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Title: Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads

Abstract

Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CFmore » mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.« less

Authors:
; ;  [1];  [2];  [2]; ;  [3]
  1. Respiratory & Sleep Medicine, Women’s and Children’s Hospital, North Adelaide, South Australia (Australia)
  2. (Australia)
  3. School of Physics, Monash University, Victoria (Australia)
Publication Date:
OSTI Identifier:
22494381
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1696; Journal Issue: 1; Conference: XRM 2014: 12. international conference on X-ray microscopy, Melbourne (Australia), 26-31 Oct 2014; Other Information: (c) 2016 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND TECHNOLOGY; 71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS; COMPUTER CODES; FIBROSIS; GENES; GLASS; HYDRATION; IMAGES; LUNGS; MICE; MICROSCOPY; NOSE; PARTICLE TRACKS; PARTICLES; PATHOGENS; REFRACTIVE INDEX; SENSITIVITY; SPRING-8 STORAGE RING; SYNCHROTRONS; THERAPY; X RADIATION

Citation Formats

Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au, Farrow, Nigel, Parsons, David, Robinson Research Institute, University of Adelaide, South Australia, School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Morgan, Kaye, and Siu, Karen. Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads. United States: N. p., 2016. Web. doi:10.1063/1.4937505.
Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au, Farrow, Nigel, Parsons, David, Robinson Research Institute, University of Adelaide, South Australia, School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Morgan, Kaye, & Siu, Karen. Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads. United States. doi:10.1063/1.4937505.
Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au, Farrow, Nigel, Parsons, David, Robinson Research Institute, University of Adelaide, South Australia, School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Morgan, Kaye, and Siu, Karen. Thu . "Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads". United States. doi:10.1063/1.4937505.
@article{osti_22494381,
title = {Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads},
author = {Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au and Farrow, Nigel and Parsons, David and Robinson Research Institute, University of Adelaide, South Australia and School of Paediatrics and Reproductive Health, University of Adelaide, South Australia and Morgan, Kaye and Siu, Karen},
abstractNote = {Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.},
doi = {10.1063/1.4937505},
journal = {AIP Conference Proceedings},
number = 1,
volume = 1696,
place = {United States},
year = {Thu Jan 28 00:00:00 EST 2016},
month = {Thu Jan 28 00:00:00 EST 2016}
}
  • The prism coupling technique has been utilized to measure the refractive index in the near- and mid-IR spectral region of chalcogenide glasses in bulk and thin film form. A commercial system (Metricon model 2010) has been modified with additional laser sources, detectors, and a new GaP prism to allow the measurement of refractive index dispersion over the 1.5–10.6 μm range. The instrumental error was found to be ±0.001 refractive index units across the entire wavelength region examined. Measurements on thermally evaporated AMTIR2 thin films confirmed that (i) the film deposition process provides thin films with reduced index compared to thatmore » of the bulk glass used as a target, (ii) annealing of the films increases the refractive index of the film to the level of the bulk glass used as a target to create it, and (iii) it is possible to locally increase the refractive index of the chalcogenide glass using laser exposure at 632.8 nm.« less
  • The prism coupling technique has been utilized to measure the refractive index in the near- and mid-IR spectral region of chalcogenide glasses in bulk and thin film form. A commercial system (Metricon model 2010) has been modified with additional laser sources, detectors, and a new GaP prism to allow the measurement of refractive index dispersion over the 1.5-10.6 {mu}m range. The instrumental error was found to be {+-}0.001 refractive index units across the entire wavelength region examined. Measurements on thermally evaporated AMTIR2 thin films confirmed that (i) the film deposition process provides thin films with reduced index compared to thatmore » of the bulk glass used as a target, (ii) annealing of the films increases the refractive index of the film to the level of the bulk glass used as a target to create it, and (iii) it is possible to locally increase the refractive index of the chalcogenide glass using laser exposure at 632.8 nm.« less
  • We propose a variable-path interferometric technique for the measurement of the absolute refractive index of optical glasses. We use two interferometers to decide the ratio between changes in the optical path in a prism-shaped sample glass and in air resulting from displacement of the sample. The method allows precise measurements to be made without prior knowledge of the properties of the sample. The combined standard uncertainty of the proposed method is 1.6x10{sup -6}.
  • An optics for hard x-ray holographic microscopy has been developed and preliminary experiments have been done at SPring-8 undulator beamline 20XU. The optical system consists of an x-ray objective lens (Fresnel zone plate) and a wave front-division-type interferometer with prism optics. The illuminating x-ray beam is coherent with parallel radiation, and the spatially coherent area is much larger than the aperture of the objective lens. The refractive prism is placed behind the back focal plane of the objective lens in order to configure the wavefront-dividing interferometer. Half of the illuminating radiation is used for illuminating an object, and the othermore » half is used for forming a reference wave. The magnified image of the object is generated at an image plane, and the reference wave is superimposed on the magnified image of the object. The recorded interferogram includes both amplitude and phase information of the object. The spatial resolution is determined by the numerical aperture of the objective lens. Therefore, in principle, this method enables holographic imaging at nanometer scale to be carried out in the hard x-ray region.« less
  • Imaging holography in hard x-ray region is realized by combining imaging microscopy with a refractive prism interferometer. The prism is placed behind the back-focal-plane of objective lens in order to configure a wave-front-division interferometer, and a magnified interferogram of object image is generated at an image plane. Spatial resolution of the image hologram is essentially determined by the performance of objective lens. However, speckle noise is a serious problem for fully coherent illumination. We have tried 'asymmetric spatial coherence' to reduce the speckle noise. A synchrotron radiation light source with small coupling constant is very suitable for this purpose. Themore » spatial coherence is sufficiently high in the vertical direction to make an interferogram, and low enough in the horizontal direction to suppress the speckle noise. Preliminary experiments at BL20XU of SPring-8 are shown.« less