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- Title
698. Towards Non-Invasive Assessment of CF Airway Gene Therapy: High Resolution Propogation-Based Imaging of Airway Surface Liquid Via Synchrotron Light.
- Authors
Parsons, David W.; Siu, Karen W.; Crosbie, Jeffrey; Williams, Ivan; Richard, Boucher C.; Uesugi, Kentaro; Yagi, Naoto
- Abstract
Genetic and pharmaceutical treatments to deal with the ion-channel pathophysiology of cystic fibrosis attempt to increase the abnormally low depth of the thin (<10um) airway surface liquid. A practical therapeutic measurement of ASL depth must be non-invasive and repeatable. In this proof-of-concept study we examined whether Propagation-Based (phase-contrast) Imaging (PBI) could image the airway surface in live mice to resolve airway surface liquid.Methods: Anaesthetised C57Bl/6 mice were imaged through the skull and neck at the SPring-8 synchrotron in Hyogo, Japan. Images were obtained on a CCD detector (6.6 or 1.1 μm pixel size) over periods of up to 40 mins using a 25 keV beam and a 150 cm propagation distance. Exposure times between 100 ms and 500 ms were used.Results: Airway surfaces and skull structures were revealed with remarkable clarity. Figure 1 is a low magnification image revealing olfactory turbinates, nasopharynx, trachea, cartilage, bone suture lines, cochlea and neck vertebrae normally only observable at this resolution via histological sectioning. The nasal septum, where gene transfer assessments in CF mice are made, was easily located in adults and juveniles. The tracheal surface could also be observed, and obliquely-directed Xrays provided improved tracheal images because overlying bone was eliminated from the beam. Saline (20ul) instilled into the nasal airway produced lumenal gas bubbles that revealed well-defined edges at high magnification. Dynamic changes in these airway surface-bound bubbles, easily visible in pseudo-video animations, indicated an image spatial resolution of approximately 10um.Conclusions: High-resolution, non-invasive imaging of airway surfaces in live animals is feasible with synchrotron PBI. Ongoing technical improvements in animal preparation, Xray dose, and detector resolution suggest synchrotron PBI may provide safe and repeated non-invasive imaging of airway surfaces. Synchrotron PBI imaging has promise as a novel non-invasive assessment of ASL depth in animal models and humans undergoing acute and long-term treatment for CF airway disease.Molecular Therapy (2006) 13, S270–S270; doi: 10.1016/j.ymthe.2006.08.776
- Subjects
CYSTIC fibrosis; LABORATORY mice; LUNG diseases; OPERATIVE surgery; GENE therapy; GENETIC disorders
- Publication
Molecular Therapy, 2006, Vol 13, pS270
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.776