氢质子波谱在阿尔茨海默病中的价值

Objective To study the diagnosis value of proton magnetic resonance spectroscopy(1H-MRS)in Alzheimer disease(AD).Methods Using stimulated echo acquisition mode,29 AD patients and 20 elderlv healthy ones as control group were underwent with Magnetic ResonaJlce Spectrum (MRs)examination in hippocampus,temporal parietal cortex and cingulate gyrus,the metabolites of MRS were analvzed to have N-aeetyl aspartate(NAA),creatine(Cr),choline(Cho),myo-inositol (mI),and comDarle the ratio of each other as well as the difference between the two groups.Rmulta NAA of AD patients in hippocampus,temporal parietal cortex and ringulate gyrus were(0.40±0.06),(0.42±0.06),(0.43±0.08),respectively, and have no significant difference to the healthy group(P＞0.05);mI were(0.25±0.08).(0.23±0.06),(0.21±0.05),respectively,and have significant difference to the healthy group(P＜0.05):NAA/Cr werle(1.30±O.10),(1.40±0.11),(1.42±0.12),respectively,and have no significant differenoe to the healthy group(P＞0.05);mI/Cr were,(0.81±0.07),(0.78±0..08),(0.70±0.06),respectively,and have significant difference to the healthy group(P＜0.05);mI,NAA were(0.61±0.06),(0.55±0.08),(0.49±0.07),respeetively,and have significant difference to the healthy group(P＜0.05).In AD patients,NAA,NAA/Cr decrease and mI,mI/Cr,mI/NAA increase,and the value in hippocampus＞temporal parietal cortex＞cingulate gyrus.Conclusion The changes of MRS in AD patients,mainly reflected a decline in NAA and rise in mI,which has some reference in the diagnosis in AD.     

氢质子波谱在阿尔茨海默病中的价值

Objective To study the diagnosis value of proton magnetic resonance spectroscopy(1H-MRS)in Alzheimer disease(AD).Methods Using stimulated echo acquisition mode,29 AD patients and 20 elderlv healthy ones as control group were underwent with Magnetic ResonaJlce Spectrum (MRs)examination in hippocampus,temporal parietal cortex and cingulate gyrus,the metabolites of MRS were analvzed to have N-aeetyl aspartate(NAA),creatine(Cr),choline(Cho),myo-inositol (mI),and comDarle the ratio of each other as well as the difference between the two groups.Rmulta NAA of AD patients in hippocampus,temporal parietal cortex and ringulate gyrus were(0.40±0.06),(0.42±0.06),(0.43±0.08),respectively, and have no significant difference to the healthy group(P＞0.05);mI were(0.25±0.08).(0.23±0.06),(0.21±0.05),respectively,and have significant difference to the healthy group(P＜0.05):NAA/Cr werle(1.30±O.10),(1.40±0.11),(1.42±0.12),respectively,and have no significant differenoe to the healthy group(P＞0.05);mI/Cr were,(0.81±0.07),(0.78±0..08),(0.70±0.06),respectively,and have significant difference to the healthy group(P＜0.05);mI,NAA were(0.61±0.06),(0.55±0.08),(0.49±0.07),respeetively,and have significant difference to the healthy group(P＜0.05).In AD patients,NAA,NAA/Cr decrease and mI,mI/Cr,mI/NAA increase,and the value in hippocampus＞temporal parietal cortex＞cingulate gyrus.Conclusion The changes of MRS in AD patients,mainly reflected a decline in NAA and rise in mI,which has some reference in the diagnosis in AD.     

