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    ABSTRACT: Despite widespread application to human imaging, voxel-based morphometry (VBM), where images are compared following grey matter (GM) segmentation, is seldom used in mice. Here VBM is performed for the R6/2 model of Huntington's disease, a progressive neurological disorder. This article discusses issues in translating the methods to mice and shows that its statistical basis is sound in mice as it is in human studies. Whole brain images from live transgenic and control mice are segmented into GM maps after processing and compared to produce statistical parametric maps of likely differences. To assess whether false positives were likely to occur, a large cohort of ex vivo magnetic resonance brain images were sampled with permutation testing. Differences were seen particularly in the striatum and cortex, in line with studies performed ex vivo and as seen in human patients. In validation, the rate of false positives is as expected and these have no discernible distribution through the brain. The study shows that VBM successfully detects differences in the Huntington's disease mouse brain. The method is rapid compared to manual delineation and reliable. The templates created here for the mouse brain are freely released for other users in addition to an open-source software toolbox for performing mouse VBM.
    Magnetic Resonance Imaging 07/2013; 31(9). DOI:10.1016/j.mri.2013.06.001
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    ABSTRACT: We present a technique for predicting cardiac and respiratory phase on a time point by time point basis, from fMRI image data. These predictions have utility in attempts to detrend effects of the physiological cycles from fMRI image data. We demonstrate the technique both in the case where it can be trained on a subject's own data, and when it cannot. The prediction scheme uses a multiclass support vector machine algorithm. Predictions are demonstrated to have a close fit to recorded physiological phase, with median Pearson correlation scores between recorded and predicted values of 0.99 for the best case scenario (cardiac cycle trained on a subject's own data) down to 0.83 for the worst case scenario (respiratory predictions trained on group data), as compared to random chance correlation score of 0.70. When predictions were used with RETROICOR-a popular physiological noise removal tool-the effects are compared to using recorded phase values. Using Fourier transforms and seed based correlation analysis, RETROICOR is shown to produce similar effects whether recorded physiological phase values are used, or they are predicted using this technique. This was seen by similar levels of noise reduction noise in the same regions of the Fourier spectra, and changes in seed based correlation scores in similar regions of the brain. This technique has a use in situations where data from direct monitoring of the cardiac and respiratory cycles are incomplete or absent, but researchers still wish to reduce this source of noise in the image data. Hum Brain Mapp , 2011. © 2011 Wiley-Liss, Inc.
    Human Brain Mapping 04/2013; 34(4). DOI:10.1002/hbm.21487
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    ABSTRACT: Radiolabelling of cocaine-derived 3-phenyltropanes for dopamine transporter positron emission tomography with (18) F and (11) C is reviewed. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Labelled Compounds 03/2013; 56(3-4):149-158. DOI:10.1002/jlcr.3018
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    ABSTRACT: Diffusion MR data sets produce large numbers of streamlines which are hard to visualize, interact with, and interpret in a clinically acceptable time scale, despite numerous proposed approaches. As a solution we present a simple, compact, tailor-made clustering algorithm, QuickBundles (QB), that overcomes the complexity of these large data sets and provides informative clusters in seconds. Each QB cluster can be represented by a single centroid streamline; collectively these centroid streamlines can be taken as an effective representation of the tractography. We provide a number of tests to show how the QB reduction has good consistency and robustness. We show how the QB reduction can help in the search for similarities across several subjects.
    Frontiers in Neuroscience 12/2012; 6:175. DOI:10.3389/fnins.2012.00175
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    ABSTRACT: A rapid and efficient protocol to afford the title compound 2-[(18)F]-fluoro-2,2-difluoroethyl tosylate ([(18)F]7b) is described. Starting from [(18)F]fluoride ion, labelling reagent 7b was obtained in good yields and a high specific radioactivity. Compound ([(18)F]7b) was then used to synthesise a prospective radiotracer for PET-imaging in dementia.
    Organic & Biomolecular Chemistry 07/2012; 10(34):6980-6. DOI:10.1039/c2ob25802a
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    ABSTRACT: Rapid and direct: the carboxylation of boronic acid esters with (11)CO(2) provides [(11)C]carboxylic acids as a convenient entry into [(11)C]esters and [(11)C]amides. This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl).
    Angewandte Chemie International Edition 03/2012; 51(11):2698-702. DOI:10.1002/anie.201107263
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    ABSTRACT: A procedure for the radiosynthesis of aliphatic [(18)F]trifluoromethyl groups by reacting 1,1-difluorovinyl precursors with [(18)F]fluoride ions, resulting in the equivalent of direct nucleophilic addition of H[(18)F]F, has been developed. A variety of (18)F-labelled model compounds were then obtained and two potential [(18)F]radiotracers were synthesised by a two step process starting from 1,1-difluorovin-2-yl 4-toluenesulfonate. The method is widely applicable for the synthesis of novel radiotracers in high radiochemical yields and good specific activity.
    Chemical Communications 11/2011; 47(43):11873-5. DOI:10.1039/c1cc15342k
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    ABSTRACT: Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic lipid species in muscle and elsewhere, impairing insulin action on glucose metabolism. Alternatively, however, defects in insulin signaling may be primary events that result in mitochondrial dysfunction, or there may be a bidirectional relationship between these phenomena. To investigate this, we examined mitochondrial function in patients with genetic defects in insulin receptor (INSR) signaling. We found that phosphocreatine recovery after exercise, a measure of skeletal muscle mitochondrial function in vivo, was significantly slowed in patients with INSR mutations compared with that in healthy age-, fitness-, and BMI-matched controls. These findings suggest that defective insulin signaling may promote mitochondrial dysfunction. Furthermore, consistent with previous studies of mouse models of mitochondrial dysfunction, basal and sleeping metabolic rates were both significantly increased in genetically insulin-resistant patients, perhaps because mitochondrial dysfunction necessitates increased nutrient oxidation in order to maintain cellular energy levels.
    The Journal of clinical investigation 06/2011; 121(6):2457-61. DOI:10.1172/JCI46405
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    ABSTRACT: Over the past 15 years, diffusion-weighted MRI data has been used to measure the degree of diffusion anisotropy in different regions in both the healthy and the pathological brain. In this study we compared the performance of several different anisotropy indices in terms of their ability to differentiate between tissue types, using both simulated and experimental data. Simulations were performed for one-, two- and three-fibre populations. The results obtained suggest that only indices derived from tensors of rank higher than two, and indices derived from model free approaches can differentiate between an isotropic voxel and a population of three orthogonal fibres. Indices such as geodesic anisotropy (GeoA), generalised anisotropy (GA), and scaled entropy (SE) produce greater contrast-to-noise ratios than fractional anisotropy (FA) for simulated data and large anisotropy differences between brain regions. However, the biological scatter seen within brain regions is large enough to mask the expected differences between indices when looking at small anisotropy differences in the brain. The comparison of different acquisition schemes revealed that the use of multiple b-values seems to result in improved contrast-to-noise ratios for indices derived from the traditional diffusion tensor model.
    NeuroImage 03/2011; 57(3):1103-15. DOI:10.1016/j.neuroimage.2011.03.004
  • ChemMedChem 10/2010; 5(10):1686-8. DOI:10.1002/cmdc.201000237
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