Quantitative analysis of glutamate compounds in the swine brain following central analgesics nasal spray using proton magnetic resonance spectroscopy and linear combination model

摘要

BACKGROUND:In localized brain proton magnetic resonance spectroscopy(~1H-MRS),metabolite levels are often expressed as ratios,rather than absolute concentrations.Frequently,the denominator is creatine,which is assumed to be stable in normal,as well as many pathological, states.However,in vivo creatine levels do not remain constant.Therefore,absolute metabolite measurements,which provide the precise concentrations of certain chemical compounds,are superior to metabolite ratios for determining pathological and evolutional changes. OBJECTIVE:To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ~1H-MRS and linear combination model(LCModel) methods. DESIGN,TIME AND SETTING:This neuroimaging,observational,animal study was performed at the Laboratory of the Department of Medical Imaging,Second Affiliated Hospital,Medical College, Shantou University,China from July to December 2007. MATERIALS:Butorphanol tartrate nasal spray,as a mixed agonist-antagonist opioid analgesic,was purchased from Shanghai Hengrui Pharmacy,China.A General Electric Signa 1.5T System (General Electric Medical Systems,Milwaukee,Wl,USA) and LCModel software(Stephen Provencher,Oakville,Ontario,Canada) were used in this study. METHODS:MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence.A region of interest(2 cm×2 cm×2 cm) was placed in the image centers of maximum brain parenchyma.Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate.Three settings of repetition time/echo time were selected before and after nasal spray administration 3000 ms/30 ms, 1500 ms/30 ms,and 3000 ms/50 ms.Metabolite concentrations were estimated by LCModel software. MAIN OUTCOME MEASURES:~1H-MRS spectra was obtained using various repetition time/echo time settings.Concentrations of glutamate compounds(glutamate+glutamine),N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS:The glutamate compounds curve was consistent with original spectra,when a repetition time/echo time of 3 000 ms/30 ms was adopted.Concentrations of glutamate compounds,N-acetyl aspartate,and choline decreased following administration.The most significant reduction was observed in glutamate compound concentrations from(9.28±0.54) mmol/kg to(7.28±0.54) mmol/kg (P<0.05). CONCLUSION:~1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites.Glutamate compounds might be an important neurotransmitter in central analgesia.