title: Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples.
abstract: Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.
authors.affiliation: Institute for Diagnostic and Interventional Radiology, University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.affiliation: Cluster in Biomedicine, AREA Science Park Basovizza, Trieste, Italy.
authors.forename: Simeone
authors.initials: S
authors.lastname: dal Monego
authors.affiliation: Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste), Italy.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste), Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Institute for X-ray Physics, University of Göttingen, Göttingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Krenkel
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Garrovo
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Biffi
authors.affiliation: Cluster in Biomedicine, AREA Science Park Basovizza, Trieste, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lorenzon
authors.affiliation: Department of Haematology and Medical Oncology, University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markus
authors.affiliation: Institute for Diagnostic and Interventional Radiology, University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Napp
authors.affiliation: Institute for X-ray Physics, University of Göttingen, Göttingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Salditt
authors.affiliation: Department of Architecture and Engineering, University of Trieste, Trieste, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Accardo
authors.affiliation: Institute for Diagnostic and Interventional Radiology, University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
authors.affiliation: Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste), Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Tromba
mesh_terms: D000465:Algorithms; D000485:Allergens / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D001466:Barium Sulfate / Q000493:pharmacokinetics; D002461:Cell Line, Transformed; D002465:Cell Movement; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000166:cytology* / Q000000981:diagnostic imaging; D016676:Macrophages, Alveolar / Q000000981:diagnostic imaging* / Q000502:physiology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D017356:Synchrotrons; D014057:Tomography, X-Ray Computed / Q000295:instrumentation* / Q000379:methods
chemical_list: D000485:Allergens; D003287:Contrast Media; D001466:Barium Sulfate; D010047:Ovalbumin
keywords: functional CT imaging; phase-contrast CT; single-distance phase retrieval