Cerebral Metabolites Research Articles

Magnetic resonance spectroscopy: an in vivo molecular imaging biomarker for Parkinson's disease?

Parkinson's disease (PD) is a neurodegenerative disorder caused by selective loss of dopaminergic neurons in the substantia nigra pars compacta which leads to dysfunction of cerebral pathways critical for the control of movements. The diagnosis of PD is based on motor symptoms, such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor, which are evident only after the degeneration of a significant number of dopaminergic neurons. Currently, a marker for early diagnosis of PD is still not available. Consequently, also the development of disease-modifying therapies is a challenge. Magnetic resonance spectroscopy is a quantitative imaging technique that allows in vivo measurement of certain neurometabolites and may produce biomarkers that reflect metabolic dysfunctions and irreversible neuronal damage. This review summarizes the abnormalities of cerebral metabolites found in MRS studies performed in patients with PD and other forms of parkinsonism. In addition, we discuss the potential role of MRS as in vivo molecular imaging biomarker for early diagnosis of PD and for monitoring the efficacy of therapeutic interventions.

AGE-SPECIFIC CHARACTERISTICS OF CEREBRAL HEMODYNAMICS AND METABOLISM REORGANIZATION IN STROKE RECOVERY PERIOD PATIENTS

Complex examination results of ischemic atherothrombotic stroke patients of mean and middle age (282 ones) are presented in the article. It was assigned that in mean age patients comparing with control group of corresponding age cerebral hemodynamics changes are more marked than in middle age ones. At the same time in middle age patients is observed more intensive decreasing of main cerebral metabolites (NAA, Cr) than in mean age group. Also there are age-specific characteristics in structure interrelations of cerebral hemodynamics and metabolism reorganization.

Value of proton magnetic resonance spectroscopy of brain to study the cerebral metabolic abnormalities in COPD: Initial experience

BackgroundChronic obstructive pulmonary disease (COPD) patients were found to have cerebral metabolic abnormalities. Proton magnetic resonance spectroscopy (1H MRS) is a sensitive technique that detects metabolic changes of the brain. ObjectiveTo study the cerebral metabolic changes in COPD patients using 1H MRS. MethodsThis study was carried-out on twenty symptomatic COPD patients (16 male and 4 female) and age matched group of 20 healthy controls (11 male and 19 female). Pulmonary function tests, respiratory muscle strength, resting arterial blood gases, and 1H MRS of the brain were carried out on all subjects. The parieto-temporal and occipital regions were localized for 1H MRS. The metabolic ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) were calculated by the single voxel technique. ResultsIn comparison with healthy control subjects, the mean values of Cho/Cr in COPD patients were lower in parieto-temporal and occipital areas (0.99±0.21 vs. 1.10±0.31; P=0.22) (0.81±0.26 vs. 0.88±0.21; P=0.37), respectively while, the mean values of NAA/Cr in COPD patients were higher in both parieto-temporal and occipital areas of the brain (1.82±0.35 vs. 1.68±0.22; P=0.14) (1.59±0.31 vs. 1.39±0.39; P=0.08), respectively. In COPD patients, significant positive correlations were observed between maximal expiratory pressure (MEP) and NAA/Cr in parieto-temporal area of the brain. ConclusionsThe cerebral metabolites, arterial blood gases, respiratory muscle strength, and pulmonary function tests are altered in symptomatic COPD patients. 1H MRS is a non invasive technique that detects cerebral metabolic changes in COPD patients.

P.3.b.032 Hippocampal myo-inositol and glutamate concentrations are predictive of positive symptom severity in ultra-high risk for psychosis

The aim of this study was to quantitatively investigate the chronic ethanol-induced cerebral metabolic changes in various regions of the rat brain, using the proton high resolution magic angle spinning spectroscopy technique. The rats were divided into two groups (control group: N = 11, ethanol-treated group: N = 11) and fed with the liquid diets for 10 weeks. In each week, the mean intake volumes of liquid diet were measured. The brain tissues, including cerebellum (Cere), frontal cortex (FC), hippocampus (Hip), occipital cortex (OC) and thalamus (Thal), were harvested immediately after the end of experiments. The ex vivo proton spectra for the five brain regions were acquired with the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence at 500-MHz NMR spectrometer. All of the spectra were processed using the LCModel software, with simulated basis-set file, and the metabolite levels were referenced to total creatine. In the ethanol liquid diet group, there were significant increases in the metabolites ratio levels, as compared to control (Cere: alanine, glutathione, and N-acetlyaspartate; FC: phosphocholine and taurine; Hip: alanine, glutamine, and N-acetylaspartate; OC: glutamine; Thal: alanine, γ-aminobutyric acid, glutamate, glycerophosphocholine, phosphocholine, taurine, and free choline). However, in the ethanol liquid diet group, the myo-inositol levels of the OC were significantly lower. The present study demonstrates how chronic ethanol consumption affects cerebral metabolites in the chronic ethanol-treated rat. Therefore, this result could be useful to pursue clinical applications for quantitative diagnosis in human alcoholism.

The Effect of Insulin Infusion on the Metabolites in Cerebral Tissues Assessed With Proton Magnetic Resonance Spectroscopy in Young Healthy Subjects With High and Low Insulin Sensitivity

OBJECTIVEInsulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy (1H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity.RESEARCH DESIGN AND METHODSWe studied 16 healthy young men. 1H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity.RESULTSBaseline neurometabolic substrates were not different between the groups. Insulin infusion resulted in an increase in frontal NAA/Cr and NAA/H2O and frontal and temporal Glx/Cr and Glx/H2O and a decrease in frontal Cho/Cr and temporal Cho/H2O and myo-inositol/H2O (all P < 0.05, except temporal Glx/H2O, P = 0.054, NS) in the high-IS, but not in the low-IS, group. Insulin sensitivity correlated positively with frontal NAA/Cr and NAA/H2O and temporal Glx/H2O and negatively with temporal myo-inositol/Cr and myo-inositol/H2O assessed during the second 1H-MRS (all P < 0.05).CONCLUSIONSInsulin might influence cerebral metabolites, and this action is impaired in subjects with low whole-body insulin sensitivity. Thus, our results provide a potential link between insulin resistance and altered metabolism of the central nervous system.

SU-E-I-63: In Vivo Proton MR Spectroscopy Quantification of Cerebral Neurochemical Changes in Acute Binge Ethanol Exposed Rats

Purpose: The cerebral metabolite changes in vivo were quantitatively assessed in binge ethanol ‐ intoxicated rats by using a 4.7‐T proton magnetic resonance spectroscopy (1H‐MRS). Methods: Thirteen 8‐week‐old, male Sprague‐Dawley rats were used and divided into 2 groups (control group: n=6; binge ‐ ethanol group: n=7). 7 binge ethanol group rats received an initial dose of 5 g/kg (30% w/v solution) via oral gavage method, followed by a maximum dose of 2 g/kg (25% w/v solution) every 8‐h (at 1400, 2200, and 0600) for 4 days. The 6 control group rats simultaneously received equal volumes (about 3.55ml) of normal saline (at 1500, 2300, and 0700). Oral gavage ethanol was administered based on body weight. After 4‐days of oral gavage, in vivo scanning was performed on all animals by using a 4.7‐T Bruker BIOSPEC. The volume of interest (VOI, 6×2×3 mm3; volume: 36 μL; Thirteen water suppressed 1H‐MRS spectra were acquired using PRESS sequences (TR/TE = 4000/20 ms; number of acquisitions = 384; number of data points = 2048). Results: Figure 1 shows the representative fitted spectra from hippocampus of binge ethanol and control group rats. Our results showed that total choline (tCho; phosphocholine+glycerophosphocholine [GPC+PCh]) concentrations were significantly lower (p=0.038) in the binge ethanol group than that in the control group (Fig.2). Moreover, tCho/total N‐acetylaspartate (tNAA: NAA+N‐acetylaspartylglutamate [NAAG]) ratios were significantly lower (p=0.043) in the binge‐ethanol group than that in the control group (Fig.3). However, Glutamine/Glutamate ratios showed no significant differences between the 2 groups. Conclusion: According to our findings and from results in previous studies, significantly low tCho concentrations and tCho/tNAA ratios may indicate the cell membrane turnover abnormalities of phosphatidylcholine and changed adaptive mechanism in the hippocampus of binge ethanol intoxicated rats. Thus, we provide quantitative in vivo evidence that binge‐ethanol exposure causes cerebral neurochemical profile changes in rats, in the hippocampal region.

