33,186 research outputs found
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In silico modeling of oxygen-enhanced MRI of specific ventilation.
Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to capture signal change as subjects alternatively breathe room air and 100% O2 provides an estimate of specific ventilation distribution in the lung. How well this technique measures SV and the effect of currently adopted approaches of the technique on resulting SV measurement is open for further exploration. We investigated (1) How well does imaging a single sagittal lung slice represent whole lung SV? (2) What is the influence of pulmonary venous blood on the measured MRI signal and resultant SVI measure? and (3) How does inclusion of misaligned images affect SVI measurement? In this study, we utilized two patient-based in silico models of ventilation, perfusion, and gas exchange to address these questions for normal healthy lungs. Simulation results from the two healthy young subjects show that imaging a single slice is generally representative of whole lung SV distribution, with a calculated SV gradient within 90% of that calculated for whole lung distributions. Contribution of O2 from the venous circulation results in overestimation of SV at a regional level where major pulmonary veins cross the imaging plane, resulting in a 10% increase in SV gradient for the imaging slice. A worst-case scenario simulation of image misalignment increased the SV gradient by 11.4% for the imaged slice
Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice
<p>Abstract</p> <p>Background</p> <p>Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.</p> <p>Methods</p> <p>Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.</p> <p>Results</p> <p>DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH<sub>2</sub>O·s·mL<sup>-1 </sup>in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH<sub>2</sub>O·s·mL<sup>-1 </sup>in acute airway inflammation (both <it>P </it>< 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 ± 1.5% to 5.6 ± 0.6% (<it>P </it>< 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 ± 6.6% to 14.3 ± 1.3% (<it>P </it>< 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both <it>P </it>< 0.0001) and chronic allergen-treated animals (G and H both <it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.</p
Polarized Helium to Image the Lung
The main findings of the european PHIL project (Polarised Helium to Image the
Lung) are reported. State of the art optical pumping techniques for polarising
^3He gas are described. MRI methodological improvements allow dynamical
ventilation images with a good resolution, ultimately limited by gas diffusion.
Diffusion imaging appears as a robust method of lung diagnosis. A discussion of
the potential advantage of low field MRI is presented. Selected PHIL results
for emphysema are given, with the perspectives that this joint work opens up
for the future of respiratory medicine.Comment: To be published in Proc. ICAP 2004 (19th Int. Conf. on Atomic
Physics, Rio, July 26-30 2004
Theoretical open-loop model of respiratory mechanics in the extremely preterm infant
Non-invasive ventilation is increasingly used for respiratory support in
preterm infants, and is associated with a lower risk of chronic lung disease.
However, this mode is often not successful in the extremely preterm infant in
part due to their markedly increased chest wall compliance that does not
provide enough structure against which the forces of inhalation can generate
sufficient pressure. To address the continued challenge of studying treatments
in this fragile population, we developed a nonlinear lumped-parameter model of
respiratory system mechanics of the extremely preterm infant that incorporates
nonlinear lung and chest wall compliances and lung volume parameters tuned to
this population. In particular we developed a novel empirical representation of
progressive volume loss based on compensatory alveolar pressure increase
resulting from collapsed alveoli. The model demonstrates increased rate of
volume loss related to high chest wall compliance, and simulates laryngeal
braking for elevation of end-expiratory lung volume and constant positive
airway pressure (CPAP). The model predicts that low chest wall compliance
(chest stiffening) in addition to laryngeal braking and CPAP enhance breathing
and delay lung volume loss. These results motivate future data collection
strategies and investigation into treatments for chest wall stiffening.Comment: 22 pages, 5 figure
Linking ventilation heterogeneity quantified via hyperpolarized He-3 MRI to dynamic lung mechanics and airway hyperresponsiveness
Advancements in hyperpolarized helium-3 MRI (HP 3He-MRI) have introduced the ability to render and quantify ventilation patterns throughout the anatomic regions of the lung. The goal of this study was to establish how ventilation heterogeneity relates to the dynamic changes in mechanical lung function and airway hyperresponsiveness in asthmatic subjects. In four healthy and nine mild-to-moderate asthmatic subjects, we measured dynamic lung resistance and lung elastance from 0.1 to 8 Hz via a broadband ventilation waveform technique. We quantified ventilation heterogeneity using a recently developed coefficient of variation method from HP 3He-MRI imaging. Dynamic lung mechanics and imaging were performed at baseline, post-challenge, and after a series of five deep inspirations. AHR was measured via the concentration of agonist that elicits a 20% decrease in the subject’s forced expiratory volume in one second compared to baseline (PC20) dose. The ventilation coefficient of variation was correlated to low-frequency lung resistance (R = 0.647, P < 0.0001), the difference between high and low frequency lung resistance (R = 0.668, P < 0.0001), and low-frequency lung elastance (R = 0.547, P = 0.0003). In asthmatic subjects with PC20 values <25 mg/mL, the coefficient of variation at baseline exhibited a strong negative trend (R = -0.798, P = 0.02) to PC20 dose. Our findings were consistent with the notion of peripheral rather than central involvement of ventilation heterogeneity. Also, the degree of AHR appears to be dependent on the degree to which baseline airway constriction creates baseline ventilation heterogeneity. HP 3He-MRI imaging may be a powerful predictor of the degree of AHR and in tracking the efficacy of therapy.This work was funded by the National Heart, Lung, and Blood Institute Grants R01 HL62269-04 and R01 HL-096797
Physiological modeling of isoprene dynamics in exhaled breath
Human breath contains a myriad of endogenous volatile organic compounds
(VOCs) which are reflective of ongoing metabolic or physiological processes.
