scholarly journals Modelling structural determinants of ventilation heterogeneity: a perturbative approach

2018 ◽  
Author(s):  
Carl A. Whitfield ◽  
Alex Horsley ◽  
Oliver E. Jensen
Keyword(s):  
Structural Changes ◽  
Human Lung ◽  
Clinical Test ◽  
Computationally Efficient ◽  
Structural Determinants ◽  
Perturbative Approach ◽  
Lung Structure ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Clinically Significant

AbstractWe have developed a computational model of gas mixing and ventilation in the human lung represented as a bifurcating network. We have simulated multiple-breath washout (MBW), a clinical test for measuring ventilation heterogeneity (VH) in patients with obstructive lung conditions. By applying airway constrictions inter-regionally, we have predicted the response of MBW indices to obstructions and found that they detect a narrow range of severe constrictions that reduce airway radius to 10%–30% of healthy values. These results help to explain the success of the MBW test to distinguish obstructive lung conditions from healthy controls. Further, we have used a perturbative approach to account for intra-regional airway heterogeneity that avoids modelling each airway individually. We have found, for random airway heterogeneity, that the variance in MBW indices is greater when indices are already elevated due to constrictions. By quantifying this effect, we have shown that variability in lung structure and mechanical properties alone can lead to clinically significant variability in LCI and Scond, but only in cases simulating obstructive lung conditions. This method is a computationally efficient way to probe the lung’s sensitivity to structural changes, and to quantify uncertainty in predictions due to random variations in lung mechanical and structural properties.

scholarly journals Ventilation heterogeneity in smokers: role of unequal lung expansion and peripheral lung structure

2020 ◽  
Vol 129 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Sylvia A.B. Verbanck ◽  
Mathias Polfliet ◽  
Daniel Schuermans ◽  
Bart Ilsen ◽  
Johan de Mey ◽  
...  
Keyword(s):  
Computer Tomography ◽  
Response Mapping ◽  
Lung Structure ◽  
Lung Expansion ◽  
Peripheral Structure ◽  
Peripheral Lung ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Parametric Response

A head-on comparison between imaging and multiple breath washout in supine smokers shows that computer tomography-measured unequal local lung expansion accounts for 50% or less of smoking-induced increase in ventilation heterogeneity. The contributions from unequal lung expansion and peripheral structure to the two main washout indices also explain their respective association with parametric response mapping indices.

scholarly journals Nondestructive cryomicro-CT imaging enables structural and molecular analysis of human lung tissue

2017 ◽  
Vol 122 (1) ◽  
pp. 161-169 ◽  
Author(s):  
Dragoş M. Vasilescu ◽  
André B. Phillion ◽  
Naoya Tanabe ◽  
Daisuke Kinose ◽  
David F. Paige ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Structural Changes ◽  
Human Lung ◽  
Three Dimensional ◽  
Ct Imaging ◽  
Matrix Composition ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Human Lung Tissue ◽  
Lung Structure

Micro-computed tomography (CT) enables three-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryostage that permits micro-CT imaging of unfixed frozen human lung samples at an isotropic voxel size of (11 µm)3 under conditions where the sample is maintained frozen at −30°C during imaging. The cryostage was tested for thermal stability to maintain samples frozen up to 8 h. This report describes the methods used to choose the materials required for cryostage construction and demonstrates that whole genome mRNA integrity and expression are not compromised by exposure to micro-CT radiation and that the tissue can be used for immunohistochemistry. The new cryostage provides a novel method enabling integration of 3D tissue structure with cellular and molecular analysis to facilitate the identification of molecular determinants of disease. NEW & NOTEWORTHY The described micro-CT cryostage provides a novel way to study the three-dimensional lung structure preserved without the effects of fixatives while enabling subsequent studies of the cellular matrix composition and gene expression. This approach will, for the first time, enable researchers to study structural changes of lung tissues that occur with disease and correlate them with changes in gene or protein signatures.

scholarly journals Modelling structural determinants of ventilation heterogeneity: A perturbative approach