Examining cerebral metabolic abnormalities in chronic obstructive pulmonary disease (COPD) patients by localized proton magnetic resonance spectroscopy (MRS).

The study was planned based on the hypothesis that cerebral metabolism is impaired in chronic obstructive pulmonary disease (COPD) by using localized in vivo proton magnetic resonance spectroscopy. The study comprised 30 male patients, aged 45-70 years, with moderate level COPD and an aged matched group of 30 healthy males as the control group. Cerebral metabolism was investigated with proton magnetic resonance spectroscopy (MRS) using multivoxel technique. Data normal distribution conformity was evaluated by the One Sample Kolmogorov Smirnov Test and homogeneity by the One-Way ANOVA test. For both the COPD and control group, data were obtained as mean, standard deviations, minimum and maximum values. Independent sample t-test was used for the comparison of means between the two groups. The frontal and parietal white matter in patients with COPD showed an overall reduction in cerebral metabolites. The NAA (N-acetylaspartate)/Cr (Creatinine), Cho (Choline)/Cr ratios of the cerebral frontal and parietal white matter regions in the COPD group were significantly lower than the control group. The findings of this study through the use of MRS confirmed that most patients with symptomatic COPD have cerebral metabolic abnormalities.

Single spin-echo T 2 relaxation times of cerebral metabolites at 14.1 T in the in vivo rat brain

To determine the single spin-echo T2 relaxation times of uncoupled and J-coupled metabolites in rat brain in vivo at 14.1 T and to compare these results with those previously obtained at 9.4 T. Measurements were performed on five rats at 14.1 T using the SPECIAL sequence and TE-specific basis-sets for LCModel analysis. The T2 of singlets ranged from 98 to 148 ms and T2 of J-coupled metabolites ranged from 72 ms (glutamate) to 97 ms (myo-inositol). When comparing the T2s of the metabolites measured at 14.1 T with those previously measured at 9.4 T, a decreasing trend was found (p<0.0001). We conclude that the modest shortening of T2 at 14.1 T has a negligible impact on the sensitivity of the 1H MRS when performed at TE shorter than 10 ms.

Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter

We evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs). In this cross-sectional study, 35 HIV+ subjects aged ≥40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA <10 copies/10(6) cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV+ subjects were on combination antiretroviral therapy ≥1 year; all but 1 had plasma HIV RNA <50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV+ subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age. Relative to the HIV+ group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (-14%, p = 0.020) and total subcortical (-10%, p = 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p < 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels. Inability to clear peripheral blood of HIV DNA is associated with regional brain atrophy in well-controlled HIV infection, supporting the involvement of peripheral viral reservoirs in the neuropathogenesis of persistent HIV-related neurocognitive disorders.

Neurochemical Changes in the Rat Occipital Cortex and Hippocampus after Repetitive and Profound Hypoglycemia During the Neonatal Period: An Ex Vivo 1H Magnetic Resonance Spectroscopy Study

The brain of a human neonate is more vulnerable to hypoglycemia than that of pediatric and adult patients. Repetitive and profound hypoglycemia during the neonatal period (RPHN) causes brain damage and leads to severe neurologic sequelae. Ex vivo high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy was carried out in the present study to detect metabolite alterations in newborn and adolescent rats and investigate the effects of RPHN on their occipital cortex and hippocampus. Results showed that RPHN induces significant changes in a number of cerebral metabolites, and such changes are region-specific. Among the 16 metabolites detected by ex vivo (1)H NMR, RPHN significantly increased the levels of creatine, glutamate, glutamine, γ-aminobutyric acid, and aspartate, as well as other metabolites, including succine, taurine, and myo-inositol, in the occipital cortex of neonatal rats compared with the control. By contrast, changes in these neurochemicals were not significant in the hippocampus of neonatal rats. When the rats had developed into adolescence, the changes above were maintained and the levels of other metabolites, including lactate, N-acetyl aspartate, alanine, choline, glycine, acetate, and ascorbate, increased in the occipital cortex. By contrast, most of these metabolites were reduced in the hippocampus. These metabolic changes suggest that complementary mechanisms exist between these two brain areas. RPHN appears to affect occipital cortex and hippocampal activities, neurotransmitter transition, energy metabolism, and other metabolic equilibria in newborn rats; these effects are further aggravated when the newborn rats develop into adolescence. Changes in the metabolism of neurotransmitter system may be an adaptive measure of the central nervous system in response to RPHN.

NMR-based metabonomic in hippocampus, nucleus accumbens and prefrontal cortex of methamphetamine-sensitized rats

1H NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus, nucleus accumbens (NAC) and prefrontal cortex (PFC) of the rats subjected to subcutaneous twice-daily injections of 2.5mg/kg methamphetamine (MAP) for 7 days. The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats. The neurotransmitters glutamate, glutamine and GABA significantly decreased in hippocampus, NAC and PFC. Specifically, increased succinic acid semialdehyde, a metabolism product of GABA, was observed in hippocampus. Additionally, decreased serotonin was observed in both NAC and PFC, whereas decreased dopamine was only observed in NAC after repeated MAP treatment. Glutathione obviously decreased in above brain regions, whereas acetylcysteine declined in hippocampus and NAC, and taurine declined in NAC and PFC. Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration. Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC. N-Acetyl-aspartate, a marker of neuronal viability, decreased in the three regions; however, myo-inositol, a glial cell marker, increased in hippocampus and PFC. Tricarboxylic acid cycle intermediate products, such as α-ketoglutarate, succinate, citrate and the methionine significantly decreased in above three brain regions after MAP administration; however, ADP decreased in hippocampus. These results indicate that repeated MAP treatment causes neurotransmitters disturbance, imbalance between oxidative stress and antioxidants, and gliosis in hippocampus, NAC and PFC. Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP-induced sensitized rats.

Metabolic Changes in Patients with Aneurysmal Subarachnoid Hemorrhage Apart from Perfusion Deficits: Neuronal Mitochondrial Injury?

Neuronal damage in aSAH apart from perfusion deficits has been widely discussed. We aimed to test if cerebral injury occurs in aSAH independently from visible perfusion deficit by measuring cerebral metabolites in patients with aSAH without infarction or impaired perfusion. We performed 3T MR imaging including (1)H-MR spectroscopy, DWI, and MR perfusion in 58 patients with aSAH and 11 age-matched and sex-matched control patients with incidental aneurysm. We compared changes of NAA, Cho, Glx, Lac, and Cr between all patients with aSAH and controls, between patients with and without visible perfusion deficit or infarction and controls, and between patients with and without visible perfusion deficit or infarction by using the Wilcoxon signed-rank test. We found that NAA significantly (P < .005) decreased in all patients with aSAH. Cho was significantly increased in all patients compared with controls (P < .05). In patients without impaired perfusion or infarction, Glx was significantly decreased compared with both controls (P = .005) and patients with impaired perfusion or infarction (P = .006). The significant decrease of NAA and Glx in patients with aSAH but without impaired perfusion or infarction strongly suggests global metabolic changes independent from visible perfusion deficits that might reflect neuronal mitochondrial injury. Further, impaired perfusion in aSAH seems to induce additional metabolic changes from increasing neuronal stress that might, to some extent, mask the global metabolic changes.

Modulation of neural activation following treatment of hepatic encephalopathy

To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed. Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level-dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation. These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance.

