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Introduction: The Elastography Software Library (ESL) was developed to achieve clinically feasible, super-resolution (SR) Magnetic Resonance Elastography (MRE). ESL was created by accomplishing four objectives: 1. perform a critical analysis of MRE inversion, using discrete-time Fourier transform (DTFT) methods, to enable selection of the wave inversion approach most suitable to high- and SR MRE (Chapter 2) 2. develop a new method for real-time 4D phase unwrapping, to enable large acquisitions to be processed in clinical work ow (Chapter 3) 3. develop a new inversion pipeline that recovers fine features in elastograms (Chapter 4) 4. extend this pipeline with a novel interpolation technique to achieve super-resolution (Chapter 5) The results of these experiments were combined to make the ESL. Over the course of the work, two objectives also resulted in software applications in their own right (PhaseTools for phase unwrapping, and Elastography Software Pipeline (ESP) for fine feature elasticity map recovery). Methods: Critical Analysis: Two-filter cascades were designed to model the signal processing pipelines found in the present MRE literature. These models were subjected to DTFT-based analysis to determine the relative advantage of various mathematical approaches to the MRE inverse problem. Phase Unwrapping: A test data set was developed to measure algorithm performance in 4D on data sets with varying levels of wrap, gradient and noise. The algorithms that performed most accurately and efficiently on test data were then applied to in vivo brain, liver, and muscle data, of both moderate and severe wrap, and inspected for wrap failure. Fine Feature Recovery: A new MRE image processing pipeline was developed that incorporates wavelet-domain denoising, image-driven noise estimation, and feature detection. ESP was first validated using simulated data, including viscoelastic Finite Element Method (FEM) simulations, at multiple noise levels. ESP images were then compared with Multifrequency Dual Elasto-Visco Inversion (MDEV) pipeline images in three ten-subject cohorts of brain, thigh, and liver acquisitions. Finally the proportion of spectral energy at fine frequencies was quantified using the Reduced Energy Ratio (RER) for both ESP and MDEV. Super-Resolution: An extension of the ESP pipeline was developed that incorporated a new image fusion technique to combine non-redundant information. The algorithm was validated on an analytic simulation program developed for the study. An in vivo cross-validation was performed between 1X, 2X and 4X magnification levels measuring both spectral gains and shear modulus values. Results: Critical Analysis: The more complex, heterogeneous FEM models were found to only outperform Algebraic Helmholtz Inversion (AHI) in very low noise, with Gaussian smoothing of σ > 0:8px or Butterworth low-pass cutoffs of < 0:8π negating any advantages from assumption of local heterogeneity. Phase Unwrapping: Three algorithms were determined to perform with sufficient robustness in real-time on 4D data sets with challenging phase wrap. These algorithms were then applied to in vivo brain, skeletal muscle, liver and phantom data and shown to successfully resolve heavy phase wrap within a \real-time" criterion of under 3 minutes. Fine Feature Recovery: For FEM inversions, mean values of background and soft target simulated results remained within 8% of prescribed up to σ = 10% for both jG*j and ϕ, though inspection of the ϕ image showed scatter- and boundary-related artefacts around the soft target. Hard target results showed jG*j means within 7% of prescribed up to σ = 5% but unreliable ϕ means, and inspection showed showed scatter- and boundary-related artefacts. For the in vivo cohorts, ESP results showed mean correlation of R = 0:83 with MDEV and liver stiffness estimates within 7% of Local Frequency Estimation (LFE) results. Finally, ESP showed statistically significant increase in fine feature spectral energy as measured with RER for both jG*j (p < 1X10-9) and ϕ (p < 1X10-3). Super-Resolution: At 4X SR, both brain and liver cohorts showed a highly significant (p ≤ 10-6) increase in both number of recovered frequencies and normalised spectral energy in those recovered frequencies. Both the 2X and 4X SR techniques showed a decrease in stiffness estimate from the original resolution (mean decrease of 11.6% and 14.0%) respectively; however cohort correlations between SR and original values were upwards of R = 0:988. Discussion: Established as a technique highly sensitive to important tissue changes, MR Elastography is now also a finely-featured super resolution technique in two parameters, enabling new clinical and research applications. Future work includes statistical mapping of both localised and diffuse soft tissue changes, rapid computation on heterogeneous processing architectures, and two-parameter super-resolution MRI-based lesion mapping.

