N-acetyl Aspartate (n-acetyl + aspartate)

Distribution by Scientific Domains

Selected Abstracts

Quantitative multivoxel proton spectroscopy of the brain in developmental delay

Krijn T. Verbruggen MD
Abstract Purpose To assess whether proton MR spectroscopy of the brain in children with developmental delay reveals a consistent pattern of abnormalities. Materials and Methods Eighty-eight patients (median age, 4.6 years; interquartile range, 3.1,8.1 years) with unexplained developmental delay, were compared with 48 normally developing age-matched controls. Patients and controls were assigned to five age-groups. Multivoxel MR spectroscopy was performed on a volume of interest superior to the lateral ventricles. The relative levels of choline, creatine, N-acetyl aspartate, and glutamate/glutamine in 24 voxels containing white matter and 12 voxels containing gray matter were quantified in an operator-independent manner and expressed in proportion to the total metabolite peak area in the volume of interest. Results White matter choline in DD showed less decrease with age. Mean choline levels, compared with mean control levels, increased from 99 to 111% with increasing age. This was statistically significant in the highest age groups (P = 0.015 [7 < yr , 12.8] and P = 0.039 [12.8 < yr]). Other metabolites did not show clear alterations. Conclusion Proton MR spectroscopy in a group of patients with unexplained DD shows small differences in the metabolite pattern, compared with normally developing controls, that is, higher choline in the white matter. The pathophysiological origin and significance may relate to myelination and maturation of the white matter. J. Magn. Reson. Imaging 2009;30:716,721. © 2009 Wiley-Liss, Inc. [source]

1H spectroscopic imaging of human brain at 3 Tesla: Comparison of fast three-dimensional magnetic resonance spectroscopic imaging techniques

Matthew L. Zierhut PhD
Abstract Purpose To investigate the signal-to-noise-ratio (SNR) and data quality of time-reduced three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H MRSI) techniques in the human brain at 3 Tesla. Materials and Methods Techniques that were investigated included ellipsoidal k -space sampling, parallel imaging, and echo-planar spectroscopic imaging (EPSI). The SNR values for N-acetyl aspartate, choline, creatine, and lactate or lipid peaks were compared after correcting for effective spatial resolution and acquisition time in a phantom and in the brains of human volunteers. Other factors considered were linewidths, metabolite ratios, partial volume effects, and subcutaneous lipid contamination. Results In volunteers, the median normalized SNR for parallel imaging data decreased by 34,42%, but could be significantly improved using regularization. The normalized signal to noise loss in flyback EPSI data was 11,18%. The effective spatial resolutions of the traditional, ellipsoidal, sensitivity encoding (SENSE) sampling scheme, and EPSI data were 1.02, 2.43, 1.03, and 1.01 cm3, respectively. As expected, lipid contamination was variable between subjects but was highest for the SENSE data. Patient data obtained using the flyback EPSI method were of excellent quality. Conclusion Data from all 1H 3D-MRSI techniques were qualitatively acceptable, based upon SNR, linewidths, and metabolite ratios. The larger field of view obtained with the EPSI methods showed negligible lipid aliasing with acceptable SNR values in less than 9.5 min without compromising the point-spread function. J. Magn. Reson. Imaging 2009;30:473,480. © 2009 Wiley-Liss, Inc. [source]

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

Laura Guerrini MD PhD
Abstract Purpose To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel 1H-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, T2 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. J. Magn. Reson. Imaging 2009;30:11,17. © 2009 Wiley-Liss, Inc. [source]

Proton MR spectroscopic imaging of the medulla and cervical spinal cord,

Richard A.E. Edden PhD
Abstract Purpose To demonstrate the feasibility of quantitative, one-dimensional proton MR spectroscopic imaging (1D-MRSI) of the upper cervical spine and medulla at 3.0 Tesla. Materials and Methods A method was developed for 1D-point-resolved spectroscopy sequence (PRESS)-MRSI, exciting signal in five voxels extending from the pontomedullary junction to the level of the C3 vertebra, and performed in 10 healthy volunteers to generate control data. Results High-resolution 1D-MRSI data were obtained from all 10 subjects. Upper cervical spine concentrations of choline, creatine, and N-acetyl aspartate were estimated to be 2.8 ± 0.5, 8.8 ± 1.8, and 10.9 ± 2.7 mM, respectively, while in the medulla they were 2.6 ± 0.5, 9.1 ± 1.7, and 10.8 ± 0.9 mM. Conclusion Quantitative 1D-MRSI of the upper cervical spine has been shown to be feasible at 3.0 Tesla. J. Magn. Reson. Imaging 2007;26:1101,1105. © 2007 Wiley-Liss, Inc. [source]

A multi-center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysis

Patricia Lani Lee PhD
Abstract Purpose To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). Materials and Methods Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. Results A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. Conclusion This is the first study to ascertain and validate the reliability and reproducibility of a short echo time 1H-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting. J. Magn. Reson. Imaging 2003;17:625,633. © 2003 Wiley-Liss, Inc. [source]

Proton spectroscopic metabolite signal relaxation times in preterm infants: A prerequisite for quantitative spectroscopy in infant brain

Harald Kugel PhD
Abstract Purpose To determine relaxation times of metabolite signals in proton magnetic resonance (MR) spectra of immature brain, which allow a correction of relaxation that is necessary for a quantitative evaluation of spectra acquired with long TE. Proton MR spectra acquired with long TE allow a better definition of metabolites as N-acetyl aspartate (NAA) and lactate especially in children. Materials and Methods Relaxation times were determined in the basal ganglia of 84 prematurely born infants at a postconceptional age of 37.8 ± 2.2 (mean ± SD) weeks. Metabolite resonances were investigated using the double-spin-echo volume selection method (PRESS) at 1.5 T. T1 was determined from intensity ratios of signals obtained with TRs of 1884 and 6000 msec, measured at 3 TEs (25 msec, 136 msec, 272 msec). T2 was determined from signal intensity ratios obtained with TEs of 136 msec and 272 msec, measured at 2 TR. Taking only long TEs reduced baseline distortions by macromolecules and lipids. For myo-inositol (MI), an apparent T2 for short TE was determined from the ratio of signals obtained with TE = 25 msec and 136 msec. Intensities were determined by fitting a Lorentzian to the resonance, and by integration. Results Relaxation times were as follows: trimethylamine-containing compounds (Cho): T1 = 1217 msec/T2 = 273 msec; total creatine (Cr) at 3.9 ppm: 1010 msec/111 msec; Cr at 3.0 ppm: 1388 msec/224 msec; NAA: 1171 msec/499 msec; Lac: 1820 msec/1022 msec; MI: 1336 msec/173 msec; apparent T2 at short TE: 68 msec. Conclusion T1 and T2 in the basal ganglia of premature infants do not differ much from previously published data from basal ganglia of older children and adults. T2 of Cho was lower than previous values. T2 of Cr at 3.9 ppm and Lac have been measured under different conditions before, and present values differ from these data. J. Magn. Reson. Imaging 2003;17:634,640. © 2003 Wiley-Liss, Inc. [source]

In vivo and in vitro MR spectroscopic profile of central neurocytomas

Rama Jayasundar PhD
Abstract This study reports in vivo and in vitro magnetic resonance spectroscopic findings in two cases of central neurocytomas (CNC) confirmed by immunohistochemistry. Volume localized in vivo proton magnetic resonance spectroscopy (MRS) was carried out before surgery using a point resolved spectroscopy (PRESS) sequence with a repetition time of six seconds and an echo time of 135 msec. Normal spectrum was obtained from gray matter from a volunteer for comparison. 1H and 31P in vitro MRS studies were carried out at 9.4 T on the extracts prepared from the surgically excised tumors. The in vivo spectra showed prominent glycine (Gly) and choline (Cho) and low N-acetyl aspartate compared to the normal. The Gly peak was assigned using the in vitro studies. These studies showed that the major contribution to the Cho peak observed in vivo is from phosphocholine. A combination of the presence of NAA and an increased Gly in the proton MR spectrum could be a characteristic feature of CNCs, which are rare intraventricular tumors of neuronal origin. J. Magn. Reson. Imaging 2003;17:256,260. © 2003 Wiley-Liss, Inc. [source]

In vivo quantitative proton MRSI study of brain development from childhood to adolescence,

Alena Horská PhD
Abstract Purpose To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI). Materials and Methods Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus. Results In cortical gray matter regions, the ratio of NAA/Cho increased to a maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined. Conclusion Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with age-related increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination. J. Magn. Reson. Imaging 2002;15:137,143. Published 2002 Wiley-Liss, Inc. [source]

NAALADase (GCP II) inhibitors protect in models of amyotrophic lateral sclerosis (ALS)

