Regional Pulmonary Ventilation Research Articles

Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

BACKGROUNDThere is currently no sensitive, non-invasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized 129Xe MRI is a sensitive tool for 3D imaging of regional pulmonary ventilation and gas exchange abnormalities and may aid in early detection of CLAD. METHODSAdult patients post bilateral lung transplant were screened for CLAD based on the ISHLT criteria. Those with established allografts (n=10) underwent 129Xe gas exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and RBC defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTSThe analysis included nine lung transplant recipients, seven with CLAD and two without. CLAD patients exhibited VDP values consistent with their FEV1 decline (rho=0.79, p=0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs. young healthy controls (median [first quartile–third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], P=0.003) as well as vs. age-matched controls (5.5% [2% - 9.25%], p=0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs. 0.62 [0.50-0.66], p< 0.001 and vs. 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7]ppm vs 218.2 [218.0-218.5]ppm, p=0.009 and vs. 218.3 [218.2-218.5]ppm, p=0.003), and increased RBC oscillation amplitude vs. the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p=0.003). CONCLUSIONSPatients with CLAD exhibited significant ventilation defects that correlated with FEV1 decline, that, along with RBC transfer defects and other 129Xe gas exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.

Bedside monitoring of lung perfusion by electrical impedance tomography

As a non-invasive and radiation-free bedside imaging method, electrical impedance tomography (EIT) can perform real-time regional pulmonary ventilation evaluation and pulmonary blood flow monitoring for patients, thus realizing bedside ventilation/perfusion matching visualization, effectively guiding the pathophysiological mechanism of hypoxemia, and providing a new method for the study of pulmonary blood flow. EIT has also played a unique and irreplaceable role in COVID-19 research and treatment. At the same time, as functional imaging, the operation details and image reconstruction algorithm of this technology still need to be further optimized by more researches to provide a more robust evaluation in clinical application. In this paper, EIT pulmonary blood flow monitoring methods, operation and implementation of monitoring indicators, application and related research progress will be described.

Quantification of lung function on CT images based on pulmonary radiomic filtering.

To develop a radiomics filtering technique for characterizing spatial-encoded regional pulmonary ventilation information on lung computed tomography (CT). The lung volume was segmented on 46 CT images, and a 3D sliding window kernel was implemented across the lung volume to capture the spatial-encoded image information. Fifty-three radiomic features were extracted within the kernel, resulting in a fourth-order tensor object. As such, each voxel coordinate of the original lung was represented as a 53-dimensional feature vector, such that radiomic features could be viewed as feature maps within the lungs. To test the technique as a potential pulmonary ventilation biomarker, the radiomic feature maps were compared to paired functional images (Galligas PET or DTPA-SPECT) based on the Spearman correlation (ρ) analysis. The radiomic feature maps GLRLM-based Run-Length Non-Uniformity and GLCOM-based Sum Average are found to be highly correlated with the functional imaging. The achieved ρ (median [range]) for the two features are 0.46 [0.05, 0.67] and 0.45 [0.21, 0.65] across 46 patients and 2 functional imaging modalities, respectively. The results provide evidence that local regions of sparsely encoded heterogeneous lung parenchyma on CT are associated with diminished radiotracer uptake and measured lung ventilation defects on PET/SPECT imaging. These findings demonstrate the potential of radiomics to serve as a complementary tool to the current lung quantification techniques and provide hypothesis-generating data for future studies.

Are alveolar recruitment maneuvers and peep ventilation effective in the intraoperative period of laparoscopic bariatric surgery? A systematic review

The purpose of the study is to systematically review about alveolar recruitment maneuvers followed by mechanical ventilation with PEEP guided by electrical impedance tomography (EIT) in laparoscopic bariatric surgery. Metodology: The primary outcomes were: regional pulmonary ventilation (regional impedance variation), end-expiratory lung impedance, and end-expiratory lung volume. Results: The survey identified three eligible studies. The sample consisted of 136 participants of both genders. The alveolar recruitment maneuver (ARM) was performed through the mechanical ventilator and using the EIT in the patient’s chest. The studies showed moderate to high risk of bias, and the quality of the evidence was classified as very low quality due to the methodological limitations found and absence of directionality. Conclusion: ARM with PEEP guided by EIT does not significantly improve the respiratory system mechanics in the intraoperative period in obese patients undergoing laparoscopic bariatric surgery.

Automatic triangulated mesh generation of pulmonary airways from segmented lung 3DCTs for computational fluid dynamics.

Computational fluid dynamics (CFD) of lung airflow during normal and pathophysiological breathing provides insight into regional pulmonary ventilation. By integrating CFD methods with 4D lung imaging workflows, regions of normal pulmonary function can be spared during treatment planning. To facilitate the use of CFD simulations in a clinical setup, a robust, automated, and CFD-compliant airway mesh generation technique is necessary. We define a CFD-compliant airway mesh to be devoid of blockages of airflow and leaks in the airway path, both of which are caused by airway meshing errors that occur when using conventional meshing techniques. We present an algorithm to create a CFD-compliant airway mesh in an automated manner. Beginning with a medial skeleton of the airway segmentation, the branches were tracked, and 3D points at which bifurcations occur were identified. Airway branches and bifurcation features were isolated to allow for automated and careful meshing that considered their anatomical nature. We present the meshing results from three state-of-the-art tools and compare them with the meshes generated by our algorithm. The results show that fully CFD-compliant meshes were automatically generated for an ideal geometry and patient-specific CT scans. Using an open-source smoothed-particle hydrodynamics CFD implementation, we compared the airflow using our approach and conventionally generated airway meshes. Our meshing algorithm was able to successfully generate a CFD-compliant mesh from pre-segmented lung CT scans, providing an automatic meshing approach that enables interventional CFD simulations to guide lung procedures such as radiotherapy or lung volume reduction surgery.

Evaluation of Regional Pulmonary Ventilation in Spontaneously Breathing Patients with Idiopathic Pulmonary Fibrosis (IPF) Employing Electrical Impedance Tomography (EIT): A Pilot Study from the European IPF Registry (eurIPFreg).

Objectives: In idiopathic pulmonary fibrosis (IPF), alterations in the pulmonary surfactant system result in an increased alveolar surface tension and favor repetitive alveolar collapse. This study aimed to assess the usefulness of electrical impedance tomography (EIT) in characterization of regional ventilation in IPF. Materials and methods: We investigated 17 patients with IPF and 15 healthy controls from the University of Giessen and Marburg Lung Center (UGMLC), Germany, for differences in the following EIT parameters: distribution of ventilation (TID), global inhomogeneity index (GI), regional impedance differences through the delta of end-expiratory lung impedance (dEELI), differences in surface of ventilated area (SURF), as well as center of ventilation (CG) and intratidal gas distribution (ITV). These parameters were assessed under spontaneous breathing and following a predefined escalation protocol of the positive end-expiratory pressure (PEEP), applied through a face mask by an intensive care respirator (EVITA, Draeger, Germany). Results: Individual slopes of dEELI over the PEEP increment protocol were found to be highly significantly increased in both groups (p < 0.001) but were not found to be significantly different between groups. Similarly, dTID slopes were increasing in response to PEEP, but this did not reach statistical significance within or between groups. Individual breathing patterns were very heterogeneous. There were no relevant differences of SURF, GI or CGVD over the PEEP escalation range. A correlation of dEELI to FVC, BMI, age, or weight did not forward significant results. Conclusions: In this study, we did see a significant increase in dEELI and a non-significant increase in dTID in IPF patients as well as in healthy controls in response to an increase of PEEP under spontaneous breathing. We propose the combined measurements of EIT and lung function to assess regional lung ventilation in spontaneously breathing subjects.

Positional Therapy and Regional Pulmonary Ventilation.

