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Dive into the research topics where Stephen Dubsky is active.

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Featured researches published by Stephen Dubsky.


Journal of the Royal Society Interface | 2012

Synchrotron-based dynamic computed tomography of tissue motion for regional lung function measurement

Stephen Dubsky; Stuart B. Hooper; Karen K. W. Siu; Andreas Fouras

During breathing, lung inflation is a dynamic process involving a balance of mechanical factors, including trans-pulmonary pressure gradients, tissue compliance and airway resistance. Current techniques lack the capacity for dynamic measurement of ventilation in vivo at sufficient spatial and temporal resolution to allow the spatio-temporal patterns of ventilation to be precisely defined. As a result, little is known of the regional dynamics of lung inflation, in either health or disease. Using fast synchrotron-based imaging (up to 60 frames s−1), we have combined dynamic computed tomography (CT) with cross-correlation velocimetry to measure regional time constants and expansion within the mammalian lung in vivo. Additionally, our new technique provides estimation of the airflow distribution throughout the bronchial tree during the ventilation cycle. Measurements of lung expansion and airflow in mice and rabbit pups are shown to agree with independent measures. The ability to measure lung function at a regional level will provide invaluable information for studies into normal and pathological lung dynamics, and may provide new pathways for diagnosis of regional lung diseases. Although proof-of-concept data were acquired on a synchrotron, the methodology developed potentially lends itself to clinical CT scanning and therefore offers translational research opportunities.


Applied Physics Letters | 2008

Phase retrieval for improved three-dimensional velocimetry of dynamic x-ray blood speckle

Sarah C. Irvine; David M. Paganin; Stephen Dubsky; Robert A. Lewis; Andreas Fouras

High-resolution synchrotron-based x-ray phase-contrast images of in vitro blood flow have been collected. We demonstrate that the application of a single-image phase retrieval algorithm to the images leads to improved detail in particle image velocimetry correlation peaks. Out-of-plane variation in flow has been extracted from the peaks leading to the three-dimensional reconstruction of velocity across an axially symmetric cylinder.


Applied Physics Letters | 2010

Computed tomographic x-ray velocimetry

Stephen Dubsky; R. A. Jamison; Sarah C. Irvine; Karen Siu; Kerry Hourigan; Andreas Fouras

An x-ray velocimetry technique is described which provides three components of velocity measurement in three dimensional space. Current x-ray velocimetry techniques, which use particle images taken at a single projection angle, are limited to two components of velocity measurement, and are unable to measure in three dimensions without a priori knowledge of the flow field. The proposed method uses multiple projection angles to overcome these limitations. The technique uses a least-squares iterative scheme to tomographically reconstruct the three-dimensional velocity field directly from two-dimensional image pair cross-correlations, without the need to reconstruct three-dimensional particle images. Synchrotron experiments demonstrate the effectiveness of the technique for blood flow measurement in opaque vessels, with applications for the diagnosis and treatment of cardiovascular disease.


6th International Conference on Medical Applications of Synchrotron Radiation, | 2010

Computed Tomographic X‐ray Velocimetry

Stephen Dubsky; R. A. Jamison; Sarah C. Irvine; Karen Siu; Kerry Hourigan; Andreas Fouras

An X‐ray velocimetry technique is described which provides three components of velocity measurement in three‐dimensional space. Current X‐ray velocimetry techniques, which use particle images taken at a single projection angle, are limited to two components of velocity measurement, and are unable to measure in three dimensions without a priori knowledge of the flow field. The proposed method uses multiple projection angles to overcome these limitations. The technique uses a least‐squares iterative scheme to tomographically reconstruct the three‐dimensional velocity field directly from two‐dimensional image pair cross‐correlations, without the need to reconstruct three‐dimensional particle images. Synchrotron experiments demonstrate the effectiveness of the technique for blood flow measurement in opaque vessels, with applications for the diagnosis and treatment of cardiovascular disease.


PLOS ONE | 2012

Functional Lung Imaging during HFV in Preterm Rabbits

Jordan Thurgood; Stuart B. Hooper; Melissa L. Siew; Megan J. Wallace; Stephen Dubsky; Marcus J. Kitchen; R. Aidan Jamison; Richard Carnibella; Andreas Fouras

Although high frequency ventilation (HFV) is an effective mode of ventilation, there is limited information available in regard to lung dynamics during HFV. To improve the knowledge of lung function during HFV we have developed a novel lung imaging and analysis technique. The technique can determine complex lung motion information in vivo with a temporal resolution capable of observing HFV dynamics. Using high-speed synchrotron based phase contrast X-ray imaging and cross-correlation analysis, this method is capable of recording data in more than 60 independent regions across a preterm rabbit lung in excess of 300 frames per second (fps). This technique is utilised to determine regional intra-breath lung mechanics of preterm rabbit pups during HFV. Whilst ventilated at fixed pressures, each animal was ventilated at frequencies of 1, 3, 5 and 10 Hz. A 50% decrease in delivered tidal volume was measured at 10 Hz compared to 1 Hz, yet at the higher frequency a 500% increase in minute activity was measured. Additionally, HFV induced greater homogeneity of lung expansion activity suggesting this ventilation strategy potentially minimizes tissue damage and improves gas mixing. The development of this technique permits greater insight and further research into lung mechanics and may have implications for the improvement of ventilation strategies used to support severe pulmonary trauma and disease.


Optics Express | 2010

Vector tomographic X-ray phase contrast velocimetry utilizing dynamic blood speckle

Sarah C. Irvine; David M. Paganin; R. Aidan Jamison; Stephen Dubsky; Andreas Fouras

We present a time-resolved tomographic reconstruction of the velocity field associated with pulsatile blood flow through a rotationally-symmetric stenotic vessel model. The in-vitro sample was imaged using propagation-based phase contrast with monochromated X-rays from a synchrotron undulator source, and a fast shutter-synchronized detector with high-resolution used to acquire frames of the resulting dynamic speckle pattern. Having used phase retrieval to decode the phase contrast from the speckle patterns, the resulting projected-density maps were analysed using the statistical correlation methods of particle image velocimetry (PIV). This yields the probability density functions of blood-cell displacement within the vessel. The axial velocity-field component of the rotationally-symmetric flow was reconstructed using an inverse-Abel transform. A modified inverse-Abel transform was used to reconstruct the radial component. This vector tomographic phase-retrieval velocimetry was performed over the full pumping cycle, to completely characterize the velocity field of the pulsatile blood flow in both space and time.


Advanced Drug Delivery Reviews | 2015

Imaging regional lung function: a critical tool for developing inhaled antimicrobial therapies.

Stephen Dubsky; Andreas Fouras

Alterations in regional lung function due to respiratory infection have a significant effect on the deposition of inhaled treatments. This has consequences for treatment effectiveness and hence recovery of lung function. In order to advance our understanding of respiratory infection and inhaled treatment delivery, we must develop imaging techniques that can provide regional functional measurements of the lung. In this review, we explore the role of functional imaging for the assessment of respiratory infection and development of inhaled treatments. We describe established and emerging functional lung imaging methods. The effect of infection on lung function is described, and the link between regional disease, function, and inhaled treatments is discussed. The potential for lung function imaging to provide unique insights into the functional consequences of infection, and its treatment, is also discussed.


Journal of Synchrotron Radiation | 2012

X-ray velocimetry within the ex vivo carotid artery

R. A. Jamison; Karen Kit Wan Siu; Stephen Dubsky; James A. Armitage; Andreas Fouras

X-ray velocimetry offers a non-invasive method by which blood flow, blood velocity and wall shear stress can be measured in arteries prone to atherosclerosis. Analytical tools for measuring haemodynamics in artificial arteries have previously been developed and here the first quantification of haemodynamics using X-ray velocimetry in a living mammalian artery under physiologically relevant conditions is demonstrated. Whole blood seeded with a clinically used ultrasound contrast agent was pumped with a steady flow through live carotid arterial tissue from a rat, which was kept alive in a physiological salt solution. Pharmacological agents were then used to produce vascular relaxation. Velocity measurements were acquired with a spatial resolution of 14 µm × 14 µm and at a rate of 5000 acquisitions per second. Subtle velocity changes that occur are readily measurable, demonstrating the ability of X-ray velocimetry to sensitively and accurately measure haemodynamics ex vivo. Future applications and possible limitations of the technique are discussed, which allows for detailed living tissue investigations to be carried out for various disease models, including atherosclerosis and diabetic vasculopathy.


Scientific Reports | 2016

Quantification of heterogeneity in lung disease with image-based pulmonary function testing

Charlene S. Stahr; Chaminda R. Samarage; Martin Donnelley; Nigel Farrow; Kaye S. Morgan; Graeme R. Zosky; Richard C. Boucher; Karen K. W. Siu; Marcus A. Mall; David Parsons; Stephen Dubsky; Andreas Fouras

Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.


Journal of Applied Physiology | 2017

Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge

Stephen Dubsky; Graeme R. Zosky; Kara L. Perks; Chaminda R. Samarage; Yann Henon; Stuart B. Hooper; Andreas Fouras

Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo.NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.

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Stuart B. Hooper

Hudson Institute of Medical Research

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Megan J. Wallace

Hudson Institute of Medical Research

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