While research into the diagnostic potential and general medical relevance of
these trace gases is conducted on a considerable scale, little focus has been
given so far to a sound analysis of the quantitative relationships between
breath levels and the underlying systemic concentrations. This paper is devoted
to a thorough modeling study of the end-tidal breath dynamics associated with
isoprene, which serves as a paradigmatic example for the class of low-soluble,
blood-borne VOCs.
Real-time measurements of exhaled breath under an ergometer challenge reveal
characteristic changes of isoprene output in response to variations in
ventilation and perfusion. Here, a valid compartmental description of these
profiles is developed. By comparison with experimental data it is inferred that
the major part of breath isoprene variability during exercise conditions can be
attributed to an increased fractional perfusion of potential storage and
production sites, leading to higher levels of mixed venous blood concentrations
at the onset of physical activity. In this context, various lines of supportive
evidence for an extrahepatic tissue source of isoprene are presented.
Our model is a first step towards new guidelines for the breath gas analysis
of isoprene and is expected to aid further investigations regarding the
exhalation, storage, transport and biotransformation processes associated with
this important compound.Comment: 14 page
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Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome.
In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS
Physiological modeling of isoprene dynamics in exhaled breath
Human breath contains a myriad of endogenous volatile organic compounds
(VOCs) which are reflective of ongoing metabolic or physiological processes.
While research into the diagnostic potential and general medical relevance of
these trace gases is conducted on a considerable scale, little focus has been
given so far to a sound analysis of the quantitative relationships between
breath levels and the underlying systemic concentrations. This paper is devoted
to a thorough modeling study of the end-tidal breath dynamics associated with
isoprene, which serves as a paradigmatic example for the class of low-soluble,
blood-borne VOCs.
Real-time measurements of exhaled breath under an ergometer challenge reveal
characteristic changes of isoprene output in response to variations in
ventilation and perfusion. Here, a valid compartmental description of these
profiles is developed. By comparison with experimental data it is inferred that
the major part of breath isoprene variability during exercise conditions can be
attributed to an increased fractional perfusion of potential storage and
production sites, leading to higher levels of mixed venous blood concentrations
at the onset of physical activity. In this context, various lines of supportive
evidence for an extrahepatic tissue source of isoprene are presented.
Our model is a first step towards new guidelines for the breath gas analysis
of isoprene and is expected to aid further investigations regarding the
exhalation, storage, transport and biotransformation processes associated with
this important compound.Comment: 14 page
Patterns of recruitment and injury in a heterogeneous airway network model
In respiratory distress, lung airways become flooded with liquid and may collapse due
to surface-tension forces acting on air-liquid interfaces, inhibiting gas exchange. This pa-
per proposes a mathematical multiscale model for the mechanical ventilation of a network
of occluded airways, where air is forced into the network at a fixed tidal volume, allowing
investigation of optimal recruitment strategies. The temporal response is derived from
mechanistic models of individual airway reopening, incorporating feedback on the airway
pressure due to recruitment. The model accounts for stochastic variability in airway di-
ameter and stiffness across and between generations. For weak heterogeneity, the network
is completely ventilated via one or more avalanches of recruitment (with airways recruited
in quick succession), each characterised by a transient decrease in the airway pressure;
avalanches become more erratic for airways that are initially more flooded. However, the
time taken for complete ventilation of the network increases significantly as the network
becomes more heterogeneous, leading to increased stresses on airway walls. The model
predicts that the most peripheral airways are most at risk of ventilation-induced damage.
A positive-end-expiratory pressure (PEEP) reduces the total recruitment time but at the
cost of larger stresses exerted on airway walls
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