Motor and Premotor Cortices in Subcortical Stroke

Background. Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. Objective. We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. Methods. In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. Results. N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively). Conclusions. Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

Cerebral Low-Molecular Metabolites Influenced by Intestinal Microbiota: A Pilot Study

Recent studies suggest that intestinal microbiota influences gut-brain communication. In this study, we aimed to clarify the influence of intestinal microbiota on cerebral metabolism. We analyzed the cerebral metabolome of germ-free (GF) mice and Ex-GF mice, which were inoculated with suspension of feces obtained from specific pathogen-free mice, using capillary electrophoresis with time-of-flight mass spectrometry (CE-TOFMS). CE-TOFMS identified 196 metabolites from the cerebral metabolome in both GF and Ex-GF mice. The concentrations of 38 metabolites differed significantly (p < 0.05) between GF and Ex-GF mice. Approximately 10 of these metabolites are known to be involved in brain function, whilst the functions of the remainder are unclear. Furthermore, we observed a novel association between cerebral glycolytic metabolism and intestinal microbiota. Our work shows that cerebral metabolites are influenced by normal intestinal microbiota through the microbiota-gut-brain axis, and indicates that normal intestinal microbiota closely connected with brain health and disease, development, attenuation, learning, memory, and behavior.

Quantitative Assessment of Metabolic Changes in the Developing Brain of C57BL/6 Mice by In Vivo Proton Magnetic Resonance Spectroscopy

Localized proton MRS was used to quantify cerebral metabolite concentrations in the thalamus of mice to assess the variation of major metabolites during brain development. Three sets of C57BL/6 mice were followed in a longitudinal study from a very early phase at post-natal day four (p4) until today 57 (p57). Experiments were conducted in accordance with Canadian animal care guidelines on a 7-Tesla small animal MR system. Specimens were examined under inhalation anesthesia using single-voxel MRS. A cubic volume with edge lengths of 1.9 mm was placed in the thalamus region of animals and point-resolved spectroscopy (PRESS) spectra were acquired with the following parameters (TR/TE/NEX=2500 ms/20 ms/600; Bandwidth=4000 Hz). Absolute metabolite quantification using LCModel was obtained by assigning water signal intensity measured by MRS to water concentrations determined by histobiochemical analysis and interpolation. Optimized anesthesia, immobilization, and careful monitoring led to a survival rate of 100% throughout the study. The brain water content was 84.8, 78.8, and 77.6% at p12, p31, and p66. Variation of metabolites revealed similar patterns for the total of creatine and phosphocreatine (tCr), glutamate and glutamine (Glx), and the total of N-acetyl aspartic compounds (tNAA), with steady increases from p4 to reaching a plateau after p21. The total of Cholinecontaining compounds (tCho) and myo-inositol (Ins) had high concentrations at early exam points, decreased to minima between p14 and p19, and increased to adult levels thereafter. Taurine (Tau) had highest levels at p4, decreased persistently but fast in the early development and slow in the later stages of brain development. Our results indicate that biological variance must be considered if results from studies on mouse models of pathologies are compared with results from healthy controls during development. This aspect seems to be especially important between p10 and p21. Due to the high temporal resolution used at early time points in our study and the inclusion of multiple groups of animals at time points, our data contribute important aspects to the existing literature about mouse brain development.

Disrupted cerebral metabolite levels and lower nadir CD4+ counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatmentpatients on stable treatment

Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV + patients scanned with whole-brain MRI at 1.5 T (mean age: 48.6 ± 8.4 years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4 + count, with a 1–2% white matter volume reduction for each 25-point reduction in nadir CD4 +. Even so, brain volume measured by TBM showed no detectable association with current CD4 + count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex — were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage.

