Three-Dimensional Reconstruction Algorithm for a Reverse-Geometry Volumetric CT System With a Large-Array Scanned Source

We have proposed a CT system design to rapidly produce volumetric images with negligible cone beam artifacts. The investigated system uses a large array scanned source with a smaller array of fast detectors. The x-ray source is electronically steered across a 2D target every few milliseconds as the system rotates. The proposed reconstruction algorithm for this system is a modified 3D filtered backprojection method. The data are rebinned into 2D parallel ray projections, most of which are tilted with respect to the axis of rotation. Each projection is filtered with a 2D kernel and backprojected onto the desired image matrix. To ensure adequate spatial resolution and low artifact level, we rebin the data onto an array that has sufficiently fine spatial and angular sampling. Due to finite sampling in the real system, some of the rebinned projections will be sparse, but we hypothesize that the large number of views will compensate for the data missing in a particular view. Preliminary results using simulated data with the expected discrete sampling of the source and detector arrays suggest that high resolution

Noise Simulations For an Inverse-Geometry Volumetric CT System

This paper examines the noise performance of an inverse-geometry volumetric CT (IGCT) scanner through simulations. The IGCT system uses a large area scanned source and a smaller array of detectors to rapidly acquire volumetric data with negligible cone-beam artifacts. The first investigation compares the photon efficiency of the IGCT geometry to a 2D parallel ray system. The second investigation models the photon output of the IGCT source and calculates the expected noise. For the photon efficiency investigation. the same total number of photons was modeled in an IGCT acquisition and a comparable multi-slice 2D parallel ray acquisition. For both cases noise projections were simulated and the central axial slice reconstructed. In the second study. to investigate the noise in an IGCT system, the expected x-ray photon flux was modeled and projections simulated through ellipsoid phantoms. All simulations were compared to theoretical predictions. The results of the photon efficiency simulations verify that the IGCT geometry is as efficient in photon utilization as a 2D parallel ray geometry. For a 10 cm diameter 4 cm thick ellipsoid water phantom and for reasonable system parameters, the calculated standard deviation was approximately 15 HU at the center of the ellipsoid. For the same size phantom with maximum attenuation equivalent to 30 cm of water, the calculated noise was approximately 131 HU. The theoretical noise predictions for these objects were 15 HU and 112 HU respectively. These results predict acceptable noise levels for a system with a 0.16 second scan time and 12 lp/cm isotropic resolution

Treating anemia of chronic kidney disease in the primary care setting: cardiovascular outcomes and management recommendations

Anemia is an underrecognized but characteristic feature of chronic kidney disease (CKD), associated with significant cardiovascular morbidity, hospitalization, and mortality. Since their inception nearly two decades ago, erythropoiesis-stimulating agents (ESAs) have revolutionized the care of patients with renal anemia, and their use has been associated with improved quality of life and reduced hospitalizations, inpatient costs, and mortality. Hemoglobin targets ≥13 g/dL have been linked with adverse events in recent randomized trials, raising concerns over the proper hemoglobin range for ESA treatment. This review appraises observational and randomized studies of the outcomes of erythropoietic treatment and offers recommendations for managing renal anemia in the primary care setting

Geometry Analysis of an Inverse-Geometry Volumetric CT System With Multiple Detector Arrays

An inverse-geometry volumetric CT (IGCT) system for imaging in a single fast rotation without cone-beam artifacts is being developed. It employs a large scanned source array and a smaller detector array. For a single-source/single-detector implementation, the FOV is limited to a fraction of the source size. Here we explore options to increase the FOV without increasing the source size by using multiple detectors spaced apart laterally to increase the range of radial distances sampled. We also look at multiple source array systems for faster scans. To properly reconstruct the FOV, Radon space must be sufficiently covered and sampled in a uniform manner. Optimal placement of the detectors relative to the source was determined analytically given system constraints (5cm detector width, 25cm source width, 45cm source-to-isocenter distance). For a 1x3 system (three detectors per source) detector spacing (DS) was 18deg and source-to-detector distances (SDD) were 113, 100 and 113cm to provide optimum Radon sampling and a FOV of 44cm. For multiple-source systems, maximum angular spacing between sources cannot exceed 125deg since detectors corresponding to one source cannot be occluded by a second source. Therefore, for 2x3 and 3x3 systems using the above DS and SDD, optimum spacing between sources is 115deg and 61deg respectively, requiring minimum scan rotations of 115deg and 107deg. Also, a 3x3 system can be much faster for full 360deg dataset scans than a 2x3 system (120deg vs. 245deg). We found that a significantly increased FOV can be achieved while maintaining uniform radial sampling as well as a substantial reduction in scan time using several different geometries. Further multi-parameter optimization is underway

Body composition estimated by bioelectrical impedance analyses is diminished by prenatal stress in neonatal lambs and by heat stress in feedlot wethers

