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. We measured elastance and hysteresis; pulmonary IL-6, IL-1ß, and MIP-2 (macrophage inflammatory protein 2); wet-to-dry ratio; and blood gases. Survival was greater in the protective group (60%) than in the injurious group (25%). Nonsurvivors showed increased pulmonary cytokines, particularly in the injurious group, with the increase of elastance reflecting IL-6 concentration. Survivors instead showed only modest increases of cytokines, independent of Vt and unrelated to the increase of elastance. No single lung strain threshold could discriminate survivors from nonsurvivors. Hysteresis increased faster in the protective group, but, contrary to our hypothesis, its change was inversely related to the concentration of cytokines. In this model, significant mortality associated with pulmonary inflammation occurred even for strain values as low as about 0.8. Low Vt improved survival. The accompanying increase of hysteresis was not associated with greater inflammation.

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. The authors aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS and to assess gene expression in differentially activated regions. METHODS: The authors produced ARDS in sheep with intravenous lipopolysaccharide (10 ng ⋅ kg ⋅ h) and mechanical ventilation for 20 h. Using positron emission tomography, the authors assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with NN-saline, and aeration using transmission scans. Species-specific microarray technology was used to assess regional gene expression. RESULTS: Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histologic injury, suggesting its predictive value for severity of disease progression. Local time courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than nondependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. CONCLUSIONS: Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets.

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. Secondary measurements included checklist usage and clinician satisfaction. RESULTS: Sixty-nine handoffs were observed (39 with and 30 without the checklist). Significant improvements in the frequency of information relay occurred with checklist use, most notably related to administration of vasopressors and antiemetics (85% vs 44%, P = 0.008; 46% vs 15%, P = 0.015, respectively); estimated blood loss and urine output (85% vs 57%, P = 0.014; 85% vs 52%, P = 0.006, respectively); communication about potential areas of concern (92% vs 57%, P = 0.001), postoperative planning (92% vs 43%, P < 0.001), and introduction of the relieving anesthesiologist to the operating team (51% vs 3%, P < 0.001). When queried after the handoff, relieving anesthesiologists more frequently knew the antibiotic (97% vs 75%, P = 0.020), muscle relaxant (97% vs 63%, P = 0.003), and amount of fluid administered (97% vs 72%, P = 0.008) when the checklist was used. Voluntary use of the checklist occurred in 60% of the handoffs by the end of the observation period (99% control limits: 58%-75%.). Clinicians who reported using the checklist in at least two-thirds of their handoffs reported higher satisfaction with quality of communication at handoff (P = 0.003). CONCLUSIONS: An electronic checklist improved relay and retention of critical patient information and clinician communication at intraoperative handoff of care.

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. We examined PBF in an experimental model at a later stage (2 hours after injury). METHODS: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. RESULTS: CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). CONCLUSIONS: The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

