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.

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.

Liver fat content determined by magnetic resonance imaging and spectroscopy

Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fatcontaining vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the invasive technique, various other non-invasive techniques have been developed, such as ultrasound, computed tomography (CT), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) based methods. Among these techniques, ultrasound and CT provide only qualitative information about hepatic steatosis, whereas MRS-or MRI-based methods are able to determine even small amounts of fat accurately. These non-invasive magnetic resonance techniques have already proven their great potential, especially in longitudinal and cross-sectional studies regarding various metabolic conditions and medical treatment regimens. In this review, the most common, non-invasive MRS/MRI techniques for assessment of intrahepatic lipid content are described with their inherent advantages and limitations.

3.0T 1H magnetic resonance spectroscopy for assessment ofsteatosis in patients with chronic hepatitis C

AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.

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.

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 leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA 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 MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-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 threefactor 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. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag 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.

3.0 T proton magnetic resonance spectroscopy of the liver: Quantification of choline

AIM: To investigate the normal hepatic magnetic resonance spectroscopy findings choline/lipid2 (Cho/Lip2) associated with age and body mass index (BMI).METHODS: A total of 58 single-voxel proton spectra of the liver were acquired at 3.0 T using the eightchannel phased array abdominal coil as the receiver coil. Consecutive stacks of breath-hold spectra were acquired using the point resolved spectroscopy technique at a short echo time of 30 ms and a repetition time of 1500 ms. The spectra were processed with the SAGE software package. Areas and heights for metabolite resonance were obtained. Student's t test for unpaired data was used for comparisons of shimming, Cho/Lip2, and lipid content. RESULTS: There were significant negative correlations between the Cho/Lip2 peak height ratios and BMI (r=-0.615) and age (r=-0.398) (all P<0.01). Compared with the high-BMI group, the low-BMI group was younger (39.1±13.0 years vs 47.6±8.5 years, t=-2.954,P=0.005); had better water suppression (93.4%±1.4% vs 85.6%±11.6%, t=2.741, P=0.014); had higher Cho/Lip2 peak heights ratio (0.2±0.14 vs 0.05±0.04,t=6.033,P<0.000); and had lower lipid content (0.03±0.08 vs 0.29±0.31, t=-3.309, P=0.004). Compared with the older group, the younger group had better shimming effects (17.1±3.6 Hz vs 22.0±6.8 Hz, t=-2.919, P=0.008); higher Cho/Lip2 peak heights ratios (0.03±0.05vs 0.09±0.12,t=2.4, P=0.020); and lower lipid content (0.05±0.11 vs 0.23±0.32,t=-2.337,P=0.031). Compared with the lowcholine peak group, the high-choline peak group had lower lipid content (0.005±0.002 vs 0.13±0.23, t=-3.796,P<0.000); lower BMI (19.6±2.4vs 23.9±3.0, t=-4.410, P<0.000); and younger age (34.7±10.0 years vs 43.2±12.5 years, t=-2.088, P=0.041). CONCLUSION: Lipid accumulation could result from the increased fat in the body depending on age and BMI. Lipid can mask the resonance signal of choline.

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.

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.

Characterization of gold nanoparticle bioconjugation by resonance light scattering correlation spectroscopy

Gold nanoparticles （GNPs） have been widely used as probes and nanomaterials in certain biological and biomedical fields thanks to its special physical and chemical properties. However, it is still difficult to characterize GNPs-bioconjugates in solution, which has greatly limited further bioapplications of GNPs. In this study, we reported a single particle method for characterizing GNPs- biomolecules in solution using resonance light scattering correlation spectroscopy （RLSCS）. The interaction of GNPs with bovine serum albumin （BSA） and thiol-modified oligonucletides were investigated.

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.

