A (1)H magnetic resonance spectroscopy study of aging in parietal white matter: implications for trials in multiple sclerosis

1H magnetic resonance spectroscopy (MRS) provides a unique tool to detect and quantify brain metabolites. In multiple sclerosis it can be used to investigate axonal loss or dysfunction through measurement of N-acetyl aspartate (NAA), a neuronal marker. Previous studies in adults have reported variable effects of aging on metabolite concentrations but have predominantly focused on changes in the elderly. This study has examined a younger adult age group to provide a reference database more applicable to the multiple sclerosis population. Single voxel (1)H MRS was carried out in 44 subjects between 22 and 62 years of age. Sixteen subjects underwent repeat examination after one year. Absolute concentrations of NA (the sum of NAA and N-acetyl aspartate glutamate), NAA, creatine/phosphocreatine (Cr), choline containing compounds (Cho) and myo-inositol (mI) were measured. NA, NAA and mI concentrations did not correlate with age but there were significant correlations between age and Cr (r = 0.43, p = 0.004) and Cho (r = 0.38, p = 0. 011) concentrations. No significant differences in metabolite concentrations were seen over one year. This study provides evidence that age-related changes of metabolite concentrations occur even in a young to middle aged adult population. This emphasizes the need to perform absolute quantification of metabolite concentrations rather than ratios and the importance of age-matching in (1)H MRS studies of multiple sclerosis.     

Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolite distributions and reliability.

Multislice proton magnetic resonance spectroscopic imaging (1H MRSI) at 25 ms echo time was used to measure concentrations of myo-inositol (mI), N-acetylaspartate (NAA), and creatine (Cr) and choline (Cho) in ten normal subjects between 22 and 84 years of age (mean age 44 +/- 18 years). By co-analysis with MRI based tissue segmentation results, metabolite distributions were analyzed for each tissue type and for different brain regions. Measurement reliability was evaluated using intraclass correlation coefficients (ICC). Significant differences in metabolite distributions were found for all metabolites. mI of frontal gray matter was 84% of parietal gray matter and 87% of white matter. NAA of frontal gray matter was 86% of parietal gray matter and 85% of white matter. Cho of frontal gray matter was 125% of parietal gray matter and 59% of white matter and Cho of parietal gray matter was 47% of white matter. Cr of parietal gray matter was 113% of white matter. Reliability was relatively high (ICC from.70 to.93) for all metabolites in white matter and for NAA and Cr in gray matter, though limited (ICC less than.63) for mI and Cho in gray matter. These findings indicate that voxel gray/white matter contributions, regional variations in metabolite concentrations, and reliability limitations must be considered when interpreting 1H MR spectra of the brain.     

Single-voxel proton MR spectroscopy in toluene abuse

Inhalation of toluene, which is an organic solvent, causes toxic encephalopathy characterized by cognitive impairment, cerebellar and extra-pyramidal symptoms. We studied cranial MR images and single-voxel MR spectroscopy of 22 toluene abusers and age-matched control subjects. The mean age of the abusers and mean duration of abuse were 18,1 years and 47 months, respectively. We got three MR spectra from the centrum semiovale, cerebellum and thalamus by using STEAM sequence with a TE value of 30 ms. N-acetyl aspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, myo-inositol (mI)/Cr peak integral ratios were calculated. NAA/Cr in the cerebellum and centrum semiovale of the abusers were significantly lower than those of the control subjects. mI/Cr in centrum semiovale and cerebellum were higher in toluene abusers. No significant difference was found in the metabolite ratios of the thalami. The association of NAA/Cr and mI/Cr ratios in cerebellum and centrum semiovale with the duration of abuse was significant. Normal level of NAA in thalamus, which was a neuron rich gray matter structure, might imply that toluene inhalation did not cause direct neuronal injury. Selective reduction of NAA and increased level of mI in white matter supported the theory of that axonopathy and gliosis were the main mechanisms of pathophysiology in chronic toluene encepholopathy. Insignificance of elevation of Cho/Cr ratios demonstrated that toluene inhalation did not cause active demyelination.     

