Deliverables Documents, reports (14) Evaluation of NQR-CR with MRI Test of uptake of particles into endothelial cells and into human PBMCs by microscopy and MRI. MRI will be done after cells have been incubated with different dilutions of the NPs and embedded in agarose. Contrast changes due to switching of B0 in phantoms and in cell cultures after cellular uptake will be studied and documented. Quantum-mechanical model 1 An NQR-modeling approach which has been developed for solids will be extended towards different motional scenarios to account for rotational, translational and internal dynamics as well as exchange processes. Existing numerical tools will be used for initial simulations but the software will be continuously developed to account for the complex relaxation scenario. Optimisation is likely to be required as the computational complexity increases significantly for high spin (9/2) nuclei. Where necessary, the quantum-mechanical models will be combined with molecular dynamics simulations. Scientific papers of reporting period 2 8 Scientific papers planned on theoretical modelling, synthesis of NQR-CR compounds and their characterisation as well as on toxicology and imaging results. Papers on the proof of concept. Report on publications and events Report on publications (journal and book articles, patents etc. as well as events such as workshops and mini-symposia on conferences. Scientific papers of reporting period 1 3 Scientific papers planned on theoretical modelling, synthesis of NQR-CR compounds and their characterisation. Cytotoxicity, uptake, inflammation Cell cultures for MRI experiments will be prepared. Absence of biological contamination, sufficient cellular uptake and lack of adverse cellular effects will be shown with endothelial cells and blood cells. Contamination will be detected by subjecting the NPs to limulus amoebocyte lysate assay to test endotoxin levels Cytotoxicity and potential influence on the immune system will be studied and documented. Tuned NPs characterised After optimisation of the prototype particle system (size, chemistry and hydrophilicity the NQR properties will be tuned in order to fulfil the 3T conditions. Thus a fine tuning of the particle size, shape and slight chemical modifications may be required. Modified MRI scanner characterised "The existing clinical 3T scanner will be equipped with a coil insert for shifting B0 so as to change the NQR-CR (custom manufacturing by ""Resonance Research""). The RF coils used will be dedicated animal coils. Existing pulse sequences will be modified to control the coil insert and optimised for high SNR. The complete MRI setup will be validated and characterized with dedicated MRI phantoms. " Extended quantum-mechanical model Theoretical models and simulations for systems containing QN and paramagnetic ions, different kinds of QN, will be developed to explore the possibilities offered by multi-quantum effects. Although a comprehensive model is necessary for predicting in detail the contrast properties of the CA, we will also develop simplified, phenomenological ‗master rules‘ relating the shape of the NQR-CR peaks with structural and dynamical parameters. Due to their complexity the developed models will be thoroughly tested against experiments Relaxometry data base tuned NPs 1H NMR Field Cycling studies for the final, fine-tuned compounds synthetised by WPs 3 and 4 will be carried out. The results will again be documented and stored in a database. ZF-NQRS database Zero field NQRS of promising prototype compounds from WP3 will be carried out. From the spectra the resonance frequencies and the facor eta will be deduced and the quantum-chemical computations in WP3 will be validated. The relative strength of the NQR peaks and the NQR relaxation times will be characterised to study the magnitude of the effects in different compounds. All data will be stored in a database. Relaxometry database prototyping 1H NMR Field Cycling studies for selected prototype compounds synthesised by WPs 3 and 4 will be carried out. Preliminary measurements will be carried out in parallel to the theoretical simulations. The preliminary studies will be followed by detailed experimental investigations of specific systems selected on the basis of simulations to confirm or negate their potential as CA. All experimental results will be documented and stored in a database. Dextran based NPs characterised Immobilisation of the most promising candidates from WP3 (TUG) in terms of NQR frequencies onto dextranes differing in molecular weight and the degree of branching. The immobilisation will be performed by reacting the Bi compounds bearing a functional spacer group (e.g. carboxylic groups) with the polymers. For example, carbodiimide chemistry is a well-known procedure for coupling OH with COOH groups in a very efficient way, and several literature procedures are known. Purification (e.g. dialysis) of the polymers and nanoprecipitation under sonication conditions to create nano- and micro-particles with defined sizes according to the guidelines WP2 from UWM and UU. The sizes will be varied over two orders of magnitudes in order to explore the influence on relaxivity. (Task 4.2, UM, TUG, UWM) Characterisation of the NPs by state of the art techniques (Infrared spectroscopy, SWAXS, TEM, dynamic light scattering, zeta potential, ZF-NQRS, fast field cycling relaxometry). NQR-CR polymers characterised Immobilisation of the most promising candidates from WP3 in terms of NQR frequencies onto PEG differing in molecular weight and the degree of branching. The immobilisation will be performed by reacting the Bi compounds bearing a functional spacer group (e.g. carboxylic groups) with the polymers. For example, carbodiimide chemistry is a