Single-voxel Proton Magnetic Resonance Spectroscopy Research Articles

Reliability Of Glutamate And Gaba Quantification Using Magnetic Resonance Spectroscopy

Proton magnetic resonance (MR) spectroscopy is a non-invasive technique used to determine relative concentrations of target metabolites in the brain. PURPOSE: The aim of this study was to determine the reliability of glutamate and GABA measures using a single-voxel proton MR spectroscopy protocol in healthy men and women. METHODS: Seven (4 female) healthy college age participants were tested at two time points separated by two weeks. The study was performed at 3T using a single voxel PRESS sequence for glutamate (TR/TE=1500/30ms) and an adapted MEGA-PRESS sequence for GABA (TR/TE=2000/68ms). Quantitation of glutamate and GABA was performed at two regions of interest, the primary motor cortex and the dorsolateral prefrontal cortex (DLPFC). Reliability across days was assessed with the intraclass correlation coefficient (ICC 2,1). RESULTS: There was no significant difference across time or region for glutamate (p=0.50 and p=0.06 respectively) or GABA (p=0.57 and p=0.91 respectively). There were no significant time-by-region interactions for glutamate (p=0.19) or GABA (p=0.26). Reliability across days was very strong for both glutamate (R=0.96) and GABA (R=0.88). CONCLUSIONS: These results support the use of MR spectroscopy measurements to reliably quantify concentrations of glutamate and GABA within the motor cortex and DLPFC.

Usefulness of quantitative peritumoural perfusion and proton spectroscopic magnetic resonance imaging evaluation in differentiating brain gliomas from solitary brain metastases.

The purpose of our study was to evaluate whether peritumoural perfusion weighted and proton spectroscopic magnetic resonance imaging can be used in differentiating between primary gliomas and solitary metastases. Ten low-grade gliomas, eight high-grade gliomas and 10 metastases were prospectively evaluated with magnetic resonance imaging, dynamic susceptibility contrast enhanced perfusion imaging and single-voxel proton magnetic resonance spectroscopy before surgical resection or stereotactic biopsy. Maximal relative cerebral blood volume values were calculated drawing three regions of interest of 2 cm(2) in the non-enhancing peritumoural areas. Maximal relative cerebral blood volume values were normalised to that of contralateral normal-appearing white matter. Maximal choline/creatine ratios were calculated from three voxels of 10 cm(3) placed in the peritumoural areas defined as non-enhancing peritumoural white matter surrounding the tumour. The tumour grade presumed with these values was compared to histopathological grading. Differences in the study parameters between groups were assessed using the Mann-Whitney test. A receiver operating characteristic analysis was performed to determine cut-off values. A clear relative cerebral blood volume cut-off value of 1.88 was detected for differentiating low-grade gliomas from high-grade gliomas. A clear relative cerebral blood volume cut-off value of 1.20 was detected for differentiation of metastases from gliomas. The differences in the choline/creatine ratios in the peritumoural regions of high-grade gliomas and of solitary metastasis were statistically significant (P < 0.001) but a clear cut-off value was not found. Our preliminary data support the hypothesis that peritumoural perfusion-weighted imaging can assist in preoperative differentiation between a glioma and a solitary metastasis.

Relationship between body mass index and hippocampal glutamate/glutamine in bipolar disorder.

We previously reported that patients with early-stage bipolar disorder, but not healthy comparison controls, had body mass index (BMI)-related volume reductions in limbic brain areas, suggesting that the structural brain changes characteristic of bipolar disorder were more pronounced with increased weight. To determine whether the most consistently reported neurochemical abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was also more prominent with higher BMI. We used single-voxel proton magnetic resonance spectroscopy to measure hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1) and 28 healthy controls (mean BMI = 23.3). In patients, but not healthy controls, linear regression demonstrated that higher BMI predicted greater Glx. Factorial ANCOVA showed a significant BMI × diagnosis interaction, confirming a distinct effect of weight on Glx in patients. Together with our volumetric studies, these results suggest that higher BMI is associated with more pronounced structural and neurochemical limbic brain changes in bipolar disorder, even in early-stage patients with low obesity rates.

Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case–control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks’ lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings.

Abstract P149: Distinct Profiles of Brain Medullary Metabolites Detected by 1 H-Magnetic Resonance Spectroscopy Correlate with Indices of Autonomic Function and Visceral Fat in Healthy Adults

Higher forebrain myoinositol (mIns), a marker of glial inflammation/proliferation as detected by proton magnetic resonance spectroscopy (MRS), correlates with systemic inflammation. Elevated circulating markers of inflammation are associated with lower baroreceptor reflex sensitivity (BRS) and heart rate variability (HRV) as well as visceral fat or central obesity. To determine whether transmitters/metabolites in a cardiovascularly (CV) relevant brain region correlate with age-related declines in BRS and HRV and markers of abdominal fat, autonomic profiles were determined by spectral and sequence analysis from continuous blood pressure and HR values in the supine position of healthy subjects 22 - 76 yrs old (12F, 4M); subjects later underwent a single voxel (10 x 7 x 20mm) proton MRS scan of dorsal medulla on a 3T magnet (n = 11; 9F, 2M) and measures of abdominal fat by computerized tomography (CT) (n = 9; 7F,2M). The mean arterial pressure was 88 ± 3 mm Hg, HR 64 ± 3 beats/min and BMI 27 ± 1 kg/m 2 . Glutamate (Glu) correlated directly with vagal (HF RRI r = 0.72, p &lt; 0.02) and inversely with sympathetic (LF RRI r = -0.72, p &lt; 0.02) control of HR. Markers of Glu metabolism and neuronal integrity/activity, N-acetyl-aspartate acid (NAA) + N-acetyl aspartyl glutamate (NAAG), did not correlate with age, but did correlate inversely with BRS (Seq ALL: r = -0.69, P &lt; 0.02), HRV (rMSSD: r = -0.76, p &lt; 0.008) and directly with HR (r = 0.68, p &lt; 0.03). Total visceral fat had a negative correlation with BRS (Seq Up: r = -0.70, p &lt; 0.02). mIns and markers of demyelination and reduced axonal integrity such as Glycerophosphocholine (GPC) and total choline containing compounds (GPC+PCh) exhibited striking positive correlations with percent visceral fat (r = 0.97, 0.81 and 0.82, P &lt; 0.02). BMI and GPC correlated with HR (r = 0.55, 0.72, p &lt; 0.04), but neither these nor mIns or choline compounds correlated with autonomic function. Thus, in healthy adults, Glu concentration in dorsal medulla directly correlates with cardiac vagal function, whereas markers of Glu metabolism inversely correlate with BRS and HRV. In contrast, markers of glial inflammation directly associate with increases in visceral adiposity, but not autonomic dysfunction. P30-AG21332, Farley Hudson, Hypertension &amp; Vasc Res Ctr

Viability assessment of magnetic resonance spectroscopy for the detection of minimal hepatic encephalopathy severity

ObjectiveTo evaluate regional cerebral metabolic changes in minimal hepatic encephalopathy (MHE) patients using magnetic resonance spectroscopy (MRS) in 3T scanner. Materials and methodsThis study comprised 30 cirrhotic patients with MHE, 29 cirrhotic patients without MHE and 30 healthy volunteers. Single-voxel proton MRS data in the anterior cingulate cortex (ACC) and basal ganglia were acquired using a 3-T scanner. The concentrations of N-acetylaspartate (NAA), mI (myo-inositol), glutamate (Glu), glutamine (Gln) and creatine (Cr) were obtained by LC-model software. Statistical analysis was performed to evaluate the differences between the three groups. ResultsThere was a significant increase in Glu for the cirrhotic patients, particularly the MHE patients. There was an elevation of Gln in the cirrhotic patients, but not in all cirrhotic patients or controls. There was a significant decrease in mI for the cirrhotic patients, but no significant difference between the two cirrhosis groups. There was no significant difference in NAA between the three groups. ConclusionsMRS using a 3-T MR scanner could detect cerebral metabolic changes in cirrhotic patients with MHE. Glu levels were elevated in cirrhotic patients with MHE; Glu levels could be used as a sensitive indicator to evaluate the severity of MHE in patients with cirrhosis.