MR image-based measurement of rates of change in volumes of brain structures. Part II: application to a study of Alzheimer's disease and normal aging

We present global and regional rates of brain atrophy measured on serially acquired T1-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups. However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD.     

Fast quantification of proton magnetic resonance spectroscopic imaging with artificial neural networks

Accurate quantification of the MRSI-observed regional distribution of metabolites involves relatively long processing times. This is particularly true in dealing with large amount of data that is typically acquired in multi-center clinical studies. To significantly shorten the processing time, an artificial neural network (ANN)-based approach was explored for quantifying the phase corrected (as opposed to magnitude) spectra. Specifically, in these studies radial basis function neural network (RBFNN) was used. This method was tested on simulated and normal human brain data acquired at 3T. The N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate+glutamine (Glx)/Cr, and myo-inositol (mI)/Cr ratios in normal subjects were compared with the line fitting (LF) technique and jMRUI-AMARES analysis, and published values. The average NAA/Cr, Cho/Cr, Glx/Cr and mI/Cr ratios in normal controls were found to be 1.58+/-0.13, 0.9+/-0.08, 0.7+/-0.17 and 0.42+/-0.07, respectively. The corresponding ratios using the LF and jMRUI-AMARES methods were 1.6+/-0.11, 0.95+/-0.08, 0.78+/-0.18, 0.49+/-0.1 and 1.61+/-0.15, 0.78+/-0.07, 0.61+/-0.18, 0.42+/-0.13, respectively. These results agree with those published in literature. Bland-Altman analysis indicated an excellent agreement and minimal bias between the results obtained with RBFNN and other methods. The computational time for the current method was 15s compared to approximately 10 min for the LF-based analysis.     

Using nine degrees-of-freedom registration to correct for changes in voxel size in serial MRI studies

Quantitative longitudinal brain magnetic resonance (MR) studies may be confounded by scanner-related drifts in voxel sizes. Total intracranial volume (TIV) normalisation is commonly used to correct serial cerebral volumetric measurements for these drifts. We hypothesised that automated rigid-body registration of whole brain incorporating automatic scaling correction might also correct for such fluctuations, and might be a more practical alternative. Twenty-three subjects (12 patients with Alzheimer's disease [AD] and 11 controls) had at least two serial T1-weighted volumetric brain MR scans. Ten scans from the control subjects were artificially scaled (stretched) by 1.5, 3.0, 4.6 and 6.1%. A 9-degrees-of-freedom (9dof) registration was used to register the scaled scans back onto the original scans and corresponding scaling factors compared to TIV measurements. A further nine 1-year repeat scans from the AD subjects were artificially scaled and registered (9dof) to baseline. The two correction methods were further assessed using multiple serial scans for each of the 23 subjects (resulting in 49 scan pairs). All serial scans were registered (9dof) to baseline. TIV was measured on all scans. It was found that the 9dof registration successfully recovered the artificially generated scaling changes. Scaling correction using 9dof registration did not alter the amount of brain atrophy measured over the 1-year period in the AD subjects. The 9dof volume scaling factors were very similar to the TIV ratios (repeat TIV over baseline TIV), but less variable (p < 0.001), in both artificial and 'real' scenarios. In the latter, the volume scaling factors allowed identification of two time-points in which a 3% change in voxel size had occurred. Both the 9dof brain registration and TIV correction were successfully able to correct for these fluctuations. Significant shifts in voxel size are a problem in longitudinal brain imaging studies. It is important that such changes are adjusted for: 9dof registration, which is automated and computationally inexpensive, may be superior to the more labour-intensive TIV correction for this purpose.     

Proton spectroscopy of human stroke: Assessment of transverse relaxation times and partial volume effects in single volume STEAM MRS

Proton T₂ relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T₂ values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T₂ for lactate in patients was 780 ± 257 ms, respectively (mean ± SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T₂, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.     

Computerized MRS voxel registration and partial volume effects in single voxel H-MRS

Partial volume effects in proton magnetic resonance spectroscopy in the brain have been studied previously in terms of proper water concentration calculations, but there is a lack of disclosure in terms of voxel placement techniques that would affect the calculations. The purpose of this study is to facilitate a fully automated MRS voxel registration method which is time efficient, accurate, and can be extended to all imaging modalities. A total of thirteen healthy adults underwent single voxel 1H-MRS scans in 3.0 T MRI scanners. Transposition of a MRS voxel onto an anatomical scan is derived along with a full calculation of water concentration with a correction term to account for the partial volume effects. Five metabolites (tNAA, Glx, tCr, mI, and tCho) known to yield high reliability are studied. Pearson’s correlation analyses between tissue volume fractions and metabolite concentrations were statistically significant in parietal (tCr, Glx, and tNAA) lobe and occipital lobe (tNAA). MRS voxel overlaps quantified by dice metric over repeated visits yielded 60% ~ 70% and coefficients of variance in metabolites concentration were 4% ~ 10%. These findings reiterate an importance of considering the partial volume effects when tissue water is used as an internal concentration reference so as to avoid misinterpreting a morphometric difference as a metabolic difference.     

Quantitative MRS study of Baló's concentric sclerosis lesions

Baló's concentric sclerosis (BCS) lesions display specific metabolite changes detected by magnetic resonance spectroscopy (MRS). We report on two cases of BCS lesions examined by MRS; the first case was evaluated 36 days after the onset of symptoms, whereas the second case was evaluated 9 days after the onset of symptoms. MRS data were obtained from single voxels located in the lesion and in the contralateral region. Relative to the creatine/phosphocreatine peak, BCS lesions displayed decreases of N-acetyl aspartate and increases of choline, myo-inositol (mI), glutamine/glutamate (Glx), lactate and lipid+macromolecule signals, in agreement with previous reports. In addition, previously unreported decreases of mI (-19% to -29%) and increases of Glx (+55% to +198%) were measured; these could be useful in characterizing BCS lesions.     

Reproducibility of metabolite peak areas in 1H MRS of brain

We studied the reproducibility of metabolite signals (from N-acetyl aspartate [NAA], choline, and creatine) measured with a standard single-voxel proton magnetic resonance spectroscopy technique (PRESS, TE = 135 ms, 8 ml VOI) in vitro and in two groups of normal volunteers. Spectral peak areas were quantified both by integration and by curve-fitting. In the in vitro study, the “between-days” variability (coefficient of variation [CV]) of measurements ranged from 0.9% to 2.3%. In the first group of volunteers (n = 12), single voxel spectroscopic measurements (8 ml VOI, 256 acquisitions [ACQs]) were made from mirrorimage parts of the right and left hemispheres on 2 separate days. The “between-days” CV of measurements ranged from 9% to 18% for metabolite areas, and from 10% to 26% for metabolite area ratios. There were no significant differences between quantification method or hemisphere. After checking and optimising the MR scanner performance (in fact, it was virtually optimal), the second group (n = 4) each had six sequential single voxel spectroscopic measurements (each of 64 ACQs) from the right hemisphere (without moving the voxel) on each of 4 separate days. Even when the metabolites were measured from the same place in the same hemisphere sequentially six times in a 20-min period, the “within-run” CVs ranged from 4.4% to 17.2% for metabolite areas and from 9.7% to 17.0% for metabolite area ratios. The between-days CVs for the subjects ranged from 7.7% to 25.8% (metabolite areas) and from 10.1% to 22.6% (metabolite area ratios). The variability is due to a combination of random noise, subject motion, baseline artefacts in the spectra, and uncertainties in repositioning the VOIs. It is likely to represent the best reproducibility possible with 8-ml VOIs in cooperative, healthy volunteers carefully positioned on each occasion in a standard clinical scanner. Changes in metabolite levels in individuals must therefore be of the order of 20–40% before we can be reasonably confident of measuring them. Reproducibility in patients, who may be less cooperative, will probably be no better, and this must be taken into account in the interpretation of MRS studies in patients with brain pathology; for example, stroke, head injury, and tumours.     

3-D echo planar (1)HMRS imaging in MS: metabolite comparison from supratentorial vs. central brain

To determine if metabolite ratios as measured by 3-dimensional echo planar spectroscopy imaging (3D-EPSI) from central brain regions of interest (ROI) centered at the corpus callosum reflect imaging metrics of large volumes of supratentorial brain (STB) from patients with multiple sclerosis. METHODS: 48 MS patients with relapsing-remitting, secondary progressive, and primary progressive disease underwent a 3D-EPSI sequence covering large volumes of STB. Metabolite ratios were first estimated from all voxels within a STB mask using a linear regression of N-acetylaspartate (NAA) over Creatine (Cr), NAA over choline (Cho) and Cho over Cr. Secondly, spectroscopic voxels from a central brain (CB) ROI centered at the corpus callosum were selected within the STB. Ratios were compared using Bland-Altman regression analysis and Spearman's correlation coefficients between STB versus central brain. Ratios from studied ROIs were correlated with the EDSS and compared to normal controls. RESULTS: Very strong correlations ranging from 0.884 and 0.938 (p < 0.0001) were found for all metabolite ratios between STB versus central brain. NAA/Cr ratios were similarly and negatively correlated with the EDSS across all ROIs, trends ranging from -0.257 to -0.314 (p < 0.1). NAA/Cr from all MS patients was similarly decreased compared to controls across all ROIs (p < 0.01). CONCLUSION: Metabolite ratios from a central brain ROI were statistically equivalent and highly correlated with ratios from the STB. The study of NAA/Cr using (1)HMRS from a central brain ROI centered at the corpus callosum seems to be representative of brainwide axonal changes in patients with MS.     

Occupational prolonged organic solvent exposure in shoemakers: brain MR spectroscopy findings

Our purpose was to investigate, by magnetic resonance (MR) spectroscopy, the metabolite changes in the brains of subjects in the shoemaking industry who had been chronically exposed to organic solvents. A total of 49 male subjects and 30 age-matched healthy volunteers underwent detailed neurological and psychiatric examinations. All subjects had long-echo [repetition time (TR) 2000 ms, echo time (TE) 136 ms] single-voxel MR spectroscopy. Voxels (15 x 15 x 15 mm(3)) were placed in the parietal white matter, thalamus, and basal ganglia. N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from thalamus, basal ganglia, and parietal white matter. Cho/Cr ratios in thalamus, basal ganglia, and parietal white matter were found to be significantly increased compared to controls. There was a positive correlation between basal ganglia Cho/Cr ratio and duration of exposure (r = 0.63). MR spectroscopy should be performed to reveal metabolite changes and determine the degree of brain involvement in solvent-related industry workers.     

A chemical shift imaging study on regional metabolite distribution in a CADASIL family

A chemical shift imaging (CSI) study was performed to directly assess relative concentrations of N-acetylaspartate (NAA), Cho and Cr metabolites in normal- and abnormal-appearing brain tissue of asymptomatic and symptomatic members of a single family with a neuropathologic, genetic and electrophysiological confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The aim of the investigation was to evaluate clinical findings and metabolite abnormalities as early appearance of axonal injury in this syndrome. The main findings related statistically significant decreases in the mean metabolite ratios for NAA/Cr, NAA/Cho and Cho/Cr in the anterior parts in comparison with the posterior parts of the centrum semiovale in symptomatic and asymptomatic patients. The effect was considerably greater in the symptomatic patients, indicating a strong correlation between CSI and pathology results. No differences were found between the two areas in the control group. Although lactate signals were hardly detectable in individual spectra, there was a trend toward increased Lac/Cr values in the anterior parts with respect to the posterior parts in the patient group, with the effect particularly evident in the asymptomatic subjects with the gene mutation.     

Serial Precision of Metabolite Peak Area Ratios and Water Referenced Metabolite Peak Areas in Proton MR Spectroscopy of the Human Brain

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that “disappointing in vivo repeatability…is likely to limit” the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H₂O = 0.5%, Cho/H₂O = 1.2%, Cr + PCr/H₂O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H₂O = 1.5%, Cho/H₂O = 2.4%, Cr + PCr/H₂O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H₂O = 1.4%, Cho/H₂O = 4.9%, Cr + PCr/H₂O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H₂O = 2.5%, Cho/H₂O = 6.4%, Cr + PCr/H₂O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall’s assertion regarding disappointing repeatability of in vivo MRS.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

Background  

The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.     

