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    ABSTRACT: PURPOSE: To examine the effects of the reconstruction algorithm of magnitude images from multichannel diffusion MRI on fibre orientation estimation. THEORY AND METHODS: It is well established that the method used to combine signals from different coil elements in multichannel MRI can have an impact on the properties of the reconstructed magnitude image. Using a root-sum-of-squares approach results in a magnitude signal that follows an effective noncentral-χ distribution. As a result, the noise floor, the minimum measurable in the absence of any true signal, is elevated. This is particularly relevant for diffusion-weighted MRI, where the signal attenuation is of interest. RESULTS: In this study, we illustrate problems that such image reconstruction characteristics may cause in the estimation of fibre orientations, both for model-based and model-free approaches, when modern 32-channel coils are used. We further propose an alternative image reconstruction method that is based on sensitivity encoding (SENSE) and preserves the Rician nature of the single-channel, magnitude MR signal. We show that for the same k-space data, root-sum-of-squares can cause excessive overfitting and reduced precision in orientation estimation compared with the SENSE-based approach. CONCLUSION: These results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition. Magn Reson Med, 2013. ©2013 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 12/2013; 70(6). DOI:10.1002/mrm.24623
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    ABSTRACT: Transcranial direct current stimulation (tDCS) has been used to modify motor performance in healthy and patient populations. However, our understanding of the large-scale neuroplastic changes that support such behavioural effects is limited. Here, we used both seed-based and independent component analyses (ICA) approaches to probe tDCS-induced modifications in resting state activity with the aim of establishing the effects of tDCS applied to the primary motor cortex (M1) on both motor and non-motor networks within the brain. Subjects participated in three separate sessions, during which resting fMRI scans were acquired before and after ten minutes of 1 mA anodal, cathodal, or sham tDCS. Cathodal tDCS increased the inter-hemispheric coherence of resting fMRI signal between the left and right supplementary motor area (SMA), and between the left and right hand areas of M1. A similar trend was documented for the premotor cortex (PMC). Increased functional connectivity following cathodal tDCS was apparent within the ICA-generated motor and default mode networks. Additionally, the overall strength of the default mode network was increased. Neither anodal nor sham tDCS produced significant changes in resting state connectivity. This work indicates that cathodal tDCS to M1 affects the motor network at rest. In addition, the effects of cathodal tDCS on the default mode network support the hypothesis that diminished top-down control may contribute to the impaired motor performance induced by cathodal tDCS.
    NeuroImage 11/2013; 88. DOI:10.1016/j.neuroimage.2013.11.037
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    ABSTRACT: Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI (rfMRI) for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image-processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project and highlight some upcoming challenges in functional connectomics.
    Trends in Cognitive Sciences 11/2013; DOI:10.1016/j.tics.2013.09.016
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    ABSTRACT: The existence of transsynaptic retrograde degeneration (TRD) in the human visual system has been established, however the dependence of TRD on different factors such as lesion location, size and manner of lesion acquisition has yet to be quantified. We obtained T1-weighted structural and diffusion-weighted images for 26 patients with adult-acquired or congenital hemianopia and 12 age-matched controls. The optic tract (OT) was defined and measured in the structural and diffusion-weighted images, and degeneration assessed by comparing the integrity of tracts in the lesioned and in the undamaged hemisphere. OT degeneration was found in all patients with established lesions, regardless of lesion location. In patients with acquired lesions, the larger the initial lesion, the greater is the resulting TRD. However, this was not the case for congenital patients, who generally showed greater degeneration than would be predicted by lesion size. A better predictor of TRD was the size of the visual field deficit, which was correlated with degeneration across all patients. Interestingly, although diffusion-weighted imaging (DWI) is more frequently used to examine white matter tracts, in this study the T1-weighted scans gave a better indication of the extent of tract degeneration. We conclude that TRD of the OT occurs in acquired and congenital hemianopia, is correlated with visual field loss, and is most severe in congenital cases. Understanding the pattern of TRD may help to predict effects of any visual rehabilitation training.
    Journal of neurology, neurosurgery, and psychiatry 10/2013; 85(4). DOI:10.1136/jnnp-2013-306577
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    ABSTRACT: Amide Proton Transfer (APT) reports on contrast derived from the exchange of protons between amide groups and water. Commonly, APT contrast is quantified by asymmetry analysis, providing an ensemble contrast of both amide proton concentration and exchange rate. An alternative is to sample the off-resonant spectrum and fit an exchange model, permitting the APT effect to be quantified, correcting automatically for confounding effects of spillover, field inhomogeneity, and magnetization transfer. Additionally, it should permit amide concentration and exchange rate to be independently quantified. Here, a Bayesian method is applied to this problem allowing pertinent prior information to be specified. A three-pool model was used incorporating water protons, amide protons, and magnetization transfer effect. The method is demonstrated in simulations, creatine phantoms with varying pH and in vivo (n = 7). The Bayesian model-based approach was able to quantify the APT effect accurately (root-mean-square error < 2%) even when subject to confounding field variation and magnetization transfer effect, unlike traditional asymmetry analysis. The in vivo results gave approximate APT concentration (relative to water) and exchange rate values of 3 × 10(-3) and 15 s(-1) . A degree of correlation was observed between these parameter making the latter difficult to quantify with absolute accuracy, suggesting that more optimal sampling strategies might be required. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 08/2013; 70(2). DOI:10.1002/mrm.24474
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    ABSTRACT: Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of a Special Issue entitled 'Neuroimaging'.
    Neuropharmacology 07/2013; 84. DOI:10.1016/j.neuropharm.2013.06.035
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    ABSTRACT: Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy and or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1-M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients' behavioural response to TDCS. There were three main findings: 1) Unlike Anodal and Cathodal TDCS, Bilateral M1-M1 TDCS (1mA, 20 minutes) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; 2) GABA levels in ipsilesional M1 predicted patients' behavioural gains from Anodal TDCS; 3) Although patients were in the chronic phase, time since stroke (and its combination with Fugl-Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor cortico-spinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.
    NeuroImage 05/2013; 85(Pt 3). DOI:10.1016/j.neuroimage.2013.05.096
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    ABSTRACT: Significant resources are now being devoted to large-scale international studies attempting to map the connectome - the brain's wiring diagram. This review will focus on the use of human neuroimaging approaches to map the connectome at a macroscopic level. This emerging field of human connectomics brings both opportunities and challenges. Opportunities arise from the ability to apply a powerful toolkit of mathematical and computational approaches to interrogate these rich datasets, many of which are being freely shared with the scientific community. Challenges arise in methodology, interpretability and biological or clinical validity. This review discusses these challenges and opportunities and highlights potential future directions.
    NeuroImage 05/2013; 80. DOI:10.1016/j.neuroimage.2013.05.082
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    ABSTRACT: Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of 1h of whole-brain rfMRI data at 3T, with a spatial resolution of 2×2×2mm and a temporal resolution of 0.7s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses.
    NeuroImage 05/2013; 80. DOI:10.1016/j.neuroimage.2013.05.039
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    ABSTRACT: Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2013; 69(5). DOI:10.1002/mrm.24372
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