Airway Tree Research Articles

Segmental Bronchial Diameter Measurement at Inspiration-Expiration Phase by Low-dose MSCT in Healthy Volunteers

Objective: This study aimed to evaluate the normal range of quantitative CT in measuring the airway diameter at inspiration-expiration phase using 3D imaging in healthy adults. Materials and Methods: 68 healthy volunteers, including 42 males and 26 females, with the mean age of 49.3 (SD14.7) years, had undergone low-dose CT scan at full inspiration and the end of expiration. All CT scans were performed within the range from the lung apices to the diaphragm, at a tube potential of 120kVp and an effective mAs of 60. Afterwards, all CT images were analyzed using the 3D software (FUJIFILM Corporation SYNAPSE), and the airway tree was generated according to the automated region-growing technique, which was perpendicular to the cross section measurement of the segmental bronchus in bilateral lower lobes. Meanwhile, the imaging of segmental bronchus was classified as at inspiration and expiration phase in male group, and at inspiration and expiration phase in female group. Moreover, the Din-L and Din-S of the segmental bronchus were analyzed quantitatively. Difference in the segmental bronchial diameter between the inspiration and expiration phase group with the same sex was evaluated with paired-t test, while that between the male and female groups was analyzed by a 2-tailed unpaired t test. In addition, the impact of age, height, weight and BMI on Din-L and Din-S was assessed through multiple linear regression analysis. Results: 378 segmental branches in the lower lobe of lung from male group and 234 from female group were shown using the low-dose multi-slice spiral CT (MSCT) scan. All segmental bronchi were detected automatically using the 3D software. Our results suggested that, Din-L and Din-S in segmental bronchus of both male and female groups at inspiration phase were larger than those at expiration phase; and those in male group were greater than those in female group at both inspiration and expiration phases (P < 0.01). Meanwhile, the average of Din-L and Din-S was markedly related to age at both inspiration and expiration phases. Conclusions: The normal reference values and the likely ranges are determined for segmental bronchus diameter in the lower lobe of adult lung at inspiration-expiration phase. The average of Din-L and Din-S is evidently correlated with age and sex at both inspiration and expiration phases. The segmental bronchus diameter at inspiration phase in adolescents is larger than that at expiration phase.

Seeing the forest for the trees: fractal dimensions measure COPD airway remodeling.

Chronic obstructive pulmonary disease (COPD) is extremely heterogenous in its effects on airway remodeling. Parsing the complex and interrelated morphologic changes and understanding their contribution to disease severity has posed a significant challenge to the field. In the current issue of the JCI, Bodduluri et al. measured the complex effects of COPD on the airway tree using airway fractal dimension (AFD) on computerized tomography in a large cohort of smokers with and without COPD. They found that lower AFD was independently associated with disease severity and mortality in COPD. This work highlights AFD as a noninvasive approach to analyze complex changes in airway geometry.

Improvement of fully automated airway segmentation on volumetric computed tomographic images using a 2.5 dimensional convolutional neural net.

We propose a novel airway segmentation method in volumetric chest computed tomography (CT) and evaluate its performance on multiple datasets. The segmentation is performed voxel-by-voxel by a 2.5D convolutional neural net (2.5D CNN) trained in a supervised manner. To enhance the accuracy of the segmented airway tree, we simultaneously took three adjacent slices in each of the orthogonal directions including axial, sagittal, and coronal and fine-tuned the parameters that influence the tree length and the number of leakage. The gold standard of airway segmentation was generated by a semi-automated method using AVIEW™. The 2.5D CNN was trained and evaluated on a subset of inspiratory thoracic CT scans taken from the Korean obstructive lung disease study, which includes normal subjects and chronic obstructive pulmonary disease patients. The reliability and further practicality of our proposed method was demonstrated in multiple datasets. In eight test datasets collected by the same imaging protocol, the percentage detected tree length, false positive rate, and Dice similarity coefficient of our method were 92.16%, 7.74%, and 0.8997 ± 0.0892, respectively. In 20 test datasets of the EXACT'09 challenge, the percentage detected tree length was 60.1% and the false positive rate was 4.56%. Our fully automated (end-to-end) segmentation method could be applied in radiologic practice.

Particle Disposition in the Realistic Airway Tree Models of Subjects with Tracheal Bronchus and COPD.

Dispositions of inhalable particles in the human respiratory tract trigger and exacerbate airway inflammatory diseases. However, the particle deposition (PD) in airway of subjects with tracheal bronchus (TB) and chronic obstructive pulmonary diseases (COPD) is unknown. We therefore propose to clarify the disrupted PD associated with TB and COPD using the computational fluid dynamics (CFD) simulation. Totally nine airway tree models are included. Six are extracted from CT images of different individuals (two with TB, two with COPD, and two healthy controls (HC)). The others are the artificially modified models (AMMs) generated by the virtual lesion. Specifically, they are constructed through artificially adding a tracheal bronchus or a stenosis on one HC model. The deposition efficiency (DE) and deposition fraction (DF) in these models are obtained by the Euler-Lagrange approach, analyzed, and compared across models, locations, and particle sizes (0.1-10.0 micrometers). It is found that the PD in models with TB and COPD has been disrupted by the geometrical changes and followed airflow alternations. DE of the tracheal bronchus is higher for TB models. For COPD, the stenosis location determines the effects on DE and DF. Higher DF at the trachea is observed in TB1, TB2, and COPD2 models. DE increases with the particle size, and DE of the terminal bronchi is higher than that of central regions. Combined with AMMs, the CFD simulation using realistic airway models demonstrates disruptions of DP. The methods and findings might help understand the etiology of pulmonary diseases and improve the efficacy of inhaled medicines.

Efficient Bronchoscopic Video Summarization.

Bronchoscopy enables many minimally invasive chest procedures for diseases such as lung cancer and asthma. Guided by the bronchoscope's video stream, a physician can navigate the complex three-dimensional (3-D) airway tree to collect tissue samples or administer a disease treatment. Unfortunately, physicians currently discard procedural video because of the overwhelming amount of data generated. Hence, they must rely on memory and anecdotal snapshots to document a procedure. We propose a robust automatic method for summarizing an endobronchial video stream. Inspired by the multimedia concept of the video summary and by research in other endoscopy domains, our method consists of three main steps: 1) shot segmentation, 2) motion analysis, and 3) keyframe selection. Overall, the method derives a true hierarchical decomposition, consisting of a shot set and constituent keyframe set, for a given procedural video. No other method to our knowledge gives such a structured summary for the raw, unscripted, unedited videos arising in endoscopy. Results show that our method more efficiently covers the observed endobronchial regions than other keyframe-selection approaches and is robust to parameter variations. Over a wide range of video sequences, our method required on average only 6.5% of available video frames to achieve a video coverage = 92.7%. We also demonstrate how the derived video summary facilitates direct fusion with a patient's 3-D chest computed-tomography scan in a system under development, thereby enabling efficient video browsing and retrieval through the complex airway tree.

Quantitative Analysis of Airway Tree in Low-dose Chest CT with a New Model-based Iterative Reconstruction Algorithm: Comparison to Adaptive Statistical Iterative Reconstruction in Routine-dose CT

We aimed to evaluate a new model-based iterative reconstruction (MBIRn) algorithm either with spatial resolution and noise reduction balance (MBIRSTND) or spatial resolution preference (MBIRRP20) for quantitative analysis of airway in low-dose chest computed tomography (CT) with a computer-aided detection (CAD) software, in comparison to adaptive statistical iterative reconstruction (ASIR) in routine-dose CT. Thirty patients who underwent both the routine-dose (noise index [NI] = 14 HU) and low-dose (at 30% level with NI = 28 HU) CT examination for pulmonary disease were included. Image acquisition was performed with 120 kVp tube voltage and automatic tube current modulation. Routine-dose scans were reconstructed with ASIR, whereas low-dose scans were reconstructed with ASIR, MBIRSTND, and MBIRRP20. Airway dimensions of the right middle lobe bronchus from the four reconstructions were measured using CAD software. Two radiologists used a semiquantitative 5 scoring criteria (-2, inferior to; +2, superior to; -1 slightly inferior to; +1, slightly superior to; and 0, equal to ASIR in routine-dose CT) to rate the subjective image quality of MBIRSTND and MBIRRP20 of airway trees. The paired t test and Wilcoxon signed-rank test were used for statistical comparison. The low-dose CT provided 70.76% dose reduction compared to the routine-dose CT (0.88 ± 0.83 mSv vs 3.01 ± 1.89 mSv). MBIRSTND and MBIRRP20 with low-dose CT provided longer bronchial length measurements and were better in measurement variability and continuity and completeness of bronchial walls than ASIR in routine-dose CT (P < .05). MBIRSTND was better for subjective noise and MBIRRP20 for showing distal branches. CONCLUSIONS: MBIRSTND and MBIRRP20 algorithms provide better airway quantification at 30% of the radiation dose, compared to ASIR at routine-dose CT.

Unsupervised CT Lung Image Segmentation of a Mycobacterium Tuberculosis Infection Model

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that produces pulmonary damage. Radiological imaging is the preferred technique for the assessment of TB longitudinal course. Computer-assisted identification of biomarkers eases the work of the radiologist by providing a quantitative assessment of disease. Lung segmentation is the step before biomarker extraction. In this study, we present an automatic procedure that enables robust segmentation of damaged lungs that have lesions attached to the parenchyma and are affected by respiratory movement artifacts in a Mycobacterium Tuberculosis infection model. Its main steps are the extraction of the healthy lung tissue and the airway tree followed by elimination of the fuzzy boundaries. Its performance was compared with respect to a segmentation obtained using: (1) a semi-automatic tool and (2) an approach based on fuzzy connectedness. A consensus segmentation resulting from the majority voting of three experts’ annotations was considered our ground truth. The proposed approach improves the overlap indicators (Dice similarity coefficient, 94% ± 4%) and the surface similarity coefficients (Hausdorff distance, 8.64 mm ± 7.36 mm) in the majority of the most difficult-to-segment slices. Results indicate that the refined lung segmentations generated could facilitate the extraction of meaningful quantitative data on disease burden.

Airway Segmentation from 3D Chest CT Volumes Based on Volume of Interest Using Gradient Vector Flow

Some lung diseases are related to bronchial airway structures and morphology. Although airway segmentation from chest CT volumes is an important task in the computer-aided diagnosis and surgery assistance systems for the chest, complete 3-D airway structure segmentation is a quite challenging task due to its complex tree-like structure. In this paper, we propose a new airway segmentation method from 3D chest CT volumes based on volume of interests (VOI) using gradient vector flow (GVF). This method segments the bronchial regions by applying the cavity enhancement filter (CEF) to trace the bronchial tree structure from the trachea. It uses the CEF in the VOI to segment each branch. And a tube-likeness function based on GVF and the GVF magnitude map in each VOI are utilized to assist predicting the positions and directions of child branches. By calculating the tube-likeness function based on GVF and the GVF magnitude map, the airway-like candidate structures are identified and their centrelines are extracted. Based on the extracted centrelines, we can detect the branch points of the bifurcations and directions of the airway branches in the next level. At the same time, a leakage detection is performed to avoid the leakage by analysing the pixel information and the shape information of airway candidate regions extracted in the VOI. Finally, we unify all of the extracted bronchial regions to form an integrated airway tree. Preliminary experiments using four cases of chest CT volumes demonstrated that the proposed method can extract more bronchial branches in comparison with other methods.

