Absolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations

doi:10.1006/jmrb.1993.1056

Journal of Magnetic Resonance, Series B

Volume 102, Issue 1, August 1993, Pages 9-19

https://doi.org/10.1006/jmrb.1993.1056 Get rights and content

Abstract

A method for determining absolute metabolite concentrations with in vivo¹H magnetic resonance spectroscopy is presented. Using the compartmentation model introduced in the preceding paper of this series (J. Magn. Reson. B102, 1, 1993), it is possible to express NMR results in terms of most commonly used concentration units. The proposed scheme, involving the measurement of an external standard as well as of the localized water signal, is verified on cerebral spectra obtained from 22 subjects. Besides concentrations, longitudinal and transverse relaxation times are determined for parietal white and occipital gray matter. The determination of these quantities crucially depends on the analysis of the T₂ signal decay as a function of echo time. The in vivo concentrations of the four metabolites N-acetyl aspartate, creatine plus phosphocreatine, choline, and myo-inositol are in good agreement with biochemical determinations performed in vitro. Two clinical examples emphasize the relevance of absolute quantitation in the investigation of human neuropathology and normal development.

References (0)

Cited by (508)

Meta-analysis and open-source database for in vivo brain Magnetic Resonance spectroscopy in health and disease
2023, Analytical Biochemistry
Proton (¹H) Magnetic Resonance Spectroscopy (MRS) is a non-invasive tool capable of quantifying brain metabolite concentrations in vivo. Prioritization of standardization and accessibility in the field has led to the development of universal pulse sequences, methodological consensus recommendations, and the development of open-source analysis software packages. One on-going challenge is methodological validation with ground-truth data. As ground-truths are rarely available for in vivo measurements, data simulations have become an important tool. The diverse literature of metabolite measurements has made it challenging to define ranges to be used within simulations. Especially for the development of deep learning and machine learning algorithms, simulations must be able to produce accurate spectra capturing all the nuances of in vivo data. Therefore, we sought to determine the physiological ranges and relaxation rates of brain metabolites which can be used both in data simulations and as reference estimates. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we've identified relevant MRS research articles and created an open-source database containing methods, results, and other article information as a resource. Using this database, expectation values and ranges for metabolite concentrations and T₂ relaxation times are established based upon a meta-analyses of healthy and diseased brains.
Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection
2021, NeuroImage
Citation Excerpt :
Cr+PCr, involved in the Krebs cycle, is a measure of cellular energy levels and Glu is an important excitatory neurotransmitter (Keller et al., 2006; Zhu and Barker, 2011). Few cross-sectional MRS studies have examined age-dependent regional metabolic changes from birth to adulthood, establishing that the most significant changes are in infancy (Blüml et al., 2013; Hashimoto et al., 1995; Kreis et al., 1993; Pouwels et al., 1999; van der Knaap et al., 1990). Within studies encompassing ages 5–11 years, some age-related changes in NAA levels as well as NAA/GPC+PCh or NAA/Cr+PCr ratios are reported in gray and white matter (Blüml et al., 2013; Horská et al., 2002; Kadota et al., 2001; Keller et al., 2004; Pouwels et al., 1999), with one study (Blüml et al., 2013) finding accompanying Cr+PCr levels increasing in gray matter.
Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation.
Elevated thalamic glutamate levels and reduced water diffusivity in alcohol use disorder: Association with impulsivity
2020, Psychiatry Research - Neuroimaging
Alcohol induces neuroinflammation but its role in cognitive impairment and impulsivity in alcohol use disorder (AUD) has been poorly investigated. We used proton magnetic resonance spectroscopy to measure brain glutamate (Glu) levels and diffusion-weighted imaging to measure functional anisotropy (FA) in the thalamus and ventral anterior cingulate cortex (vACC) in 15 recently detoxified patients with AUD and 14 matched controls. Compared to controls, AUD patients showed higher Glu levels (p = 0.04) and lower FA in the thalamus (p = 0.04) but not in the vACC. In AUD, thalamic Glu levels (r = 0.62, p = 0.019) and FA (r=-0.55, p = 0.034) were associated with severity of drinking (drinks/week). Compared to controls, AUD patients showed higher scores on Conners’ Adult ADHD Rating Scale for impulsivity (p = 0.03), which correlated with glutamate levels in the thalamus (r = 0.58, p = 0.03) and vACC (r = 0.55, p = 0.036). In a second cohort of AUD patients (n = 32), Glu in dorsal ACC (dACC) also correlated with Barrett Impulsiveness Scale total score (r = 0.43, p = 0.014). We interpret the elevated thalamic Glu levels and the parallel reduction in FA in AUD—which correlated with drinking severity—as possible evidence of neurotoxicity from neuroinflammation. The association of Glu with impulsivity suggests that neurotoxic effects of chronic alcohol exposure in the thalamus and dACC may contribute to impulsivity.
Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain
2024, Magnetic Resonance in Medicine
Improving magnetic resonance spectroscopy in the brainstem periaqueductal gray using spectral registration
2024, Magnetic Resonance in Medicine
Multi-echo single-shot spectroscopy combined with simultaneous 2D model fitting for fast and accurate measurement of metabolite-specific concentrations and T<inf>2</inf> relaxation times
2023, NMR in Biomedicine

View all citing articles on Scopus

View full text

Regular ArticleAbsolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations

Abstract

Regular Article
Absolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations