In recent times, the study and use of induced pluripotent stem cells (iPSC) have become important... more In recent times, the study and use of induced pluripotent stem cells (iPSC) have become important in order to avoid the ethical issues surrounding the use of embryonic stem cells. Therapeutic, industrial and research based use of iPSC requires large quantities of cells generated in vitro. Mammalian cells, including pluripotent stem cells, have been expanded using 3D culture, however current limitations have not been overcome to allow a uniform, optimized platform for dynamic culture of pluripotent stem cells to be achieved. In the current work, we have expanded mouse iPSC in a spinner flask using Cytodex 3 microcarriers. We have looked at the effect of agitation on the microcarrier survival and optimized an agitation speed that supports bead suspension and iPS cell expansion without any bead breakage. Under the optimized conditions, the mouse iPSC were able to maintain their growth, pluripotency and differentiation capability. We demonstrate that microcarrier survival and iPS cell expansion in a spinner flask are reliant on a very narrow range of spin rates, highlighting the need for precise control of such set ups and the need for improved design of more robust systems.
As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progre... more As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progression of this process is required to guide ongoing care. We investigated whether expired CO 2 (ECO 2 ) levels indicate the degree of lung aeration immediately after birth in two animal models and in preterm infants. Lambs were delivered by caesarean section and ventilated from birth. In lambs, ECO 2 levels were significantly (p,0.0001) related to tidal volumes and CO 2 clearance/breath increased exponentially when tidal volumes were greater than 6 mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered by caesarean section and lung aeration was measured using phase contrast X-ray imaging. In rabbit kittens, ECO 2 levels were closely related (p,0.001) to lung volumes at end-inflation and were first detected when ,7% of the distal lung regions were aerated. ECO 2 levels in preterm infants at birth also correlated with tidal volumes. In each infant, ECO 2 levels increased to .10 mmHg 28 (median) (21-36) seconds before the heart rate increased above 100 beats per minute. These data demonstrate that ECO 2 levels can indicate the relative degree of lung aeration after birth and can be used to clinically assess ventilation in the immediate newborn period.
Anatomical visualization of airspace-containing organs in intact small animals has been limited b... more Anatomical visualization of airspace-containing organs in intact small animals has been limited by the resolution and contrast available from current imaging methods such as X-ray, micro-computed tomography and magnetic resonance imaging. Determining structural relationships and detailed anatomy has therefore relied on suitable fixation, sectioning and histological processing. More complex and informative analyses such as orthogonal views of an organ and three-dimensional structure visualizations have required different animals and image sets, laboriously processed to gather this complementary structural information. Precise three-dimensional anatomical views have always been difficult to achieve in small animals. Here we report the ability of phase-contrast synchrotron X-ray imaging to provide detailed two-and three-dimensional visualization of airspace organ structures in intact animals. Using sub-micrometre square pixel charge-coupled device array detectors, the structure and anatomy of hard and soft tissues, and of airspaces, is readily available using phase-contrast synchrotron X-ray imaging. Moreover, software-controlled volume-reconstructions of tomographic images not only provide unsurpassed image clarity and detail, but also selectable anatomical views that cannot be obtained with established histological techniques. The morphology and structure of nasal and lung airways and the middle ear are illustrated in intact mice, using two-and three-dimensional representations. The utility of phase-contrast synchrotron X-ray imaging for noninvasively localizing objects implanted within airspaces, and the detection of gas bubbles transiting live airways, are other novel features of this visualization methodology. The coupling of phase-contrast synchrotron X-ray imaging technology with software-based reconstruction techniques holds promise for novel and high-resolution non-invasive examination of airspace anatomy in small animal models.
Alterations in regional lung function due to respiratory infection have a significant effect on t... more 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.
The high flux and coherence produced at long synchrotron beamlines makes them well suited to perf... more The high flux and coherence produced at long synchrotron beamlines makes them well suited to performing phase-contrast X-ray imaging of the airways and lungs of live small animals. Here, findings of the first live-animal imaging on the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron are reported, demonstrating the feasibility of performing dynamic lung motion measurement and high-resolution micro-tomography. Live anaesthetized mice were imaged using 30 keV monochromatic X-rays at a range of sample-todetector propagation distances. A frame rate of 100 frames s À1 allowed lung motion to be determined using X-ray velocimetry. A separate group of humanely killed mice and rats were imaged by computed tomography at high resolution. Images were reconstructed and rendered to demonstrate the capacity for detailed, user-directed display of relevant respiratory anatomy. The ability to perform X-ray velocimetry on live mice at the IMBL was successfully demonstrated. High-quality renderings of the head and lungs visualized both large structures and fine details of the nasal and respiratory anatomy. The effect of sample-to-detector propagation distance on contrast and resolution was also investigated, demonstrating that soft tissue contrast increases, and resolution decreases, with increasing propagation distance. This new capability to perform live-animal imaging and high-resolution microtomography at the IMBL enhances the capability for investigation of respiratory diseases and the acceleration of treatment development in Australia. research papers 4 of 7 Rhiannon P. Murrie et al. Live small-animal imaging at the Australian Synchrotron J. Synchrotron Rad. (2015). 22 Figure 1
We have developed a custom-designed ventilator to deliver a stable pressure to the lungs of small... more We have developed a custom-designed ventilator to deliver a stable pressure to the lungs of small animals for use in imaging experiments. Our ventilator was designed with independent pressure vessels to separately control the Peak Inspiratory Pressure (PIP) and Positive End Expiratory Pressure (PEEP) to minimise pressure fluctuations during the ventilation process. The ventilator was computer controlled through a LabVIEW
ASME 2008 Summer Bioengineering Conference, Parts A and B, 2008
The ability of platelets to adhere and aggregate to form a stable thrombus plays a key role in th... more The ability of platelets to adhere and aggregate to form a stable thrombus plays a key role in the normal haemostatic process at sites of vascular injury. However, thrombus formation plays a sinister role in arterial diseases leading to heart attacks or strokes. Platelet activation ...
Imaging techniques employed to measure the structure of granular, particulate and porous material... more Imaging techniques employed to measure the structure of granular, particulate and porous materials are limited by scale, temporal resolution and, for biological samples, radiation exposure. This paper describes a technique for determining the distribution of particle sizes in opaque samples, for particle volume fractions less than ten percent, using a single projection radiograph. The method is based on the derived property of the additivity of the particles' spatial autocorrelation function in projection images. Simulations and experiments demonstrate the ability to use this property to determine the distribution of particle sizes in a material.
Purpose: Described herein is a new technique for measuring regional lung air volumes from twodime... more Purpose: Described herein is a new technique for measuring regional lung air volumes from twodimensional propagation-based phase contrast x-ray (PBI) images at very high spatial and temporal resolution. Phase contrast dramatically increases lung visibility and the outlined volumetric reconstruction technique quantifies dynamic changes in respiratory function. These methods can be used for assessing pulmonary disease and injury and for optimizing mechanical ventilation techniques for preterm infants using animal models. Methods: The volumetric reconstruction combines the algorithms of temporal subtraction and single image phase retrieval (SIPR) to isolate the image of the lungs from the thoracic cage in order to measure regional lung air volumes. The SIPR algorithm was used to recover the change in projected thickness of the lungs on a pixel-by-pixel basis (pixel dimensions ∼16.2 μm). The technique has been validated using numerical simulation and compared results of measuring regional lung air volumes with and without the use of temporal subtraction for removing the thoracic cage. To test this approach, a series of PBI images of newborn rabbit pups mechanically ventilated at different frequencies was employed. Results: Regional lung air volumes measured from PBI images of newborn rabbit pups showed on average an improvement of at least 20% in 16% of pixels within the lungs in comparison to that measured without the use of temporal subtraction. The majority of pixels that showed an improvement was found to be in regions occupied by bone. Applying the volumetric technique to sequences of PBI images of newborn rabbit pups, it is shown that lung aeration at birth can be highly heterogeneous. Conclusions: This paper presents an image segmentation technique based on temporal subtraction that has successfully been used to isolate the lungs from PBI chest images, allowing the change in lung air volume to be measured over regions as small as the pixel size. Using this technique, it is possible to measure changes in regional lung volume at high spatial and temporal resolution during breathing at much lower x-ray dose than would be required using computed tomography.
