Browsing by Subject "Magnetic resonance spectroscopy"
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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 iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study(Elsevier, 2018-01) Casjens, Swaantje; Dydak, Urike; Dharmadhikari, Shalmali; Lotz, Anne; Lehnert, Martin; Quetscher, Clara; Stewig, Christoph; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Edmondson, David; Yeh, Chien-Lin; Weiss, Tobias; van Thriel, Christoph; Herrmann, Lennard; Muhlack, Siegfried; Woitalla, Dirk; Aschner, Michael; Brüning, Thomas; Pesch, Beate; Radiology and Imaging Sciences, School of MedicineOBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). RESULTS: The median shift exposure to respirable Mn and Fe in active welders was 23μg/m3 and 110μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β)=0.87, p<0.01) and choline (exp(β)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. CONCLUSIONS: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.Item DHA Modifies the Size and Composition of Raftlike Domains: A Solid-State 2H NMR Study(Elsevier, 2018-01-23) Kinnun, Jacob J.; Bittman, Robert; Shaikh, Saame Raza; Wassall, Stephen R.; Physics, School of ScienceDocosahexaenoic acid is an omega-3 polyunsaturated fatty acid that relieves the symptoms of a wide variety of chronic inflammatory disorders. The structural mechanism is not yet completely understood. Our focus here is on the plasma membrane as a site of action. We examined the molecular organization of [2H31]-N-palmitoylsphingomyelin (PSM-d31) mixed with 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), as a monounsaturated control, and cholesterol (chol) (1:1:1 mol) in a model membrane by solid-state 2H NMR. The spectra were analyzed in terms of segregation into ordered SM-rich/chol-rich (raftlike) and disordered PC-rich/chol-poor (nonraft) domains that are nanoscale in size. An increase in the size of domains is revealed when POPC was replaced by PDPC. Spectra that are single-component, attributed to fast exchange between domains (<45 nm), for PSM-d31 mixed with POPC and chol become two-component, attributed to slow exchange between domains (r > 30 nm), for PSM-d31 mixed with PDPC and chol. The resolution of separate signals from PSM-d31, and correspondingly from [3α-2H1]cholesterol (chol-d1) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31), in raftlike and nonraft domains enabled us to determine the composition of the domains in the PDPC-containing membrane. Most of the lipid (28% SM, 29% chol, and 23% PDPC with respect to total lipid at 30°C) was found in the raftlike domain. Despite substantial infiltration of PDPC into raftlike domains, there appears to be minimal effect on the order of SM, implying the existence of internal structure that limits contact between SM and PDPC. Our results suggest a significant refinement to the model by which DHA regulates the architecture of ordered, sphingolipid-chol-enriched domains (rafts) in membranes.Item Frontal Metabolites and Alzheimer’s Disease Biomarkers in Healthy Older Women and Women Diagnosed with Mild Cognitive Impairment(IOS Press, 2022) Hone-Blanchet, Antoine; Bohsali, Anastasia; Krishnamurthy, Lisa C.; Shahid, Salman S.; Lin, Qixiang; Zhao, Liping; Bisht, Aditya S.; John, Samantha E.; Loring, David; Goldstein, Felicia; Levey, Allan; Lah, James; Qiu, Deqiang; Crosson, Bruce; Radiology and Imaging Sciences, School of MedicineBackground: Women account for two thirds of the prevalence and incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Evidence suggest that sex may differently influence the expression of proteins amyloid-beta (Aβ1-42) and tau, for which early detection is crucial in prevention of the disease. Objective: We investigated the effect of aging and cerebrospinal fluid (CSF) levels of Aβ1-42 and tau on frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) in a cohort of cognitively normal older women and women with MCI. Methods: 3T single-voxel MRS was performed on the medial frontal cortex, using Point Resolved Spectroscopy (PRESS) and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) in 120 women (age range 50-85). CSF samples of Aβ1-42 and tau and scores of general cognition were also obtained. Results: Levels of frontal gamma aminobutyric acid (GABA+) were predicted by age, independently of disease and CSF biomarkers. Importantly, levels of GABA+ were reduced in MCI patients. Additionally, we found that levels of N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and were not related to CSF biomarkers. Conclusion: This study is the first to demonstrate a strong association between frontal GABA+ levels and neurological aging in a sample consisting exclusively of healthy older women with various levels of CSF tau and Aβ1-42 and women with MCI. Importantly, our results show no correlation between CSF biomarkers and MRS metabolites in this