Thesis advisor: Michael Graf / The purpose of this dissertation was to investigate the temporal limit on the ability to measure temperature changes using magnetic resonance imaging (MRI). The limit was examined in experiments using a variety of imaging techniques for MRI-based temperature measurements. We applied these methods for monitoring temperature changes in focused ultrasound (FUS) heating experiments. FUS is an attractive alternative to surgical resection due to its noninvasive character. FUS treatments have been successfully conducted in several clinical applications. MRI and MR thermometry is a natural choice for the guidance of FUS surgeries, given its ability to visualize, monitor, and evaluate the success of treatments. MR thermometry, however, can be a very challenging application, as good resolution is often needed along spatial, temporal as well as temperature axes. These three quantities are strictly related to each other, and normally it is theoretically impossible to simultaneously achieve high resolutions for all axes. In this dissertation, techniques were developed to achieve this at cost of some reduction in spatial coverage. Given that the heated foci produced during thermal therapies are typically much smaller than the anatomy being imaged, much of the imaged field-of-view is not actually being heated and may not require temperature monitoring. By sacrificing some of the in-plane spatial coverage outside the region-of-interest (ROI), significant gains can be obtained in terms of temporal resolution. In the extreme, an ROI can be chosen to be a narrow pencil-like column, and a sampling time for temperature imaging is possible with a temporal resolution of a few milliseconds. MRI-based thermal imaging, which maps temperature-induced changes in the proton resonance frequency, was implemented in two projects. In the first project, three previously described, fast MR imaging techniques were combined in a hybrid method to significantly speed up acquisition compared to the conventional thermometry. Acceleration factors up to 24-fold were obtained, and a temporal resolution as high as 320 milliseconds was achieved. The method was tested in a gel phantom and in bovine muscle samples in FUS heating experiments. The robustness of the hybrid method with respect to the cancellation of the fat signal, which causes temperature errors, and the incorporation of the method into an ultrafast, three dimensional sequence were also investigated. In the second project, a novel MR spectroscopic sequence was investigated for ultrafast one-dimension thermometry. Temperature monitoring was examined during FUS sonications in a gel phantom, SNR performance was evaluated in vivo in a rabbit brain, and feasibility was tested in a human heart. It was shown capable in a FUS heating experiment in a gel phantom of increasing temporal resolution to as high as 53 milliseconds in a three Tesla MRI. The temporal resolution achieved is an order of magnitude faster than any other rapid MR thermometry sequences reported. With this one-dimensional approach, a short sampling time as low as 3.6 milliseconds was theoretically achievable. However, given the SNR that could be achieved and the limited heating induced by FUS in the gel phantom in a few milliseconds, any temperature changes in such a short period were obscured by noise. We have analyzed the conditions whereby a temporal resolution of a few-milliseconds could be obtained. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

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.