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. DESIGN: Interventional animal study. SETTING: Experimental laboratory and PET facility. SUBJECTS: Eighteen 2- to 4-month-old sheep. INTERVENTIONS: Three groups of sheep (n = 6) were mechanically ventilated to the same plateau pressure (30-32 cm H2O) with high-strain (VT = 18.2 ± 6.5 mL/kg, positive end-expiratory pressure = 0), high-strain plus IV lipopolysaccharide (VT = 18.4 ± 4.2 mL/kg, positive end-expiratory pressure = 0), or low-strain plus lipopolysaccharide (VT = 8.1 ± 0.2 mL/kg, positive end-expiratory pressure = 17 ± 3 cm H2O). At baseline, we acquired respiratory-gated PET scans of inhaled NN to measure tidal strain from end-expiratory and end-inspiratory images in six regions of interest. After 3 hours of mechanical ventilation, dynamic [F]fluoro-2-deoxy-D-glucose scans were acquired to quantify metabolic activation, indicating local neutrophilic inflammation, in the same regions of interest. MEASUREMENTS AND MAIN RESULTS: Baseline regional tidal strain had a significant effect on [F]fluoro-2-deoxy-D-glucose net uptake rate Ki in high-strain lipopolysaccharide (p = 0.036) and on phosphorylation rate k3 in high-strain (p = 0.027) and high-strain lipopolysaccharide (p = 0.004). Lipopolysaccharide exposure increased the k3-tidal strain slope three-fold (p = 0.009), without significant lung edema. The low-strain lipopolysaccharide group showed lower baseline regional tidal strain (0.33 ± 0.17) than high-strain (1.21 ± 0.62; p < 0.001) or high-strain lipopolysaccharide (1.26 ± 0.44; p < 0.001) and lower k3 (p < 0.001) and Ki (p < 0.05) than high-strain lipopolysaccharide. CONCLUSIONS: Local inflammation develops proportionally to regional tidal strain during early lung injury. The regional inflammatory effect of strain is greatly amplified by IV lipopolysaccharide. Tidal strain enhances local [F]fluoro-2-deoxy-D-glucose uptake primarily by increasing the rate of intracellular [F]fluoro-2-deoxy-D-glucose phosphorylation.

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. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected. METHODS: In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [F]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. RESULTS: The pulmonary [F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min; P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02; P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01; P < 0 .05). CONCLUSION: Using noninvasive imaging, the authors demonstrated that increased pulmonary [F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.

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. METHODS: Six anesthetized supine sheep were ventilated with VT=8 ml/kg and positive end-expiratory pressure=0. Transmission scans were performed at 2-h intervals to assess regional aeration. Emission scans were acquired at baseline and after 16 h for the following tracers: (1) F-fluorodeoxyglucose to evaluate lung inflammation and (2) NN to calculate regional perfusion and shunt fraction. RESULTS: Gas fraction decreased from baseline to 16 h in dorsal (0.31±0.13 to 0.14±0.12, P<0.01), but not in ventral regions (0.61±0.03 to 0.63±0.07, P=nonsignificant), with time constants of 1.5-44.6 h. Although the vertical distribution of relative perfusion did not change from baseline to 16 h, shunt increased in dorsal regions (0.34±0.23 to 0.63±0.35, P<0.01). The average pulmonary net F-fluorodeoxyglucose uptake rate in six regions of interest along the ventral-dorsal direction increased from 3.4±1.4 at baseline to 4.1±1.5 10(-3)/min after 16 h (P<0.01), and the corresponding average regions of interest F-fluorodeoxyglucose phosphorylation rate increased from 2.0±0.2 to 2.5±0.2 10(-2)/min (P<0.01). CONCLUSIONS: When normal lungs are mechanically ventilated without positive end-expiratory pressure, loss of aeration occurs continuously for several hours and is preferentially localized to dorsal regions. Progressive lung derecruitment was associated with increased regional shunt, implying an insufficient hypoxic pulmonary vasoconstriction. The increased pulmonary net uptake and phosphorylation rates of F-fluorodeoxyglucose suggest an incipient inflammation in these initially normal lungs.