氢质子波谱在阿尔茨海默病中的价值

目的探讨质子磁共振波谱（ZH—MRS）在阿尔茨海默病（AD）中的诊断价值。方法采用刺激激励回波采样方式对29例AD患者和20例老年健康者的海马、颞顶叶和扣带回行MRS检查;分析的代谢产物有N－乙酰天门冬氨酸（NAA）、肌酸（Cr）、胆碱（Cho）、肌醇（mI）,并比较分析其相互间比值在两组间的差异结果AD患者在海马、颞顶叶和扣带回的NAA分别为（0．40±0．06）、（0．42±0．06）、（0．43±0．08）,与健康组比较差异无显著性（P〉0．05）;mI分别为（0．25±0．08）、（0．23±0．06）、（0．21±0．05）,与健康组比较差异有显著性（R0．05）NAA／Cr分别为（1．30±0．10）、（1．40±0．11）、（1．42±0．12）,与健康组比较差异无显著性（P〉0．05）;mI／Cr分别为（0．81±0,07）、（0．78±0．08）、（0．70±0．06）,与健康组比较差异有显著性（P〈0．05kmI／NAA分别为（0．61±0．06）、（0．55±0．08）、（0．49±O．07）,与健康组比较差异有显著性（P〈O．05）。AD患者NAA、NAA／Cr的下降和mI、mI／Cr、mI／NAA的上升,海马〉颞顶叶〉扣带回。结论AD患者MRS改变,主要体现在NAA的下降和mI的上升,对AD的诊断有一定的参考作用。     

氢质子波谱在阿尔茨海默病中的价值

Objective To study the diagnosis value of proton magnetic resonance spectroscopy(1H-MRS)in Alzheimer disease(AD).Methods Using stimulated echo acquisition mode,29 AD patients and 20 elderlv healthy ones as control group were underwent with Magnetic ResonaJlce Spectrum (MRs)examination in hippocampus,temporal parietal cortex and cingulate gyrus,the metabolites of MRS were analvzed to have N-aeetyl aspartate(NAA),creatine(Cr),choline(Cho),myo-inositol (mI),and comDarle the ratio of each other as well as the difference between the two groups.Rmulta NAA of AD patients in hippocampus,temporal parietal cortex and ringulate gyrus were(0.40±0.06),(0.42±0.06),(0.43±0.08),respectively, and have no significant difference to the healthy group(P＞0.05);mI were(0.25±0.08).(0.23±0.06),(0.21±0.05),respectively,and have significant difference to the healthy group(P＜0.05):NAA/Cr werle(1.30±O.10),(1.40±0.11),(1.42±0.12),respectively,and have no significant differenoe to the healthy group(P＞0.05);mI/Cr were,(0.81±0.07),(0.78±0..08),(0.70±0.06),respectively,and have significant difference to the healthy group(P＜0.05);mI,NAA were(0.61±0.06),(0.55±0.08),(0.49±0.07),respeetively,and have significant difference to the healthy group(P＜0.05).In AD patients,NAA,NAA/Cr decrease and mI,mI/Cr,mI/NAA increase,and the value in hippocampus＞temporal parietal cortex＞cingulate gyrus.Conclusion The changes of MRS in AD patients,mainly reflected a decline in NAA and rise in mI,which has some reference in the diagnosis in AD.     

Magnetic resonance spectroscopy: neurochemistry and treatment effects in affective disorders

Recent developments in the clinical capabilities of magnetic resonance spectroscopy (MRS) have provided researchers with considerable insight into potential neurochemical alterations associated with the pathology and treatment of affective disorders. This review focuses on the clinical application of MRS to the study of affective disorders, discusses the major MRS visible neurochemicals, and addresses some essential principles of MRS methodology, such as pulse sequences and neurochemical quantitation. Additionally, some of the more recent key findings in the area of mood disorders and their treatment are highlighted, including pharmacological effects and mechanisms. For example, several independent groups have reported alterations in levels of choline, myoinositol, N-acetylaspartate, and gamma-aminobutyric acid in the central nervous systems of patients with major depression, bipolar disorder, panic disorder, or obsessive-compulsive disorder. Finally, the current direction of advances and areas of further investigation are discussed. This review will afford the reader a fundamental foundation in the applications of MRS in mood disorders and an update on some of the current findings in this rapidly developing discipline.     

海马磁共振波谱分析在颞叶癫痫症中的价值

目的探讨海马氢质子磁共振波谱分析（1H—MRS）在颞叶癫痫症中的应用价值。方法采用PhihpsAchieva1．5T双梯度磁共振扫描仪,对38例颞叶癫痫患者和20例健康志愿者行颅脑MRI和海马’H—MRs检查,观察NAA、Cr、Cho浓度和NAA／（Cho＋Cr）、NAA／Cr和NAA／Cho值。分别对癫痫患者病灶侧与正常侧,病灶侧与正常对照组海马的NAA／（Cho＋Cr）、NAA~r和NAA／Cho值进行t检验,分析两者之间差异有无显著性。结果癫痫患者组癫痫侧、正常侧和对照组海马的NAA／（Cho＋Cr）值分别为（O．424-0．06）、（0．67±0．09）、（O．72±0．07）,癫痫组癫痫侧与正常侧、对照组比较差异有显著性（尸〈0．05）,而正常侧与对照组比较差异无显著性（尸〉0．05）。以NAA／fCho＋c0来检出癫痫,灵敏度曲线呈现低一高一低的变化,在0．60时,灵敏度最高。结论-H—MRS不仅能早期诊断海马硬化,而且可进一步提高术前癫痫灶定位的准确性。     

脑外伤的质子磁共振波谱成像研究

目的探讨氢质子磁共振波谱(1H-MRS)对创伤性脑损伤(TBI)的诊断价值。方法对30例TBI患者和10例健康志愿者行磁共振波谱成像,选择双侧额叶白质、胼胝体膝部左右侧及中线位置各一个点(共5个)为感兴趣区(ROI),分别测定Cho、NAA、Cr、NAA/Cr、NAA/Cho、Cho/Cr。对不同程度TBI患者组1H-MRS所测定值与GCS、GOS评分间进行相关性分析。结果TBI患者与正常对照组Cho/Cr、NAA/Cr、NAA/Cho有统计学差异(P<0.05)。TBI患者组NAA/Cho、NAA/Cr与GCS评分及GOS评分均存在正相关,Cho/Cr比值与GCS评分及GOS评分呈负相关。正常对照组均未检测到Lac峰,TBI患者特重度中2例出现Lac峰。结论氢质子磁共振波谱(1HMRS)能定量测定创伤性脑损伤后脑组织代谢的情况,对TBI患者的受伤程度、预后预测有重要价值。     

High resolution proton magnetic resonance spectroscopy of human cervical mucus

High resolution 1H NMR spectroscopy is a powerful method for qualitative and quantitative analysis of the highly viscous human cervical mucus (CM). Up to 23 compounds could be identified in this study and can be observed in the 1H NMR spectra of native mucus without the need of any complicated preparative chemistry. Storage conditions could be excluded as a possible reason for variations observed between different samples. pH values decreased after freezing and storing at 253 K. For NMR studies, lyophilization proved to be most useful, allowing the determination of the water content, replacement of H2O by D2O, and most importantly, absolute quantification of low molecular mass compounds. In a small collective of women the concentrations of some of the small constituents of the CM are strongly correlated; an example is the mutual positive correlation of taurine, citrate and creatinine. In conclusion, high resolution 1H NMR spectroscopy is a valid method to investigate mucus composition and to determine absolute concentrations of low molecular mass compounds in CM.     

Rapid determination of dimethyl polysiloxane by proton magnetic resonance spectroscopy.

A new procedure is described for the quantitative extraction and determination of dimethyl polysiloxane by 1H-NMR spectroscopy, using tetrachloroethylene as the solvent and dioxane as the internal reference.     

Determination of scutellarin in breviscapine preparations using quantitative proton nuclear magnetic resonance spectroscopy

The objective of the present study was to develop the selection criteria of proton signals for the determination of scutellarin using quantitative nuclear magnetic resonance (qNMR), which is the main bioactive compound in breviscapine preparations for the treatment of cerebrovascular disease. The methyl singlet signal of 3-(trimethylsilyl)propionic-2,2,3,3-d₄ acid sodium salt was selected as the internal standard for quantification. The molar concentration of scutellarin was determined by employing different proton signals. To obtain optimum proton signals for the quantification, different combinations of proton signals were investigated according to two selection criteria: the recovery rate of qNMR method and quantitative results compared with those obtained with ultra-performance liquid chromatography. As a result, the chemical shift of H-2′ and H-6′ at δ 7.88 was demonstrated as the most suitable signal with excellent linearity range, precision, and recovery for determining scutellarin in breviscapine preparations from different manufacturers, batch numbers, and dosage forms. Hierarchical cluster analysis was employed to evaluate the determination results. The results demonstrated that the selection criteria of proton signals established in this work were reliable for the qNMR study of scutellarin in breviscapine preparations.     

Identification of a lactam by mass spectrometry and proton magnetic resonance spectroscopy

Clebopride, a new drug, related to metoclopramide and sulpiride, was incubated with fortified 9000 g supernatant of liver homogenates of maleNzw rabbits. A lactam,N-(4′-piperidyl-2′-one)-4-amino-5-chloro-2-methoxybenzamide, was identified as a metabolic product, using electron impact (low and high resolution) and field desorption mass spectrometry andCat proton magnetic resonance spectroscopy.     

Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a proton magnetic resonance spectroscopy study.

We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment remitters and nonremitters. Secondary aims of this study were to identify neurochemical predictors of successful olanzapine treatment and other neurochemical effects of olanzapine. In all, 20 adolescents admitted for their first hospitalization for bipolar disorder, type I, manic or mixed and 10 demographically matched healthy subjects were recruited. Manic adolescents were treated with olanzapine monotherapy and scanned at three time points (N = 19). Medial and left and right lateral ventral prefrontal NAA, choline, creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at baseline, prior to receiving medication, and on days 7 and 28 of treatment. Healthy subjects did not receive medication but underwent 1H MRS scans at the same time points to assess for normal variability in metabolites over time. Although there was no overall increase in NAA in manic adolescents following 28 days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a greater increase in medial ventral prefrontal NAA compared with nonremitters (N = 8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic adolescents treated with olanzapine had an increase from baseline to day 7 in medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline. Baseline medial ventral prefrontal choline was greater in olanzapine remitters than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine may lead to increased ventral prefrontal neuronal viability and/or function as compared to unsuccessful treatment with olanzapine. Additionally, olanzapine-induced increases in choline may lead to alteration of abnormalities in cell membrane metabolism or second messenger pathways that are thought to be involved in the pathophysiology of bipolar disorder.     

Interaction of L-tryptophan with alpha-cyclodextrin: studies with calorimetry and proton nuclear magnetic resonance spectroscopy

The interaction of L-tryptophan with alpha-cyclodextrin was investigated in a 0.1 M phosphate buffer at pH 7.4 with a LKB 2277 microcalorimeter, using flow mixed mode at 25 degrees C. The thermodynamic parameters for inclusion complex formation obtained are as follows; DeltaG(0) = - 7.03 kJ/mol (K = 17.0), DeltaH(0) = - 9.50 kJ/mol, DeltaS(0) = - 8.3 J/mol K. The driving force for inclusion complex formation was considered to be mainly van der Waals-London dispersion force, and the contribution of hydrogen bonding was secondary in importance. Also, from the measurements of the proton nuclear magnetic resonance spectra and the model building with Corey-Pauling-Koltum atomic models, the probable structures of the complex, together with conformational change of L-tryptophan by complexation, were determined.     

A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania

BACKGROUND: Several neurochemical abnormalities have been reported in bipolar disorder (BD), but the exact mechanisms that underlie its pathophysiology remain to be elucidated. Proton magnetic resonance spectroscopy (1HMRS) allows in vivo measurements of certain neurometabolites in the human brain. 1HMRS was used to investigate the dorsolateral prefrontal cortex (DLPFC) in bipolar subjects during a manic or mixed phase. N-acetyl-L-aspartate (NAA), choline-containing molecules (Cho), creatine plus phosphocreatine (Cr) and myoinositol (Ino) were measured. METHOD: Ten bipolar patients (nine manic, one mixed), diagnosed by a semi-structured clinical interview (SCID), and ten age- and gender-matched healthy volunteers were studied. Absolute neurometabolites levels were measured from two 8 cm3 voxels placed in left and right DLPFC using a short TE 1HMRS method at 1.5 T. T1- and T2-weighted anatomical magnetic resonance imaging was performed to exclude any neuroanatomical abnormality. RESULTS: No significant differences were found for NAA, Cho, Cr, Ino, NAA/Cr, Cho/Cr or Ino/Cr between patients and controls. Manic/mixed patients had significantly higher left-to-right myoinositol ratios in DLPFC (p = 0.044). CONCLUSIONS: Increased left-to-right myoinositol ratios in the DLPFC in bipolar patients during acute mania may represent a dysfunction in the phosphoinositide-signaling pathway. Longitudinal studies with larger samples of unmedicated patients assessing pre- and post-treatment times will be required for further clarification of the time course of these abnormalities and the relationship with treatment effects.     

