Concentrations Of N-acetylaspartate Research Articles

In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese

BackgroundExposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable.ObjectivesOur goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure.MethodsWe used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)].ResultsSeven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = −0.93; p < 0.001).ConclusionsWe demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study

Background and Purpose Human immunodeficiency virus (HIV)-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 T. Higher magnetic field strengths (such as 3 T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3-T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln). Methods Eighty-six HIV+ subjects were evaluated at 3 T using quantitative short echo time single-voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into three groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia (clinical MSK stage=0.5), and 34 had dementia (HAD) (MSK≥1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed and motor and psychomotor speed. Between-group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive results. Results FWM Glx was lower in HAD (8.1±2.1 mM) compared to both the MCI (9.17±2.1 mM) and NC groups (10.0±1.6 mM) ( P=.006). FWM myo-inositol (mI) was higher in HAD (4.15±0.75 mM) compared to both MCI (3.86±0.85 mM) and NC status (3.4±0.67 mM) ( P=.006). FWM Glx/creatine (Cr) was lower and FWM mI/Cr was significantly higher in the HAD compared to the MCI and NC groups ( P=.01 and P=.004, respectively). BG N-acetyl aspartate (NAA) was lower in the HAD group (6.79±1.53 mM), compared to the MCI (7.5±1.06 mM) and NC (7.6±1.01 mM) groups ( P=.036). Significant negative correlations were observed between Glu, Glx and NAA concentrations with Trail-Making Test B ( P=.006, P=.0001 and P=.007, respectively), and significant positive correlation was found with the Digit symbol test ( P=.02, P=.002 and P=.008, respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved Pegboard nondominant hand ( P=.02 and P=.04, respectively). Conclusion Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. Three-Tesla MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection.

Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia

Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin-induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14-day-old rats using in vivo(1)H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 micromol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N-acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre-hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus.

The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus

To determine the histopathologic basis of altered brain neurometabolites in neuropsychiatric systemic lupus erythematosus (NPSLE). Brain neurometabolite concentrations in a 20-voxel area of the brain were determined premortem by magnetic resonance spectroscopy (MRS) in 7 individuals with NPSLE. Absolute concentrations of neurometabolite for N-acetylaspartate (NAA), choline, creatine, and lactate were measured. After the death of the patients, histopathologic changes were determined at autopsy of the brain and were matched voxel-by-voxel with the neurometabolites. The mean +/- SD absolute concentrations of NAA (9.15 +/- 1.78 mM in patients versus 12.2 +/- 0.8 mM in controls; P < 0.01) and creatine (6.43 +/- 0.16 mM in patients versus 6.90 +/- 0.60 mM in controls; P < 0.003) were significantly reduced and the concentration of choline (2.51 +/- 0.42 mM in patients versus 1.92 +/- 0.32 mM in controls; P < 0.04) was significantly elevated in NPSLE patients as compared with controls. Widespread heterogeneous changes in the histologic features of the brain were present, including microinfarcts, microhemorrhages, bland angiopathy, thrombotic angiopathy with platelet and fibrin thrombi, neuronal necrosis in various states of resolution, reduced numbers of axons and neurons, vacuole and space formation among the fibers, reduced numbers of oligodendrocytes, reactive microglia and astrocytes, lipid-laden macrophages, and cyst formation. Neurometabolite abnormalities were closely associated with underlying histopathologic changes in the brain: 1) elevated choline levels were independently associated with gliosis, vasculopathy, and edema (r = 0.75, P < 0.004 in the multivariate model); 2) reduced creatine levels with reduced neuronal-axonal density and gliosis (r = 0.72, P < 0.002 in the multivariate model); 3) reduced NAA levels with reduced neuronal-axonal density (r = 0.66, P < 0.001 in the multivariate model); and 4) the presence of lactate with necrosis, microhemorrhages, and edema (r = 0.996, P < 0.0001 in the multivariate model). Altered neurometabolites in NPSLE patients, as determined by MRS, are a grave prognostic sign, indicating serious underlying histologic brain injury.