In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study.

Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T₁ and T₂ weighted. In order to evaluate the extent to which changes in metabolite signals during the course of infarction can be explained by changes in T₁ and T₂ relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T₁ and T₂ of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T₁ or T₂ of the metabolites between the patients and the normal controls. The T₂ of CHO was longer than that of NAA and Cr+PCr. Our results indicate that spectra obtained in brain infarcts and normal tissue with the same acquisition parameters are directly comparable with respect to relative signal intensities as well as signals scaled with internal and external standards.     

Brain metabolite concentration ratios in vivo: multisite reproducibility by single-voxel 1H MR spectroscopy

Ten normal subjects were scanned identically at three separate sites (Little Rock, Houston, and New Orleans) to evaluate the reproducibility of brain metabolite ratios in single-voxel (1)H point-resolved spectroscopy sequence (PRESS) magnetic resonance (MR) spectroscopy in vivo. All scans were processed by a single individual at a single site. Coefficients of variation of the measured metabolite ratios generally were in the range found for previous single-voxel, single-site reproducibility studies. No differences were found among the sites for ratios of N-acetylaspartate to creatine (NAA/Cr) or choline to Cr (Cho/Cr) in left thalamus by multivariate ANOVA. Metabolite ratios of Cr or Cho relative to local brain H(2)O did not vary among the sites. However, by multivariate ANOVA, NAA/H(2)O differed between Little Rock and New Orleans, but not between those sites and Houston. Intraclass correlation coefficients suggested reasonable reproducibility between Little Rock and New Orleans, but not between those sites and Houston.     

Ex vivo proton MR spectroscopy (1H-MRS) for evaluation of human gastric carcinoma

The present study was performed to determine the characteristics of the biochemical metabolites related to gastric cancer using ex vivo (1)H magnetic resonance spectroscopy (MRS), and to assess the clinical usefulness. A total of 35 gastric specimens resected during surgery for gastric cancer were used to compare MR spectra. A 1.5-T (64-MHz) clinical MR imager equipped with facilities for spectroscopy was used to obtain MR spectra from 33 gastric specimens. High-resolution (1)H nuclear magnetic resonance (NMR) spectra of the remains of two specimens were also examined with a 9.4-T (400-MHz) NMR spectrometer. Localized spectroscopic measurements were performed in two layers of gastric tissue, the proper muscle layer and the composite mucosa/submucosa layer. T(2) FSE and 3D SPGR images were used to determine the voxel size and the location for MRS data collection. MR spectra were obtained using the single-voxel PRESS technique with parameters of TR/TE = 2000/30 ms, NA = 256, and voxel size = 3 x 3 x 3 mm(3) (27 microL). Cancerous and noncancerous gastric tissues in the voxel were determined by histopathological analysis. On 9.4-T ex vivo NMR spectroscopy, the following metabolite peaks were found: lipids at 0.9 ppm (CH(3)) and 1.3 ppm (CH(2)); alanine (beta-CH(3)) at 1.58 ppm; N-Acetyl neuraminic acid (NANA: sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in normal gastric tissue layers. In the 1.5-T MR system, broad and featureless spectral peaks of the various metabolites in normal human gastric tissue were observed at 0.9 ppm, 1.3 ppm, 2.0 ppm, and 2.2 ppm regardless of gastric tissue layer. In specimens (Borrmann type III) with tubular adenocarcinoma, resonance peaks were observed at 1.26 ppm, 1.36 ppm (doublet of lactate), and 3.22 ppm (choline). Cancer lesions showed decreased levels of lipid peaks, showing the significant lactate doublet peaks, and increased intensity of the choline peak as compared with noncancerous gastric tissue. We found that decreased levels of lipids and increases in lactate and choline peaks in gastric tissue were markers for malignancy in gastric lesions. Information provided by ex vivo (1)H MRS, together with the development of in vivo (1)H MRS with high field strength and high resolution, may be very useful for the diagnosis of gastric cancer in clinical situation.