ORCID Profile
0000-0002-3211-6337
Current Organisation
The University of Auckland
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Publisher: American Physiological Society
Date: 04-2011
DOI: 10.1152/JAPPLPHYSIOL.00775.2010
Abstract: Recent experimental and imaging studies suggest that the influence of gravity on the measured distribution of blood flow in the lung is largely through deformation of the parenchymal tissue. To study the contribution of hydrostatic effects to regional perfusion in the presence of tissue deformation, we have developed an anatomically structured computational model of the pulmonary circulation (arteries, capillaries, veins), coupled to a continuum model of tissue deformation, and including scale-appropriate fluid dynamics for blood flow in each vessel type. The model demonstrates that both structural and the multiple effects of gravity on the pulmonary circulation make a distinct contribution to the distribution of blood. It shows that postural differences in perfusion gradients can be explained by the combined effect of tissue deformation and extra-acinar blood vessel resistance to flow in the dependent tissue. However, gravitational perfusion gradients persist when the effect of tissue deformation is eliminated, highlighting the importance of the hydrostatic effects of gravity on blood distribution in the pulmonary circulation. Coupling of large- and small-scale models reveals variation in microcirculatory driving pressures within isogravitational planes due to extra-acinar vessel resistance. Variation in driving pressures is due to heterogeneous large-vessel resistance as a consequence of geometric asymmetry in the vascular trees and is lified by the complex balance of pressures, distension, and flow at the microcirculatory level.
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.RESP.2010.12.018
Abstract: Embolus occlusion of pulmonary arteries can result in elevated pulmonary blood pressures, often resulting in pulmonary hypertension (PH). Experimental observations have shown that small emboli (diameter <170 μm) can have a disproportionate effect on pulmonary vascular resistance (PVR) compared with larger emboli for the same tissue occlusion. We present an anatomically based theoretical model of perfusion in the acinar blood vessels designed to investigate changes in PVR following occlusion of arteries <500 μm in diameter. The model predicts that emboli lodged near proximal capillary beds have a greater effect on PVR--regardless of their size--than emboli occluding 200 μm diameter arterioles, with PH occurring for 10% less tissue occlusion. Capillary blood pressures are predicted to exceed 24 mmHg (levels initiating capillary wall damage) in regions of the capillary bed at approximately the onset of PH. This study focuses on the effect of mechanical obstruction alone however, we present simple models of vasoconstriction illustrating an increased impact on PVR.
Publisher: IEEE
Date: 05-2012
Publisher: IEEE
Date: 08-2012
Publisher: Cambridge University Press (CUP)
Date: 04-2018
DOI: 10.1017/S1446181118000111
Abstract: Heterogeneity in pulmonary microvascular blood flow (perfusion) provides an early indicator of lung disease or disease susceptibility. However, most computational models of the pulmonary vasculature neglect structural heterogeneities, and are thus not accurate predictors of lung function in disease that is not diffuse (spread evenly through the lung). Models that do incorporate structural heterogeneity have either neglected the temporal dynamics of blood flow, or the structure of the smallest blood vessels. Larger than normal oscillations in pulmonary capillary calibre, high oscillatory stress contribute to disease progression. Hence, a model that captures both spatial and temporal heterogeneity in pulmonary perfusion could provide new insights into the early stages of pulmonary vascular disease. Here, we present a model of the pulmonary vasculature, which captures both flow dynamics, and the anatomic structure of the pulmonary blood vessels from the right to left heart including the micro-vasculature. The model is compared to experimental data in normal lungs. We confirm that spatial heterogeneity in pulmonary perfusion is time-dependent, and predict key features of pulmonary hypertensive disease using a simple implementation of increased vascular stiffness.
Publisher: Wiley
Date: 04-2011
Abstract: Biophysically‐based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study in idual mechanisms that contribute to lung perfusion, to sophisticated multi‐scale and ‐physics structure‐based models that predict integrated structure‐function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation.
Publisher: The Royal Society
Date: 06-04-2015
Abstract: The goal of translating multiscale model analysis of pulmonary function into population studies is challenging because of the need to derive a geometric model for each subject. This could be addressed by using a generic model with appropriate customization to subject-specific data. Here, we present a quantitative comparison of simulating two fundamental behaviours of the lung—its haemodynamic response to vascular occlusion, and the forced expiration in 1 s (FEV 1 ) following bronchoconstriction—in subject-specific and generic models. When the subjects are considered as a group, there is no significant difference between predictions of mean pulmonary artery pressure (mPAP), pulmonary vascular resistance or forced expiration however, significant differences are apparent in the prediction of arterial oxygen, for both baseline and post-occlusion. Despite the apparent consistency of the generic and subject-specific models, a third of subjects had generic model under-prediction of the increase in mPAP following occlusion, and half had the decrease in arterial oxygen over-predicted two subjects had considerable differences in the percentage reduction of FEV 1 following bronchoconstriction. The generic model approach can be useful for physiologically directed studies but is not appropriate for simulating pathophysiological function that is strongly dependent on interaction with lung structure.