Use of Submicron Vaterite Particles Serves as an Effective Delivery Vehicle to the Respiratory Portion of the Lung.

Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses.

Airway obstruction and pulmonary mechanics remain understudied despite lung disease being the third cause of death in the United States. Lack of relevant data has led computational pulmonary models to infer mechanical properties from available material data for the trachea. Additionally, the time-dependent, viscoelastic behaviors of airways have been largely overlooked, despite their potential physiological relevance and utility as metrics of tissue remodeling and disease progression. Here, we address the clear need for airway-specific material characterization to inform biophysical studies of the bronchial tree. Specimens from three airway levels (trachea, large bronchi, and small bronchi) and two orientations (axial and circumferential) were prepared from five fresh pig lungs. Uniaxial tensile tests revealed substantial heterogeneity and anisotropy. Overall, the linear pseudoelastic modulus was significantly higher axially than circumferentially (30.5 ± 3.1 vs. 8.4 ± 1.1 kPa) and significantly higher among circumferential samples for small bronchi than for the trachea and large bronchi (12.5 ± 1.9 vs. 6.0 ± 0.6 and 6.6 ± 0.9 kPa). Circumferential samples exhibited greater percent stress relaxation over 300 s than their axial counterparts (38.0 ± 1.4 vs. 23.1 ± 1.5%). Axial and circumferential trachea samples displayed greater percent stress relaxation (26.4 ± 1.6 and 42.5 ± 1.7%) than corresponding large and small bronchi. This ex vivo pseudoelastic and viscoelastic characterization reveals novel anisotropic and heterogeneous behaviors and equips us to construct airway-specific constitutive relations. Our results establish necessary fundamentals for airway mechanics, laying the groundwork for future studies to extend to clinical questions surrounding lung injury, and further directly enables computational tools for lung disease obstruction predictions. NEW & NOTEWORTHY Understanding the mechanics of the lung is necessary for investigating disease progression. Trachea mechanics comprises the vast majority of ex vivo airway tissue characterization despite distal airways being the site of disease manifestation and occlusion. Furthermore, viscoelastic studies are scarce, whereas time-dependent behaviors could be potential physiological metrics of tissue remodeling. In this study, the critical need for airway-specific material properties is addressed, reporting bronchial tree anisotropic and heterogeneous material properties.

Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

The pulmonary route presents an attractive delivery pathway for topical treatment of lung diseases. While significant progress has been achieved in understanding the physical underpinnings of aerosol deposition in the lungs, our ability to target or confine the deposition of inhalation aerosols to specific lung regions remains meagre. Here, we present a novel inhalation proof-of-concept in silico for regional targeting in the upper airways, quantitatively supported by computational fluid dynamics (CFD) simulations of inhaled micron-sized particles (i.e. 1-10 μm) using an intubated, anatomically-realistic, multi-generation airway tree model. Our targeting strategy relies on selecting the particle release time, whereby a short-pulsed bolus of aerosols is injected into the airways and the inhaled volume of clean air behind the bolus is tracked to reach a desired inhalation depth (i.e. airway generations). A breath hold maneuver then follows to facilitate deposition, via sedimentation, before exhalation resumes and remaining airborne particles are expelled. Our numerical findings showcase how particles in the range 5-10 μm combined with such inhalation methodology are best suited to deposit in the upper airways, with deposition fractions between 0.68 and unity. In contrast, smaller (< 2 μm) particles are less than optimal due to their slow sedimentation rates. We illustrate further how modulating the volume inhaled behind the pulsed bolus, prior to breath hold, may be leveraged to vary the targeted airway sites. We discuss the feasibility of the proposed inhalation framework and how it may help pave the way for specialized topical lung treatments.