A novel, accurate and simple stereo particle image velocimetry (SPIV) technique utilising three c... more A novel, accurate and simple stereo particle image velocimetry (SPIV) technique utilising three cameras is presented. The key feature of the new technique is that there is no need of a separate calibration phase. The calibration data are measured concurrently with the PIV data by a third paraxial camera. This has the benefit of improving ease of use and reducing the time taken to obtain data. This third camera also provides useful velocity information, considerably improving the accuracy of the resolved 3D vectors. The additional redundancy provided by this third perspective in the stereo reconstruction equations suggests a least-squares approach to their solution. The least-squares process further improves the utility of the technique by means of the reconstruction residual. Detailed error analysis shows that this residual is an accurate predictor of resolved vector errors. The new technique is rigorously validated using both pure translation and rotation test cases. However, while this kind of validation is standard, it is shown that such validation is substantially flawed. The case of the well-known confined vortex breakdown flow is offered as an alternative validation. This flow is readily evaluated using CFD methods, allowing a detailed comparison of the data and evaluation of PIV errors in their entirety for this technique.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
Journal of applied physiology (Bethesda, Md. : 1985), 2014
At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large ... more At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Withi...
To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel m... more To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials. M ucociliary transport (MCT) requires the coordinated beating of cilia, microscopic hair-like structures, to propel the airway surface liquid (ASL) across the surfaces of epithelial cells. This integrated activity provides the primary method for removing deposited pathogens and particulates from airway surfaces. In cystic fibrosis (CF), a dysfunctional CF transmembrane conductance regulator (CFTR) ion channel in airway epithelial cells results in dehydration of the ASL and impaired MCT. The MCT failure produces retention of inhaled pathogens and particulates, mucus obstruction, chronic infection, and eventually lung failure 1 . Current clinical assessments of CF airway disease and its treatment are indirect. A logical method to assess the effect of CF treatments on airway surfaces is to directly measure restoration of MCT activity by tracking the movement of deposited marker particles along the airways. The ability to directly visualise deposited particle MCT behaviour in live animal model airways could provide spatio-temporal information pertaining to the initiation and maintenance of CF pathophysiology and potentially reveal novel directions for the development of preventative therapies for CF airway disease.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
In recent times, the study and use of induced pluripotent stem cells (iPSC) have become important... more In recent times, the study and use of induced pluripotent stem cells (iPSC) have become important in order to avoid the ethical issues surrounding the use of embryonic stem cells. Therapeutic, industrial and research based use of iPSC requires large quantities of cells generated in vitro. Mammalian cells, including pluripotent stem cells, have been expanded using 3D culture, however current limitations have not been overcome to allow a uniform, optimized platform for dynamic culture of pluripotent stem cells to be achieved. In the current work, we have expanded mouse iPSC in a spinner flask using Cytodex 3 microcarriers. We have looked at the effect of agitation on the microcarrier survival and optimized an agitation speed that supports bead suspension and iPS cell expansion without any bead breakage. Under the optimized conditions, the mouse iPSC were able to maintain their growth, pluripotency and differentiation capability. We demonstrate that microcarrier survival and iPS cell expansion in a spinner flask are reliant on a very narrow range of spin rates, highlighting the need for precise control of such set ups and the need for improved design of more robust systems.
As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progre... more As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progression of this process is required to guide ongoing care. We investigated whether expired CO 2 (ECO 2 ) levels indicate the degree of lung aeration immediately after birth in two animal models and in preterm infants. Lambs were delivered by caesarean section and ventilated from birth. In lambs, ECO 2 levels were significantly (p,0.0001) related to tidal volumes and CO 2 clearance/breath increased exponentially when tidal volumes were greater than 6 mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered by caesarean section and lung aeration was measured using phase contrast X-ray imaging. In rabbit kittens, ECO 2 levels were closely related (p,0.001) to lung volumes at end-inflation and were first detected when ,7% of the distal lung regions were aerated. ECO 2 levels in preterm infants at birth also correlated with tidal volumes. In each infant, ECO 2 levels increased to .10 mmHg 28 (median) (21-36) seconds before the heart rate increased above 100 beats per minute. These data demonstrate that ECO 2 levels can indicate the relative degree of lung aeration after birth and can be used to clinically assess ventilation in the immediate newborn period.
Anatomical visualization of airspace-containing organs in intact small animals has been limited b... more Anatomical visualization of airspace-containing organs in intact small animals has been limited by the resolution and contrast available from current imaging methods such as X-ray, micro-computed tomography and magnetic resonance imaging. Determining structural relationships and detailed anatomy has therefore relied on suitable fixation, sectioning and histological processing. More complex and informative analyses such as orthogonal views of an organ and three-dimensional structure visualizations have required different animals and image sets, laboriously processed to gather this complementary structural information. Precise three-dimensional anatomical views have always been difficult to achieve in small animals. Here we report the ability of phase-contrast synchrotron X-ray imaging to provide detailed two-and three-dimensional visualization of airspace organ structures in intact animals. Using sub-micrometre square pixel charge-coupled device array detectors, the structure and anatomy of hard and soft tissues, and of airspaces, is readily available using phase-contrast synchrotron X-ray imaging. Moreover, software-controlled volume-reconstructions of tomographic images not only provide unsurpassed image clarity and detail, but also selectable anatomical views that cannot be obtained with established histological techniques. The morphology and structure of nasal and lung airways and the middle ear are illustrated in intact mice, using two-and three-dimensional representations. The utility of phase-contrast synchrotron X-ray imaging for noninvasively localizing objects implanted within airspaces, and the detection of gas bubbles transiting live airways, are other novel features of this visualization methodology. The coupling of phase-contrast synchrotron X-ray imaging technology with software-based reconstruction techniques holds promise for novel and high-resolution non-invasive examination of airspace anatomy in small animal models.
Alterations in regional lung function due to respiratory infection have a significant effect on t... more 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.
The high flux and coherence produced at long synchrotron beamlines makes them well suited to perf... more The high flux and coherence produced at long synchrotron beamlines makes them well suited to performing phase-contrast X-ray imaging of the airways and lungs of live small animals. Here, findings of the first live-animal imaging on the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron are reported, demonstrating the feasibility of performing dynamic lung motion measurement and high-resolution micro-tomography. Live anaesthetized mice were imaged using 30 keV monochromatic X-rays at a range of sample-todetector propagation distances. A frame rate of 100 frames s À1 allowed lung motion to be determined using X-ray velocimetry. A separate group of humanely killed mice and rats were imaged by computed tomography at high resolution. Images were reconstructed and rendered to demonstrate the capacity for detailed, user-directed display of relevant respiratory anatomy. The ability to perform X-ray velocimetry on live mice at the IMBL was successfully demonstrated. High-quality renderings of the head and lungs visualized both large structures and fine details of the nasal and respiratory anatomy. The effect of sample-to-detector propagation distance on contrast and resolution was also investigated, demonstrating that soft tissue contrast increases, and resolution decreases, with increasing propagation distance. This new capability to perform live-animal imaging and high-resolution microtomography at the IMBL enhances the capability for investigation of respiratory diseases and the acceleration of treatment development in Australia. research papers 4 of 7 Rhiannon P. Murrie et al. Live small-animal imaging at the Australian Synchrotron J. Synchrotron Rad. (2015). 22 Figure 1
We have developed a custom-designed ventilator to deliver a stable pressure to the lungs of small... more We have developed a custom-designed ventilator to deliver a stable pressure to the lungs of small animals for use in imaging experiments. Our ventilator was designed with independent pressure vessels to separately control the Peak Inspiratory Pressure (PIP) and Positive End Expiratory Pressure (PEEP) to minimise pressure fluctuations during the ventilation process. The ventilator was computer controlled through a LabVIEW
ASME 2008 Summer Bioengineering Conference, Parts A and B, 2008
The ability of platelets to adhere and aggregate to form a stable thrombus plays a key role in th... more The ability of platelets to adhere and aggregate to form a stable thrombus plays a key role in the normal haemostatic process at sites of vascular injury. However, thrombus formation plays a sinister role in arterial diseases leading to heart attacks or strokes. Platelet activation ...
Imaging techniques employed to measure the structure of granular, particulate and porous material... more Imaging techniques employed to measure the structure of granular, particulate and porous materials are limited by scale, temporal resolution and, for biological samples, radiation exposure. This paper describes a technique for determining the distribution of particle sizes in opaque samples, for particle volume fractions less than ten percent, using a single projection radiograph. The method is based on the derived property of the additivity of the particles' spatial autocorrelation function in projection images. Simulations and experiments demonstrate the ability to use this property to determine the distribution of particle sizes in a material.
