Description du sujet de thèse

MAGNETIC RESONANCE METHODOLOGY: INSTRUMENTATION IN MRI AND APPLICATION TO INFLAMMATION

Context: The development of personalized medicine involves the implementation of new diagnostic approaches. It's goal is to identify the molecular mechanisms specific to the emergence of pathologies. In this context, the activity of enzymes, such as proteases, are involved in many inflammatory processes and certain cancers, and constitute a target of choice for early diagnosis.

The partners of this project have acquired experience over more than a decade to develop new radical molecules (nitroxides) specific to proteases which are detectable by a very original approach of low-field Magnetic Resonance Imaging based; the presence of radicals induces signal enhancement (positive contrast) by the Overhauser effect.

This project aims to develop new very low field MRI instruments using Dynamic Polarization and to evaluate new radical molecules for their ability to produce contrast in MRI in the context of inflammatory pathologies in rodents.

Thesis objective and subject:
The objective of the thesis is to achieve the operability of new instruments in magnetic resonance imaging enhanced by dynamic polarization, operating in a field of around 200 µT. The candidate's areas of skills and knowledge must include solid physical knowledges, particularly in magnetic resonance, an appetite for instrumental developments (detection probes, measurement of weak signals, magnets) and a possible interest in biological questions.

Scientific domain and themes :
The project is located at the crossroads of radical organic chemistry, chemistry-physics (notably spin spectroscopy), enzymology and imaging. The recruited person will mainly focus on physical and instrumental issues.

Program:
- Learn to use existing instruments at UMR 5536: MRI at 0.19T, MRI at 200 µT
Develop instruments at 200 µT
Validate dynamic polarization in vitro in the presence of dedicated chemical probes
Measure in vivo an enzymatic activity by MRI enhanced by dynamic polarization

Scientific material and financial conditions of the research project:
Our Team in the UMR 5536 is expert in MRI enhanced by the Overhauser effect. The doctoral supervision includes physicists, physico-chemists, biochemists who are able to help the recruited person to be efficient in its research. The team also has material resources in MRI and collaborations to develop this type of multi-disciplinary project.

Valorization of the doctoral student's research work
Given the deeply multi-disciplinary aspect of the project, the future graduate will be able to perform the functions of researcher or project manager in a variety of environments, both in the public and private sectors.

Bibliographic references
"In vivo High-Resolution 3D OMRI in Mice at 0.2T." Massot, P.; Parzy, E.; Pourtau, L.; Mellet, P.; Marque, S.; Franconi, J.-M.; Thiaudière, E. Contrast Media Molecul. Imaging 2012, 7, 45-50
“An Elastase Activity Reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a Line-Shifting Nitroxide” Jugniot, N.; Duttagupta, I.; Rivot, A.; Massot, P.; Cardiet, C.; Pissocarro, A.; Jean, M.; Vanthuyne, N.; Franconi, J.-M.; Voisin, P.; Devouassoux, G.; Parzy, E.; Thiaudière, E.; Marque, S. R. A., Audran, G.; Bentaher, A.; Mellet, P. Free Rad. Biol. Med. 2018, 126, 101-112
"New Concepts in Molecular Imaging: Non-Invasive MRI Spotting of Proteolysis Using an Overhauser Effect Switch." Mellet, P.; Massot, P.; Madelin, G.; Marque, S. R. A.; Harte, E.; Franconi, J.-M.; Thiaudière, E. PLoS ONE, 2009, 4, 4, e5244.
''Magnetic Resonance Imaging of Protease-Mediated Lung Tissue Inflammation and Injury“ Rivot, A.; Jugniot, N.; Jacoutot, S.; Vanthuyne, N.; Massot, P.; Mellet, P.; Marque, S. R. A.; Audran, G.; Voisin, P.; Delles, M.; Devouassoux, G.; Thiaudière, E.; Bentaher, A.; Parzy, E. ACS Omega 2021, 6, 23, 15012-15016.
“Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field“ Parzy E, Boudries D, Jacoutot S, Albalat M, Vanthuyne N, Franconi JM, Mellet P, Thiaudiere E, Audran G, Marque SRA, Massot P. J Magn Reson. 2021 Dec;333:107095.

“A system for in vivo on-demand ultra-low field Overhauser-enhanced 3D-Magnetic resonance imaging“ Boudries, Massot P, Parzy E, Seren S, Mellet P, Franconi JM, Miraux S, Bezançon E, Marque SRA, Audran G, Muetzel M, Wintzheimer S, Fidler F, Thiaudiere E. J Magn Reson. 2023 348 : 107383.

Contexte de travail

The Research Unit involved in the project is a Joint CNRS-University Unit. The CNRS is a French national organization which aims to produce and promote scientific knowledge in all fields. It is a stakeholder in numerous laboratories (950) throughout the country. It is the main fundamental research organization in France and implements a research policy which allows the production of 43,000 scientific articles per year. The doctoral schools involved are: - The Doctoral School of Physical and Engineering Sciences (University of Bordeaux)

The Laboratory involved: - The Center for Magnetic Resonance of Biological Systems, UMR5536, Bordeaux. https://www.rmsb.u-bordeaux.fr/fr/ This laboratory was created in 1995. It has around 50 researchers, engineers and technicians. Its field of activity is the design and use of new tools in Magnetic Resonance to characterize living organisms, particularly in vivo on intact individuals. Among the themes of the unit, we will note the development of low-field Magnetic Resonance, which opens the way to new MRI practices.

The supervisor of the proposed thesis is: - Dr Elodie Parzy Physicist (trained at UPMC), specialist in in vivo MRI, particularly at low fields. Author of 23 international publications. Involved (WP leader) in a European project on low-field MRI.

Contraintes et risques

Constraints and specificities of the position:
The PhD will be carried out at UMR 5536 (Bordeaux). The site offers numerous training opportunities for the recruited person. Safety conditions will be met according to current standards. The Unit has a department dedicated to health and safety, and dedicated training will be provided in this regard. No major risk is associated with the research activity

Informations complémentaires

Expected skills: The candidate must have a Master's or Engineering degree, preferably in Physics or Chemistry-Physics. Advanced knowledge in the field of Magnetic Resonance is strongly desired. In addition, an open mind (even without prior knowledge) towards biological applications and biochemical methods will be highly appreciated. The doctoral student will be required to have a strong degree of autonomy in the scientific approach, a real aptitude for oral and written expression in French or in English, as well as a strong ability to interact with other members of the laboratories, whether or not they are stakeholder in the project.

Documents to provide: A detailed CV, a digital version of the Master's report, a detailed statement of grades and rankings for the academic years at Bac+4 and Bac+5 level, as well as the names of two people who may be contacted to recommend you will be to be attached to the file.
Deadline for receipt of applications October 31, 2023