Ferumoxytol-enhanced 4D multiphase, steady-state imaging with magnetic resonance in congenital heart disease: ventricular volume and function across 2D and 3D software platforms.

Background: Quantitative ventricular volumetry and function are important in the management of congenital heart disease (CHD). Ferumoxytol-enhanced (FE) 4D multiphase, steady state imaging with contrast enhancement (MUSIC) enables high-resolution, 3D cardiac phase-resolved magnetic resonance imaging (MRI) of the beating heart and extracardiac vessels in a single acquisition and without concerns about renal impairment. We aim to evaluate the semi-automatic quantification of ventricular volumetry and function of 4D MUSIC MRI using 2D and 3D software platforms. Methods: This HIPAA-compliant and IRB-approved study prospectively recruited 50 children with CHD (3 days to 18 years) who underwent 4D MUSIC MRI at 3.0T between 2013-2017 for clinical indications. Each patient was either intubated in the neonatal intensive care unit (NICU) or underwent general anesthesia at MRI suite. For 2D analysis, we reformatted MUSIC images in Digital Imaging and Communications in Medicine (DICOM) format into ventricular short-axis slices with zero interslice gap. For 3D analysis, we imported DICOMs into a commercially available 3D software platform. Using semi-automatic thresholding, we quantified biventricular volume and ejection fraction (EF). We assessed the bias between MUSIC-derived 2D vs. 3D measurements and correlation between MUSIC vs. conventional 2D balanced steady-state free precession (bSSFP) cine images. We evaluated intra- and inter-observer agreement. Results: There was a high degree of correlation between MUSIC-derived volumetric and functional measurements using 2D vs. 3D software (r=0.99, P<0.001). Volumes derived using 3D software platforms were larger than 2D by 0.2 to 2.0 mL/m2 whereas EF measurements were higher by 1.2-3.0%. MUSIC volumetric and functional measures derived from 2D and 3D software platforms corresponded highly with those derived from multi-slice SSFP cine images (r=0.99, P<0.001). The mean difference in volume for reformatted 4D MUSIC relative to bSSFP cine was 1.5 to 3.9 mL/m2. Intra- and inter-observer reliability was excellent. Conclusions: Accurate and reliable ventricular volumetry and function can be derived from FE 4D MUSIC MRI studies using commercially available 2D and 3D software platforms. If fully validated in multicenter studies, the FE 4D-MUSIC pulse sequence may supercede conventional multislice 2D cine cardiovascular MRI acquisition protocols for functional evaluation of children with complex CHD.

Headache in an Obese Adolescent Male: A Nonclassical Presentation of an Uncommon Disease.

Background. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a diagnosis of exclusion in the clinical scenario of increased intracranial pressure without an identifiable cause. This case report provides a brief review of current literature on IIH, important differential considerations to rule out prior to diagnosis, and relevant imaging findings of IIH. Case Presentation. An 18-year-old male presenting with headache and blurry vision was found to have signs of increased intracranial pressure on imaging without other abnormalities to explain the cause, suggesting IIH as a diagnosis. Conclusion. IIH is classically seen in overweight females of childbearing age but should be considered in all obese patients, including the pediatric population given the increasing rate of childhood obesity.

Ambient Ultrafine Particle Ingestion Alters Gut Microbiota in Association with Increased Atherogenic Lipid Metabolites.

Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp < 0.1-0.2 µm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr-/-) mice on a high-fat diet were orally administered with vehicle control or UFP (40 µg/mouse/day) for 3 days a week. After 10 weeks, UFP ingested mice developed macrophage and neutrophil infiltration in the intestinal villi, accompanied by elevated cholesterol but reduced coprostanol levels in the cecum, as well as elevated atherogenic lysophosphatidylcholine (LPC 18:1) and lysophosphatidic acids (LPAs) in the intestine and plasma. At the phylum level, Principle Component Analysis revealed significant segregation of microbiota compositions which was validated by Beta diversity analysis. UFP-exposed mice developed increased abundance in Verrocomicrobia but decreased Actinobacteria, Cyanobacteria, and Firmicutes as well as a reduced diversity in microbiome. Spearman's analysis negatively correlated Actinobacteria with cecal cholesterol, intestinal and plasma LPC18:1, and Firmicutes and Cyanobacteria with plasma LPC 18:1. Thus, ultrafine particles ingestion alters gut microbiota composition, accompanied by increased atherogenic lipid metabolites. These findings implicate the gut-vascular axis in a atherosclerosis model.

Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis.

AIM: Temporal and spatial variations in shear stress are intimately linked with vascular metabolic effects. Autophagy is tightly regulated in intracellular bulk degradation/recycling system for maintaining cellular homeostasis. We postulated that disturbed flow modulates autophagy with an implication in mitochondrial superoxide (mtO2(•-)) production. RESULTS: In the disturbed flow or oscillatory shear stress (OSS)-exposed aortic arch, we observed prominent staining of p62, a reverse marker of autophagic flux, whereas in the pulsatile shear stress (PSS)-exposed descending aorta, p62 was attenuated. OSS significantly increased (i) microtubule-associated protein light chain 3 (LC3) II to I ratios in human aortic endothelial cells, (ii) autophagosome formation as quantified by green fluorescent protein (GFP)-LC3 dots per cell, and (iii) p62 protein levels, whereas manganese superoxide dismutase (MnSOD) overexpression by recombinant adenovirus, N-acetyl cysteine treatment, or c-Jun N-terminal kinase (JNK) inhibition reduced OSS-mediated LC3-II/LC3-I ratios and mitochondrial DNA damage. Introducing bafilomycin to Earle's balanced salt solution or to OSS condition incrementally increased both LC3-II/LC3-I ratios and p62 levels, implicating impaired autophagic flux. In the OSS-exposed aortic arch, both anti-phospho-JNK and anti-8-hydroxy-2'-deoxyguanosine (8-OHdG) staining for DNA damage were prominent, whereas in the PSS-exposed descending aorta, the staining was nearly absent. Knockdown of ATG5 with siRNA increased OSS-mediated mtO2(•-), whereas starvation or rapamycin-induced autophagy reduced OSS-mediated mtO2(•-), mitochondrial respiration, and complex II activity. INNOVATION: Disturbed flow-mediated oxidative stress and JNK activation induce autophagy. CONCLUSION: OSS impairs autophagic flux to interfere with mitochondrial homeostasis. Antioxid. Redox Signal. 23, 1207-1219.