Halogenated volatile anesthetics alter brain metabolism as revealed by proton magnetic resonance spectroscopy of mice in vivo

Halogenated volatile anesthetics (HVA) are widely used in medicine and research but their effects on brain metabolism in intact organisms are still largely unknown. Here, localized proton magnetic resonance spectroscopy (MRS) of anesthetized mice was applied to evaluate HVA effects on cerebral metabolites in vivo. Experimental protocols combined different concentrations of isoflurane, halothane, sevoflurane, and desflurane with known modulators of adrenergic, GABAergic, and glutamatergic neurotransmission. As a most striking finding, brain lactate increased in individual mice from 1.0 ± 0.6 mM (awake state) to 6.2 ± 1.5 mM (1.75% isoflurane). In addition, relative to total creatine, there were significant isoflurane-induced increases of alanine by 111%, GABA by 20%, choline-containing compounds by 20%, and myo-inositol by 10% which were accompanied by significant decreases of glucose by 51% and phosphocreatine by 9%. The elevation of lactate was most pronounced in the striatum. The HVA effects correlated with the respective minimal alveolar concentrations and were mostly reversible within minutes. The observed alterations are best explained by an HVA-induced stimulation of adrenergic pathways in conjunction with an inhibition of the respiratory chain. Apart from casting new light on cerebral energy metabolism, the present results challenge brain studies of HVA-anesthetized animals.

Postoperative Changes in Cerebral Metabolites Associated with Cognitive Improvement and Impairment after Carotid Endarterectomy: A 3T Proton MR Spectroscopy Study

Cognitive function can improve or decline after carotid endarterectomy. Proton MR spectroscopy can be used evaluate cerebral metabolites, such as N-acetylaspartate, choline, and creatine, in vivo. The purpose of the present study was to determine whether postoperative changes in cerebral metabolites measured by using 3T proton MR spectroscopy were associated with changes in cognitive function after CEA. In 100 patients undergoing CEA for ipsilateral cervical internal carotid artery stenosis (≥70%), brain proton MR spectroscopy was performed before and after surgery. NAA/Cr and Cho/Cr ratios were measured in regions of interest placed in the centrum semiovale of both cerebral hemispheres. Neuropsychological testing was also performed preoperatively and 1 month postoperatively. Multivariate statistical analysis of factors related to postoperatively changed cognition was performed, and odds ratios with 95% confidence intervals were calculated. On the basis of the neuropsychological assessments, 10 (10%), 80 (80%), and 10 (10%) patients were defined as having postoperatively improved, unchanged, and impaired cognition, respectively. A positive and high ΔNAA/Cr ratio (postoperative value-preoperative value) in the cerebral hemisphere ipsilateral to the operative site was significantly associated with postoperatively improved cognition (95% CI, 13.3-21.3; P = .0016). Negative and high absolute values of the ΔNAA/Cr ratio (95% CI, 0.018-0.101; P = .0039) and ΔCho/Cr ratio (95% CI, 0.042-0.135; P = .0046) in the ipsilateral cerebral hemisphere were significantly associated with postoperatively impaired cognition. Postoperative changes in cerebral metabolites measured by using proton MR spectroscopy were associated with changes in cognitive function after CEA.

Effects of isoflurane anesthesia on hyperpolarized (13)C metabolic measurements in rat brain.

Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose-dependent increase in cerebral blood flow and cerebral blood volume. Despite the widespread use of isoflurane in hyperpolarized (13)C preclinical research studies, a quantitative assessment of its effect on metabolic measurements is limited. This work investigates the effect of isoflurane anesthesia dose on hyperpolarized (13)C MR metabolic measurements in rat brain for [1-(13)C]pyruvate and 2-keto[1-(13)C]isocaproate. Dynamic 2D and 3D spiral chemical shift imaging was used to acquire metabolic images of rat brain as well as kidney and liver following bolus injections of hyperpolarized [1-(13)C]pyruvate or 2-keto[1-(13)C]isocaproate. The impact of a "low dose" vs. a "high dose" of isoflurane on cerebral metabolite levels and apparent conversion rates was examined. The cerebral substrate signal levels, and hence the metabolite-to-substrate ratios and apparent conversion rates, were found to depend markedly on isoflurane dose, while signal levels of metabolic products and their ratios, e.g. bicarbonate/lactate, were largely insensitive to isoflurane levels. No obvious dependence on isoflurane was observed in kidney or liver for pyruvate. This study highlights the importance of careful attention to the effects of anesthesia on the metabolic measures for hyperpolarized (13)C metabolic imaging in brain.