Browsing by Author "Dydak, Ulrike"
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Item Anterior Cingulate Cortex Metabolites and White Matter Microstructure: A Multimodal Study of Emergent Alcohol Use Disorder(Springer, 2021) Grecco, Gregory G.; Chumin, Evgeny J.; Dzemidzic, Mario; Cheng, Hu; Finn, Peter; Newman, Sharlene; Dydak, Ulrike; Yoder, Karmen K.; Radiology and Imaging Sciences, School of MedicineMultimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.Item Association of exposure to manganese and fine motor skills in welders - Results from the WELDOX II study(Elsevier, 2021) Lotz, Anne; Pesch, Beate; Casjens, Swaantje; Lehnert, Martin; Zschiesche, Wolfgang; Taeger, Dirk; Yeh, Chien-Lin; Weiss, Tobias; Schmidt-Wilcke, Tobias; Quetscher, Clara; Gabriel, Stefan; Samis Zella, Maria Angela; Woitalla, Dirk; Dydak, Ulrike; van Thriel, Christoph; Brüning, Thomas; Behrens, Thomas; Radiology and Imaging Sciences, School of MedicineThe aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.Item Association of exposure to manganese and iron with relaxation rates R1 and R2*- magnetic resonance imaging results from the WELDOX II study(Elsevier, 2017) Pesch, Beate; Dydak, Ulrike; Lotz, Anne; Casjens, Swaantje; Quetscher, Clara; Lehnert, Martin; Abramowski, Jessica; Stewig, Christoph; Yeh, Chien-Lin; Weiss, Tobias; van Thriel, Christoph; Herrmann, Lennard; Muhlack, Siegfried; Woitalla, Dirk; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Brüning, Thomas; Department of Radiology and Imaging Sciences, School of MedicineObjective Magnetic resonance imaging is a non-invasive method that allows the indirect quantification of manganese (Mn) and iron (Fe) accumulation in the brain due to their paramagnetic features. The WELDOX II study aimed to explore the influence of airborne and systemic exposure to Mn and Fe on the brain deposition using the relaxation rates R1 and R2* as biomarkers of metal accumulation in regions of interest in 161 men, including active and former welders. Material and methods We obtained data on the relaxation rates R1 and R2* in regions that included structures within the globus pallidus (GP), substantia nigra (SN), and white matter of the frontal lobe (FL) of both hemispheres, as well as Mn in whole blood (MnB), and serum ferritin (SF). The study subjects, all male, included 48 active and 20 former welders, 41 patients with Parkinson's disease (PD), 13 patients with hemochromatosis (HC), and 39 controls. Respirable Mn and Fe were measured during a working shift for welders. Mixed regression models were applied to estimate the effects of MnB and SF on R1 and R2*. Furthermore, we estimated the influence of airborne Mn and Fe on the relaxation rates in active welders. Results MnB and SF were significant predictors of R1 but not of R2* in the GP, and were marginally associated with R1 in the SN (SF) and FL (MnB). Being a welder or suffering from PD or HC elicited no additional group effect on R1 or R2* beyond the effects of MnB and SF. In active welders, shift concentrations of respirable Mn > 100 μg/m3 were associated with stronger R1 signals in the GP. In addition to the effects of MnB and SF, the welding technique had no further influence on R1. Conclusions MnB and SF were significant predictors of R1 but not of R2*, indicative of metal accumulation, especially in the GP. Also, high airborne Mn concentration was associated with higher R1 signals in this brain region. The negative results obtained for being a welder or for the techniques with higher exposure to ultrafine particles when the blood-borne concentration was included into the models indicate that airborne exposure to Mn may act mainly through MnB.Item Associations between sensory processing and electrophysiological and neurochemical measures in children with ASD: an EEG-MRS study(BMC, 2021-01-06) Pierce, Sarah; Kadlaskar, Girija; Edmondson, David A.; McNally Keehn, Rebecca; Dydak, Ulrike; Keehn, Brandon; Pediatrics, School of MedicineBackground: Autism spectrum disorder (ASD) is associated with hyper- and/or hypo-sensitivity to sensory input. Spontaneous alpha power, which plays an important role in shaping responsivity to sensory information, is reduced across the lifespan in individuals with ASD. Furthermore, an excitatory/inhibitory