Multiple abdominal burst patterns observed during tracheobronchial coughing in anesthetized cats

The cough motor pattern is classically defined as a neuromechanical sequence of inspiration, compression, and expulsion. This definition is most applicable to single coughs. However, humans routinely produce multiple expulsions per each inspiratory effort during single or repetitive coughing. The functional significance of this coughing pattern is not fully understood, but it could represent a mechanism to facilitate the stairstep movement of particulates and mucus up the airway tree against gravity in humans. This repetitive expulsion pattern following single inspiratory cough efforts has not been reported in animal models of coughing. In the anesthetized cat, repetitive coughing can be produced by either mechanical or chemical stimulation of airway afferents. We hypothesized that expulsive cough motor patterns consistent with those seen in humans could be observed in the anesthetized cat. Further, we have previously observed that thoracotomy depresses cough excitability, presumably though a decrease in pulmonary volume‐related feedback. We also hypothesized that thoracotomy would reduce the occurrence of coughs in which multiple expiratory bursts were observed. We investigated the cough patterns of 9 cats pre‐ (n=5) and post‐thoracotomy (n=4) for multiple abdominal bursting patterns during cough. Thoracotomized animals were artificially ventilated at a positive end expiratory pressure of 5 cmH2O. Electromyograms (EMGs) were recorded from the diaphragm, thyroarytenoid, and internal oblique muscles. Repetitive coughing was produced by mechanical stimulation of the intrathoracic airway. The percentage of cough epochs that contained at least one cough with a multiple bursting pattern was similar for closed (CC, 44±18%) and open chested (OC, 42±11%) animals. These patterns consisted of double abdominal bursts (71%), three abdominal bursts (23%) and four bursts (5%). Corresponding abdominal bursts had similar amplitudes in both CC and OC animals. In OC animals, the amplitude of the second abdominal burst (CC − 45±11 to 31±7%, p=n.s.; OC − 43±4 to 28±5, p&lt;0.05) was significantly lower than the first. Thoracotomy prolonged E2 duration for coughs with only 1 expiratory burst (CC 1±0.2s; OC 2±0.4 s, p &lt; 0.05), but not for multiple expiratory bursts (CC 0.6±0.1 s; OC 0.9±0.4 s). The time between multiple abdominal bursts (CC 232±16 msec; OC 233±32 msec) was not different after thoracotomy. In some animals, small amplitude bursts in thyroarytenoid EMGs occurred out of phase with multiple abdominal bursting, consistent with adductor/abdominal oscillations. We conclude that the anesthetized cat is capable of expressing multiple abdominal bursting following a single inspiratory effort during tracheobronchial coughing. Our results support the existence of multiple oscillatory patterns during repetitive tracheobronchial coughing in the cat. This pattern may be analogous to that exhibited by awake humans.Support or Funding InformationSupported by NIH HL 103415 and 1OT20D001983.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modeling Inspiratory Flow in a Porcine Lung Airway.

Inspiratory flow in a multigeneration pig lung airways was numerically studied at a steady inlet flow rate of 3.2 × 10-4 m3/s corresponding to a Reynolds number of 1150 in the trachea. The model was validated by comparing velocity distributions with previous measurements and simulations in simplified airway geometries. Simulation results provided detailed maps of the axial and secondary flow patterns at different cross sections of the airway tree. The vortex core regions in the airways were visualized using absolute helicity values and suggested the presence of secondary flow vortices where two counter-rotating vortices were observed at the main bifurcation and in many other bifurcations. Both laminar and turbulent flows were considered. Results showed that axial and secondary flows were comparable in the laminar and turbulent cases. Turbulent kinetic energy (TKE) vanished in the more distal airways, which indicates that the flow in these airways approaches laminar flow conditions. The simulation results suggested viscous pressure drop values comparable to earlier studies. The monopodial asymmetric nature of airway branching in pigs resulted in airflow patterns that are different from the less asymmetric human airways. The major daughters of the pig airways tended to have high airflow ratios, which may lead to different particle distribution and sound generation patterns. These differences need to be taken into consideration when interpreting the results of animal studies involving pigs before generalizing these results to humans.

Oscillometry and pulmonary MRI measurements of ventilation heterogeneity in obstructive lung disease: relationship to quality of life and disease control.

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized 3He magnetic resonance imaging (MRI) and determined their relationships with quality of life scores and disease control/exacerbations. We also coregistered MRI ventilation maps to a computational airway tree model to generate patient-specific respiratory impedance predictions for comparison with experimental measurements. In COPD and asthma patients, respectively, forced oscillation technique (FOT)-derived peripheral resistance (5-19 Hz) and MRI ventilation defect percentage (VDP) were significantly related to quality of life (FOT: COPD ρ = 0.4, P = 0.004; asthma ρ = -0.3, P = 0.04; VDP: COPD ρ = 0.6, P = 0.003; asthma ρ = -0.3, P = 0.04). Patients with poorly controlled asthma (Asthmatic Control Questionnaire >2) had significantly increased resistance (5 Hz: P = 0.01; 5-19 Hz: P = 0.006) and reactance (5 Hz: P = 0.03). FOT-derived peripheral resistance (5-19 Hz) was significantly related to VDP in patients with asthma and COPD patients (asthma: ρ = 0.5, P < 0.001; COPD: ρ = 0.5, P = 0.01), whereas total respiratory impedance was related to VDP only in patients with asthma (resistance 5 Hz: ρ = 0.3, P = 0.02; reactance 5 Hz: ρ = -0.5, P < 0.001). Model-predicted and FOT-measured reactance (5 Hz) were correlated in patients with asthma (ρ = 0.5, P = 0.001), whereas in COPD patients, model-predicted and FOT-measured resistance (5-19 Hz) were correlated (ρ = 0.5, P = 0.004). In summary, in patients with asthma and COPD patients, we observed significant, independent relationships for FOT-measured impedance and MRI ventilation heterogeneity measurements with one another and with quality of life scores. NEW & NOTEWORTHY In 100 patients, including patients with asthma and ex-smokers, 3He MRI ventilation heterogeneity and respiratory system impedance were correlated and both were independently related to quality of life scores and asthma control. These findings demonstrated the critical relationships between respiratory system impedance and ventilation heterogeneity and their role in determining quality of life and disease control. These observations underscore the dominant role that abnormalities in the lung periphery play in ventilation heterogeneity that results in patients' symptoms.

Early Acoustic Warning for the Onset of Acute Chest Syndrome in Sickle Cell Patients

Acute chest syndrome (ACS) is a leading cause of death for those with sickle cell disease (SCD). ACS is defined by the development of a new pulmonary infiltrate on chest X-ray, with fever and respiratory symptoms. Efforts have been made to apply various technologies in the hospital setting to provide earlier detection of ACS than X-ray, but they are expensive, increase radiation exposure to the patient, and are not technologies that are easily transferrable for home use to help with early diagnosis. We present preliminary studies on patients suggesting that acoustical measurements recorded quantitatively with contact sensors (electronic stethoscopes) and analyzed using advanced computational analysis methods may provide an earlier diagnostic indicator of the onset of ACS than is possible with current clinical practice. Novel in silico models of respiratory acoustics utilizing image-based and algorithmically developed lungs with full conducting airway trees support and help explain measured acoustic trends and provide guidance on the next steps in developing and translating a diagnostic approach. More broadly, the experimental and computational techniques introduced herein, while focused on monitoring and predicting the onset of ACS, could catalyze further advances in mobile health (mhealth)-enabled, computer-based auscultative diagnoses for a wide range of cardiopulmonary pathologies.

Localization of adventitious respiratory sounds.