well-known procedure for coupling OH with COOH groups in a very efficient way, and several literature procedures are known. Purification (e.g. dialysis) of the polymers and nanoprecipitation under sonication conditions to create nano- and micro-particles with defined sizes according to the guidelines WP2 from UWM and UU. The sizes will be varied over two orders of magnitudes in order to explore the influence on relaxivity. Characterisation of the NPs by state of the art techniques (Infrared spectroscopy, SWAXS, TEM, dynamic light scattering, zeta potential, ZF-NQRS, fast field cycling relaxometry). Open Research Data Pilot (1) Data management plan Detailed rules for data management, enabling data exchange by supplying appropriate channels and assurance of data security (server management). Other (1) Webpage with open access database Design and implementation of a webpage for communicating general information and results, providing open access to data and for facilitating networking activities. Publications Peer reviewed articles (13) An electronically tuned wideband probehead for NQR spectroscopy in the VHF range Author(s): Hermann Scharfetter Published in: Journal of Magnetic Resonance, Issue 271, 2016, Page(s) 90-98, ISSN 1090-7807 Publisher: Academic Press DOI: 10.1016/j.jmr.2016.08.008 A cryostatic, fast scanning, wideband NQR spectrometer for the VHF range Author(s): Hermann Scharfetter, Markus Bödenler, Dominik Narnhofer Published in: Journal of Magnetic Resonance, Issue 286, 2018, Page(s) 148-157, ISSN 1090-7807 Publisher: Academic Press DOI: 10.1016/j.jmr.2017.12.004 R 1 dispersion contrast at high field with fast field-cycling MRI Author(s): Markus Bödenler, Martina Basini, Maria Francesca Casula, Evrim Umut, Christian Gösweiner, Andreas Petrovic, Danuta Kruk, Hermann Scharfetter Published in: Journal of Magnetic Resonance, Issue 290, 2018, Page(s) 68-75, ISSN 1090-7807 Publisher: Academic Press DOI: 10.1016/j.jmr.2018.03.010 209 Bi quadrupole relaxation enhancement in solids as a step towards new contrast mechanisms in magnetic resonance imaging Author(s): D. Kruk, E. Umut, E. Masiewicz, C. Sampl, R. Fischer, S. Spirk, C. Goesweiner, H. Scharfetter Published in: Physical Chemistry Chemical Physics, Issue 20/18, 2018, Page(s) 12710-12718, ISSN 1463-9076 Publisher: Royal Society of Chemistry DOI: 10.1039/c8cp00993g 1 H relaxation and dynamics of triphenylbismuth in deuterated solvents Author(s): Danuta Kruk, Elzbieta Masiewicz, Evrim Umut, Hermann Scharfetter Published in: Molecular Physics, 2018, Page(s) 1-6, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1513175 Tuning Nuclear Quadrupole Resonance: A Novel Approach for the Design of Frequency-Selective MRI Contrast Agents Author(s): Christian Gösweiner, Perttu Lantto, Roland Fischer, Carina Sampl, Evrim Umut, Per-Olof Westlund, Danuta Kruk, Markus Bödenler, Stefan Spirk, Andreas Petrovič, Hermann Scharfetter Published in: Physical Review X, Issue 8/2, 2018, ISSN 2160-3308 Publisher: American Physical Society DOI: 10.1103/PhysRevX.8.021076 Model – free approach to quadrupole spin relaxation in solid 209 Bi-aryl compounds Author(s): Danuta Kruk, Christian Goesweiner, Elzbieta Masiewicz, Evrim Umut, Carina Sampl, Hermann Scharfetter Published in: Physical Chemistry Chemical Physics, Issue 20/36, 2018, Page(s) 23414-23423, ISSN 1463-9076 Publisher: Royal Society of Chemistry DOI: 10.1039/C8CP03848A 1 H spin–lattice relaxation in water solution of 209 Bi counterparts of Gd 3+ contrast agents Author(s): Danuta Kruk, Evrim Umut, Elzbieta Masiewicz, Petr Hermann, Hermann Scharfetter Published in: Molecular Physics, 2018, Page(s) 1-8, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1517907 Predicting quadrupole relaxation enhancement peaks in proton R 1 -NMRD profiles in solid Bi-aryl compounds from NQR parameters Author(s): Christian Gösweiner, Danuta Kruk, Evrim Umut, Elzbieta Masiewicz, Markus Bödenler, Hermann Scharfetter Published in: Molecular Physics, 2018, Page(s) 1-11, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1519201 Aspects of structural order in 209 Bi-containing particles for potential MRI contrast agents based on quadrupole enhanced relaxation Author(s): Hermann Scharfetter, Christian Gösweiner, Paul Josef Krassnig, Carina Sampl, Martin Thonhofer, Roland Fischer, Stefan Spirk, Rupert Kargl, Karin Stana-Kleinschek, Evrim Umut, Danuta Kruk Published in: Molecular Physics, 2018, Page(s) 1-9, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1511869 Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives Author(s): Markus Bödenler, Ludovic de Rochefort, P. James Ross, Nicolas Chanet, Geneviève Guillot, Gareth R. Davies, Christian Gösweiner, Hermann Scharfetter, David J. Lurie, Lionel M. Broche Published in: Molecular Physics, Issue 117/7-8, 2018, Page(s) 832-848, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1557349 Quadrupole relaxation enhancement and polarisation transfer in DMSO solution of [Bi(NO 3 ) 3 (H 2 O) 3 ]*18-crown-6 in solid state Author(s): Danuta Kruk, Elzbieta Masiewicz, Evrim Umut, Martin Schlögl, Roland Fischer, Hermann Scharfetter Published in: Molecular Physics, Issue 117/7-8, 2018, Page(s) 944-951, ISSN 0026-8976 Publisher: Taylor & Francis DOI: 10.1080/00268976.2018.1552798 Effect of different surface active polysaccharide derivatives on the formation of ethyl cellulose particles by the emulsion-solvent evaporation method Author(s): Mojca Božič, Thomas Elschner, Doris Tkaučič, Matej Bračič, Silvo Hribernik, Karin Stana Kleinschek, Rupert Kargl Published in: Cellulose, Issue 25/12, 2018, Page(s) 6901-6922, ISSN 0969-0239 Publisher: Blackie Academic & Professional DOI: 10.1007/s10570-018-2062-2 Searching for OpenAIRE data... 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