<p>Magnetic resonance imaging is a research and clinical tool that has been applied in a wide variety of sciences. One area of magnetic resonance imaging that has exhibited terrific promise and growth in the past decade is magnetic susceptibility imaging. Imaging tissue susceptibility provides insight into the microstructural organization and chemical properties of biological tissues, but this image contrast is not well understood. The purpose of this work is to develop effective approaches to image, assess, and model the mechanisms that generate both isotropic and anisotropic magnetic susceptibility contrast in biological tissues, including myocardium and central nervous system white matter. </p><p>This document contains the first report of MRI-measured susceptibility anisotropy in myocardium. Intact mouse heart specimens were scanned using MRI at 9.4 T to ascertain both the magnetic susceptibility and myofiber orientation of the tissue. The susceptibility anisotropy of myocardium was observed and measured by relating the apparent tissue susceptibility as a function of the myofiber angle with respect to the applied magnetic field. A multi-filament model of myocardial tissue revealed that the diamagnetically anisotropy α-helix peptide bonds in myofilament proteins are capable of producing bulk susceptibility anisotropy on a scale measurable by MRI, and are potentially the chief sources of the experimentally observed anisotropy.</p><p>The growing use of paramagnetic contrast agents in magnetic susceptibility imaging motivated a series of investigations regarding the effect of these exogenous agents on susceptibility imaging in the brain, heart, and kidney. In each of these organs, gadolinium increases susceptibility contrast and anisotropy, though the enhancements depend on the tissue type, compartmentalization of contrast agent, and complex multi-pool relaxation. In the brain, the introduction of paramagnetic contrast agents actually makes white matter tissue regions appear more diamagnetic relative to the reference susceptibility. Gadolinium-enhanced MRI yields tensor-valued susceptibility images with eigenvectors that more accurately reflect the underlying tissue orientation.</p><p>Despite the boost gadolinium provides, tensor-valued susceptibility image reconstruction is prone to image artifacts. A novel algorithm was developed to mitigate these artifacts by incorporating orientation-dependent tissue relaxation information into susceptibility tensor estimation. The technique was verified using a numerical phantom simulation, and improves susceptibility-based tractography in the brain, kidney, and heart. This work represents the first successful application of susceptibility-based tractography to a whole, intact heart.</p><p>The knowledge and tools developed throughout the course of this research were then applied to studying mouse models of Alzheimer’s disease in vivo, and studying hypertrophic human myocardium specimens ex vivo. Though a preliminary study using contrast-enhanced quantitative susceptibility mapping has revealed diamagnetic amyloid plaques associated with Alzheimer’s disease in the mouse brain ex vivo, non-contrast susceptibility imaging was unable to precisely identify these plaques in vivo. Susceptibility tensor imaging of human myocardium specimens at 9.4 T shows that susceptibility anisotropy is larger and mean susceptibility is more diamagnetic in hypertrophic tissue than in normal tissue. These findings support the hypothesis that myofilament proteins are a source of susceptibility contrast and anisotropy in myocardium. This collection of preclinical studies provides new tools and context for analyzing tissue structure, chemistry, and health in a variety of organs throughout the body.</p> / Dissertation

The main purpose of this research was to develop improved methods for RF coil characterisation, and for non-invasive spatio-temporal mapping of temperature in the living body, in order to utilise the full potential of magnetic resonance imaging (MRI) at high magnetic fields by ensuring radiofrequency (RF) safety. Current RF power limits are often overly conservative, unnecessarily limiting the full potential of MRI, especially at high field. Thus it is useful to monitor tissue temperature while running MR imaging sequences which may deposit high RF power. Proton resonance frequency (PRF) MR thermometry can employ the phase of the complex MR signal to estimate temperature change over time. However, the shift of the water PRF with temperature is relatively small, making phase-based MR thermometry inherently sensitive to any extraneously caused changes of local frequency or MR phase. A potential source of error to PRF MR thermometry is a change in surround air susceptibility. The considerable impact of air susceptibility changes on PRF MR thermometry was demonstrated and quantified in experiments and magnetic field simulations. One way of correcting MR thermometry is to use a chemically shifted reference substance, in combination with a phase-sensitive chemical shift-selective MR thermometry sequence. The requirement of having a reliable separation of substances based on their resonance frequency was met by a novel frequency-selective phase-sensitive spin-echo (SE) MR thermometry sequence. This sequence was thoroughly tested in phantom and in-vivo experiments as well as in extensive Bloch simulations. The sequence limitations and advantages are discussed in detail. This technique acquires unsaturated water and fat images in rapid succession at the same position in space. The acquisition of a water and fat slice in less than 100 ms allows the correction of rapid field fluctuations in the brain caused by breathing and heartbeat, while still ensuring the correction of long term drift. With no assumptions required regarding temperature distribution in the tissue, this novel MR thermometry technique can measure brain temperature within a single (1.5 mm)3 voxel with a very low standard deviation (SD) of 0.3 K. Using an MRI phantom with a dimethyl sulfoxide reference, heating experiments achieved a MR temperature measurement with an SD of approximately 0.1 K in a single (1.5 mm)3 voxel. In conclusion, the work presented in this thesis assists the development of a real-time in-vivo temperature monitoring system that guarantees patient RF safety at high field.