Publisher: American Thoracic Society
Date: 05-2010
DOI: 10.1164/AJRCCM-CONFERENCE.2010.181.1_MEETINGABSTRACTS.A3647
Publisher: Elsevier BV
Date: 2015
Publisher: American Thoracic Society
Date: 05-2010
DOI: 10.1164/AJRCCM-CONFERENCE.2010.181.1_MEETINGABSTRACTS.A3645
Publisher: American Thoracic Society
Date: 05-2010
DOI: 10.1164/AJRCCM-CONFERENCE.2010.181.1_MEETINGABSTRACTS.A3644
Publisher: JMIR Publications Inc.
Date: 20-12-2019
DOI: 10.2196/15466
Abstract: Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic respiratory diseases, but the uptake of and adherence to PR programs is low. There is potential for mobile health (mHealth) to provide an alternative modality for the delivery of PR, overcoming many of the barriers contributing to poor attendance to current services. The objective of this study was to understand the needs, preferences, and priorities of end users for the development of an adaptive mobile PR (mPR) support program. A mixed methods (qualitative and quantitative) approach was used to assess the needs, preferences, and priorities of the end users (ie, patients with chronic respiratory disorders) and key stakeholders (ie, clinicians working with patients with chronic respiratory disorders and running PR). The formative studies included the following: (1) a survey to understand the preferences and priorities of patients for PR and how mobile technology could be used to provide PR support, (2) ethnographic semistructured interviews with patients with chronic respiratory disorders to gain perspectives on their understanding of their health and potential features that could be included in an mPR program, and (3) key informant interviews with health care providers to understand the needs, preferences, and priorities for the development of an mPR support program. Across all formative studies (patient survey, n=30 patient interviews, n=8 and key stakeholder interviews, n=8), the participants were positive about the idea of an mPR program but raised concerns related to digital literacy and confidence in using technology, access to technology, and loss of social support currently gained from traditional programs. Key stakeholders highlighted the need for patient safety to be maintained and ensuring appropriate programs for different groups within the population. Finding a balance between ensuring safety and maximizing access was seen to be essential in the success of an mPR program. These formative studies found high interest in mHealth-based PR intervention and detailed the potential for an mPR program to overcome current barriers to accessing traditional PR programs. Key considerations and features were identified, including the importance of technology access and digital literacy being considered in utilizing technology with this population.
Publisher: American Physiological Society
Date: 05-2010
DOI: 10.1152/JAPPLPHYSIOL.01177.2009
Abstract: This study presents a theoretical model of combined series and parallel perfusion in the human pulmonary acinus that maintains computational simplicity while capturing some important features of acinar structure. The model provides a transition between existing models of perfusion in the large pulmonary blood vessels and the pulmonary microcirculation. Arterioles and venules are represented as distinct elastic vessels that follow the branching structure of the acinar airways. These vessels are assumed to be joined at each generation by capillary sheets that cover the alveoli present at that generation, forming a “ladderlike” structure. Compared with a model structure in which capillary beds connect only the most distal blood vessels in the acinus, the model with combined serial and parallel perfusion provides greater capacity for increased blood flow in the lung via capillary recruitment when the blood pressure is elevated. Stratification of acinar perfusion emerges in the model, with red blood cell transit time significantly larger in the distal portion of the acinus compared with the proximal portion. This proximal-to-distal pattern of perfusion may act in concert with diffusional screening to optimize the potential for gas exchange.
Publisher: The Royal Society
Date: 06-04-2015
Abstract: The placenta provides all the nutrients required for the fetus through pregnancy. It develops dynamically, and, to avoid rejection of the fetus, there is no mixing of fetal and maternal blood rather, the branched placental villi ‘bathe’ in blood supplied from the uterine arteries. Within the villi, the feto–placental vasculature also develops a complex branching structure in order to maximize exchange between the placental and maternal circulations. To understand the development of the placenta, we must translate functional information across spatial scales including the interaction between macro- and micro-scale haemodynamics and account for the effects of a dynamically and rapidly changing structure through the time course of pregnancy. Here, we present steps towards an anatomically based and multiscale approach to modelling the feto–placental circulation. We assess the effect of the location of cord insertion on feto–placental blood flow resistance and flow heterogeneity and show that, although cord insertion does not appear to directly influence feto–placental resistance, the heterogeneity of flow in the placenta is predicted to increase from a 19.4% coefficient of variation with central cord insertion to 23.3% when the cord is inserted 2 cm from the edge of the placenta. Model geometries with spheroidal and ellipsoidal shapes, but the same volume, showed no significant differences in flow resistance or heterogeneity, implying that normal asymmetry in shape does not affect placental efficiency. However, the size and number of small capillary vessels is predicted to have a large effect on feto–placental resistance and flow heterogeneity. Using this new model as an ex le, we highlight the importance of taking an integrated multi-disciplinary and multiscale approach to understand development of the placenta.
