Dataset Information

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

ABSTRACT:

Introduction

Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.

Methods

In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (³¹P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.

Results

The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.

Discussion

These results illustrate favorable outcomes of our first attempt to use ultrahigh field ³¹P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

SUBMITTER: Guo R

PROVIDER: S-EPMC11190064 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Guo Rong R Yang Shaolin S Wiesner Hannes M HM Li Yudu Y Zhao Yibo Y Liang Zhi-Pei ZP Chen Wei W Zhu Xiao-Hong XH

Frontiers in neuroscience 20240607

<h4>Introduction</h4>Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for <i>in vivo</i> measurement and imaging.<h4>Methods</h4>In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic reson ...[more]

PMID: 38911598

Similar Datasets

Project description:PurposePhosphorus (31 P) metabolites are emerging liver disease biomarkers. Of particular interest are phosphomonoester and phosphodiester (PDE) "peaks" that comprise multiple overlapping resonances in 31 P spectra. This study investigates the effect of improved spectral resolution at 7 Tesla (T) on quantifying hepatic metabolites in cirrhosis.MethodsFive volunteers were scanned to determine metabolite T1 s. Ten volunteers and 11 patients with liver cirrhosis were scanned at 7T. Liver spectra were acquired in 28 min using a 16-channel 31 P array and 3D chemical shift imaging. Concentrations were calculated using γ-adenosine-triphosphate (γ-ATP) = 2.65 mmol/L wet tissue.ResultsT1 means ± standard deviations: phosphatidylcholine 1.05 ± 0.28 s, nicotinamide-adenine-dinucleotide (NAD+ ) 2.0 ± 1.0 s, uridine-diphosphoglucose (UDPG) 3.3 ± 1.4 s. Concentrations in healthy volunteers: α-ATP 2.74 ± 0.11 mmol/L wet tissue, inorganic phosphate 2.23 ± 0.20 mmol/L wet tissue, glycerophosphocholine 2.34 ± 0.46 mmol/L wet tissue, glycerophosphoethanolamine 1.50 ± 0.28 mmol/L wet tissue, phosphocholine 1.06 ± 0.16 mmol/L wet tissue, phosphoethanolamine 0.77 ± 0.14 mmol/L wet tissue, NAD+ 2.37 ± 0.14 mmol/L wet tissue, UDPG 2.00 ± 0.22 mmol/L wet tissue, phosphatidylcholine 1.38 ± 0.31 mmol/L wet tissue. Inorganic phosphate and phosphatidylcholine concentrations were significantly lower in patients; glycerophosphoethanolamine concentrations were significantly higher (P < 0.05).ConclusionWe report human in vivo hepatic T1 s for phosphatidylcholine, NAD+ , and UDPG for the first time at 7T. Our protocol allows high signal-to-noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med 78:2095-2105, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Project description:Study objectivesPrimary insomnia (PI) is a sleep disorder characterized by difficulty with sleep initiation, maintenance, and/or the experience of nonrestorative sleep combined with a subsequent impairment of daytime functioning. The hyperarousal hypothesis has emerged as the leading candidate to explain insomnia symptoms in the absence of specific mental, physical, or substance-related causes. We hypothesized that the cellular energetic metabolites, including beta nucleoside triphosphate, which in magnetic resonance spectroscopy approximates adenosine triphosphate (ATP), and phosphocreatine (PCr), would show changes in PI reflecting increased energy demand.Design and settingMatched-groups, cross-sectional study performed at two university-based hospitals.PatientsSixteen medication-free individuals (eight males, eight females; mean ± standard deviation (SD) age = 37.2 ± 8.4 y) with PI and 16 good sleepers (nine males, seven females; mean ± SD age = 37.6 ± 4.7 y).MeasurementsDiagnosis was established for all individuals by unstructured clinical interview, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), sleep diary, and actigraphy. Polysomnography was collected in individuals with PI. Phosphorous magnetic resonance spectroscopy (31P MRS) data were collected on all individuals at 4 Tesla. We assessed cell membrane (anabolic precursors and catabolic metabolites) and bioenergetic (ATP, phosphocreatine) metabolites in gray matter and white matter to determine their relationship to the presence and severity of PI.ResultsIndividuals with PI showed lower phosphocreatine in gray matter and an unexpected decrease of phosphocholine, a precursor of the cell membrane compound phosphatidylcholine, in white matter. In addition, there was a trend toward a negative association between polysomnographically determined wake after sleep onset and gray matter beta-nucleoside triphosphate and white matter phosphocholine in the primary insomnia group.ConclusionsThese results support the hyperarousal hypothesis in PI based on lower phosphocreatine in gray matter in the PI group.

Project description:Nonalcoholic fatty liver disease (NAFLD) is a growing health problem, and a major challenge in NAFLD management is identifying which patients are at risk of progression to more serious disease. Simple measurements of liver fat content are not strong predictors of clinical outcome, but biomarkers related to fatty acid composition (ie, saturated vs. unsaturated fat) may be more effective. MR spectroscopic imaging (MRSI) methods allow spatially resolved, whole-liver measurements of chemical composition but are traditionally limited by slow acquisition times. In this work we present an accelerated MRSI acquisition based on spin echo single point imaging (SE-SPI), which, using appropriate sampling and compressed sensing reconstruction, allows free-breathing acquisition in a mouse model of fatty liver disease. After validating the technique's performance in oil/water phantoms, we imaged mice that had received a normal diet or a methionine and choline deficient (MCD) diet, some of which also received supplemental injections of iron to mimic hepatic iron overload. SE-SPI was more resistant to the line-broadening effects of iron than single-voxel spectroscopy measurements, and was consistently able to measure the amplitudes of low-intensity spectral peaks that are important to characterizing fatty acid composition. In particular, in the mice receiving the MCD diet, SE-SPI showed a significant decrease in a metric associated with unsaturated fat, which is consistent with the literature. This or other related metrics may therefore offer more a specific biomarker of liver health than fat content alone. This preclinical study is an important precursor to clinical testing of the proposed method. MR-based quantification of fatty acid composition may allow for improved characterization of non-alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole-liver mapping of fat composition metrics in a free-breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared to a normal diet; such metrics may prove useful in future clinical studies of liver disease.

Dataset Information

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction

Methods

Results

Discussion

Publications

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets