This work concerns practical quantitative magnetic resonance (MR) imaging techniques and their implementation and use in clinical MR systems. First, background information on MR imaging is given, including the physics of the magnetic resonance, relaxation effects and how imaging is accomplished.Subsequently, the first part of this work describes the estimation of the T2 relaxation parameter from fast spin-echo (FSE) data. Various complications are considered, including partial volume and data from multiple receiver coils along with the effects of the timing parameters on the accuracy of T2 estimates. Next, the problem of classifying small (1 cm diameter) liver lesions using T2 estimates obtained from radially-acquired FSE data collected in a single breath-hold is considered. Several algorithms are proposed for obtaining lesion T2 estimates, and these algorithms are evaluated with a task-based metric, their ability to separate two classes of lesions, benign and malignant. A novel computer-generated phantom is developed for the generation of the data used in this evaluation.The second part of this work describes techniques that perform the separation of water and lipid signals while simultaneously estimating relaxation parameters that have clinical relevance. The acquisition sequences used here are Cartesian and radial versions of Gradient and Spin-Echo (GRASE). The radial GRASE technique is post-processed with a novel algorithm that estimates the T2 of the water signal independent of the lipid signal. The accuracy of this algorithm is evaluated in phantom and its potential use for detecting inflammation of the liver is evaluated using clinical data. Cartesian GRASE data is processed to obtain T2-dagger and lipid fraction estimates in bone which can be used to assess bone quality. The algorithm is tested in phantom and in vivo, and preliminary results are given.In the concluding chapter results are summarized and directions for future work are indicated.

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In certain neuro-degenerative diseases likemultiple sclerosis (MS), the rate of brain atrophy can be measured by monitoring the brain parenchymal fraction (BPF) in such patients. The BPF is defined as the ratio of brain parenchymal volume (BPV, defined as the total volume of gray matter tissue, white matter tissue and other unidentified tissue) and intracranial volume (ICV, the total volume of the skull). It can be represented by the formula in equation 1: <img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Csmall%20BPF%20=%20%5Cfrac%20%7BPBV%7D%7BICV%7D%20%5C;%20%5C;%20%5C;%20%5C;%20(1)" /> A complication with this measure is that the BPF is affected by the presence of edema in the brain, which leads to swelling and hence may obscure the true rate of brain atrophy. This leads to uncertainty when establishing “normal values” of BPF when analyzing different magnetic resonance imaging (MRI) scans of the same patient. Another problem is that different MRI scans of the same patient cannot be compared directly, due to the fact that the head of the patient will be in a different position for every scan. The SyMRI software used in this master thesis has the functionality to perform brain tissue characterization and measurement of brain volume, given a number of MR images of a patient. Using tissue properties such as longitudinal relaxation time (T1), transverse relaxation time (T2) and proton density (PD), each voxel in a volume can be classified to belong to a certain tissue type. From these measurements, the intracranial volume, brain volume, white matter, gray matter and cerebrospinal fluid volumes can easily be estimated. In this master thesis, the BPF of several patients were analyzed based on quantitative MRI (qMRI) images, in order to identify the change of BPF due to the presence of edema over time. Volumes obtained from the same patients at different time points were aligned (registered), such that the BPF can be easily compared between years. A correlation analysis between the BPF and R1, R2 and PD was performed (R1 is the longitudinal relaxation rate defined as 1/T1 relaxation time and R2 Is transverse relaxation rate defined as 1/T2 relaxation time) to investigate if any of these variables can explain the change in BPF. The results show that due to image registration, and removing some of the slices from the top and bottom of the head, the BPF of the patients was corrected to a certain extent. The change in the mean BPF of each patient over four years was less than 1% post registration and slice removal. However, the decrease in standard deviation was between 6.9% to 52% after registration and removing of slices. The BPF of the follow-up years also came closer to the initial BPF value measured in the first year. The statistical analysis of the BPF and R1, R2 and PD, showed a very low correlation (0.1) between BPF and PD, and intermediate correlations between BPF and R1, R2 (0.385 and -0.51, respectively). Future work will focus on understanding how these results relate to edema.

