Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.

Application of proton magnetic resonance spectroscopy in metabolic alterations of prefrontal white and gray matter in depression adolescents

BACKGROUND Cases of depression among adolescents are gradually increasing.The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention.Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus,frontal lobe white matter,and the thalamus.AIM To explore the application of proton magnetic resonance spectroscopy(1H-MRS)in the metabolic alterations in the prefrontal white matter(PWM)and gray matter(GM)in adolescents with depression.METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate(NAA),choline(Cho)complexes,creatine(Cr),and myoinositol(mI)in bilateral PWM,anterior cingulate GM,and thalami of 31 adolescent patients with depression(research group)and 35 healthy adolescents(control group),and the NAA/Cr,Cho/Cr,and mI/Cr ratios were calculated.Meanwhile,Hamilton Depression Scale(HAMD)and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents.The correlation of brain metabolite levels with scale scores was also analyzed.RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient(MQ)compared with the control group(P<0.05).Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents(P<0.05).The mI/Cr ratios were found to be similar in both groups(P>0.05).The bilateral anterior cingulate GM NAA/Cr,Cho/Cr,and mI/Cr also did not demonstrate marked differences(P>0.05).No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami(P>0.05),while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents(P<0.05).A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr(P<0.05).In adolescents with depressions,MQ positively correlated with right PWH NAA/Cr,left PWH Cho/Cr,and bilateral thalamic Cho/Cr and mI/Cr.CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression,and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment.There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.

Brain metabolic profile assessed by magnetic resonance spectroscopy in children with Down syndrome:Relation to intelligence quotient

BACKGROUND Down syndrome(DS)is one of the most common causes of intellectual disability.Children with DS have varying intelligence quotient(IQ)that can predict their learning abilities.AIM To assess the brain metabolic profiles of children with DS and compare them to standard controls,using magnetic resonance spectroscopy(MRS)and correlating the results with IQ.METHODS This case-control study included 40 children with DS aged 6-15 years and 40 age and sex-matched healthy children as controls.MRS was used to evaluate ratios of choline/creatine(Cho/Cr),N-acetyl aspartic acid/creatine(NAA/Cr),and myoinositol/creatine(MI/Cr(in the frontal,temporal,and occipital lobes and basal ganglia and compared to controls and correlated with IQ.RESULTS Children with DS showed significant reductions in NAA/Cr and MI/Cr and a non-significant reduction in Cho/Cr in frontal lobes compared to controls.Additionally,we observed significant decreases in NAA/Cr,MI/Cr,and Cho/Cr in the temporal and occipital lobes and basal ganglia in children with DS compared to controls.Furthermore,there was a significant correlation between IQ and metabolic ratios in the brains of children with DS.CONCLUSION Brain metabolic profile could be a good predictor of IQ in children with DS.

Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents

AIM To establish a threshold value for liver fat content between healthy children and those with nonalcoholic fatty liver disease(NAFLD) by using magnetic resonance imaging(MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel pointresolved 1H MR-Spectroscopy(1H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cutoff value. Lin coefficient test was used to evaluate thecorrelation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.

IN VIVO ~1 H MAGNETIC RESONANCE SPECTROSCOPY IN EVALUATION OF HEPATOCELLULAR CARCINOMA AND ITS EARLY RESPONSE TO TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial chemoembolization （TACE）. Mothoda In this prospective study, 28 consecutive patients with large HCC （ ≥3 cm in diameter） confirmed by fine needle aspiration biopsy were recruited. The ^1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor. The technical success rate of IH MRS in liver was high （33/41, 80% ）, closely related to breath motion, location of lesion, and size of voxeL In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended （ choline-to-lipid ratios from 0.352±0. 080 to 0. 167±0. 030, P = 0. 026; from 0. 205±0. 060 to 0. 070±0. 020, P = 0. 042, respectively ） ; yet lipid resonance peak ascended. Conclusions In vivo tH MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. IH MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

In vivo magnetic resonance spectroscopy of liver tumors and metastases

Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism, in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRSapproaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.

Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease

Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiologi- cal processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.

Magnetic resonance spectroscopy to study hepatic metabolism in diffuse liver diseases, diabetes and cancer

This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used as a research tool rather than a clinical tool. The liver is particularly suitable for static and dynamic metabolic studies due to its high metabolic activity. Furthermore, its relatively superfi cial position allows excellent MRS localization, while its large volume allows detection of signals with relatively low intensity. This review describes the application of MRS to study the metabolic consequences of different conditions including diffuse and chronic liver diseases, congenital diseases, diabetes, and the presence of a distant malignancy on hepatic metabolism. In addition, future prospects of MRS are discussed. It is anticipated that future technical developments such as clinical MRS magnets with higher fi eld strength (3 T) and improved delineation of multicomponent signals such as phosphomonoester and phosphodiester using proton decoupling, especially if combined with price reductions for stable isotope tracers, will lead to intensifi ed research into metabolic syndrome, cardiovascular disease, hepato-biliary diseases, as well as non-metastatic liver metabolism in patients with a distant malignant tumor.

Early Biomarkers in 1H Nuclear Magnetic Resonance Spectroscopy of Striatal Pathological Mechanisms after Acute Carbon Monoxide Poisoning in Rats

Objective In vivo Proton Magnetic Resonance Spectroscopy （1H-MRS） can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain. Methods We conducted T2-Weighted Magnetic Resonance Imaging （MRI） and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide （CO） poisoning. Results Compared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine （Cr） ratios of N-acetylaspartate （NAA） was observed as early as 1 h after the last CO administration, while the lactate （Lac） levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline （Cho）/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning. Conclusion The present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.

Quantification of choline concentration following liver cell apoptosis using ~1H magnetic resonance spectroscopy

AIM: To evaluate the feasibility of quantifying liver choline concentrations in both normal and apoptotic rabbit livers in vivo, using 1H magnetic resonance spectroscopy (1H-MRS). METHODS: 1H-MRS was performed in 18 rabbits using a 1.5T GE MR system with an eight-channel head/neck receiving coil. Fifteen rabbits were injected with sodium selenite at a dose of 10 μmol/kg to induce the liver cell apoptosis. Point-resolved spectroscopy sequencelocalized spectra were obtained from 10 livers once before and once 24 h after sodium selenite injection in vivo. T1 and T2 relaxation time of water and choline was measured separately in the livers of three healthy rabbits and three selenite-treated rabbits. Hematoxylin and eosin and dUTP-biotin nick end labeling (TUNEL) staining was used to detect and confirm apoptosis. Choline peak areas were measured relative to unsuppressed water using LCModel. Relaxation attenuation was corrected using the average of T1 and T2 relaxation time. The choline concentration was quantified using a formula, which was tested by a phantom with a known concentration. RESULTS: Apoptosis of hepatic cells was confirmed by TUNEL assay. In phantom experiment, the choline concentration (3.01 mmol/L), measured by 1H-MRS, was in good agreement with the actual concentration (3 mmol/L). The average T1 and T2 relaxation time of choline was 612 ± 15 ms and 74 ± 4 ms in the control group and 670 ± 27 ms and 78 ± 5 ms in apoptotic livers in vivo, respectively. Choline was quantified in 10 rabbits, once before and once after the injection with sodium selenite. The choline concentration decreased from 14.5 ± 7.57 mmol/L before sodium selenite injection to 10.8 ± 6.58 mmol/L (mean ± SD, n = 10) after treatment (Z = -2.395, P < 0.05, two-sample paired Wilcoxon test). CONCLUSION: 1H-MRS can be used to quantify liver choline in vivo using unsuppressed water as an internal reference. Decreased liver choline concentrations are found in sodium selenite-treated rabbits undergoing liver cell apoptosis.