Purpose: Described herein is a new technique for measuring regional lung air volumes from twodime... more Purpose: Described herein is a new technique for measuring regional lung air volumes from twodimensional propagation-based phase contrast x-ray (PBI) images at very high spatial and temporal resolution. Phase contrast dramatically increases lung visibility and the outlined volumetric reconstruction technique quantifies dynamic changes in respiratory function. These methods can be used for assessing pulmonary disease and injury and for optimizing mechanical ventilation techniques for preterm infants using animal models. Methods: The volumetric reconstruction combines the algorithms of temporal subtraction and single image phase retrieval (SIPR) to isolate the image of the lungs from the thoracic cage in order to measure regional lung air volumes. The SIPR algorithm was used to recover the change in projected thickness of the lungs on a pixel-by-pixel basis (pixel dimensions ∼16.2 μm). The technique has been validated using numerical simulation and compared results of measuring regional lung air volumes with and without the use of temporal subtraction for removing the thoracic cage. To test this approach, a series of PBI images of newborn rabbit pups mechanically ventilated at different frequencies was employed. Results: Regional lung air volumes measured from PBI images of newborn rabbit pups showed on average an improvement of at least 20% in 16% of pixels within the lungs in comparison to that measured without the use of temporal subtraction. The majority of pixels that showed an improvement was found to be in regions occupied by bone. Applying the volumetric technique to sequences of PBI images of newborn rabbit pups, it is shown that lung aeration at birth can be highly heterogeneous. Conclusions: This paper presents an image segmentation technique based on temporal subtraction that has successfully been used to isolate the lungs from PBI chest images, allowing the change in lung air volume to be measured over regions as small as the pixel size. Using this technique, it is possible to measure changes in regional lung volume at high spatial and temporal resolution during breathing at much lower x-ray dose than would be required using computed tomography.
A novel, accurate and simple stereo particle image velocimetry (SPIV) technique utilising three c... more A novel, accurate and simple stereo particle image velocimetry (SPIV) technique utilising three cameras is presented. The key feature of the new technique is that there is no need of a separate calibration phase. The calibration data are measured concurrently with the PIV data by a third paraxial camera. This has the benefit of improving ease of use and reducing the time taken to obtain data. This third camera also provides useful velocity information, considerably improving the accuracy of the resolved 3D vectors. The additional redundancy provided by this third perspective in the stereo reconstruction equations suggests a least-squares approach to their solution. The least-squares process further improves the utility of the technique by means of the reconstruction residual. Detailed error analysis shows that this residual is an accurate predictor of resolved vector errors. The new technique is rigorously validated using both pure translation and rotation test cases. However, while this kind of validation is standard, it is shown that such validation is substantially flawed. The case of the well-known confined vortex breakdown flow is offered as an alternative validation. This flow is readily evaluated using CFD methods, allowing a detailed comparison of the data and evaluation of PIV errors in their entirety for this technique.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
Journal of applied physiology (Bethesda, Md. : 1985), 2014
At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large ... more At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Withi...
To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel m... more To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials. M ucociliary transport (MCT) requires the coordinated beating of cilia, microscopic hair-like structures, to propel the airway surface liquid (ASL) across the surfaces of epithelial cells. This integrated activity provides the primary method for removing deposited pathogens and particulates from airway surfaces. In cystic fibrosis (CF), a dysfunctional CF transmembrane conductance regulator (CFTR) ion channel in airway epithelial cells results in dehydration of the ASL and impaired MCT. The MCT failure produces retention of inhaled pathogens and particulates, mucus obstruction, chronic infection, and eventually lung failure 1 . Current clinical assessments of CF airway disease and its treatment are indirect. A logical method to assess the effect of CF treatments on airway surfaces is to directly measure restoration of MCT activity by tracking the movement of deposited marker particles along the airways. The ability to directly visualise deposited particle MCT behaviour in live animal model airways could provide spatio-temporal information pertaining to the initiation and maintenance of CF pathophysiology and potentially reveal novel directions for the development of preventative therapies for CF airway disease.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
A technique capable of simultaneous measurement of free surface topography and velocity vector fi... more A technique capable of simultaneous measurement of free surface topography and velocity vector field data is developed. This technique offers substantial benefits of both reduced complexity and enhanced accuracy over all other techniques known to offer the same measurements. The flow behind a circular cylinder at low Reynolds numbers is measured using this technique. The velocity and vorticity fields as well as Strouhal number closely match the expected results. The free surface topography, which can be related to the pressure field, exhibits an intimate relationship to the vorticity field.
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Papers by Andreas Fouras