Prone ventilation redistributes lung inflation along the gravitational axis; however, localized, nongravitational effects of body position are less well characterized. The authors hypothesize that positional inflation improvements follow both gravitational and nongravitational distributions. This study is a nonoverlapping reanalysis of previously published large animal data. Five intubated, mechanically ventilated pigs were imaged before and after lung injury by tracheal injection of hydrochloric acid (2 ml/kg). Computed tomography scans were performed at 5 and 10 cm H2O positive end-expiratory pressure (PEEP) in both prone and supine positions. All paired prone-supine images were digitally aligned to each other. Each unit of lung tissue was assigned to three clusters (K-means) according to positional changes of its density and dimensions. The regional cluster distribution was analyzed. Units of tissue displaying lung recruitment were mapped. We characterized three tissue clusters on computed tomography: deflation (increased tissue density and contraction), limited response (stable density and volume), and reinflation (decreased density and expansion). The respective clusters occupied (mean ± SD including all studied conditions) 29.3 ± 12.9%, 47.6 ± 11.4%, and 23.1 ± 8.3% of total lung mass, with similar distributions before and after lung injury. Reinflation was slightly greater at higher PEEP after injury. Larger proportions of the reinflation cluster were contained in the dorsal versus ventral (86.4 ± 8.5% vs. 13.6 ± 8.5%, P < 0.001) and in the caudal versus cranial (63.4 ± 11.2% vs. 36.6 ± 11.2%, P < 0.001) regions of the lung. After injury, prone positioning recruited 64.5 ± 36.7 g of tissue (11.4 ± 6.7% of total lung mass) at lower PEEP, and 49.9 ± 12.9 g (8.9 ± 2.8% of total mass) at higher PEEP; more than 59.0% of this recruitment was caudal. During mechanical ventilation, lung reinflation and recruitment by the prone positioning were primarily localized in the dorso-caudal lung. The local effects of positioning in this lung region may determine its clinical efficacy.

Análise de perfil epidemiológico e parâmetros ventilatórios de puérperas submetidas à ventilação mecânica por meio da tomografia por impedância elétrica

Introdução: As doenças relacionadas à gravidez tem agravado o quadro de puérperas, que acabam fazendo uso de Ventilação Mecânica (VM) quando internadas em Unidades de Terapia Intensiva (UTI). A VM, apesar de trazer benefícios, está associada a efeitos deletérios que podem ser minimizados com o uso da Tomografia por Impedância Elétrica (TIE). Objetivo: Analisar o perfil epidemiológico e parâmetros ventilatórios de puérperas que evoluíram com Síndrome HELLP, Sepse e/ou Síndrome do Desconforto Respiratório Agudo (SDRA), sob VM e monitoradas com a TIE. Métodos: Estudo observacional, transversal retrospectivo e prospectivo, realizado entre março e setembro de 2018, por meio de fichas de coletas preenchidas a partir de banco de dados/prontuários sociodemográficos, obstétricos e ventilatórios de puérperas internadas em UTI. Resultados: Amostra composta por 13 puérperas, oito com Sepse (61,5%), sete com Síndrome HELLP (53,8%) e quatro com SDRA (30,8%), demonstrando que cinco (38,5%) pacientes evoluíram com mais de uma dessas patologias. Acerca dos parâmetros ventilatórios avaliados, observou-se VT 378.9 (± 103.9) e que valores médios encontrados para PEEP 9.8 (±1.9) e driving pressure 11.1 (±1.4) estão abaixo dos preconizados pela literatura, predizendo menores índices de mortalidade e morbidade. Conclusão: Demonstrou-se relevância da avaliação de driving pressure no cenário da VM, parâmetro avaliado por meio da TIE e diretamente relacionado à Cst, PEEP, VT e otimização da ventilação pulmonar regional. Destaca-se a necessidade de pesquisas futuras que apresentem maiores significâncias clínicas voltadas ao perfil de puérperas em relação às doenças cada vez mais frequentes nesta população.

CT-based Airway Flow Model to Assess Ventilation in Chronic Obstructive Pulmonary Disease: A Pilot Study.

Background The lack of functional information in thoracic CT remains a limitation of its use in the clinical management of chronic obstructive pulmonary disease (COPD). Purpose To compare the distribution of pulmonary ventilation assessed by a CT-based full-scale airway network (FAN) flow model with hyperpolarized xenon 129 (129Xe) MRI (hereafter, 129Xe MRI) and technetium 99m-diethylenetriaminepentaacetic acid aerosol SPECT ventilation imaging (hereafter, V-SPECT) in participants with COPD. Materials and Methods In this prospective study performed between May and August 2017, pulmonary ventilation in participants with COPD was computed by using the FAN flow model. The modeled pulmonary ventilation was compared with functional imaging data from breath-hold time-series 129Xe MRI and V-SPECT. FAN-derived ventilation images on the coronal plane and volumes of interest were compared with functional lung images. Percentage lobar ventilation estimated by the FAN model was compared with that measured at 129Xe MRI and V-SPECT. The statistical significance of ventilation distribution between FAN and functional images was demonstrated with the Spearman correlation coefficient and χ2 distance. Results For this study, nine participants (seven men [mean age, 65 years ± 5 {standard deviation}] and two women [mean age, 63 years ± 7]) with COPD that was Global Initiative for Chronic Obstructive Lung Disease stage II-IV were enrolled. FAN-modeled ventilation profile showed strong positive correlation with images from 129Xe MRI (ρ = 0.67; P < .001) and V-SPECT (ρ = 0.65; P < .001). The χ2 distances of the ventilation histograms in the volumes of interest between the FAN and 129Xe MRI and FAN and V-SPECT were 0.16 ± 0.08 and 0.28 ± 0.14, respectively. The ratios of lobar ventilations in the models were linearly correlated to images from 129Xe MRI (ρ = 0.67; P < .001) and V-SPECT (ρ = 0.59; P < .001). Conclusion A CT-based full-scale airway network flow model provided regional pulmonary ventilation information for chronic obstructive pulmonary disease and correlates with hyperpolarized xenon 129 MRI and technetium 99m-diethylenetriaminepentaacetic acid aerosol SPECT ventilation imaging. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Schiebler and Parraga in this issue.

Optimized and accelerated 19 F-MRI of inhaled perfluoropropane to assess regional pulmonary ventilation.

PurposeTo accelerate 19F‐MR imaging of inhaled perfluoropropane using compressed sensing methods, and to optimize critical scan acquisition parameters for assessment of lung ventilation properties.MethodsSimulations were performed to determine optimal acquisition parameters for maximal perfluoropropane signal‐to‐noise ratio (SNR) in human lungs for a spoiled gradient echo sequence. Optimized parameters were subsequently employed for 19F‐MRI of inhaled perfluoropropane in a cohort of 11 healthy participants using a 3.0 T scanner. The impact of 1.8×, 2.4×, and 3.0× undersampling ratios on 19F‐MRI acquisitions was evaluated, using both retrospective and prospective compressed sensing methods.Results3D spoiled gradient echo 19F‐MR ventilation images were acquired at 1‐cm isotropic resolution within a single breath hold. Mean SNR was 11.7 ± 4.1 for scans acquired within a single breath hold (duration = 18 s). Acquisition of 19F‐MRI scans at shorter scan durations (4.5 s) was also demonstrated as feasible. Application of both retrospective (n = 8) and prospective (n = 3) compressed sensing methods demonstrated that 1.8× acceleration had negligible impact on qualitative image appearance, with no statistically significant change in measured lung ventilated volume. Acceleration factors of 2.4× and 3.0× resulted in increasing differences between fully sampled and undersampled datasets.ConclusionThis study demonstrates methods for determining optimal acquisition parameters for 19F‐MRI of inhaled perfluoropropane and shows significant reduction in scan acquisition times (and thus participant breath hold duration) by use of compressed sensing.

Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial.

Rationale: In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. Objectives: To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. Methods: In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Measurements and Main Results: Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 μg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF (P = 0.006) and regional PMBF (P values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo (P = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; P = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo (P < 0.0001). Conclusions: Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).

Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography.

Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.

Assessing the variability in respiratory acoustic thoracic imaging (RATHI)

Multichannel analysis of lung sounds (LSs) has enabled the generation of a functional image for the temporal and spatial study of LS intensities in healthy and diseased subjects; this method is known as respiratory acoustic thoracic imaging (RATHI). This acoustic imaging technique has been applied to diverse pulmonary conditions, but it is important to contribute to the understanding of RATHI characteristics, such as acoustic spatial distribution, dependence on airflow and variability. The purpose of the current study is to assess the intra-subject and inter-subject RATHI variabilities in a cohort of 12 healthy male subjects (24.3±1.5 years) using diverse quantitative indices. The indices were obtained directly from the acoustic image and did not require scores from human raters, which helps to prevent inter-observer variability. To generate the acoustic image, LSs were acquired at 25 positions on the posterior thoracic surface by means of airborne sound sensors with a wide frequency band from 75up to 1000Hz under controlled airflow conditions at 1.0, 1.5 and 2.0L/s. To assess intra-subject variability, the degree of similitude between inspiratory acoustic images was evaluated through quadratic mutual information based on the Cauchy–Schwartz inequality (ICS). The inter-subject variability was assessed by an image registration procedure between RATHIs and X-ray images to allow the computation of average and variance acoustic image in the same coordinate space. The results indicated that intra-subject RATHI similitude, reflected by ICS-global, averaged 0.960±0.008, 0.958±0.008 and 0.960±0.007 for airflows of 1.0, 1.5, and 2L/s, respectively. As for the inter-subject variability, the variance image values for three airflow conditions indicated low image variability as they ranged from 0.01 to 0.04. In conclusion, the assessment of intra-subject and inter-subject variability by similitude indices indicated that the acoustic image pattern is repeatable along different respiratory cycles and across different subjects. Therefore, RATHI could be used to explore different aspects of spatial distribution and its association with regional pulmonary ventilation.

Respiratory effort correction strategies to improve the reproducibility of lung expansion measurements

Four-dimensional computed tomography (4DCT) can be used to make measurements of pulmonary function longitudinally. The sensitivity of such measurements to identify change depends on measurement uncertainty. Previously, intrasubject reproducibility of Jacobian-based measures of lung tissue expansion was studied in two repeat prior-RT 4DCT human acquisitions. Difference in respiratory effort such as breathing amplitude and frequency may affect longitudinal function assessment. In this study, the authors present normalization schemes that correct ventilation images for variations in respiratory effort and assess the reproducibility improvement after effort correction. Repeat 4DCT image data acquired within a short time interval from 24 patients prior to radiation therapy (RT) were used for this analysis. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. In addition to computing the ventilation maps from end expiration to end inspiration, the authors investigated the effort normalization strategies using other intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Scatter plots and mean square error of the repeat ventilation maps and the Jacobian ratio map were generated for four conditions: no effort correction, global normalization, ETV, and ELV. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2 mm distance-to-agreement and 5% ventilation difference. The pattern of regional pulmonary ventilation changes as lung volume changes. All effort correction strategies improved reproducibility when changes in respiratory effort were greater than 150 cc (p < 0.005 with regard to the gamma pass rate). Improvement of reproducibility was correlated with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal volume difference greater than 100 cc). In general for all subjects, global normalization, ETV and ELV significantly improved reproducibility compared to no effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume difference was small (less than 100 cc), none of the three effort correction strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46 respectively). For the cohort (N = 13) with tidal volume difference greater than 100 cc, the average gamma pass rate improves from 57.3% before correction to 66.3% after global normalization, and 76.3% after ELV. ELV was found to be significantly better than global normalization (p = 0.04 for all subjects, and p = 0.003 for the cohort with tidal volume difference greater than 100 cc). All effort correction strategies improve the reproducibility of the authors' pulmonary ventilation measures, and the improvement of reproducibility is highly correlated with the changes in respiratory effort. ELV gives better results as effort difference increase, followed by ETV, then global. However, based on the spatial and temporal heterogeneity in the lung expansion rate, a single scaling factor (e.g., global normalization) appears to be less accurate to correct the ventilation map when changes in respiratory effort are large.

Optimization of Dual-Energy Xenon–Computed Tomography for Quantitative Assessment of Regional Pulmonary Ventilation

Dual-energy x-ray computed tomography (DECT) offers visualization of the airways and quantitation of regional pulmonary ventilation using a single breath of inhaled xenon gas. In this study, we sought to optimize scanning protocols for DECT xenon gas ventilation imaging of the airways and lung parenchyma and to characterize the quantitative nature of the developed protocols through a series of test-object and animal studies. The Institutional Animal Care and Use Committee approved all animal studies reported here. A range of xenon/oxygen gas mixtures (0%, 20%, 25%, 33%, 50%, 66%, 100%; balance oxygen) were scanned in syringes and balloon test-objects to optimize the delivered gas mixture for assessment of regional ventilation while allowing for the development of improved 3-material decomposition calibration parameters. In addition, to alleviate gravitational effects on xenon gas distribution, we replaced a portion of the oxygen in the xenon/oxygen gas mixture with helium and compared gas distributions in a rapid-prototyped human central-airway test-object. Additional syringe tests were performed to determine if the introduction of helium had any effect on xenon quantitation. Xenon gas mixtures were delivered to anesthetized swine to assess airway and lung parenchymal opacification while evaluating various DECT scan acquisition settings. Attenuation curves for xenon were obtained from the syringe test-objects and were used to develop improved 3-material decomposition parameters (Hounsfield unit enhancement per percentage xenon: within the chest phantom, 2.25 at 80 kVp, 1.7 at 100 kVp, and 0.76 at 140 kVp with tin filtration; in open air, 2.5 at 80 kVp, 1.95 at 100 kVp, and 0.81 at 140 kVp with tin filtration). The addition of helium improved the distribution of xenon gas to the gravitationally nondependent portion of the airway tree test-object, while not affecting the quantitation of xenon in the 3-material decomposition DECT. The mixture 40% Xe/40% He/20% O2 provided good signal-to-noise ratio (SNR), greater than the Rose criterion (SNR > 5), while avoiding gravitational effects of similar concentrations of xenon in a 60% O2 mixture. Compared with 100/140 Sn kVp, 80/140 Sn kVp (Sn = tin filtered) provided improved SNR in a swine with an equivalent thoracic transverse density to a human subject with a body mass index of 33 kg/m. Airways were brighter in the 80/140 Sn kVp scan (80/140 Sn, 31.6%; 100/140 Sn, 25.1%) with considerably lower noise (80/140 Sn, coefficient of variation of 0.140; 100/140 Sn, coefficient of variation of 0.216). To provide a truly quantitative measure of regional lung function with xenon-DECT, the basic protocols and parameter calibrations need to be better understood and quantified. It is critically important to understand the fundamentals of new techniques to allow for proper implementation and interpretation of their results before widespread usage. With the use of an in-house derived xenon calibration curve for 3-material decomposition rather than the scanner supplied calibration and a xenon/helium/oxygen mixture, we demonstrate highly accurate quantitation of xenon gas volumes and avoid gravitational effects on gas distribution. This study provides a foundation for other researchers to use and test these methods with the goal of clinical translation.

A novel alveolar Krebs cycle-triggered CO2 sensing mechanism regulates regional pulmonary ventilation.

AbstractPulmonary perfusion disorders provoke atelectasis in order to minimize ventilation/perfusion mismatch. However, the underlying mechanisms remain unknown. Because intraalveolar CO2 concentration ([CO2]iA) declines as a consequence of poor pulmonary perfusion we postulated the existence a novel alveolar CO2-sensing mechanism which adapts the ventilation to perfusion. Real-time fluorescence imaging of rat lungs revealed that low [CO2]iA decreased cytosolic and increased mitochondrial Ca2+ in alveolar epithelial cells (AEC), leading to reduction of surfactant secretion and alveolar ventilation. Mitochondrial inhibition by ruthenium red or rotenone blocked the hypocapnia-induced responses. In cultured Type 2 AEC hypocapnia decreased cytosolic Ca2+ independently from pH and increased the NADH production, the mitochondrial transmembrane potential, and subsequently the mitochondrial Ca2+ uptake. All responses were completely blocked by the gene knockdown of the NADH producing Krebs cycle enzyme isocitrate dehydrogenase. Furthermore, ligature of the pulmonary artery of rabbits decreased alveolar ventilation, surfactant secretion, and lung compliance. Addition of 5% CO2 to the inspiratory gas inhibited all responses. Accordingly, we provide evidence for a novel CO2-sensing mechanism of AEC regulated by the Krebs cycle activity in terms of a negative feedback loop adapting surfactant secretion and thus regional ventilation to pulmonary perfusion.

Influência da variação dos decúbitos laterais na deposição pulmonar de aerossol

The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p≤0.05. Inhalation in the right lateral decubitus position presented higher counts (p≤0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p≤0.02) than in the posterior ROI of the right lung. The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy.

Electrical impedence tomography and heterogeneity of pulmonary perfusion and ventilation in porcine acute lung injury

The heterogeneity of pulmonary ventilation (V), perfusion (Q) and V/Q matching impairs gas exchange in an acute lung injury (ALI). This study investigated the feasibility of electrical impedance tomography (EIT) to assess the V/Q distribution and matching during an endotoxinaemic ALI in pigs. Mechanically ventilated, anaesthetised pigs (n=11, weight 30-36 kg) were studied during an infusion of endotoxin for 150 min. Impedance changes related to ventilation (Z(V)) and perfusion (Z(Q)) were monitored globally and bilaterally in four regions of interest (ROIs) of the EIT image. The distribution and ratio of Z(V) and Z(Q) were assessed. The alveolar-arterial oxygen difference, venous admixture, fractional alveolar dead space and functional residual capacity (FRC) were recorded, together with global and regional lung compliances and haemodynamic parameters. Values are mean+/-standard deviation (SD) and regression coefficients. Endotoxinaemia increased the heterogeneity of Z(Q) but not Z(V). Lung compliance progressively decreased with a ventral redistribution of Z(V). A concomitant dorsal redistribution of Z(Q) resulted in mismatch of global (from Z(V)/Z(Q) 1.1+/-0.1 to 0.83+/-0.3) and notably dorsal (from Z(V)/Z(Q) 0.86+/-0.4 to 0.51+/-0.3) V and Q. Changes in global Z(V)/Z(Q) correlated with changes in the alveolar-arterial oxygen difference (r(2)=0.65, P<0.05), venous admixture (r(2)=0.66, P<0.05) and fractional alveolar dead space (r(2)=0.61, P<0.05). Decreased end-expiratory Z(V) correlated with decreased FRC (r(2)=0.74, P<0.05). EIT can be used to assess the heterogeneity of regional pulmonary ventilation and perfusion and V/Q matching during endotoxinaemic ALI, identifying pivotal pathophysiological changes.

Sporadic coordinated shifts of regional ventilation and perfusion in juvenile pigs with normal gas exchange

Repeated high-resolution measurements of both regional pulmonary ventilation and regional blood flow (r ) have revealed that approximately 6 to 10% of the summed spatial and temporal heterogeneity can be attributed to spontaneous temporal variability. To test the hypothesis that the spontaneous temporal shifts of r and r are coordinated, 12 anaesthetized juvenile pigs had pairs of colours of aerosol and intravenous fluorescent microspheres (FMS) administered simultaneously at 20 min intervals to mark r and r . The animals were killed, the lungs inflated, air-dried and cut into approximately 2 cm(3) cubes. The concentrations of FMS colours from each cube, representing r and r at every 20 min interval, were measured with a fluorescence spectrophotometer. The correlation between per-piece temporal shifts in r and r , calculated as the mean within-piece covariance, was positive (P < 0.001) for every temporally adjacent pair of measurements in every animal, although there were large differences in the magnitude of the mean temporal covariance among animals. The individual cubes with the most positive temporal covariance across all measurement periods usually demonstrated a large single-interval coordinated shift of r and r , with average temporal covariance observed at the other intervals. The largest between-interval shifts in r and r included equal proportions of coordinated increases and coordinated decreases. High-resolution measurements of r and r acquired over 20 min intervals reveal that the overall positive correlation between temporal changes in r and r is driven by relatively infrequent large-magnitude changes within small regions of the lung.

Inspiratory muscle endurance testing: Pulmonary ventilation and electromyographic analysis

This study analyzed regional pulmonary ventilation and electromyographic (EMG) activity of the respiratory muscles during an inspiratory muscle endurance (IME) test in 10 young women. Radioaerosol (99mTc-DTPA) was generated using a jet nebulizer connected to a linear inspiratory loading system. The lung scintigraphic analysis showed an increase in the radioaerosol deposition using loads of 20 and 30 cmH(2)O (p<0.01). The vertical gradient showed a larger radioaerosol deposition in the medium third of the lungs during the control period (p<0.001). There were larger amounts of radioaerosol deposition in the medium third when compared with the upper and lower third at 30 cmH(2)O (p<0.001). The horizontal gradient showed a larger deposition in the intermediate and central segments during all phases (p<0.00). Electromyographic activity from the muscles of the lower rib cage increased with loads of 20 and 30 cmH(2)O (p<0.03). There was an increase in deposition of radioaerosol when the load increased (r=0.584, p=0.000 for the left lung and r=0.609, p=0.000 for right lung). These findings suggest that during the IME test, EMG activity in the muscles of the lower rib cage increase during progressive respiratory workloads is associated with a greater radioaerosol deposition in the medium third and intermediate and central segments of the lungs.