L’hyperthermie guidée par IRM permet l’ablation thermique des tumeurs, l’activation de l’expression d’un transgène sous contrôle d’un promoteur thermo-sensible ainsi que le dépôt local de médicaments à l’aide de nanovéhicules sensibles à la température ou à la pression locale. L’imagerie de température par IRM, basée sur la technique du décalage de la fréquence de résonance du proton permet le monitorage des interventions d’hyperthermie. Les procèdes interventionnels guides par IRM sur cible mobile requièrent des séquences d’imagerie rapides afin d’obtenir des images de phases ayant une résolution spatio-temporelle élevée. Nous avons démontré l’efficacité de l’association des méthodes adaptatives d’imagerie parallèle telles que TSENSE et TGRAPPA et de la méthode multi-référence de l’atlas de mouvement afin de compenser les variations du champ magnétique induites par les organes en mouvement. Les procédés interventionnels guides par IRM sont basés sur des séquences d’imagerie rapides capables de fournir des images en temps-réel ayant une relation précise entre la position de la cible représentée dans l’image et sa vraie position spatiale. Les séquences écho-planar sont très rapides mais possèdent des distorsions géométriques. Nous avons proposé une méthode de correction des distorsions des images EPI. Cette technique est basée sur des approches existantes utilisant l’acquisition de deux images EPI ayant deux temps d’écho différents. L’efficacité de la méthode proposée a été démontrée pour une expérience de thermométrie par IRM. La rapidité du traitement des données, associée à une faible diminution de la rapidité d’acquisition, rend cette méthode particulièrement adaptée pour les procédés interventionnels guides par IRM. La perfusion sanguine, la diffusion thermique ainsi que le coefficient d’absorption des ondes acoustiques ou électromagnétiques déterminent la distribution de la température durant les procédés interventionnels. Certaines tumeurs ont des taux de perfusion élevés conduisant à une évacuation importante de la chaleur et par conséquent, un refroidissement rapide de la cible. Cet effet réduit la température maximale atteinte pour une puissance donne et peut conduire à des zones d’ablation plus petites réduisant ainsi l’efficacité de l’intervention. La connaissance précise des paramètres thermiques du tissu peut aider à la planification des procédés interventionnels. Dans ce but, nous avons proposé une méthode permettant la détermination précise des paramètres cités précédemment. / MR-guided HIFU-induced hyperthermia allows for thermal ablation of tumors, for gene therapy by thermal induction of transgenic expression (based on a thermo-sensitive promoter) and for local drug delivery using thermo-sensitive liposomes. These applications require accurate temperature measurement during the therapeutic intervention. Dynamic MR-temperature imaging based on the proton resonance frequency shift technique allows monitoring the local temperature evolution during hyperthermia. MR-guided thermotherapy on moving organs requires imaging sequences providing phase images with high temporal and spatial resolution. We demonstrated the feasibility of combining adaptive parallel imaging techniques such as TSENSE or TGRAPPA with the atlas-based multi-baseline method for compensating the magnetic field variations produced by moving organs during the respiratory cycle. Many MR-guided interventional procedures rely on real-time imaging sequences for providing precise relations between the target position in the image and the true position in the scanner. Although echo-planar imaging (EPI) sequences are very fast, they are prone to geometric distortions. For correcting these distortions, we proposed a real-time correction method by applying existing approaches based on a dual EPI acquisition with varying echo times. It is demonstrated that this method works well in combination with MR-thermometry for guiding thermal therapies. Short data-processing times as well as a small penalty in acquisition speed make this method well-adapted for MR-guided interventions. Local blood perfusion, thermal conductivity and the absorption coefficient of acoustic or electro-magnetic waves determine the temperature distribution in living tissue. Some tumors have high perfusion rates resulting in considerable heat evacuation. This effect reduces the maximal temperature increase achievable for a given deposited energy and produces smaller ablation zones, which can impair the efficiency of the therapeutic procedure. A method for accurately estimating the above mentioned tissue parameters, was presented. This method could thus be useful in quantifying the influence of perfusion during thermal interventions.