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. METHODS: Anesthetized sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either injurious or protective mechanical ventilation (n = 6 per group). We used positron emission tomography to obtain images of regional perfusion and shunting with infused ¹³N[nitrogen]-saline and images of neutrophilic inflammation with ¹8F-fluorodeoxyglucose (¹8F-FDG). The Sokoloff model was used to quantify ¹8F-FDG uptake (Ki), as well as its components: the phosphorylation rate (k3, a surrogate of hexokinase activity) and the distribution volume of ¹8F-FDG (Fe) as a fraction of lung volume (Ki = Fe × k3). Regional gas fractions (fgas) were assessed by examining transmission scans. RESULTS: Before endotoxin administration, protective (vs. injurious) ventilation was associated with a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2) (351 ± 117 vs. 255 ± 74 mmHg; P < 0.01) and higher whole-lung fgas (0.71 ± 0.12 vs. 0.48 ± 0.08; P = 0.004), as well as, in dependent regions, lower shunt fractions. Following 2 h of endotoxemia, PaO2/FiO2 ratios decreased in both groups, but more so with injurious ventilation, which also increased the shunt fraction in dependent lung. Protective ventilation resulted in less nonaerated lung (20-fold; P < 0.01) and more normally aerated lung (14-fold; P < 0.01). Ki was lower during protective (vs. injurious) ventilation, especially in dependent lung regions (0.0075 ± 0.0043/min vs. 0.0157 ± 0.0072/min; P < 0.01). ¹8F-FDG phosphorylation rate (k3) was twofold higher with injurious ventilation and accounted for most of the between-group difference in Ki. Dependent regions of the protective ventilation group exhibited lower k3 values per neutrophil than those in the injurious ventilation group (P = 0.01). In contrast, Fe was not affected by ventilation strategy (P = 0.52). Lung neutrophil counts were not different between groups, even when regional inflation was accounted for. CONCLUSIONS: During systemic endotoxemia, protective ventilation may reduce the magnitude and heterogeneity of pulmonary inflammatory cell metabolic activity in early lung injury and may improve gas exchange through its effects predominantly in dependent lung regions. Such effects are likely related to a reduction in the metabolic activity, but not in the number, of lung-infiltrating neutrophils.

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-[18F]fluoro-2-deoxy-D-glucose ([18F]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. H2 15O and radiolabeled plasma proteins are inert molecules with the same physical characteristics as their nonradioactive counterparts and are used to measure edema and vascular permeability. Tagged enzyme or receptor inhibitors are used to probe expression of these targets induced by inflammatory stimuli. Lastly, cell-specific tracers are being developed to differentiate the cell types that contribute to the inflammatory response. Taken together, these methods cast PET imaging as a versatile and quantitative tool to measure inflammation in vivo noninvasively during acute and ventilator-induced lung injury.

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. METHODS: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [(18)F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. MEASUREMENTS AND MAIN RESULTS: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H(2)O, and with regional Vt normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. CONCLUSIONS: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional Vt normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity.

Positron emission tomography: a tool for better understanding of ventilator-induced and acute lung injury.

PURPOSE OF REVIEW: PET has recently gained traction among several groups of investigators as an imaging tool to study lung pathophysiology in vivo noninvasively on a regional basis. This review aims to present the major findings of PET studies on acute lung injury (ALI) and ventilator-induced lung injury (VILI) with a perspective relevant to the physiologist-intensivist. RECENT FINDINGS: Using various tracers, PET has been used to investigate the relationship between the distributions of pulmonary perfusion, ventilation and aeration, and the effect of positive end-expiratory pressure, recruitment maneuvers, prone positioning, and endotoxin on these distributions in ALI. More recently, PET with 2-[18F]fluoro-2-deoxy-D-glucose has been used to measure regional neutrophil metabolic activation in ALI and VILI. Because gas exchange impairment and inflammation are two hallmarks of ALI and VILI, these studies have provided significant insights into the pathophysiology of these conditions. SUMMARY: PET is a versatile imaging tool for physiologic investigation. By imaging the regional effects of interventions commonly performed in critically ill patients with ALI, PET has improved our understanding of the mechanism by which such interventions can exert their positive or negative effects as well as of the pathophysiology of ALI and VILI.

Self-organized patchiness in asthma as a prelude to catastrophic shifts.