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls.METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P &#x0003c; 0.05.RESULTS: There were significant differences in age (P &#x0003c; 0.001), weight (P &#x0003c; 0.001), and body mass index (P &#x0003c; 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P &#x0003c; 0.001); serum &#x003b1;-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine (DMA), formate, glycine, hippurate, and trimethylamine-N-oxide (TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBeAg negative patients showed a significant increase in creatinine (P = 0.001) compared to HBeAg positive patients in the chronic hepatitis B subgroup, whilst HBeAg negative patients showed a significant decrease in DMA (P = 0.004) in the cirrhosis subgroup compared to HBeAg positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment.CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.

Biochemical metabolic changes assessed by ^(31)P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

AIM： To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy （^31p MRS） with the liver damage score （LDS） and pathologic changes in rabbits and to investigate the diagnostic value of ^31p MRS in acute hepatic radiation injury. METHODS： A total of 30 rabbits received different radiation doses （ranging 5-20 Gy） to establish acute hepatic injury models. Blood biochemical tests, ^31p MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LD5 and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H/^31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters （PME）, phosphodiesters （PDE）, inorganic phosphate （Pi） and adenosine triphosphate （ATP） were measured. The data were statistically analyzed. RESULTS： （1） Relative quantification of phosphorus metabolites： （a） ATP： there were significant differences （P 〈 0.05） （LDS-groups：control group vs mild group vs moderate group vs severe group, 1.83±0.33 vs 1.55±0.24 vs 1.27±0.09 vs 0.98±0.18; pathological groups： control group vs mild group vs moderate group vs severe group, 1.83±0.33 vs 1.58±0.25 vs 1.32±0.07 vs 1.02±0.18） of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury （r = -0.723, P = 0.000）. （b） PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant （P 〈 0.05） （PME： 1DS- control group vs LDS-severe group, 0.86±0.23 vs 0.58±0.22, P = 0.031; pathological control group vs pathological severe group, 0.86±0.23 vs 0.60±0.21, P = 0.037; Pi： LDS-control group vs LDS-severe group, 0.74±0.18 vs 0.43±0.14, P = 0.013; pathological control group vs pathological severe group, 0.74±0.18 vs 0.43±0.14, P = 0.005） according to LDS grading and pathological grading, respectively. （c） PDE; there were no significant differences among groups according to LDS grading, and no significant differences between the control group and experimental groups according to pathological grading. （2） The ratio of relative quantification of phosphorus metabolites： significant differences （P 〈 0.05） （LDS- moderate group and LDS-severe group vs LDS-control group and LDS-mild group, 1.94±0.50 and 1.96±0.72 vs 1.43±0.31 and 1.40±0.38） were only found in PDE/ATP between the moderate injured group, the severe injured group and the control group, the mild injured group. No significant difference was found in other ratios of relative quantification of phosphorus metabolites.CONCLUSION： ^31p MRS is a useful method to evaluate early acute hepatic radiation injury. The relative quantification of hepatic ATP levels, which can reflect the pathological severity of acute hepatic radiation injury, is correlated with LDS.

Neurochemical metabolites in the medial prefrontal cortex in bipolar disorder A proton magnetic resonance spectroscopy study

The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type I and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.

Application of Proton Magnetic Resonance Spectroscopy and Computerized Tomography in the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease

In order to investigate the application of proton magnetic resonance spectroscopy （ill-MRS） and computerized tomography （CT） in the quantitative diagnosis of nonalcoholic fatty liver disease （NAFLD） and evaluation of therapeutic effects, 22 patients with NAFLD were selected according to the Chinese Medical Association＇s （CMA） standard of the NAFLD in comparison with 20 healthy volunteers （as control group）. Blood samples for biochemistry were collected. The severity of hepatosteatosis was evaluated by ^1H-MRS scan and CT scan of liver. The intrahepatic content of lipid （IHCL） and CT value ratio of liver to spleen were calculated. The patients in NAFLD group were treated with Ganzhixiao Capsule for 8 weeks. The changes in IHCL and CT value ratio of liver to spleen were observed before and after treatment. In NAFLD group serum ALT, TG, IHCL calculated by ^1HMRS were increased and CT value ratio of liver to spleen decreased significantly as compared with control group. After treatment for 8 weeks serum ALT, TG, IHCL were decreased significantly, while CT value ratio of liver to spleen increased significantly in NAFLD group. It was suggested that IHCL could be measured precisely by ^1HMRS. NAFLD was treated effectively by Ganzhixiao capsule.

Imaging changes in neural circuits in patients with depression using 1 H-magnetic resonance spectroscopy and diffusion tensor imaging

1 H-magnetic resonance spectroscopy imaging and diffusion tensor imaging were performed in 19 patients with mild depression and in 13 controls.The mean age of the patients was 31 years.The mean Hamilton depression score of the patients was 22.5±13.2.N-acetylaspartate,choline and creatine concentrations and the average diffusion coefficient and fractional anisotropy values were measured in the bilateral hippocampus,striatum,thalamus and prefrontal deep white matter. Compared with the control group,the mild depressed patients had：（1）a higher choline/creatine ratio and a negative correlation between the choline/creatine ratio and the average diffusion coefficient in the hippocampus;（2）a lower choline/creatine ratio and a higher fractional anisotropy in the striatum;（3）a lower fractional anisotropy and a positive correlation between the fractional anisotropy and the choline/creatine ratio in the prefrontal deep white matter;and（4）a higher average diffusion coefficient and a positive correlation between the choline/creatine ratio and the N-acetylaspartate/creatine ratio in the thalamus,as well as positive correlation between the choline/creatine ratio and Hamilton depression scores.These data suggest evidence of abnormal connectivity in neurofibrotic microstructures and abnormal metabolic alterations in the limbic-cortical-striatal-pallidal-thalamic neural circuit in patients with mild depression.

Metabolic changes of prefrontal cerebral lobe,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

BACKGROUND： Proton magnetic resonance spectroscopy （IH-MRS） non-invasively detects changes in chemical substances in the brain, which reflects the pathological metabolism.OBJECTIVE： To investigate changes in N-acetyl-aspartate （NAA）, choline （Cho）, creatine （Cr）, and myoinositol （MI） in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression （PSD） using ^1H-MRS. DESIGN： A case control study. SETTING： The First Affiliated Hospital of the Dalian Medical University. PARTICIPANTS： A total of 38 patients with stroke （28 male and l0 female patients, aged 40 to 79 years） were selected from the Department of Neurology, 1st Affiliated Hospital, Dalian Medical University, from February to October in 2004. All subjects met the DSM-IV criteria for cerebrovascular disease and depression. The degree of depression was defined according to Hamilton criteria. 38 patients with PSD were divided into two groups according to the time after ischemia, 20 patients in the acute group with less than 10 days after ischemic attack （mild： 16 patients, moderate/severe： 4 patients） and 18 patients in the chronic group with more than l l days after ischemic attack （mild： 15 patients, moderate/severe： 3 patients）. Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group. The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, and each participant signed an informed consent form. METHODS： Spectra were acquired by multi-voxel point-resolved spectroscopy （PRESS） sequence with GE signal.5T MR/i, localized in prefrontal cerebral lobe and cerebellum. Values of NAA, Cho, MI, and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS 11.5. MAIN OUTCOME MEASURES： Metabolite concentration in different brain regions of interest. Difference in metabolites between distinctly graded PSD patients and control subjects. Exclusion of age-effects on metabolites. RESULTS： Metabolite concentrations of different brain regions： A significant rise in the Cho/Cr ratio was detected in the acute and chronic group compared to the control group. The ratio change was more significant in the acute group （P 〈 0.05）. There was no significant difference between these three groups for other metabolites detected by IH-MRS in the right frontal white matter, bilateral frontal grey matter, and cerebellum （P 〉 0.05）. Comparison of metabolite levels among differently graded PSD patients and control subjects： a significant increase in the Cho/Cr ratio was detected in the left frontal white matter compared to the control group （P 〈 0.05）. There was no significant difference in age between patients in the stroke groups and the control group （P 〉 0.05）, and similarly, there was no significant correlation between age and absolute or relative values in the control group （P 〉 0.05）. CONCLUSION： Abnormalities of frontal lobe in PSD were located in the white matter. There was early abnormality of metabolic substance in PSD.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase Ⅱ trial