Brain metabolite differences in one-year-old infants born small at term and association with neurodevelopmental outcome

We assessed brain metabolite levels by magnetic resonance spectroscopy (MRS) in 1-year-old infants born small at term, as compared with infants born appropriate for gestational age (AGA), and their association with neurodevelopment at 2 years of age. A total of 40 infants born small (birthweight <10th centile for gestational age) and 30 AGA infants underwent brain MRS at age 1 year on a 3-T scanner. Small-born infants were subclassified as late intrauterine growth restriction or as small for gestational age, based on the presence or absence of prenatal Doppler and birthweight predictors of an adverse perinatal outcome, respectively. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired from the frontal lobe at short echo time. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, Third Edition, assessing cognitive, language, motor, social-emotional, and adaptive behavior scales. As compared with AGA controls, infants born small showed significantly higher levels of glutamate and total N-acetylaspartate (NAAt) to creatine (Cr) ratio at age 1 year, and lower Bayley Scales of Infant and Toddler Development, Third Edition scores at 2 years. The subgroup with late intrauterine growth restriction further showed lower estimated glutathione levels at age 1 year. Significant correlations were observed for estimated glutathione levels with adaptive scores, and for myo-inositol with language scores. Significant associations were also noticed for NAA/Cr with cognitive scores, and for glutamate/Cr with motor scores. Infants born small show brain metabolite differences at 1 year of age, which are correlated with later neurodevelopment. These results support further research on MRS to develop imaging biomarkers of abnormal neurodevelopment.

Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings

Although posttraumatic stress disorder (PTSD) is associated with a variety of structural and functional brain changes, the molecular pathophysiological mechanisms underlying these macroscopic alterations are unknown. Recent studies support the existence of an altered excitation–inhibition balance in PTSD. Further, there is preliminary evidence from blood-sample studies suggesting heightened oxidative stress in PTSD, potentially leading to neural damage through excessive brain levels of free radicals. In this study we investigated PTSD (n=12) and non-PTSD participants (n=17) using single-voxel proton magnetic resonance spectroscopy (MRS) in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). We found significantly higher levels of γ-amino butyric acid (GABA) (a primary inhibitory neurotransmitter) and glutathione (a marker for neuronal oxidative stress) in PTSD participants. Atypically high prefrontal inhibition as well as oxidative stress may be involved in the pathogenesis of PTSD.

Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings.

Rationale: Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control.Objective: To evaluate the effects of 12-week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC) and functional changes within the cognitive control network.Methods: We used single-voxel proton magnetic resonance spectroscopy (1H-MRS) in the dACC and functional MRI (fMRI) during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design). Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI) analysis.Results: We observed a significant decrease in dACC glutamate + glutamine (Glx)/Cr levels as well as significant blood oxygen level-dependent signal (BOLD) decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN) function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.Conclusions: These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD connectivity between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size), future studies are needed to replicate these findings.

Preliminary study for differential diagnosis of intracranial tumors using in vivo quantitative proton MR spectroscopy with correction for T2 relaxation time

IntroductionThe intent of this study was to differentiate intracranial tumors using the metabolite concentrations obtained by quantification with correction for T2 relaxation time, and to analyze whether the spectrum peak was generated by the existence of metabolites in proton magnetic resonance spectroscopy (MRS). MethodsAll proton MRS studies were performed on a clinical 1.5T MR system. 7 normal volunteers and 57 patients (gliomas, metastases, meningiomas, acoustic neuromas, and pituitary adenomas) underwent single voxel proton MRS with different echo times (TE: 68, 136, 272 ms) for T2 correction of signal derived from metabolites and tissue water. With tissue water employed as an internal reference, the concentrations of metabolite (i.e. N-acetylaspartate (NAA), total creatine (t-Cr) and choline-containing compounds (Cho)) were calculated. Moreover, proton MRS data of previously published typical literatures were critically reviewed and compared with our data. ResultsExtramedullary tumors were characterized by absence of NAA compared with intramedullary tumors. High-grade glioma differed from low-grade glioma by lower t-Cr concentrations. Metastasis differed from cystic glioblastoma by higher Cho concentrations, lower t-Cr concentrations, an absence of NAA, and a prominent Lipids peak. Based on these results and review of previous reports, we suggest a clinical pathway for the differentiation of intracranial tumors. ConclusionThe metabolite concentrations obtained by quantification with correction for T2 relaxation time, and to analyze whether the spectrum peak was generated by the existence of metabolites in proton MRS is useful for the diagnosis of the intracranial tumors.

Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation.

Recent studies demonstrate that chronic pelvic pain is associated with altered afferent sensory input resulting in maladaptive changes in the neural circuitry of pain. To better understand the central changes associated with chronic pelvic pain, we investigated the contributions of critical pain-related neural circuits using single-voxel proton magnetic resonance spectroscopy (MRS) and transcranial direct current stimulation (tDCS). We measured concentrations of neural metabolites in 4 regions of interest (thalamus, anterior cingulate cortex, primary motor, and occipital cortex [control]) at baseline and after 10days of active or sham tDCS in patients with chronic pelvic pain. We then compared our results to those observed in healthy controls, matched by age and gender. We observed a significant increase in pain thresholds after active tDCS compared with sham conditions. There was a correlation between metabolite concentrations at baseline and quantitative sensory assessments. Chronic pelvic pain patients had significantly lower levels of NAA/Cr in the primary motor cortex compared with healthy patients. tDCS increases pain thresholds in patients with chronic pelvic pain. Biochemical changes in pain-related neural circuits are associated with pain levels as measured by objective pain testing. These findings support the further investigation of targeted cortical neuromodulatory interventions for chronic pelvic pain.

Advances in high-field magnetic resonance spectroscopy in Alzheimer's disease.

Alzheimer’s disease (AD) affects several important molecules in brain metabolism. The resulting neurochemical changes can be quantified non-invasively in localized brain regions using in vivo single-voxel proton magnetic resonance spectroscopy (SV 1H MRS). Although the often heralded diagnostic potential of MRS in AD largely remains unfulfilled, more recent use of high magnetic fields has led to significantly improved signal-to-noise ratios and spectral resolutions, thereby allowing clinical applications with increased measurement reliability. The present article provides a comprehensive review of SV 1H MRS studies on AD at high magnetic fields (3.0 Tesla and above). This review suggests that patterned regional differences and longitudinal alterations in several neurometabolites are associated with clinically established AD. Changes in multiple metabolites are identifiable even at early stages of AD development. By combining information of neurochemicals in different brain regions revealing either pathological or compensatory changes, high field MRS can be evaluated in AD diagnosis and in the detection of treatment effects. To achieve this, standardization of data acquisition and analytical approaches is needed.

Increased Hippocampal Glutamate and Volumetric Deficits in Unmedicated Patients With Schizophrenia

Alterations in glutamatergic neurotransmission have been postulated to be a key pathophysiologic mechanism in schizophrenia. To evaluate hippocampal volumetric measures and neurometabolites in unmedicated patients with schizophrenia and the correlations between these markers. Our a priori hypothesis was that glutamate levels would negatively correlate with hippocampal volume in schizophrenia. Combined 3-T structural magnetic resonance imaging and single-voxel proton magnetic resonance spectroscopy study at the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, of 27 unmedicated patients with schizophrenia and 27 healthy controls. Hippocampal volumetric measures and neurometabolites, and the correlations between volumetric measurements and neurometabolites. Hippocampal volumetric deficits, increased ratios of hippocampal glutamate and glutamine to creatine (Glx/Cr), and a loss of correlation between hippocampal N-acetylaspartate (NAA)/Cr and Glx/Cr in patients with schizophrenia were found. Significant correlations between hippocampal volumetric measures and Glx/Cr were also found in patients with schizophrenia but not healthy controls. Our findings support the theory that alterations in hippocampal glutamate levels potentially account for structural deficits in the hippocampus observed in schizophrenia neuroimaging studies.

White Matter NAA/Cho and Cho/Cr Ratios at MR Spectroscopy Are Predictive of Motor Outcome in Preterm Infants

To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging. The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests. NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P < .05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P < .05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P < .03) and a reduced NAA/Cho ratio (P < .01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88). The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation.

Comparative evaluation of MRS and SPECT in prognostication of patients with mild to moderate head injury

Magnetic resonance spectroscopy (MRS) and single-photon emission computed tomography (SPECT) have only been individually studied in patients with head injury. This study aimed to comparatively assess both in patients with mild to moderate head injury. Patients with a Glasgow Coma Scale (GCS) score of 9–14 who underwent MRS and/or SPECT were evaluated in relation to various clinical factors and neurological outcome at 3months. There were 56 SPECT (Tc99m-ethylcysteinate dimer [ECD]) studies and 41 single voxel proton MRS performed in 53 patients, with 41 patients having both. Of the 41 who underwent MRS, 13 had a lower N-acetyl-aspartate/creatine (NAA/Cr) ratio, 14 had a higher choline (Cho)/Cr ratio, 19 were normal, and nine had bilateral MRS abnormalities. Of the 56 who underwent SPECT, 22 and 19 had severe and moderate hypoperfusion, respectively. Among those in Traumatic Coma Data Bank CT scan category 1 and 2, 50% had MRS abnormalities, whereas 64% had SPECT hypoperfusion, suggesting greater incremental validity of SPECT over MRS. In univariate analyses, GCS, moderate/severe hypoperfusion and bilateral SPECT changes were found to have significant association with unfavorable outcome (odds ratio 13.2, 15.9, and 4.4, and p values <0.01, 0.01, and 0.05, respectively). Patients with lower NAA/Cr ratio in MRS had more unfavorable outcomes, however this was not significant. In multivariate analysis employing binary logistic regression, GCS and severe hypoperfusion on SPECT were noted to have significant association with unfavorable outcome, independent of age, CT scan category, and MRS abnormalities (p values=0.02 and 0.04, respectively). To conclude, ECD-SPECT seems to have greater sensitivity, incremental validity and prognostic value than single voxel proton MRS in select patients with head injury, with only severe hypoperfusion in SPECT significantly associated with unfavorable outcome independent of other confounding factors.

Increased ratio of glutamate/glutamine to creatine in the right hippocampus contributes to depressive symptoms in patients with epilepsy

PurposeOur study aimed to investigate whether the glutamatergic system in the hippocampus is correlated with depressive symptoms in patients with epilepsy. MethodsFifty patients with epilepsy were recruited and divided into three groups on the basis of their Hamilton Depression Rating Scale (HAMD) scores. Single-voxel proton magnetic resonance spectroscopy (1H-MRS) was carried out. Pearson correlation analysis and multiple linear regression analysis were performed to investigate any correlation between the variables of hippocampal metabolites and HAMD scores. ResultsProton magnetic resonance spectroscopy analysis showed that the ratio of glutamate/glutamine to creatine (Glx/Cr) in the right hippocampus was significantly increased in patients with moderate depression and correlated positively with HAMD scores. Multiple linear regression analysis showed that the ratio of Glx/Cr in the right hippocampus was an independent risk factor relating to depressive symptoms in patients with epilepsy. ConclusionA disturbance of the hippocampal glutamatergic system may be involved in the pathogenesis of depression in epilepsy.

