Hyperpolarized Xenon NMR to probe the functionality of biological barriers
Optical pumping of xenon, giving rise to an intense NMR signal, is a specialty of the LSDRM team. Xenon, which is soluble in biological media, has a wide range of chemical shifts, which we use here to study the properties of cell barriers. Numerous pathologies stem from an alteration of these barriers.
In this thesis, we aim to develop a specific methodology using hyperpolarized xenon to study the functionality (integrity, permeability, selectivity) of biological barriers, using in vitro and in vivo spectroscopy and imaging. The thesis will be divided into two parts: in vitro, the aim will be to develop a device and NMR protocols for studying model cell assemblies; in vivo, studies on rodents will enable us to assess xenon's ability to reach organs more or less close to the lungs while maintaining its polarization, and to measure kinetics across barriers. This topic will enable major instrumental and methodological advances, as well as a deepening of our knowledge of selective transport processes at different biological barriers.
Multiplexed whole-body in vivo imaging monitoring of pathogen dissemination and immune responses dynamics in tuberculosis
This thesis is dedicated to set up a multiplexed medical imaging monitoring of pathogen colonization and associated immune responses dynamics at the whole body scale for various infectious diseases. This could provide an innovative and non-invasive tool to better understand dynamics links between immune responses and pathogen distribution throughout the body and potentially provide new biomarkers associated to several diseases. To tackle this issue this thesis would implement such strategy in tuberculosis disease. The main aim is to determine the relationship between Mycobacterium tuberculosis dissemination and associated immune responses across the whole body during the course of tuberculosis infection from early infection to latent or active tuberculosis thanks to innovative multiplexed imaging protocols. The goal of this study is to provide correlations in time and space between local bacterial burden and several immune cell infiltrations (activated macrophages and T lymphocytes subsets) occurring following infection and detected over time by imaging. These findings could then provide, with minimal invasiveness, predictive biomarkers on disease or local granuloma progression and may provide also valuable insight on potential immune targets for future preventive or curative strategies based on modulation of the immune system. To do so, this thesis would take advantage of the preclinical Non-human primate model of tuberculosis developed in France and on our in vivo imaging of pathogens and immune cells expertise in NHPs. Of note, deeper immune cell profiling in samples of interest (imaging guided) will be assessed by spatial or single-cell transcripomic technologies in tissue samples to provide additional readouts on TB pathophysiology and potential treatment efficacy.
Optimization of gamma radiation detectors for medical imaging. Time-of-flight positron emission tomography
Positron emission tomography (PET) is a nuclear medical imaging technique widely used in oncology and neurobiology.
We're proposing you to contribute to the development of an ambitious, patented technology: ClearMind. This gamma photon detector uses a monolithic PbWO4 crystal, in which Cherenkov and scintillation photons are produced. These optical photons are converted into electrons by a photoelectric layer and multiplied in a MicroChannel plate. The induced electrical signals are amplified by gigahertz amplifiers and digitized by SAMPIC fast acquisition modules. The opposite side of the crystal will be fitted with a matrix of silicon photomultiplier (SiPM).
You will work in an advanced instrumentation laboratory in a particle physics environment .
The first step will be to optimize the "components" of ClearMind detectors, in order to achieve nominal performance. We'll be working on scintillating crystals, optical interfaces, photoelectric layers and associated fast photodetectors, and readout electronics.
We will then characterize the performance of the prototype detectors on our measurement benches.
The data acquired will be interpreted using in-house analysis software written in C++ and/or Python.
Finally, we will compare the physical behavior of our detectors to Monté-Carlo simulation software (Geant4/Gate).
A particular effort will be devoted to the development of ultra-fast scintillating crystals in the context of a European collaboration.