Evaluating the role of sex-related structure-function differences on airway aerosol transport and deposition.

Several experimental studies have found that females have higher particle deposition in the airways than males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of one-dimensional (1-D) ventilation distribution, particle transport, and deposition.

Quantitative Analysis of Lung Shape in Idiopathic Pulmonary Fibrosis: Insights Into Disease- and Age-Associated Patterns.

Rationale And Objectives: Fibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging.

A Wearable Open-Source electrical impedance tomography device.

Electrical impedance tomography (EIT) is medical imaging technique in which small electrical signals are used to map the electrical impedance distribution within the body. It is safe and non-invasive, which make it attractive for use in continuous monitoring or outpatient applications, but the high cost of commercial devices is an impediment to its adoption. Over the last 10 years, many research groups have developed their own EIT devices, but few designs for open-source EIT hardware are available.

A novel two-dimensional phantom for electrical impedance tomography using 3D printing.

Electrical impedance tomography (EIT) is an imaging method that can be used to image electrical impedance contrasts within various tissues of the body. To support development of EIT measurement systems, a phantom is required that represents the electrical characteristics of the imaging domain. No existing type of EIT phantom combines good performance in all three characteristics of resistivity resolution, spatial resolution, and stability.

Pulmonary response prediction through personalized basis functions in a virtual patient model.

Background And Objective: Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings.

Methods: This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance.

Sustained vs. Intratidal Recruitment in the Injured Lung During Airway Pressure Release Ventilation: A Computational Modeling Perspective.

Introduction: During mechanical ventilation, cyclic recruitment and derecruitment (R/D) of alveoli result in focal points of heterogeneous stress throughout the lung. In the acutely injured lung, the rates at which alveoli can be recruited or derecruited may also be altered, requiring longer times at higher pressure levels to be recruited during inspiration, but shorter times at lower pressure levels to minimize collapse during exhalation. In this study, we used a computational model to simulate the effects of airway pressure release ventilation (APRV) on acinar recruitment, with varying inspiratory pressure levels and durations of exhalation.

Evaluating Tissue Heterogeneity in the Radiologically Normal-Appearing Tissue in IPF Compared to Healthy Controls.

Rationale And Objectives: Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterised by heterogeneously distributed fibrotic lesions. The inter- and intra-patient heterogeneity of the disease has meant that useful biomarkers of severity and progression have been elusive. Previous quantitative computed tomography (CT) based studies have focussed on characterising the pathological tissue.

Improved Electrical Impedance Tomography Reconstruction via a Bayesian Approach With an Anatomical Statistical Shape Model.

Objective: electrical impedance tomography (EIT) is a promising technique for rapid and continuous bedside monitoring of lung function. Accurate and reliable EIT reconstruction of ventilation requires patient-specific shape information. However, this shape information is often not available and current EIT reconstruction methods typically have limited spatial fidelity.

Roadmap for an imaging and modelling paediatric study in rural NZ.

Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child.

Pulmonary vessel volume in idiopathic pulmonary fibrosis compared with healthy controls aged > 50 years.

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive fibrosing interstitial pneumonia with an associated irreversible decline in lung function and quality of life. IPF prevalence increases with age, appearing most frequently in patients aged > 50 years. Pulmonary vessel-like volume (PVV) has been found to be an independent predictor of mortality in IPF and other interstitial lung diseases, however its estimation can be impacted by artefacts associated with image segmentation methods and can be confounded by adjacent fibrosis.

Simulating Multi-Scale Pulmonary Vascular Function by Coupling Computational Fluid Dynamics With an Anatomic Network Model.

The function of the pulmonary circulation is truly multi-scale, with blood transported through vessels from centimeter to micron scale. There are scale-dependent mechanisms that govern the flow in the pulmonary vascular system. However, very few computational models of pulmonary hemodynamics capture the physics of pulmonary perfusion across the spatial scales of functional importance in the lung.

Non-invasive over-distension measurements: data driven vs model-based.

Clinical measurements offer bedside monitoring aiming to minimise unintended over-distension, but have limitations and cannot be predicted for changes in mechanical ventilation (MV) settings and are only available in certain MV modes. This study introduces a non-invasive, real-time over-distension measurement, which is robust, predictable, and more intuitive than current methods. The proposed over-distension measurement, denoted as OD, is compared with the clinically proven stress index (SI).

Reconstructing asynchrony for mechanical ventilation using a hysteresis loop virtual patient model.

Background: Patient-specific lung mechanics during mechanical ventilation (MV) can be identified from measured waveforms of fully ventilated, sedated patients. However, asynchrony due to spontaneous breathing (SB) effort can be common, altering these waveforms and reducing the accuracy of identified, model-based, and patient-specific lung mechanics.

Methods: Changes in patient-specific lung elastance over a pressure-volume (PV) loop, identified using hysteresis loop analysis (HLA), are used to detect the occurrence of asynchrony and identify its type and pattern.

A computational model of contributors to pulmonary hypertensive disease: impacts of whole lung and focal disease distributions.

Pulmonary hypertension has multiple etiologies and so can be difficult to diagnose, prognose, and treat. Diagnosis is typically made via invasive hemodynamic measurements in the main pulmonary artery and is based on observed elevation of mean pulmonary artery pressure. This static mean pressure enables diagnosis, but does not easily allow assessment of the severity of pulmonary hypertension, nor the etiology of the disease, which may impact treatment.