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The study of brain temperature is important for a number of clinical conditions such as stroke, traumatic brain injury, schizophrenia and birth asphyxia (for neonates). A direct method to estimate brain temperature non-invasively will allow assessment of brain thermoregulation and its variation in clinical conditions. Magnetic resonance imaging is a powerful technique widely used for diagnosis of a range of neurological conditions. All magnetic resonance procedures involve manipulation of the hydrogen nuclei in the water molecules of the human body. The resonance frequency of the water molecules is temperature dependent, thus MR thermometry is a powerful tool for non-invasive temperature measurement. Using internal reference MR spectroscopic imaging (MRSI), absolute brain temperature maps can be estimated. However a number of temperature independent factors influence MRSI data acquisition, thus a thorough validation is necessary and is the focus of this PhD study. In this PhD study using phantom (test object) studies it was shown that optimization of the MRSI pulse sequence is necessary to reduce systematic error in temperature maps and extensive in-vitro validation of MRSI temperature mapping was performed. A custom made temperature-controlled phantom was designed for this purpose and is presented in this thesis. MRSI data acquired from healthy (young and elderly) volunteers was employed to assess regional brain temperature variations and repeatability. Finally, the feasibility of employing fast echo planar spectroscopic imaging for volumetric MRSI temperature mapping will be presented in this thesis.

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In this thesis the pH dependency of the coordination modes of lanthanide complexes with macrocyclic ligands based on 1,4,7,10-tetraazacyclododecane skeleton was studied. The cyclen-based ligand structures in this work contained three acetate and one aminoethyl group with a N-alkyl-N-methylphosphonate substituent, DO3AN(R)P, where R is an alkyle substituent on the nitrogen atom of the pendant arm (R = methyl, benzyl). Lanthanide complexes of a previously studied prototype ligand DO3ANP with secondary amino group (R = H) have shown interesting properties in the field of 31 P NMR imaging because of their various coordination properties, which allow in situ pH measurement. These complexes can also be used for monitoring the kinetics of the chemical exchange of the amino group proton in 1 H NMR imaging using the chemical exchange saturation transfer (CEST NMR). In this thesis, two new derivatives DO3ANMeP and DO3ANBnP were prepared in order to better understand the coordination modes changes in this ligand series. Also, their coordination behaviour with selected lanthanide ions was studied (Eu3+ , Gd3+ , Dy3+ , Yb3+ ). Based on a series of NMR and luminescence measurements, it was found out, that in acidic conditions the complexes containing DO3ANP motif bind a water molecule in their coordination...

Leaflet replacement in aortic valve repair (AVr) is associated with increased long-term repair failure. Hemodynamic performance and mechanical stress levels were investigated after porcine AVr with 5 types of clinically relevant replacement materials to ascertain which material(s) would be best suited for repair. Porcine aortic roots with intact aortic valves were placed in a left-heart simulator mounted with a high-speed camera for baseline valve assessment. Then, the non-coronary leaflet was excised and replaced with autologous porcine pericardium (APP), glutaraldehyde-fixed bovine pericardial patch (BPP; Synovis™), extracellular matrix scaffold (CorMatrix™), or collagen-impregnated Dacron (HEMASHIELD™). Hemodynamic parameters were measured over a range of cardiac outputs (2.5–6.5L/min) post-repair. Material properties of the above materials along with St. Jude Medical™ Pericardial Patch with EnCapTM Technology (SJM) were determined using pressurization experiments. Finite element models of the aortic valve and root complex were then constructed to verify the hemodynamic characteristics and determine leaflet stress levels. This study demonstrates that APP and SJM have the closest profiles to normal aortic valves; therefore, use of either replacement material may be best suited. Increased stresses found in BPP, HEMASHIELD™, and CorMatrix™ groups may be associated with late repair failure.

Leaflet replacement in aortic valve repair (AVr) is associated with increased long-term repair failure. Hemodynamic performance and mechanical stress levels were investigated after porcine AVr with 5 types of clinically relevant replacement materials to ascertain which material(s) would be best suited for repair. Porcine aortic roots with intact aortic valves were placed in a left-heart simulator mounted with a high-speed camera for baseline valve assessment. Then, the non-coronary leaflet was excised and replaced with autologous porcine pericardium (APP), glutaraldehyde-fixed bovine pericardial patch (BPP; Synovis™), extracellular matrix scaffold (CorMatrix™), or collagen-impregnated Dacron (HEMASHIELD™). Hemodynamic parameters were measured over a range of cardiac outputs (2.5–6.5L/min) post-repair. Material properties of the above materials along with St. Jude Medical™ Pericardial Patch with EnCapTM Technology (SJM) were determined using pressurization experiments. Finite element models of the aortic valve and root complex were then constructed to verify the hemodynamic characteristics and determine leaflet stress levels. This study demonstrates that APP and SJM have the closest profiles to normal aortic valves; therefore, use of either replacement material may be best suited. Increased stresses found in BPP, HEMASHIELD™, and CorMatrix™ groups may be associated with late repair failure.