Molecular imaging of inflammation with PET in acute and ventilator-induced lung injury.

This review focuses on methods to image acute lung inflammation with Positron Emission Tomography (PET). Four approaches are discussed that differ for biologic function of the PET reporter probe, radiotracer employed, and the specific aspect of the inflammatory response that is targeted. 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) is an enzyme substrate whose uptake is used to measure the metabolic activation of inflammatory cells during acute lung injury in the noncancerous lung.

New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications.

This review focuses on the advances in the understanding of the pathophysiology of ventilator-induced and acute lung injury that have been afforded by technological development of imaging methods over the last decades. Examples of such advances include the establishment of regional lung mechanical strain as a determinant of ventilator-induced lung injury, the relationship between alveolar recruitment and overdistension, the regional vs. diffuse nature of pulmonary involvement in acute respiratory distress syndrome (ARDS), the identification of the physiological determinants of the response to recruitment interventions, and the pathophysiological significance of metabolic alterations in the acutely injured lung.

Multi-resolution convolutional neural networks for fully automated segmentation of acutely injured lungs in multiple species.

Segmentation of lungs with acute respiratory distress syndrome (ARDS) is a challenging task due to diffuse opacification in dependent regions which results in little to no contrast at the lung boundary. For segmentation of severely injured lungs, local intensity and texture information, as well as global contextual information, are important factors for consistent inclusion of intrapulmonary structures. In this study, we propose a deep learning framework which uses a novel multi-resolution convolutional neural network (ConvNet) for automated segmentation of lungs in multiple mammalian species with injury models similar to ARDS.

A Window on the Lung: Molecular Imaging as a Tool to Dissect Pathophysiologic Mechanisms of Acute Lung Disease.

In recent years, imaging has given a fundamental contribution to our understanding of the pathophysiology of acute lung diseases. Several methods have been developed based on computed tomography (CT), positron emission tomography (PET), and magnetic resonance (MR) imaging that allow regional, in vivo measurement of variables such as lung strain, alveolar size, metabolic activity of inflammatory cells, ventilation, and perfusion. Because several of these methods are noninvasive, they can be successfully translated from animal models to patients.

Relation between Respiratory Mechanics, Inflammation, and Survival in Experimental Mechanical Ventilation.

Low-tidal volume (Vt) ventilation might protect healthy lungs from volutrauma but lead to inflammation resulting from other mechanisms, namely alveolar derecruitment and the ensuing alveolar collapse and tidal reexpansion. We hypothesized that the different mechanisms of low- and high-volume injury would be reflected in different mechanical properties being associated with development of pulmonary inflammation and mortality: an increase of hysteresis, reflecting progressive alveolar derecruitment, at low Vt; an increase of elastance, as a result of overdistension, at higher Vt. Mice were allocated to "protective" (6 ml/kg) or "injurious" (15-20 ml/kg) Vt groups and ventilated for 16 hours or until death.

Lung Metabolic Activation as an Early Biomarker of Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity.

Background: Acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS.

Imaging in acute respiratory distress syndrome.

Purpose: Imaging has become increasingly important across medical specialties for diagnostic, monitoring, and investigative purposes in acute respiratory distress syndrome (ARDS).

Methods: This review addresses the use of imaging techniques for the diagnosis and management of ARDS as well as gaining knowledge about its pathogenesis and pathophysiology. The techniques described in this article are computed tomography, positron emission tomography, and two easily accessible imaging techniques available at the bedside-ultrasound and electrical impedance tomography (EIT).

Estimation of noise-free variance to measure heterogeneity.

Variance is a statistical parameter used to characterize heterogeneity or variability in data sets. However, measurements commonly include noise, as random errors superimposed to the actual value, which may substantially increase the variance compared to a noise-free data set. Our aim was to develop and validate a method to estimate noise-free spatial heterogeneity of pulmonary perfusion using dynamic positron emission tomography (PET) scans.

Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

Background: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments.

An electronic checklist improves transfer and retention of critical information at intraoperative handoff of care.

Background: Communication failures are a significant cause of preventable medical errors, and poor-quality handoffs are associated with adverse events. We developed and implemented a simple checklist to improve communication during intraoperative transfer of patient care.

Methods: A prospective observational assessment was performed to compare relay and retention of critical patient information between the outgoing and incoming anesthesiologist before and after introduction of an electronic handoff checklist.

18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.

Unlabelled: PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion.

Methods: Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H2O; plateau pressure, 30 cm H2O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS+] group; n = 6) or not (lipopolysaccharide-negative group; n = 6).

Effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep*.

Objectives: Regional tidal lung strain may trigger local inflammation during mechanical ventilation, particularly when additional inflammatory stimuli are present. However, it is unclear whether inflammation develops proportionally to tidal strain or only above a threshold. We aimed to 1) assess the relationship between regional tidal strain and local inflammation in vivo during the early stages of lung injury in lungs with regional aeration heterogeneity comparable to that of humans and 2) determine how this strain-inflammation relationship is affected by endotoxemia.

Lung [(18)F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation.

Background: Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury.

Effects of ventilation strategy on distribution of lung inflammatory cell activity.

Introduction: Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin administration.

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.

Regional lung derecruitment and inflammation during 16 hours of mechanical ventilation in supine healthy sheep.

Background: Lung derecruitment is common during general anesthesia. Mechanical ventilation with physiological tidal volumes could magnify derecruitment, and produce lung dysfunction and inflammation. The authors used positron emission tomography to study the process of derecruitment in normal lungs ventilated for 16 h and the corresponding changes in regional lung perfusion and inflammation.

Ventilation defect formation in healthy and asthma subjects is determined by lung inflation.

Background: Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion.

Modeling 18F-FDG kinetics during acute lung injury: experimental data and estimation errors.

Background: There is increasing interest in Positron Emission Tomography (PET) of 2-deoxy-2-[18F]flouro-D-glucose ((18)F-FDG) to evaluate pulmonary inflammation during acute lung injury (ALI). We assessed the effect of extra-vascular lung water on estimates of (18)F-FDG-kinetics parameters in experimental and simulated data using the Patlak and Sokoloff methods, and our recently proposed four-compartment model.

Methodology/principal Findings: Eleven sheep underwent unilateral lung lavage and 4 h mechanical ventilation.

Pulmonary pathophysiology and lung mechanics in anesthesiology: a case-based overview.

Anesthesia, surgical requirements, and patients' unique pathophysiology all combine to make the accumulated knowledge of respiratory physiology and lung mechanics vital in patient management. This article take a case-based approach to discuss how the complex interactions between anesthesia, surgery, and patient disease affect patient care with respect to pulmonary pathophysiology and clinical decision making. Two disparate scenarios are examined: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass.

Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs.

Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (13)NN with positron emission tomography to examine how specific ventilation (sV) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (Vt; 18.

18F-FDG uptake rate is a biomarker of eosinophilic inflammation and airway response in asthma.

Unlabelled: In asthma, the relationship among airway inflammation, airway hyperresponsiveness, and lung function is poorly understood. Methods to noninvasively assess these relationships in human subjects are needed. We sought to determine whether (18)F-FDG uptake rate (K(i), min(-1)) could serve as a biomarker of eosinophilic inflammation and local lung function.

Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation.

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation.

Lung regional metabolic activity and gas volume changes induced by tidal ventilation in patients with acute lung injury.

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [(18)F]fluoro-2-deoxy-D-glucose.

Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI.