N-acetyl Asparate Research Articles

Quantitative GABA magnetic resonance spectroscopy as a measure of motor learning function in the motor cortex after subarachnoid hemorrhage.

The neural mechanisms underlying gross and fine motor dysfunction after subarachnoid hemorrhage (SAH) remain unknown. The γ-aminobutyric acid (GABA) deficit hypothesis proposes that reduced neuronal GABA concentrations and the subsequent lack of GABA-mediated inhibition cause motor impairment after SAH. This study aimed to explore the correlation between GABA levels and a behavioral measure of motor performance in patients with SAH. Motor cortical GABA levels were assessed in 40 patients with SAH and 10 age-matched healthy controls using proton magnetic resonance spectroscopy. The GABA and N-acetylasparate (NAA) ratio was measured in the normal gray matter within the primary motor cortex. The relationship between GABA concentration and hand-motor performance was also evaluated. Results showed significantly lower GABA levels in patients with SAH's left motor cortex than in controls (GABA/NAA ratio: 0.282 ± 0.085 vs. 0.341 ± 0.031, respectively; p = 0.041). Reaction times (RTs), a behavioral measure of motor performance potentially dependent on GABAergic synaptic transmission, were significantly longer in patients than in controls (936.8 ± 303.8 vs. 440.2 ± 67.3 ms, respectively; p < 0.001). Moreover, motor cortical GABA levels and RTs exhibited a significant positive linear correlation among patients (r = 0.572, rs = 0.327, p = 0.0001). Therefore, a decrease in GABA levels in the primary motor cortex after SAH may lead to impaired cortical inhibition of neuronal function and indicates that GABA-mediated synaptic transmission in the motor cortex is critical for RT.

Peripheral triggering receptor expressed on myeloid cells 2 expression is associated with myoinositol level at posterior cingulate cortex in Alzheimer’s disease

AbstractBackgroundTriggering receptor expressed on myeloid cells 2 (TREM2) is up‐regulated in activated microglia related neuroinflammation in Alzheimer’s disease (AD). Most magnetic resonance spectroscopy (MRS) studies consistently demonstrated neuroinflammatory changes with elevated glial marker myoinositol (MI) or MI/total creatine (tCr) and lower levels of neuronal marker N‐acetylasparate (NAA) or NAA/tCr in patients with AD. We propose that the higher systemic TREM2 expression measured by TREM2 mRNA expression in peripheral blood might be associated with the neuroinflammatory marker in MRS.MethodWe recruited subjects with mild cognitive impairment (MCI) and dementia due to AD from two teaching hospitals in Taiwan. All of the subjects underwent clinically functional assessments and a neuropsychological test battery. Quantitative estimates of TREM2 mRNA and the soluble form of TREM2 (an alternatively spliced TREM2 transcript (TREM2alt)) mRNA levels were measured. Proton magnetic resonance spectroscopy (MRS) was performed by using a 2 × 2 × 2 cm3 voxel situated in the midsagittal posterior cingulate cortex (PCC)/precuneus region. We analyzed the association between MRS and peripheral TREM2 mRNA expression.ResultIn total, 15 MCI patients and 26 AD patients were recruited. The mean age of MCI and AD patients was 72.1 ± 6.0 and 76.7 ± 7.6 years. The mean MMSE score was 25.8 ± 2.1 in MCI patients and 20.8 ± 3.4 in AD patients. The percentage of apolipoprotein (APOE) ɛ4 carrier status in MCI and AD patients was 21.4% and 38.5%. The correlation analysis showed the TREM2alt mRNA expression level was associated with MI/tCr at PCC in AD (r = ‐0.68, p &lt; 0.001) and MCI (r = ‐0.63, p = 0.013) subjects, but TREM2 mRNA expression was not.ConclusionThe TREM2alt mRNA expression is associated with the MI/tCr at PCC in both AD and MCI patients, which suggested the peripheral soluble TREM2 expression might reflect the central neuroinflammatory changes in AD patients.

PROSEDUR PEMERIKSAAN MAGNETIC RESONANCE SPECTROSCOPY (MRS) CEREBRAL PADA KASUS GLIOBLASTOMA

ABSTRACT&#x0D; Background: Magnetic Resonance Imaging (MRS) can be applied to characterize existing musculoskeletal disorders to help determine the next medical examination. According to Florez-Alvarez et al. (2020), MRS examination in glioblastoma cases was carried out with multi voxel technique using 144 ms TE to optimally evaluate Choline (Cho) and N-acetyl asparate (NAA). Meanwhile, MRS examination in glioblastoma cases at the Radiology Department of RSUP DR. Sardjito was performed with multi voxel method using a TE of 40 ms.&#x0D; Methods: This research was conduted at the Radiology Department of RSUP DR. Sardjito Yogyakarta used a Siemens Sykra 3T in April 2021 for a patient with a diagnosis of glioblastoma who had complaints of dizziness and weakness of the right side of the body. This cerebral MRS examination using multi voxel method using a TE of 40 ms.&#x0D; Results: Based on the results of cerebral MRS examination in cases of glioblastoma at the Radiology Department of RSUP DR. Sardjito Yogyakarta, obtained the spectrum of Cho (11.0) NAA (0.00) in the tumor area, Cho (3.89) NAA (3.23) in the panumbra area, and Cho (5.91) NAA (12.7) in the healthy tissue area that can indicate a cell damage and can be graded with more complex calculation.&#x0D; Conclusions: The MRS examination was carried out using a 40 ms TE with multi voxel localixzer technique could more optimally evaluate the spectrum of Cho and NAA metabolites, where the two metabolites became the main reference in determining tumor pathology, especially glioblastoma when compare to 144 ms TE.

Accelerated radial echo-planar spectroscopic imaging using golden angle view-ordering and compressed-sensing reconstruction with total variation regularization.

To implement a novel, accelerated, 2D radial echo-planar spectroscopic imaging (REPSI) sequence using undersampled radial k-space trajectories and compressed-sensing reconstruction, and to compare results with those from an undersampled Cartesian spectroscopic sequence. The REPSI sequence was implemented using golden-angle view-ordering on a 3T MRI scanner. Radial and Cartesian echo-planar spectroscopic imaging (EPSI) data were acquired at six acceleration factors, each with time-equivalent scan durations, and reconstructed using compressed sensing with total variation regularization. Results from prospectively and retrospectively undersampled phantom and in vivo brain data were compared over estimated concentrations and Cramer-Rao lower-bound values, normalized RMS errors of reconstructed metabolite maps, and percent absolute differences between fully sampled and reconstructed spectroscopic images. The REPSI method with compressed sensing is able to tolerate greater reductions in scan time compared with EPSI. The reconstruction and quantitation metrics (i.e., spectral normalized RMS error maps, metabolite map normalized RMS error values [e.g., for total N-acetyl asparate, REPSI = 9.4% vs EPSI = 16.3%; acceleration factor = 2.5], percent absolute difference maps, and concentration and Cramer-Rao lower-bound estimates) showed that accelerated REPSI can reduce the scan time by a factor of 2.5 while retaining image and quantitation quality. Accelerated MRSI using undersampled radial echo-planar acquisitions provides greater reconstruction accuracy and more reliable quantitation for a range of acceleration factors compared with time-equivalent compressed-sensing reconstructions of undersampled Cartesian EPSI. Compared to the Cartesian approach, radial undersampling with compressed sensing could help reduce 2D spectroscopic imaging acquisition time, and offers a better trade-off between imaging speed and quality.

N-Acetylaspartate Improves Cell Survival When Glucose is Limiting

N-acetylasparate (NAA), previously considered a brain-specific metabolite, is found in several cancers. However, whether it plays a role in tumor growth or survival is not fully understood. We provide evidence that NAA prevents cell death in low-glucose conditions via sustaining intracellular UDP-N-acetylglucosamine (UDP-GlcNac) levels, suppressing endoplasmic reticulum (ER) stress, and enabling continued protein synthesis. NAA production is critical for in vivo tumor growth where lower glucose levels are present than those in cell culture. Furthermore, the breakdown of NAA leads to ER stress and cell death, suggesting that the role of NAA in low-glucose is independent of its catabolism to produce aspartate or acetate. Together, these data suggest NAA can support the growth of some tumors by helping them cope with glucose limitations in vivo.

Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in Early Phase Psychosis

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.

Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset

This study used Magnetic Resonance Spectroscopy (MRS) to identify potential neurometabolitic markers of cognitive performance in male (n = 7) and female (n = 8) middle-aged (∼5 years old) common marmosets (Callithrix jacchus). Anesthetized marmosets were scanned with a 4.7 T/40 cm horizontal magnet equipped with 450 mT/m magnetic field gradients and a 20 G/cm magnetic field gradient insert, within 3 months of completing the CANTAB serial Reversal Learning task. Neurometabolite concentrations of N-Acetyl Asparate, Myo-Inositol, Choline, Phosphocreatine + creatine, Glutamate and Glutamine were acquired from a 3 mm3 voxel positioned in the Prefrontal Cortex (PFC). Males acquired the reversals (but not simple discriminations) faster than the females. Higher PFC Glx (glutamate + glutamine) concentration was associated with faster acquisition of the reversals. Interestingly, the correlation between cognitive performance and Glx was significant in males, but not in females. These results suggest that MRS is a useful tool to identify biochemical markers of cognitive performance in the healthy nonhuman primate brain and that biological sex modulates the relationship between neurochemical composition and cognition.

Accuracy of 1H magnetic resonance spectroscopy for quantification of 2-hydroxyglutarate using linear combination and J-difference editing at 9.4 T

Non-invasive detection of 2-hydroxyglutarate (2HG) by magnetic resonance spectroscopy is attractive since it is related to tumor metabolism. Here, we compare the detection accuracy of 2HG in a controlled phantom setting via widely used localized spectroscopy sequences quantified by linear combination of metabolite signals vs. a more complex approach applying a J-difference editing technique at 9.4T.Different phantoms, comprised out of a concentration series of 2HG and overlapping brain metabolites, were measured with an optimized point-resolved-spectroscopy sequence (PRESS) and an in-house developed J-difference editing sequence. The acquired spectra were post-processed with LCModel and a simulated metabolite set (PRESS) or with a quantification formula for J-difference editing.Linear regression analysis demonstrated a high correlation of real 2HG values with those measured with the PRESS method (adjusted R-squared: 0.700, p<0.001) as well as with those measured with the J-difference editing method (adjusted R-squared: 0.908, p<0.001). The regression model with the J-difference editing method however had a significantly higher explanatory value over the regression model with the PRESS method (p<0.0001). Moreover, with J-difference editing 2HG was discernible down to 1mM, whereas with the PRESS method 2HG values were not discernable below 2mM and with higher systematic errors, particularly in phantoms with high concentrations of N-acetyl-asparate (NAA) and glutamate (Glu).In summary, quantification of 2HG with linear combination of metabolite signals shows high systematic errors particularly at low 2HG concentration and high concentration of confounding metabolites such as NAA and Glu. In contrast, J-difference editing offers a more accurate quantification even at low 2HG concentrations, which outweighs the downsides of longer measurement time and more complex postprocessing.

A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy

Ventricular enlargement, a common in vivo marker of aging, disease, and insult, is presumed to reflect atrophy of surrounding brain regions. Pathological mechanisms underlying ventricular enlargement, however, are likely specific to the condition under investigation. Here, multimodal imaging, incorporating structural magnetic resonance imaging (MRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI), was used in rats exposed to binge ethanol (EtOH) to provide insight into a mechanism of reversible ventricular enlargement. During intoxication, MRI revealed expansion of ventricles, but volume changes in dorsal or ventral hippocampi, caudate-putamen, or thalamus were not detectible. MRS of whole-brain parenchyma showed decreases in N-acetylasparate (NAA) and tissue water T2, and increases in choline-containing compounds (Cho). DWI showed decreased diffusivity selective to the thalamus. All MR parameters returned to baseline with 7 days of recovery. Rapid recovery of ventricular volume and the absence of detectable tissue volume reductions in brain regions adjacent to ventricles argue against atrophy as a mechanism of ventricular expansion. Decreased tissue water T2 and decreased thalamic diffusivity suggest lower tissue water content and a role for both NAA and Cho, as osmolytes is proposed. Together, these data support a model of fluid redistribution during acute EtOH intoxication and recovery to account for rapid ventricular volume changes.

N-acetylaspartate concentration in corpus callosum is positively correlated with intelligence in adolescents

The corpus callosum is the largest white matter bundle in the brain and integrates inter-hemispheric cortices during sensory-motor and high-order cognitive processes. The aim of the present study was to investigate the associations between the metabolite concentrations in the corpus callosum and intelligence among adolescents. Thirty male adolescents aged between 14 and 16 years were included into the study. We measured the intelligence quotient (IQ) scores of the subjects by using the Wechsler Intelligence Scale for Children-Revised (verbal, performance and full-scale IQ) test. We used proton MR spectroscopy to measure the absolute concentrations of N-acetylasparate (NAA), creatine (Cr) and choline (Cho) in the genu, midbody and isthmus/splenium regions of the corpus callosum. We also measured the whole brain parenchymal size and used it as a confounding factor in the statistical analyses. We assessed the correlations between neurometabolite concentrations and verbal, performance and full-scale IQ scores. We found a significant positive correlation between the whole brain parenchymal size and the full-scale IQ scores. And, the NAA concentration in the isthmus/splenium region was positively correlated with the performance IQ and full-scale IQ scores. NAA is a marker of neuro/axonal integrity. NAA concentration in white matter is related to the structural and functional integrity of axonal fibers. The positive correlation of the IQ scores with the NAA concentrations in the isthmus/splenium region indicates that more efficient inter-hemispheric data transfer between parieto-occipital cortices may enhance intellectual performance.

Abstract 3813: Metabolites as biomarkers for ovarian cancer diagnosis and treatment

Abstract Ovarian cancer is the most lethal malignancy of the female reproductive track, mainly due to a lack of a reliable detection method during the early stages of this disease when it is most treatable. Currently, most cases of ovarian cancer are detected at stage IV due to a lack of symptoms. As current detection methods identify 50-60% of early stage ovarian cancer, it is important to identify novel biomarkers that are both specific and sensitive. In this study, we compared the comprehensive metabolic profile in normal, primary epithelial ovarian cancer (EOC), and metastatic tumors resulting from primary ovarian cancer (MOC) using gas chromatograph mass spectroscopy (GC/MS) or liquid chromatograph mass spectroscopy (LC/MS). Despite a small sample size, we were able to detect significant changes in energy utilization, shifting from oxidative phosphorylation to fatty acid utilization marked by increases in several fatty acids and carnitine metabolism_such as carnitine, acetylcarnitine, and propionylcartine _and by increases in fatty acid metabolism. EOC and MOC also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate, phenylpyruvate, phenyllactate (PLA), and several isoforms of tocopherols. By using this method, we have also identified novel metabolites in the ovary, specifically N-acetylasparate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), for which a biological function has yet to be determined. Using these findings, potential biomarkers can be identified for both preliminary cancer diagnosis and metastatic disease progression. Supported by NCI CA 124630 (SSK). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3813. doi:10.1158/1538-7445.AM2011-3813

Measuring mania metabolites: a longitudinal proton spectroscopy study of hypomania

Using single-voxel proton spectroscopy we aimed to investigate changes in metabolite levels in key brain regions during hypomania and euthymia in patients with bipolar disorder (BD). Nine patients with a diagnosis of BD and nine age, sex, education, and handedness-matched comparison subjects underwent magnetic resonance proton spectroscopy (H(1)-MRS) using a 1.5 T magnet. Patients were assessed whilst hypomanic and euthymic. Metabolite (N-acetyl asparTate, NAA; myo-inositol, mI; choline, Cho) levels in the basal ganglia (BG), anterior cingulate cortex (AC), and frontal cortex (FC) were compared both between groups and within the patient group. Multivariate analysis revealed significant complex relationships between metabolite levels and brain regions with significant differences observed both between bipolar patients (hypomanic and euthymic) and controls, and across the two mood states. Hypomanic patients had lower mean metabolite levels when averaged across the AC and FC regions, compared with the controls. They also had a smaller difference in mean metabolite levels between the BG and FC than the control group. Euthymic patients were also found to have a smaller difference in the level of NAA between the BG and AC than the control group. This exploratory study of BD demonstrates significant differences in metabolite levels that vary both with respect to brain region and mood state. Not withstanding the confounding effects of medication and the limitation of small sample size the findings are important as they demonstrate that a longitudinal approach is a useful design especially in the context of a long-term phasic illness.

Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy

Creatine (Cr) levels in skeletal muscle and brain of a mouse model of Cr deficiency caused by guanidinoacetate methyltransferase absence (GAMT-/-) were studied after Cr supplementation with 2 g.kg body wt-1.day-1 Cr for 35 days. Localized 1H magnetic resonance spectroscopy (MRS) was performed in brain (cerebellum and thalamus/hippocampus) and in hind leg muscle of GAMT-/- mice before and after Cr supplementation and in control (Con) mice. As expected, a signal for Cr was hardly detectable in MR spectra of GAMT-/- mice before Cr supplementation. In the thalamus/hippocampus region of these mice, an increase in N-acetylasparate (NAA) was observed. During Cr administration, Cr levels increased faster in skeletal muscle compared with brain, but this occurred only during the first day of supplementation. Thereafter, Cr levels increased by 0.8 mM/day in all studied locations. After 35 days of Cr supplementation, Cr levels in all locations were higher compared with Con mice on a Cr-free diet and NAA levels normalized. Only because of the repeated MRS measurements performed in this longitudinal Cr supplementation study on GAMT-/- mice were we able to discover the initial faster uptake of Cr in skeletal muscle compared with brain, which may represent muscular Cr uptake independent of Cr transporter expression. Our results can provide the basis for additional experiments to optimize Cr supplementation in GAMT deficiency, as increases in brain Cr are slow in patients after Cr supplementation.

Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Study of Deficits in Hippocampal Structure in Fire Victims with Recent-Onset Posttraumatic Stress Disorder

To explore hippocampal structural abnormalities in fire victims with recent-onset posttraumatic stress disorder (PTSD). We compared 12 patients with recent-onset PTSD diagnosed according to DSM-IV criteria 6 to 8 months after a major fire with 12 individuals without PTSD who were victims of the same fire accident. Voxel-based morphometry (VBM) and magnetic resonance spectroscopy (MRS) were combined to examine hippocampal structural abnormalities in patients with recent-onset PTSD. Results of VBM showed that the grey matter density of the left hippocampus was lower in the group with PTSD than it was in the group without PTSD. Results of MRS showed that the ratio of N-acetyl asparate and creatine in the left hippocampus was significantly lower in patients with PTSD than in control subjects. Patients with recent-onset PTSD had hippocampal structural abnormalities.

Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

Background: Previous magnetic resonance imaging studies of posttraumatic stress disorder reported hippocampal volume loss. The goals of this study were 1) to determine the relationship between hippocampal atrophy and posttraumatic stress disorder in the absence of alcohol abuse, and 2) to test if loss of N-acetylaspartate (a neuron marker) in the hippocampus of posttraumatic stress disorder occurs separate from atrophy. In addition, volume changes in the entorhinal cortex were also explored. Methods: Eighteen male patients with combat-related posttraumatic stress disorder (mean age 51.2 ± 2.5 years) and 19 male control subjects (mean age 51.8 ± 3.2 years) were studied using magnetic resonance imaging and Proton magnetic resonance spectroscopic imaging. Both groups had no alcohol and drug abuse during the past 5 years. Results: Posttraumatic stress disorder and control subjects had similar volumes of hippocampus and entorhinal cortex. In contrast to volume, N-acetylaspartate was significantly reduced by about 23% bilaterally in the hippocampus of posttraumatic stress disorder when compared with control subjects, and creatine-containing compounds were reduced by 26% in the right hippocampus of posttraumatic stress disorder. Conclusions: N-acetyl asparate and creatine reductions imply that there are hippocampal abnormalities in posttraumatic stress disorder. Furthermore, these metabolite changes seem to be better indicators of posttraumatic stress disorder pathology than volume losses.

Serial proton magnetic resonance spectroscopy in lesions of Balò concentric sclerosis.

Balò concentric sclerosis is a rare demyelinating disorder. Serial proton magnetic resonance spectroscopic (1H-MRS) studies were carried out to better understand the biochemical changes within concentric lesions. Five concentric lesions in four patients with Balò concentric sclerosis were chosen as the objects of serial observation. They included two early acute lesions (showing as concentric ring enhancement on magnetic resonance imaging (MRI) after gadolinium administration), two late acute lesions (showing as marginal enhancement on MRI), and one early subacute lesion (showing as edematous concentric lesions without enhancement on MRI). The duration of follow-up ranged from 2-23 months (mean 10 months). A total of 20 1H-MRS studies were performed. On each 1H-MRS study, short-echo (30 ms) and long-echo (136 ms) spectra were obtained. The peaks of N-acetyl-asparate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), lactate, and mobile lipid were observed and compared. Generally, a decrease of NAA/Cr ratio and an increase of Cho/Cr ratio were seen on all the spectra. Observing longitudinally, a trend of decreasing NAA/Cr ratio first and then partially recovering later was noted. The lowest level of NAA/Cr ratio was noted at the late acute stage or early subacute stage. The Cho/Cr ratio and amplitude of the lactate peak showed a similar trend as that of NAA/Cr, but in an opposite direction. It was rising first and descending later. The highest levels of Cho/Cr ratio and lactate peak were also observed at the late acute or early subacute stage. In addition, lactate peaks could be detected as long as 7 months after onset of symptoms. Lipid metabolite (two broad peaks at 0.9-1.5 ppm) was seen at the initial study of each group, but fluctuated in size on follow-up. The characteristic biochemical changes of concentric sclerosis were a decreased NAA/Cr ratio, an increased Cho/Cr ratio, two broad peaks at 0.9-1.5 ppm, lactate production, and a reversible NAA/Cr ratio on follow-up. The serial 1H-MRS studies revealed a strong biochemical association between NAA, Cho, and lactate, which may be caused by the same pathogenetic process of demyelination and inflammatory cellular infiltration. The specificity of the serial changes may provide information about the stage of the concentric lesion and perhaps aid in monitoring progression of concentric lesions and evaluating therapy.

Connectivity maps of regional brain N-acetyl asparate for cognitive interference

Connectivity maps of regional brain N-acetyl asparate for cognitive interference

Mismatch between lactate and the apparent diffusion coefficient of water in progressive focal ischemia.

In this study, we examined mismatch in the area indicated by the normal apparent diffusion coefficient (ADC) of water and increased lactate in the early stage of focal cerebral ischemia. Five rats were subjected to permanent middle cerebral artery (MCA) occlusion. Diffusion-weighted echo planar imaging (DWEPI) and proton echo planar spectroscopic imaging (EPSI) were performed from 20 to 170 min after MCA occlusion, and lactate and N-acetyl asparate images were obtained by EPSI. Postmortem histological analysis was also performed. The areas of increased lactate and normal ADC were observed in the surrounding border zone of ischemia at approximately 20 min after MCA occlusion. This initial lactate in the border zone was significantly higher than that in the normal area, but lower than that in the ischemic core, which showed a reduction of ADC. However, this area was progressively involved in the ischemic core at 170 min without any treatment. The lactate-ADC mismatch in the initial period of ischemia may offer unique diagnostic information for ischemic tissue at high risk, followed by progressive involvement in the ischemic core without treatment. Considering that the accumulation of initial lactate in this area was not excessive, our findings may suggest that the lactate-ADC mismatch in the early period of ischemia indicates potentially salvageable tissue at high risk, requiring aggressive treatment.

Proton magnetic resonance spectroscopy of patients with parkinsonism

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson’s disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ( 1H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. 1H-MRS may be useful in monitoring patients with various types of parkinsonism.

Evidence of altered energy metabolism in autistic children

1. 1. In this pilot study, the authors investigated the hypotheses there are increased concentrations of lactate in brain and plasma and reduced brain concentrations of N-acetyl-asparate (NAA) in autistic children. 2. 2. NAA and lactate levels in the frontal lobe, temporal lobe and the cerebellum of 9 autistic children were compared to 5 sibling controls using MRS. Plasma lactate levels were measured in 15 autistic children compared to 15 children with epilepsy. 3. 3. Preliminary results show lower levels of NAA cerebellum in autistic children (p = 0.043). Lactate was detected in the frontal lobe in one autistic boy, but was not detected any of the other autistic subjects or siblings. 4. 4. Plasma lactate levels were higher in the 15 autistic children compared to 15 children with epilepsy (p = 0.0003). 5. 5. Higher plasma lactate in the autistic group is consistent with metabolic changes in some autistic children. The findings of altered brain NAA and lactate in autistic children suggest that MRS may be useful characterizing regional neurochermcal and metabolic abnormalities in autistic children.