Over-distension prediction via hysteresis loop analysis and patient-specific basis functions in a virtual patient model.

Background And Objective: Recruitment maneuvers (RMs) with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveolar collapse. However, a suboptimal PEEP could induce undesired injury in lungs by insufficient or excessive breath support. Thus, a predictive model for patient response under PEEP changes could improve clinical care and lower risks.

Integrative Computational Models of Lung Structure-Function Interactions.

Anatomically based integrative models of the lung and their interaction with other key components of the respiratory system provide unique capabilities for investigating both normal and abnormal lung function. There is substantial regional variability in both structure and function within the normal lung, yet it remains capable of relatively efficient gas exchange by providing close matching of air delivery (ventilation) and blood delivery (perfusion) to regions of gas exchange tissue from the scale of the whole organ to the smallest continuous gas exchange units. This is despite remarkably different mechanisms of air and blood delivery, different fluid properties, and unique scale-dependent anatomical structures through which the blood and air are transported.

Lung and fissure shape is associated with age in healthy never-smoking adults aged 20-90 years.

Lung shape could hold prognostic information for age-related diseases that affect lung tissue mechanics. We sought to quantify mean lung shape, its modes of variation, and shape associations with lung size, age, sex, and Body Mass Index (BMI) in healthy subjects across a seven-decade age span. Volumetric computed tomography from 83 subjects (49 M/34 F, BMI [Formula: see text]) was used to derive two statistical shape models using a principal component analysis.

Prediction of lung mechanics throughout recruitment maneuvers in pressure-controlled ventilation.

Mechanical ventilation (MV) is a core therapy in the intensive care unit (ICU). Some patients rely on MV to support breathing. However, it is a difficult therapy to optimise, where inter- and intra- patient variability leads to significantly increased risk of lung damage.

Wave reflection in an anatomical model of the pulmonary circulation in local and global hypertensive disease.

Pulmonary hypertension is a disease of the pulmonary vasculature which can occur for many different reasons, including pathological remodeling of the pulmonary vessels and occlusion of these vessels (amongst others). Pulmonary hypertension can lead to right heart failure and significantly reduces the quality of life of patients living with the condition. It is difficult to distinguish clinically between different classifications of pulmonary hypertension, and doing so accurately is critical for the management of an individual's condition.

High-Frequency Oscillatory Ventilation and Ventilator-Induced Lung Injury: Size Does Matter.

Objectives: The theoretical basis for minimizing tidal volume during high-frequency oscillatory ventilation may not be appropriate when lung tissue stretch occurs heterogeneously and/or rapidly. The objective of this study was to assess the extent to which increased ventilation heterogeneity may contribute to ventilator-induced lung injury during high-frequency oscillatory ventilation in adults compared with neonates on the basis of lung size, using a computational model of human lungs.

Design: Computational modeling study.

Ventilation/Perfusion Matching: Of Myths, Mice, and Men.

Despite a huge range in lung size between species, there is little measured difference in the ability of the lung to provide a well-matched air flow (ventilation) to blood flow (perfusion) at the gas exchange tissue. Here, we consider the remarkable similarities in ventilation/perfusion matching between species through a biophysical lens and consider evidence that matching in large animals is dominated by gravity but in small animals by structure.

Strain, strain rate, and mechanical power: An optimization comparison for oscillatory ventilation.

The purpose of this study was to assess the potential for optimization of mechanical ventilator waveforms using multiple frequencies of oscillatory flow delivered simultaneously to minimize the risk of ventilator-induced lung injury (VILI) associated with regional strain, strain rate, and mechanical power. Optimization was performed using simulations of distributed oscillatory flow and gas transport in a computational model of anatomically derived branching airway segments and viscoelastic terminal acini under healthy and injured conditions. Objective functions defined by regional strain or strain rate were minimized by single-frequency ventilation waveforms using the highest or lowest frequencies available, respectively.

Optimizing human pulmonary perfusion measurement using an in silico model of arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is an imaging methodology that uses blood as an endogenous contrast agent to quantify flow. One limitation of this method of capillary blood quantification when applied in the lung is the contribution of signals from non-capillary blood. Intensity thresholding is one approach that has been proposed for minimizing the non-capillary blood signal.

1D network simulations for evaluating regional flow and pressure distributions in healthy and asthmatic human lungs.

This study aimed to introduce a one-dimensional (1D) computational fluid dynamics (CFD) model for airway resistance and lung compliance to examine the relationship between airway resistance, pressure, and regional flow distribution. We employed five healthy and five asthmatic subjects who had dynamic computed tomography (CT) scans (4D CT) along with two static scans at total lung capacity and functional residual capacity. Fractional air-volume change ( ) from 4D CT was used for a validation of the 1D CFD model.

Computational Modeling of Primary Blast Lung Injury: Implications for Ventilator Management.

Primary blast lung injury (PBLI) caused by exposure to high-intensity pressure waves is associated with parenchymal tissue injury and severe ventilation-perfusion mismatch. Although supportive ventilation is often required in patients with PBLI, maldistribution of gas flow in mechanically heterogeneous lungs may lead to further injury due to increased parenchymal strain and strain rate, which are difficult to predict in vivo. In this study, we developed a computational lung model with mechanical properties consistent with healthy and PBLI conditions.