Surface-enhanced resonance Raman scattering spectroscopy of single R6G molecules

Surface-enhanced resonance Raman scattering （SERRS） of Rhodamine 6G （R6G） adsorbed on colloidal silver clusters has been studied. Based on the great enhancement of the Raman signal and the quench of the fluorescence, the SERRS spectra of R6G were recorded for the samples of dye colloidal solution with different concentrations. Spectral inhomogeneity behaviours from single molecules in the dried sample films were observed with complementary evidences, such as spectral polarization, spectral diffusion, intensity fluctuation of vibrational lines and even ＂breathing＂ of the molecules. Sequential spectra observed from a liquid sample with an average of 0.3 dye molecules in the probed volume exhibited the expected Poisson distribution for actually measuring 0, 1 or 2 molecules. Difference between the SERRS spectra of R6G excited by linearly and circularly polarized light were experimentally measured.

Selective excitation of molecular mode in a mixture by femtosecond resonance-enhanced coherent anti-Stokes Raman scattering spectroscopy

Femtosecond time-resolved coherent anti-Stokes Raman scattering （CARS） spectroscopy is used to investigate gaseous molecular dynamics. Due to the spectrally broad laser pulses, usually poorly resolved spectra result from this broad spectroscopy. However, it can be demonstrated that by the electronic resonance enhancement optimization control a selective excitation of specific vibrational mode is possible. Using an electronically resonance-enhanced effect, iodine molecule specific CARS spectroscopy can be obtained from a mixture of iodine-air at room temperature and a pressure of 1 atm （corresponding to a saturation iodine vapour as low as about 35 Pa）. The dynamics on either the electronically excited state or the ground state of iodine molecules obtained is consistent with previous studies （vacuum, heated and pure iodine） in the femtoseeond time resolved CARS spectroscopy, showing that an effective method of suppressing the non-resonant CARS background and other interferences is demonstrated.

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.

Body mass index and its effects on liver fat content in overweight and obese young adults by proton magnetic resonance spectroscopy technique

AIM To assess the association between liver fat content(LFC) and weight status in young adults using proton magnetic resonance spectroscopy(1H MRS) technique.METHODSSeventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group(OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1 H MRS was performed for LFC assessment.RESULTS LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower highdensity lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex(multiple linear regression; β = 0.459, P <0.001).CONCLUSION Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content.

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.

Longitudinal follow-up of patients with mild traumatic brain injury by magnetic resonance spectroscopic technique

Objective:To explore the changes in the concentrations of neural markers immediately or several months after mild traumatic brain injury(mTBI).Methods:The metabolic markers of neurons in white matter tissues above the lateral ventricle were semi-quantitatively determined by employing 1H magnetic resonance spectroscopic technique(1-H-MRS) in 30 clinically diagnosed cases of mTBI.At the same time,the neurological functions of the subjects,including ability to pay attention,memory,working memory and operational capacity etc were also assessed. Results:The patients were followed up for,on average,13 days after mTB1 and the results showed that Cre,PCre and Glx in the white matter tissues were significantly elevated in mTBI patients.17 patients(57%) recovered from the injury during the follow-up(median was defined as the 40th post-trauma day).Comparison in terms of intelligence among groups revealed that the levels of neural markers of intelligence development was positively related with intelligence scores).Conclusions:Change in Clx concentrations is most sensitive during trauma or in ensuing repairing processes,and might be different from normal status in the following months and Clx level tends to be accompanied with change in Cre,another energy-related marker.

Using Nuclear Magnetic Resonance and MS/MS Spectroscopy for the Identification of Brodimoprim Metabolites in Rat Urine

Eight metabolites of brodimoprim (BDP) in rat urine were detected by NMR and ESIMS/MS. They were demethyl-BDP glucuronide, demethyl-BDP sulfurate, demethyl-BDP glucuronide sulfurate, alpha -hydroxyl-BDP, alpha -hydroxyl-BDP glucuronide, BDP sulfurate, N-oxide-BDP sulfurate, and alpha -hydroxyl-N-oxide-BDP sulfurate. All the sulfurates are reported for the first time.

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3 , the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiationtreated pancreatic tumor tissues were compared. RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.