| Opioid dependence has been one of the most serious social,economic and public health problems in the world.A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years.Prescription opioid dependents enhance euphoria and pleasure feeling by using a large dose of drugs,which can lead to cause strong drug craving and compulsive drug seeking behavior.The clinical diagnosis of opioid dependence is based primarily on the subjective judgment by using the syndrome self-evaluation scales,and yet there is no clear objective neurobiological makers.It is necessary to seek the objective neurobiological makers to assist in the diagnosis of prescription opioid dependence,and to monitor disease developments and treatment response.Magnetic resonance spectroscopy(MRS)is a noninvasive technique for the quantitative detection of the changes in the levels of metabolites in vivo.It is expected to provide a quantitative method for the diagnosis of prescription opioid dependence.The brain reward circuitry is the neuroanatomical basis produced the rewarding effects of opiates.And the prefrontal cortex is a key area of reward circuitry,which participate in the senior executive function and is seem to be associated with substance addiction.Glutamate(Glu)andγ-aminobutyric acid(GABA)are mainly inhibitory and excitatory neurotransmitter in reward circuitry,respectively.Opioid dependence may be associated with GABA and Glu levels in the prefrontal cortex,which may be involved in the formation of dependence,but the mechanism of long-term dependent effect is still not clear.Therefore,this study intend to use MEGA-PRESS editing and Optimal TE editing sequence to quantitatively measure the absolute GABA and Glu concentration at 3.0 T MRI system,and to explore the feasibility and reproducibility of quantitative measurement of absolute GABA and Glu concentration using the MEGA-PRESS editing and Optimal TE editing sequence at a 70-cm wide-bore clinical 3.0 T MRI system.Then,this method will be used to detect the absolute concentration of GABA and Glu in the prefrontal cortex of opioid dependents,and to explore the correlation among the absolute concentration of GABA and Glu in the prefrontal cortex and neuropsychological indexes,and to provide more possible biomarkers to evaluate prescription opioid dependence.Part 1: Feasibility of quantitative detection of absolute γ-aminobutyric acid concentration in the prefrontal cortex of the human brain in vivo using a 70-cm wide-bore clinical 3.0 T MRI systemObjective:This study aimed to explore the feasibility of quantitative measurement of absolute GABA concentration in the prefrontal cortex of the human brain in vivo using the MEGA-PRESS editing sequence at a 70-cm wide-bore clinical 3.0 T MRI system.Material and Methods:The subjects who include thirty-two healthy right-handed volunteers(25 males,7 females;age range 18-33 years,mean age 22.6 ± 3.0 years)without a previous history of neuropsychiatric or other disorders known to affect brain functioning or a contraindication to MR examination,were recruited in this study.1H-MRS of the ventromedial prefrontal cortex of the volunteer brain was acquired on a Siemens MAGNETOM Skyra 3.0 T MR scanner with the MEGA-PRESS editing sequence.And then the phantom with 50 mM GABA concentration was placed into the MRI coil and scanned again with the same sequence corresponding to the human brain in vivo as the external reference for the quantitative analysis.The spectra data was post-processed using the jMRUI v5.0 software package,and the absolute concentration(Mean ± SD),and the coefficient variation of GABA in the ventromedial prefrontal cortex were calculated.Results:The spectral data of GABA were acquired successfully using the MEGA-PRESS editing sequence in all 32 volunteers.The spectral peak of GABA was well shown by the jMRUI v5.0 software,and the average concentration of GABA was 1.58 ± 0.26 mM,the coefficient of variation was 16.2%.Conclusion:Quantitative detection of absolute GABA concentration in the prefrontal cortex of the human brain in vivo using the MEGA-PRESS editing sequence at a 70-cm wide-bore clinical 3.0 T MRI system is feasible,and the highly stable GABA spectrum could be acquired.Part 2: Reproducibility of quantitative measurement of absolute γ-aminobutyric acid concentration in the prefrontal cortex of the human brain in vivo using a 70-cm wide-bore clinical 3.0 T MRI system.Objective:This study aimed to explore the reproducibility of quantitative measurement of absolute GABA concentration in the prefrontal cortex of the human brain in vivo using the MEGA-PRESS editing sequence at a 70-cm wide-bore clinical 3.0 T MRI system.Material and Methods:Sixteen healthy right-handed volunteers(10 males,6 females;age range 19-28 years,mean age 23.1 ± 2.3 years)without a previous history of neuropsychiatric or other disorders known to affect brain functioning or a contraindication for undergoing an MRI scan were recruited in this study.1H MRS of the prefrontal cortex of all volunteer brain was acquired on a Siemens MAGNETOM Skyra 3.0 T MR