Absolute N-acetylaspartate Research Articles

Impact of adapted physical activity on hippocampal N-Acetyl Aspartate in patients with schizophrenia

IntroductionAdapted physical activity (APA) has beneficial neurobiological impact but the underlying pathophysiological mechanisms remain poorly described. APA is currently recognized as an adjuvant therapy to antipsychotic treatments in patients with schizophrenia (SCZs) to reduce the severity of negative symptoms and cognitive impairment. SCZs exhibit hippocampal N-acetylaspartate (NAA) reduction, a marker of neuronal viability and integrity whose concentrations can be assessed by proton magnetic resonance spectroscopy (1H-MRS).ObjectivesThe purpose of this study was to evaluate the impact of remote physical activity (e-APA) via the web on the NAA relative variations in the left hippocampus in SCZs compared to a patient control group benefiting from an health education program (HE). This study concerns one of the secondary objectives of the PEPsy V@SI study co-financed by the Pierre Deniker Foundation, the European Union and the Normandy Region within the framework of the FEDER/FSE 2014-2020 operational program.MethodsThirty-five SCZs were randomized in the e-APA active group or in the control group (HE). Participants received the interventions during 16 weeks, with two visioconference sessions per week. A 1H-MRS sequence positioned on the left hippocampus (MRI-3T) was acquired before and after both interventions. Absolute NAA concentrations in the left hippocampus were obtained using Osprey software after partial volume correction. After checking the quality criteria, the spectra of 6 SCZs in the e-APA group and 8 SCZs in the HE group were analyzed. To test the difference between interventions on the NAA relative variations, a Wilcoxon-Mann-Whitney test and effect size were performed. Paired Wilcoxon tests were used in each group before and after the interventions.ResultsNo significant difference was found in NAA relative variations in the left hippocampus between the e-APA group and the HE group (p = 0.18), although the effect size was 0.38 (considered as moderate). However, a trend towards an increase of NAA was observed in the e-APA group (before intervention: 12.08 International Units (I.U); after: 13.81 I.U) (p = 0.06) but not in the HE group (before intervention: 13.75 I.U ; after: 13.85 I.U) (p = 0.84).ConclusionsOur results showed a NAA significant increase in SCZs after an e-APA program, indicating a beneficial impact of e-APA on neuronal viability that might reflect an hippocampal plasticity. However, this increase did not differ significantly between active and control groups probably due to a weak statistical power.Disclosure of InterestL. Metivier: None Declared, F. Briend: None Declared, M. Tréhout: None Declared, L. Bigot: None Declared, G. Quarck: None Declared, A. Herbinet: None Declared, E. Leroux: None Declared, S. Dollfus Consultant of: Fabre,Gedeon,Roche and Takeda, inivited Conferences by Lundbeck, Otsuka, Janssen ; at contracts with Prophase MedAvances and NeuroCogTrials

Characterization of the 1H-MRS Metabolite Spectra in Transgender Men with Gender Dysphoria and Cisgender People.

Much research has been conducted on sexual differences of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual differences at the metabolite level using magnetic resonance spectroscopy (1H-MRS) have not been explored in transgender people. In this study, 28 cisgender men (CM) and 34 cisgender women (CW) and 29 transgender men with GD (TMGD) underwent 1H-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, levels of N–acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate and glutamine (Glx), and myo-inositol + glycine (mI + Gly) were assessed in two brain regions, the amygdala-anterior hippocampus and the lateral parietal cortex. The results indicated a sex-assigned at birth pattern for Cho/Cr in the amygdala of TMGD. In the parietal cortex, a sex-assigned at birth and an intermediate pattern were found. Though assessed post-hoc, exploration of the age of onset of GD in TMGD demonstrated within-group differences in absolute NAA and relative Cho/Cr levels, suggestive for a possible developmental trend. While brain metabolite levels in TMGD resembled those of CW, some interesting findings, such as modulation of metabolite concentrations by age of onset of GD, warrant future inquiry.

