Accelerated high-resolution anatomical MRI at 11.7T using SPARKLING
Magnetic resonance Imaging (MRI) has become the reference neuroimaging technique for probing brain structure and function non-invasively. In particular, anatomical MRI is a gold standard for clinical imaging diagnosis and research, with T1-weighted imaging being the most commonly used sequence. However, the use of this imaging modality is limited by long acquisition times, especially for high resolution anatomical imaging. In this regard, non-Cartesian sampling can accelerate acquisitions through flexible sampling trajectories like SPARKLING, which can efficiently sample k-space and allow efficient and optimal iterative reconstructions with minimal degradation in image quality. In this PhD thesis, the SPARKLING framework which was originally developed for T2*-w imaging will be extended to MPRAGE T1-w imaging, with a goal to accelerate the acquisitions by a factor of 10-15 times, thereby allowing us to reach 1-mm isotropic acquisitions within a minute. Additionally, for extensions of anatomical imaging schemes involving redundant sampling at different inversion times (TI) like MP2RAGE, we propose a novel interleaved under-sampling acquisition and corresponding reconstruction scheme, which minimizes redundancy across different readouts, allowing us to maximally accelerate the acquisition process. In practice, this is achieved through 3D+time extension of the SPARKLING algorithm, that can be combined through the proposed 4D reconstruction scheme. Finally, the thesis will also focus on characterizing the noise profile in k-space for non-Cartesian acquisitions and its effect on the observed resolution in the reconstructed MR images. This will help us build SNR-optimized sampling trajectories, which will be validated against state-of-the-art and clinically utilized protocols (like MP2RAGE) at varying field strengths from 3T to 11.7T. Benchmarking of all the acquisition schemes will be performed through quantitative metrics and also qualitative radiological evaluations, through collaboration of radiologists at NeuroSpin and AP-HP Henri Mondor hospital.
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.