Search

We designed and generated pulmonary imaging biomarker pipelines to facilitate high-throughput research and point-of-care use in patients with chronic lung disease. Image processing modules and algorithm pipelines were embedded within a graphical user interface (based on the .NET framework) for pulmonary magnetic resonance imaging (MRI) and x-ray computed-tomography (CT) datasets. The software pipelines were generated using C++ and included: (1) inhaled He3/Xe129 MRI ventilation and apparent diffusion coefficients, (2) CT-MRI coregistration for lobar and segmental ventilation and perfusion measurements, (3) ultrashort echo-time H1 MRI proton density measurements, (4) free-breathing Fourier-decomposition H1 MRI ventilation/perfusion and free-breathing H1 MRI specific ventilation, (5) multivolume CT and MRI parametric response maps, and (6) MRI and CT texture analysis and radiomics. The image analysis framework was implemented on a desktop workstation/tablet to generate biomarkers of regional lung structure and function related to ventilation, perfusion, lung tissue texture, and integrity as well as multiparametric measures of gas trapping and airspace enlargement. All biomarkers were generated within 10 min with measurement reproducibility consistent with clinical and research requirements. The resultant pulmonary imaging biomarker pipeline provides real-time and automated lung imaging measurements for point-of-care and high-throughput research.

Multi-b diffusion-weighted hyperpolarized gas MRI measures pulmonary airspace enlargement using apparent diffusion coefficients (ADC) and mean linear intercepts (Lm). Rapid single-breath acquisitions may facilitate clinical translation, and, hence, we aimed to develop single-breath three-dimensional multi-b diffusion-weighted 129Xe MRI using k-space undersampling. We evaluated multi-b (0, 12, 20, 30 s/cm2) diffusion-weighted 129Xe ADC/morphometry estimates using a fully sampled and retrospectively undersampled k-space with two acceleration-factors (AF = 2 and 3) in never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD) or alpha-one anti-trypsin deficiency (AATD). For the three sampling cases, mean ADC/Lm values were not significantly different (all p > 0.5); ADC/Lm values were significantly different for the COPD subgroup (0.08 cm2s−1/580 µm, AF = 3; all p < 0.001) as compared to never-smokers (0.05 cm2s−1/300 µm, AF = 3). For never-smokers, mean differences of 7%/7% and 10%/7% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and Lm values, respectively. For the COPD subgroup, mean differences of 3%/4% and 11%/10% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and Lm, respectively. There was no relationship between acceleration factor with ADC or Lm (p = 0.9); voxel-wise ADC/Lm measured using AF = 2 and AF = 3 were significantly and strongly related to fully-sampled values (all p < 0.0001). Multi-b diffusion-weighted 129Xe MRI is feasible using two different acceleration methods to measure pulmonary airspace enlargement using Lm and ADC in COPD participants and never-smokers. [ABSTRACT FROM AUTHOR]

Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia. Am J Physiol Lung Cell Mol Physiol 286: L1260-L1267, 2004. First published February 6, 2004; 10.1152/ajplung.00273.2003.--Recently, we demonstrated that pulmonary CYP2J4 content, a prominent source of EETs and HETEs formation in rat lungs, is reduced in pneumonia. Therefore, the purpose of this study was to determine the role of iNOS-derived NO in reduced pulmonary CYP2J4 protein content and decreased CYP metabolites in pneumonia. Rats were randomized to control, control plus 1400W (iNOS inhibitor), pneumonia, and pneumonia plus 1400W groups. Pseudomonas organisms were injected into lungs of pneumonia rats. At 40 h after surgery, rats were treated with either saline or 1400W for 4 h before death. Venous plasma samples were obtained for measuring nitrites/nitrates (NOx). There was no significant effect of 1400W on blood pressure measured in control or pneumonia rats, whereas 1400W reduced the elevated plasma NOx levels in pneumonia rats by half. CYP primary metabolites of AA formed at significantly lower rates in pulmonary microsomes from pneumonia rats compared with control rats. Treatment of pneumonia rats with 1400W resulted in a significant increase in the rate of formation of pulmonary EETs and to-terminal HETEs compared with untreated pneumonia rats. The reduction in CYP2J4 protein content in pneumonia lung microsomes was also partially prevented by 1400W. Therefore, excess NO from iNOS decreases the pulmonary production of EETs and [omega]-HETEs in acute pneumonia. Inhibition of iNOS restores CYP2J4 protein content and CYP activity in acute pneumonia, indicating an important NOCYP interaction in pulmonary responses to infection. We speculate CYP2J4 and its AA metabolites are involved in the modulation of pulmonary function in health and disease. inflammation; CYP2J4 protein content; CYP450 activity assays; epoxyeicosatrienoic acids and to-terminal hydroxyeicosatetraenoic acids; 1400W

Yaghi, Asma, J. Alyce Bradbury, Darryl C. Zeldin, Sanjay Mehta, John R. Bend, and David G. McCormack. Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia. Am J Physiol Lung Cell Mol Physiol 285: L1099-L1105, 2003. First published July 25, 2003; 10.1152/ajplung.00039.2003.--We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later (44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands (51-52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats. cytochrome P-450; inflammation; Western blotting; cytochrome P-2J4 and cytochrome P-4A protein content; peptide antibodies

Positive-pressure ventilation (PPV) applied through a face mask does not appear to benefit critically ill patients who develop respiratory failure after they are taken off a ventilator. This was the conclusion of a study of 81 patients who were treated with PPV or oxygen therapy after they developed respiratory failure within two days after they were taken off a ventilator., Context Noninvasive positive-pressure ventilation (NPPV) has been demonstrated to be effective in preventing the need for endotracheal intubation in some patients who present with acute respiratory failure. It is also used for patients who develop acute respiratory distress after extubation, but there are no randomized controlled trials that address its effectiveness in this population. Objective To determine the effectiveness of NPPV compared with standard medical therapy in preventing the need for endotracheal reintubation in high-risk patients who develop respiratory distress during the first 48 hours after extubation. Design Randomized, controlled, unblinded study with concealed allocation conducted between August 1,1996 and October 31, 1999. Setting An intensive care unit (ICU) in an academic, tertiary care hospital in Ontario. Patients Eighty-one patients with a history of cardiac or respiratory disease or who initially required ventilatory support for more than 2 days and who developed respiratory distress within 48 hours of extubation. Interventions Patients were randomly assigned to receive standard medical therapy alone (supplemental oxygen to maintain oxygen saturation by pulse oximetry [greater than or equal to]95%; n=42) or NPPV by face mask plus standard medical therapy (n=39). Main Outcome Measures Rates of reintubation, duration of mechanical ventilation, lengths of ICU and hospital stay, and hospital mortality. Results Comparing the NPPV group with the standard-therapy group, there was no difference in the rate of reintubation (72% vs 69%; relative risk, 1.04; 95% confidence interval, 0.78-1.38) or hospital mortality (31% for both groups; relative risk, 0.99; 95% confidence interval, 0.52-1.91). Similarly, no difference was found in duration of mechanical ventilation or length of ICU or hospital stay. Conclusions The addition of NPPV to standard medical therapy does not improve outcome in heterogeneous groups of patients who develop respiratory distress during the first 48 hours after extubation.