Magnetisation Transfer (MT) imaging exploits magnetisation exchange between 'free' protons and 'restricted' protons attached to macromolecules in biological tissue, to indirectly provide access to the restricted protons, which are invisible using conventional MR imaging techniques. The Magnetisation Transfer Ratio (MTR) is calculated from a pair of images with different MT "weightings", however it reflects a complex combination of biological and acquisition dependent factors. Quantitative MT (qMT) imaging allows the examination of fundamental parameters underlying the MT exchange process independently of sequence details. The effect of B errors on MTR measurements was investigated, both theoretically and experimentally, and a method for correcting for B errors was proposed, based on the collection of a B map in addition to MTR data. The temperature dependence of many quantitative MR properties may cause systematic errors in phantom Quality Assurance (QA) measurements, which could have an impact on the interpretation of quantitative changes observed in long-term clinical studies. Many traditional thermometry methods are unsuitable for use in an MRI scanner. Using localised 1H-MRS acquisition sequences routinely available on clinical MRI scanners, and commonly available analysis packages, internal thermometry in phantoms using DSS (sodium 3-(trimethylsilyl)propane-1-sulphonate)) as a chemical shift reference was shown to be realistic, with a minimum detectable temperature difference of 100 ( 20) mK. The qMT acquisition parameters (combinations of MT pulse amplitude and offset frequency) were optimised, via the minimisation of the Cramer-Rao Minimum Variance Bound (CRMVB). Compared to a conventional acquisition, the optimisation enables less data to be acquired, reducing acquisition time without compromising uncertainties in estimated parameters. Alternatively, for the same number of MT-weighted data points, the parameter map noise could be reduced. This analytical approach was verified numerically, using Monte Carlo simulations, and experimentally, and optimised acquisition schemes were shown to be applicable to a range of brain tissues.

The objective of this thesis is the development of automatic methods to measure the changes in volume and growth of brain structures in prematurely born infants. Automatic tools for accurate tissue quantification from magnetic resonance images can provide means for understanding how the neurodevelopmental effects of the premature birth, such as cognitive, neurological or behavioural impairment, are related to underlying changes in brain anatomy. Understanding these changes forms a basis for development of suitable treatments to improve the outcomes of premature birth. In this thesis we focus on the segmentation of brain structures from magnetic resonance images during early childhood. Most of the current brain segmentation techniques have been focused on the segmentation of adult or neonatal brains. As a result of rapid development, the brain anatomy during early childhood differs from anatomy of both adult and neonatal brains and therefore requires adaptations of available techniques to produce good results. To address the issue of anatomical differences of the brain during early childhood compared to other age-groups, population-specific deformable and probabilistic atlases are introduced. A method for generation of population-specific prior information in the form of a probabilistic atlas is proposed and used to enhance existing segmentation algorithms. The evaluation of registration-based and intensity-based approaches shows the techniques to be complementary in the quality of automatic segmentation in different parts of the brain. We propose a novel robust segmentation method combining the advantages of both approaches. The method is based on multiple label propagation using B-spline non-rigid registration followed by EM segmentation. Intensity in homogeneity is a shading artefact resulting from the acquisition process, which significantly affects modern high resolution MR data acquired at higher magnetic field strengths. A novel template based method focused on correcting the intensity inhomogeneity in data acquired at higher magnetic field strengths is therefore proposed. The proposed segmentation method combined with proposed intensity in homogeneity correction method offers a robust tool for quantification of volumes and growth of brain structures during early childhood. The tool has been applied to 67 T1-weigted images of subject at one and two years of age.

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Imaging in the presence of subject motion has been an ongoing challenge for magnetic resonance imaging (MRI). Motion makes MRI data inconsistent, causing artifacts in conventional anatomical imaging as well as invalidating diffusion tensor imaging (DTI) reconstruction. In this thesis some of the important issues regarding the acquisition and reconstruction of anatomical and DTI imaging of moving subjects are addressed; methods to achieve high resolution and high signalto- noise ratio (SNR) volume data are proposed. An approach has been developed that uses multiple overlapped dynamic single shot slice by slice imaging combined with retrospective alignment and data fusion to produce self consistent 3D volume images under subject motion. We term this method as snapshot MRI with volume reconstruction or SVR. The SVR method has been performed successfully for brain studies on subjects that cannot stay still, and in some cases were moving substantially during scanning. For example, awake neonates, deliberately moved adults and, especially, on fetuses, for which no conventional high resolution 3D method is currently available. Fine structure of the in-utero fetal brain is clearly revealed for the first time with substantially improved SNR. The SVR method has been extended to correct motion artifacts from conventional multi-slice sequences when the subject drifts in position during data acquisition. Besides anatomical imaging, the SVR method has also been further extended to DTI reconstruction when there is subject motion. This has been validated successfully from an adult who was deliberately moving and then applied to inutero fetal brain imaging, which no conventional high resolution 3D method is currently available. Excellent fetal brain 3D apparent diffusion coefficient (ADC) maps in high resolution have been achieved for the first time as well as promising fractional Anisotropy (FA) maps. Pilot clinical studies using SVR reconstructed data to study fetal brain development in-utero have been performed. Growth curves for the normally developing fetal brain have been devised by the quantification of cerebral and cerebellar volumes as well as some one dimensional measurements. A Verhulst model is proposed to describe these growth curves, and this approach has achieved a correlation over 0.99 between the fitted model and actual data.

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The work in this thesis examines the potential of using magnetic resonance imaging and spectroscopy (MRI & MRS) as a quantitative tool for diagnosing bone abnormalities at multiple skeletal sites, which could be used in conjunction with routine clinical imaging. MRI and MRS are routinely used in the clinical setting for the diagnosis of various types of diseases and abnormalities due to its advantages of providing excellent soft tissue contrast and also providing physiological and metabolic information. The use of MRI and MRS as a direct diagnostic tool for bone abnormalities is very limited at the moment due to issues of costs and standardisation. The aim in this thesis was to use the clinical 3.0 T MR scanner to acquire data from bone and bone marrow for identification of structural and chemical properties and to use those features to identify differences in bone strength and condition. The volunteers in this thesis were part of the high bone mass (HBM) study and they had additional acquisitions from dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). MR acquisition protocols have been successfully optimised for each type of bone region and in-house software has also been created to process the acquired data and quantify various types of structural and chemical properties. The MR data from distal radius and tibia demonstrated good correlation with pQCT data (e.g. Figure 8-2 & Figure 8-3) and were also able to differentiate between HBM-affected and control populations (e.g. Figure 8-26). The MR data from lumbar vertebrae also demonstrated good correlation with DEXA data and some of the measurements were also able to differentiate between the HBM-affected and control populations. The combined results from this thesis demonstrate that both MRI and MRS are sensitive techniques for measurement of bone quantity and quality, and they are ready to be applied for clinical investigation as part of routine clinical imaging to identify bone strength in relation to abnormalities and treatments.

Multimodality imaging agents have the potential to be detected in both MRI and optical imaging experiments allowing for visualisation of biological systems from the cellular level up to the whole body. Lanthanide complexes have shown great promise as components of compounds that can act as either MRI contrast agents or luminescent imaging agents dependent on the metal centre incorporated (e.g. gadolinium(III) or europium(III)/terbium(III)respectively). This thesis describes the design, synthesis and characterisation of multimodality lanthanide imaging agents. The synthesis of a series of lanthanide chelators based on DO3A bearing a benzimidazole or a benzyl derivative that can act as both a chromophore unit and a linking group for conjugation that has the functionality to couple to an optical dye (either rhodamine or BODIPY derivatives) is discussed. A series of lanthanide complexes with either a nitro- or amino-benzyl benzimidazole DO3A chelator or with an aminobenzyl DO3A chelator have been prepared. A number of strategies have been attempted to couple the complexes to an optical dye to form a multimodality imaging agent. Physical properties and cellular uptake of the lanthanide complexes have been investigated. It was shown that the benzimidazole ligands can sensitise the luminescence of both the europium(III) and terbium(III) metal ions. Relaxation rates of the gadolinium(III) benzimidazole DOS A complexes are comparable to that of commercial contrast agents. The relaxivity of the gadolinium(III) complex formed with the ligand l,4,7-tris(carboxymethyl)-10-(l-(4-nitrobenzyl)-2-methyl benzimidazole)-1,4,7,10-tetraazacyclododecane (34) is 6.22 mM"1 s" 1 , with the relaxivity of the gadolinium(III) complex formed with 1,4,7-tris(carboxymethyl)-10-( 1 -(4-aminobenzyl)-2-methyl benzimidazole)-1,4,7,10-tetraazacyclododecane (37) was found to be lower at 4.51 mM"1 s" 1 . The luminescence lifetimes of the europium(III) and terbium(III) complexes in and D2O were used to calculate the number of coordinated water molecules in aqueous solution [q = 1.19 for the europium(III) complex of (34), 0.7-0.8 for the europium(III) complex of (37) and 1.25 for the terbium(III) complexes of (34)]

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

In this thesis, the probes were modelled and constructed at the SPMMRC. All measurements were performed on a 7T Philips scanner. The coils have been successfully evaluated. The dipole, loops, strip line and wrist probes for imaging the pelvis, knee and wrist were tested for clinical use at 7T. Two elements wrist coil can pick up signals from the whole region of interest. The advantage is more uniformity of field of view and better sensitivity. The in vivo MRI images acquired in the wrist showed the two elements provided the good quality images for the human wrist. The second study is microstrip line probe. The current flows over the flat-strip were computed, it showed that a significant increase of current close to the edges. This result agrees with theory. We did not use the strip line coil to image a human body, because the coil generated a high SAR/B1 +2 level in the region of interest. The third study was of a coil of two square loops. One way of achieving decoupling is to use the overlapping technique to decouple the coils in the simulation. It produced high signal-to-noise ratio and provides a large field of view. Finally, the dipole has been developed for in vivo MRI applications. We presented a novel model for determining the length of the PECs required for tuning the dipole at 298 MHz. The efficiency, field of view and homogeneity were improved by adding the flat strip, two strips and array strips dipole. The SAR/B1 +2 generated by the dipoles was much less than produced by the loop coil and strip line coil in the pelvis. The dipoles showed the desired improvement in SNR and homogenous coverage. Coverage goes much further into the pelvis and knee as well.