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Alveolar recruitment in acute respiratory distress syndrome (ARDS) is defined as the penetration of gas into previously unventilated areas or poorly ventilated areas. Alveolar recruitment during recruitment maneuvering (RM) depends on the duration of the maneuver, the recruitable lung tissue, and the balance between the recruitment of collapsed areas and over-insufflation of the ventilated areas. Alveolar recruitment is estimated using computed tomography of the lung and, at the patient bedside, through assessment of the recruited volume using pressure-volume curves and assessing lung morphology with pulmonary ultrasound and/or impedance tomography. The scientific evidence on RM in patients with ARDS remains subject to controversy. Randomized studies on ARDS have shown no benefit or have even reflected an increase in mortality. The routine use of RM is therefore not recommended.

Intratracheal bleomycin causes pulmonary injury, inflammation and fibrosis. The characteristic patchy nature of the injury makes analysis challenging. Histological assessment of lung injury is a useful tool to evaluate damage, however quantification is not standardized. We propose a multi-factorial approach to assess morphological changes subsequent to intratracheal bleomycin mediated lung injury. Lungs were inflation fixed with paraformaldehyde, sectioned and stained with hematoxylin and eosin. Whole slide images were scanned and ten 400x images were randomly chosen throughout the tissue for further analysis. Using ImageJ software, alveolar wall width was measured, nuclei were counted and airspace was quantified. Morphological changes were identified in mice instilled with bleomycin. This combination offers a robust measure of lung morphology especially in a heterogenous injury.

Background: The identification of phenotypes based on lung morphology can be helpful to better target mechanical ventilation of individual patients with acute respiratory distress syndrome (ARDS). We aimed to assess the accuracy of lung ultrasound (LUS) methods for classification of lung morphology in critically ill ARDS patients under mechanical ventilation. Methods: This was a post hoc analysis on two prospective studies that performed LUS and chest computed tomography (CT) scanning at the same time. Expert panels from the two participating centers separately developed two LUS methods for classifying lung morphology based on LUS aeration scores from a 12-region exam (Amsterdam and Lombardy method). Moreover, a previously developed LUS method based on anterior LUS scores was tested (Piedmont method). Sensitivity and specificity of all three LUS methods was assessed in the cohort of the other center(s) by using CT as the gold standard for classification of lung morphology. Results: The Amsterdam and Lombardy cohorts consisted of 32 and 19 ARDS patients, respectively. From these patients, 23 (45%) had focal lung morphology while others had non-focal lung morphology. The Amsterdam method could classify focal lung morphology with a sensitivity of 77% and a specificity of 100%, while the Lombardy method had a sensitivity and specificity of 100 and 61%. The Piedmont method had a sensitivity and specificity of 91 and 75% when tested on both cohorts. With both the Amsterdam and Lombardy method, most patients could be classified based on the anterior regions alone. Conclusion: LUS-based methods can accurately classify lung morphology in invasively ventilated ARDS patients compared to gold standard chest CT. The anterior LUS regions showed to be the most discriminant between focal and non-focal lung morphology, although accuracy increased moderately when lateral and posterior LUS regions were integrated in the method., SCOPUS: ar.j, info:eu-repo/semantics/published

Respiration is an unconscious but essential activity for us to maintain our lives. Lungs are the organs that play the most important role of gas exchange between blood and air, referred to as external respiration. The function and morphology of the lungs are inseparable and the understanding of pulmonary morphology and microstructure is essential for the interpretation of pulmonary functional imaging fully. In this chapter, we provide radiology- and histology-based lung morphology and correlation with physiology for the understanding of pulmonary functional imaging.

Objective:To investigate the therapeutic roles of hyperbaric oxygen exposure on high-altitude pulmonary edema and to determine whether aquaporin-1 and aquaporin-5 were involved in the pathogenesis of HAPE in rats.Methods:Rats were divided into 5 groups: The control group, the HAPE group (HAPE model), the HBO group (hyperbaric oxygen exposure), the NBO group (normobaric oxygen exposure), and the NA group (normal air exposure). Western blot and real-time PCR were used to analyze the pulmonary expressions of AQP1 and AQP5. The wet-to-dry (W/D) weight ratio and the morphology of the lung were also examined.Results:The lung W/D weight ratio in the HAPE group was increased compared with the control group. The injury score in the HBO group was noticeably lower than that in the control group. The mRNA and proteins expressions of AQP1 and AQP5 were significantly downregulated in the HAPE group.Conclusions:Oxygen exposure alleviated high-altitude hypobaric hypoxia-induced lung injury in rats. Additionally, HBO therapy had significant advantage on interstitial HAPE.

Neonatal mortality in wild-type laboratory mice is an overlooked welfare and financial problem in animal facilities around the world. Causes of death are often not reported and its causes remain unknown.In this study, 324 newborn pups from two breeding colonies of healthy wildtype C57BL/6 mice underwent post-mortem analysis with special focus on obtaining proof of life after birth, evaluation of stomach contents and observation of congenital abnormalities that could compromise survival.Based on a combination of lung morphology findings, outcome of lung float test, stomach contents and brown adipose tissue colouration, 21.6% of the pups found dead were considered stillbirths. Of the livebirths, only 3.2% were observed to have milk inside the stomach, indicating successful suckling. Congenital abnormalities were diagnosed only in a small fraction of the pups analysed. These results suggest that starvation was the most common cause of death, followed by stillbirth.

Background: Preterm birth is associated with abnormal lung architecture, and a reduction in pulmonary function related to the degree of prematurity. A thorough understanding of the impact of gestational age on lung microarchitecture requires reproducible quantitative analysis of lung structure abnormalities. The objectives of this study were (1) to use quantitative histological software (ImageJ) to map morphological patterns of injury resulting from delivery of an identical ventilation strategy to the lung at varying gestational ages and (2) to identify associations between gestational age-specific morphological alterations and key functional outcomes.Method: Lung morphology was compared after 60 min of a standardized ventilation protocol (40 cm H2O sustained inflation and then volume-targeted positive pressure ventilation with positive end-expiratory pressure 8 cm H2O) in lambs at different gestations (119, 124, 128, 133, 140d) representing the spectrum of premature developmental lung states and the term lung. Age-matched controls were compared at 124 and 128d gestation. Automated and manual functions of Image J were used to measure key histological features. Correlation analysis compared morphological and functional outcomes in lambs aged ≤128 and >128d.Results: In initial studies, unventilated lung was indistinguishable at 124 and 128d. Ventilated lung from lambs aged 124d gestation exhibited increased numbers of detached epithelial cells and lung tissue compared with 128d lambs. Comparing results from saccular to alveolar development (120–140d), lambs aged ≤124d exhibited increased lung tissue, average alveolar area, and increased numbers of detached epithelial cells. Alveolar septal width was increased in lambs aged ≤128d. These findings were mirrored in the measures of gas exchange, lung mechanics, and molecular markers of lung injury. Correlation analysis confirmed the gestation-specific relationships between the histological assessments and functional measures in ventilated lambs at gestation ≤128 vs. >128d.Conclusion: Image J allowed rapid, quantitative assessment of alveolar morphology, and lung injury in the preterm lamb model. Gestational age-specific patterns of injury in response to delivery of an identical ventilation strategy were identified, with 128d being a transition point for associations between morphological alterations and functional outcomes. These results further support the need to develop individualized respiratory support approaches tailored to both the gestational age of the infant and their underlying injury response.

Background Quantifying morphologic changes is critical to our understanding of the pathophysiology of the lung. Mean linear intercept (MLI) measures are important in the assessment of clinically relevant pathology, such as emphysema. However, qualitative measures are prone to error and bias, while quantitative methods such as mean linear intercept (MLI) are manually time consuming. Furthermore, a fully automated, reliable method of assessment is nontrivial and resource-intensive. Methods We propose a semi-automated method to quantify MLI that does not require specialized computer knowledge and uses a free, open-source image-processor (Fiji). We tested the method with a computer-generated, idealized dataset, derived an MLI usage guide, and successfully applied this method to a murine model of particulate matter (PM) exposure. Fields of randomly placed, uniform-radius circles were analyzed. Optimal numbers of chords to assess based on MLI were found via receiver-operator-characteristic (ROC)-area under the curve (AUC) analysis. Intraclass correlation coefficient (ICC) measured reliability. Results We demonstrate high accuracy (AUCROC > 0.8 for MLIactual > 63.83 pixels) and excellent reliability (ICC = 0.9998, p https://med.nyu.edu/nolanlab. Conclusions Our semi-automated method is reliable, equally fast as fully automated methods, and uses free, open-source software. Additionally, we quantified the optimal number of chords that should be measured per lung field.

Pulmonary tuberculosis (TB) is still an important cause of death worldwide, even after being almost eradicated 40 years ago. Early identification of TB in computed tomography (CT) scans can influence therapeutical decisions, thus improving patient outcome. In this paper, a graph model of the lungs is proposed for the classification of TB types using local texture features in thorax CT scans of TB patients. Based on lung morphology, an automatic patient-specific lung field parcellation was initially computed. Local visual features were then extracted from each region and were used to build a personalized lung graph model. A new graph-based patient descriptor enables comparisons between lung graphs with a different number of nodes and edges, encoding the distribution of several node measures from graph theory. The proposed model was trained and tested on a public dataset of 1,513 CT scans of 994 TB patients. The evaluation was performed on data from a scientific challenge together with 39 participant algorithms, obtaining the best unweighted Cohen kappa coefficient of 0.24 in a 5-class setup with 505 test CTs. Even though each lung graph has a unique structure, the proposed method was able to identify key texture changes associated with the different manifestations of TB.

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4–1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology., Video abstract

The aging lung is associated with increased susceptibility to chronic inflammatory diseases such as chronic obstructive pulmonary disease where females have been reported to be more susceptible than males. The changes in reproductive hormones due to aging may directly or indirectly affect lung structure and function and little is known on the mechanism of these changes. Twenty female rhesus macaques were divided into four groups. Ovariectomy (OVX) was performed on eight animals with three receiving estrogen/progesterone therapy (HRT) and five animals given implants containing vehicle. The remaining 12 animals represented control groups of ages 10-14 years (n = 6) and ages 20-24 (n = 6). A design-based stereological method was employed to estimate the number of alveoli in the right middle lung lobe along with hormone analysis for possible correlation. A significant decrease was found in the number of alveoli in the vehicle OVX animals compared to intact younger adult females (P

