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Browsing by Author "Edden, Richard A. E."
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Item Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites(Elsevier, 2019-05) Mikkelsen, Mark; Rimbault, Daniel L.; Barker, Peter B.; Bhattacharyya, Pallab K.; Brix, Maiken K.; Buur, Pieter F.; Cecil, Kim M.; Chan, Kimberly L.; Chen, David Y.-T.; Craven, Alexander R.; Cuypers, Koen; Dacko, Michael; Duncan, Niall W.; Dydak, Ulrike; Edmondson, David A.; Ende, Gabriele; Ersland, Lars; Forbes, Megan A.; Gao, Fei; Greenhouse, Ian; Harris, Ashley D.; He, Naying; Heba, Stefanie; Hoggard, Nigel; Hsu, Tun-Wei; Jansen, Jacobus F. A.; Kangarlu, Alayar; Lange, Thomas; Lebel, R. Marc; Li, Yan; Lin, Chien-Yuan E.; Liou, Jy-Kang; Lirng, Jiing-Feng; Liu, Feng; Long, Joanna R.; Ma, Ruoyun; Maes, Celine; Moreno-Ortega, Marta; Murray, Scott O.; Noah, Sean; Noeske, Ralph; Noseworthy, Michael D.; Oeltzschner, Georg; Porges, Eric C.; Prisciandaro, James J.; Puts, Nicolaas A.; Roberts, Timothy P. L.; Sack, Markus; Sailasuta, Napapon; Saleh, Muhammad G.; Schallmo, Michael-Paul; Simard, Nicholas; Stoffers, Diederick; Swinnen, Stephan P.; Tegenthoff, Martin; Truong, Peter; Wang, Guangbin; Wilkinson, Iain D.; Wittsack, Hans-Jörg; Woods, Adam J.; Xu, Hongmin; Yan, Fuhua; Zhang, Chencheng; Zipunnikov, Vadim; Zöllner, Helge J.; Edden, Richard A. E.; Radiology and Imaging Sciences, School of MedicineAccurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.Item Thalamic GABA Predicts Fine Motor Performance in Manganese-Exposed Smelter Workers(Public Library of Science, 2014-02-04) Long, Zaiyang; Li, Xiang-Rong; Xu, Jun; Edden, Richard A. E.; Qin, Wei-Ping; Long, Li-Ling; Murdoch, James B.; Zheng, Wei; Jiang, Yue-Ming; Dydak, Ulrike; Radiology and Imaging Sciences, School of MedicineOverexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R(2) = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2) = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.