Diffusion Tensor Magnetic Resonance Imaging (DTI) is a recently-developed technique that can image in vivo the white matter pathways of the central nervous system. This study used 12-direction diffusion-weighted MRI data from nine stroke patients acquired as part of a three-year stroke rehabilitation study coordinated by the Movement Neuroscience Laboratory at the University of Auckland. DTI was used to investigate corticospinal connectivity. From the FA maps, it is found that in those patients whose motor connectivity has been compromised by the stroke to the extent that no motor evoked potential (MEP) can be elicited from a selected affected muscle group, the asymmetry in mean FA values in the posterior limbs of the internal capsules (PLICs) is correlated with functional recovery as measured by the Fugl-Meyer clinical score. Using probabilistic tractography in the contralesional hemisphere produced CST location and somatotopy results that were consistent with those of previous studies. However, in the ipsilesional hemisphere, connectivity results were highly variable. A measure of change in symmetry of mean connectivity is found to correlate with functional recovery as measured by change in FM score. This supports previous work which has correlated CST integrity and functional improvement and it supports the theory that functional recovery after stroke depends on the extent to which motor CNS symmetry can be regained in the new post-stroke architecture. It also suggests that the movement of the fMRI activations occurs in such a way as to make the most of the preserved white matter connectivity.

With an estimated prevalence of ~1%, Autism Spectrum Disorder (ASD) is relatively common. Whilst accepted as a neurodevelopmental disorder, currently the diagnosis of autism is based on the observation of characteristic behaviour: deficits in language, communication and social skills in addition to unusual or restricted interests. Research in the condition has been approached with psychological and physiological methodology however a full understanding of the underlying neuropathology of autism is still unclear. Functional Magnetic Resonance Imaging (fMRI) has been employed to study face processing in ASD with varied results. The processing of other types of social cues has been far less extensively explored and similarly, whilst there have been some reports of aberrant neural responsiveness to emotion in ASD, this component of social cognition requires further study. In particular, it is unclear whether there is a specific deficit in processing faces in ASD or rather a global deficit in emotion processing which is present across stimulus types, sensory domains and emotions. In this study basic emotion labelling using a range of stimulus types has been investigated within the same ASD cohort. In comparison to a control group, deficits were apparent in the ASD group when processing emotion in face, whole body and voice stimuli. This indicates a global emotion processing deficit in ASD that cannot be fully accounted for by deficits in basic face processing alone. Processing neutral and emotional faces and static whole body images was subsequently investigated using fMRI. When neutral faces, neutral bodies, fearful faces and fearful bodies were contrasted with fixation baseline, both groups broadly recruited the expected network of brain regions. When the emotional condition was contrasted with the neutral condition for each stimulus type significant between groups differences were apparent. The bilateral inferior parietal lobe responded significantly differently in response to facial emotion and the right supplementary motor area and superior temporal sulcus region was differentially activated in response to emotion in body stimuli. Findings reported here suggest that there are wide ranging social deficits in ASD which relate to the processing of a variety of social cues. fMRI evidence suggests that these deficits have a neural basis, in which elements of the social brain, including regions associated with mirror neuron function, activate in an atypical manner in ASD.

The management of advanced cervical and ovarian cancers remains a significant challenge as many women fail to respond to recommended therapy, resulting in disease progression and ultimately patient death. Because of tumour heterogeneity, it is rare for all cancers of a particular type to respond to a specific therapy. Many patients therefore receive treatment from which they derive little or no benefit, leading to increased morbidity and costs. A marker that could rapidly predict disease outcome would clearly be beneficial in allowing the administration of tailored therapy while reducing toxicity and cost. Novel functional imaging techniques have the ability to characterise biological tissues and non-invasively integrate physical and metabolic information. These include diffusion weighted MRI (DW-MRI), which is particularly sensitive to the microscopic motion of water molecules and changes in tissue cellularity, as well as dynamic contrast-enhanced MRI (DCE-MRI) which can assess tumour vascular characteristics during the passage of a paramagnetic contrast agent through tissues. Both imaging techniques have demonstrated potential as biomarkers of tumour response in various malignancies such as brain tumours, but have not been fully explored in gynaecological cancers.

MRI scan-related emotional distress leads to motion artefact and scan incompletion. A number of intervention studies therefore targeted to reduce anxiety. However, there is little research specifically on the development and evaluation of theory- and evidence-based psychological preparation for MRI. This research was aimed at developing and evaluating a theory- and evidence-based psychological preparation for patients undergoing MRI scanning through three empirical studies which involved 193 outpatients. Study 1: a predictive study investigated the effects of illness perceptions, MRI self-efficacy and emotional distress on scan behavioural and emotional outcomes, Study 2: a randomised controlled trial investigated the effects of a psychological preparation integrating self-efficacy enhancement and information provision techniques on scan behaviour, MRI self-efficacy and scan emotional outcomes. Study 3 aimed to: generate the items of MRI-SEQ, pre-test the measure, investigate the reliability and validity and reassess them in a replication study. Participants completed prescan and post-scan questionnaires. Scan behaviour was recorded by the radiographer. Analyses were conducted using correlation, multiple regression, logistic regression and Guttman Scaling. MRI self-efficacy significantly predicted scan behaviour and contributed to scan emotional outcomes. The developed psychological preparation had a significant effect increasing the likelihood of successful scan completion. It also significantly predicted MRI self-efficacy, and scan emotional outcomes. The intervention was also found to be acceptable and feasible for delivery to MRI outpatients. MRI-SEQ was found to have excellent internal consistency, good content validity, good predictive and criterion validity and was strongly associated with conceptually related measures. Self-efficacy is a major predictor for MRI scan outcomes. The psychological preparation intervention integrating self-efficacy enhancement and information provision was successful in improving MRI scan completion and may have potential for implementation in routine services. The MRI-SEQ possesses good psychometric quality is predictive of MRI outcomes and has potential as a screening tool in the MRI centre.

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Functional neuroimaging studies of autobiographical memory have grown dramatically in recent years. These studies are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: (i) complex constructive processes, (ii) recollective qualities of emotion and vividness, and (iii) remote memory retrieval. Constructing autobiographical memories involves search, monitoring and self-referential processes that are associated with activity in separable prefrontal regions. The contributions of emotion and vividness have been linked to the amygdala and visual cortex respectively. Finally, there is evidence that recent and remote autobiographical memories might activate the hippocampus equally, which has implications for memory-consolidation theories. The rapid development of innovative methods for eliciting personal memories in the scanner provides the opportunity to delve into the functional neuroanatomy of our personal past. / Dissertation

Late-life depression (LLD) is common illness, frequently associated with neuropsychological impairment. Disruption of frontal-subcortical and limbic networks may play a key role in LLD and can be examined using magnetic resonance imaging (MRI). Grey matter (GM) can be examined using T1-weighted MRI, white matter (WM) using diffusion tensor imaging (DTI), and functional connectivity using resting-state functional MRI (fMRI). To clarify the roles of GM, WM and functional connectivity in LLD, systematic reviews and meta-analyses of T1-weighted MRI, DTI and resting-state fMRI studies of depression were performed. The literature provided evidence for GM and WM abnormalities within frontal-subcortical and limbic networks, and increased functional connectivity within the default-mode network, in depression. To examine whether results gained from different techniques are complementary, multi-modal MRI was used to compare GM, WM and functional connectivity between thirty-six participants with LLD and twenty-five control participants. WM integrity was widely reduced in LLD, without significant group differences in GM or functional connectivity. To investigate whether neuropsychological deficits represent independent processes with specific neural correlates, or whether they can be explained by a core deficit, the relationships between neuropsychological and MRI measures were explored. Executive function and processing speed were found to represent core deficits that contribute to impairment in other domains; and impaired performance was correlated with reduced frontal WM integrity. Episodic memory deficits were dependent on executive function and processing speed; and associated with reduced frontal and hippocampal WM integrity. The relationships between age at onset, severity and MRI measures of GM, WM and functional connectivity were also investigated. Later onset was associated with reduced WM integrity, in line with the vascular hypothesis. Earlier onset was associated with greater duration of illness and reduced hippocampal volume, consistent with the glucocorticoid cascade hypothesis. Severity was not associated with any MRI measure. This thesis strongly supports the hypothesis that WM abnormalities in frontal-subcortical and limbic networks play a key role in LLD, with abnormalities related to neuropsychological impairment and compatible with the vascular hypothesis.

