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Optimization of the loading efficacy for dual-modal CT/MRI macrophage tracking in lungs of an asthma mouse model
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska högskolan. Elettra Sincrotrone Trieste, Italy; University of Trieste, Italy.
Institute of Diagnostic and Interventional Radiology, University Hospital Goettingen, Germany.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
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2015 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

We present novel cell uptake methodologies related to the usage of MRI/CT contrast agents for the purpose of performing dual-modal cell tracking with macrophages in both MRI and CT. Two different techniques, namely Synchrotron X-rays microtomography and Micro Magnetic Resonance Imaging were used to investigate the contrast  enhancement, as an effect of the MRI/CT contrast agent cell uptake of mouse alveolar macrophages. Macrophages loaded with the  commercial contrast agent Micropaque® CT, containing barium sulphate (BaSO4) immersed in Sorbitol, showed a much higher contrast enhancement in CT, than an MRI/CT contrast agent based on Gadolinium nanoparticles (GdNPs). The CT contrast of GdNPs (at 5 mM of Gd) could be increased, by immersing the GdNPs in Sorbitol, while still maintaining a positive T1-contrast in MRI. The idea of co-loading macrophages with both BaSO4 and GdNP inside the same cells  presented a valid "trade off" between the optimal contrast in CT vs. MRI etc. It was concluded that while optimizing the cell uptake of contrast agent for cell tracking in MRI/CT, it is important to make a "trade off" between the following 3 parameters, 1) optimal contrast in CT, 2) optimal contrast in MRI and 3) metabolic cell activity, depending on the given application. These cell optimization ideas may be of importance to every field aiming to image an inflammatory disease, based on the utilization of contrast agent loaded macrophages.

Ort, förlag, år, upplaga, sidor
2015.
Nyckelord [en]
Gd2O3 nanoparticle; Gadolinium oxide; dual-modal MRI/CT contrast agent; barium sulphate; macrophages; cell loading efficacy
Nationell ämneskategori
Fysik
Identifikatorer
URN: urn:nbn:se:liu:diva-122602OAI: oai:DiVA.org:liu-122602DiVA, id: diva2:868591
Tillgänglig från: 2015-11-11 Skapad: 2015-11-11 Senast uppdaterad: 2015-11-11Bibliografiskt granskad
Ingår i avhandling
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
Öppna denna publikation i ny flik eller fönster >>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 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2015. s. 73
Serie
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1707
Nationell ämneskategori
Fysik Radiologi och bildbehandling
Identifikatorer
urn:nbn:se:liu:diva-122607 (URN)10.3384/diss.diva-122607 (DOI)978-91-7685-936-0 (ISBN)
Disputation
2015-12-07, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-11-11 Skapad: 2015-11-11 Senast uppdaterad: 2015-12-02Bibliografiskt granskad

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Larsson, EmanuelAbrikossova, NataliaBrommesson, CarolineUvdal, Kajsa

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Larsson, EmanuelAbrikossova, NataliaBrommesson, CarolineUvdal, Kajsa
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