Absolute Quantification in Proton Magnetic Resonance Spectroscopy Is Useful to Differentiate Amnesic Mild Cognitive Impairment from Alzheimer’s Disease and Healthy Aging

Background/Aims: Amnesic mild cognitive impairment (aMCI) is thought to represent a transitional state between healthy aging and very mild Alzheimer’s disease (AD). It is very important to diagnose aMCI for early treatment. In order to investigate biochemical changes in aMCI, we measured metabolite concentrations using proton magnetic resonance spectroscopy (¹H-MRS) from patients with aMCI and compared the results with healthy controls (HCs) and patients with AD. Methods: The subjects were 52 HCs, 70 AD patients and 47 aMCI patients. ¹H-MR spectra with single-voxel point-resolved spectroscopy at a short echo time (TE) were acquired from 8 volumes of interest in the brain. Results: The bilateral hippocampal N-acetylaspartate (NAA) concentrations from aMCI patients showed intermediate values, which were lower than those from HC subjects but higher than those from AD patients. The patients with aMCI also had lower concentrations of NAA than HCs in the bilateral posterior periventricular and deep white matters (PDWM) and posterior cingulate gyrus and had lower levels of choline compounds in the left posterior PDWM. Conclusion: Using a single-voxel ¹H-MRS at a short TE, we revealed that absolute quantification is useful to detect the characteristic patterns of metabolite concentrations in patients with aMCI as compared with AD patients and HCs.

Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

BackgroundVolume deficits assessed with magnetic resonance imaging (MRI) and neurochemical dysfunctions (N-acetylaspartate, NAA) diagnosed using proton MR spectroscopy (1H-MRS) are reliable observations in the hippocampus of schizophrenic patients. NAA is an important cerebral amino acid in the synthesis pathways of glutamate, which has been implicated as a pathobiological core of schizophrenic symptomatology, of histological alterations and brain volume deficits in schizophrenia. However, the possible interaction between regional NAA reduction and volume deficits has been targeted only marginally in previous investigations. MethodsIn 29 schizophrenic patients and 44 control subjects, a multimodal imaging study with 1H-MRS and MRI volumetry of the left hippocampus was performed on a 3-Tesla scanner. ResultsCompared to the control group, the hippocampus of the patients exhibited a significant volume reduction and a significant NAA concentration decrease. In schizophrenic patients, but not in healthy controls, a significant negative correlation between hippocampal NAA concentration and volume (r=−0.455, p=0.017) was observed. None of the imaging parameters was associated with clinical parameters. ConclusionsThe results argue for a coexistent neurochemical and structural deficit in the hippocampus of schizophrenic patients. The inverse relationship between the two parameters observed in patients only may reflect an interaction of neurochemistry and brain morphology as a pathobiological mechanism in schizophrenia. This observation is compatible with the important role of NAA in the synthesis of excitatory neurotransmitters and the hypothesized role of glutamate for brain morphology. The independence of the measured imaging parameters from clinical parameters is in line with the neurodevelopmental hypothesis of schizophrenia.

Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine

As one of the most widespread drugs of abuse, nicotine has long been known to impact the brain, particularly with respect to addiction. However, the regional effects of nicotine on the concentrations and kinetics of amino acid neurotransmitters and some energetically related neurochemicals have been little studied. In this investigation, acute effects of nicotine were measured by (1)H-observed/(13)C-edited nuclear magnetic resonance spectroscopy method in extracts obtained from nicotine-naïve, freely moving rats given 0.7 mg/kg nicotine or saline, with [1-(13)C] glucose to track metabolism. Nicotine was observed to exert significant effects on the concentrations of N-acetylaspartate and GABA, particularly in the striatum. Nicotine decreased brain glucose oxidation, glutamate-glutamine neurotransmitter cycling, and GABA synthesis regionally, including in the parietal and occipital cortices and the striatum. The olfactory bulb showed kinetics that differed markedly from those observed in the rest of the brain. Independently of nicotine, the concentration of glutamate was found to be correlated significantly with levels of N-acetylaspartate and GABA, suggesting a potential interplay of energetics and excitatory and inhibitory neurotransmission. In summary, the study revealed that the neurochemicals were most affected in the cortex and striatum of the rat brain after acute nicotine treatment.

