Dataset Information

Integrating ¹H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans.

ABSTRACT: In the technique presented here, dubbed 'qMRS', we quantify the change in ¹H MRS signal following administration of ²H-labeled glucose. As in recent human DMRS studies, we administer [6,6'-²H₂]-glucose orally to healthy subjects. Since ²H is not detectable by ¹H MRS, the transfer of the ²H label from glucose to a downstream metabolite leads to a reduction in the corresponding ¹H MRS resonance of the metabolite, even if the total concentration of both isoforms remains constant. Moreover, introduction of the deuterium label alters the splitting pattern of the proton resonances, making indirect detection of the deuterated forms- as well as the direct detection of the decrease in unlabeled form- possible even without a ²H coil. Because qMRS requires only standard ¹H MRS acquisition methods, it can be performed using commonly implemented single voxel spectroscopy (SVS) and chemical shift imaging (CSI) sequences. In this work, we implement qMRS in semi-LASER based CSI, generating dynamic maps arising from the fitted spectra, and demonstrating the feasibility of using qMRS and qCSI to monitor dynamic metabolism in the human brain using a 7T scanner with no auxiliary hardware.

SUBMITTER: Cember ATJ

PROVIDER: S-EPMC9166154 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans.

Cember Abigail T J ATJ Wilson Neil E NE Rich Laurie J LJ Bagga Puneet P Nanga Ravi Prakash Reddy RPR Swago Sophia S Swain Anshuman A Thakuri Deepa D Elliot Mark M Schnall Mitchell D MD Detre John A JA Reddy Ravinder R

NeuroImage 20220207

In the technique presented here, dubbed 'qMRS', we quantify the change in 1H MRS signal following administration of 2H-labeled glucose. As in recent human DMRS studies, we administer [6,6'-2H2]-glucose orally to healthy subjects. Since 2H is not detectable by 1H MRS, the transfer of the 2H label from glucose to a downstream metabolite leads to a reduction in the corresponding 1H MRS resonance of the metabolit ...[more]

PMID: 35143973

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Project description:BackgroundPrevious literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM.MethodsA total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal-Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction.ResultsThere were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p < 0.001). The prevalence of nonalcoholic fatty liver disease (NAFLD) was also found to be increased in nT2DM (91.48%) than in PDM (85.41%) and that of NC (32.07%) groups. Correlation analysis revealed that the increase of LFC positively associated with fast plasma glucose (FPG), 2 h plasma glucose (PG), Delta G30 and homeostatic model assessment of insulin resistance (HOMA-IR), negatively associated with Delta Ins30, Delta C30, Ins30/G30 AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for β-cell function index (HOMA-β) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-β.ConclusionsOur study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.

Project description:IntroductionDeuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6'- 2 H 2 ]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2 H MRSI (DMI) and 1 H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T.MethodsFive volunteers (4m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8g/kg oral [6,6'- 2 H 2 ]-glucose administration using time-resolved 3D 2 H FID-MRSI with elliptical phase encoding at 7T and 3D 1 H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T.ResultsOne hour after oral tracer administration regionally averaged deuterium labeled Glx 4 concentrations and the dynamics were not significantly different over all participants between 7T 2 H DMI and 3T 1 H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc 6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2 H and 1 H data points a weak to moderate negative correlation was observed for Glx 4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc 6 data GM (r=- 0.61, p<0.001) and WM (r=-0.70, p<0.001).ConclusionThis study demonstrates that indirect detection of deuterium labeled compounds using 1 H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2 H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.

Project description:BackgroundSupply of choline is not guaranteed in current preterm infant nutrition. Choline serves in parenchyma formation by membrane phosphatidylcholine (PC), plasma transport of poly-unsaturated fatty acids (PUFA) via PC, and methylation processes via betaine. PUFA-PC concentrations are high in brain, liver and lung, and deficiency may result in developmental disorders. We compared different deuterated (D9-) choline components for kinetics of D9-choline, D9-betaine and D9-PC.MethodsProspective study (1/2021-12/2021) in 32 enterally fed preterm infants (28 0/7-32 0/7 weeks gestation). Patients were randomized to receive enterally a single dose of 2.7 mg/kg D9-choline-equivalent as D9-choline chloride, D9-phosphoryl-choline, D9-glycerophosphorylcholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-PC(D9-POPC), followed by blood sampling at 1 + 24 h or 12 + 60 h after administration. Plasma concentrations were analyzed by tandem mass spectrometry. Results are expressed as median (25th/75th percentile).ResultsAt 1 h, plasma D9-choline was 1.8 (0.9/2.2) µmol/L, 1.3 (0.9/1.5) µmol/L and 1.2 (0.7/1.4) µmol/L for D9-choline chloride, D9-GPC and D9-phosphoryl-choline, respectively. D9-POPC did not result in plasma D9-choline. Plasma D9-betaine was maximal at 12 h, with lowest concentrations after D9-POPC. Maximum plasma D9-PC values at 12 h were the highest after D9-POPC (14.4 (9.1/18.9) µmol/L), compared to the other components (D9-choline chloride: 8.1 [5.6/9.9] µmol/L; D9-GPC: 8.4 (6.2/10.3) µmol/L; D9-phosphoryl-choline: 9.8 (8.6/14.5) µmol/L). Predominance of D9-PC comprising linoleic, rather than oleic acid, indicated fatty-acyl remodeling of administered D9-POPC prior to systemic delivery.ConclusionD9-Choline chloride, D9-GPC and D9-phosphoryl-choline equally increased plasma D9-choline and D9-betaine. D9-POPC shifted metabolism from D9-betaine to D9-PC. Combined supplementation of GPC and (PO) PC may be best suited to optimize choline supply in preterm infants. Due to fatty acid remodeling of (PO) PC during its assimilation, PUFA co-supplementation with (PO) PC may increase PUFA-delivery to critical organs. This study was registered (22.01.2020) at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502.Study registrationThis study was registered at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502.

Dataset Information

Integrating ¹H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans.

Publications

Integrating <sup>1</sup>H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans.

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