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Paul S. Morgan

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6 papers

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YNIMG Journal 2017 Journal Article

Activation induced changes in GABA: Functional MRS at 7 T with MEGA-sLASER

Chen Chen
Hilmar P. Sigurdsson
Sophia E. Pépés
Dorothee P. Auer
Peter G. Morris
Paul S. Morgan
Penny A. Gowland
Stephen R. Jackson

Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (−12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10min of hand-clenching, compared to an initial baseline level (GABA/tCr =0. 11±0. 02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7T.

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YNIMG Journal 2015 Journal Article

Histologic validation of locus coeruleus MRI contrast in post-mortem tissue

Noam I. Keren
Saeid Taheri
Elena M. Vazey
Paul S. Morgan
Ann-Charlotte E. Granholm
Gary S. Aston-Jones
Mark A. Eckert

The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78μm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease.

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YNICL Journal 2013 Journal Article

Diffusion tensor imaging of nigral degeneration in Parkinson's disease: A region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis

Stefan T. Schwarz
Maryam Abaei
Vamsi Gontu
Paul S. Morgan
Nin Bajaj
Dorothee P. Auer

There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results. To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes. We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10(- 3) mm(2)/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I(2) = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I(2) = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = - 0.5, p = 0.22, I(2) = 28%). The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson's disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker.

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YNIMG Journal 2011 Journal Article

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study

Jeffrey R. Binder
William L. Gross
Jane B. Allendorfer
Leonardo Bonilha
Jessica Chapin
Jonathan C. Edwards
Thomas J. Grabowski
John T. Langfitt

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story–Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

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YNIMG Journal 2010 Journal Article

Brain tractography using Q-ball imaging and graph theory: Improved connectivities through fibre crossings via a model-based approach

Stamatios N. Sotiropoulos
Li Bai
Paul S. Morgan
Cris S. Constantinescu
Christopher R. Tench

Brain tractography techniques utilize a set of diffusion-weighted magnetic resonance images to reconstruct white matter tracts, non-invasively and in-vivo. Streamline tracking techniques propagate curves from a seed to imply connectivity to distal voxels. Alternative approaches have been developed that attempt to quantify connection strength between all voxels and the seed. Tractography based on graph theory is amongst them. Despite its potential, graph-based tracking through complex fibre configurations has not been extensively studied and existing methods have inherent limitations. Anatomically unlikely connections may be identified in fibre crossing regions, by assigning relatively high connection strengths to all crossing populations. In this study, we discuss these limitations and present a new approach for robustly propagating through fibre crossings, as described by the orientation distribution functions (ODFs) derived from Q-ball imaging. Each image voxel is treated as a graph node and graph arcs connect neighbouring voxels. Weights representative of both structural and diffusivity features are assigned to each arc. To account for the existence of crossing fibre populations within a voxel, complex ODFs are decomposed into components representative of single-fibre populations and an image multigraph is created. The multigraph is searched exhaustively, but efficiently, to find the strongest paths and assign connectivity strengths between a seed and all the other image voxels. A comparison with the existing graph-based tractography as well as Q-ball driven front evolution tractography is performed on simulated data, and on human Q-ball imaging data acquired from five healthy volunteers. The new approach improves the connection strengths through fibre crossing regions, reducing the strengths of paths that are less anatomically plausible.

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YNIMG Journal 2009 Journal Article

In vivo mapping of the human locus coeruleus

Noam I. Keren
Carl T. Lozar
Kelly C. Harris
Paul S. Morgan
Mark A. Eckert

The locus coeruleus (LC) is a brainstem structure that has widespread cortical and sub-cortical projections to modulate states of attention. Our understanding of the LC's role in both normal attention and clinical populations affected by disrupted attention would be advanced by having in vivo functional and structural markers of the human LC. Evidence for LC activation can be difficult to interpret because of uncertainty about whether brainstem activity can be accurately localized to the LC. High resolution T1-turbo spin echo (T1-TSE) magnetic resonance imaging (MRI) (in-plane resolution of 0. 4 mm×0. 4 mm) was used in this study to characterize the location and distribution probability of the LC across 44 adults ranging in age from 19 to 79 years. Utilizing a study-specific brainstem template, the individual brainstems were aligned into standard space, while preserving variations in LC signal intensity. Elevated T1-TSE signal was observed in the rostral pons that was strongly correlated with the position and concentration of LC cells previously reported in a study of post-mortem brains (r =0. 90). The elevated T1-TSE signal was used to produce a probabilistic map of the LC in standard Montreal Neurological Institute (MNI) coordinate space. This map can be used to test hypotheses about the LC in human structural and functional imaging studies. Such efforts will contribute to our understanding of attention systems in normal and clinical populations.

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