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Introduction The diagnosis of psychoactive substance use disorders has been based primarily on descriptive, symptomatic checklist criteria. In opioid addiction, there are no objective biological indicators specific enough to guide diagnosis, monitor disease status, and evaluate efficacy of therapeutic interventions. Proton magnetic resonance spectroscopy ( 1 H MRS) of the brain has potential to identify and quantify biomarkers for the diagnosis of opioid dependence. The purpose of this study was to detect the absolute glutamate concentration in the nucleus accumbens (NAc) of patients with prescription opioid dependence using 1 H MRS, and to analyze its clinical associations. Methods Twenty patients with clinically diagnosed definitive prescription opioid dependent (mean age = 26.5 ± 4.3 years) and 20 matched healthy controls (mean age = 26.1 ± 3.8 years) participated in this study. Patients were evaluated with the Barratt Impulsiveness Scale (BIS‐11), the Self‐Rating Anxiety Scale (SAS), and the opiate Addiction Severity Inventory (ASI). We used point‐resolved spectroscopy to quantify the absolute concentrations of metabolites (glutamate, choline, N ‐acetylaspartate, glutamine, creatine) within the NAc. The difference between metabolite levels of groups and Pearson's correlation between glutamate levels and psychometric scores in patients were analyzed statistically. Results Glutamate concentrations in the NAc were significantly higher in prescription opiate addicts than in controls ( t = 3.84, p = .001). None of the other metabolites differed significantly between the two groups (all p s > .05). The glutamate concentrations correlated positively with BIS‐11 scores in prescription opiate addicts ( r = .671, p = .001), but not with SAS score and ASI index. Conclusions Glutamate levels in the NAc measured quantitatively with in vivo 1 H MRS could be used as a biomarker to evaluate disease condition in opioid‐dependent patients.

The human nucleus accumbens is a challenging region to study using proton magnetic resonance spectroscopy (1H-MRS) on a 70-cm wide-bore clinical 3T MRI system. The aim of this study was to investigate the reliability for quantitative measurement of glutamate concentration in the nucleus accumbens using a 70-cm wide-bore clinical 3T MRI. 1H-MRS of the nucleus accumbens was acquired using the Point-Resolved Spectroscopic Sequence (PRESS) with echo time of 40 ms from 10 healthy volunteers (5 female; age range: 18–30 years) on two separate visits (a baseline, and 1-month time point). The Java-based Magnetic Resonance User Interface (jMRUI) software package was used to quantitatively measure the absolute metabolite concentrations. The test-retest reliability and reproducibility were assessed using intraclass correlations coefficients (ICC), and coefficients of variation (CV). Glutamate concentrations were similar across visits (P = 0.832). Reproducibility measures for all metabolites were good with CV ranging from 7.8 to 14.0%. The ICC values of all metabolites for the intra-class measures were excellent (ICC > 0.8), except that the reliability for Glx (glutamate + glutamine) was good (ICC = 0.768). Pearson correlations for all metabolites were all highly significant (r = 0.636–0.788, P < 0.05). In conclusion, the short-echo-time PRESS can reliably obtain high quality glutamate spectrum from a ~3.4 cm3 voxel of the nucleus accumbens using a 70-cm wide-bore clinical 3T MRI.