Asthma is a common disease affecting an increasing number of children throughout the world. In asthma, pulmonary airways narrow in response to contraction of surrounding smooth muscle. The precise nature of functional changes during an acute asthma attack is unclear. The tree structure of the pulmonary airways has been linked to complex behaviour in sudden airway narrowing and avalanche-like reopening. Here we present experimental evidence that bronchoconstriction leads to patchiness in lung ventilation, as well as a computational model that provides interpretation of the experimental data. Using positron emission tomography, we observe that bronchoconstricted asthmatics develop regions of poorly ventilated lung. Using the computational model we show that, even for uniform smooth muscle activation of a symmetric bronchial tree, the presence of minimal heterogeneity breaks the symmetry and leads to large clusters of poorly ventilated lung units. These clusters are generated by interaction of short- and long-range feedback mechanisms, which lead to catastrophic shifts similar to those linked to self-organized patchiness in nature. This work might have implications for the treatment of asthma, and might provide a model for studying diseases of other distributed organs.

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. Taken together, these advances portray multimodality imaging as the next frontier to both advance knowledge of the pathophysiology of these conditions and to tailor treatment to the individual patient's condition.

Mild endotoxemia during mechanical ventilation produces spatially heterogeneous pulmonary neutrophilic inflammation in sheep.

BACKGROUND: There is limited information on the regional inflammatory effects of mechanical ventilation and endotoxemia on the production of acute lung injury. Measurement of F-fluorodeoxyglucose (F-FDG) uptake with positron emission tomography allows for the regional, in vivo and noninvasive, assessment of neutrophilic inflammation. The authors tested whether mild endotoxemia combined with large tidal volume mechanical ventilation bounded by pressures within clinically acceptable limits could yield measurable and anatomically localized neutrophilic inflammation. METHODS: Sheep were mechanically ventilated with plateau pressures = 30-32 cm H2O and positive end-expiratory pressure = 0 for 2 h. Six sheep received intravenous endotoxin (10 ng x kg x min), whereas six did not (controls), in sequentially performed studies. The authors imaged with positron emission tomography the intrapulmonary kinetics of infused N-nitrogen and F-FDG to compute regional perfusion and F-FDG uptake. Transmission scans were used to assess aeration. RESULTS: Mean gas fraction and perfusion distribution were similar between groups. In contrast, a significant increase in F-FDG uptake was observed in all lung regions of the endotoxin group. In this group, F-FDG uptake in the middle and dorsal regions was significantly larger than that in the ventral regions. Multivariate analysis showed that the F-FDG uptake was associated with regional aeration (P < 0.01) and perfusion (P < 0.01). CONCLUSIONS: Mild short-term endotoxemia in the presence of heterogeneous lung aeration and mechanical ventilation with pressures within clinically acceptable limits produces marked spatially heterogeneous increases in pulmonary neutrophilic inflammation. The dependence of inflammation on aeration and perfusion suggests a multifactorial basis for that finding. F-FDG uptake may be a sensitive marker of pulmonary neutrophilic inflammation in the studied conditions.

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. The multi-resolution model eliminates the need to tradeoff between high-resolution and global context by using a cascade of low-resolution to high-resolution networks. Transfer learning is used to accommodate the limited number of training datasets. The model was initially pre-trained on human CT images, and subsequently fine-tuned on canine, porcine, and ovine CT images with lung injuries similar to ARDS. The multi-resolution model was compared to both high-resolution and low-resolution networks alone. The multi-resolution model outperformed both the low- and high-resolution models, achieving an overall mean Jacaard index of 0.963 ±â€¯0.025 compared to 0.919 ±â€¯0.027 and 0.950 ±â€¯0.036, respectively, for the animal dataset (N=287). The multi-resolution model achieves an overall average symmetric surface distance of 0.438 ±â€¯0.315 mm, compared to 0.971 ±â€¯0.368 mm and 0.657 ±â€¯0.519 mm for the low-resolution and high-resolution models, respectively. We conclude that the multi-resolution model produces accurate segmentations in severely injured lungs, which is attributed to the inclusion of both local and global features.

Lungs of patients with acute respiratory distress syndrome show diffuse inflammation in normally aerated regions: a [18F]-fluoro-2-deoxy-D-glucose PET/CT study.