In a recent publication by Henry and Royston [J. Acoust. Soc. Am. 142, 1774-1783 (2017)], an algorithm was introduced to calculate the acoustic response to externally introduced and endogenous respiratory sounds within a realistic, patient-specific subglottal airway tree. This work is extended using an efficient numerical boundary element (BE) approach to calculate the resulting radiated sound field from the airway tree into the lung parenchyma taking into account the surrounding chest wall. Within the BE model of the left lung parenchyma, comprised of more than 6000 triangular surface elements, more than 30 000 monopoles are used to approximate complex airway-originated acoustic sources. The chest wall is modeled as a boundary condition on the parenchymal surface. Several cases were simulated, including a bronchoconstricted lung that had an internal acoustic source introduced in a bronchiole, approximating a wheeze. An acoustic source localization algorithm coupled to the BE model estimated the wheeze source location to within a few millimeters based solely on the acoustic field at the surface. Improved noninvasive means of locating adventitious respiratory sounds may enhance an understanding of acoustic changes correlated to pathology, and potentially provide improved noninvasive tools for the diagnosis of pulmonary diseases that uniquely alter acoustics.

COPD risk: Clues from the tree branches

Lung Disease Chronic obstructive pulmonary disease (COPD) is estimated to affect 250 million people worldwide. Smoking is a major risk factor, but intrinsic host factors likely also play a role. Smith et al. hypothesized that variations in central airway tree branching might affect COPD risk. They

Cournand's and Richards' Post-Nobel Challenge: "Do Anything on the Structure of the Lung That Is of Interest for Physiology".

In their Nobel Lectures of 1956, the two cardiopulmonary physiologists André Cournand and Dickinson Richards described the future projects that they considered important for rounding up their impressive scientific achievements. One of them called for work that brought together structure and function of the lung in a systematic way. They challenged a young anatomist to undertake this in their cardiopulmonary laboratory at Bellevue Hospital. The first steps established the need for quantitative information on the structures that form the pulmonary gas exchanger as well as the airway tree. This resulted in a new approach to lung anatomy: morphometry would provide the quantitative information for modeling structure-function relations in the lung, and eventually in the entire respiratory system, thus allowing a rational analysis of how structures affect or limit functions.

Particulate Deposition in a Patient With Tracheal Stenosis

The presence of obstructions such as tracheal stenosis has important effects on respiratory functions. Tracheal stenosis impacts the therapeutic efficacy of inhaled medications as a result of alterations in particle transport and deposition pattern. This study explores the effects of the presence and absence of stenosis/obstruction in the trachea on air flow characteristics and particle depositions. Computational fluid dynamics (CFD) simulations were performed on three-dimensional (3D) patient-specific models created from computed tomography (CT) images. The analyzed model was generated from a subject with tracheal stenosis and includes the airway tree up to eight generations. CT scans of expiratory and inspiratory phases were used for patient-specific boundary conditions. Pre- and post-intervention CFD simulations' comparison reveals the effect of the stenosis on the characteristics of air flow, transport, and depositions of particles with diameters of 1, 2.5, 4, 6, 8, and 10 μm. Results indicate that the existence of the stenosis inflicts a major pressure force on the flow of inhaled air, leading to an increased deposition of particles both above and below the stenosis. Comparisons of the decrease in pressure in each generation between pre- and post-tracheal stenosis intervention demonstrated a significant reduction in pressure following the stenosis, which was maintained in all downstream generations. Good agreements were found using experimental validation of CFD findings with a model of the control subject up to the third generation, constructed via additive layer manufacturing from CT images.

Morphological and functional properties of the conducting human airways investigated by in vivo computed tomography and in vitro MRI.

The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyzed CT scans of a cohort of healthy subjects and obtained comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. Although some of the geometric parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluated several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we used phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the three-dimensional-printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e., transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models and persists within the first seven generations. NEW & NOTEWORTHY We performed a comprehensive computed tomography-based study of the conductive airway morphology in normal human subjects, including branch diameter, length, and mutual angles. We found significant departure from classic homothetic relationships. We also carried out MRI measurements of the three-dimensional inspiratory flow in an anatomy-based model and directly assessed structure-function relationships that have so far been assumed. We found that strong secondary flows (i.e., transverse velocity components) persist through the first seven generations of bronchial branching.