sample.Item Impairment of Motor Function Correlates with Neurometabolite and Brain Iron Alterations in Parkinson’s Disease(MDPI, 2019-01-29) Pesch, Beate; Casjens, Swaantje; Woitalla, Dirk; Dharmadhikari, Shalmali; Edmondson, David A.; Zella, Maria Angela Samis; Lehnert, Martin; Lotz, Anne; Herrmann, Lennard; Muhlack, Siegfried; Kraus, Peter; Yeh, Chien-Lin; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Gold, Ralf; van Thriel, Christoph; Brüning, Thomas; Tönges, Lars; Dydak, Ulrike; Department of Radiology and Imaging Sciences, Indiana University School of MedicineWe took advantage of magnetic resonance imaging (MRI) and spectroscopy (MRS) as non-invasive methods to quantify brain iron and neurometabolites, which were analyzed along with other predictors of motor dysfunction in Parkinson's disease (PD). Tapping hits, tremor amplitude, and the scores derived from part III of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS3 scores) were determined in 35 male PD patients and 35 controls. The iron-sensitive MRI relaxation rate R2* was measured in the globus pallidus and substantia nigra. γ-aminobutyric acid (GABA)-edited and short echo-time MRS was used for the quantification of neurometabolites in the striatum and thalamus. Associations of R2*, neurometabolites, and other factors with motor function were estimated with Spearman correlations and mixed regression models to account for repeated measurements (hands, hemispheres). In PD patients, R2* and striatal GABA correlated with MDS-UPDRS3 scores if not adjusted for age. Patients with akinetic-rigid PD subtype (N = 19) presented with lower creatine and striatal glutamate and glutamine (Glx) but elevated thalamic GABA compared to controls or mixed PD subtype. In PD patients, Glx correlated with an impaired dexterity when adjusted for covariates. Elevated myo-inositol was associated with more tapping hits and lower MDS-UPDRS3 scores. Our neuroimaging study provides evidence that motor dysfunction in PD correlates with alterations in brain iron and neurometabolites.Item In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls(Springer Nature, 2018-04) Louis, Elan D.; Hernandez, Nora; Dyke, Jonathan P.; Ma, Ruoyun E.; Dydak, Ulrike; Radiology and Imaging Sciences, School of MedicineDespite its high prevalence, essential tremor (ET) is among the most poorly understood neurological diseases. The presence and extent of Purkinje cell (PC) loss in ET is the subject of controversy. PCs are a major storehouse of central nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA concentration could be an in vivo marker of PC number. We used in vivo 1H magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two cerebellar volumes of interest, left and right, which included the dentate nucleus, comparing 45 ET cases to 35 age-matched controls. 1H MRS was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in two cerebellar volumes of interest (left and right) that included the dentate nucleus. The two groups did not differ with respect to our primary outcome of GABA concentration (given in institutional units). For the right dentate nucleus, [GABA] in ET cases = 2.01 ± 0.45 and [GABA] in controls = 1.86 ± 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases = 1.68 ± 0.49 and [GABA] controls = 1.80 ± 0.53, p = 0.33. The controls had similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52); however, in ET cases, the value on the right was considerably higher than that on the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA concentration in ET cases vs. CONTROLS: One interpretation of the finding is that it does not support the existence of PC loss in ET; however, an alternative interpretation is the observed pattern could be due to the effects of terminal sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the loss of GABA-ergic terminals from PC degeneration). Further research is needed.Item An Investigation of Neurochemical Changes in Chronic Cannabis Users(Frontiers Media, 2019-09-19) Newman, Sharlene D.; Cheng, Hu; Martin, Ashley Schnakenberg; Dydak, Ulrike; Dharmadhikari, Shalmali; Hetrick, William; O’Donnell, Brian; Radiology and Imaging Sciences, School of MedicineWith the legalization of recreational cannabis (CB) the characterization of how it may impact brain chemistry is essential. Magnetic resonance spectroscopy (MRS) was used to examine neurometabolite concentrations in the dorsal anterior cingulate (dACC) in chronic CB users (N = 26; 10 females) and controls (N = 24; 10 females). The concentrations of glutamate (Glu), total creatine (tCr), choline (Cho), total N-acetylaspartate (tNAA), and myo-inositol (mI) were estimated using LCModel. The ANCOVAs failed to show significant differences between controls and CB users. Regression analyses were then performed on the CB group to model each neurometabolite to determine its relationship to monthly CB use, sex, the interaction between CB use and sex. tCr was found to be predicted by both monthly CB use and sex. While the regression model was not significant the relationship between monthly CB use and Glu appears to be modulated by sex with the effect of monthly use (dose) being stronger in males. tNAA failed to show an effect of CB use but did reveal an effect of sex with females showing larger tNAA levels. Although the results presented are preliminary due to the small sample size they do guide future research. The results presented provide direction for further studies as they suggest that dose may significantly influence the observance of CB effects and that those effects may be modulated by sex. Studies with significantly larger sample sizes designed specifically to examine individuals with varying usage as well as sex effects are necessary.Item Location of dopamine in lipid bilayers and its relevance to neuromodulator function(Elsevier, 2023) Shafieenezhad, Azam; Mitra, Saheli; Wassall, Stephen R.; Tristram-Nagle, Stephanie; Nagle, John F.; Petrache, Horia I.; Physics, School of ScienceDopamine (DA) is a neurotransmitter that also acts as a neuromodulator, with both functions being essential to brain function. Here, we present the first experimental measurement of DA location in lipid bilayers using x-ray diffuse scattering, solid-state deuterium NMR, and electron paramagnetic resonance. We find that the association of DA with lipid headgroups as seen in electron density profiles leads to an increase of intermembrane repulsion most likely due to electrostatic charging. DA location in the lipid headgroup region also leads to an increase of the cross-sectional area per lipid without affecting the bending rigidity significantly. The order parameters measured by solid-state deuterium NMR decrease in the presence of DA for the acyl chains of PC and PS lipids, consistent with an increase in the area per lipid due to DA. Most importantly, these results support the hypothesis that three-dimensional diffusion of DA to target membranes could be followed by relatively more efficient two-dimensional diffusion to receptors within those membranes.Item A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder(Wiley, 2020-04) Edmondson, David A.; Xia, Pingyu; McNally Keehn, Rebecca; Dydak, Ulrike; Keehn, Brandon; Radiology and Imaging Sciences, School of MedicineAlthough diagnosed on the basis of deficits in social communication and interaction, autism spectrum disorder (ASD) is also characterized by superior performance on a variety of visuospatial tasks, including visual search. In neurotypical individuals, region-specific concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) are associated with individual differences in attention and perception. While it has been hypothesized that ASD may be associated with an excitatory-inhibitory imbalance, it remains unclear how this may contribute to accelerated visual search performance in individuals with ASD. To investigate this, 21 children with ASD and 20 typically developing children participated in a visual search task and a magnetic resonance spectroscopy study to detect neurochemical concentrations, including GABA. Region-specific neurochemicals were examined in the right frontal eye fields, right temporal-parietal junction (rTPJ), and bilateral visual cortex (VIS). GABA concentrations did not differ between groups; however, in children with ASD, greater GABA concentration in the VIS was related to more efficient search. Additionally, lower VIS GABA levels were also associated with increased social impairment. Finally, we found reduced N-acetyl aspartate, total creatine, glutamate and glutamine (Glx), GABA/Glx in the rTPJ, suggestive of neuronal dysfunction in a critical network hub. Our results show that GABA concentrations in the VIS are related to efficient search in ASD, thus providing further evidence of enhanced discrimination in ASD. Autism Res 2020, 13: 550-562. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum disorder (ASD) often perform better than their non-ASD peers on visual search tasks; however, it is unclear how they achieve this superior performance. Using magnetic resonance spectroscopy to measure neurochemicals in the brain, we found that the level of one, gamma-aminobutyric acid, in the visual cortex was directly related to search abilities in children with ASD. These results suggest that faster search may relate to enhanced perceptual functioning in children with ASD.Item Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults(Elsevier, 2022) Hone-Blanchet, Antoine; Bohsali, Anastasia; Krishnamurthy, Lisa C.; Shahid, Salman; Lin, Qixiang; Zhao, Liping; Loring, David; Goldstein, Felicia; John, Samantha E.; Fleischer, Candace C.; Levey, Allan; Lah, James; Qiu, Deqiang; Crosson, Bruce; Radiology and Imaging Sciences, School of MedicineElevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.