The brainstem plays a crucial role in a great number of vital functions such as respiratory regulation, visual reflexes, and the perception of pain. The small size and close proximity of the nuclei requires high-resolution functional magnetic resonance imaging (FMRI). However, brainstem FMRI using conventional gradient-echo echo-planar imaging (GRE-EPI) techniques is challenging due to the increased signal dropout and geometric distortions in the brainstem. The primary aim of the work presented in this thesis was to investigate alternative methods for brainstem FMRI in order to overcome some of the challenges associated with single-shot GRE-EPI techniques. Towards this goal 3D segmented sequences were explored, which have the advantage that the size of the geometric distortions is not proportional to the resolution at which is scanned. In particular, two sequences were investigated: balanced steady-state free-precession (bSSFP) and spoiled gradient echo (SPGR). First, a set of experiments was conducted, in which each experiment aimed to isolate a limited range of sequence properties in order to characterize and assess the potential of the candidate sequences. It was found that bSSFP has better noise characteristics compared to GRE-EPI when applied with a 2D acquisition, but when 3D readouts were used the signal instabilities increased dramatically. Based on these findings, experiments that investigate the influence of multishot acquisitions on signal instabilities caused by physiological noise were performed. The signal instabilities were found to mainly originate from regions of CSF and blood and were highly correlated to the cardiac cycle. Several correction methods were explored and one method was identified to be implemented in vivo. A novel method that allows real-time cardiac synchronization of the k-space acquisition was developed. The developed methods used a custom parallel imaging reconstruction to allow for acquisition with a fixed volume frame rate, which is desirable for FMRI purposes. The method was found to reduce the signal instabilities in 3D SPGR and bSSFP significantly. A comprehensive assessment of two currently available retrospective correction techniques was conducted and their practicalities were compared. Recommendations are made to improve the robustness of the investigated correction methods. A novel optimization method was implemented, which was developed to determine the optimal regressor set for retrospective corrections. The method can be applied to image based as well as k-space based methods.

The aim of this project was to investigate the nature and possible significance of first-person kinaesthetic vocal sensations observed in association with musical listening. Hearing and voice are known to be closely linked but the mechanisms that underlie their close relationship are not yet understood. The presence of kinaesthetic vocal sensations challenges accounts of auditory processing that are divorced from peripheral vocal input and, instead, suggests the hypothesis that auditory and vocal processing mechanisms rely on shared peripheral substrates in addition to their increasingly recognized shared (brain-based) central substrates. To investigate this hypothesis, I used MRI and developed a measurement protocol (informed by established methods in cephalometry) that would allow me to relate vocal structures to their direct and indirect bony attachments to the craniofacial skeleton, cervical spine and sternum. After establishing the method's validity in subjects at rest, I acquired midsagittal MR images (under conditions where articulatory and postural input was negligible) while subjects (1) hummed and (2) listened (in a focused way) to low and high notes at each end of their range. Geometric and shape analysis of craniocaudal, craniocervical and anteroposterior variables revealed significant differences between low- and high-note conditions and widespread correlations between variables for both humming and listening investigations. An unexpected association between pitch change and changes of cervical alignment was also found. These results were complemented and extended by using the same MR images to build an active shape model (ASM). In addition to showing how vocal structures move together, ASM showed goal-related vocal activity to consist of one or more independent modes of variation. Together, the observations, experimental results, and evidence from diverse historical and contemporary sources, support the hypothesis that mechanisms underlying auditory and vocal processing rely on shared central and peripheral substrates. Wide-ranging implications arising from this hypothesis are also discussed.

