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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
University of Medical Centre Gottingen, Germany.
Cluster Biomed, Italy.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology. Elettra Sincrotrone Trieste, Italy; University of Trieste, Italy.
Elettra Sincrotrone Trieste, Italy.
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2015 (English)In: Journal of Synchrotron Radiation, ISSN 0909-0495, E-ISSN 1600-5775, Vol. 22, 143-155 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
International Union of Crystallography , 2015. Vol. 22, 143-155 p.
Keyword [en]
phase-contrast CT; single-distance phase retrieval; functional CT imaging
National Category
Physical Sciences
URN: urn:nbn:se:liu:diva-113733DOI: 10.1107/S1600577514021730ISI: 000346850200022PubMedID: 25537601OAI: diva2:784600

Funding Agencies|European Commission [230739]; Deutsche Forschungsgemeinschaft (DFG) [DU 1403/1-1]; EXTREMA COST action [MP1207]

Available from: 2015-01-30 Created: 2015-01-29 Last updated: 2015-11-11
In thesis
1. Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models
Open this publication in new window or tab >>Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

¨This thesis focuses on evaluating the dual-modal Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) capabilities of contrast agents. For such purposes a gadolinium based contrast agent is of high interest, due to its paramagnetic properties, which while present inside a magnetic field will hence interact with the protons spins of water (in tissue and fat) and shorten their the T1 relaxation time, thereby creating a positive image contrast in MRI. Furthermore, the X-ray Mass Attenuation Coefficient (MAC) of gadolinium is relatively high, thus suggesting its potential use, also as a CT contrast agent.

Gadolinium nanoparticles (GdNPs) can be loaded into cells, such as macrophages, which offers the possibility to track cells inside entire organisms. In the first step the uptake of GdNPs inside cells was investigated, together with a test for toxicity. To show the potential of using GdNP loaded macrophages for functional imaging of inflammation, an acute allergic airway inflammation mouse model (mimicking asthma in humans) was used and analyzed by in-situ synchrotron phase contrast CT. In the first step this approach was evaluated using macrophages loaded with a clinical contrast agent containing barium sulphate (BaSO4), since this agent is known to provide high contrast in CT. In the ultimate step a combination of both BaSO4 and GdNP loaded macrophages was used in the same asthmatic mouse model and analyzed by dual modal Synchrotron phase contrast CT and Micro Magnetic Resonance Imaging (μ-MRI).

Complementary results in terms of the biodistribution of injected macrophages could only be obtained by the combination of both synchrotron phase contrast CT and μ-MRI, where the first modality allows a detailed localization of clustered BaSO4 loaded macrophages, but fails to detect single macrophages, which could instead be indirectly observed by μ-MRI as an increase of the T1-contrast, coming from the soft tissue of mice injected with GdNP loaded macrophages.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 73 p.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1707
National Category
Physical Sciences Radiology, Nuclear Medicine and Medical Imaging
urn:nbn:se:liu:diva-122607 (URN)10.3384/diss.diva-122607 (DOI)978-91-7685-936-0 (print) (ISBN)
Public defence
2015-12-07, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (English)
Available from: 2015-11-11 Created: 2015-11-11 Last updated: 2015-12-02Bibliographically approved

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