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0208049 ◽  
Author(s):  
Carl A. Whitfield ◽  
Alex Horsley ◽  
Oliver E. Jensen
Keyword(s):  
Structural Determinants ◽  
Perturbative Approach ◽  
Ventilation Heterogeneity

scholarly journals Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-214717
Author(s):  
Frederik Trinkmann ◽  
Máté Maros ◽  
Katharina Roth ◽  
Arne Hermanns ◽  
Julia Schäfer ◽  
...  
Keyword(s):  
Reference Values ◽  
Sulfur Hexafluoride ◽  
Early Adulthood ◽  
Anthropometric Parameters ◽  
Cross Sectional ◽  
Outcome Parameters ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Registration Number ◽  
Never Smokers

BackgroundMultiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults.MethodsWe evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20–88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile.ResultsAge was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond.ConclusionSF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range.Trial registration numberNCT04099225.

scholarly journals Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout

2018 ◽  
Vol 52 (5) ◽  
pp. 1800821 ◽  
Author(s):  
Laurie J. Smith ◽  
Guilhem J. Collier ◽  
Helen Marshall ◽  
Paul J.C. Hughes ◽  
Alberto M. Biancardi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cystic Fibrosis ◽  
Total Lung Capacity ◽  
Resonance Imaging ◽  
Ventilation Distribution ◽  
Lung Clearance ◽  
Lung Capacity ◽  
Lung Clearance Index ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection–diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVT strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=−0.79 and r=−0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIVT, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.

Quantification of human lung structure and physiology using hyperpolarized 129 Xe

2013 ◽  
Vol 71 (1) ◽  
pp. 339-344 ◽  
Author(s):  
Yulin V. Chang ◽  
James D. Quirk ◽  
Iulian C. Ruset ◽  
Jeffrey J. Atkinson ◽  
F. William Hersman ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Structure

The aging lung

1999 ◽  
Vol 9 (2) ◽  
pp. 103-115 ◽  
Author(s):  
Christopher AE Dyer ◽  
Robert A Stockley
Keyword(s):  
Lung Disease ◽  
Elderly People ◽  
Human Lung ◽  
Environmental Pollutants ◽  
Tobacco Consumption ◽  
Structure And Function ◽  
Lung Structure ◽  
Pulmonary Changes ◽  
And Function ◽  
Disease Exposure

Over a lifetime, the human lung is exposed to a multitude of factors capable of altering its structure and function. The frequency of acute, self-limiting lung disease, exposure to environmental pollutants and previous tobacco consumption in elderly people makes it difficult to identify pulmonary changes that can be attributed to ‘normal aging’ alone. It is likely that all these factors may have some influence on both lung structure and function.

Structural determinants of glomerular hydraulic permeability

1994 ◽  
Vol 266 (1) ◽  
pp. F1-F12 ◽  
Author(s):  
M. C. Drumond ◽  
W. M. Deen
Keyword(s):  
Basement Membrane ◽  
Hydraulic Resistance ◽  
Structural Changes ◽  
Water Movement ◽  
Capillary Wall ◽  
Hydraulic Permeability ◽  
Structural Determinants ◽  
Membrane Area

To elucidate which structures determine the resistance to water movement, we used a computational fluid dynamics approach to determine velocity and pressure fields within the glomerular capillary wall. The model included representations of the endothelial fenestrae, basement membrane, and epithelial filtration slits with slit diaphragms. The input data included dimensions of the various structures from previous electron microscopy studies, as well as the hydraulic permeability recently measured for isolated films of glomerular basement membrane in vitro. The hydraulic resistance of the endothelium was predicted to be small, whereas the basement membrane and filtration slits were each found to contribute roughly one-half of the total hydraulic resistance of the capillary wall. It was calculated that, for a given filtrate flux, the pressure drop within basement membrane in vivo is roughly twice that of “bare” or isolated basement membrane, because of the small fraction of basement membrane area exposed. The dominant resistance in the filtration slit was found to be the slit diaphragm. Predicted values for the overall hydraulic permeability of the capillary wall were within the experimental range derived from micropuncture measurements in normal rats. The model should be a useful tool for analyzing the effects of various structural changes on glomerular hydraulic permeability. This is illustrated by applying the model to recent physiological and morphometric data in nephrotic rats.

Sign in / Sign up

Export Citation Format

Share Document