imbalance has also been linked to sensory dysfunction in ASD and has been hypothesized to underlie atypical patterns of spontaneous brain activity. The present study examined whether resting-state alpha power differed in children with ASD as compared to TD children, and investigated the relationships between alpha levels, concentrations of excitatory and inhibitory neurotransmitters, and atypical sensory processing in ASD. Methods: Participants included thirty-one children and adolescents with ASD and thirty-one age- and IQ-matched typically developing (TD) participants. Resting-state electroencephalography (EEG) was used to obtain measures of alpha power. A subset of participants (ASD = 16; TD = 16) also completed a magnetic resonance spectroscopy (MRS) protocol in order to measure concentrations of excitatory (glutamate + glutamine; Glx) and inhibitory (GABA) neurotransmitters. Results: Children with ASD evidenced significantly decreased resting alpha power compared to their TD peers. MRS estimates of GABA and Glx did not differ between groups with the exception of Glx in the temporal-parietal junction. Inter-individual differences in alpha power within the ASD group were not associated with region-specific concentrations of GABA or Glx, nor were they associated with sensory processing differences. However, atypically decreased Glx was associated with increased sensory impairment in children with ASD. Conclusions: Although we replicated prior reports of decreased alpha power in ASD, atypically reduced alpha was not related to neurochemical differences or sensory symptoms in ASD. Instead, reduced Glx in the temporal-parietal cortex was associated with greater hyper-sensitivity in ASD. Together, these findings may provide insight into the neural underpinnings of sensory processing differences present in ASD.Item Atlas-based GABA-mapping with 3D MEGA-MRSI: Cross-correlation to single voxel MRS(Wiley, 2021) Ma, Ruoyun E.; Murdoch, James B.; Bogner, Wolfgang; Andronesi, Ovidiu; Dydak, Ulrike; Radiology and Imaging Sciences, School of MedicineThe purpose of this work is to develop and validate a new atlas-based metabolite quantification pipeline for edited magnetic resonance spectroscopic imaging (MEGA-MRSI) that enables group comparisons of brain structure-specific GABA levels. By using brain structure masks segmented from high-resolution MPRAGE images and coregistering these to MEGA-LASER 3D MRSI data, an automated regional quantification of neurochemical levels is demonstrated for the example of the thalamus. Thalamic gamma-aminobutyric acid + coedited macromolecules (GABA+) levels from 21 healthy subjects scanned at 3 T were cross-validated both against a single-voxel MEGA-PRESS acquisition in the same subjects and same scan sessions, as well as alternative MRSI processing techniques (ROI approach, four-voxel approach) using Pearson correlation analysis. In addition, reproducibility was compared across the MRSI processing techniques in test-retest data from 14 subjects. The atlas-based approach showed a significant correlation with SV MEGA-PRESS (correlation coefficient r [GABA+] = 0.63, P < 0.0001). However, the actual values for GABA+, NAA, tCr, GABA+/tCr and tNAA/tCr obtained from the atlas-based approach showed an offset to SV MEGA-PRESS levels, likely due to the fact that on average the thalamus mask used for the atlas-based approach only occupied 30% of the SVS volume, ie, somewhat different anatomies were sampled. Furthermore, the new atlas-based approach showed highly reproducible GABA+/tCr values with a low median coefficient of variance of 6.3%. In conclusion, the atlas-based metabolite quantification approach enables a more brain structure-specific comparison of GABA+ and other neurochemical levels across populations, even when using an MRSI technique with only cm-level resolution. This approach was successfully cross-validated against the typically used SVS technique as well as other different MRSI analysis methods, indicating the robustness of this quantification approach.