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Dual-modal CT and MRI functional and anatomical imaging using barium sulphate and gadolinium nanoparticle loaded macrophages in a preclinical asthma mouse model
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.
Institute of Diagnostic and Interventional Radiology, University Hospital Goettingen, Germany.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
Jožef Stefan Institute, Ljubljana, Slovenia.
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2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives In this study we investigated the potentials of dual-modal CT-MRI macrophage tracking, by a intratracheal instillation of a mixture of either gadolinium nanoparticles or barium sulphate loaded alveolar macrophages into mice of an allergic airway inflammation (asthma) model and their respective healthy control, imaged with Synchrotron X-rays microtomography (SR μCT) and Micro Magnetic Resonance Imaging (μMRI).

Materials and Methods The mice were scanned ex vivo using SRμCT at 22 keV and with a 9.4 Tesla μMRI scanner. The CT and MRI data sets were registered and fused together, followed by quantitative and statistical analysis.

Results The asthmatic sample injected with contrast agent loaded macrophages showed high absorbing spots inside the soft-tissue regions of the lung for the CT data set, as well as higher contrast for the soft-tissue in the MRI data set. Furthermore, the correlation analysis showed a perfect negative correlation between the soft tissue mean grey value in CT and the soft tissue mean grey value in MRI.

Conclusion The dual-modal CT-MRI cell tracking of intratracheally administered macrophages (loaded with contrast agent) in an asthmatic mouse helps to extract synergistic information about the migration  behaviour of macrophages, where clusters of cells were detected in CT, while as a general increase of the soft-tissue contrast could be observed in MRI, due to a homogeneous cell distribution.

Place, publisher, year, edition, pages
2015.
Keyword [en]
Gadolinium oxide (Gd2O3); alveolar macrophages; asthma; magnetic resonance imaging; Synchrotron X-Ray Computed Microtomography
National Category
Physical Sciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-122603OAI: oai:DiVA.org:liu-122603DiVA: diva2:868592
Available from: 2015-11-11 Created: 2015-11-11 Last updated: 2015-11-11Bibliographically approved
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.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1707
National Category
Physical Sciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
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)
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Supervisors
Available from: 2015-11-11 Created: 2015-11-11 Last updated: 2015-12-02Bibliographically approved

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