Automation Process for Morphometric Analysis of Volumetric CT Data from Pulmonary Vasculature in Rats

With advances in medical imaging scanners, it has become commonplace to generate large multidimensional datasets. These datasets require tools for a rapid, thorough analysis. To address this need, we have developed an automated algorithm for morphometric analysis incorporating A Visualization Workshop computational and image processing libraries for three-dimensional segmentation, vascular tree generation and structural hierarchical ordering with a two-stage numeric optimization procedure for estimating vessel diameters. We combine this new technique with our mathematical models of pulmonary vascular morphology to quantify structural and functional attributes of lung arterial trees. Our physiological studies require repeated measurements of vascular structure to determine differences in vessel biomechanical properties between animal models of pulmonary disease. Automation provides many advantages including significantly improved speed and minimized operator interaction and biasing. The results are validated by comparison with previously published rat pulmonary arterial micro-CT data analysis techniques, in which vessels were manually mapped and measured using intense operator intervention

Oscillation theorems for nth-order functional differential equations

AbstractTwo oscillation theorems for even-order equations x(n)(t) + p(t)ƒ(x(t), x(h(t))) = 0 are established. These results are the extensions of those reported by Hamedani for the second-order equation x″(t) + p(t) ƒ(x(t), x(h(t))) = 0

COSMIC: US-based Conversion Master\u27s Degree in Computing

COSMIC is an NSF S-STEM graduate curriculum initiative/conversion program that strives to provide an accelerated pathway to a Master of Science (MS) degree for individuals who do not have an undergraduate degree in computing, but who wish to cross over into the computing field. The structure of our conversion program, the context that motivated it, and insights from conversion students\u27 instructors are presented. Program successes with students from under-represented populations and the limitations that are also experienced are discussed. Our conversion program is based on a highly focused summer bridge course, combined with a customized curriculum pathway that enables people without undergraduate computing degrees to merge quickly and efficiently into a professional MS in computing degree program. The program is similar in concept to post-baccalaureate conversion programs in New Zealand (e.g., the Master of Software Development at the Victoria University of Wellington) and the extensive conversion choices in the UK. Undergraduate and graduate student enrollment statistics from past and current (2018) CRA Taulbee Surveys strongly suggest the computing profession has a moral obligation to seek out and encourage individuals from under-represented populations to become a significant part of the computing professional community. We encourage other institutions to join in the effort to recruit and provide pathways for post-baccalaureate individuals from under-represented populations to become a significant part of the computing community

Preferential utilization of NADPH as the endogenous electron donor for NAD(P)H:quinone oxidoreductase 1 (NQO1) in intact pulmonary arterial endothelial cells

The goal was to determine whether endogenous cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1) preferentially uses NADPH or NADH in intact pulmonary arterial endothelial cells in culture. The approach was to manipulate the redox status of the NADH/NAD+ and NADPH/NADP+ redox pairs in the cytosolic compartment using treatment conditions targeting glycolysis and the pentose phosphate pathway alone or with lactate, and to evaluate the impact on the intact cell NQO1 activity. Cells were treated with 2-deoxyglucose, iodoacetate, or epiandrosterone in the absence or presence of lactate, NQO1 activity was measured in intact cells using duroquinone as the electron acceptor, and pyridine nucleotide redox status was measured in total cell KOH extracts by high-performance liquid chromatography. 2-Deoxyglucose decreased NADH/NAD+ and NADPH/NADP+ ratios by 59 and 50%, respectively, and intact cell NQO1 activity by 74%; lactate restored NADH/NAD+, but not NADPH/NADP+ or NQO1 activity. Iodoacetate decreased NADH/NAD+ but had no detectable effect on NADPH/NADP+ or NQO1 activity. Epiandrosterone decreased NQO1 activity by 67%, and although epiandrosterone alone did not alter the NADPH/NADP+ or NADH/NAD+ ratio, when the NQO1 electron acceptor duroquinone was also present, NADPH/NADP+ decreased by 84% with no impact on NADH/NAD+. Duroquinone alone also decreased NADPH/NADP+ but not NADH/NAD+. The results suggest that NQO1 activity is more tightly coupled to the redox status of the NADPH/NADP+ than NADH/NAD+ redox pair, and that NADPH is the endogenous NQO1 electron donor. Parallel studies of pulmonary endothelial transplasma membrane electron transport (TPMET), another redox process that draws reducing equivalents from the cytosol, confirmed previous observations of a correlation with the NADH/NAD+ ratio

Lung Circulation Modeling: Status and Prospect

Mathematical modeling has been used to interpret anatomical and physiological data obtained from metabolic and hemodynamic studies aimed at investigating structure-function relationships in the vasculature of the lung, and how these relationships are affected by lung injury and disease. The indicator dilution method was used to study the activity of redox processes within the lung. A steady-state model of the data was constructed and used to show that pulmonary endothelial cells may play an important role in reducing redox active compounds and that those reduction rates can be altered with oxidative stress induced by exposure to high oxygen environments. In addition, a morphometric model of the pulmonary vasculature was described and used to detect, describe,and predict changes in vascular morphology that occur in response to chronic exposure to low-oxygen environments, a common model of pulmonary hypertension. Finally, the model was used to construct simulated circulatory networks designed to aid in evaluation of competing hypotheses regarding the relative contribution of various morphological and biomechanical changes observed with hypoxia. These examples illustrate the role of mathematical modeling in the integration of the emerging metabolic, hemodynamic, and morphometric databases

Imaging Radiation Pneumonitis in a Rat Model of a Radiological Terrorism Incident

We have developed a rat model of single, sub-lethal thoracic irradiation. Our irradiation protocol is considered representative of exposures near the detonation site of a dirty bomb or small nuclear device. The model is being used to investigate techniques for identifying, triaging and treating possible victims. In addition to physiological markers of right ventricular hypertrophy, pulmonary vascular resistance, and arterial distensibility, we present two methods for quantifying microvascular density. We used methods including microfocal X-ray imaging to investigate changes in lung structure/function resulting from radiation exposure. Radiation pneumonitis is a complication in subjects receiving thoracic irradiation. A radiographic hallmark of acute radiation pneumonitis is a diffuse infiltrate corresponding to the radiation treatment field. We describe two methods for quantifying small artery dropout that occurs in the model at the same time-period. Rats were examined 3-days, 2-weeks, 1-month (m), 2-m, 5-m, and 12-m post-irradiation and compared with aged-matched controls. Right ventricular hypertrophy and increases in pulmonary vascular resistance were present during the pneumonitis phase. Vascular injury was dependent on dose and post-irradiation duration. Rats irradiated with 5 Gy had few detectable changes, whereas 10 Gy resulted in a significant decrease in both microvascular density and arterial distensibility around 2- m, the decrease in each lessening, but extending through 12-m. In conclusion, rats irradiated with a 10 Gy dose had changes in vascular structure concurrent with the onset of radiation pneumonitis that were detectable with our imaging techniques and these structural changes persist after resolution of the pneumonitis

Characterization of theThreshold for NAD(P)H:quinone Oxidoreductase Activity in Intact Sulforaphane-treated Pulmonary Arterial Endothelial Cells

Treatment of bovine pulmonary arterial endothelial cells in culture with the phase II enzyme inducer sulforaphane (5 μM, 24 h; sulf-treated) increased cell-lysate NAD(P)H:quinone oxidoreductase (NQO1) activity by 5.7 ± 0.6 (mean ± SEM)-fold, but intact-cell NQO1 activity by only 2.8 ± 0.1-fold compared to control cells. To evaluate the hypothesis that the threshold for sulforaphane-induced intact-cell NQO1 activity reflects a limitation in the capacity to supply NADPH at a sufficient rate to drive all the induced NQO1 to its maximum activity, total KOH-extractable pyridine nucleotides were measured in cells treated with duroquinone to stimulate maximal NQO1 activity. NQO1 activation increased NADP+ in control and sulf-treated cells, with the effect more pronounced in the sulf-treated cells, in which the NADPH was also decreased. Glucose-6-phosphate dehydrogenase (G-6-PDH) inhibition partially blocked NQO1 activity in control and sulf-treated cells, but G-6-PDH overexpression via transient transfection with the human cDNA alleviated neither the restriction on intact sulf-treated cell NQO1 activity nor the impact on the NADPH/NADP+ ratios. Intracellular ATP levels were not affected by NQO1 activation in control or sulf-treated cells. An increased dependence on extracellular glucose and a rightward shift in the Km for extracellular glucose were observed in NQO1-stimulated sulf-treated vs control cells. The data suggest that glucose transport in the sulf-treated cells may be insufficient to support the increased metabolic demand for pentose phosphate pathway-generated NADPH as an explanation for the NQO1 threshold

Distensibility Differs Between Sall Arteries and Veins in the Newborn Piglet Lung

BACKGROUND: We previously used micro-CT techniques to measure pulmonary artery distensibility in 3 week old piglets. Pressure/diameter relationships were measured for each artery and the slope (a) was then plotted against its diameter intercept at 0 pressure (Do). The resultant diameter independent distensibility parameter, a, was estimated by linear regression to be 1.6% per mmHg for arteries between 0.2 and 3.0 mm Do. OBJECTIVE: This study sought to determine whether; 1) distensibility of smaller arteries was similar to that of arteries with Do\u3e 0.2 mm; and 2) whether small vein and artery distensibility was similar. DESIGN/METHODS: Lower lobes were isolated and perfused with papaverine/saline to remove blood and tone. Lobar bronchi were cannulated and lobes inflated to 3 mmHg. Lobar arteries (n=13) or veins (n=12) were cannulated and perfluoroctyl bromide instilled. Small arteries (0.033 to 0.34 mm Do) and veins (0.024 to 0.33 mm Do) were imaged by planar X-ray at static pressures ranging from 21 to 3 mmHg in 3 mmHg increments. The slope of the pressure/diameter curve was estimated by linear regression (0 = Do + ~P ) for 4·8 arteries or veins per lobe. The linear relationship of all ~ vs their respective Do was plotted (0/00 = 1 + oP) to estimate distensibility. RESULTS: In small arteries, a determined by linear regression was 1.5 ± 0.1% per mmHg as previously described in larger arteries. a estimated in the same way in small veins was significantly lower at 0.9 ± 0.1% per mmHg (p \u3c 0.05). However, the X-ray images suggested that venous diameter increased more at lower than higher pressures. a estimated over the 3-9 mmHg pressure range was 1.4 ± 0.23% per mmHg. while over the 12-21 mmHg pressure range ~ was significantly lower at 0.9% ± 0.13%. CONCLUSIONS: Distensibility of the entire arterial tree over a wide range of pressures seems well described by a single, diameter independent parameter. In contrast, distensibility of small veins appears to be higher at low versus high pressures. Future studies must further examine distensibility of large and small veins at various pressures and relate the findings to pulmonary vascular hemodynamics

2008 Inter-laboratory Comparison Study of a Reference Material for Nutrients in Seawater

Autoclaved natural seawater collected in the North Pacific Ocean was used as a reference material for nutrients in seawater (RMNS) during an inter-laboratory comparison (I/C) study conducted in 2008. This study was a follow-up to previous studies conducted in 2003 and 2006. A set of six samples was distributed to each of 58 laboratories in 15 countries around the globe, and results were returned by 54 of those laboratories (15 countries). The homogeneities of samples used in the 2008 I/C study, based on analyses for three determinants, were improved compared to those of samples used in the 2003 and 2006 I/C studies. Results of these I/C studies indicate that most of the participating laboratories have an analytical technique for nutrients that is sufficient to provide data of high comparability. The differences between reported concentrations from the same laboratories in the 2006 and 2008 I/C studies for the same batch of RMNS indicate that most of the laboratories have been maintaining internal comparability for two years. Thus, with the current high level of performance in the participating laboratories, the use of a common reference material and the adaptation of an internationally accepted nutrient scale system would increase comparability among laboratories worldwide, and the use of a certified reference material would establish traceability. In the 2008 I/C study we observed a problem of non-linearity of the instruments of the participating laboratories similar to that observed among the laboratories in the 2006 I/C study. This problem of non-linearity should be investigated and discussed to improve comparability for the full range of nutrient concentrations. For silicate comparability in particular, we see relatively larger consensus standard deviations than those for nitrate and phosphate