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Quantification of structural alterations in lung disease—a proposed analysis methodology of CT scans of preclinical mouse models and patients
Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering. Elettra Sincrotrone Trieste, Italy; University of Trieste, Italy..
Elettra Sincrotrone Trieste, Italy.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
University of Trieste, Italy.
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2015 (English)In: Biomedical Physics & Engineering Express, ISSN 2057-1976, Vol. 1, no 3, 035201Article in journal (Refereed) Published
Abstract [en]

In this paper we have established a general investigative methodology for quantitative computed tomography (CT) lung image analysis in the sagittal, coronal and transversal orientation of lungs with various lung diseases. Mean values were recorded for the two parameters percentage volume and structural thickness based on stripe shaped volumes of interest (VOIs) from the XY (transversal), YZ (sagittal) and ZX (coronal) orientation, placed out in the left and right lung side. A one-way ANOVA with Tukey–Kramer 90% simultaneous confidence intervals for pair wise comparison of means was performed on each considered parameter, in order to detect any statistically significant differences in between the samples. This methodology was first tested on high resolution synchrotron micro-computed tomography images of a preclinical asthma mouse model, injected with barium sulfate filled alveolar macrophages, with the purpose of marking out asthmatic inflammation sites. Preclinical mouse models are today commonly used as artificial models for studying various human diseases, e.g. asthma. Therefore, in order to translate our methodology protocol also to clinical applications the proposed methodology was also tested on lung data sets of patients, with various lung diseases. The presented general methodology was proven to be successful for the quantification of lung structural differences in an asthma mouse model, as well as being applicable also on patient lungs with various lung diseases. The outlined analysis protocol was tested on images obtained only by means of CT, but could also potentially be applied on images of the lung obtained by other 3D-imaging techniques.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2015. Vol. 1, no 3, 035201
Keyword [en]
lung imaging, asthma mouse model, quantitative image analysis, computed tomography, synchrotron microtomography, phase contrast
National Category
Medical Image Processing
Identifiers
URN: urn:nbn:se:liu:diva-121940DOI: 10.1088/2057-1976/1/3/035201OAI: oai:DiVA.org:liu-121940DiVA: diva2:860562
Funder
EU, FP7, Seventh Framework Programme, GA 230739Swedish Research Council
Available from: 2015-10-13 Created: 2015-10-13 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.
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)
Opponent
Supervisors
Available from: 2015-11-11 Created: 2015-11-11 Last updated: 2015-12-02Bibliographically approved

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Publisher's full texthttp://dx.doi.org/10.1088/2057-1976/1/3/035201

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