Magnetic Resonance Spectroscopy in Gender Dysphoria

Background: Much research has been conducted on sexual dimorphisms of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual dimorphisms at the metabolite level in transgender people have not been explored using magnetic resonance spectroscopy (1H-MRS). Methods: In this study, 29 transgender men, 30 cisgender men and 35 cisgender women underwent 1H-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, absolute levels of N –acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate (Glu), myo-inositol (mI) and their respective ratios were assessed in two brain regions, i.e. the amygdala-anterior hippocampus and the lateral parietal cortex. Influences of nicotine consumption, physical activity, education and psychopathology were considered. Results: The results indicated a sex-assigned at birth pattern for choline and glutamate ratios in the amygdala-anterior hippocampus of trans men. In the lateral parietal cortex cis men and cis women differed in the majority of metabolites (i.e. mI; Cr; NAA/Cr; Cho/Cr; mI/Cr; NAA/mI). Moreover, except for mI, trans men did not differ from either cisgender group, showing a pattern subtly moving towards the experienced gender identity. Post-hoc, careful exploration of the age of onset of GD in transgender men demonstrated the possibility of a developmental trend in absolute NAA levels, as a measure of neuronal function. Conclusion: We found sex-typical 1H-MRS spectra and they appear to be brain region specific. While the brain metabolite levels in trans men mostly resembled that of cis women, interesting findings such as modulation by age of onset warrant future enquiry to address potential neurobiological underpinnings of GD.

Insular Cell Integrity Markers Linked to Weight Concern in Anorexia Nervosa-An MR-Spectroscopy Study.

Objective: An insular involvement in the pathogenesis of anorexia nervosa (AN) has been suggested in many structural and functional neuroimaging studies. This magnetic resonance spectroscopy (MRS) study is the first to investigate metabolic signals in the anterior insular cortex in patients with AN and recovered individuals (REC). Method: The MR spectra of 32 adult women with AN, 21 REC subjects and 33 healthy controls (HC) were quantified for absolute N-acetylaspartate (NAA), glutamate + glutamine (Glx), total choline, myo-inositol, creatine concentrations (mM/L). After adjusting the metabolite concentrations for age and partial gray/white matter volume, group differences were tested using one-way multivariate analyses of variance (MANOVA). Post-hoc analyses of variance were applied to identify those metabolites that showed significant group effects. Correlations were tested for associations with psychometric measures (eating disorder examination), duration of illness, and body mass index. Results: The MANOVA exhibited a significant group effect. The NAA signal was reduced in the AN group compared to the HC group. The REC and the HC groups did not differ in metabolite concentrations. In the AN group, lower NAA and Glx signals were related to increased weight concern. Discussion: We interpret the decreased NAA availability in the anterior insula as a signal of impaired neuronal integrity or density. The association of weight concern, which is a core feature of AN, with decreased NAA and Glx indicates that disturbances of glutamatergic neurotransmission might be related to core psychopathology in AN. The absence of significant metabolic differences between the REC and HC subjects suggests that metabolic alterations in AN represent a state rather than a trait phenomenon.

Sex differences in brain metabolite concentrations in healthy children – proton magnetic resonance spectroscopy study (<sup>1 </sup>HMRS)

PurposeThe aim of this 1HMRS study was to define sex-related differences in metabolic spectrum between healthy children. Forty-nine girls and boys aged 6-15 years were examined.Material and methodsVolume of interest was located in seven brain regions: frontal lobes, basal ganglia, hippocampi, and cerebellum.ResultsStatistical analysis of the results showed significantly higher (p < 0.05) myo-inositol concentrations relative to the total concentrations in the boys than the girls, as well as higher absolute N-acetyl aspartate concentrations in the left frontal lobes in girls. No other significant differences were shown, except for trends in differences.ConclusionsIn clinical practice the diagnostic process first of all focuses on assessing concentrations of metabolites to relative cerebellum concentration. Thus, the findings of the present study allow the conclusion that when analysing the results of 1HMRS studies in children it is not necessary to take into account the child’s gender.

