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.

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.

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.

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.

AQP4 expression and its correlation with the Lac and NAA using proton magnetic resonance spectroscopy after rat cerebral ischemia

Objective： To determine whether AQP4 expression is associated with lactate （Lac） and Nacetyl aspartate （NAA） and with apparent diffusion coefficient （ADC） abnormality after rat cerebral ischemia. Methods： The time courses of ADC and lactate and NAA assessed by proton magnetic resonance spectroscopy （^1HMRS） were investigated at the time point of 6 h, and 1, 3, 7 d after rat cerebral ischernia induced by middle cerebral artery occlusion. Expression of AQP4 mRNA and protein were measured using RT-PCR and Western blot analysis respectively. Results： Significant reductions of NAA concentration and increases of lactate concentration were found after rat cerebral ischemia. The expressions of AQP4 mRNA t and protein were increased at 6 h, and reached the peak at 1-3 d, then began to decrease at 7 d after rat cerebral ischemia. The expression of AQP4 was significantly correlated with NAA （rRT = -0. 856, rw = -0. 927, P〈0.01）, and with lactate （rw=0. 473, rRT=0. 413, P〈0.05）, and with ADC values during the period of 1-7d after rat cerebralischemia （rw=0.984, rRT=0.925, P〈0.05）. In addition, correlations between Lac and the ADC values（r=-0. 677, P〈0.05）and between NAA and ADC values during the period of 1-7 d after rat cerebralischemia （r=0.909, P（0.05） were also observed. Conclusion： The data suggest that AQP4 is involved in the transport of water when brain edema is formed and cell membrane integrity is lost.

Preliminary study in vitro brain tumor with high resolution magic angle spinning proton magnetic resonance spectroscopy

Objective： To explore water soluble metabolite features of brain tumor specimens with HRMAS-^1HMRS and its potential clinical value. Methods： There were thirty cases of pathologically proven brain tumor, including 6 Ⅰ-Ⅱ grade astrocytomas, 7 Ⅲ grade anaplastic astrocytomas, 10 IV grade glioblastomas and 7 meningiomas. Used Varian Company 600 MHz spectrometer with the Nano-probe for acquisition HRMASJHMRS, which was postprocessed with jMRUI 3.2 version software. These metabolic probability and their ratios to Cr were summed. Results： （1） HRMAS-^1HMRS could resolve NAA, PCr/Cr, GPC ± PCho ± Cho, Glu/GIn, Gly, Tau, Ala, Lac, ml and so on. All samples showed Lac, 6 samples showed unknown single peak at 3.72 ppm or 3.90 ppm. （2） The mean Cho/Cr of 6 Ⅰ-ⅡI grade astrocytomas was 2.42 ± 1.01 （P = 0.003, compared with glioblastoma）. The mean Cho/Cr of 7 anaplastic astrocytomas was 3.48 ± 0.59 （P = 0.01, compared with glioblastoma）. The Cho/Cr of 10 glioblastomas broadly ranged from 0.9 to 11.3 （mean 5.40 ± 1.23）. From Ⅰ-Ⅱ grade astrocytoma to glioblastoma, Ala/Cr, Tau/Cr and Gly/Cr trends were increased; the mean Ala/Cr of glioma was 0.31 ± 0.13. （3） Meningiomas showed higher Ala and Cho. Their Cr was lower than that of gliomas. 4/7 cases had no NAA, 3/7 patients had lower NAA. Mean Cho/Cr was 3.56 ± 1.01, Ala/Cr was 0.53 ±0.28 （P = 0.006, compared with glioma）. Conclusion： HRMAS-^1HMRS can show further details in vivo MRS, resolve in vivo spectroscopic metabolite of Cho compound and differentiate the extent of benign and malignant glioma. With the increase in the malignant degree of gliomas, Cho, ml, Ala, Tau and Gly will increase. HRMAS-^1HMRS is the only method of isotropic spectroscopy for pathological specimens.

Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

Previous studies have found that methylmercury can damage hippocampal neurons and accord- ingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmercury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/ creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride.