Correlation between hippocampal volumes and proton magnetic resonance spectroscopy of the posterior cingulate gyrus and hippocampi in Alzheimer's disease.

Prior studies have reported hippocampal volume loss, decrease in N-Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration in patients with Alzheimer’s disease (AD). The purpose of this study was to evaluate hippocampal volumes of AD patients and their correlation with metabolic changes detected by proton spectroscopy (1H MRS) of hippocampal formations and the posterior cingulate region.Materials and Methods22 patients with probable AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were enrolled in the study. Hippocampal volumetric measurements, single-voxel 1H MRS of the posterior cingulate region and of hippocampal formations were obtained. The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA. Statistical analysis was performed to detect differences and correlations between these parameters in patients and controls.ResultsThe hippocampal volume of patients and controls did not differ significantly. The results of 1H MRS differed significantly between patients and controls in the hippocampal formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr, mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate region, having a sensitivity of 0.899 and specificity of 0.800. There was no correlation between hippocampal volumes and the results of 1H MRS in patients with AD.ConclusionsThe results of 1H MRS differed significantly between patients and controls in hippocampal formations and the posterior cingulate region, with NAA/Cr proving to be the best predictor for AD. No correlation between hippocampal volumes and the results of 1H MRS in patients with AD was observed.

Differential regional N-acetylaspartate deficits in postmortem brain in schizophrenia, bipolar disorder and major depressive disorder

There is substantial evidence for the involvement of the hippocampus and subcortical regions in the neuropathology of schizophrenia. Deficits of N-acetylaspartate (NAA) have been found in schizophrenia and bipolar disorder which may reflect neuronal loss and/or dysfunction. N-acetylaspartylglutamate (NAAG) is the most abundant peptide transmitter in the mammalian nervous system. It is an agonist at presynaptic metabotropic glutamate receptors mGluR3, inhibiting glutamate release. NAA and NAAG and were measured in hippocampal, striatal, amygdala and cingulate gyrus regions of human postmortem tissue from controls and subjects with schizophrenia, bipolar disorder and major depressive disorder. There are significant deficits in hippocampal NAA concentrations in all patient groups. In the amygdala there are significant NAA deficits in schizophrenia and depression and significant deficits of NAAG in the amygdala in the depression group. The deficits in NAA reported in this study confirm the importance of hippocampal and other subcortical structures in the neuropathology of the major psychiatric disorders.

N-acetyl aspartate concentration in the anterior cingulate cortex in patients with schizophrenia: A study of clinical and neuropsychological correlates and preliminary exploration of cognitive behaviour therapy effects

This study investigated the clinical and neuropsychological correlates of N-acetyl aspartate (NAA) concentration in the anterior cingulate cortex (ACC) in schizophrenia, and explored whether ACC NAA concentration is sensitive to symptom change following cognitive behaviour therapy for psychosis (CBTp). Participants comprised 30 patients and 15 healthy controls who underwent magnetic resonance spectroscopy of the ACC and were assessed on frontal lobe based neuropsychological tasks. Twenty-four (of 30) patients were followed-up; 11 subsequently received 8–9months of CBTp in addition to standard care (CBTp+SC) and 13 received SC only. At baseline (i) NAA and Cr concentrations were lower in patients compared to controls, (ii) in patients, NAA concentration correlated inversely with positive symptoms and general psychopathology (positive symptoms explained 21% of the variance; total variance explained=25%) and Cho concentration correlated inversely with positive symptoms, and (iii) in controls, NAA concentration correlated positively with working and short-term memory and Cr concentration inversely with executive function. NAA concentration tended to increase in CBTp+SC patients at follow-up (n=7 with usable data) concomitant with improvement in positive symptoms. NAA concentration may be more closely associated with symptoms and symptom change than frontal lobe based neuropsychological function in schizophrenia, perhaps because the latter is relatively stable during the long-term illness course.

