Gas Exchange in the Lung.

Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇AQ̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO2 elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange.

The fractal geometry of bronchial trees differs by strain in mice.

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains.NEW & NOTEWORTHY Similar to larger mammals such as humans, the geometries of the bronchial tree in mice are fractal structures that have repeating patterns from the trachea to the terminal branches. The airway geometries of the four most commonly studied mice are different and need to be considered when comparing results that employ different mouse strains. This variability in mouse airway geometries should be incorporated into computer models exploring toxicology and aerosol deposition in mouse models.

Aerobic Exercise Effects on Quality of Life and Psychological Distress After an Implantable Cardioverter Defibrillator.

PURPOSE: The purpose of this study was to evaluate quality of life (QOL), psychological function, and self-efficacy outcomes in the Anti-Arrhythmic Effects of Exercise After an ICD Trial. METHODS: In the Anti-Arrhythmic Effects of Exercise After an ICD Trial, 160 patients (124 men and 36 women) who had an implantable cardioverter defibrillator for primary (43%) or secondary (57%) prevention were randomized to exercise (EX, n = 84) or usual care (UC, n = 76). The EX consisted of 8 wk of home walking 1 hr/d 5 d/wk, followed by 16 wk of maintenance home walking for 150 min/wk. Adherence was determined from exercise logs, ambulatory HR recordings, and phone calls. Assessments were conducted at baseline, 8, and 24 wk for QOL: Patient Concerns Assessment and Short Form-36; anxiety: State Trait Anxiety Inventory; depression: Physician Health Questionnaire-Depression; and self-efficacy: Self-Efficacy for Walking Scale. RESULTS: Participants averaged 55 ± 12 yr of age with ejection fraction = 40.6 ± 15.7%. The EX significantly decreased depression severity (EX: 1.33 ± 0.64; UC: 1.51 ± 0.86, P = .05) and improved self-efficacy (EX: 7.65 ± 1.97; UC: 6.85 ± 2.40, P = .05) at 8 wk. There were no significant effects at 24 wk. Adherent exercisers had significant improvements in QOL, psychological, and self-efficacy outcomes at 8 and 24 wk compared with those who were nonadherent. There were no implantable cardioverter defibrillator shocks associated with exercise. CONCLUSIONS: The EX conferred significant effects on depression and self-efficacy at 8 wk, without effects on QOL. Adherent exercisers experienced significant improvements in outcomes over those who were nonadherent or received UC.

lapdMouse: associating lung anatomy with local particle deposition in mice.

To facilitate computational toxicology, we developed an approach for generating high-resolution lung-anatomy and particle-deposition mouse models. Major processing steps of our method include mouse preparation, serial block-face cryomicrotome imaging, and highly automated image analysis for generating three-dimensional (3D) mesh-based models and volume-based models of lung anatomy (airways, lobes, sublobes, and near-acini structures) that are linked to local particle-deposition measurements. Analysis resulted in 34 mouse models covering 4 different mouse strains (B6C3F1: 8, BALB/C: 11, C57Bl/6: 8, and CD-1: 7) as well as both sexes (16 male and 18 female) and different particle sizes [2 µm (n = 15), 1 µm (n = 16), and 0.5 µm (n = 3)]. On average, resulting mouse airway models had 1,616.9 ± 298.1 segments, a centerline length of 597.6 ± 59.8 mm, and 1,968.9 ± 296.3 outlet regions. In addition to 3D geometric lung models, matching detailed relative particle-deposition measurements are provided. All data sets are available online in the lapdMouse archive for download. The presented approach enables linking relative particle deposition to anatomical structures like airways. This will in turn improve the understanding of site-specific airflows and how they affect drug, environmental, or biological aerosol deposition.NEW & NOTEWORTHY Computer simulations of particle deposition in mouse lungs play an important role in computational toxicology. Until now, a limiting factor was the lack of high-resolution mouse lung models and measured local particle-deposition information, which are required for developing accurate modeling approaches (e.g., computational fluid dynamics). With the developed imaging and analysis approach, we address this issue and provide all of the raw and processed data in a publicly accessible repository.

A perpetual switching system in pulmonary capillaries.

Of the 300 billion capillaries in the human lung, a small fraction meet normal oxygen requirements at rest, with the remainder forming a large reserve. The maximum oxygen demands of the acute stress response require that the reserve capillaries are rapidly recruited. To remain primed for emergencies, the normal cardiac output must be parceled throughout the capillary bed to maintain low opening pressures. The flow-distributing system requires complex switching. Because the pulmonary microcirculation contains contractile machinery, one hypothesis posits an active switching system. The opposing hypothesis is based on passive switching that requires no regulation. Both hypotheses were tested ex vivo in canine lung lobes. The lobes were perfused first with autologous blood, and capillary switching patterns were recorded by videomicroscopy. Next, the vasculature of the lobes was saline flushed, fixed by glutaraldehyde perfusion, flushed again, and then reperfused with the original, unfixed blood. Flow patterns through the same capillaries were recorded again. The 16-min-long videos were divided into 4-s increments. Each capillary segment was recorded as being perfused if at least one red blood cell crossed the entire segment. Otherwise it was recorded as unperfused. These binary measurements were made manually for each segment during every 4 s throughout the 16-min recordings of the fresh and fixed capillaries (>60,000 measurements). Unexpectedly, the switching patterns did not change after fixation. We conclude that the pulmonary capillaries can remain primed for emergencies without requiring regulation: no detectors, no feedback loops, and no effectors-a rare system in biology. NEW & NOTEWORTHY The fluctuating flow patterns of red blood cells within the pulmonary capillary networks have been assumed to be actively controlled within the pulmonary microcirculation. Here we show that the capillary flow switching patterns in the same network are the same whether the lungs are fresh or fixed. This unexpected observation can be successfully explained by a new model of pulmonary capillary flow based on chaos theory and fractal mathematics.

Leadership Primer for Current and Aspiring Pulmonary, Critical Care, and Sleep Medicine Academic Division Chiefs.

An academic medical career traditionally revolves around patient care, teaching, and scholarly projects. Thus, when an opportunity for a leadership role arises, such as division chief, the new leader is often unprepared with little or no formal leadership training. In this focused review, academic leaders of the Association of Pulmonary, Critical Care, and Sleep Division Directors describe several leadership concepts adapted from the business sector and apply their years of experience to aid new division chiefs with their first day on the job. The first 90 days are highlighted to include achieving early wins; performing a division-wide Strengths, Weaknesses, Opportunities, Threats analysis; establishing division rapport; redefining the division infrastructure; avoiding conflicts; and managing the relationship with the department chair. The five levels of leadership applicable to academic medicine are discussed: position, permission, production, people, and pinnacle. Finally, emotional intelligence and behavior styles crucial to leadership success are reviewed.

Gas Exchange in the Prone Posture.

The prone posture is known to have numerous effects on gas exchange, both under normal conditions and in patients with ARDS. Clinical studies have consistently demonstrated improvements in oxygenation, and a multi-center randomized trial found that, when implemented within 48 h of moderate-to-severe ARDS, placing subjects in the prone posture decreased mortality. Improvements in gas exchange occur via several mechanisms: alterations in the distribution of alveolar ventilation, redistribution of blood flow, improved matching of local ventilation and perfusion, and reduction in regions of low ventilation/perfusion ratios. Ventilation heterogeneity is reduced in the prone posture due to more uniform alveolar size secondary to a more uniform vertical pleural pressure gradient. The prone posture results in more uniform pulmonary blood flow when compared with the supine posture, due to an anatomical bias for greater blood flow to dorsal lung regions. Because both ventilation and perfusion heterogeneity decrease in the prone posture, gas exchange improves. Other benefits include a more uniform distribution of alveolar stress, relief of left-lower-lobe lung compression by the heart, enhanced secretion clearance, and favorable right-ventricular and systemic hemodynamics.

Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD.

Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predictions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1 = 50-80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 µm-diameter particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 µm particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.798 ± 0.205 vs. 0.527 ± 0.122 mL/mL, p=0.01; MS: -0.271±0.129 vs. -0.145 ± 0.076 mL/mL, p=0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to-moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease.

Prospective randomized trial of moderately strenuous aerobic exercise after an implantable cardioverter defibrillator.

BACKGROUND: Despite its salutary effects on health, aerobic exercise is often avoided after receipt of an implantable cardioverter defibrillator (ICD) because of fears that exercise may provoke acute arrhythmias. We prospectively evaluated the effects of a home aerobic exercise training and maintenance program (EX) on aerobic performance, ICD shocks, and hospitalizations exclusively in ICD recipients. METHODS AND RESULTS: A total of 160 patients (124 men and 36 women) were randomly assigned who had an ICD for primary (43%) or secondary (57%) prevention to EX or usual care (UC). The primary outcome was peak oxygen consumption, measured with cardiopulmonary exercise testing at baseline and 8 and 24 weeks. EX consisted of 8 weeks of home walking for 1 h/d, 5 d/wk at 60% to 80% of heart rate reserve, followed by 16 weeks of maintenance home walking for 150 min/wk. Adherence to EX was determined from exercise logs, ambulatory heart rate recordings of exercise, and weekly telephone contacts. Patients assigned to UC received no exercise directives and were monitored by monthly telephone contact. Adverse events were identified by ICD interrogations, patient reports, and medical charts. ICD recipients averaged 55±12 years and mean ejection fraction of 40.6±15.7; all were taking ß-blocker medications. EX significantly increased peak oxygen consumption (EX, 26.7±7.0 mL/kg per minute; UC, 23.9±6.6 mL/kg per minute; P=0.002) at 8 weeks, which persisted during maintenance exercise at 24 weeks (EX, 26.9±7.7 mL/kg per minute; UC, 23.4±6.0 mL/kg per minute; P<0.001). ICD shocks were infrequent (EX=4 versus UC=8), with no differences in hospitalizations or deaths between groups. CONCLUSIONS: Prescribed home exercise is safe and significantly improves cardiovascular performance in ICD recipients without causing shocks or hospitalizations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00522340.

Comparison of CT-derived ventilation maps with deposition patterns of inhaled microspheres in rats.

PURPOSE: Computer models for inhalation toxicology and drug-aerosol delivery studies rely on ventilation pattern inputs for predictions of particle deposition and vapor uptake. However, changes in lung mechanics due to disease can impact airflow dynamics and model results. It has been demonstrated that non-invasive, in vivo, 4DCT imaging (3D imaging at multiple time points in the breathing cycle) can be used to map heterogeneities in ventilation patterns under healthy and disease conditions. The purpose of this study was to validate ventilation patterns measured from CT imaging by exposing the same rats to an aerosol of fluorescent microspheres (FMS) and examining particle deposition patterns using cryomicrotome imaging. MATERIALS AND METHODS: Six male Sprague-Dawley rats were intratracheally instilled with elastase to a single lobe to induce a heterogeneous disease. After four weeks, rats were imaged over the breathing cycle by CT then immediately exposed to an aerosol of ∼ 1 µm FMS for ∼ 5 minutes. After the exposure, the lungs were excised and prepared for cryomicrotome imaging, where a 3D image of FMS deposition was acquired using serial sectioning. Cryomicrotome images were spatially registered to match the live CT images to facilitate direct quantitative comparisons of FMS signal intensity with the CT-based ventilation maps. RESULTS: Comparisons of fractional ventilation in contiguous, non-overlapping, 3D regions between CT-based ventilation maps and FMS images showed strong correlations in fractional ventilation (r = 0.888, p < 0.0001). CONCLUSION: We conclude that ventilation maps derived from CT imaging are predictive of the 1 µm aerosol deposition used in ventilation-perfusion heterogeneity inhalation studies.

Gas exchange and ventilation-perfusion relationships in the lung.

This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to clinical scenarios. For each gas exchanging unit, the alveolar and effluent blood partial pressures of oxygen and carbon dioxide (PO2 and PCO2) are determined by the ratio of alveolar ventilation to blood flow (V'A/Q') for each unit. Shunt and low V'A/Q' regions are two examples of V'A/Q' mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation, hypoventilation and low inspired PO2 cause hypoxaemia, even in the absence of V'A/Q' mismatch. In contrast to other causes, hypoxaemia due to shunt responds poorly to supplemental oxygen. Gas exchanging units with little or no blood flow (high V'A/Q' regions) result in alveolar dead space and increased wasted ventilation, i.e. less efficient carbon dioxide removal. Because of the respiratory drive to maintain a normal arterial PCO2, the most frequent result of wasted ventilation is increased minute ventilation and work of breathing, not hypercapnia. Calculations of alveolar-arterial oxygen tension difference, venous admixture and wasted ventilation provide quantitative estimates of the effect of V'A/Q' mismatch on gas exchange. The types of V'A/Q' mismatch causing impaired gas exchange vary characteristically with different lung diseases.

Airway tree segmentation in serial block-face cryomicrotome images of rat lungs.

A highly automated method for the segmentation of airways in the serial block-face cryomicrotome images of rat lungs is presented. First, a point inside of the trachea is manually specified. Then, a set of candidate airway centerline points is automatically identified. By utilizing a novel path extraction method, a centerline path between the root of the airway tree and each point in the set of candidate centerline points is obtained. Local disturbances are robustly handled by a novel path extraction approach, which avoids the shortcut problem of standard minimum cost path algorithms. The union of all centerline paths is utilized to generate an initial airway tree structure, and a pruning algorithm is applied to automatically remove erroneous subtrees or branches. Finally, a surface segmentation method is used to obtain the airway lumen. The method was validated on five image volumes of Sprague-Dawley rats. Based on an expert-generated independent standard, an assessment of airway identification and lumen segmentation performance was conducted. The average of airway detection sensitivity was 87.4% with a 95% confidence interval (CI) of (84.9, 88.6)%. A plot of sensitivity as a function of airway radius is provided. The combined estimate of airway detection specificity was 100% with a 95% CI of (99.4, 100)%. The average number and diameter of terminal airway branches was 1179 and 159 µm, respectively. Segmentation results include airways up to 31 generations. The regression intercept and slope of airway radius measurements derived from final segmentations were estimated to be 7.22 µm and 1.005, respectively. The developed approach enables the quantitative studies of physiology and lung diseases in rats, requiring detailed geometric airway models.

Ischemia-reperfusion lung injury is attenuated in MyD88-deficient mice.

Ischemia-reperfusion lung injury is a common cause of acute morbidity and mortality in lung transplant recipients and has been associated with subsequent development of bronchiolitis obliterans syndrome. Recognition of endogenous ligands released during cellular injury (damage-associated molecular patterns; DAMPs) by Toll-like receptors (TLRs), especially TLR4, has increasingly been recognized as a mechanism for inflammation resulting from tissue damage. TLR4 is implicated in the pathogenesis of ischemia-reperfusion injury of multiple organs including heart, liver, kidney and lung. Additionally, activation of TLRs other than TLR4 by DAMPs has been identified in tissues other than the lung. Because all known TLRs, with the exception of TLR3, signal via the MyD88 adapter protein, we hypothesized that lung ischemia-reperfusion injury was mediated by MyD88-dependent signaling. To test this hypothesis, we subjected C57BL/6 wildtype, Myd88(-/-), and Tlr4(-/-) mice to 1 hr of left lung warm ischemia followed by 4 hr of reperfusion. We found that Myd88(-/-) mice had significantly less MCP-1/CCL2 in the left lung following ischemia-reperfusion as compared with wildtype mice. This difference was associated with dramatically reduced lung permeability. Interestingly, Tlr4(-/-) mice had only partial protection from ischemia-reperfusion as compared to Myd88(-/-) mice, implicating other MyD88-dependent pathways in lung injury following ischemia-reperfusion. We also found that left lung ischemia-reperfusion caused remote inflammation in the right lung. Finally, using chimeric mice with MyD88 expression restricted to either myeloid or non-myeloid cells, we found that MyD88-dependent signaling in myeloid cells was necessary for ischemia-reperfusion induced lung permeability. We conclude that MyD88-dependent signaling through multiple receptors is important in the pathogenesis of acute lung inflammation and injury following ischemia and reperfusion.

Heterogeneity and matching of ventilation and perfusion within anatomical lung units in rats.

Prior studies exploring the spatial distributions of ventilation and perfusion have partitioned the lung into discrete regions not constrained by anatomical boundaries and may blur regional differences in perfusion and ventilation. To characterize the anatomical heterogeneity of regional ventilation and perfusion, we administered fluorescent microspheres to mark regional ventilation and perfusion in five Sprague-Dawley rats and then using highly automated computer algorithms, partitioned the lungs into regions defined by anatomical structures identified in the images. The anatomical regions ranged in size from the near-acinar to the lobar level. Ventilation and perfusion were well correlated at the smallest anatomical level. Perfusion and ventilation heterogeneity were relatively less in rats compared to data previously published in larger animals. The more uniform distributions may be due to a smaller gravitational gradient and/or the fewer number of generations in the distribution trees before reaching the level of gas exchange, making regional matching of ventilation and perfusion less extensive in small animals.

Late infusion of cloned marrow fibroblasts stimulates endogenous recovery from radiation-induced lung injury.

In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6)/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT). At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact). Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct), the total inspiratory capacity (IC), and the total lung capacity (TLC), which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1) positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC) of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.

Visualizing regional myocardial blood flow in the mouse.

RATIONALE: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information. OBJECTIVE: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice. METHODS AND RESULTS: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice. CONCLUSIONS: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.

Development and safety of an exercise testing protocol for patients with an implanted cardioverter defibrillator for primary or secondary indication.

PURPOSE: Performing exercise tests in patients with an implantable cardioverter defibrillator (ICD) presents specific challenges because of susceptibility to ventricular arrhythmias during maximal levels of exertion. The purpose of this paper is to outline the exercise testing protocol from the Anti-Arrhythmic Effects of Exercise after an ICD trial and to report baseline test results and safety outcomes using the protocol. METHODS AND RESULTS: Maximal cardiopulmonary exercise testing was performed to assess levels of physical fitness as part of a randomized trial of walking exercise in patients with ICDs. Subjects were randomized after baseline testing to aerobic exercise plus usual care or usual care alone. A modified Balke treadmill exercise test was used and specific ICD programming procedures were implemented to avoid unnecessary shocks, which included programming off ventricular tachycardia (VT) therapies during testing. To date, 161 baseline tests have been performed. One ventricular fibrillation (VF) cardiac arrest occurred following completion of an exercise test and three tests were stopped by the investigators due to nonsustained ventricular tachycardia. Eleven subjects were not able to achieve maximum exercise, defined as reaching an anaerobic threshold (AT) at baseline testing. There have been no deaths as a result of exercise testing. CONCLUSIONS: Symptom-limited maximal exercise testing can be performed safely and effectively in patients with ICDs for both primary and secondary prevention indications. Specific strategies for ICD programming and preparation for treating ventricular arrhythmias needs to be in place before exercise testing is performed.

Imaging regional PAO2 and gas exchange.

Several methods allow regional gas exchange to be inferred from imaging of regional ventilation and perfusion (V/Q) ratios. Each method measures slightly different aspects of gas exchange and has inherent advantages and drawbacks that are reviewed. Single photon emission computed tomography can provide regional measure of ventilation and perfusion from which regional V/Q ratios can be derived. PET methods using inhaled or intravenously administered nitrogen-13 provide imaging of both regional blood flow, shunt, and ventilation. Electric impedance tomography has recently been refined to allow simultaneous measurements of both regional ventilation and blood flow. MRI methods utilizing hyperpolarized helium-3 or xenon-129 are currently being refined and have been used to estimate local PaO(2) in both humans and animals. Microsphere methods are included in this review as they provide measurements of regional ventilation and perfusion in animals. One of their advantages is their greater spatial resolution than most imaging methods and the ability to use them as gold standards against which new imaging methods can be tested. In general, the reviewed methods differ in characteristics such as spatial resolution, possibility of repeated measurements, radiation exposure, availability, expensiveness, and their current stage of development.

Branch-based model for the diameters of the pulmonary airways: accounting for departures from self-consistency and registration errors.

We examine a previously published branch-based approach for modeling airway diameters that is predicated on the assumption of self-consistency across all levels of the tree. We mathematically formulate this assumption, propose a method to test it and develop a more general model to be used when the assumption is violated. We discuss the effect of measurement error on the estimated models and propose methods that take account of error. The methods are illustrated on data from MRI and CT images of silicone casts of two rats, two normal monkeys, and one ozone-exposed monkey. Our results showed substantial departures from self-consistency in all five subjects. When departures from self-consistency exist, we do not recommend using the self-consistency model, even as an approximation, as we have shown that it may likely lead to an incorrect representation of the diameter geometry. The new variance model can be used instead. Measurement error has an important impact on the estimated morphometry models and needs to be addressed in the analysis.