Dataset Information

Magnetic Field Dependence of Spectral Correlations between ³¹P-Containing Metabolites in Brain.

ABSTRACT: Spectral correlations between metabolites in ³¹P magnetic resonance spectroscopy (MRS) spectra of human brain were compared at 3 and 7 Tesla, the two commonly used magnetic field strengths for clinical research. It was found that at both field strengths, there are significant correlations between ³¹P-containing metabolites arising from spectral overlap, and their downfield correlations are markedly altered by the background spectral baseline. Overall, the spectral correlations between ³¹P-containing metabolites are markedly reduced at 7 Tesla with the increased chemical shift dispersion and the decreased membrane phospholipid signal. The findings provide the quantitative landscape of pre-existing correlations in ³¹P MRS spectra due to overlapping signals. Detailed procedures for quantifying the pre-existing correlations between ³¹P-containing metabolites are presented to facilitate incorporation of spectral correlations into statistical modeling in clinical correlation studies.

SUBMITTER: Hong S

PROVIDER: S-EPMC9967573 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Magnetic Field Dependence of Spectral Correlations between 31P-Containing Metabolites in Brain.

Hong Sungtak S Shen Jun J

Metabolites 20230131 2

Spectral correlations between metabolites in 31P magnetic resonance spectroscopy (MRS) spectra of human brain were compared at 3 and 7 Tesla, the two commonly used magnetic field strengths for clinical research. It was found that at both field strengths, there are significant correlations between 31P-containing metabolites arising from spectral overlap, and their downfield correlations are markedly altered by the background spectral baseline. Overall, the spectral correlati ...[more]

PMID: 36837829

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Project description:The phosphorus-31 (31P) spectral modulus (PSM) is a measure of the metabolic status of cells, tissues, and organs. The PSM can be calculated from 31P nuclear magnetic resonance (31P NMR) spectra obtained from cell, tissue, or organ preparations. These 31P NMR spectra can be a measure of intact living cells, tissues, or organs, or appropriate biochemical extracts of such preparations. The 31P NMR spectrum is comprised of signals derived from organophosphate metabolites that resonate from 10 δ to -25 δ on the phosphorus chemical shift δ scale. The PSM is the ratio of the high-energy phosphate to that of the low-energy phosphate spectral integrals. These integrals may be conveniently grouped into high-energy and low-energy spectral regions, respectively, into 31P chemical shifts located between -0.13 δ to -25 δ and between 10 δ to -0.13 δ. High-energy phosphates are typically described as providing the energy necessary for the activity of cellular metabolism; chemically, they contain one or more phosphate anhydride bonds. This study demonstrates that, (1) in general, the higher the metabolic activity, the higher the PSM, and (2) the modulus calculation does not require a highly resolved 31P spectrum and can be calculated solely from the integral. The PSM was calculated among cells, tissues, and organs considered normal, diseased, and stressed. In diseased (mean 1.29 ± 0.73) and stressed (mean 1.23 ± 0.75) cells, tissues, and organs, PSM values are typically low or low relative to normal cells, tissues, or organs (mean 1.65 ± 0.90), following time-course measurements, in dynamic decline. The PSM is useful in determining the metabolic status of cells, tissues, or organs and can be employed as a calculable numeric assay for determining health status statically or over time. Calculation of the PSM can be carried out with spectra of low signal-to-noise; it relies on the minimal resolution required to detect an integral curve having a clear spectral integral inflection point at ca. -0.13 δ. Detection of an integral curve alone enables the calculation of a PSM even at levels of phosphorus concentration so low as to prevent detection of the individual or groups of metabolites, such as with in vivo or ex vivo cell, tissue, or organ determinations. This study (1) presents the foundations and fundamentals of the PSM, a living index of tissue metabolic health, and (2) demonstrates the use of spectral scan analysis in opening new vistas of biology and medicine for measuring the metabolic status of stressed and diseased tissues at a range of detectable levels for monitoring therapeutic interventions.

Project description:IntroductionMitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer's disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study's first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups.MethodsForty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH].ResultsThirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD.ConclusionTo our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.

Dataset Information

Magnetic Field Dependence of Spectral Correlations between ³¹P-Containing Metabolites in Brain.

Publications

Magnetic Field Dependence of Spectral Correlations between <sup>31</sup>P-Containing Metabolites in Brain.

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