Age-modulated association between prefrontal NAA and the BDNF gene

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p=0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480×age interaction on NAA level (p=0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17yr. NAA level decreased with advancing age for genotype TT (p=0.001) but not for genotype CT (p=0.82) or CC (p=0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

Improved diagnostic accuracy in differentiating malignant and benign lesions using single-voxel proton MRS of the breast at 3 T MRI

To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV (1)H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes. A prospective study of SV 1H MRS was performed following dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 61 women using a 3 T MR system. All lesions (n=57) were analysed for characteristics of morphology, contrast-enhancement kinetics, and tCho peak heights at SV (1)H MRS that were two-times above baseline. Subsequently, the tCho in selected lesions (n=32) was quantified by calculating the area under the curve, and a tCho concentration equal to or greater than the cut-off value was considered to represent malignancy. The relationship between tCho in invasive ductal carcinomas (IDCs) and their Bloom & Richardson grading of malignancy was assessed. Fifty-two patients (57 lesions; 42 malignant and 15 benign) were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of predicting malignancy were 100, 73.3, 91.3, and 100%, respectively, using DCE-MRI and 95.2, 93.3, 97.6, and 87.5%, respectively, using SV (1)H MRS. The tCho cut-off for receiver operating characteristic (ROC) curve was 0.33mmol/l. The relationship between tCho levels in malignant breast lesions with their histopathological subtypes was not statistically significant (p=0.3). Good correlation between tCho peaks and malignancy, enables SV (1)H MRS to be used as a clinically applicable, simple, yet non-invasive tool for improved specificity and diagnostic accuracy in detecting breast cancer.

Proton magnetic resonance spectroscopy of the substantia nigra in schizophrenia

BackgroundConverging evidence in schizophrenia points to disruption of the dopamine and glutamate neurotransmitter systems in the pathophysiology of the disorder. Dopamine is produced in the substantia nigra, but few neuroimaging studies have specifically targeted this structure. In fact, no studies of the substantia nigra in schizophrenia have used proton magnetic resonance spectroscopy (MRS). We sought to demonstrate the feasibility of acquiring single-voxel MRS measurements at 3T from the substantia nigra and to determine which metabolites could be reliably quantified in schizophrenia patients and healthy controls. MethodsWe used a turbo spin echo sequence with magnetization transfer contrast to visualize the substantia nigra and single-voxel proton MRS to quantify levels of N-acetylaspartate, glutamate and glutamine (Glx), and choline in the left substantia nigra of 35 people with schizophrenia and 22 healthy controls. ResultsWe obtained spectra from the substantia nigra and quantified neurometabolites in both groups. We found no differences in levels of N-acetylaspartate/creatine, Glx/creatine, or choline/creatine between the groups. We found a significant correlation between Glx/creatine and overall cognitive performance, measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), in controls but not patients, a difference that was statistically significant. ConclusionsOur study demonstrates the feasibility of obtaining single-voxel MRS data from the substantia nigra in schizophrenia. Such measurements may prove useful in understanding the biochemistry underlying cellular function in a region implicated in the pathophysiology of schizophrenia.

Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case-control study using proton magnetic resonance spectroscopy.

Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. Metabolic abnormalities in brain areas associated with cognitive functions could give rise to neuropsychiatric symptomatology. The aim of this study was to use single-voxel proton magnetic resonance spectroscopy to identify metabolic abnormalities in regions implicated in neuropsychiatric symptoms in patients with mitochondrial disorders. N-acetyl-aspartate and creatine levels were measured in the caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with mitochondrial disorders compared with 15 healthy controls matched for age and sex. N-acetyl-aspartate levels were significantly lower in the caudate nucleus among patients with mitochondrial disorders (mean 7.04 ± 1.19 standard deviation [SD] institutional units) compared with healthy controls (mean 8.19 ± 1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate nucleus among patients compared with controls (patients: mean 6.84 ± 1.42 SD institutional units; controls: mean 7.52 ± 0.76 SD institutional units; p = 0.03), but the results were no longer significant after correction for multiple comparisons. There were no significant differences in metabolite measurements between patients and controls in the anterior cingulate cortex and the hippocampus. Metabolic abnormalities were identified exclusively in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among patients compared with controls. These results suggest that the corpus striatum may be highly susceptible to mitochondrial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive functions, our findings raise the possibility that metabolic abnormalities in the caudate nucleus may contribute to cognitive impairment and neuropsychiatric symptoms in patients with mitochondrial disorders, which could be investigated in future studies.