Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker.

Background: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.

Optimization and use of near infrared imaging to guide lymph node collection in rhesus macaques (Macaca mulatta).

Background: Identification of lymph nodes (LNs) draining a specific site or in obese macaques can be challenging.

Methods: Indocyanine Green (ICG) was administered intradermal (ID), intramuscular, in the oral mucosa, or subserosal in the colon followed by Near Infrared (NIR) imaging.

Results: After optimization to maximize LN identification, intradermal ICG was successful in identifying 50-100% of the axillary/inguinal LN at a site.

Lung parenchymal and airway changes on CT imaging following allergen challenge and bronchoalveolar lavage in atopic and asthmatic subjects.

Background: Computed tomography (CT) imaging findings in the lungs in the setting of an acute allergic response and following bronchoalveolar lavage (BAL) are not well established. Our goals are to characterize the pulmonary CT findings of acute allergic response in both asthmatic and non-asthmatic subjects and, secondarily, to characterize the pulmonary imaging findings following BAL.

Methods: In this prospective observational (cohort) study, we identified atopic, asthmatic (AA) and atopic, non-asthmatic (ANA) subjects.

PET Imaging Reveals Early Pulmonary Perfusion Abnormalities in HIV Infection Similar to Smoking.

Chronic obstructive pulmonary disease (COPD) is the most common noninfectious pulmonary disease among people living with HIV, independent of smoking. However, the cause for this enhanced susceptibility remains unclear, and the effects of HIV on pulmonary perfusion and ventilation are unknown. We used PET/CT in 46 smokers and nonsmokers, 23 of whom had documented HIV infection.

Preclinical evaluation of an In/Ac theranostic targeting transformed MUC1 for triple negative breast cancer.

: Transformed MUC1 (tMUC1) is a cancer-associated antigen that is overexpressed in >90% of triple-negative breast cancers (TNBC), a highly metastatic and aggressive subtype of breast cancer. TAB004, a murine antibody targeting tMUC1, has shown efficacy for the targeted delivery of therapeutics to cancer cells. Our aim was to evaluate humanized TAB004 (hTAB004) as a potential theranostic for TNBC.

Elevation in lung volume and preventing catastrophic airway closure in asthmatics during bronchoconstriction.

Background: Asthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalation. However, because the increase in volume is also concurrent with activation of inspiratory muscles during exhalation it is unclear whether hyperinflation in broncho-constriction is a passive phenomenon or is actively controlled to avoid airway closure.

Hypoxic Pulmonary Vasoconstriction Does Not Explain All Regional Perfusion Redistribution in Asthma.

Rationale: Regional hypoventilation in bronchoconstricted patients with asthma is spatially associated with reduced perfusion, which is proposed to result from hypoxic pulmonary vasoconstriction (HPV).

Objectives: To determine the role of HPV in the regional perfusion redistribution in bronchoconstricted patients with asthma.

Methods: Eight patients with asthma completed positron emission tomographic/computed tomographic lung imaging at baseline and after bronchoconstriction, breathing either room air or 80% oxygen (80% O) on separate days.

Regional Ventilation and Aerosol Deposition with Helium-Oxygen in Bronchoconstricted Asthmatic Lungs.

Background: Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributions from subjects with asthma inhaling He-O2 as carrier gas.

Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge.

Background: Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways.

Methods: In 6 ANA subjects, bronchoalveolar lavages (BAL) were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes.

A method for mapping regional oxygen and CO2 transfer in the lung.

This paper presents a novel approach to visualizing regional lung function, through quantitative three-dimensional maps of O2 and CO2 transfer rates. These maps describe the contribution of anatomical regions to overall gas exchange and demonstrate how transfer rates of the two gas species' differ regionally. An algorithm for generating such maps is presented, and for illustration, regional gas transfer maps were generated using values of ventilation and perfusion imaged by PET/CT for a healthy subject and an asthmatic patient after bronchoprovocation.

What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study.

Background: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability.

Methods: A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs.

Analysis of three-dimensional aerosol deposition in pharmacologically relevant terms: beyond black or white ROIs.

Background: This article presents a novel methodological approach to evaluate images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or-White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider blurring effects due to limited spatial resolution or breathing motion, and do not consider uncertainty in the AR position within the PET image.

Respiratory system reactance is an independent determinant of asthma control.

The mechanisms underlying not well-controlled (NWC) asthma remain poorly understood, but accumulating evidence points to peripheral airway dysfunction as a key contributor. The present study tests whether our recently described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma control. The aim of this study was to investigate the contribution of Xrs to asthma control.

The effect of omalizumab on ventilation and perfusion in adults with allergic asthma.

Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulmonary function is unclear. One possibility is that omalizumab improves asthma symptoms through effects on the regional distributions of ventilation, perfusion, and ventilation/perfusion matching, metrics which can be assessed with Nitrogen-13-saline Position Emission Tomography (PET). Four adults with moderate to severe uncontrolled allergic asthma underwent symptom assessment, spirometry and functional pulmonary imaging with Nitrogen-13-saline PET before and after 4-5 months of treatment with omalizumab.

Peripheral lung function in patients with stable and unstable asthma.

Background: Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function.

Objective: We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma.

Dissemination bottleneck in a murine model of inhalational anthrax.

Inhalational anthrax is caused by the sporulating bacterium Bacillus anthracis. A current model for progression in mammalian hosts includes inhalation of bacterial spores, phagocytosis of spores in the nasal mucosa-associated lymphoid tissue (NALT) and lungs by macrophages and dendritic cells, trafficking of phagocytes to draining lymph nodes, germination of spores and multiplication of vegetative bacteria in the NALT and lymph nodes, and dissemination of bacteria via the bloodstream to multiple organs. In previous studies, the kinetics of infection varied greatly among mice, leading us to hypothesize the existence of a bottleneck past which very few spores (perhaps only one) progress to allow the infection to proceed.

Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma.

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e.

Nonhuman primate model of pertussis.

Pertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Despite nearly universal vaccine coverage, pertussis rates in the United States have been rising steadily over the last 20 years. Our failure to comprehend and counteract this important public health concern is due in large part to gaps in our knowledge of the disease and the mechanisms of vaccine-mediated protection.

Automated detection of the phase III slope during inert gas washout testing.

We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S(acin) and S(cond), from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A sample set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters.

The bronchodilator response of in vivo specific airway compliance in adults with asthma.

A new technique has been developed to determine in vivo airway compliance in humans that is specific to airway size and transpulmonary pressure, and can be represented as a three-dimensional surface. As yet, the ability of this technique to detect changes in specific airway compliance with disease status has not been demonstrated. The aim of this study was to assess whether this technique could determine changes in airway compliance which are thought to occur with altered smooth muscle tone in adults with asthma.

Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities.

Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens.

Outreach, engagement, and practical assistance: essential aspects of PTSD care for urban victims of violent crime.

The purpose of this article is to examine the literature on the increased risk factors of disadvantaged inner-city residents for becoming victims of violence and for developing posttraumatic stress disorder (PTSD) and barriers to accessing comprehensive mental health services. Second, the article discusses the limitations of evidence-based treatments for early intervention with urban victims of violence and provides a new model of care emphasizing outreach, engagement, and practical assistance. Finally, the article concludes with recommendations for comprehensive hospital-based urban programs in terms of practice, policy, and research.

Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea.

Rationale: Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear.

Objectives: We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a result, there is a surge in pulmonary O(2) uptake that rapidly depletes the finite alveolar O(2) store, thereby accelerating arterial O(2) desaturation.

Methods: Recurrent apneas were simulated in an experimental lamb model.