scanner with the MEGA-PRESS editing sequence.All subjects were scanned at least twice for intervals of at least five days.In six subjects selected randomly,four continuous scans were performed,at intervals of at least one week.Post-processing of the MRS date was carried out using the jMRUI v5.0 software package.GABA levels were quantified by relative quantification(GABA/NAA),absolute quantification(|GABA|).The mean,standard deviation and coefficient variation was calculated accordingly.Results:The spectral data of GABA were acquired successfully using the MEGE-PRESS editing sequence in all 16 subjects.The spectral peak of GABA was well shown by the jMRUI v5.0 software package.The coefficient variations of two quantitative methods were less than 20%,and there was no significant difference(p<0.05)between relative quantification and absolute quantification.The showed coefficient variation of absolute quantification(|GABA|)was lower than relative quantification(GABA/NAA)(P<0.05),either the intra-individual or inter-individual reproducibility.Furthermore,there were no significant difference(p>0.05)between men and women groups of relative quantification,and were significant difference(P<0.05)between men and women groups of absolute quantification.Conclusion:GABA signal in the prefrontal cortex of the human brain in vivo using the MEGA-PRESS editing sequence at a 70-cm wide-bore clinical 3.0 T MRI system has high stability and repeatability.For GABA quantitative methods,absolute quantification was more reliable than relative quantification.Moreover the absolute quantification was gender specific,and had a good inter-individual reproducibility.These results show that this technique could be used to detect GABA level changes in normal and diseased brain at a 70-cm wide-bore clinical 3.0 T MRI system.Part 3.Clinical significance of quantitative γ-aminobutyric acid and glutamate detection in the prefrontal cortex of prescription opioid dependents using in vivo proton magnetic resonance spectroscopyObjective:This study aimed to detect absolute concentration of GABA and Glu in the prefrontal cortex of prescription opioid dependents by resting-state 1H magnetic resonance spectroscopy,and to explore the correlation among absolute concentration of GABA and Glu in the prefrontal cortex and clinical indexes.Material and Methods:Thirty-one prescription-opioid dependents(29 male,2 female;age range 18-35 years,mean age 24.94 ± 4.19 years)and 32 matched healthy controls(25 male,7 female;age range 18-35 years,mean age 22.6 ± 3.0 years)participated in this study.1H MRS of the prefrontal cortex of all volunteer brain was acquired on a Siemens MAGNETOM Skyra 3.0 T MR scanner with the MEGA-PRESS editing sequence for GABA and Optimal TE editing sequence for Glu.Two phantom as quality control,which with a concentration of 50 mM GABA and a concentration of 50 mM Creatine respectively,were measured before each MRS session using the standard study protocol.Post-processing of the MRS date was carried out using the jMRUI v5.0 software package.The Opiate Addiction Severity Inventory(OASI)was used to record severity of addiction levels,and the Barratt Impulsivity Scale(BIS-11)was used as a self-administered questionnaire to measure impulsiveness,and the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS)and Montreal Cognitive Assessment(MoCA)were used to evaluate anxiety,depression and cognition symptoms respectively.The metabolite levels were analyzed to identify between-group differences using the unpaired t-test for independent samples.Spearman correlation coefficients were computed to determine the correlations between metabolite levels and clinical indexes.Results:The inter-group comparisons revealed significantly lower GABA concentrations and higher Glu concentrations in the PFC in prescription opioid dependents relative to the controls(P<0.001).And BIS-11 score in prescription opioid dependents was higher than the controls,while MOCA score in prescription opioid dependents was lower than 26 scores,and there were significant difference between the two groups(P<0.05).The absolute concentrations of GABA in prescription opioid dependents was oppositely correlated with Glu concentrations,BIS-11 score and SAS score,while was positively correlated with MOCA score.And the absolute concentration of Glu was positively correlated with BIS-11 and oppositely correlated with MOCA score.Conclusion:The abnormity of GABA and Glu level are related to impulsivity of drug seeking,anxiety and impaired cognitive function.Therefore,the neurotransmitter system disorders of inhibition GABAergic and excitatory glutamatergic may be an important pathophysiological mechanism in prescription opioid dependents’ craving and relapse.The absolute concentration of GABA and Glu detected quantitatively by MRS in the prefrontal cortex is expected to become a clinical predictive index for the objective estimate of the addiction severity,psychological state,disease development and treatment response in prescription opioid dependents. |
PDF Full Text Request