Introduction There is a pressing clinical need to treat patients with acute coronary syndrome (ACS) timely and efficiently in order to improve their prognosis. Standard tools available in ED, while useful, do not comprehensively characterize ACS for either diagnosis or risk stratification. The role of CMR in ACS is emerging because it allows assessment of both myocardial composition and function. Newer CMR techniques such as: a) T2 W imaging for assessing myocardial oedema and area at risk B) pre contrast T1 mapping techniques for quantitative characterization of the tissue composition, are adding further utility for CMR in ACS. At present the clinical use of these techniques is still limited and further investigations are needed to assess their clinical applicability in ACS patients. Aims The aims of this thesis were several. Firstly we sought to establish a CMR protocol for imaging ACS patients on a 3T CMR scanner. In order to do so, we validated a novel T2 W technique for oedema imaging (T2 prep SSFP) at 3T. Second, we aimed to perform a detailed study of the time course of oedema in ACS patients in order to establish the appropriate imaging time for the assessment of area at risk. Third, by applying T2W acute oedema imaging, we sought to investigate the functional and pathological meaning of complicated remote plaques in patients with multivessel disease. Finally, we aimed to establish whether, in comparison to standard CMR techniques, novel precontrast Tl mapping allows better characterisation of the acutely injured myocardium and whether it can predict long-term functional recovery. Methods The research studies were all performed on a 3T Trio Siemens scanner. In the initial stage of the research, we validated the T2 W technique performing phantom work and scanning both volunteers and patients to assess the uniformity of signal intensity in the myocardium and to establish a threshold based method to post process the images. We then established a CMR protocol for ACS including oedema imaging, T1 mapping imaging, perfusion, functional and late gadolinium enhancement imaging. Patients with acute myocardial infarction (both ST elevation myocardial infarction (STEMI) and non STEMI) were scanned at 4 different time points after the acute event (3 scans within 2 weeks and one at 6 months). All STEMI patients underwent primary percutaneous coronary intervention (PCI) while the non-STEMI patients underwent coronary angiography and for PCI. Results We validated the T2prep SSFP technique at 3T, highlighting its limitations and establishing a threshold of mean ± 2SD to assess myocardial oedema. We found that the optimal imaging window to assess the maximal expression of myocardial oedema was within 1 week from the acute event in patients with ST elevation MI. Also, our results showed a reduction of LGE over time (from acute to chronic) in segments which also showed improvement in contractile function indicating that even segments with transmural LGE assessed in the early hours post event could be viable. By applying these techniques in acute patients with bystander disease undergoing percutaneous coronary intervention, we found that: l) T2W imaging can detect myocardial injury downstream from a vessel identified as "non culprit" 2) in 20% of NSTEMI patients, the angiographic assessment alone failed to identify the culprit vessel. Finally, we found that the diagnostic performance of acute pre-contrast Tl-mapping was at least as good as that ofT2W CMR for detecting myocardial injury. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental Tl values and the likelihood of improvement of segmental function at 6 months decreased progressively as acute Tl values increased. Conclusions In summary, we defined a stable imaging window for the retrospective evaluation of area at risk and we also indicated that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium. Furthermore, in NSTEMI patients with multivessel disease, by revealing acute myocardial damage in territories pertaining to vessels not treated acutely, we raised the issue of the need for better tools for the correct identification of the culprit vessel and to stratify patients rather than by angiographic assessment alone. Finally, we demonstrated how pre-contrast Tl mapping allows for assessment of the extent of myocardial damage and how Tl mapping might become an important complementary technique to LGE and T2W for the identification of reversible myocardial injury and the prediction of functional recovery in acute MI.