A. G. Thomas
Chronic glutamate toxicity is implicated in the pathogenesis of ALS. The neuropeptide N-acetyl-aspartyl glutamate (NAAG) appears to function both as a storage form for glutamate and as a neuromodulator at glutamatergic synapses. Catabolism of NAAG by N-acetylated-,-linked acidic dipeptidase (NAALADase; also termed glutamate carboxypeptidase II), yields N-acetyl aspartate (NAA) and glutamate. Since prior studies demonstrate an up-regulation of NAALADase in motor cortex and increased levels of NAA and glutamate in the CSF of ALS patients, we hypothesized that inhibition of NAALADase could protect against neuronal degeneration in ALS. Neuroprotective effects of two NAALADase inhibitors were assessed. 2-(Phosphonomethyl)pentanedioic acid (2-PMPA) decreased motor neuron loss and prevented loss of choline acetyltransferase (ChAT) activity in an in vitro model of ALS wherein chronic glutamate toxicity was induced by blocking glutamate transport. Gross morphology was preserved in 2-PMPA-treated cultures. In a SOD-1 transgenic mouse model of ALS, oral administration of a structurally different NAALADase inhibitor (GPI 5693) increased survival by 29 days and delayed onset of clinical symptoms by 17 days. Preliminary analysis of spinal cord pathology revealed severe neuronal depletion and astrocytosis with white matter changes in control mice. In mice treated with GPI 5693, normal neuronal populations with modest vacuolar changes were observed. These data suggest that NAALADase inhibition may provide an exciting therapeutic approach to the devastating disease, ALS. [source]

In vivo differentiation of N-acetyl aspartyl glutamate from N-acetyl aspartate at 3 Tesla

Richard A.E. Edden
Abstract A method is described that allows the in vivo differentiation of N-acetyl aspartate (NAA) from N-acetyl aspartyl glutamate (NAAG) by in vivo MR spectroscopy (MRS) at 3 Tesla (3T). The method, which is based on MEGA-point-resolved spectroscopy (PRESS) editing, selectively targets the aspartyl spin system of one species while deliberately removing the other species from the spectrum. This allows quantitative measurements of NAA and NAAG without the need for fitting of unresolved peaks. White matter concentrations of NAA (6.7 ± 0.3 mM) and NAAG (2.2 ± 0.3 mM) were measured in 10 healthy volunteers to demonstrate the method. Magn Reson Med 57:977,982, 2007. © 2007 Wiley-Liss, Inc. [source]

Unaliasing lipid contamination for MR spectroscopic imaging of gliomas at 3T using sensitivity encoding (SENSE),

Esin Ozturk-Isik
Abstract 3D magnetic resonance spectroscopic imaging (MRSI) has been successfully employed to extract information about brain tumor metabolism, such as cell membrane breakdown, cellular energetics, and neuronal integrity, through its ability to differentiate signals coming from choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA) molecules. The additional presence of lipids within subregions of the tumor may indicate cellular membrane breakdown due to cell death. Another potential source of lipids is subcutaneous fat, which may be excited with point-resolved spectroscopy (PRESS) volume selection and aliased into the spectral field of view (FOV) due to the chemical shift artifact and the low bandwidth of the selection pulses. The purpose of our study was to employ a postprocessing method for unaliasing lipid resonances originating from in-slice subcutaneous lipids from the 3D MRSI of gliomas at 3T, using an eight-channel phased-array coil and sensitivity encoding (SENSE). Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source]

Changes in the proton T2 relaxation times of cerebral water and metabolites during forebrain ischemia in rat at 9.4 T

Hao Lei
Abstract Proton T2 relaxation times of cerebral water and metabolites were measured before, during, and after transient forebrain ischemia in rat at 9.4 T using localized proton magnetic resonance spectroscopy (1H-MRS) with Hahn echoes formed at different echo times (TEs). It was found that the T2 values of water and N-acetyl aspartate (NAA) methyl, but not total creatine (tCr) methyl, decrease significantly (,10%) during ischemia, and this T2 reduction is reversed by reperfusion. The T2 reduction observed for NAA was most likely caused by the extravascular component of the blood oxygenation level-dependent (BOLD) effect induced by a drastically increased deoxyhemoglobin content during ischemia. The absence of T2 changes for tCr can probably be explained by the fact that the BOLD-related T2 decrease was counterbalanced by the conversion of phosphocreatine (PCr) to creatine (Cr), which has a longer T2 than PCr, during ischemia. The changes in T2 should be taken into account for the quantification of metabolite concentrations during ischemia. Magn Reson Med 49:979,984, 2003. © 2003 Wiley-Liss, Inc. [source]