Voxel Proton Magnetic Resonance Spectroscopy Research Articles

Espectroscopia de prótons e perfusão por ressonância magnética na avaliação dos tumores do sistema musculoesquelético

OBJETIVO: Avaliar a espectroscopia de prótons e o estudo dinâmico do contraste por ressonância magnética na diferenciação dos tumores musculoesqueléticos benignos e malignos. MATERIAIS E MÉTODOS: Foram estudados 55 pacientes com tumores musculoesqueléticos (27 malignos e 28 benignos). Os exames foram realizados em aparelho de ressonância magnética de 1.5 T com protocolo convencional e espectroscopia de prótons com TE de 135 ms. O estudo dinâmico do contraste foi adquirido pela sequência T1 gradiente-eco após a administração intravenosa de gadolínio. Curvas de intensidade de sinal versus tempo e valores de slope foram calculados. A análise estatística foi realizada pelo teste de Levene, seguido pelo teste t de Student, além dos testes qui-quadrado de Pearson e exato de Fischer. RESULTADOS: A sensibilidade, especificidade e acurácia da espectroscopia de prótons foram, respectivamente, de 87,5%, 92,3% e 90,9% (p < 0,0001). Além disso, houve significativa diferença entre o valor quantitativo da curva entre as lesões benignas (média de 27,5% por minuto) e malignas (média de 110,9% por minuto) (p < 0,0001). CONCLUSÃO: Os estudos quantitativo e qualitativo da análise dinâmica do contraste por ressonância magnética associados à presença do pico de colina são úteis na diferenciação dos tumores musculoesqueléticos em benignos e malignos.

Hippocampal metabolic abnormalities at first onset and with recurrent episodes of a major depressive disorder: A proton magnetic resonance spectroscopy study

The neural underpinnings of major depressive disorder (MDD) are unknown but there is evidence for structural alteration in the hippocampus that may become more pronounced over the course of illness. The aim of the present study was to examine metabolite levels of N-acetyl-aspartate (NAA), Myo-inositol (MI), Glutamate–glutamine (Glx) and choline-containing compounds (GPC and GPC+PCh) in patients presenting for first treatment of a depressive episode compared to those with multiple past episodes and age and sex matched controls. We used single voxel proton magnetic resonance spectroscopy (1H-MRS) centered on the hippocampus. Choline-containing compounds were significantly increased in patients with a high past illness burden relative to controls after controlling for hippocampal volume. The group presenting for first treatment had only increases in MI levels compared with matched controls. These results suggest that abnormal membrane turnover in the hippocampus is greater in patients with highly recurrent illness, and provide support for the hypothesis that there are neuronal changes in this region over the course of illness.

Hippocampal Metabolite Abnormalities in Fibromyalgia: Correlation With Clinical Features

Although the pathology of fibromyalgia is poorly understood, a growing body of evidence suggests involvement of the central nervous system. The hippocampus is a brain center that is sensitive to the effects of stress exposure and has been demonstrated to be affected in a variety of disorders whose onset, like fibromyalgia, are associated with stressful experience. We therefore interrogated the bilateral hippocampus of 16 female fibromyalgia patients in comparison to 8 age- and gender-matched healthy control subjects using single voxel proton magnetic resonance spectroscopy. Our results demonstrate a significant reduction in the ratio of N-acetylaspartate to creatine (NAA/Cr) in fibromyalgia patients versus matched control subjects specifically in the right temporal lobe from a voxel centered on the right hippocampus (patient vs control, mean +/- standard deviation: 1.20 +/- 0.13 vs 1.34 +/- 0.10, P = .03). Moreover, correlation analysis demonstrated a significant negative correlation between patient scores on the Fibromyalgia Impact Questionnaire and NAA/Cr ratio within the right hippocampus (Spearman rank correlation, rho = -0.681, P = .018). Our results indicate that fibromyalgia is associated with brain metabolite abnormalities within the right hippocampus that correlate with patient symptoms. We have demonstrated an abnormality in hippocampal brain metabolites in premenopausal female fibromyalgia patients with no psychiatric comorbidity. A significant negative correlation between patient subjective experience of symptoms and a reduced NAA/Cr ratio suggests a role for hippocampal pathology in fibromyalgia.

1H-MRS experiences after bilateral DBS of the STN in Parkinson's disease

The objective of this study was to evaluate the changes in the concentrations of certain brain metabolites in 13 patients with Parkinson's disease before and after bilateral subthalamic nucleus (STN DBS). The N-acetylaspartate (NAA)/choline (Chol), NAA/creatine (Cr), Chol/Cr ratios were determined by single voxel Proton magnetic resonance spectroscopy ( 1H-MRS) studies on 1.0 T unit using short TE stimulated echo acquisition mode (STEAM) sequence. Spectra were obtained from the right and left globus pallidus, and left fronto-basal cortex. The patients were also assessed according to the UPDRS part III, in the “medication-on and off” conditions. Conclusions: after STN DBS cortical NAA/Cho, NAA/Cr ratios increased significantly, which were highly correlated with the significant improvements of the UPDRS scores.

Proton magnetic resonance spectroscopy study of dyskinesia patients

Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (-13%, P = 0.020) and SOD patients (-12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (-11%, P = 0.079). All other metabolite ratios (N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction.

Decreased GABA levels in anterior cingulate and basal ganglia in medicated subjects with panic disorder: A proton magnetic resonance spectroscopy ( 1H-MRS) study

The purpose of this study was to investigate the brain gamma-aminobutyric acid (GABA) concentration and its relationship with clinical variables in patients with panic disorder (PD). Single voxel proton magnetic resonance spectroscopy ( 1H-MRS) scan was performed on 22 medicated subjects with PD and 25 age and sex-matched healthy comparison subjects. GABA and other metabolite levels were measured in the anterior cingulate cortex (ACC) and basal ganglia. GABA levels were significantly lower in the ACC and basal ganglia of PD patients relative to comparison subjects. Lactate and choline concentrations in the ACC in PD patients were also higher than in the comparison subjects. Our data suggested in part that alterations of the GABA function and the energy metabolism in ACC and basal ganglia may play an important role in the pathophysiology of panic disorder.

Single voxel proton magnetic resonance spectroscopy in post-stroke depression

Mood disorders are associated with structural, metabolic and spectroscopic changes in prefrontal regions. In the case of depression associated with stroke, there is little information about the biochemical profile of these regions, as assessed by proton magnetic resonance spectroscopy ( 1H-MRS). In a group of first-ever stroke patients, we studied the association between post-stroke depression and 1H-MRS measurements in unaffected frontal lobes. Twenty-six patients with a first ischemic stroke located outside the frontal lobes were included in the study. Single voxel proton magnetic resonance spectroscopy ( 1H-MRS) was performed to assess N-acetylaspartate/creatine (NAA)/Cr, glutamate + glutamine (Glx)/Cr, choline (Cho)/Cr and myo-inositol (mI)/Cr ratios. Patients were assessed within the first 10 days after stroke and again four months later. The diagnosis of depression was made on the basis of clinical observation, interview and Hamilton Depression Rating Scale scores. In a group of 26 patients, eight (31%) met criteria for depression at the first assessment, and nine (35%) met criteria for depression at follow-up. Patients with depression in the immediate post-stroke phase had significantly higher Glx/Cr ratios in the contralesional hemisphere than non-depressive patients. No biochemical differences were found between the groups at 4-month follow-up. These findings suggest that post-stroke depression is accompanied by changes in frontal lobe glutamate/glutamine levels, perhaps reflecting abnormalities in glutamatergic transmission in the immediate post-stroke period.

Magnetic Resonance Spectroscopy of the Thalamus in Essential Tremor Patients

Although essential tremor (ET) is one of the most common movement disorders, its pathogenesis remains obscure. The ventral intermediate nucleus of the thalamus (VIM nucleus) is suggested to play an important role in the occurrence of disease. In this study, the authors investigated the presence of biochemical or metabolic alterations in the thalamus of patients with ET using magnetic resonance (MR) spectroscopy. The study group included 14 patients with ET who suffered from tremor predominantly in their right arm and 9 healthy controls. All patients and controls were right handed. Following conventional cranial MR imaging, single voxel proton MR spectroscopy of the thalamus involving the VIM nuclei was performed bilaterally in both the patients with ET and controls. Metabolite peaks of choline (Cho), creatine (Cr), and Nacetylaspartate (NAA) were obtained from each spectroscopic volume of interest. The right and left thalamic NAA/Cr and Cho/ Cr ratios were compared first within the patient group and then between the control and patient groups. The differences in age and spectroscopic data between groups were assessed using the Mann-Whitney U test, whereas the comparison within groups between left thalamus and right thalamus was done by the Wilcoxon test. In patients with ET, the NAA/Cr ratio of the right thalamus was found to be significantly higher than the NAA/Cr ratio of the left thalamus (P= .02). However, NAA/Cr and Cho/Cr ratios were found to be similar (P> .05) when we compared the control and patient groups for the right thalamus and then the left thalamus. These data present preliminary evidence for metabolic alterations of the contralateral thalamus (namely, low NAA/Cr ratio) in ET patients with predominantly involved right arm. However, the series is small and further data are necessary to clear the subject adequately.

Relationship of in vivo medial temporal lobe magnetic resonance spectroscopy to documented combat exposure in veterans with chronic posttraumatic stress disorder

Veterans diagnosed with combat-related posttraumatic stress disorder (PTSD) and comparison subjects underwent single voxel proton magnetic resonance spectroscopy ( 1H-MRS) of the medial temporal lobe (MTL). PTSD subjects were divided into combat and non-combat groups based on military records. Combat PTSD subjects did not have lower MTL levels of N-acetylaspartate compared with non-combat PTSD subjects.

Effect of seizure on hippocampus in mesial temporal lobe epilepsy and neocortical epilepsy: an MRS study

This study was performed to evaluate the effect of seizures on the bilateral hippocampus in mesial temporal lobe epilepsy (mTLE) and neocortical epilepsy by single voxel proton magnetic resonance spectroscopy (MRS). Forty-one patients with mTLE having unilateral hippocampal sclerosis and 43 patients with a neocortical epilepsy who underwent subsequent epilepsy surgery were recruited. Ninety-five percent confidence intervals of N-acetyl aspartate/choline (NAA/Cho) and NAA/creatine (NAA/Cr) ratios in 20 healthy control subjects were used as threshold values to determine abnormal NAA/Cho and NAA/Cr. NAA/Cho and NAA/Cr were significantly lower in the ipsilateral hippocampus of mTLE and neocortical epilepsy. Using asymmetry indices for patients with bilaterally abnormal ratios of NAA/Cho and NAA/Cr in addition to using unilateral abnormal ratio, the seizure focus was correctly lateralized in 65.9% of patients with mTLE and 48.8% of neocortical epilepsy patients. Bilateral NAA/Cho abnormality was significantly related to a poor surgical outcome in mTLE. No significant relationship was found between the results of NAA/Cho or NAA/Cr and surgical outcome in neocortical epilepsy. The mean contralateral NAA/Cr ratio of the hippocampus in mTLE was significantly lower in patients with a history of secondary generalized tonic-clonic seizure (SGTCS) than in those without. Our results demonstrate effects of seizures on the hippocampi in neocortical epilepsy and the relation between SGTCS and NAA/Cr of the contralateral hippocampus in mTLE. This proves the presence of a seizure effect on the hippocampus in neocortical epilepsy as well as in mTLE.

Reduced Anterior Cingulate Glutamate in Pediatric Major Depression: A Magnetic Resonance Spectroscopy Study

Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. Fitting to individually quantify anterior cingulate glutamate and glutamine was performed in these subjects with a new basis set created from data acquired on a 1.5 Tesla General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen, Germany). Reduced anterior cingulate glutamate was observed in MDD patients versus control subjects (8.79 +/- 1.68 vs. 11.46 +/- 1.55, respectively, p = .0002; 23% decrease). Anterior cingulate glutamine did not differ significantly between patients with MDD and control subjects. These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.

Single voxel proton magnetic resonance spectroscopy in women with and without intimate partner violence-related posttraumatic stress disorder

Preliminary in vivo proton magnetic spectroscopic ( 1H-MRS) studies of N-acetylaspartate (a putative marker of neuronal viability and function) in combat veterans and maltreated children with posttraumatic stress disorder (PTSD) suggest altered neuronal integrity in anterior cingulate and medial temporal lobe structures. In this study, 1H-MRS was used to measure N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) relative to creatine (Cr) in the anterior cingulate of 16 women with histories of intimate partner violence (7 with a DSM-IV diagnosis of PTSD, 9 without PTSD) and 11 healthy, non-abused comparison subjects. The relationship between anterior cingulate chemistry and performance on the Stroop Color-Word task and Part B of the Trail Making Test was also examined. There were no significant differences in anterior cingulate or occipital gray matter metabolite ratios of NAA/Cr and Cho/Cr between intimate partner violence and healthy comparison subjects. Intimate partner violence subjects with PTSD had significantly higher anterior cingulate Cho/Cr than intimate partner violence subjects without PTSD. There was evidence that the subjects with PTSD suffered more severe intimate partner violence as measured by the Conflict Tactics Scale-Revised. Metabolite ratios were not significantly correlated with performance on the Stroop or Trails B. Our findings, in agreement with earlier studies, showed significant alterations in anterior cingulate chemistry in women with PTSD. In contrast to other studies, we found an increase in Cho/Cr rather than a decrease in NAA/Cr, indicating alterations in glia, instead of neuronal dropout.

Incidence of Brain Creatine Transporter Deficiency in Males with Developmental Delay Referred for Brain Magnetic Resonance Imaging

Several case reports describe children with global developmental delay who have brain creatine deficiency, where the deficiency was due to a lack of creatine transport into the brain or altered creatine synthesis. The purpose of this study was to determine what percentage of males with developmental delay referred for brain magnetic resonance imaging (MRI) at the authors' institution in a 12-month period was found to have brain creatine deficiency due to a defect in the creatine transporter gene. In the authors' facility, single voxel proton magnetic resonance spectroscopy (MRS) is routinely performed on any male child age 2 to 18 years with a history of language and/or developmental delay referred for a brain MRI. Charts for the 12-month time period were retrospectively reviewed. Fourteen subjects met inclusion criteria for global developmental delay. Two of the 14 patients had brain creatine deficiency on MRS. In the remaining 12, other structural and white matter abnormalities were identified. This study suggests that brain creatine deficiency is an important consideration in the differential diagnosis of males with global developmental delay referred for brain MRI; brain MRS should be considered in such cases.

Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients

The dorsolateral prefrontal cortex (DLPFC) plays an essential role in mood regulation and integration of cognitive functions that are abnormal in major depressive disorder (MDD). Few neuroimaging studies have evaluated the still maturing DLPFC in depressed children and adolescents. We conducted single voxel proton magnetic resonance spectroscopy ( 1H MRS) of the left DLPFC in 14 depressed children and adolescents (13.3 ± 2.3 years old, 10 males) and 22 matched healthy controls (13.6 ± 2.8 years old, 13 males). Depressed subjects had significantly lower levels of glycerophosphocholine plus phosphocholine (GPC + PC; or choline-containing compounds) and higher myo-inositol levels in the left DLPFC compared to healthy controls. In the depressed subjects, we found significant inverse correlations between glutamate levels and both duration of illness and number of episodes. In healthy controls there was a significant direct correlation between age and glutamine levels, which was not present in the patient group. Lower GPC + PC levels in pediatric MDD may reflect lower cell membrane content per volume in the DLPFC. Increased myo-inositol levels in MDD may represent a disturbed secondary messenger system. GPC + PC and myo-inositol abnormalities further demonstrate the involvement of DLPFC in pediatric MDD.

Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study

Patients with obstructive sleep apnoea syndrome frequently have cognitive deficits, especially related to executive functions, which cannot be fully explained by daytime sleepiness and are partial irreversible after nasal continuous positive airway pressure treatment. The causal mechanism of these cognitive deficits is not yet known, but it has been proposed that they are associated with chemical and structural brain cell injury. The aim of this study was to investigate brain metabolism in patients with sleep apnoea syndrome. Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of comparable age were studied using single voxel proton magnetic resonance spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex, parieto-occipital and frontal periventricular white matter. N-acetylaspartate-to-creatine and choline-to-creatine ratios were significantly lower in the frontal white matter of obstructive sleep apnoea patients when compared to controls. Absolute concentrations of N-acetylaspartate and choline were also significantly reduced in the frontal white matter of patients with sleep apnoea. Frontal lobe white matter lesions are known to be associated with cognitive executive dysfunction. The findings of this study may offer an explanation for the sometimes irreversible cognitive deficits associated with sleep apnoea.

Serial cranial MR imaging and single voxel proton MR spectroscopy in paraneoplastic limbic encephalitis

We report the serial cranial MR imaging (MRI) and single voxel proton magnetic resonance spectroscopy ( 1 H -MRS) findings of the brain, at 3 and 11 weeks after the onset of symptoms in a patient with paraneoplastic limbic encephalitis (PLE) in association with anti-Hu antibodies. There was a suspiciously detectable hyperintensity in temporal lobes on initial MRI and increased myoinositol (mI) and minimally decreased N-acetylaspartate (NAA) levels were seen in 1 H -MRS from the right superior temporal neocortex. Follow-up cranial MRIs showed more striking hyperintensity in bilateral medial temporal regions on T2-weighted images. Repeat single voxel 1 H -MRS from the bilateral medial temporal region showed the lactate peak, prominent NAA decrease, both choline and mI increase. These findings provided suggestive evidence in vivo for neuronal loss and gliosis, even there may be inflammatory cell infiltration in the PLE brain. To our knowledge, this is the first description of single voxel 1 H -MRS findings associated with PLE.

Proton Magnetic Resonance Spectroscopy Investigation of the Right Frontal Lobe in Children With Attention-Deficit/Hyperactivity Disorder

To investigate neurometabolite concentrations in right prefrontal white matter in children with attention-deficit/hyperactivity disorder (ADHD) and relations of neurometabolites with attention skill and frontal anatomy. Single voxel proton magnetic resonance spectroscopy ( H-MRS), quantitative morphometric analysis of left and right dorsolateral frontal volumes, and assessment of attentional problems with the Conners Continuous Performance Test were undertaken in 23 children (17 male) with ADHD (with no comorbid learning disabilities) and 24 matched controls (16 male). No overall group differences were found for any neurometabolite. However, a group by sex interaction was noted for -acetylaspartate, such that girls with ADHD had especially low concentrations. Morphological analyses revealed smaller right (but not left) dorsolateral volumes in children with ADHD, and in the ADHD group this volume correlated with neurometabolite concentrations. In the ADHD group Continuous Performance Test performance was related to both dorsolateral volume and the creatine-phosphocreatine peak from H-MRS. These results add to a growing body of evidence suggesting sex-specific neurobiological differences in ADHD and draw attention to relationships between neurochemistry, neuroanatomy, and performance in children with ADHD. Study limitations include small sample size and clinical heterogeneity among the children with ADHD.

Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus, thalamus, and prefrontal cortex.

Single voxel proton magnetic resonance spectroscopy (1H MRS) was used to study the metabolites N-acetylaspartate (NAA), choline (CHO), and myo-inositol (ml) in order to test a neurodegenerative hypothesis in schizophrenia (decrease of NAA, increase of CHO, and increase of ml) and a cerebral asymmetry of these metabolites. 1H MRS was performed in 17 schizophrenia patients and 14 healthy subjects in three cerebral areas highly involved in the pathophysiology of schizophrenia (the prefrontal cortex, the thalamus, and the hippocampus). The ratio amplitudes between metabolites and creatine plus phosphocreatine (Cr) were determined. No difference in the metabolites existed between patients and healthy subjects. However, relationships were noted between NAA/Cr and age in the thalami of the schizophrenia patients (r = -0.37; p = 0.14) and healthy subjects (r = -0.52; p = 0.05). A significant correlation was observed between NAA/Cr and age of onset of illness in the hippocampi of schizophrenia patients (r = -0.59; p < 0.05). Moreover, NAA/Cr was lower in the right than in the left prefrontal cortex in both schizophrenia patients and healthy subjects. There was no relationship between the metabolites and duration of illness or dose of antipsychotics. These findings might suggest a neurodegenerative process in the hippocampi of schizophrenia patients with late onset of illness, and the NAA/Cr ratio could be a marker of aging in the thalami.

Dual Voxel Proton Magnetic Resonance Spectroscopy in the Healthy Elderly: Subcortical-Frontal Axonal N-Acetylaspartate Levels Are Correlated with Fluid Cognitive Abilities Independent of Structural Brain Changes

The published literature suggests that degeneration of the subcorticofrontal networks may underlie cognitive ageing, but appropriate methods to examine this in vivo have been lacking. Proton Magnetic Resonance Spectroscopy (1H-MRS) has now been used in a number of clinical studies to assess cerebral pathophysicochemistry and recently has been utilized to examine the relationship between neurochemical markers and cognitive functioning in normal individuals. Results have been somewhat conflicting and difficult to interpret. To further clarify the role of the cognitive spectroscopy technique, we measured N-acetylaspartate (NAA) levels in the frontal subcortical white matter and the occipitoparietal grey matter and correlated them with performance in different cognitive domains in a group of twenty healthy elderly individuals. Subjects underwent whole brain T1- and T2-weighted magnetic resonance imaging (MRI), dual voxel short echo-time 1H-MRS, and a comprehensive neuropsychological assessment. Individual tests of executive and attentional abilities, and a principal components composite score reflecting these skills, but not measures of memory or verbal abilities, were correlated with NAA concentration in the frontal white matter only. These relationships were independent of other neurocognitive predictors of executive impairment such as age, midventricular dilation, frontal white matter disease, and presenescent verbal proficiency. This study suggests the ability of 1H-MRS to differentiate anatomically distinct neurochemical markers related to specific cognitive abilities. In particular, neurometabolic fitness of the frontal subcortical-cortical axonal fibers may be important in mediating fluid intellectual processing. Longitudinal MRS studies are required to determine if the present results reflect different rates of neurocellular degeneration or preexisting individual differences in neuronal density.

Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study

The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate cortices are involved in some types of chronic pain. Animal models of chronic pain suggest abnormal spinal cord chemistry. Does chronic pain cause brain chemistry changes? We examined brain chemistry changes in patients with chronic back pain using in vivo single- voxel proton magnetic resonance spectroscopy ( 1H-MRS). In vivo 1H-MRS was used to measure relative concentrations of N-acetyl aspartate, creatine, choline, glutamate, glutamine, γ-aminobutyric acid, inositol, glucose and lactate in relation to the concentration of creatine. These measurements were performed in six brain regions of nine chronic low back pain patients and 11 normal volunteers. All chronic back pain subjects underwent clinical evaluation and perceptual measures of pain and anxiety. We show that chronic back pain alters the human brain chemistry. Reductions of N-acetyl aspartate and glucose were demonstrated in the dorsolateral prefrontal cortex. Cingulate, sensorimotor, and other brain regions showed no chemical concentration differences. In chronic back pain, the interrelationship between chemicals within and across brain regions was abnormal, and there was a specific relationship between regional chemicals and perceptual measures of pain and anxiety. These findings provide direct evidence of abnormal brain chemistry in chronic back pain, which may be useful in diagnosis and future development of more effective pharmacological treatments.