Early Life Stress Associated With Increased Striatal N-Acetyl-Aspartate: Cerebrospinal Fluid Corticotropin-Releasing Factor Concentrations, Hippocampal Volume, Body Mass, and Behavioral Correlates

Introduction Using proton magnetic resonance spectroscopy imaging, the effects of early life stress on nonhuman primate striatal neuronal integrity were examined as reflected by N-acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented early life stress markers—cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens. We hypothesized that rearing under conditions of early life stress (variable foraging demand, VFD) would produce persistent elevations of NAA concentrations (in absolute or ratio form) in ventral striatum/caudate nucleus (VS/CN) with altered correlation to early life stress markers. Methods Eleven bonnet macaque males reared under VFD conditions and seven age-matched control subjects underwent proton magnetic resonance spectroscopy imaging during young adulthood. Voxels were placed over VS/CN to capture nucleus accumbens. Cisternal cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and response to a human intruder had been previously determined. Results VFD-reared monkeys exhibited significantly increased NAA/creatine concentrations in right VS/CN in comparison to normally reared controls, controlling for multiple comparisons. In comparison to controls, VFD cerebrospinal fluid corticotropin-releasing factor concentrations were directly associated with right VS/CN absolute NAA. Left hippocampal volume was inversely associated with left VS/CN NAA/creatine in VFD reared but not in controls. Disruption of a normative inverse correlation between left VS/CN NAA and body mass was noted in VFD. Only non-VFD subjects exhibited a direct relationship between timidity response to an intruder and right VS/CN NAA. Conclusion Early life stress produced persistent increases in VS/CN NAA, which demonstrated specific patterns of association (or lack thereof) to early life stress markers in comparison to non-VFD subjects. The data are broadly consistent with a stable nonhuman primate phenotype of anxiety and mood disorder vulnerability whereby in vivo indicators of neuronal integrity, although reduced in hippocampus, are increased in striatum. The findings may provide a catalyst for further studies in humans and other species regarding a reciprocal hippocampal/nucleus accumbens relationship in affective disorders.

Whole brain neuronal abnormalities in focal quantified with proton MR spectroscopy

ObjectiveTo test the hypothesis that localization-related epilepsy is associated with widespread neuronal dysfunction beyond the ictal focus, reflected by a decrease in patients’ global concentration of their proton MR spectroscopy (1H-MRS) observed marker, N-acetyl-aspartate (NAA). MethodsThirteen patients with localization-related epilepsy (7 men, 6 women) 40 ± 13 (mean ± standard-deviation) years old, 8.3 ± 13.4 years of disease duration; and 14 matched controls, were scanned at 3 T with MRI and whole-brain (WB) 1H MRS. Intracranial fractions of brain volume, gray and white matter (fBV, fGM, fWM) were segmented from the MRI, and global absolute NAA creatine (Cr) and choline (Cho) concentrations were estimated from their WB 1H MRS. These metrics were compared between patients and controls using an unequal variance t test. ResultsPatients’ fBV, fGM and fWM: 0.81 ± 0.07, 0.47 ± 0.04, 0.31 ± 0.04 were not different from controls’ 0.79 ± 0.05, 0.48 ± 0.04, 0.32 ± 0.02; nor were their Cr and Cho concentrations: 7.1 ± 1.1 and 1.3 ± 0.2 millimolar (mM) versus 7.7 ± 0.7 and 1.4 ± 0.1 mM (p > 0.05 all). Patients’ global NAA concentration: 11.5 ± 1.5 mM, however, was 12% lower than controls’ 13.0 ± 0.8 mM (p = 0.004). ConclusionsThese findings indicate that neuronal dysfunction in localization-related epilepsy extends globally, beyond the ictal zone, but without atrophy or spectroscopic evidence of other pathology. This suggests a diffuse decline in the neurons’ health, rather than their number, early in the disease course. WB 1H-MRS assessment, therefore, may be a useful tool for quantification of global neuronal dysfunction load in epilepsy.

Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8‐depleted rhesus macaques: proton MRS imaging at 3 T

To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 × 16 × 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm(3) spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 ± 0.4 to 6.0 ± 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 ± 0.2 to 1.0 ± 0.1 mM (p < 0.003); global mI increased 11%: 5.7 ± 0.4 to 6.5 ± 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response.

Brain structure and function in borderline personality disorder

The spotlight on borderline personality disorder (BPD) has been growing in recent years, with the number of papers discussing potential causes and triggers of the disorder rapidly on the increase. Also on the increase, though still lacking sufficient numbers to produce well-supported hypotheses, are studies employing neuroimaging techniques as investigative tools in BPD. In this review, we investigate the current state and findings of neuroimaging studies in BPD, focusing in particular, on the studies examining structural, functional, and neurometabolic abnormalities in the disorder. Some suspected trends in the data are highlighted, including reductions in the hippocampi and amygdalae of BPD patients compared to healthy controls, exaggerated amygdala activity in BPD patients when confronted with emotion-related stimulus, and negative correlations between increases in left amygdalar creatine and reductions in amygdalar volume, reductions in absolute N-acetylaspartate concentration in the dorsolateral prefrontal cortex of BPD patients, and increases in glutamate concentration in the anterior cingulate cortices of BPD patients. We also discuss the limitations of some of the current studies including hindrances due to sample effects and techniques used and the potential of future neuroimaging research in BPD.

Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex

Decreased levels of N-acetylaspartate (NAA) and brain-derived neurotrophic factor (BDNF) in the anterior cingulate cortex (ACC) have been linked to neuronal loss and psychiatric disorders like schizophrenia and bipolar disorder.We previously found that BDNF serum concentration was predicted by the concentration of NAA in the ACC, indicating that neuronal integrity and vitality of a cortical region like the ACC, as reflected by a high concentration of NAA, might be related to high concentrations of BDNF in serum. Moreover, our recent finding that Val66Met genotype appears to predict the BDNF serum level in healthy human volunteers suggests the Met allele to be connected to higher concentrations of BDNF in serum.We examined absolute NAA concentrations in the ACC and hippocampus of 40 male and 42 female healthy volunteers (age: 33.3±9 years).We found NAA in the ACC to be significantly increased in Met carriers (F=5.2, df=1, p=0.025). On the other hand, the concentration of creatine+phosphocreatine in the hippocampus was significantly decreased in Met carriers.We hypothesize that higher NAA levels in the ACC might contribute to the protection of Met allele carriers against major psychiatric disorders as schizophrenia and bipolar disorder.

MR spectroscopic evaluation of N-acetylaspartate's T2 relaxation time and concentration corroborates white matter abnormalities in schizophrenia

Magnetic resonance spectroscopy enables the in vivo analysis of certain aspects of brain biochemistry. Reduced N-acetylaspartate in key regions of schizophrenia has been reported repeatedly but not without controversy. Our objective is to investigate whether reduced N-acetylaspartate concentrations determined without correction for individual T2 relaxation time (referred to as ‘apparent tNAA concentration’) are due to a reduced absolute N-acetylaspartate concentration or to altered relaxation properties. For this purpose we measured absolute concentrations while evaluating individual T2 relaxation times. We evaluated the metabolite concentrations and metabolite/water relaxation times of a frontal white matter voxel from 23 patients who met DSM-IV criteria for schizophrenia and 29 healthy control subjects with similar age at a 3 T magnetic resonance scanner. A significantly reduced N-acetylaspartate concentration as well as shortened N-acetylaspartate's T2 relaxation time in the schizophrenic patient group was found. The apparent N-acetylaspartate concentration difference between healthy controls and patients with schizophrenia increased with the echo time due to a decreased N-acetylaspartate's T2 in the schizophrenic group. No group difference was found for any other metabolite concentration or metabolite/brain water relaxation time. These findings of reduced N-acetylaspartate as well as shortened N-acetylaspartate's T2 relaxation time give further evidence for microstructural white matter changes in schizophrenia. Furthermore, they elucidate why reports of a reduced N-acetylaspartate concentration in schizophrenia were not always corroborated.

Combined 3T Diffusion Tensor Tractography and1H-MR Spectroscopy in Motor Neuron Disease

Diagnostic confidence in motor neuron disease may be improved by the use of advanced MR imaging techniques. Our aim was to assess the accuracy (sensitivity/specificity) and agreement of combined (1)H-MR spectroscopy (proton MR spectroscopy) and diffusion tensor imaging (DTI) at 3T in patients with suspected motor neuron disease regarding detection of upper motor neuron (UMN) dysfunction. Eighteen patients with suspected motor neuron disease were studied with MR spectroscopy/DTI and clinically rated according to the El-Escorial and ALSFRS-R scales. For MR spectroscopy, absolute N-acetylaspartate (NAA), choline (Cho), and phosphocreatine (PCr) concentrations and relative NAA/Cho and NAA/PCr ratios of corresponding volumes of interest within the primary motor cortex were calculated. For DTI, fractional anisotropy (FA) and mean diffusivity (MD) were measured bilaterally at the level of the precentral gyrus, corona radiata, internal capsule, cerebral peduncles, pons, and pyramid. FA and MD statistics were averaged on the corticospinal tracts (CSTs) as a whole to account for a region-independent analysis. MR spectroscopy indicated NAA reduction beyond the double SD of controls in 6 of 8 patients with clinical evidence for UMN involvement. Congruently, the mean FA of these patients was significantly lower in the upper 3 regions of measurements (P < .01). Overall, MR spectroscopy and DTI were concordant in all except 3 cases: 1 was correctly excluded from motor neuron disease by DTI (genetically proved Kennedy syndrome), whereas MR spectroscopy indicated CST involvement. MR spectroscopy and DTI each were false-positive for CST affection in 1 patient with lower motor neuron involvement only. Combined MR spectroscopy/DTI at 3T effectively adds to the detection of motor neuron disease with a high degree of accordance.

Anteroposterior hippocampal metabolic heterogeneity: three-dimensional multivoxel proton 1H MR spectroscopic imaging--initial findings.