The response of the rat liver in situ to bromobenzene--in vivo proton magnetic resonance imaging and 31P magnetic resonance spectroscopy studies

Proton magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) have been used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity was seen in the perihilar region of the liver 24 hr after injection of a sublethal dose of bromobenzene. The signal intensity of the entire liver was increased at 48 hr with a gradual return approaching control values by 120 hr. These results are consistent with acute hepatic edema followed by repair of the damaged tissue. In vivo 31P MRS studies of the same rat livers were performed under conditions whereby localized, quantitative spectra could be obtained without surgical intervention. Initial concentrations of the major endogenous phosphorus-containing metabolites within the livers of control rats were 2.97 +/- 0.43 mM for the phosphomonoesters (PME), 2.92 +/- 0.56 mM for inorganic phosphate, 11.3 +/- 1.0 mM for phosphodiesters (PDE), 4.09 +/- 0.54 mM for ATP, and 0.56 +/- 0.50 mM for ADP and the intracellular pH was 7.39 +/- 0.14 (mean +/- SD, n = 10). Bromobenzene was found to cause statistically significant (p less than 0.05) changes in several of these metabolites: a decrease in hepatic ATP levels (20% at 24 hr; 27% at 48 hr), a decrease in PDE levels (15% at 24 hr; 18% at 48 hr), and an increase in the PME (63% at 24 hr; 84% at 48 hr). Both the proton MRI and the 31P MRS changes have an onset of 15-20 hr and maximum effect at 25-60 hr, but the MRS changes returned to normal well before the MRI changes. The decreased ATP levels indicate deleterious effects of bromobenzene on the bioenergetic status of the liver in situ, while the increase in PME, due to a selective increase in phosphocholine, suggests the activation of a phosphatidylcholine-specific phospholipase C in response to tissue damage. Trolox C, a potent inhibitor of lipid peroxidation, prevented the bromobenzene-induced hepatic edema (i.e., the increase in proton MRI signal intensity) and the bioenergetic deterioration (i.e., the decrease in ATP levels). However, the bromobenzene-induced increase in PME levels was not prevented by Trolox C. These results indicate that the process of lipid peroxidation plays a significant role in the hepatotoxicity of bromobenzene within the intact animal.     

Chiral discrimination of sibutramine enantiomers by capillary electrophoresis and proton nuclear magnetic resonance spectroscopy

Capillary electrophoresis (CE) and proton nuclear magnetic resonance spectroscopy (¹H-NMR) have been used to discriminate the enantiomers of sibutramine using cyclodextrin derivatives. Possible correlation between CE and ¹H-NMR was examined. Good correlation between the ¹H-NMR shift non-equivalence data for sibutramine and the degree of enantioseparation in CE was observed. In CE study, a method of enantiomeric separation and quantitation of sibutramine was developed using enantiomeric standards. The method was based on the use of 50 mM of phosphate buffer of pH 3.0 with 10 mM of methyl-beta-cyclodextrin (M-β-CD). 0.05% of LOD, 0.2% of LOQ for S-sibutramine enantiomer was achieved, and the method was validated and applied to the quantitative determination of sibutramine enantiomers in commercial drugs. On a 600 MHz ¹H-NMR analysis, enantiomer signal separation of sibutramine was obtained by fast diastereomeric interaction with a chiral selector M-β-CD. For chiral separation and quantification, N-methyl proton peaks (at 2.18 ppm) were selected because of its being singlet and simple for understanding of diastereomeric interaction. Effects of temperature and concentration of chiral selector on enantiomer signal separation were investigated. The optimum condition was 0.5 mg/mL of sibutramine and 10 mg/mL of M-β-CD at 10°C. Distinguishment of 0.5% of S-sibutramine in R-sibutramine was found to be possible by ¹H-NMR with M-β-CD as chiral selector. Host-guest interaction between sibutramine and M-β-CD was confirmed by ¹H-NMR studies and CE studies. A Structure of the inclusion complex was proposed considering ¹H-NMR and 2D ROESY studies.