Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra.

Michaelis, Thomas; Merboldt, Klaus‐Dietmar; Bruhn, H.; Hänicke, W.; Frahm, Jens

doi:10.1148/radiology.187.1.8451417

Cited by 529 publications

(442 citation statements)

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“…For example, glucose is detectable in the CSF at over three times its concentration in GM or WM 28, 29, 30. This is also the case for lactate, which is detectable in CSF but negligible in normal brain tissue 26.…”

Section: Methodsmentioning

confidence: 90%

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Mullins

Reiter

Kapogiannis

2018

Ann Clin Transl Neurol

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ObjectiveBrain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case–control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD‐related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.MethodsJ‐modulated Point‐Resolved Spectroscopy (J‐PRESS) and Prior‐Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers.Results AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo‐inositol correlated with CSF p‐Tau181P, total Tau, and the Clinical Dementia Rating (CDR) sum‐of‐boxes score within the AD group.InterpretationHigher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker.

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Section: Methodsmentioning

confidence: 90%

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Mullins

Reiter

Kapogiannis

2018

Ann Clin Transl Neurol

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“…The absolute in vivo brain metabolite concentrations are the subject of an ongoing debate in the literature, a result of different levels reported by different groups (17). These variations are attributed, in the order they are encountered, to: 1) hardware (coils, field strength, and RF electronics); 2) localization techniques used (single voxel vs. 2D or 3D multivoxel acquisition methods); 3) reconstruction strategies and their approach to baseline irregularities, peak area estimation, voxel "bleed," and partial volumes; and 4) quantification methods, internal vs. external standards, and correction for B 0 , B 1 , T 1, T 2 , TE, TR, etc.…”

Section: Discussionmentioning

confidence: 99%

“…These variations are attributed, in the order they are encountered, to: 1) hardware (coils, field strength, and RF electronics); 2) localization techniques used (single voxel vs. 2D or 3D multivoxel acquisition methods); 3) reconstruction strategies and their approach to baseline irregularities, peak area estimation, voxel "bleed," and partial volumes; and 4) quantification methods, internal vs. external standards, and correction for B 0 , B 1 , T 1, T 2 , TE, TR, etc. (17). To circumvent controversy, we assessed reproducibility rather than absolute levels.…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of 3D proton spectroscopy in the human brain

Babb

Soher

et al. 2002

Magnetic Resonance in Med

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The inter-and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy ( 1 H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, ؎1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm 3 voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels Key words: absolute quantification; brain; multivoxel localization; proton spectroscopy; reproducibility 1 H-MRS frequently augments MRI in studies of focal as well as diffuse brain pathologies, e.g., for multiple sclerosis (MS), cancer, AIDS, trauma, Alzheimer's disease (AD), and stroke (1). Due to the progressive nature of these disorders, MRS is usually performed serially, over time, to assess the disease's advance or its response to treatment. The evaluation of the MRS data is based primarily on the comparison of either relative or absolute levels of the three major 1 H-MRS-observable metabolites: NAA, Cr, and Cho, in regions of suspected pathology, with corresponding healthy ones. Reported metabolite variations in these diseases range between 10 -20% for HIV infection and focal epilepsy to upwards of 30% in MS and AD (1).However, to objectively evaluate the significance of such changes, it is necessary to establish how reproducible the measured metabolite levels are in normal controls, both cross-sectionally and temporally. Only then, when changes in suspected region(s) in a patient are significant compared with these normal variations, can one be confident that they represent true pathology and not normal biological fluctuations or intrinsic errors of the instrumentation and method(s).To address the reproducibility issues, we conducted a study to identify and quantify the: 1) stability of the machine and the methodology, using back-to-back measurements on a phantom; 2) intraindividual temporal variations in the brain of a volunteer; and 3) interindividual variations across a cohort of healthy subjects. Previous studies on this topic mostly employed single-voxel MRS techniques (2-5), and more recently, s...

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“…No T 2 correction was performed, because acetate spectra were acquired with TE ϭ 30 ms, that is much shorter than acetate T 2 relaxation time (ա 400 ms). For each spectrum a correction was performed for different coil loading between the in vivo and the phantom measurements (10,11).…”

Section: Quantitative 1 H-mrsmentioning

confidence: 99%

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

Guerrini

Belli

Mazzoni

et al. 2009

Magnetic Resonance Imaging

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Purpose:To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel 1 H-MRS in normal subjects and patients with degenerative ataxias. Materials and Methods:Twenty-nine healthy volunteers and 38 patients with degenerative ataxias and cerebellar atrophy were examined on a 1.5 Tesla scanner. Proton spectra of a volume of interest placed in the superior vermis were acquired using a four TE PRESS technique. We calculated N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios, T 2 relaxation times and concentrations of the same metabolites using the external phantom method. Finally, concentrations were corrected taking into account the proportion of nervous tissue and CSF, that was determined as Volume Fraction (VF). Results:In healthy subjects, a significant difference was observed between metabolite concentrations with and without correction for VF. As compared to controls, patients with ataxias showed significantly reduced NAA/Cr and NAA concentrations, while only corrected Cr concentration was significantly increased. The latter showed an inverse correlation with VF. Conclusion:CSF contamination has a not negligible effect on the estimation of brain metabolites. The increase of Cr concentration in patients with cerebellar atrophy presumably reflects the substitutive gliosis which takes place along with loss of neurons. EVALUATION IN VIVO of the amount of the brain metabolites with proton MR spectroscopy ( 1 H-MRS) is an important clinical tool in several diseases (1). This can be accomplished using a semiquantitative approach, in which metabolite ratios are computed by assuming that a reference metabolite, usually creatine (Cr), is constant, or using a quantitative approach in which the concentration of each brain metabolite is determined with several different techniques. These include external phantoms, reference to water signal, and compartmental analysis (2).A controversial issue in clinical 1 H-MRS of the brain is the evaluation of spectra obtained from volume of interest (VOI) containing cerebrospinal fluid (CSF). In particular, it is unclear the relevance of correction for the CSF contained in the VOI. In a prior study corrections from CSF inclusion were found to decrease the coefficient of variation of spectral data acquired in the hippocampus (3).The peripheral cerebellum is a region particularly suited to investigate the impact of CSF contamination on metabolite assessment. In fact, because of the thinness of the cerebellar folia, spectra of the peripheral cerebellum contain variable amounts of nervous tissue and CSF also in normal subjects. While spectra from the cerebellar hemispheres can be of suboptimal quality due to difficult shimming caused by the nearby skull and blood flow in the venous dural sinuses, good quality spectra are consistently obtained when the VOI is placed in the superior vermis (4).To investigate the impact of CSF contamination on the metabolite evaluation we examined the c...

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Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra.

Cited by 529 publications

References 0 publications

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Reproducibility of 3D proton spectroscopy in the human brain

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

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Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra.

Cited by 529 publications

References 0 publications

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Reproducibility of 3D proton spectroscopy in the human brain

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

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Impact of cerebrospinal fluid contamination on brain metabolites evaluation with ¹H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias