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Fetal growth restriction (FGR) is a common pregnancy complication resulting in increased neonatal mortality and morbidity. The aetiology of fetal growth restriction is not fully understood, but abnormalities in placental development are, leading to abnormalities in placental structure which are thought to affect supply of oxygen to the fetus. The source of fetal hypoxia is unknown due to the difficulty in obtaining oxygenation data in the context of pregnancy using existing techniques. There is also an absence of data relating to oxygenation in FGR pregnancies. Oxygen-Enhanced MRI (OE-MRI) and Blood Oxygen-Level Dependent (BOLD) MRI permit noninvasive acquisition of data related to changes in the concentration of dissolved oxygen (pO2) and changes in hemoglobin saturation (sO2) under air- and oxygen- breathing (hyperoxic challenge).The aim of this project was to determine whether MRI methods can provide information relating to placental oxygenation in normal and FGR-compromised pregnancy, to investigate fetal brain oxygenation and to assess the potential confound of placental perfusion changes under hyperoxic challenge. After optimization of sequences in non-pregnant volunteers, similar pO2 and sO2 increases under hyperoxic challenge were seen in normal and FGR pregnancy. This suggested placental oxygenation was similar and that fetal extraction of oxygen may be a likelier cause of fetal hypoxia. Normal fetal brain oxygenation was found not to increase under hyperoxic challenge, which may be due to hemodynamic adaptation to limit cerebral hyperoxygenation. Finally, the robustness of these oxygenation results was supported by the lack of placental perfusion changes observed under hyperoxia using Arterial Spin Labeling (ASL).In conclusion, MRI methods successfully provided information on placental and fetal oxygenation in normal and abnormal pregnancy, obtaining novel data informing the aetiology of FGR and the physiology of the fetal brain.

[Truncated abstract] Clinical magnetic resonance imaging (MRI) scanners were used to investigate the measurement and imaging of ferrimagnetic particle concentrations in biological tissues in vivo. The presence of ferrimagnetic particles tends to increase the proton transverse relaxation rate (R2) of water protons in tissue. A quantitative image of R2 can be generated using a series of single spin echo magnetic resonance images acquired using clinical MRI scanners and analysing the images using techniques based on that reported by Clark and St. Pierre (2000). If ferrimagnetic particles have a high enough concentration, there is a monotonic relationship between particle concentration and R2; therefore an image of R2 gives a map of the ferrimagnetic particle concentration in the tissue. These techniques were used to investigate the feasibility of in vivo measurement of the concentration and distribution of both synthetic and biogenic ferrimagnetic particles in tissue. Rabbit liver was loaded with ferrimagnetic particles of ?-Fe2O3 (designed for magnetic hyperthermia treatment of liver tumours) by injecting various doses of a suspension of the particles into the hepatic artery in vivo. R2 images of the livers in vivo, excised, and dissected were generated from a series of single spin-echo images. Mean R2 values for samples of ferrimagnetic-particle-loaded liver dissected into approximate 1 cm cubes were found to linearly correlate with tissue iron concentration over the range from approximately 0.1 to at least 2.7 mg Fe/g dry tissue when measured at room temperature. Changing the temperature of ferrimagnetic-particle-loaded samples of liver from 1?C to 37?C had no observable effect on tissue R2 values. However, a small but significant decrease in R2 was found for control samples containing no ferrimagnetic material on raising the temperature from 1?C to 37?C. Both chemically measured iron ii concentrations and mean R2 values for rabbit livers with implanted tumours tended to be higher than those measured for tumour-free liver. This study indicates that tissue R2 measurement and imaging by nuclear magnetic resonance may have a useful role in magnetic hyperthermia therapy protocols for the treatment of liver cancer. In order to investigate the use of clinical MRI scanners to measure biogenic ferrimagnetic particle concentrations in human brain tissue, agar gel based phantoms containing ferrimagnetic particles were made in order to determine the lower concentration detection limit for such particles in a homogenous medium. Magnetite/maghemite nanoparticles were synthesized in the presence of either dextran or polyvinyl alcohol, yielding cluster- and necklace-like aggregates, respectively. Magnetization, Mossbauer spectroscopy, and microscopy measurements indicated that the arrangement of the particles within the aggregates affects the magnetic properties of the particles resulting in smaller particles in the clusters having higher superparamagnetic blocking temperatures than larger particles in the necklaces.

Brassica napus est une des cultures oléagineuse majeure dans le monde. En raison de sa faible efficacité d’utilisation de l’azote (NUE) comparée aux autres grandes cultures, la gestion de cette ressource présente un objectif écologique et économique majeur pour cette culture. La remobilisation des nutriments des organes sources vers les organes puits est une composante de la NUE qui se déroule durant la sénescence et qui est associée aux processus de recyclages métaboliques et à des modifications de la structure foliaire. L’objectif de cette thèse était de comprendre et de quantifier ces modifications structurales afin d’évaluer à travers ces processus les capacités de remobilisation du colza en fonction de son génotype et de son statut nutritionnel (eau et azote). La structure foliaire a été étudiée grâce à la relaxométrie RMN qui donne accès au statut et à la distribution de l’eau au niveau cellulaire. Ces travaux de thèse ont mis en évidence que la distribution des temps de relaxation transversale (T2) dépend non seulement de la structure cellulaire, mais aussi de l’organisation tissulaire. Cette étude a aussi mis en évidence le processus d’élargissement cellulaire et d’hydratation pendant la sénescence, spécifiquement dans le parenchyme palissadique. Il a été également démontré que le signal RMN reflète la déstructuration progressive se déroulant durant la sénescence au niveau subcellulaire et est un marqueur de sénescence précis permettant de suivre le développement de la feuille. De plus, le statut nutritionnel de la plante modifié par les carences azotées ou le stress hydrique, impacte grandement la sénescence séquentielle et les conséquences en termes d’efficacité de la remobilisation peuvent être suivies par RMN. Ce travail a permis de renforcer les connaissances sur la structure et le fonctionnement de la feuille au niveau tissulaire et cellulaire. De plus, il a été démontré que le signal de relaxométrie RMN donne accès à des informations sur la structure foliaire inaccessible par des méthodes courantes. Une des principales applications de ce travail serait le phénotypage, particulièrement la sélection de génotypes caractérisés par une forte efficacité de remobilisation en particulier en cas de carence azoté ou de stress hydrique. / Brassica napus is one of the major oil crops of the world. Due to its low NUE (Nitrogen Use Efficiency) compared to other species, Nitrogen management presents a major economic and environmental goal for improvement of that crop production. As a component of NUE, nutrient remobilization from source to sink tissues takes place mainly during the leaf senescence and is associated to metabolic recycling processes and modification of the cellular organization and structure. The aim of this work was therefore to understand and estimate the amplitude of these structural modifications with the objective to appreciate through these processes remobilization performance according to oilseed rape genotypes and nutritional status in terms of nitrogen and water supply. The leaf structure was investigated through NMR relaxometry, providing access to cellular water status and distribution. The present work demonstrated that the transverse relaxation time (T2) distribution depends on both leaf tissue structure and cellular compartmentalization. The study revealed a process of cell enlargement and hydration during leaf senescence, specifically in the palisade parenchyma and showed that the T2 relaxation time was able to discriminate parenchyma tissues at an early phase of senescence induction. Moreover, the NMR relaxometry signal was shown to reflect specific chronological loss of sub-cellular structuring all along the senescence process progression and was demonstrated to be an accurate non-invasive monitoring method of leaf development. Finally, plant nutrition status experienced through nitrogen and water availability limitation has been demonstrated to strongly affect regular sequential leaf senescence. Consequences on remobilization efficiency by stress conditions have been also assessed through the NMR signal. This work has improved the understanding of leaf structure and functioning at the cell and tissue levels after the onset and during the progression of senescence. Moreover, it was demonstrated that NMR relaxometry provides access to leaf structural information that are not accessible with currently used techniques for plant structural investigations. One of the main applications would be for plant phenotyping, especially for selecting genotypes with higher nutrient remobilization efficiency especially under environmental stresses like nitrogen and water limitations for sustainable oil and protein production.