Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types

Urenjak, Jutta; Williams, Steve; Gadian, David G.; Noble, Mark

doi:10.1523/jneurosci.13-03-00981.1993

Cited by 934 publications

(620 citation statements)

References 47 publications

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“…Therefore, Glu reduction with age may signify deficits in neuronal metabolism or possible neuronal loss or shrinkage during normal aging. NAA, like Glu, is also localized primarily in neurons and is considered to be a putative neuronal marker [27,42]. Our finding of reduced NAA in the motor cortex region with normal aging is consistent with previous MRS studies that demonstrated decreased NAA with age in certain regions of the normal brain [4,6,35].…”

Section: Discussionsupporting

confidence: 92%

“…Several 1 H MRS studies demonstrated that compared to younger populations, older subjects have reduced cerebral N-acetyl aspartate (NAA), a putative neuronal marker [27,42], suggesting neuronal loss or deficit in neuronal metabolism [4,6,35]. Since Glu is also located primarily in neurons [28,29] and its concentration in the brain most likely reflects neuronal integrity, it should also decrease with age, similar to the NAA.…”

Section: Introductionmentioning

confidence: 99%

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Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Kaiser

Schuff

Cashdollar

et al. 2005

Neurobiology of Aging

219

150

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Proton magnetic resonance spectroscopy was performed at 4 T to determine effects of age, region and gender on glutamate and glutamine in the normal human brain. Furthermore, glutamate and glutamine alterations with age were tested for correlations with other cerebral metabolites. Two 8 cm 3 volumes were selected in corona radiata and mesial motor cortex in normal subjects (N = 24) between 24 and 68 years old. Older subjects had lower glutamate concentration in the motor cortex compared to younger subjects (p < 0.001). In corona radiata, older subjects demonstrated a trend in higher glutamine compared to younger subjects (p = 0.05). Glutamate in the motor cortex was positively correlated with glutamine, N-acetyl aspartate and creatine. Reduced glutamate and Nacetyl aspartate in the motor cortex is consistent with neuronal loss/shrinkage with age. In conclusion, different patterns in association with normal aging in these brain regions were detected in this study.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Kaiser

Schuff

Cashdollar

et al. 2005

Neurobiology of Aging

219

150

View full text Add to dashboard Cite

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“…Another explanation is that the [Cr] corr increase is a general phenomenon associated with the gliosis often co-existing with brain atrophy at the neuropathological examination in patients with degenerative diseases of the CNS (27). This explanation is in line with the observations that [Cr] is higher in astrocytes than in neurons (28,29) and that neurodegeneration suggests death of NAA containing neurons which are partially substituted by proliferation of glial cells. This hypothesis was purported in a prior study in patients with ataxia (23) but needs to be further investigated.…”

Section: Discussionsupporting

confidence: 90%

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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“…In rodents, methamphetamine administration has been shown to increase glial cells (Hess et al 1990;Pu and Vorhees 1993), and the increased levels of Cho are found in glial cells (Urenjak et al 1993). Therefore, the decrease in CrϩPCr/Cho could be accounted by the elevated Cho level in methamphetamine users.…”

Section: Discussionmentioning

confidence: 99%

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

Sekine

Minabe

Kawai

et al. 2002

Neuropsychopharmacology

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Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users.In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr ϩ PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) The number of abusers of the highly addictive drug methamphetamine has risen substantially worldwide and this has raised important concerns (Woolverton et al. 1984;Baberg et al. 1996;Shaw 1999). For example, chronic methamphetamine users show psychosis and anxiety following intoxication and withdrawal (Seivewright 2000). In addition, in some individuals, these psychiatric states may be present for months or even years after cessation of methamphetamine use (Sato et al. 1992;Iwanami et al. 1994;Buffenstein et al. 1999;Iyo et al. 1999). Although there are growing clinical observations on the neurotoxicology of chronic methamphetamine use, the mechanism by which the residual psychiatric problems arise from chronic methamphetamine NO . 3 use remains unknown. In rodents and baboons, methamphetamine has been shown to be toxic to dopaminergic and serotonergic neurons (Nakayama et al. 1993;Villemagne et al. 1998;Kokoshka et al. 1998). These neurotoxic effects include decreased concentrations of dopamine and serotonin in the brain and a reduction of dopamine and serotonin transporters, as well as loss of ATP and mitochondrial dysfunction in dopaminergic neurons (Chan et al. 1994;Burrows et al. 2000;Lotharius and O'Malley 2001). Human positron emission tomography (PET) studies have reported a significant reduction of dopamine transporter density in methamphetamine users Volkow et al. 2001), and that the reduction observed in methamphetamine users is associated with psychomotor impairment (Volkow et al. 2001). Recently, we have also found that the dopamine transporter density in methamphetamine users is inversely related to the length of methamphetamine use and the magnitude of psychiatric symptoms, including psychotic symptoms (Sekine et al. 2001).In vivo proton magnetic resonance spectroscopy ( 1 H MRS) and its variant 1 H MRS techniques provide insight into the metabolism of several endogenous brain chemicals (Miller 1991;Jackson 1992). A recent 1 H MRS study showed evidence for long-term metabolite alterations in currently abstinent former methamphetamine users, that is, reduced concentration of both N-acetylaspartate (NAA) and creatine plus phosphocreatine (Cr ϩ PCr) in the right basal ganglia (Ernst et al. 2000). However, it is unclear whether these abnormalities detected by 1 H MRS are related to psychiatric symptoms that are frequently observed in abstinent methamphetamine users.In this study, we investigated changes of the chemistry in the basal ganglia of abstinent methamphetamine users by 1 H MRS, and examined any relationship between the changes and clinical cha...

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Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types

Cited by 934 publications

References 47 publications

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

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

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

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Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types

Cited by 934 publications

References 47 publications

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

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

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms A Proton MRS Study

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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