Motion-compensated low-rank reconstruction for simultaneous structural and functional UTE lung MRI.

PURPOSE: Three-dimensional UTE MRI has shown the ability to provide simultaneous structural and functional lung imaging, but it is limited by respiratory motion and relatively low lung parenchyma SNR. The purpose of this paper is to improve this imaging by using a respiratory phase-resolved reconstruction approach, named motion-compensated low-rank reconstruction (MoCoLoR), which directly incorporates motion compensation into a low-rank constrained reconstruction model for highly efficient use of the acquired data. THEORY AND METHODS: The MoCoLoR reconstruction is formulated as an optimization problem that includes a low-rank constraint using estimated motion fields to reduce the rank, optimizing over both the motion fields and reconstructed images. The proposed reconstruction along with XD and motion state-weighted motion-compensation (MostMoCo) methods were applied to 18 lung MRI scans of pediatric and young adult patients. The data sets were acquired under free-breathing and without sedation with 3D radial UTE sequences in approximately 5 min. After reconstruction, they went through ventilation analyses. Performance across reconstruction regularization and motion-state parameters were also investigated. RESULTS: The in vivo experiments results showed that MoCoLoR made efficient use of the data, provided higher apparent SNR compared with state-of-the-art XD reconstruction and MostMoCo reconstructions, and yielded high-quality respiratory phase-resolved images for ventilation mapping. The method was effective across the range of patients scanned. CONCLUSION: The motion-compensated low-rank regularized reconstruction approach makes efficient use of acquired data and can improve simultaneous structural and functional lung imaging with 3D-UTE MRI. It enables the scanning of pediatric patients under free-breathing and without sedation.

Rate of head ultrasound abnormalities at one month in very premature and extremely premature infants with normal initial screening ultrasound.

BACKGROUND: Premature infants are at risk for multiple types of intracranial injury with potentially significant long-term neurological impact. The number of screening head ultrasounds needed to detect such injuries remains controversial. OBJECTIVE: To determine the rate of abnormal findings on routine follow-up head ultrasound (US) performed in infants born at ≤ 32 weeks' gestational age (GA) after initial normal screening US. MATERIALS AND METHODS: A retrospective study was performed on infants born at ≤ 32 weeks' GA with a head US at 3-5 weeks following a normal US at 3-10 days at a tertiary care pediatric hospital from 2014 to 2020. Exclusion criteria included significant congenital anomalies, such as congenital cardiac defects necessitating surgery, congenital diaphragmatic hernia or spinal dysraphism, and clinical indications for US other than routine screening, such as sepsis, other risk factors for intracranial injury besides prematurity, or clinical neurological abnormalities. Ultrasounds were classified as normal or abnormal based on original radiology reports. Images from initial examinations with abnormal follow-up were reviewed. RESULTS: Thirty-three (14.2%) of 233 infants had 34 total abnormal findings on follow-up head US after normal initial US. Twenty-seven infants had grade 1 germinal matrix hemorrhage, and four had grade 2 intraventricular hemorrhage. Two had periventricular echogenicity and one had a focus of cerebellar echogenicity that resolved and was determined to be artifactual. CONCLUSION: When initial screening head ultrasounds in premature infants are normal, follow-up screening ultrasounds are typically also normal. Abnormal findings are usually limited to grade 1 germinal matrix hemorrhage.

Incorporating Radiomics into Machine Learning Models to Predict Outcomes of Neuroblastoma.

Neuroblastoma is one of the most common pediatric cancers. This study used machine learning (ML) to predict the mortality and a few other investigated intermediate outcomes of neuroblastoma patients non-invasively from CT images. Performances of multiple ML algorithms over retrospective CT images of 65 neuroblastoma patients are analyzed. An artificial neural network (ANN) is used on tumor radiomic features extracted from 3D CT images. A pre-trained 2D convolutional neural network (CNN) is used on slices of the same images. ML models are trained for various pathologically investigated outcomes of these patients. A subspecialty-trained pediatric radiologist independently reviewed the manually segmented primary tumors. Pyradiomics library is used to extract 105 radiomic features. Six ML algorithms are compared to predict the following outcomes: mortality, presence or absence of metastases, neuroblastoma differentiation, mitosis-karyorrhexis index (MKI), presence or absence of MYCN gene amplification, and presence of image-defined risk factors (IDRF). The prediction ranges over multiple experiments are measured using the area under the receiver operating characteristic (ROC-AUC) for comparison. Our results show that the radiomics-based ANN method slightly outperforms the other algorithms in predicting all outcomes except classification of the grade of neuroblastic differentiation, for which the elastic regression model performed the best. Contributions of the article are twofold: (1) noninvasive models for the prognosis from CT images of neuroblastoma, and (2) comparison of relevant ML models on this medical imaging problem.

Use of Digital Tomosynthesis in Assessing Accurate Medial Epicondyle Fracture Displacement as Compared With Conventional Radiography and Computed Tomography.

INTRODUCTION: Medial epicondyle fracture displacement is notoriously difficult to determine on conventional radiography, and follow-up computed tomography (CT) is often obtained to measure precise displacement. Another option for fracture characterization is digital tomosynthesis (DT), a technology providing high in-plane resolution of bony anatomy by acquiring multiple low-dose images in a linear arc. Advantages of DT include lower radiation exposure and lower cost than CT, rapid image acquisition, and a similar patient experience to conventional radiography. The digital application of tomosynthesis is relatively new and is integrated as an add-on feature with modern radiography equipment. This study compares DT, CT and conventional radiography for measurement accuracy in medial epicondyle fractures with the goal of determining relative accuracy in measuring medial epicondyle fracture displacement. METHODS: Medial epicondyle fractures were created in 5 cadaveric elbow specimens. Each specimen was imaged with conventional radiography, DT, and CT. True displacement measured by digital calipers was compared with "measured" displacement for each image acquisition. CT images included axial, sagittal, and coronal reformats. DT images of the elbow included anteroposterior (AP) longitudinal and transverse, lateral longitudinal and transverse, and axial longitudinal and transverse. Conventional radiographs included AP, lateral, and axial distal humerus images. Four physicians reviewed all images 3 months later. Each reviewer independently measured maximum apparent fracture displacement to the nearest 0.1 mm. Measurement accuracy was calculated as percent difference [(measured displacement-actual displacement)/actual displacement] for each acquisition. Mean, median, and SD for measurement accuracy were calculated. Two-tailed paired t tests were performed on each acquisition to compare the measurement accuracy. RESULTS: Compared with conventional radiographs, accuracy of DT was superior in AP longitudinal (P=0.03), AP transverse (P=0.01), axial longitudinal (P=0.0001), and axial transverse projections (P=0.001). Accuracy of CT was superior to conventional radiography in the AP projection (P=0.03), but was equivalent in the axial projection (P=0.9). Accuracy of CT was similar to DT in AP longitudinal (P=0.6), AP transverse (P=0.5), and axial longitudinal projections (P=0.07). Accuracy of DT in the axial transverse projection was superior to CT (P=0.03). CONCLUSION: DT is more accurate than conventional radiography (both AP and axial views) and as accurate as CT in assessing millimeters of displacement of medial epicondyle fracture fragments. LEVEL OF EVIDENCE: Level IV-diagnostic study.

Improved diagnostic confidence and accuracy of pediatric elbow fractures with digital tomosynthesis.

BACKGROUND: Pediatric elbow fractures are common but remain challenging to accurately diagnose. Digital tomosynthesis is a technique that has shown promise in difficult adult fracture patterns but has not been formally studied in the pediatric population. OBJECTIVE: To assess the added value of digital tomosynthesis on the detection and diagnostic confidence of pediatric elbow fractures. MATERIALS AND METHODS: A retrospective study was performed between January 2016 and December 2017 in pediatric patients (≤18 years) to assess the ability of conventional elbow radiographs and digital tomosynthesis to detect elbow fractures. One hundred twenty-one pediatric patients with concern for pediatric elbow trauma (64 males, 57 females; mean age: 8.1 years, range: 1 year to 17 years) were imaged with both conventional elbow radiographs and digital tomosynthesis. Two blinded pediatric radiologists identified fractures and indicated their diagnostic confidence. Observer agreement was assessed with Cohen's Kappa coefficient and a nonparametric Wilcoxon rank sum test was used to compare the degree of diagnostic confidence between standard radiographs alone and standard radiographs with digital tomosynthesis. McNemar's test was used to assess the difference in the rate of fracture detection between the two methods and sensitivity, specificity, precision, accuracy and diagnostic odds ratios were calculated. RESULTS: Compared with standard radiographs alone, standard radiographs with digital tomosynthesis improved inter-rater agreement, sensitivity, specificity, accuracy, precision and the diagnostic odds ratio for fracture detection and increased diagnostic confidence (Rater 1: P=0.01, Rater 2: P=0.003). CONCLUSION: The addition of digital tomosynthesis with conventional elbow radiographs improves diagnostic confidence and performance for the detection of pediatric elbow fractures.

Digital tomosynthesis of the pediatric elbow.

Imaging pediatric elbow trauma in the acute setting remains diagnostically challenging given difficult patient positioning, multiple ossification centers of the pediatric elbow, overlapping structures, and complex joint anatomy. Digital tomosynthesis is a technique where the X-ray source travels across a limited arc angle, obtaining a series of low-dose exposures that are in turn digitally reconstructed to produce high in-plane resolution at a relatively low overall radiation dose. Digital tomosynthesis is now more commonly integrated into standard radiographic machines and offers a new and exciting way to assess the pediatric elbow. In this review article we discuss the clinical applications of digital tomosynthesis in pediatric elbow trauma along with challenges related to technique, patient positioning and artifacts.

Comparison of Mechanical Versus Hand Administration of IV Contrast Agents for Pediatric Pulmonary CT Angiography.

OBJECTIVE: The purpose of this study was to assess the difference between mechanical versus hand administration of IV contrast agents on the diagnostic quality of pediatric pulmonary CT angiography (CTA). MATERIALS AND METHODS: A retrospective review of the medical records was performed to detect pediatric patients (≤ 18 years) with pulmonary CTA performed between September 2012 and March 2015. Patients were placed into two cohorts on the basis of the method of contrast administration (mechanical vs hand). Additional information obtained included IV size or gauge, IV site, amount and type of contrast agent administered, and rate of administration (mL/s). The quality of the CT images was independently evaluated by two pediatric radiologists using a qualitative 4-point visual assessment scale and quantitatively with attenuation (HU). An ANOVA controlling for age compared the contrast enhancement in the central pulmonary arteries between the cohorts. RESULTS: One hundred forty-eight consecutive pediatric patients (71 boys and 77 girls; mean age, 11.1 years; age range, 8 days-17.9 years) were identified between September 2012 and March 2015. Mechanical administration of contrast material was performed in 117 patients (79.1%; mean age [± SD], 13.7 ± 3.7 years), and hand administration of contrast material was performed in 31 patients (20.9%; mean age, 1.6 ± 1.8 years). After adjusting for age, the degree of enhancement within the pulmonary arteries was not statistically different between the two IV contrast administration methods at the main pulmonary artery (mechanical vs hand administration: mean attenuation, 310 ± 128 vs 338 ± 142 HU, respectively, p = 0.505), right pulmonary artery (305 ± 124 vs 329 ± 146 HU, p = 0.556), and left pulmonary artery (303 ± 125 vs 340 ± 151 HU, p = 0.349). CONCLUSION: It is possible to perform diagnostic-quality pulmonary CTA for the assessment of the central pulmonary arteries with hand administration of IV contrast material in pediatric patients with small-gauge IV catheters.

Intussusception: past, present and future.

Intussusception is a common etiology of acute abdominal pain in children. Over the last 70 years, there have been significant changes in how we diagnose and treat intussusception, with a more recent focus on the role of ultrasound. In this article we discuss historical and current approaches to intussusception, with an emphasis on ultrasound as a diagnostic and therapeutic modality.

Assessing 3D T2 FSE sequence for identification of the normal appendix: working toward a single-sequence MR appendicitis protocol.

PURPOSES: To assess the ability of a single isotropic 3D T2 FSE sequence to identify the normal appendix in children with potential implication as alternative second-line modality in pediatric appendicitis. MATERIALS AND METHODS: Retrospective review of MR abdomino-pelvis or pelvis in children from Oct 2014-Dec 2016 was done. Only exams with 3D T2 FSE sequence performed on a single scanner type were selected. Patients with history of post appendectomy, studies in which field of view did not include ileocecal valve, with technical and protocol errors, or with fat-saturated acquisition were excluded. All images were blindly reviewed by three radiologists. The following questions were asked: (1) Is the appendix visualized?, (2) What is the most clearly demonstrable plane?, (3) Where is the appendix located?, (4) Are there any findings indicating appendicitis? Average pairwise percentage and Fleiss Kappa were used to assess the inter-rater agreement on the visualization and location of the appendix. RESULTS: A total of 22 MRI studies were reviewed (F = 13:M = 9, Mean age = 11.45 yrs. [SD = 4.3]). Total MRI scan time was estimated at 6 mins. Readers saw appendix in 72.7-81.8%, and saw with high confidence in 12 cases (54.5%), low confidence in 4-6 case (18.2-27.3%), and did not see in 4-6 cases(18.2-27.3%). The average pairwise percentage agreement was 71.2%. Fleiss Kappa of overall rating of visualization was 0.52 (p < 0.001). Fleiss Kappa of high confidence of visualization was 0.76 (p < 0.001). Reader 1 and reader 2 saw the appendix best on the axial plane. Reader 3 saw the appendix best on the coronal plane. For location, deep pelvis was the most common identified location. The average pairwise percentage agreement was 68.2% and Fleiss Kappa was 0.76 (p < 0.001). There is no findings indicating appendicitis. CONCLUSION: A single 3D T2 FSE sequence had good ability to detect normal appendices and also allowed multiplanar reconstructions, which may use as a single-sequence protocol in cases of suspected appendicitis in children when ultrasound is inconclusive.

Growth recovery lines are more common in infants at high vs. low risk for abuse.

BACKGROUND: Growth recovery lines, also known as growth arrest lines, are transverse radiodense metaphyseal bands that develop due to a temporary arrest of endochondral ossification caused by local or systemic insults. OBJECTIVE: To determine if growth recovery lines are more common in infants at high risk versus low risk for abuse. MATERIALS AND METHODS: Reports of American College of Radiology compliant skeletal surveys (1999-2013) were reviewed with clinical records. Infants at low risk for abuse had a skull fracture without significant intracranial injury, history of a fall and clinical determination of low risk (child protection team/social work assessment). Infants at high risk had significant intracranial injury, retinal hemorrhages, other skeletal injuries and clinical determination of high risk. There were 52 low-risk infants (mean: 4.7 months, range: 0.4-12 months) and 21 high-risk infants (mean: 4.2 months, range: 0.8-9.1 months). Two blinded radiologists independently evaluated the skeletal survey radiographs of the knees/lower legs for the presence of at least one growth recovery line. RESULTS: When growth recovery lines are scored as probably present or definitely present, their prevalence in the low-risk group was 38% (standard deviation [SD] = 8%; reader 1 = 17/52, reader 2 = 23/52) vs. 71% (SD = 7%; reader 1 = 16/21, reader 2 = 14/21) in the high-risk group (P < 0.001; odds ratio 4.0, 95% CI: 1.7-9.5). CONCLUSION: Growth recovery lines are encountered at a significantly higher rate in infants at high risk vs. low risk for abuse. This suggests that abused infants are prone to a temporary disturbance in endochondral ossification as a result of episodic physiological stresses.

Magnetic resonance imaging of Müllerian duct anomalies in children.

Müllerian duct anomalies encompass a wide variety of disorders resulting from abnormalities in the embryological development of the Müllerian ducts. In the prepubertal pediatric population, Müllerian duct anomalies are often incidental findings on studies obtained for other reasons. The onset of menses can prompt more clinical symptoms. Proper characterization of Müllerian duct anomalies is important because these anomalies can affect the development of gynecological disorders as well as fertility. Müllerian duct anomalies also carry a high association with other congenital anomalies, particularly renal abnormalities. MRI is widely considered the best modality for assessing Müllerian duct anomalies; it provides multiplanar capability, clear anatomical detail and tissue characterization without ionizing radiation. MRI allows for careful description of Müllerian duct anomalies, often leading to classification into the most widely accepted classification system for Müllerian duct anomalies. This system, developed by the American Society of Reproductive Medicine, includes seven subtypes: uterine agenesis/hypoplasia, unicornuate, didelphys, bicornuate, septate, arcuate, and diethylstilbestrol (DES) drug-related uterus. In cases of complex anomalies that defy classification, MRI allows detailed depiction of all components of the anatomical abnormality, allowing for proper management and surgical planning.

Factors and Labor Cost Savings Associated with Successful Pediatric Imaging without Anesthesia: a Single-Institution Study.

RATIONALE AND OBJECTIVES: In pediatric imaging, sedation is often necessary to obtain diagnostic quality imaging. We aim to quantify patient and imaging-specific factors associated with successful pediatric scans without anesthesia and to evaluate labor cost savings associated with our institutional Scan Without Anesthesia Program (SWAP). MATERIALS AND METHODS: Patients who participated in SWAP between 2019-2022 were identified. Chart review was conducted to obtain sociodemographic and clinical information. Radiology database was used to obtain scan duration, modality/body part of examination, and administration of contrast. Mann-Whitney U and Chi-Square tests were used for univariate analysis of factors associated with success. Multivariate logistic regression was used to evaluate independent contributions to success. Associated hospital labor cost savings were estimated using salary information obtained through publicly available resources. RESULTS: Of 731 patients, 698 had successful and 33 had unsuccessful scans (95% success rate). In univariate analysis, older age, female sex, absence of developmental delay, and administration of contrast were significantly associated with successful scans. Multivariate analyses revealed that older age, female sex, and absence of developmental delay were significant independent factors lending toward success. Imaging-related factors were not associated with outcome in multivariate analysis. Estimated labor cost savings were $139,367.80 per year for the medical center. CONCLUSION: SWAP had an overall success rate of 95%. Older age, absence of developmental delay, and female sex were independently significantly associated with successful outcome. Cost analysis reveals substantial labor cost savings to the institution compared with imaging under anesthesia.

In silico QTL mapping of basal liver iron levels in inbred mouse strains.

Both iron deficiency and iron excess are detrimental in many organisms, and previous studies in both mice and humans suggest that genetic variation may influence iron status in mammals. However, these genetic factors are not well defined. To address this issue, we measured basal liver iron levels in 18 inbred strains of mice of both sexes on a defined iron diet and found ∼4-fold variation in liver iron in males (lowest 153 µg/g, highest 661 µg/g) and ∼3-fold variation in females (lowest 222 µg/g, highest 658 µg/g). We carried out a genome-wide association mapping to identify haplotypes underlying differences in liver iron and three other related traits (copper and zinc liver levels, and plasma diferric transferrin levels) in a subset of 14 inbred strains for which genotype information was available. We identified two putative quantitative trait loci (QTL) that contain genes with a known role in iron metabolism: Eif2ak1 and Igf2r. We also identified four putative QTL that reside in previously identified iron-related QTL and 22 novel putative QTL. The most promising putative QTL include a 0.22 Mb region on Chromosome 7 and a 0.32 Mb region on Chromosome 11 that both contain only one candidate gene, Adam12 and Gria1, respectively. Identified putative QTL are good candidates for further refinement and subsequent functional studies.

Association of image-defined risk factors with clinical features, histopathology, and outcomes in neuroblastoma.

BACKGROUND: Clinical, molecular, and histopathologic features guide treatment for neuroblastoma, but obtaining tumor tissue may cause complications and is subject to sampling error due to tumor heterogeneity. We hypothesized that image-defined risk factors (IDRFs) would reflect molecular features, histopathology, and clinical outcomes in neuroblastoma. METHODS: We performed a retrospective cohort study of 76 patients with neuroblastoma or ganglioneuroblastoma. Diagnostic CT scans were reviewed for 20 IDRFs, which were consolidated into five IDRF groups (involvement of multiple body compartments, vascular encasement, tumor infiltration of adjacent organs/structures, airway compression, or intraspinal extension). IDRF groups were analyzed for association with clinical, molecular, and histopathologic features of neuroblastoma. RESULTS: Patients with more IDRF groups had a higher risk of surgical complications (OR = 3.1, p = 0.001). Tumor vascular encasement was associated with increased risk of surgical complications (OR = 5.40, p = 0.009) and increased risk of undifferentiated/poorly differentiated histologic grade (OR = 11.11, p = 0.013). Tumor infiltration of adjacent organs and structures was associated with decreased survival (HR = 8.90, p = 0.007), MYCN amplification (OR = 9.91, p = 0.001), high MKI (OR = 6.20, p = 0.003), and increased risk of International Neuroblastoma Staging System stage 4 disease (OR = 8.96, p < 0.001). CONCLUSIONS: The presence of IDRFs at diagnosis was associated with high-risk clinical, molecular, and histopathologic features of neuroblastoma. The IDRF group tumor infiltration into adjacent organs and structures was associated with decreased survival. Collectively, these findings may assist surgical planning and medical management for neuroblastoma patients.

The effects of globin on microarray-based gene expression analysis of mouse blood.

The use of mouse blood as a model for human blood is often considered in the development of clinically relevant, gene expression-based disease biomarkers. However, the ability to derive biologically meaningful insights from microarray-based gene expression patterns in mouse whole blood, as in human whole blood, is hindered by high levels of globin mRNA. In order to characterize the effects of globin reduction on gene expression of peripheral mouse blood, we performed gene set enrichment analysis on genes identified as expressed in blood via microarray-based genome-wide transcriptome analysis. Depletion of globin mRNA enhanced the quality of microarray data as shown by improved gene expression detection and increased sensitivity. Compared to genes expressed in whole blood, genes detected as expressed in blood following globin reduction were enriched for low abundance transcripts implicated in many biological pathways, including development, g-protein signaling, and immune response. Broadly, globin reduction resulted in improved detection of expressed genes that serve as molecular binding proteins and enzymes in cellular metabolism, intracellular transport/localization, transcription, and translation, as well as genes that potentially could act as biomarkers for diseases such as schizophrenia. These significantly enriched pathways overlap considerably with those identified in globin-reduced human blood suggesting that globin-reduced mouse blood gene expression studies may be useful for identifying genes relevant to human disease. Overall, the results of this investigation provide a better understanding of the impact of reducing globin transcripts in mouse blood and highlight the potential of microarray-based, globin-reduced, mouse blood gene expression studies in biomarker development.

Evaluating the Performance of Augmented Reality in Displaying Magnetic Resonance Imaging-Derived Three-Dimensional Holographic Models.

