In vivo proton magnetic resonance spectroscopy of the normal aging human brain

Chang, Linda; Ernst, T.; Poland, Russell E.; Jenden, Donald J.

doi:10.1016/0024-3205(96)00197-x

Cited by 206 publications

(196 citation statements)

References 20 publications

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“…glial versus neuronal), and it is not clear to what extent Cr and Cho represent glial compartments. In contrast, no age-related NAA and Glu changes were detected in the COR region, consistent with other 1 H MRS studies that also report stable NAA with aging in white matter [5,6,31,33]. In this context, it is interesting to note that m-Ins concentration decreased in the MC region and increased in the COR region in older subjects compared to the younger group (m-Ins is used predominantly as glial marker in the 1 H MRS literature [3]).…”

Section: Discussionsupporting

confidence: 88%

“…Another limitation is using cerebral water as a reference without considering potential decrease of water concentration in gray matter and white matter with age, as suggested in Ref. [5]. Although we did not find significant water content correlation with age in our study and therefore did not take this effect into consideration, sensitivity of our methods to detect an effect may have been limited.…”

Section: Discussionmentioning

confidence: 71%

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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: 88%

Section: Discussionmentioning

confidence: 71%

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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“…Biological variations, including changes in the levels with gender or age, were reported to be only up to Ϯ3.8% for Cr, Ϯ6.5% for Cho, and none for NAA, for 20 -47-yearold healthy subjects (18,19). Therefore, these are not the main contributor to the overall variations.…”

Section: Discussionmentioning

confidence: 96%

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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“…MRS examinations were performed on Signa 1.5T MR imagers (GE Medical Systems, Milwaukee, WI) operating with system version 5.6 or 5.7 using the standard GE quadrature head coil and a PRESS sequence with CHESS water suppression. MRS data were obtained with the automated GE pulse sequence PROBE-P, a PRESS sequence (Bottomley 1987) with CHESS water suppression (Chang et al 1996). MRS parameters included TE=35ms, TR=3000ms, voxel size=6cm 3 (20×20×15mm 3 ), 128 acquisitions, spectral width=2500Hz, and 2k data points.…”

Section: Study Subjects and Imaging Protocolsmentioning

confidence: 99%

Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: Application to proton MR Spectroscopy (MRS) in HIV-related neurological injury

2008

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We present the multi-dimensional Receiver Operating Characteristic (ROC) surface, a plot of the true classification rates of tests based on levels of biological markers, for multi-group discrimination, as an extension of the ROC curve, commonly used in two-group diagnostic testing. The volume under this surface (VUS) is a global accuracy measure of a test to classify subjects in multiple groups and useful to detect trends in marker measurements. We used three-dimensional ROC surfaces, and associated VUS, to discriminate between HIV-negative (NEG), HIV-positive neurologically asymptomatic (NAS) subjects and patients with AIDS demential complex (ADC), using brain metabolites measured by proton MRS. These were ratios of markers of inflammation, Choline (Cho) and myoinositol (MI), and brain injury, N-acetyl aspartate (NAA), divided by Creatine (Cr), measured in the basal ganglia and the frontal white matter. Statistically significant trends were observed in the three groups with respect to MI/Cr (VUS=0.43; 95% confidence interval (CI) 0.33-0.53), Cho/Cr (0.36; 0.27-0.45) in the basal ganglia and NAA/Cr in the frontal white matter (FWM) (0.29; 0.20-0.38), suggesting a continuum of injury during the neurologically asymptomatic stage of HIV infection, particularly with respect to brain inflammation. Adjusting for age increased the combined classification accuracy of age and NAA/Cr (p=0.053). Pairwise comparisons suggested that neuronal damage associated with NAA/Cr decreases was mainly observed in individuals with ADC, raising issues of synergism between HIV infection and age and possible acceleration of neurological deterioration in an aging HIV-positive population. The threedimensional ROC surface and its associated VUS are useful for assessing marker accuracy, detecting data trends and offering insight in disease processes affecting multiple groups.

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In vivo proton magnetic resonance spectroscopy of the normal aging human brain

Cited by 206 publications

References 20 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

Reproducibility of 3D proton spectroscopy in the human brain

Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: Application to proton MR Spectroscopy (MRS) in HIV-related neurological injury

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