Body composition correlates to carcass value in livestock, which makes the ability to accurately estimate body composition in the live animal beneficial (Berg and Marchello, 1994). Bioelectrical impedance analysis (BIA) is a clinical tool used to assess body composition in humans (Lukaski et al., 1985), but its use in livestock has been minimal. Lean and fat content contribute to profitability for livestock producers, and poor body composition can be caused by stress that occurs either during in utero development (De Blasio et al., 2007) or during postnatal growth (Boyd et al., 2015). Maternal hyperthermia-induced placental insufficiency (Brown et al., 2015) and sustained maternal inflammation (Cadaret et al., 2018) are two established causes of intrauterine growth restriction (IUGR). IUGR-born animals are characterized by asymmetrical growth restriction that alters lifelong body composition due to impaired muscle growth capacity (Yates et al., 2018). In addition, acute heat stress during periods of peak postnatal growth can alter body composition in livestock (Boyd et al., 2015). We postulate that BIA can detect these changes in the live animal. Thus, the objective of this study was to determine whether BIA measurements can predict changes to body composition in live neonatal lambs exposed to intrauterine stress and in heat-stressed feedlot lambs

Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study.

Human placenta is a fetal-derived tissue that offers a unique sample of epigenetic and environmental exposures present in utero. In the MARBLES prospective pregnancy study of high-risk younger siblings of children with autism spectrum disorder (ASD), pregnancy and environmental factors collected by maternal interviews were examined as predictors of placental DNA methylation, including partially methylated domains (PMDs), an embryonic feature of the placental methylome. DNA methylation data from MethylC-seq analysis of 47 placentas of children clinically diagnosed at 3 years with ASD or typical development using standardized assessments were examined in relation to: child's gestational age, birth-weight, and diagnosis; maternal pre-pregnancy body mass index, smoking, education, parity, height, prenatal vitamin and folate intake; home ownership; pesticides professionally applied to lawns or gardens or inside homes, pet flea/tick pouches, collars, or soaps/shampoos used in the 3 months prior to or during pregnancy. Sequencing run, order, and coverage, and child race and sex were considered as potential confounders. Akaike information criterion was used to select the most parsimonious among candidate models. Final prediction models used sandwich estimators to produce homoscadisticity-robust estimates of the 95% confidence interval (CI) and P-values controlled the false discovery rate at 5%. The strongest, most robust associations were between pesticides professionally applied outside the home and higher average methylation over PMDs [0.45 (95% CI 0.17, 0.72), P = 0.03] and a reduced proportion of the genome in PMDs [-0.42 (95% CI - 0.67 to -0.17), P = 0.03]. Pesticide exposures could alter placental DNA methylation more than other factors

Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms

Vasomotor symptoms (VMS) may be associated with an increased risk of cardiovascular disease. One candidate mechanism may involve alterations in physiological responses to stress. The current study therefore examined the relationship between self-reported VMS bother and cardiovascular, hemodynamic, neuroendocrine and inflammatory responses to an acute psychosocial stress protocol

Nitrosylcobalamin Potentiates the Anti-Neoplastic Effects of Chemotherapeutic Agents via Suppression of Survival Signaling

Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-kappaB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy.Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.Eighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.The use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-kappaB or AKT

Placental-brain axis in females detected within broadly impacted metabolic gene networks protects against prenatal PCB exposure

Background Neurodevelopmental disorders have a strong male bias that is poorly understood. Placenta is a rich source of molecular information about environmental interactions with genetics (including biological sex), that affect the developing brain. We investigated placental-brain transcriptional responses in an established mouse model of prenatal exposure to a human-relevant mixture of polychlorinated biphenyls (PCBs). Results To understand sex, tissue, and dosage effects in embryonic (E18) brain and placenta by RNAseq, we used weighted gene correlation network analysis (WGCNA) to create correlated gene networks that could be compared across sex or tissue. WGCNA revealed that expression within most correlated gene networks was significantly and strongly associated with PCB exposures, but frequently in opposite directions between male-female and placenta-brain comparisons. In both WGCNA and differentially expressed gene analyses, male brain showed more PCB-induced transcriptional changes than male placenta, but the reverse pattern was seen in females. Furthermore, non-monotonic dose responses to PCBs were observed in most gene networks but were most prominent in male brain. The transcriptomic effects of low dose PCB exposure were significantly reversed by dietary folic acid supplementation across both sexes, but these effects were strongest in female placenta. PCB-dysregulated and folic acid-reversed gene networks were commonly enriched in functions in metabolic pathways involved in energy usage and translation, with female-specific protective effects enriched in PPAR, thermogenesis, glycerolipids, and O-glycan biosynthesis, as opposed to toxicant responses in male brain. Conclusions The female protective effect in prenatal PCB exposures appears to be mediated by dose-dependent sex differences in transcriptional modulation of metabolism in placenta. Graphical Abstrac