While copper is an essential micronutrient in all living organisms, copper misregulation in humans is associated with neurodegenerative disorders such as Menkes and Wilson’s diseases, amyotrophic lateral sclerosis and Alzheimer’s disease. Furthermore, copper is a widely-produced pollutant and thus the detection of Cu(II) and Cu(I) has received much attention in recent years. Copper can be detected in a number of ways including; quenching of fluorescence upon the binding of paramagnetic Cu(II) (a "turn-off" response); augmentation of fluorescence upon Cu(II) binding due to PET modulation (a "turn-on" response); and selective Cu(II)- or Cu(I)-catalysed reactions where the luminescence of the product is distinctly different to that of the starting material. A review of Cu(I) and Cu(II) sensors is described herein. The Hulme group has previously developed a sensor for ligand-bound copper(I) utilising the copper(I)-catalysed [GS-−Cu(I)] variant of the Huisgen 1,3-dipolar cycloaddition reaction. Cu(I)-catalysed alkyne-azide cycloaddition (CuAAC or “click”) was carried out between an alkynyl Eu(III)-DOTA complex and a dansyl azide yielding a 1,4-triazole with a modest turn-on response (10-fold increase in luminescence). The project described herein aimed to achieve a more significant increase in lanthanide luminescence intensity through alteration of the donor moeity, lanthanide ion, and linker length between donor and acceptor moiety. The synthesis of several lanthanide-DOTA complexes, azido fluorophores and the formation of novel Cu(I)-sensors via CuAAC is described herein. All Cu(I) sensors were excited at their individual λex and their lanthanide luminescence intensity was measured using a timedelayed phosphorimeter. The DOTA structural motif has the ability to complex a plethora of potentially useful radionuclides including; yttrium, indium, gallium, lutetium and gadolinium. In general, DOTA-complexes doped with gadolinium are utilised for the identification of tumour sites while yttrium or indium complexes are used for tumour treatment. Biotin-DOTA conjugates have previously been used for pretargeted cancer imaging and radiotherapy. Biotinidase degradation of the amide bond in some biotin constructs has been reported, rendering them unable to bind to the pre-targeted antibody-(strept)avidin site. A novel biotinyl azide lacking this vulnerable amide bond is reported, with potential for bioconjugation to a variety of biomolecules via “click” chemistry. The synthesis of two novel biotinylated Gd-DOTA complexes, with prospective application as pretargeted MRI contrast agents, are also described.

The advancements in medical technologies have allowed more accurate diagnosis and quantitative assessments. Magnetic Resonance Imaging is one of the most effective and critical technologies in modern diagnosis. However, preprocessing tasks are required to perform various research topics basing on MR image. Registration is one of the those preprocessing tasks. In this research, a semi-automatic utility was developed for doing MRI registration of small animals. It focuses on 2D rigid body registration. The test results show that this developed utility can perform registration well for MRI of small animals in both intra-subject and inter-subjects.

Accurate needle placement is critical to the success of needle-based interventions. Needle deflection due to tissue non-homogeneity and dynamic forces results in targeting error, potentially requiring repeated insertions. Real-time imaging enables closed-loop control of the needle during insertion, improving insertion accuracy. The needle localization algorithm proposed in this thesis models the needle as a parametric polynomial equation optimized to minimize beam bending energy relative to a set of observed needle coordinates. Simulated insertions using an MRI dataset show that the minimum bending energy model allows planning of subsequent imaging planes to capture the moving needle while estimating the shape of the needle with low error.

The optimal site at which to pace the right ventricle (RV) is still unclear. This study aimed to answer this question utilising cardiac magnetic resonance imaging, which up until recently was contraindicated in pacemaker patient cohorts. The objective was to determine the effect of apical and outflow tract septal pacing on cardiac function and remodeling as assessed by MRI. In addition, physcial and psychological functional parameters were assessed. A series of sub-studies were performed as part of the research. Study 1 validated the velocity phase encoding used to determine flow measurements. This found measurements were reproducible. Study 2 and 3 focused on the method of CPEX testing in pacing dependent patients and whether a training effect was observed with the CPEX testing. It found that treadmill testing resulted in a greater heart rate response and higher VO2 max results. No significant training effect was observed. Study 4 used phantom models to determine the effect of metal susceptibility artefact on mapping and velocity encoded MR sequences. An inverse relationship between artefact and distance from the pacemaker was observed. At approximinately 10 cm from the device, artefact is negligible. Study 5 determined the best methods of image optimization in the presence of the pacemaker. T1 weighted imaging along with spoiled gradient imaging was less affected by artefact compared to late gadolinium and bSSFP imaging. Study 6 evaluated in-house developed software to measure torsion using data derived from commercial available tagging and feature tracking software. At low heart rates measures were comparable but tagging became less accurate with heart rates over 100 bpm. The main study comprised of the baseline data of 50 patients from the ongoing MAPS trial and some intermediate data after 9 months for a smaller cohort. There was not a significant difference in left ventricular volumes or ejection fraction at baseline but differences were observed in deformational indices including longitudinal strain, strain rate, twist and torsion. At 9 months a difference in ejection fraction was observed between the pacing modes along with differences in deformational parameters. Clinically significant differences were not seen between pacing positions at baseline or 9 months but the outflow tract septal position was superior based on deformational data.