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease(NAFLD).METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose(400 mg) HL tablet, low dose(133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content(HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase(ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index(BMI).RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment(high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were-1.7% ± 3.1% in the high dose group(P = 0.018),-1.21% ± 4.97% in the low dose group(P = 0.254) and 0.61% ± 3.87% in the placebo group(relative changes compared to baseline, high dose were:-12.1% ± 23.5%, low dose:-3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study.CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

Applications of multi-nuclear magnetic resonance spectroscopy at 7T

AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.METHODS: Measurements of brain metabolites were made at both 3 and 7T using 1H MRS. Measurements of glycogen and lipids in muscle were measured using 13C and 1H MRS respectively.RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these metabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen (13C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) (1H) following exercise and re-feeding. Glycogen levels were significantly decreased following exercise (-28% at 50% VO2 max; -58% at 75% VO2 max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study.CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.

Nuclear magnetic resonance spectroscopy is highly sensitive for lipid-soluble metabolites

Although the water-soluble metabolite profile of human mesenchymal stem cells is known, the lipid profile still needs further investigation. In this study, methanol-chloroform was used to extract lipid-soluble metabolites and perchloric acid was used to extract water-soluble metabolites. Fur- thermore, a dual phase extraction method using methanol-chloroform and water was used to obtain both water and lipid fractions simultaneously. All metabolite extractions were analyzed on a 9.4T high-resolution nuclear magnetic resonance spectrometer. Metabolite resonance peaks were as- signed in the acquired spectra according to the chemical shift, and the extraction efficiency of dif- ferent methods was compared. Results showed that in the spectra of water-soluble extracts, major metabolites comprised low molecular weight metabolites, including lactate, acetic acid, fatty acids, threonine, glutamic acid, creatine, choline and its derivatives, while in the spectra of lipid-soluble extracts, most metabolites were assigned to fatty acids. Among the different extraction procedures, perchloric acid was more efficient in extracting water-soluble metabolites and methanol-chloroform was efficient in extracting organic components compared with the dual phase extraction method. Nuclear magnetic resonance spectroscopy showed that as low as 0.7 mg organic yield was enough to obtain clear resonance peaks, while about 6.0 mg water-soluble yield was needed to obtain rela- tively favorable spectral lines. These results show that the efficiency of extracting water and lipid fractions is higher using perchloric acid and methanol-chloroform compared with dual phase ex- traction and that nuclear magnetic resonance spectroscopy is highly sensitive for analyzing lipid-soluble extracts.

1H magnetic resonance spectroscopy and diffusion weighted imaging findings of medulloblastoma in 3.0T MRI A retrospective analysis of 17 cases

1H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. 1H magnetic resonance spectroscopy showed that in all 17 medulloblastoma patients, N-acetyl aspartate and creatine peaks were significantly decreased, the choline peak was significantly increased, and there was evidence of a myo-inositol peak. Further, 11 patients showed a low taurine peak at 3.4 ppm, five patients showed a lipid peak at 0.9-1.3 ppm, and three patients showed a negative lactic acid peak at 1.33 ppm. Compared with the control group, the ratios of N-acetyl aspartate/choline and N-acetyl aspartate/creatine were significantly decreased, and the ratio of choline/creatine was increased, in medulloblastoma patients. Diffusion weighted imaging displayed hyperintensity and decreased apparent diffusion coefficient in medulloblastoma patients. These findings indicate that 1H magnetic resonance spectroscopy and diffusion weighted imaging are useful for qualitative diagnosis of medulloblastoma.