Publisher: ASME International
Date: 18-01-2050
DOI: 10.1115/1.4029919
Abstract: Previous studies of the ex vivo lung have suggested significant intersubject variability in lung lobe geometry. A quantitative description of normal lung lobe shape would therefore have value in improving the discrimination between normal population variability in shape and pathology. To quantify normal human lobe shape variability, a principal component analysis (PCA) was performed on high resolution computed tomography (HRCT) imaging of the lung at full inspiration. Volumetric imaging from 22 never-smoking subjects (10 female and 12 male) with normal lung function was included in the analysis. For each subject, an initial finite element mesh geometry was generated from a group of manually selected nodes that were placed at distinct anatomical locations on the lung surface. Each mesh used cubic shape functions to describe the surface curvilinearity, and the mesh was fitted to surface data for each lobe. A PCA was performed on the surface meshes for each lobe. Nine principal components (PCs) were sufficient to capture % of the normal variation in each of the five lobes. The analysis shows that lobe size can explain between 20% and 50% of intersubject variability, depending on the lobe considered. Diaphragm shape was the next most significant intersubject difference. When the influence of lung size difference is removed, the angle of the fissures becomes the most significant shape difference, and the variability in relative lobe size becomes important. We also show how a lobe from an independent subject can be projected onto the study population’s PCs, demonstrating potential for abnormalities in lobar geometry to be defined in a quantitative manner.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2023
Publisher: SPIE
Date: 29-03-2013
DOI: 10.1117/12.2007054
Publisher: American Physiological Society
Date: 05-2013
DOI: 10.1152/JAPPLPHYSIOL.00868.2012
Abstract: The pig is frequently used as an experimental model for studies of the pulmonary circulation, yet the branching and dimensional geometry of the porcine pulmonary vasculature remains poorly defined. The purposes of this study are to improve the geometric definition of the porcine pulmonary arteries and to determine whether the arterial tree exhibits self-similarity in its branching geometry. Five animals were imaged using thin slice spiral computed tomography in the prone posture during airway inflation pressure at 25 cmH 2 O. The luminal diameter and distance from the inlet of the left and right pulmonary arteries were measured along the left and right main arterial pathway in each lung of each animal. A further six minor pathways were measured in a single animal. The similarity in the rate of reduction of diameter with distance of all minor pathways and the two main pathways, along with similarity in the number of branches arising along the pathways, supports self-similarity in the arterial tree. The rate of reduction in diameter with distance from the inlet was not significantly different among the five animals ( P 0.48) when normalized for main pulmonary artery diameter and total main artery pathlength, which supports intersubject similarity. Other metrics to quantify the tree geometry are strikingly similar to those from airways of other quadrupeds, with the exception of a significantly larger length to diameter ratio, which is more appropriate for the vascular tree. A simplifying self-similar model for the porcine pulmonary arteries is proposed to capture the important geometric features of the arterial tree.
Publisher: American Physiological Society
Date: 11-2014
DOI: 10.1152/JAPPLPHYSIOL.00543.2014
Abstract: Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (V̇o 2 ). The multiple-breath nitrogen washout (MBNW) technique uses the alveolar slope to determine measures of ventilation inhomogeneity in the acinar ( S acin ) and conducting ( S cond ) airway regions, as well as overall inhomogeneity, as determined by the lung clearance index (LCI). We hypothesized that measured ventilation inhomogeneity in the mouse lung while it is alive is in fact an artifact due to the high V̇o 2 in proportion to alveolar gas volume (Va), and not ventilation inhomogeneity per se. In seven male C57BL/6 mice, MBNW was performed alive and postmortem to derive measures with and without the effect of gas exchange, respectively. These results were compared with those obtained from an asymmetric multibranch point mathematical model of the mouse lung. There was no statistical difference in S acin and LCI between alive and postmortem results ( S acin alive = 0.311 ± 0.043 ml −1 and S acin postmortem = 0.338 ± 0.032 ml −1 , LCI alive = 7.0 ± 0.1 and LCI postmortem = 7.0 ± 0.1). However, there was a significant decrease in S cond from 0.086 ± 0.005 ml −1 alive to 0.006 ± 0.002 ml −1 postmortem ( P 0 .01). Model simulations replicated these results. Furthermore, in the model, as V̇o 2 increased, so did the alveolar slope. These findings suggests that the MBNW measurement of S cond in the mouse lung is confounded by the effect of gas exchange, a result of the high V̇o 2 -to-Va ratio in this small animal, and not due to inhomogeneity within the airways.