OBJECTIVE: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [F]-fluoro-2-deoxy-D-glucose (FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with FDG. DESIGN: Prospective clinical investigation. PATIENTS: Ten patients with ALI/ARDS; four spontaneously breathing and two mechanically ventilated subjects, without known lung disease, served as controls. INTERVENTIONS: In each individual we performed an FDG PET/computed tomography of the thorax. MEASUREMENTS AND MAIN RESULTS: FDG cellular influx rate constant (Ki) was computed for the imaged lung field and for regions of interest, grouping voxels with similar density. In all patients with ALI/ARDS, Ki was higher than in controls, also after accounting for the increased lung density. Ki values differed greatly among patients, but in all patients Ki of the normally aerated regions was much higher (2- to 24-fold) than in controls. Whereas in some patients the highest Ki values corresponded to regions with the lowest aeration, in others these regions had lower Ki than normally and mildly hypoaerated regions. CONCLUSION: In patients with ALI/ARDS, undergoing mechanical ventilation since days, the metabolic activity of the lungs is markedly increased across the entire lung density spectrum. The intensity of this activation and its regional distribution, however, vary widely within and between patients.

The prone position results in smaller ventilation defects during bronchoconstriction in asthma.

The effect of body posture on regional ventilation during bronchoconstriction is unknown. In five subjects with asthma, we measured spirometry, low-frequency (0.15-Hz) lung elastance, and resistance and regional ventilation by intravenous (13)NN-saline positron emission tomography before and after nebulized methacholine. The subjects were imaged prone on 1 day and supine on another, but on both days the methacholine was delivered while prone. From the residual (13)NN after washout, ventilation defective areas were defined, and their location, volume, ventilation, and fractional gas content relative to the rest of the lung were calculated. Independent of posture, all subjects developed ventilation defective areas. Although ventilation within these areas was similarly reduced in both postures, their volume was smaller in prone than supine (25 vs. 41%, P < 0.05). The geometric center of the ventilation defective areas was gravitationally dependent relative to that of the lung in both postures. Mean lung fractional gas content was greater in the prone position before methacholine and did not increase as much as in the supine position after methacholine. In the prone position at baseline, areas that became ventilation defects had lower gas content than the rest of the lung. In both positions at baseline, there was a gradient of gas content in the vertical direction. In asthma, the size and location of ventilation defects is affected by body position and likely affected by small differences in lung expansion during bronchoconstriction.

Relation between shunt, aeration, and perfusion in experimental acute lung injury.

RATIONALE: In a pulmonary process characterized by spatially heterogeneous loss of aeration, the impairment of gas exchange is expected to depend on the regional distribution of perfusion relative to that of aeration. OBJECTIVES: To investigate how regional aeration, shunt, and perfusion are interrelated at different levels of end-expiratory pressure and how their interplay relates to global shunt fraction in acute lung injury. METHODS: Regional shunt and perfusion were assessed by imaging with positron emission tomography the pulmonary kinetics of [(13)N]nitrogen infused in saline solution in five sheep after lung lavage. The lung field was divided in six horizontal regions. MEASUREMENTS AND MAIN RESULTS: Each animal showed an inverse relation between regional shunt (Fs) and gas (Fg) fractions: Fs = -m . Fg + Fs(0). This relation was similar among animals (m = 1.25 +/- 0.14, Fs(0) = 0.75 +/- 0.15) and invariant with end-expiratory pressure, despite lack of correlation between global shunt and gas fractions and large interanimal variability in global shunt fraction. When this relation was used to estimate global shunt fraction as a perfusion-weighted average of the estimates of regional shunt fraction derived from regional gas fraction, 72% of the interanimal variability in global shunt fraction could be explained. CONCLUSIONS: Despite large interanimal variability in global shunt fraction, there was a consistent inverse relation between regional shunt and gas fractions, independent of end-expiratory pressure. Most of the interanimal variability in global shunt fraction could be explained by the combined effect of this relation and the distribution of perfusion on regional shunt, rather than by differences in global aeration.