INTRODUCTION/BACKGROUND: Establishing accuracy and precision of magnetic resonance (MR)-derived augmented reality (AR) models is critical before clinical utilization, particularly in preoperative planning. We investigate the performance of an AR application in representing and displaying MR-derived three-dimensional holographic models. METHODS: Thirty gold standard (GS) measurements were obtained on a magnetic resonance imaging (MRI) phantom (six interfiducial distances and five configurations). Four MRI pulse sequences were obtained for each of the five configurations, and distances measured in Picture Archiving and Communication System (PACS). Digital imaging and communications in medicine files were translated into three-dimensional models and then loaded onto a novel AR platform. Measurements were also obtained with the software's AR caliper tool. Significant differences among the three groups (GS, PACS, and AR) were assessed with the Kruskal-Wallis test and nonsample median test. Accuracy analysis of GS vs. AR was performed. Precision (percent deviation) of the AR-based caliper tool was also assessed. RESULTS: No statistically significant difference existed between AR and GS measurements (P = .6208). PACS demonstrated mean squared error (MSE) of 0.29%. AR digital caliper demonstrated an MSE of 0.3%. Three-dimensional T2 CUBE AR measurements using the platform's AR caliper tool demonstrated an MSE of 8.6%. Percent deviation of AR software caliper tool ranged between 1.9% and 3.9%. DISCUSSION: AR demonstrated a high degree of accuracy in comparison to GS, comparable to PACS-based measurements. AR caliper tool demonstrated overall lower accuracy than with physical calipers, although with MSE <10% and greatest measured difference from GS measuring <5 mm. AR-based caliper demonstrated a high degree of precision. CONCLUSION: There was no statistically significant difference between GS measurements and three-dimensional AR measurements in MRI phantom models.

Monitoring Arteriovenous Malformation Response to Genotype-Targeted Therapy.

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.

Gene expression in mouse brain following chronic hypoxia: role of sarcospan in glial cell death.

Hypoxia is a hallmark of respiratory, neurological, or hematological diseases as well as life at high altitude. For example, chronic constant hypoxia (CCH) occurs in chronic lung diseases or at high altitude, whereas chronic intermittent hypoxia (CIH) occurs in diseases such as sleep apnea or sickle cell disease. Despite the fact that such conditions are frequent, the cellular and molecular mechanisms underlying the effect of hypoxia, whether constant or intermittent, are not well understood. In this study, we first determined the effect of CCH and CIH on global gene expression in different regions of mouse brain using microarrays and then investigated the biological role of genes of interest. We found that: 1) in the cortical region, the expression level of 80 genes was significantly altered by CIH (16 up- and 64 downregulated), and this number increased to 137 genes following CCH (34 up- and 103 downregulated); 2) a similar number of gene alterations was identified in the hippocampal area, and the majority of the changes in this region were upregulations; 3) two genes (Sspn and Ttc27) were downregulated in both brain regions and following both treatments; and 4) RNA interference-mediated knockdown of Sspn increased cell death in hypoxia in a cell culture system. We conclude that CIH or CCH induced significant and distinguishable alterations in gene expression in cortex and hippocampus and that Sspn seems to play a critical role in inducing cell death under hypoxic conditions.

Thoracic Neoplasms in Children: Contemporary Perspectives and Imaging Assessment.

This article focuses on commonly encountered primary lung, airway, mediastinal, and chest wall neoplasms that occur in the pediatric population. Although primary pediatric thoracic neoplasms are rare, imaging is critical in their diagnostic work-up. An overview of the latest imaging techniques specific to evaluate these pediatric thoracic neoplasms is presented across the spectrum of modalities from radiography to PET/MR imaging. In addition, the characteristic imaging appearances of these pediatric primary thoracic neoplasms are discussed with an emphasis on what the radiologist needs to know in routine clinical practice.