Publisher: IEEE
Date: 08-2014
Publisher: IEEE
Date: 08-2014
Publisher: IEEE
Date: 08-2012
Publisher: JMIR Publications Inc.
Date: 14-07-2019
Abstract: ulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic respiratory diseases, but the uptake of and adherence to PR programs is low. There is potential for mobile health (mHealth) to provide an alternative modality for the delivery of PR, overcoming many of the barriers contributing to poor attendance to current services. he objective of this study was to understand the needs, preferences, and priorities of end users for the development of an adaptive mobile PR (mPR) support program. mixed methods (qualitative and quantitative) approach was used to assess the needs, preferences, and priorities of the end users (ie, patients with chronic respiratory disorders) and key stakeholders (ie, clinicians working with patients with chronic respiratory disorders and running PR). The formative studies included the following: (1) a survey to understand the preferences and priorities of patients for PR and how mobile technology could be used to provide PR support, (2) ethnographic semistructured interviews with patients with chronic respiratory disorders to gain perspectives on their understanding of their health and potential features that could be included in an mPR program, and (3) key informant interviews with health care providers to understand the needs, preferences, and priorities for the development of an mPR support program. cross all formative studies (patient survey, n=30 patient interviews, n=8 and key stakeholder interviews, n=8), the participants were positive about the idea of an mPR program but raised concerns related to digital literacy and confidence in using technology, access to technology, and loss of social support currently gained from traditional programs. Key stakeholders highlighted the need for patient safety to be maintained and ensuring appropriate programs for different groups within the population. Finding a balance between ensuring safety and maximizing access was seen to be essential in the success of an mPR program. hese formative studies found high interest in mHealth-based PR intervention and detailed the potential for an mPR program to overcome current barriers to accessing traditional PR programs. Key considerations and features were identified, including the importance of technology access and digital literacy being considered in utilizing technology with this population.
Publisher: Wiley
Date: 07-2011
Abstract: Acute pulmonary embolism causes redistribution of blood in the lung, which impairs ventilation erfusion matching and gas exchange and can elevate pulmonary arterial pressure (PAP) by increasing pulmonary vascular resistance (PVR). An anatomically‐based multi‐scale model of the human pulmonary circulation was used to simulate pre‐ and post‐occlusion flow, to study blood flow redistribution in the presence of an embolus, and to evaluate whether reduction in perfused vascular bed is sufficient to increase PAP to hypertensive levels, or whether other vasoconstrictive mechanisms are necessary. A model of oxygen transfer from air to blood was included to assess the impact of vascular occlusion on oxygen exchange. Emboli of 5, 7, and 10 mm radius were introduced to occlude increasing proportions of the vasculature. Blood flow redistribution was calculated after arterial occlusion, giving predictions of PAP, PVR, flow redistribution, and micro‐circulatory flow dynamics. Because of the large flow reserve capacity (via both capillary recruitment and distension), approximately 55% of the vasculature was occluded before PAP reached clinically significant levels indicative of hypertension. In contrast, model predictions showed that even relatively low levels of occlusion could cause localized oxygen deficit. Flow preferentially redistributed to gravitationally non‐dependent regions regardless of occlusion location, due to the greater potential for capillary recruitment in this region. Red blood cell transit times decreased below the minimum time for oxygen saturation ( .25 s) and capillary pressures became high enough to initiate cell damage (which may result in edema) only after ~80% of the lung was occluded.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.RESP.2013.09.005
Abstract: Clot load scores have previously been developed with the goal of improving prognosis in acute pulmonary embolism (PE). These scores provide a simple estimate of pulmonary vascular bed obstruction, however they have not been adopted clinically as they have poor correlation with mortality and right ventricular (RV) dysfunction. This study performed a quantitative analysis of blood flow and gas exchange in 12 patient-specific models of PE, to understand the limitations of current clot load scores and how their prognostic value could be improved. Prediction of hypoxemia in the models when using estimated baseline (non-occluded) minute ventilation and cardiac output correlated closely with clinical metrics for RV dysfunction, whereas the clot load score had only a weak correlation. The model predicts that large central clots have a greater impact on function than smaller distributed clots with the same total clot load, and that the partial occlusion of a vessel only has a significant impact on pulmonary function when the vessel is close to completely occluded. The effect of clot distribution on the redistribution of blood from its normal pattern - and hence the magnitude of the potential effect on gas exchange - is represented in the model but is not included in current clot load scores. Improved scoring systems need to account for the expected normal distribution of blood in the lung, and the impact of clot on redistributing the blood flow.
Publisher: ASME International
Date: 20-09-2013
DOI: 10.1115/1.4025092
Abstract: A novel model for the blood system is postulated focusing on the flow rate and pressure distribution inside the arterioles and venules of the pulmonary acinus. Based upon physiological data it is devoid of any ad hoc constants. The model comprises nine generations of arterioles, venules, and capillaries in the acinus, the gas exchange unit of the lung. Blood is assumed incompressible and Newtonian and the blood vessels are assumed inextensible. Unlike previous models of the blood system, the venules and arterioles open up to the capillary network in numerous locations along each generation. The large number of interconnected capillaries is perceived as a porous medium in which the flow is macroscopically unidirectional from arterioles to venules openings. In addition, the large number of capillaries extending from each arteriole and venule allows introduction of a continuum theory and formulation of a novel system of ordinary, nonlinear differential equations which governs the blood flow and pressure fields along the arterioles, venules, and capillaries. The solution of the differential equations is semianalytical and requires the inversion of three diagonal, 9 × 9 matrices only. The results for the total flow rate of blood through the acinus are within the ballpark of physiological observations despite the simplifying assumptions used in our model. The results also manifest that the contribution of the nonlinear convection term of the Navier-Stokes equations has little effect (less than 2%) on the total blood flow entering/leaving the acinus despite the fact that the Reynolds number is not much smaller than unity at the proximal generations. The model makes it possible to examine some pathological cases. Here, centri-acinar and distal emphysema were investigated yielding a reduction in inlet blood flow rate.
Publisher: Begell House
Date: 2011
Publisher: SPIE
Date: 29-03-2013
DOI: 10.1117/12.2006695
Publisher: The Royal Society
Date: 13-11-2011
Abstract: Pulmonary embolism (PE) is the most common cause of acute pulmonary hypertension, yet it is commonly undiagnosed, with risk of death if not recognized promptly and managed accordingly. Patients typically present with hypoxemia and hypocapnia, although the presentation varies greatly, being confounded by co-mordidities such as pre-existing cardio-respiratory disease. Previous studies have demonstrated variable patient outcomes in spite of similar extent and distribution of pulmonary vascular occlusion, but the pathophysiological determinants of outcome remain unclear. Computational models enable exact control over many of the compounding factors leading to functional outcomes and therefore provide a useful tool to understand and assess these mechanisms. We review the current state of pulmonary blood flow models. We present a pilot study within 10 patients presenting with acute PE, where patient-derived vascular occlusions are imposed onto an existing model of the pulmonary circulation enabling predictions of resultant haemodynamics after embolus occlusion. Results show that mechanical obstruction alone is not sufficient to cause pulmonary arterial hypertension, even when up to 65 per cent of lung tissue is occluded. Blood flow is found to preferentially redistribute to the gravitationally non-dependent regions. The presence of an additional downstream occlusion is found to significantly increase pressures.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2014
DOI: 10.1007/S10439-014-1011-Y
Abstract: Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response unique to the lung whereby blood flow is erted away from areas of low alveolar oxygen to improve ventilation-perfusion matching and resultant gas exchange. Some previous experimental studies have suggested that the HPV response to hypoxia is blunted in acute pulmonary embolism (APE), while others have concluded that HPV contributes to elevated pulmonary blood pressures in APE. To understand these contradictory observations, we have used a structure-based computational model of integrated lung function in 10 subjects to study the impact of HPV on pulmonary hemodynamics and gas exchange in the presence of regional arterial occlusion. The integrated model includes an experimentally-derived model for HPV. Its function is validated against measurements of pulmonary vascular resistance in normal subjects at four levels of inspired oxygen. Our results show that the apparently disparate observations of previous studies can be explained within a single model: the model predicts that HPV increases mean pulmonary artery pressure in APE (by 8.2 ± 7.0% in these subjects), and concurrently shows a reduction in response to hypoxia in the subjects who have high levels of occlusion and therefore maximal HPV in normoxia.
Start Date: 2015
End Date: 2018
Funder: Marsden Fund
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