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 Cerebral Gray Matter Volume Losses in Essential Tremor: A Case-Control Study Using High Resolution Tissue Probability Maps(Elsevier, 2018) Cameron, Eric; Dyke, Jonathan P.; Hernandez, Nora; Louis, Elan D.; Dydak, Ulrike; Radiology and Imaging Sciences, School of MedicineIntroduction Essential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images. Methods MRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison. Results We were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls. Conclusion This study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well.Item COMPARISON OF BRAIN METABOLITE CHANGES IN MANGANESE-EXPOSED WELDERS AND SMELTERS(Office of the Vice Chancellor for Research, 2012-04-13) Long, Zaiyang; Jiang, Yueming; Li, Xiangrong; Xu, Jun; Long, Liling; Zheng, Wei; Murdoch, James; Dydak, UlrikeExcessive manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn overexposure occurs in different occupational settings, where the type and level of exposure may vary. Magnetic resonance imaging (MRI) and spectroscopy (MRS) can be used to evaluate brain Mn accumulation and to measure Mn-induced metabolite changes non-invasively. The aim of this study was to compare metabolite changes among different brain regions of welders and smelters following occupational Mn exposure. Nine Mn-exposed smelters, 14 Mn-exposed welders and 23 male matched controls were recruited from a cohort of workers from two factories in China (mean airborne Mn level: 0.227 and 0.025 mg/m3 for smelters and welders, respectively). Short-echo-time 1H MRS spectra were acquired in each subject from four volumes of interest: the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. We found that 1) in the frontal cortex, significantly decreased creatine (Cr), glutamate (Glu) and glutathione (GSH) were found in welders, whereas decreased Glu was found in smelters as compared to controls. 2) In the thalamus, reduced myo-inositol was found in both smelters and welders, while Glu and GSH were decreased in welders. These results suggest that Mn-induced brain metabolite changes may be regional in nature and more extensive in welders than in smelters. The frontal cortex seems to show a more profound change than the other brain areas tested among Mn exposed subjects. Further studies are needed to investigate the effects of exposure type and length on the mechanism of Mn neurotoxicity. (Supported by NIH/NIEHS R21 ES-017498, National Science Foundation of China Grant #81072320 and 30760210).Item 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 MedicineThe 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.Item Effect of Primidone on Dentate Nucleus γ-Aminobutyric Acid Concentration in Patients With Essential Tremor(Wolters Kluwer, 2016-01) Louis, Elan D.; Hernandez, Nora; Dyke, Jonathan P.; Ma, Ruoyun; Dydak, Ulrike; Department of Radiology and Imaging Sciences, IU School of MedicineOBJECTIVES: It is not known whether current use of the medication primidone affects brain γ-aminobutyric acid (GABA) concentrations. This is an important potential confound in studies of the pathophysiology of essential tremor (ET), one of the most common neurological diseases. We compared GABA concentrations in the dentate nucleus in 6 ET patients taking primidone versus 26 ET patients not taking primidone. METHODS: (1)H magnetic resonance spectroscopy was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in 2 cerebellar volumes of interest (left and right) that included the dentate nucleus. RESULTS: The right dentate GABA concentration was similar in the 2 groups (2.21 ± 0.46 [on primidone] vs 1.93 ± 0.39 [not on primidone], P = 0.15), as was the left dentate GABA concentration (1.61 ± 0.35 [on primidone] vs 1.67 ± 0.34 [not on primidone], P = 0.72). The daily primidone dose was not associated with either right or left dentate GABA concentrations (P = 0.89 and 0.76, respectively). CONCLUSIONS: We did not find a difference in dentate GABA concentrations between 6 ET patients taking daily primidone and 26 ET patients not taking primidone. Furthermore, there was no association between daily primidone dose and dentate GABA concentration. These data suggest that it is not necessary to exclude ET patients on primidone from magnetic resonance spectroscopy studies of dentate GABA concentration, and if assessment of these concentrations was to be developed as a biomarker for ET, primidone usage would not confound interpretation of the results.