To quantify proton magnetic resonance (MR) spectroscopy-detectable metabolite concentrations along anteroposterior axis of hippocampus in healthy young and elderly subjects. Young (three women, three men; age range, 25-35 years) and elderly (four women, two men; age range, 68-72 years) groups underwent MR imaging and proton MR spectroscopic imaging at 3 T in this HIPAA-compliant prospective study and gave institutional review board-approved written consent. Volume of interest was centered on and tilted parallel to hippocampal anteroposterior plane. Absolute N-acetylaspartate (NAA), choline, and creatine levels were obtained in each voxel, with phantom replacement. Mean NAA, creatine, and choline concentrations in the young group were higher in posterior hippocampus (12.9 mmol/L +/- 2.0 [standard deviation], 7.8 mmol/L +/- 1.2, 2.3 mmol/L +/- 0.4, respectively) than anterior hippocampus (8.0 mmol/L +/- 1.1, 6.0 mmol/L +/- 1.4, 1.5 mmol/L +/- 0.2; P = .005, .02, and .0002, respectively). In the elderly group, mean concentrations were higher in posterior hippocampus (8.6 mmol/L +/- 0.9, 5.6 mmol/L +/- 0.6, 1.5 mmol/L +/- 0.2, respectively) than anterior hippocampus (7.2 mmol/L +/- 1.0, 2.4 mmol/L +/- 0.3, 1.0 mmol/L +/- 0.2; P = .006, .0001, .04, respectively). Mean concentrations were significantly higher in the young group (13.2 mmol/L +/- 1.0, 7.4 mmol/L +/- 0.8, 2.1 mmol/L +/- 0.3, respectively) than in the elderly group (9.0 mmol/L +/- 1.0, 5.8 mmol/L +/- 0.8, 1.8 mmol/L +/- 0.3; P = .0001, .01, .05, respectively). Posteroanterior metabolic gradients differed: NAA decreased faster in the young group (-1.0 mmol/L x cm(-1)) than the elderly group (-0.7 mmol/L x cm(-1)); creatine and choline concentrations decreased faster in the elderly group (-0.8 and -0.058 mmol/L x cm(-1), respectively) than the young group (-0.16 and -0.008 mmol/L x cm(-1), respectively). No left-right metabolic differences were found. Significant metabolic heterogeneity was observed between groups and along anteroposterior axis of healthy hippocampus in both groups. Age matching and consistent voxel placement are important for correct comparisons of both absolute metabolic levels and metabolite ratios in longitudinal intra- and intersubject cross-sectional studies.

Absolute Quantification in Proton Magnetic Resonance Spectroscopy Is Superior to Relative Ratio to Discriminate Alzheimer’s Disease from Binswanger’s Disease

Background/Aims: Although many proton magnetic resonance spectroscopy studies have assessed the relative ratios of brain metabolites from patients with dementia, absolute quantification is rare. The aim of this study is to compare the diagnostic accuracy of these 2 methods in proton magnetic resonance spectroscopy in discriminating Alzheimer’s disease (AD) and Binswanger’s disease (BD) from healthy controls (HC). Methods: The subjects were 30 AD patients, 13 BD patients and 26 HC subjects. Single-voxel proton MR spectra at short echo times were acquired from 8 volumes of interest. Results: At 80% specificity, the absolute N-acetylaspartate concentration in the hippocampus was the most sensitive measure to discriminate AD from HC, and the absolute N-acetylaspartate concentration in the anterior periventricular and deep white matter to differentiate BD from HC and AD. No relative ratio using creatine as a reference had a sensitivity over 80% at 80% specificity. The cause of disparities between the 2 methods was attributed to fluctuations in the creatine concentration. Conclusion: Our study revealed that absolute quantification is superior to relative ratio to differentiate AD and BD from HC.

Occipital Proton Magnetic Resonance Spectroscopy (1H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

BackgroundProgressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative processes, are reduced in the occipital brain region.Methodology/Principal FindingsParticipants known with glaucoma, age-related macular degeneration (the two leading causes of visual impairment in the developed world), and controls were examined by proton MR spectroscopic (1H-MRS) imaging. Absolute NAA, Creatine and Choline concentrations were derived from a single-voxel in the occipital region of each brain hemisphere. No significant differences in metabolites concentrations were found between the three groups.Conclusions/SignificanceWe conclude that progressive retinal visual field defects do not affect metabolite concentration in visual brain areas suggesting that there is no ongoing occipital degeneration. We discuss the possibility that metabolite change is too slow to be detectable.

Characterizing ‘mild’ in traumatic brain injury with proton MR spectroscopy in the thalamus: Initial findings

Objective: Although most mild traumatic brain injury (mTBI) patients suffer any of several post-concussion symptoms suggestive of thalamic involvement, they rarely present with any MRI-visible pathology. The aim here, therefore, is to characterize their thalamic metabolite levels with proton MR spectroscopy (1H-MRS) compared with healthy controls.Methods: T1-weighted MRI and multi-voxel 1H-MRS were acquired at 3 Tesla from 20 mTBI (Glasgow Coma Scale score of 15–13) patients, 19–59 years old, 0–7 years post-injury; and from 17 age and gender matched healthy controls. Mixed model regression was used to compare patients and controls with respect to the mean absolute N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) levels within each thalamus.Results: The mTBI-induced thalamic metabolite concentration changes were under ±13.0% for NAA, ±13.5% for Cr and ±18.8% for Cho relative to their corresponding concentrations in the controls: NAA: 10.08 ± 0.30 (mean ± standard error), Cr: 5.62 ± 0.18 and Cho: 2.08 ± 0.09 mM. These limits represent the minimal detectable differences between the two cohorts.Conclusion: The change in metabolic levels in the thalamus of patients who sustained clinically defined mTBI could be an instrumental characteristic of ‘mildness’. 1H-MRS could, therefore, serve as an objective laboratory indicator for differentiating ‘mild’ from more severe categories of head-trauma, regardless of the presence or lack of current clinical symptoms.

Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients.

To retrospectively evaluate magnetic resonance (MR) imaging, hydrogen 1 (1H) MR spectroscopy, apparent diffusion coefficient (ADC), T1, and T2 measurements for prediction of late neurologic outcome in term neonates after severe perinatal asphyxia. This study was approved by the local ethics committee. Informed consent from parents was not required. Thirty term neonates (12 boys, 18 girls; age range, 2-12 days) with severe hypoxic-ischemic encephalopathy were examined during the first 12 days of life with conventional and diffusion-weighted cerebral MR imaging, 1H MR spectroscopy with absolute quantification, and T1 and T2 measurements. Quantitative 1H MR spectroscopy, T1, and T2 data were acquired on one 10-mm slab positioned at the level of the basal ganglia. The neonates were assigned to one of two groups according to their late (>12-month follow-up) neurologic outcome: those with an unfavorable outcome-that is, death or severe disability-and those with a favorable outcome. Clinical data, MR signal intensity abnormalities, ADCs, 1H MR spectroscopy findings, and relaxation times were compared by using Chi2 testing and analysis of variance to individualize the prognostic indicators. The unfavorable (n=16) and favorable (n=14) outcome groups were similar in terms of clinical data (ie, Apgar scores, visceral hypoxic injuries), visualization of brain edema on MR images, and T1 and T2 relaxation times. Late unfavorable neurologic outcome was associated with a mixed pattern of cortical and basal ganglia signal intensity abnormalities on MR images (13 babies with unfavorable vs three babies with favorable outcomes, P=.001) and with decreased absolute N-acetylaspartate (NAA) and choline concentrations in all brain structures, especially the basal ganglia (mean NAA concentration: 2.72 mmol/L in unfavorable outcome group vs 4.66 mmol/L in favorable outcome group, P<5x10(-9)), as measured with MR spectroscopy. In the basal ganglia, an NAA concentration lower than 4 mmol/L indicated an unfavorable individual prognosis with 94% sensitivity and 93% specificity. Significantly reduced ADCs also were noted in the unfavorable outcome group, but only during the first 6 days of life. Conventional MR imaging findings, spectroscopically measured absolute NAA and choline concentrations, and ADCs are complementary tools for predicting the individual outcomes of severely asphyxiated term neonates.

A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal lobe

Proton magnetic resonance spectroscopy ((1)H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the (1)H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel (1)H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel (1)H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying (1)H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders.

Relapsing-Remitting Multiple Sclerosis: Metabolic Abnormality in Nonenhancing Lesions and Normal-appearing White Matter at MR Imaging: Initial Experience

To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.

Subtle prefrontal neuropathology in a pilot magnetic resonance spectroscopy study in patients with borderline personality disorder.

The authors examined the brains of patients with borderline personality disorder (BPD) by using short echo time single voxel spectroscopy and found a significant 19% reduction of absolute N-acetylaspartate concentrations in the dorsolateral prefrontal cortex in BPD (P=0.01) compared with control subjects.