Lung ultrasound is commonly used to evaluate lung morphology in patients with acute respiratory distress syndrome. Aim of this study was to determine lung ultrasound reliability in assessing lung aeration and positive end-expiratory pressure-induced recruitment compared with CT.Randomized crossover study.University hospital ICU.Twenty sedated paralyzed acute respiratory distress syndrome patients: age 56 years (43-72 yr), body mass index 25 kg/m (22-27 kg/m), and PaO2/FIO2 160 (113-218).Lung CT and lung ultrasound examination were performed at positive end-expiratory pressure 5 and 15 cm H2O.Global and regional Lung Ultrasound scores were compared with CT quantitative analysis. Lung recruitment (i.e., decrease in not aerated tissue as assessed with CT) was compared with global Lung Ultrasound score variations. Global Lung Ultrasound score was strongly associated with average lung tissue density at positive end-expiratory pressure 5 (R = 0.78; p0.0001) and positive end-expiratory pressure 15 (R = 0.62; p0.0001). Regional Lung Ultrasound score strongly correlated with tissue density at positive end-expiratory pressure 5 (rs = 0.79; p0.0001) and positive end-expiratory pressure 15 (rs = 0.79; p0.0001). Each step increase of regional Lung Ultrasound score was associated with significant increase of tissue density (p0.005). A substantial agreement was found between regional Lung Ultrasound score and CT classification at positive end-expiratory pressure 5 (k = 0.69 [0.63-0.75]) and at positive end-expiratory pressure 15 (k = 0.70 [0.64-0.75]). At positive end-expiratory pressure 15, both global Lung Ultrasound score (22 [16-27] vs 26 [21-29]; p0.0001) and not aerated tissue (42% [25-57%] vs 52% [39-67%]; p0.0001) decreased. However, Lung Ultrasound score variations were not associated with lung recruitment (R = 0.01; p = 0.67).Lung Ultrasound score is a valid tool to assess regional and global lung aeration. Global Lung Ultrasound score variations should not be used for bedside assessment of positive end-expiratory pressure-induced recruitment.

Background High frequency percussive ventilation (HFPV) combines diffusive (high frequency mini-bursts) and convective ventilation patterns. Benefits include enhanced oxygenation and hemodynamics, and alveolar recruitment, while providing hypothetic lung-protective ventilation. No study has investigated HFPV-induced changes in lung aeration in patients with early acute respiratory distress syndrome (ARDS). Methods Eight patients with early non-focal ARDS were enrolled and five swine with early non-focal ARDS were studied in prospective computed tomography (CT) scan and animal studies, in a university-hospital tertiary ICU and an animal laboratory. Patients were optimized under conventional “open-lung” ventilation. Lung CT was performed using an end-expiratory hold (Conv) to assess lung morphology. HFPV was applied for 1 hour to all patients before new CT scans were performed with end-expiratory (HFPV EE) and end-inspiratory (HFPV EI) holds. Lung volumes were determined after software analysis. At specified time points, blood gases and hemodynamic data were collected. Recruitment was defined as a change in non-aerated lung volumes between Conv, HFPV EE and HFPV EI. The main objective was to verify whether HFPV increases alveolar recruitment without lung hyperinflation. Correlation between pleural, upper airways and HFPV-derived pressures was assessed in an ARDS swine-based model. Results One-hour HFPV significantly improved oxygenation and hemodynamics. Lung recruitment significantly rose by 12.0% (8.5–18.0%), P = 0.05 (Conv-HFPV EE) and 12.5% (9.3–16.8%), P = 0.003 (Conv-HFPV EI). Hyperinflation tended to increase by 2.0% (0.5–2.5%), P = 0.89 (Conv-HFPV EE) and 3.0% (2.5–4.0%), P = 0.27 (Conv-HFPV EI). HFPV hyperinflation correlated with hyperinflated and normally-aerated lung volumes at baseline: r = 0.79, P = 0.05 and r = 0.79, P = 0.05, respectively (Conv-HFPV EE); and only hyperinflated lung volumes at baseline: r = 0.88, P = 0.01 (Conv-HFPV EI). HFPV CT-determined tidal volumes reached 5.7 (1.1–8.1) mL.kg-1 of ideal body weight (IBW). Correlations between pleural and HFPV-monitored pressures were acceptable and end-inspiratory pleural pressures remained below 25cmH20. Conclusions HFPV improves alveolar recruitment, gas exchanges and hemodynamics of patients with early non-focal ARDS without relevant hyperinflation. HFPV-derived pressures correlate with corresponding pleural or upper airways pressures. Trial registration ClinicalTrials.gov, NCT02510105. Registered on 1 June 2015. The trial was retrospectively registered. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1924-6) contains supplementary material, which is available to authorized users.

Background. Despite the large number of studies devoted to the study of the functional state of the cardiovascular and respiratory systems after operations on the lungs, there are still many issues regarding the mechanisms of hemodynamic disorders in the postoperative period. It stipulates considerable difficulties in the treatment and prevention of functional disorders of respiration and circulation. Objective. The aim of this study is to determine the central hemodynamics parameters depending on the condition of ventilate lung function in thoracic oncology patients during the postoperative period and to determine the morphological features of the lungs that developed under the influence of intraoperative administration of refortan and perftoran. Methods. The condition of the central heamodynamic and morphological features of the lungs at patients with lung cancers with different level of the ventilating respiratory insufficiency in the early postoperative period after application of 3 and 1,5 ml/kg of perftoran and after traditional refortan (5 ml/kg) infusion-transfusion therapy were determined. Results and conclusion. It was proved that perftoran is much more effective than pefortan. The restoration of the normodynamic type of heamodynamic after infusion of perftoran (1,5 ml/kg) to patients with the an initial level of the ventilating respiratory insufficiency of I and II degree is observed during 1st postoperative week. The restoration of the normodynamic type of heamodynamic at to patients with the initial level of the ventilating respiratory insufficiency of III degree in postoperative period is reached by using perftoran in a dose 3 ml/kg. In the dead after pneumonectomy with intraoperative administration of perftoran there is increasing of synthetic activity of alveolocyte type II along with compensatory microcirculatory changes. Citation: Tverdokhlib IV, Novikov SP. [Сentral heamodynamic сondition and morphological characteristics of lungs at patients with lung cancer depending on components of the infusion-transfusion therapy]. Morphologia. 2015;9(4):76-84. Ukrainian.

Objective To evaluate the changes in lung morphology in subjects with adolescent idiopathic scoliosis (AIS) following posterior spinal fusion surgery. Methods From April 2009 to August 2013, 30 AIS patients (nine males and 21 females) were enrolled in this study. All scans were obtained with the patient in the supine position and the breath held in deep inspiration and performed both before and after surgery. Syngo software was used to manage the computed tomography scan imaging and to calculate the lung volume, lung height and pulmonary cross-sectional area in the apical vertebral plane. Results Left lung, right lung and total lung volumes and convex to concave lung volume ratio did not change significantly after corrective surgery. There was a statistically significant improvement in left lung and right lung heights after posterior spinal fusion surgery. However, the pulmonary cross-sectional area in the apical vertebrae plane was smaller postoperatively than preoperatively. Conclusions This study showed that lung height in AIS patients increased significantly immediately postoperatively whereas lung volume did not change significantly. Thoracic symmetry was improved postoperatively in these patients.

Purpose: The semi-quantitative Brody score measures the severity of cystic fibrosis (CF)-related lung disease. We investigated the short-term (28 – 60 days) and long-term (2 – 7 years) intra- and inter-observer reproducibility of the Brody score in low-dose multidetector row computed tomography examinations performed in inspiration (LDCTs) of adult CF patients. Materials and Methods: Composite Brody scores and respective underlying bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity, and hyperinflation subscores were evaluated twice (time interval, 1 – 84 months) by each of 3 independent radiologists (1 – 20 years of professional diagnostic radiology experience) in LDCTs (4 – 64 rows, 120 KVp, 10 – 15 mAs/slice, CTDIw approx. 1.0 mGy, effective dose approx. 0.5 mSv) of 15 adult patients with CF-related lung disease (8 female, 7 male, age, 18 – 50 years, mean, 33 years). Results: The average reproducibility of the Brody score was within +/–7 % (range, 2 – 30 %) between radiologists, and +/–6 % (3 – 12 %) within radiologists (short-term, 28 – 60 days, 4 %, 0 – 12 %, long-term, 2 – 7 years, 12 %, 1 – 36 %). For the different subscores, the reproducibility was within +/–25 % (15 – 41 %) between radiologists and +/–23 % (12 – 46 %) within radiologists. Conclusion: The Brody score shows high average inter-observer reproducibility in LDCTs of adult CF patients. The Brody score also demonstrates high average intra-observer reproducibility if subsequent assessments are made within 28 – 61 days. With time intervals of 2 – 7 years between subsequent evaluations, however, intra-observer reproducibility decreases. Respective subscores each demonstrate lower intra- and inter-observer reproducibility than does the composite Brody score. Citation Format

Background The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that encompasses multiple phenotypes, e.g. with regards to lung morphology as assessed by computed tomography (CT). Focal or non-focal lung morphology may influence the response to positive end-expiratory pressure (PEEP), recruitment manoeuvres and prone position. Lung morphology has been hypothesized to be associated with alveolar fluid clearance (AFC), thus explaining various responses to such therapeutic interventions; however, this hypothesis has not been specifically studied in humans. Methods We measured net AFC rates in 30 patients with ARDS as a secondary data analysis of a prospective single-centre study. Net AFC rates were compared between patients with focal ARDS and those with non-focal ARDS, as assessed by lung CT-scans. Results Net AFC rates were significantly lower in patients with non-focal ARDS (n = 23; median [interquartile range], 1.5 [0–5.5] %/h) as compared to those with focal ARDS (n = 7; 10.3 [4.5–15] %/h) (P = 0.01). The area under the receiver-operating characteristic curve when net AFC rates were used to differentiate the presence from absence of non-focal ARDS was 0.93 (95% confidence interval, 0.81–1). Tidal volumes and PEEP levels differed between focal and non-focal ARDS patients, but there was no difference in arterial oxygenation or in alveolar-capillary permeability. Conclusions Non-focal lung morphology may be characterized by a functional endotype consistent with marked AFC impairment. Despite study limitations and the need for validating studies in larger cohorts, such novel findings may reinforce our understanding of the association between ARDS phenotypes and therapeutic responses.

To evaluate the utility of 1.5-T noncontrast magnetic resonance (MR) imaging of the lung parenchyma and to compare it with computed tomography (CT) in the assessment of interstitial lung disease and other morphologic lung abnormalities.Institutional review board approval was obtained for retrospective image analysis. A total of 236 patients who underwent MR imaging and CT as part of their assessment for suspected pulmonary hypertension were included in this study. Lung MR imaging was performed with a 1.5-T system as a stack of axial two-dimensional balanced steady-state free precession (bSSFP) acquisitions. Two radiologists independently evaluated CT and MR images for various morphologic abnormalities, such as pulmonary fibrosis, pleural and mediastinal disease, solid lesions, bronchial disease, and emphysema. Κ statistics were used to measure interobserver agreement.Sensitivity and specificity of MR imaging in the identification of pulmonary fibrosis (n = 46) were 89% (95% confidence interval: 77%, 96%) and 91% (95% confidence interval: 76%, 98%), respectively, when compared with CT. In comparison to CT, MR imaging depicted 75% of ground-glass opacities. Nine of the 12 noncalcified nodules were identified on MR images. Lung nodules (75%, κ = 0.71) and effusions (100%, κ = 0.89) were also well visualized on MR images. MR imaging was however less effective in depicting emphysema (16%, κ = 0.60) and minor fibrosis (67%, κ = 0.79).This study shows bSSFP MR imaging is inferior to CT in imaging parenchymal lung disease; however, this study does demonstrate for the first time a potential role for the bSSFP sequence as an alternative radiation-free noncontrast imaging modality for use in patients with pulmonary fibrosis.

The emerging role of quantitative computed tomography (CT) in the evaluation of pulmonary emphysema is reviewed. CT is primarily used in the clinical setting to assess lung morphology visually. Increasingly treatments are being developed to treat patients with emphysema that require accurate quantitation of extent and distribution of the process. In addition, functional assessment can be made by inference of detailed anatomic correlates and by direct measurement of regional function using dynamic scan protocols. The aim of this review is to summarize the current role of imaging in the assessment of patients with emphysema. The review will focus on CT for the evaluation of morphologic abnormalities and on the potential role for the evaluation of functional abnormalities and treatment targeting.

Rationale: Chronic elevation of pulmonary microvascular pressure in chronic heart failure results in compensatory changes in the lung that reduce alveolar fluid filtration and protect against pulmonary microvascular rupture. Objectives: To determine whether these compensatory responses may have maladaptive effects on lung function. Methods: Six weeks after myocardial infarction (chronic heart failure model) rat lung composition, both gross and histologic; air and saline mechanics; surfactant production; and immunological mediators were examined. Measurements and Main Results: An increase in dry lung weight, due to increased insoluble protein, lipid and cellular infiltrate, without pulmonary edema was found. Despite this, both forced impedance and air pressure–volume mechanics were normal. However, there was increased tissue stiffness in the absence of surface tension (saline pressure–volume curve) with a concurrent increase in both surfactant content and alveolar type II cell numbers, suggesting a novel homeostatic phenomenon. Conclusions: These studies suggest a compensatory reduction in pulmonary surface tension that attenuates the effect of lung parenchymal remodeling on lung mechanics, hence work of breathing. Refereed/Peer-reviewed

Resumo: O tabaco está implicado na carcinogénese multiorgâni-ca, com identificação de mais de cinquenta substâncias carcinogénicas que induzem mutações, alterando o ciclo celular, a resposta auto-imune e a regulação endócrina. É um dos nove factores identificados responsáveis por um terço de mortes por neoplasias malignas juntamente com erros dietéticos, obesidade, sedentarismo, consumo de álcool, promiscuidade sexual, toxicodependência e po-luição ambiental geral e limitada. Está implicado nas doenças cardiovasculares que representam a primeira causa de morte nos países civilizados e, no aparelho respiratório, é o factor principal para o desenvolvimento de DPOC (doença pulmonar obstrutiva crónica), RB-ILD (bron-quiolite respiratória e doença pulmonar intersticial), DIP (pneumonia intersticial descamativa), bronquiolite e fi-brose intersticial bronquiolocêntrica, histiocitose de células de Langerhans, pneumonia eosinofílica, sarcoidose, metaplasia epidermóide do epitélio respiratório e carcinoma bronco-pulmonar. O estado inflamatório crónico sistémico induzido pelo tabaco constitui a base de desenvolvimento de alterações genéticas também dependentes dos contaminantes do tabaco.Rev Port Pneumol 2007; XIII (3): 383-389 Abstract: Tobacco is implicated in multisystemic carcinogenesis through more than fifty identified carcinogenic metabolites that produce mutations responsible for alterations in cell cycle, immune response and endocrine regulation. Is one of nine risk factors identified in one third of cancer deaths together with obesity, sedentary, alcohol consumption, sexual promiscuity, drug addiction, and open and closed air contamination. Answering for cardiovascular diseases as the first cause of death in civilized world, tobacco is also pointed as the major factor implicated in the development of COPD (chronic obstructive pulmonary disease), RB-ILD (respira-tory bronchiolitis and interstitial lung disease), DIP (desquamative interstitial pneumonia), bronchiolitis and bronchiolocentric interstitial fibrosis, Langerhans cells histiocytosis, eosinophilic pneumonia, sarcoidosis, epidermoid metaplasia in respiratory epithelium and lung cancer. The chronic tobacco induced inflammatory state is the basis for the acquisition of genetic alterations dependent on the tobacco contaminants.Rev Port Pneumol 2007; XIII (3): 383-389 Palavras-chave: Tabaco, morfologia pulmonar, Key-words: Tobacco, lung morphology

Measurement of the spatial distribution of aerosol deposition in human lungs can be performed using single photon emission computed tomography (SPECT). To relate deposition patterns to real lung structures, a computer model of the airway network has been developed. Computer simulations are presented that are compatible with the analysis of SPECT images. Computational techniques that are consistent with clinical procedures are used to analyze airways by type and number within transverse slices of the lung volume. The computer models serve as customized templates, which when analyzed alongside gamma scintigraphy images, can assist in the interpretation of human test data.

This article reviews the current diagnostic strategies for patients with suspected pulmonary embolism (PE) focusing on the current first choice imaging modality, computed tomographic pulmonary angiography (CTPA). Diagnostic strengths and weaknesses and associated cost-effectiveness of the diagnostic pathways will be discussed. The radiation dose risk of these pathways will be described and techniques to minimize dose will be reviewed. Finally the impact of new dual energy applications which have the potential to provide additional functional information will be briefly reviewed. Imaging plays a vital role in the diagnostic pathway for clinically suspected PE. CT has been established as the most robust morphologic imaging tool for the evaluation of patients with suspected PE. This conclusion is based on the high diagnostic utility of CT for the detection of PE and its unique capacity for accurate diagnosis of conditions that can mimic the clinical presentation of PE. Although current cost-effectiveness evaluations have established CT as integral in the PE diagnostic pathway, failure to acknowledge the impact of alternate diagnosis represents a current knowledge gap. The emerging dual energy capacity of current CT scanners offers the potential to evaluate both pulmonary vascular morphology and ventilation perfusion relationships within the lung parenchyma at high spatial resolution. This dual assessment of lung morphology and lung function at low (5 millisievert) radiation dose represents a substantial advance in PE imaging.

The impact of fast MR techniques developed for MR imaging of the lung will soon be recognized as equivalent to the high-resolution technique in chest CT imaging. In this article, the difficulties in MR imaging posed by lung morphology and its physiological motion are briefly introduced. Then, fast MR imaging techniques to overcome the problems of lung imaging and recent applications of the fast MR techniques including pulmonary perfusion and ventilation imaging are discussed. Fast MR imaging opens a new exciting window to multi-functional MR imaging of the lung. We believe that fast MR functional imaging will play an important role in the assessment of pulmonary function and disease process.

In a recently published paper by Parra-Robles and Wild, the authors challenge the in vivo lung morphometry technique (based on hyperpolarized gas diffusion MRI) developed by our Washington University research group. In this Commentary we demonstrate that the main conclusion of Parra-Robles and Wild, that our MRI-based lung morphometry technique "produces inaccurate estimates of the airway dimensions", does not have any scientific basis and is not in agreement with the considerable body of peer-reviewed scientific reports as well as with Parra-Robles and Wild's own data. On the contrary, our technique has a strong theoretical background, is validated, and provides accurate 3D tomographic information on lung microstructural parameters previously available only from invasive biopsy specimens. This technique has already produced a number of results related to lung morphology and function that were not previously available. In our Commentary we also discuss a number of other incorrect statements in and shortcomings of Parra-Robles and Wild's paper.

A system for monitoring sound transmission through the human lung is described and the possibility of using this information in order to construct a functional map of the lung is investigated. Lung morphology (structure) may be monitored by using X-rays or computerised axial tomography (CAT). However, the size, cost and the possible adverse effects of high doses of X-rays make these techniques unsuitable for routine use. The speed of sound transmission through parenchyma (lung tissue) is a function of the size of the alveoli (air sacs). Therefore, by measuring the speed of sound through the lungs it may be possible to detect areas of collapsed alveoli. This would provide a simple, cheap, and non-invasive technique for monitoring certain lung abnormalities.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:58:17Z No. of bitstreams: 1 S0102-86502012001000004.pdf: 1695052 bytes, checksum: 0ed22eb631998210513896accfb6afbe (MD5) Made available in DSpace on 2013-08-22T18:58:17Z (GMT). No. of bitstreams: 1 S0102-86502012001000004.pdf: 1695052 bytes, checksum: 0ed22eb631998210513896accfb6afbe (MD5) Previous issue date: 2012-10-01 Made available in DSpace on 2013-09-30T19:53:52Z (GMT). No. of bitstreams: 2 S0102-86502012001000004.pdf: 1695052 bytes, checksum: 0ed22eb631998210513896accfb6afbe (MD5) S0102-86502012001000004.pdf.txt: 27206 bytes, checksum: b9ef30639047fcaf277922d9f1304dae (MD5) Previous issue date: 2012-10-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:37:07Z No. of bitstreams: 2 S0102-86502012001000004.pdf: 1695052 bytes, checksum: 0ed22eb631998210513896accfb6afbe (MD5) S0102-86502012001000004.pdf.txt: 27206 bytes, checksum: b9ef30639047fcaf277922d9f1304dae (MD5) Made available in DSpace on 2014-05-20T13:37:07Z (GMT). No. of bitstreams: 2 S0102-86502012001000004.pdf: 1695052 bytes, checksum: 0ed22eb631998210513896accfb6afbe (MD5) S0102-86502012001000004.pdf.txt: 27206 bytes, checksum: b9ef30639047fcaf277922d9f1304dae (MD5) Previous issue date: 2012-10-01 OBJETIVO: Investigar os efeitos morfológicos da exposição crônica à inalação de fumaça do tabaco e o do consumo de álcool nos pulmões e no crescimento de ratos. MÉTODOS: Sessenta ratos Wistar machos foram distribuídos em quatro grupos: controle, tabaco, álcool e tabaco + álcool, e acompanhados por um período de 260 dias. No final do periodo foi realizada análise morfológica dos pulmões por microscopia óptica e eletrônica. O crescimento dos ratos foi investigado através da medição do comprimento focinho-ânus, peso corporal e índice de massa corporal. RESULTADOS: Os três grupos expostos às drogas apresentaram peso e comprimento significativamente menores que os do grupo controle. As percentagens de bronquiolite e alveolite, e o diâmetro alveolar médio foram maiores nos grupos expostos à fumaça do tabaco, mas sem significancia estatística quando comparadas ao grupo controle. A microscopia eletrônica revelou apoptose mais intensa e lesões degenerativas no grupo de fumantes, enquanto lesões degenerativas nos corpos lamelares foram mais intensas com a associação de ambas as drogas. CONCLUSÕES: Este modelo experimental mostrou alterações morfológicas observadas por microscopia eletrônica, principalmente devido à exposição ao tabaco. Tanto o alcool como o tabaco prejudicaram o crescimento dos animais, o tabaco mostrando um efeito maior sobre o comprimento e o álcool sobre o peso corporal. PURPOSE: Investigate the morphological effects of chronic exposure to tobacco smoke inhalation and alcohol consumption on the lungs and on the growth of rats. METHODS: Sixty male Wistar rats were divided into four groups: control, tobacco, alcohol, tobacco + alcohol, for a period of study 260 days. Morphological analysis was conducted by optical and electron microscopy. Rat growth was investigated by measuring the snout-anus length, body mass index and body weight. RESULTS: The three groups exposed to the drugs presented lower growth and lower weight than the control group. The percentages of alveolitis, bronchiolitis and the mean alveolar diameter were greater, particularly in the groups exposed to tobacco smoke, but were not significantly different from the control group. Electron microscopy revealed more intense apoptotic and degenerative lesions in the smoking group, while degenerative lesions in the lamellar bodies were more intense with the association of both drugs. CONCLUSIONS: This experimental model showed morphological alterations observed by electron microscopy, principally due to tobacco smoke exposure. Alcohol and tobacco hindered the growth of rats, such that tobacco showed a greater effect on body length and alcohol on body weight. UNESP University of São Paulo Department of Pathology UNESP

This is an experimental study of lung morphology in modeling sepsis on a background of severe purulent-inflammatory disease of soft tissues (necrotizing fasciitis) by original authors’ method. The study showed that early stages of sepsis (1-3 days) were characterized by manifestations of changes in lung tissue as vascular response, in the second period (the 7th day) by appearance and growth of non-obstructive microatelectases, whereas the third period (the 14th day) was characterized by progression of purulent-necrotic processes in soft tissues, development of surgical sepsis and acute respiratory distress syndrome. These changes in morphological structure of lung tissue are specific for generalized septic process and consequences of necrotizing fasciitis with its septic complication.

The efficacies of inhaled pharmacologic drugs in the prophylaxis and treatment of airway diseases could be improved if particles were selectively directed to appropriate sites. In the medical arena, planar gamma scintillation cameras may be employed to study factors affecting such particle deposition patterns within the lung. The value and versatility of such instruments, however, are compromised by the limited resolution of their images. Specifically, it is not possible to determine the composition of their central (C) or large airway, intermediate (I), and peripheral (P) or small airway zones. We present an analytical model to assist the clinician in the systematic analysis and interpretation of gamma camera images. Using the Cray Y-MP supercomputer, a range of human lung morphologies has been mapped to function as templates that can be superimposed on scans. The model is intended to complement laboratory regimens by providing a previously unavailable method to define the C, I, and P zones of the human lung generation by generation. A quantitative value now can be assigned to the degree of overlapping that exists in the images. For example, for a "typical" lung morphology consisting of 16,777,215 airways (total), the C zone itself may contain 1,608,246 airways, of which 1,595,940, or 99.2%, are alveolated airways. By identifying composition, our intent is to integrate the model into future aerosol therapy protocols and thereby assist procedures that target delivery of airborne pharmaceuticals.

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.

Septic pulmonary embolism (SPE) is a critical disorder which requires fast diagnosis for treatment, while SPE continues to pose a diagnostic challenge in radiologic imaging. We describe detailed findings on breath-hold perfusion SPECT-CT fusion images in 2 patients with SPE. Regardless of absence or nonspecific morphologic abnormality in these patients, the fusion images showed multiple wedge-shaped segmental/subsegmental perfusion defects along specific pulmonary arteries, highly suggesting embolic event. Follow-up fusion images after treatment showed changes in lung perfusion defects and morphology. Assessment of lung morphology-perfusion correlation on reliable fusion images contributes to correct diagnosis of SPE and monitoring of treatment effect.

Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

Purpose of review The aim of this article is to describe the physiologic utility, correlation with lung morphology, difficulties in interpretation and current clinical applications of static-volume curves at the bedside in patients with acute lung respiratory system pressure injury or acute respiratory distress syndrome. Recent findings Complex interpretation of pressure-volume curves indicates that alveolar reopening continues past the lower inflection point on the linear part of the curve and suggests the presence of homogeneous lung disease in which recruitment is still possible by positive end-expiratory pressure application. Setting positive end-expiratory pressure above the lower inflection point and tidal ventilation (approximately 6 ml/kg) in the linear portion of the respiratory system pressure-volume curve improved mortality and ameliorated lung and plasma inflammatory mediators compared with ventilation with the lowest positive end-expiratory pressure at traditional tidal volumes. Recent studies have found that regular use of pressure-volume curves provides useful physiological data that help to optimize mechanical ventilation at the bedside. Summary The physiologic data obtained by measuring the static pressure-volume curves have helped clinicians to better understand the behavior of the respiratory system when positive-pressure ventilation is applied. The advanced technology incorporated into modern ventilators allows routine measurement of pressure-volume curves under sedation without paralysis, with acceptable variability and no serious adverse effects.

Pulmonary ischemia resulting from chronic pulmonary embolism leads to proliferation of the systemic circulation within and surrounding the lung. However, it is not clear how well alveolar tissue is sustained during the time of complete pulmonary ischemia. In the present study, we investigated how pulmonary ischemia after left pulmonary artery ligation (LPAL) would alter lung mechanical properties and morphology. In this established mouse model of lung angiogenesis after chronic LPAL ( 10 ), we evaluated lung function and structure before (3 days) and after (14 days) a functional systemic circulation to the left lung is established. Age-matched naïve and sham-operated C57Bl/6 mice and mice undergoing chronic LPAL were studied. Left and right lung pressure-volume relationships were determined. Next, lungs were inflated in situ with warmed agarose (25–30 cmH2O) and fixed, and mean chord lengths (MCL) of histological sections were quantified. MCL of naïve mice averaged 43.9 ± 1.8 μm. No significant changes in MCL were observed at either time point after LPAL. Left lung volumes and specific compliances were significantly reduced 3 days after LPAL. However, by 14 days after LPAL, lung pressure-volume relationships were not different from controls. These results suggest that severe pulmonary ischemia causes changes in lung mechanics early after LPAL that are reversed by the time a new systemic vasculature is known to perfuse pulmonary capillaries. The LPAL model thus affords a unique opportunity to study lung functional responses to tissue ischemia and subsequent recovery.

Buts: L'hypoplasie pulmonaire et l'hypertension pulmonaire persistante sont les causes principales de la mortalite et de la morbidite dans les hernies congenitales du diaphragme (CDH). L'occlusion tracheale prenatale accelere la croissance pulmonaire mais le mecanisme demeure inconnu. Dans le but d'etablir la fiabilite de notre modele experimental pour des etudes en biologie moleculaire ulterieures, nous evaluons la structure histologique premierement de poumons foetaux soumis a une occlusion tracheale, deuxiemement de poumons foetaux normaux, troisiemement de poumons hypoplasiques avec CDH, et quatriemement des poumons neonataux normaux. Un groupe de foetus de rats Sprague-Dawley a ete soumis a une ligature intra-uterine de la trachee au 19 eme jour de la gestation (n= 7). Les foetus controle sont de la meme race que ceux qui avaient ete soumis a la ligature tracheale (n=8). Un autre groupe de rats Sprague-Dawley enceintes recevaient 100 mg de Nitrofen au jour gestationnel 9,5 pour creer une hernie de coupole diaphragmatique (n=8). Tous les foetus etaient obtenus par cesarienne au jour 21. Les poumons de rats nouveaux-nes non operes Sprague-Dawley etaient aussi examines (n = 6). Le rapport du poids pulmonaire au poids du corps etait significativement plus eleve chez les poumons soumis a une ligature tracheale (5,0±0,36%), compare au poumon controle (2,8 ± 0,15%), aux poumons avec hernie de coupole diaphragmatique (1,9±0,12%), et aux poumons neonataux normaux (4,2 ±0,18%). Le volume de l'alveole et le compte radial alveolaire (RAC) chez les poumons soumis a une ligature tracheale (52±1,4%) etait significativement plus eleve dans le groupe controle (34±3,4%)(2,2±0,17) et dans les poumons avec hernies de coupole diaphragmatique (16±1,7%) (1,7±0,07). Aucune difference significative n'a ete trouvee entre les ligatures tracheales et le groupe neonatal normal (59±1,4%) (3,6±0,11). Les poumons foetaux apres ligature tracheale montraient a l'evidence une stimulation de la croissance avec une augmentation du volume alveolaire et du compte radial alveolaire comparable a ceux trouves chez un poumon neonatal normal.

Hyperpolarized (HP) 3 helium ( 3 He) dynamic MRI was used to investigate airway response in rats following intravenous (i.v.) bolus administration of a contractile agent, methacholine (MCh). The method provides direct visualization of the ventilated regions within the lung. Heterogeneous bronchoconstriction following the i.v. MCh injection was evident using this technique. These 3 He dynamic lung images revealed that the inspired fresh air was shunted to the less-constricted regions after the MCh challenge in a similar manner as described by Laplace’s relationship for the stability between adjacent alveoli. The airways in the more-constricted regions became nearly closed, resulting in air trapping, while the airways in the lessconstricted regions remained effectively open, leading to overinflation. These data suggest a lung model of airway constriction partitioned into ventilated and nonventilated regions. These nonventilated regions are heterogeneously distributed in the lung and this distribution cannot be deduced from spirometric measurement of the whole lung. We demonstrate that a combination of functional 3 He images and anatomical 1 H images provide an effective method to diagnose regional lung abnormalities in rats. Magn Reson Med 52:1080 –1086, 2004. © 2004

The architecture of the lung is discussed with special focus on lung parenchyma. The lung parenchyma is mainly comprised of numerous air-containing passages and intervening fine structures, corresponding to alveolar ductal lumens and alveoli, as well as alveolar septa and small pulmonary vessels occupying 10% of total parenchymal volume. The shapes and relative arrangements of alveolar ducts and alveoli are discussed in detail, which is followed by a brief description of bronchial circulation and pulmonary lymphatics.

Lung computed tomography (CT) is being used increasingly to assess lung morphology in patients on mechanical ventilation. Lung CT under known levels of airway pressure (dynamic CT) can also assess the response of lung parenchyma to ventilatory therapy. We report a patient with acute respiratory distress syndrome secondary to descending necrotizing mediastinitis, in whom lung dynamic CT oriented ventilatory management. Independent lung ventilation improved gas exchange and helped patient recovery (Rev Med Chile 2003; 131: 200-8)

Over the last half of the last century, classic studies established many features of the development of the lung in humans. Early studies relied on meticulous measurement and evaluation of lung morphology and physiology. In recent years, such studies have been supplemented by carefully conducted, longitudinal studies and by the use of molecular biological methodologies to determine more detailed aspects of lung development. In addition, factors affecting the growth of the lung have been evaluated including preterm delivery, antenatal steroids, environmental factors, asthma and asthma medications. In the future, further advances are likely to come from the molecular biological approach.