosis (JFS) or atresia (JFA) with collateral emissary veins (EV) has been documented in syndromic craniosynostosis. Disruption of EV during surgery can produce massive hemorrhage. Our purpose was to describe the prevalence of prominent basal emissary foramina (EF), which transmit enlarged EV, in syndromic craniosynostosis. Our findings were correlated with phenotypic and molecular diagnoses., Methods: We reviewed the medical records and imaging examinations of 33 patients with syndromic craniosynostosis and known fibroblast growth factor receptor (FGFR) mutations. All patients underwent CT and 14 MR imaging. The cranial base was assessed for size of occipitomastoid EF and jugular foramina (JF). Vascular imaging studies were available from 12 patients. A control group (n = 76) was used to establish normal size criteria for JF and EF., Results: Phenotypic classification included Crouzon syndrome (n = 10), crouzonoid features with acanthosis nigricans (n = 3), Apert syndrome (n = 10), Pfeiffer syndrome (n = 4), and clinically unclassifiable bilateral coronal synostosis (n = 6). EF > or = 3 mm in diameter and JFS or JFA were identified in 23 patients with various molecular diagnoses. Vascular imaging in patients with JFS or JFA and enlarged EF revealed atresia or stenosis of the jugular veins and enlarged basal EV. JFA was seen in all patients with the FGFR3 mutation with crouzonoid features and acanthosis nigricans. Four patients had prominent EF without JFS. Six patients had normal JF and lacked enlarged EF., Conclusion: Enlarged basal EF are common in syndromic craniosynostosis and are usually associated with JFS or JFA. Bilateral basilar venous atresia is most common in patients with the FGFR3 ala391glu mutation and crouzonoid features with acanthosis nigricans, but may be found in patients with FGFR2 mutations. Skull base vascular imaging should be obtained in patients with syndromic craniosynostosis with enlarged EF.

Diffusion imaging has been widely used in the brain, but its application in the spinal cord has been limited. Using line-scan diffusion imaging (LSDI), a technique that is less sensitive to magnetic susceptibility and motion artifacts than are other diffusion techniques, we have successfully imaged the spinal cord in children. The apparent diffusion coefficient and relative diffusion anisotropy of the normal spinal cord were measured. LSDI was compared with echo-planar diffusion imaging of the spine in three patients.

NES2Y is a proliferating human insulin-secreting cell line that we have derived from a patient with persistent hyperinsulinemic hypoglycemia of infancy. This disease is characterized by unregulated insulin release despite profound hypoglycemia. NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. However, these cells, designated NESK beta-cells, have impaired insulin gene transcription responses to glucose. NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. These findings document that in NES2Y beta-cells, coexpression of both subunits is critically required for fully operational KATP channels and KATP channel-dependent signaling events. This article further characterizes the properties of the novel human beta-cell line, NES2Y, and documents the usefulness of these cells in diabetes-related research.

Insulin is synthesised, stored, and secreted from pancreatic beta cells. These are located within the islets of Langerhans, which are distributed throughout the pancreas. Less than 2% of the total pancreas is devoted to an endocrine function. When the mechanisms that control insulin release are compromised, potentially lethal diseases such as diabetes and neonatal hypoglycaemia are manifest. This article reviews the physiology of insulin release and illustrates how defects in these processes will result in the pathophysiology of hyperinsulinism of infancy.

A three-dimensional image registration technique for CT and MR studies of the cervical spine was evaluated for feasibility and efficacy. Registration by means of external fiducial markers was slightly more accurate than registration by anatomic landmarks. The interrelationships between bony (eg, neural foramina) and soft tissue structures (eg, nerve roots) in the cervical spine were more conspicuous on registered images than on conventional displays. Registration of CT and MR images may be used to examine more precisely the relationships between bony and soft tissue structures of the cervical spine.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia. We have discovered that islet cells, isolated from the pancreas of a PHHI patient, proliferate in culture while maintaining a beta cell-like phenotype. The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose. In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression. To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1. One selected clonal cell line (NISK9) had normal K(ATP) channel activity, and as a result of changes in intracellular Ca(2+) homeostasis ([Ca(2+)](i)) secreted insulin within the physiological range of glucose concentrations. This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus.

Background and Purpose: Infections caused by nontuberculous mycobacteria (NTM) commonly manifest as cervicofacial adenitis in otherwise healthy children. The aim of this study was to characterize the imaging findings of NTM infection of the head and neck in immunocompetent children., Methods: The medical records and imaging examinations (CT in 10, MR in two) were reviewed in 12 immunocompetent children with NTM infection of the head and neck., Results: The usual presentation (n = 9) was of an enlarging, non-tender mass with violaceous skin discoloration, unresponsive to conventional antibiotics. The duration of symptoms was 6 days to 5 months. Imaging revealed asymmetric adenopathy with contiguous low-density ring-enhancing masses in all patients. There was cutaneous extension in 10 patients. Inflammatory stranding of the subcutaneous fat was minimal (n = 9) or absent (n = 2) in 11 patients. The masses involved the submandibular space (n = 3), the parotid space (n = 2), the cheek (n = 1), the anterior triangle of the neck (n = 2), the submandibular and parotid spaces (n = 2), the parotid space and neck (n = 1), and the neck and retropharyngeal space (n = 1). Surgical management included incision and drainage only (n = 2), incision and drainage with curettage (n = 2), excisional biopsy after incision and drainage (n = 1), excisional biopsy only (n = 5), superficial parotidectomy only (n = 1), and superficial parotidectomy with contralateral excisional biopsy (n = 1). All patients improved in response to surgery and long-term antimycobacterial antibiotics., Conclusion: NTM infection of the head and neck has a characteristic clinical presentation and imaging appearance. Recognition of this disease is important; appropriate treatment is excision and, in selected cases, antimycobacterial therapy.

Background and Purpose: MR diffusion-weighted imaging provides early demonstration of neonatal brain infarction. The evolution and limitations of diffusion-weighted imaging findings in newborns, however, have not been evaluated. Using line-scan diffusion imaging (LSDI), we investigated perinatal ischemic brain injury., Methods: Nineteen term newborns (age, 9 hours to 8 days; mean age, 2.6 days) with perinatal brain ischemia were evaluated using LSDI (1520/62.5/1 [TR/TE/excitations]) (b maximum = 750 s/mm2) and T1- and T2-weighted spin-echo (conventional) MR imaging. Follow-up examinations were performed in seven patients and autopsy in one. Apparent diffusion coefficients (ADCs) were measured in deep gray matter, white matter, the cortex, and focal lesions., Results: Based on conventional MR imaging or pathologic findings, patients were divided into two groups. Group 1 (n = 12) had symmetric/diffuse injury consistent with global hypoperfusion. Group 2 (n = 7) had focal/multifocal injury suggesting cerebrovascular occlusion. ADCs were abnormal at initial examination in 10 newborns in group 1 and in all newborns in group 2. The results of LSDI were abnormal before conventional MR imaging was performed in three newborns in group 1. ADCs were maximally decreased between days 1 and 3 in deep gray matter, perirolandic white matter, and focal lesions. Delayed decreases in ADCs were observed in subcortical white matter from days 4 through 10 in three patients in group 1., Conclusion: After global hypoperfusion, LSDI showed deep gray matter and perirolandic white matter lesions before conventional MR imaging. LSDI may underestimate the extent of injury, however, possibly because of variations in the compartmentalization of edema, selective vulnerability, and delayed cell death. Differences in LSDI of symmetric/diffuse and focal/multifocal lesions may reflect differences in pathophysiology or timing of the injury. These findings may have implications for acute interventions.

Background and Purpose: MR imaging of the self-diffusion of water has become increasingly popular for the early detection of cerebral infarction in adults. The purpose of this study was to evaluate MR line scan diffusion imaging (LSDI) of the brain in children., Methods: LSDI was performed in four volunteers and 12 patients by using an effective TR/TE of 2736/89.4 and a maximum b value of 450 to 600 s/mm2 applied in the x, y, and z directions. In the volunteers, single-shot echo planar imaging of diffusion (EPID) was also performed. The patients (10 boys and two girls) ranged in age from 2 days to 16 years (average age, 6.6 years). Diagnoses included acute cerebral infarction, seizure disorder, posttraumatic confusion syndrome, complicated migraine, residual astrocytoma, encephalitis, hypoxia without cerebral infarction, cerebral contusion, and conversion disorder. In all patients, routine spin-echo images were also acquired. Trace images and apparent diffusion coefficient maps were produced for each location scanned with LSDI., Results: In the volunteers, LSDI showed less chemical-shift and magnetic-susceptibility artifact and less geometric distortion than did EPID. LSDI was of diagnostic quality in all studies. Diffusion abnormalities were present in five patients. Restricted diffusion was present in the lesions of the three patients with acute cerebral infarction. Mildly increased diffusion was present in the lesions of encephalitis and residual cerebellar astrocytoma. No diffusion abnormalities were seen in the remaining seven children., Conclusion: LSDI is feasible in children, provides high-quality diffusion images with less chemical-shift and magnetic-susceptibility artifact and less geometric distortion than does EPID, and complements the routine MR examination.

Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.

Purpose: This study was done to determine which clinical and imaging findings best correlate with outcome in children with tectal tumors., Methods: A retrospective review was done of the medical records and imaging studies of 32 children (16 boys and 16 girls; mean age, 8 years) with tectal tumors. Eight children had CT, 11 had MR imaging, and 13 had both CT and MR studies. Findings from surgical and pathologic reports as well as from follow-up examinations (mean follow-up period, 5 years; range, 3.6 months to 17 years) were included in the review., Results: All patients had hydrocephalus and all but one required CSF diversion. The tectum was the center of the tumor in all cases and the majority of the tumors appeared isodense on CT scans, isointense on T1-weighted MR images, and hyperintense on T2-weighted images. Twenty patients required no further treatment. In this group, the mean maximum tumor diameter was 1.8 cm and enhancement occurred in two cases. At follow-up, 18 patients had stable tumor size, one had an increase in tumor size with cyst formation but no worsening of symptoms, and one had a decrease in tumor size. Twelve patients required further treatment (excision and/or radiotherapy) because of progression as indicated by either increased tumor size or worsening of symptoms. In this group, the mean maximum tumor diameter was 2.5 cm and contrast enhancement occurred in nine cases. Further follow-up in this group showed decreased tumor size in eight and stable residual tumor in three., Conclusion: Tectal tumors in childhood have variable behavior. MR imaging assists in the clinical determination of which children need treatment beyond CSF diversion. Larger tumor size and enhancement are radiologic predictors of the need for further treatment.

Background: The outcome of infants who have transient seizures after open heart surgery has not been studied. Using the database of the Boston Circulatory Arrest Study involving 171 children with D-transposition of the great arteries, we explored the relationship between early postoperative clinical and EEG seizures and neurodevelopmental outcomes at ages 1 and 2 1/2 years., Methods and Results: At 1 year, children returned for developmental and neurological evaluations and MRI. Parent-completed developmental questionnaires were collected at 2 1/2 years of age. At 1 year, children with early postoperative seizures had lower Psychomotor Development Index (motor function) scores (clinical seizures: 12.9 mean difference [MD]; 95% confidence interval [CI], 2.2 to 23.6; P=.02; EEG seizures: 13.3 MD; 95% CI, 6.8 to 19.7; P<.001). Mental Developmental Index scores of children with clinical or EEG seizures were also lower, but the differences were not statistically significant. Infants with seizures were more likely to have an abnormal neurological examination (clinical seizures: 78% versus 31%; P=.008; EEG seizures: 58% versus 34%; P=.04). Children with EEG seizures were more likely to have MRI abnormalities (43% versus 13%, P=.002). At age 2 1/2, children with EEG seizures had lower scores in several areas of function., Conclusions: In infants undergoing the arterial switch operation for correction of D-transposition of the great arteries, transient postoperative clinical and EEG seizures were associated with worse neurodevelopmental outcomes at ages 1 and 2 1/2 years as well as neurological and MRI abnormalities at 1 year of age. The occurrence of such seizures may provide an early sign of brain injury with neurological and developmental sequelae.

Purpose: Our purpose was to determine the sensitivity, specificity, and receiver operator characteristic (ROC) curve of a fast screening MR protocol in children and adolescents with suspected intracranial tumors., Methods: One hundred forty-one patients (mean age, 9.7 years; range, 2 months to 23.5 years) with suspected brain tumor were entered in a case-control study. Eighty-seven patients had intracranial tumors (31 suprasellar/hypothalamic, 27 supratentorial, 26 infratentorial, and three pineal) and 54 patients in the control group had other disorders. Two neuroradiologists reviewed blindly a detailed three-sequence conventional protocol (acquisition time, 8 minutes 27 seconds) and a two-sequence fast screening MR protocol (acquisition time, 4 minutes 44 seconds)., Results: Sensitivity and specificity of the fast screening protocol for intracranial tumors was 100% and 92.6%, respectively. The areas under the ROC curves were 0.966 for the fast screening and 0.980 for the conventional MR protocol. No diagnostic performance difference was found between the ROC curves using the Az index. A kappa statistic of .93 for both examinations indicated excellent interobserver agreement. Additional MR sequences and other neuroimaging studies were not deemed necessary to exclude the presence of an intracranial tumor., Conclusion: A fast dual-plane brain MR protocol may be adequate to screen children and adolescents thought to have an intracranial tumor. The less than 5 minute acquisition time allows a complete examination (including preparation) to be performed in 10 to 15 minutes. Future studies are recommended before this time-efficient neuroimaging examination is incorporated into clinical practice.

Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation., Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients., Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients., Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.

Purpose: To emphasize the importance of imaging in children with diencephalic syndrome due to hypothalamic/chiasmatic astrocytomas., Methods: Findings in nine patients (mean age, 26 months) with diencephalic syndrome and hypothalamic/chiasmatic astrocytomas were analyzed retrospectively, including reviewing clinical records, imaging examinations, and follow-up studies., Results: Symptoms and signs included failure to thrive (n = 9), nystagmus (n = 3), visual field defects (n = 1), optic pallor (n = 1), emesis (n = 2), and headache (n = 1). All patients had hypothalamic/chiasmatic masses. Five patients underwent biopsy, and, in all cases, specimens showed low-grade astrocytoma. Imaging studies were available in eight patients. All tumors were large (median maximum diameter, 3.5 cm), involved the chiasm and hypothalamus, and showed homogeneous enhancement. Three patients had hydrocephalus and two had metastases. At follow-up, five patients had recurrent disease and two had died., Conclusion: Diencephalic syndrome is a rare cause of failure to thrive in childhood, and diagnosis of a hypothalamic/ chiasmatic astrocytoma might therefore be delayed. The astrocytomas associated with this syndrome are larger, occur at a younger age, and are often more aggressive than other astrocytomas arising in this region.

Purpose: To describe the angiographic changes accompanying the surgical treatment of moyamoya disease by pial synangiosis and to compare these changes with patient outcome., Methods: The preoperative and postoperative cerebral angiograms, MR images, and clinical records of 13 children treated with pial synangiosis for moyamoya disease were reviewed., Results: After synangiosis, 10 patients had significant neurologic improvement and three had minimal or no improvement. Postoperative MR images showed no new infarctions. Well-developed (grade A or B) transpial or transdural collaterals to the brain were present at the site of synangiosis in 84% of the surgically treated hemispheres. Cerebrovascular occlusive changes increased postoperatively in 76% of hemispheres. After synangiosis, moyamoya collaterals were increased in 48%, unchanged in 16%, and decreased in 36% of surgically treated hemispheres. All 10 patients with grade A or B collaterals bilaterally after synangiosis were asymptomatic or improved on follow-up., Conclusion: Pial synangiosis typically results in an increase in collaterals from the superficial temporal artery or middle meningeal artery to the brain. Synangiosis appears to result in stabilization or improvement in neurologic symptoms but does not prevent the angiographic progression of disease or the development of moyamoya collaterals. The angiographic demonstration of well-formed collaterals after synangiosis is associated with a favorable clinical outcome.

Purpose: To assess multivoxel proton MR spectroscopy combined with MR imaging and hemodynamic MR imaging in the evaluation of brain tumors in children and young adults., Methods: Fifteen patients with brain tumors and 10 healthy children underwent MR imaging and MR spectroscopy on a 1.5-T system. Ten patients with tumors had both MR spectroscopy and hemodynamic MR imaging. MR spectroscopy data sets with 1 cm3 to 3.4 cm3 resolution were acquired within 8.5 minutes by using a point-resolved spectroscopic, chemical-shift imaging technique in two dimensions with volume preselection. MR imaging was performed using fast spin-echo techniques. Hemodynamic MR imaging data were acquired every 2.5 seconds at one anatomic level using a spoiled gradient-echo sequence during intravenous bolus administration of contrast material., Results: Assessment with multivoxel MR spectroscopy and hemodynamic MR imaging added about 30 minutes to the total MR examination time. Normal tissue exhibited spectral peaks from biologically significant compounds such as N-acetylaspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Twelve biopsy-proved tumors exhibited prominent Cho, reduced NAA, variable tCr, and/or lactate or lipids, and two showed increased hemodynamic parameters. Three of the tumors treated with radiation did not reveal prominent levels of Cho. Tissue necrosis had no Cho, NAA, or tCr, and reduced hemodynamics., Conclusions: Preliminary findings by MR spectroscopy combined with MR imaging and hemodynamic MR imaging suggest that regions of active tumor may be differentiated from areas of normal tissue and areas of necrosis. These findings may enable metabolic and hemodynamic characterization of childhood brain tumors as well as suggest their response to therapy.