The impact of blood pressure on hippocampal glutamate and mnestic function

Hypertension is associated with an increased risk of cognitive decline, which is generally regarded as a consequence of advanced cerebral atherosclerosis. Many hypertensive patients, however, suffer from cognitive decline long before they have any signs of cerebrovascular disease. Therefore, this study examines direct effects of blood pressure on neurotransmitter status in the hippocampus, a vulnerable cerebral structure relevant for memory consolidation. Absolute glutamate concentration and N-acetylaspartate (NAA) concentration as an alternative marker of neuronal integrity were determined in the hippocampus and the cerebral cortex (anterior cingulate cortex; ACC) by 3-T proton magnetic resonance spectroscopy in 16 probands without any history of cerebrovascular disease. Memory function was tested by the auditory verbal learning test (AVLT) and the rivermead behavioural memory test (RBMT). Arterial stiffness was assessed by augmentation index (AI). Mean arterial pressure showed a significant negative age-adjusted correlation to absolute glutamate concentrations in the hippocampus (R=-0.655, P=0.011), but not in the ACC. There was no significant correlation of mean arterial pressure and NAA in either hippocampus or ACC. AI did not affect hippocampal glutamate. Moreover, there was a significant negative correlation between mean arterial pressure and AVLT (r=-0.558, P=0.025) and RBMT score (r=-0.555, P=0.026). There is an inverse relation between blood pressure and the concentration of hippocampal glutamate. Glutamate is essential for long-term potentiation, the neurobiological correlate for memory formation in the hippocampus. Thus, hypertension-associated cognitive decline may not only be mediated by structural atherosclerotic wall changes, but also by functional changes in neurotransmission.

Quantitative magnetic resonance spectroscopic imaging in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy

Magnetic resonance spectroscopy (MRS) allows the measurement of a number of brain tissue metabolites in vivo, including N-acetylaspartate (NAA), a putative marker of neuronal integrity. Unlike single voxel MRS, magnetic resonance spectroscopic imaging (MRSI) enables quantification of these metabolites simultaneously from multiple anatomically localized voxels. Both single voxel MRS and MRSI allow the absolute quantification of these metabolites and, when combined with tissue segmentation, can give accurate metabolite concentrations even in the presence of partial volume effects from nearby cerebrospinal fluid. Using MRSI with cubic voxels with a nominal volume of 1.0 cm(3), we tested the hypothesis that concentrations of NAA in the basal ganglia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) would show differences compared to Parkinson's disease (IPD). NAA values (in mM) from MRSI voxels centred to the putamen, pallidum and thalamus were obtained from 11 patients with IPD, 11 with MSA-P, six with MSA-C, 13 with PSP and 18 controls. The mean concentrations of NAA and its bulk grey and white matter values were also estimated over the whole brain slab. N-acetylaspartate concentrations in the pallidum, putamen and lentiform nucleus were significantly lower in patients with MSA-P and PSP compared to IPD and controls. The putaminal values were also significantly reduced in PSP compared to MSA-P. There were no significant differences between groups in the thalamus and over the whole brain slab. Our findings support the notion that MRSI can potentially quantify basal ganglia cellular pathology in MSA and PSP.

