Browsing by Author "Gao, Fei"

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    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 Medicine
    Accurate 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.
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    Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites
    (Radiological Society of North America, 2020-04) Považan, Michal; Mikkelsen, Mark; Berrington, Adam; 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.J.; 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.; Barker, Peter B.; Radiology and Imaging Sciences, School of Medicine
    The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols.
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    Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice
    (Elsevier, 2023) Gao, Fei; Hayashi, Yujiro; Saravanaperumal, Siva Arumugam; Gajdos, Gabriella B.; Syed, Sabriya A.; Bhagwate, Aditya V.; Ye, Zhenqing; Zhong, Jian; Zhang, Yuebo; Choi, Egan L.; Kvasha, Sergiy M.; Kaur, Jagneet; Paradise, Brooke D.; Cheng, Liang; Simone, Brandon W.; Wright, Alec M.; Kellogg, Todd A.; Kendrick, Michael L.; McKenzie, Travis J.; Sun, Zhifu; Yan, Huihuang; Yu, Chuanhe; Bharucha, Adil E.; Linden, David R.; Lee, Jeong-Heon; Ordog, Tamas; Medicine, School of Medicine
    Background & aims: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. Methods: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. Results: HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. Conclusions: Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.