Anterior to posterior hippocampal MRS metabolite difference is mainly a partial volume effect

The concentration of N-acetylaspartate (NAA) in hippocampus, as measured with magnetic resonance spectroscopy (MRS), and the ratio of NAA/(choline (Cho) + creatine (Cr)) are valuable tools in the lateralization of temporal lobe epilepsy (TLE). MRS of hippocampus is also increasingly used to study certain psychiatric and degenerative diseases. However, the reliability of such measurements of hippocampus has been questioned. To re-evaluate MRS imaging data from prior control subjects with regard to variation of metabolite concentrations in hippocampus from anterior to posterior and the partial volume (R)contribution to the measurements from adjacent tissue. Twelve healthy subjects, mean age 33 years, were studied with MRS imaging. The measurement volume was angled along the temporal horns and metabolite concentration images were reconstructed at the MR system. Regions of interest (ROIs) in the anterior, medial, and posterior parts of both hippocampi were evaluated. Signal normalization to the total MRS signal from all ROIs permitted pooling of individual data with different and unknown signal scaling. One subject was re-examined with a high resolution three-dimensional (3D) volume of the brain for evaluation of partial volumes in the MRS examination. Overall, there were significantly lower concentrations of NAA in the anterior parts, and of (Cho+Cr) in the posterior parts, while the NAA/(Cho+Cr) ratio in the posterior parts of the mesial temporal lobes was significantly higher. Hippocampus accounted for one-half, one-third, and one-quarter of the anterior, middle, and posterior ROIs, respectively. The NAA/(Cho+Cr) ratio thus showed a reverse relationship to the relative volume of hippocampal tissue within the ROI. Metabolite concentrations in the mesial temporal lobe obtained with MRS imaging represent the mean value of hippocampus and a considerable amount of adjacent tissue. To assess the hippocampus alone, an actual voxel well below 1 cm(3) and a sub-centimeter slice thickness are required.

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers.

Role of Myo-Inositol by Magnetic Resonance Spectroscopy in Early Diagnosis of Alzheimer’s Disease in APP/PS1 Transgenic Mice

Background/Aims: To explore the potential value of myo-inositol (mIns), which is regarded as a biomarker for early diagnosis of Alzheimer’s disease, in APP/PS1 transgenic (tg) mice detected by ¹H-MRS. Methods:¹H-MRS was performed in 30 APP/PS1 tg mice and 20 wild-type (wt) littermates at 3, 5 and 8 months of age. Areas under the peak of N-acetylaspartate (NAA), mIns and creatine (Cr) in the frontal cortex and hippocampus were measured, and the NAA/Cr and mIns/Cr ratios were analyzed quantitatively. Results: Compared with the wt mice, the mIns/Cr ratio of the 3-month-old tg mice was significantly higher (p < 0.05), and pathology showed activation and proliferation of astrocytes in the frontal cortex and hippocampus. The concentration of NAA was significantly lower at 8 and 8 months of age (p < 0.05). According to the threshold of mIns/Cr that was adopted to separate the tg from the wt mice, the rate of correct predictions was 82, 94 and 95%, respectively, for 3, 5 and 8 months. Conclusion: Of the early AD metabolites as detected by ¹H-MRS, mIns is the most valuable marker for assessment of AD. Quantitative analysis of mIns may provide important clues for early diagnosis of AD.

&lt;b&gt;Evaluation of brain metabolite in patients with Complex Regional Pain Syndrome &lt;/b&gt;&lt;b&gt;by MR spectroscopy &lt;/b&gt;

Recently brain imaging studies have shown that patients with chronic pain have an altered cortical processing of nociceptive inputs. We evaluated brain metabolites in patients with complex regional pain syndrome (CRPS) using MR spectroscopy. Absolute concentrations of N-acetylaspartate (NAA) and choline (Cho) were measured in anterior cingulate (ACC) and prefrontal cortices (PFC) of patients and volunteers as matched control. Psychological aspects of patients were also evaluated with Hospital Anxiety and Depression (HAD) scale, in addition to the intensity of pain by visual analog scale. In the ACC, CRPS patients had a significant decrease of NAA and a significant increase of Cho compared to the control. Furthermore, patients with anxiety scored by HAD scale had reduced NAA concentration in ACC compared to the patients without anxiety. In the PFC,there was a reduction of NAA in the patients compared with that in control. No correlation was observed between intensity of pain and these metabolites. These results suggest that metabolite changes in ACC and PFC could reflect the pathogenesis of CRPS.

Magnetic Resonance Spectroscopy Findings in Photosensitive Idiopathic Generalized Epilepsy

Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients.

1H-MRS at 4 Tesla in minimally treated early schizophrenia

We investigated glutamate-related neuronal dysfunction in the anterior cingulate (AC) early in schizophrenia before and after antipsychotic treatment. A total of 14 minimally treated schizophrenia patients and 10 healthy subjects were studied with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the AC, frontal white matter and thalamus at 4 T. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln) and Gln/Glu ratios were determined and corrected for the partial tissue volume. Patients were treated with antipsychotic medication following a specific algorithm and (1)H-MRS was repeated after 1, 6 and 12 months. There were group x region interactions for baseline NAA (P=0.074) and Gln/Glu (P=0.028): schizophrenia subjects had lower NAA (P=0.045) and higher Gln/Glu (P=0.006) in the AC before treatment. In addition, AC Gln/Glu was inversely related to AC NAA in the schizophrenia (P=0.0009) but not in the control group (P=0.92). Following antipsychotic treatment, there were no further changes in NAA, Gln/Glu or any of the other metabolites in any of the regions studied. We conclude that early in the illness, schizophrenia patients already show abnormalities in glutamatergic metabolism and reductions in NAA consistent with glutamate-related excitotoxicity.

Metabolite alterations in the hippocampus of high-functioning adult subjects with autism

The aim of the present study was to investigate metabolite alterations in the hippocampal formation as they relate to aggression in high-functioning adults with autism. We measured concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr+PCr) in the hippocampal formation by proton magnetic resonance spectroscopy in 12 non-medicated male subjects with autism and 12 age- and sex-matched controls. Aggression was scored in the autistic subjects using the Buss-Perry Aggression Questionnaire. The concentrations of Cho and Cr+PCr in the hippocampal formation in autistic subjects were significantly higher than the corresponding values in control subjects, and a significant positive correlation was observed between the concentrations of these metabolites in the hippocampal formation and scores on the Buss-Perry Aggression Questionnaire in autistic subjects. Results suggest that high-functioning adult subjects with autism have abnormal metabolite concentrations in the hippocampal formation, which may in part account for their aggression.

Processing speed is correlated with cerebral health markers in the frontal lobes as quantified by neuroimaging

We explored relationships between decline in cognitive processing speed (CPS) and change in frontal lobe MRI/MRS-based indices of cerebral integrity in 38 healthy adults (age 57–90 years). CPS was assessed using a battery of four timed neuropsychological tests: Grooved Pegboard, Coding, Symbol Digit Modalities Test and Category Fluency (Fruits and Furniture). The neuropsychological tests were factor analyzed to extract two components of CPS: psychomotor (PM) and psychophysical (PP). MRI-based indices of cerebral integrity included three cortical measurements per hemisphere (GM thickness, intergyral and sulcal spans) and two subcortical indices (fractional anisotropy (FA), measured using track-based spatial statistics (TBSS), and the volume of hyperintense WM (HWM)). MRS indices included levels of choline-containing compounds (GPC+PC), phosphocreatine plus creatine (PCr+Cr), and N-acetylaspartate (NAA), measured bilaterally in the frontal WM bundles. A substantial fraction of the variance in the PM-CPS (58%) was attributed to atrophic changes in frontal WM, observed as increases in sulcal span, declines in FA values and reductions in concentrations of NAA and choline-containing compounds. A smaller proportion (20%) of variance in the PP-CPS could be explained by bilateral increases in frontal sulcal span and increases in HWM volumes.