Quiet rest ameliorates biochemical metabolism in the brain in a simple concussion rabbit model Evaluation of hydrogen proton magnetic resonance spectroscopy

The present study analyzed changes in the biochemical metabolites N-acetyl aspartate, choline, and creatine in a simple concussion rabbit model following quiet rest, hyperbaric oxygen therapy, or interference stimulation through the use of hydrogen proton magnetic resonance spectroscopy detection. Experimental findings showed that brain N-acetyl aspartate and choline peak values significantly decreased, while creatine peak values significantly increased following simple concussion. Following treatments, N-acetyl aspartate and choline peaks returned to normal levels in the quiet rest and hyperbaric oxygen therapy groups, but no changes were observed in the interference stimulation group. Results demonstrated abnormal changes in the brain biochemical metabolism environment following simple concussion. Quiet rest was shown to play an important role in restoration of biochemical metabolism following simple concussion.

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

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, WI, 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 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 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.

Multimodality imaging using proton magnetic resonance spectroscopic imaging and ^(18)F-fluorodeoxyglucose-positron emission tomography in local prostate cancer

AIM To assess the relationship using multimodality imaging between intermediary citrate/choline metabolism as seen on proton magnetic resonance spectroscopic imaging(1H-MRSI) and glycolysis as observed on ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG-PET/CT) in prostate cancer(PCa) patients. METHODS The study included 22 patients with local PCa who were referred for endorectal magnetic resonance imaging/1HMRSI(April 2002 to July 2007) and ^(18)F-FDG-PET/CT and then underwent prostatectomy as primary or salvage treatment. Whole-mount step-section pathology was used as the standard of reference. We assessed the relationships between PET parameters [standardized uptake value(SUVmax and SUVmean)] and MRSI parameters [choline + creatine/citrate(CC/Cmax and CC/Cmean) and total number of suspicious voxels] using spearman's rank correlation, and the relationships of PET and 1H-MRSI index lesion parameters to surgical Gleason score.RESULTS Abnormal intermediary metabolism on 1H-MRSI was present in 21/22 patients, while abnormal glycolysis on ^(18)F-FDG-PET/CT was detected in only 3/22 patients. Specifically, index tumor localization rates were 0.95(95%CI: 0.77-1.00) for 1H-MRSI and 0.14(95%CI: 0.03-0.35) for ^(18)F-FDG-PET/CT. Spearman rank correlations indicated little relationship(ρ =-0.36-0.28) between 1H-MRSI parameters and ^(18)F-FDG-PET/CT parameters. Both the total number of suspicious voxels(ρ = 0.55, P = 0.0099) and the SUVmax(ρ = 0.46, P = 0.0366) correlated weakly with the Gleason score. No significant relationship was found between the CC/Cmax, CC/Cmean or SUVmean and the Gleason score(P = 0.15-0.79). CONCLUSION The concentration of intermediary metabolites detected by 1H MRSI and glycolytic flux measured ^(18)F-FDG PET show little correlation. Furthermore, only few tumors were FDG avid on PET, possibly because increased glycolysis represents a late and rather ominous event in the progression of PCa.

An Experimental Proton Magnetic Resonance Spectroscopy Analysis on Early Stage of Acute Focal Cerebral Ischemia

U sing different m odels of focal cerebral ischemia,the temporal and spatial rules of m etabolism and energy changes in the post- ischem ia brain tissue were measured by proton m agnet- ic resonance spectroscopy(1 HMRS) to provide valuable inform ation for judging the prognosis of a- cute focal cerebral ischemia and carrying out effective therapy.Nine healthy Sprague- Dawly rats (both sexes) were randomly divided into two groups:The rats in the group A(n=4 ) were occlud- ed with self- thrombus for1h;The rats in the group B(n=5 ) were occluded with thread- em boli for1h.The 1 H MRS at30 ,4 0 ,5 0 ,6 0 min respectively was examined and the m etabolic changes of NAA,Cho and L ac in the regions of interest were sem iquantitatively analyzed. The spectrum intregral calculus area ratio of NAA,Cho,L ac to Pcr+Cr was setas the criterion.The values of NAA· Cho in the regions of interest were declined gradually within 1h after ischem ia, especially,the ratio of Cho/ (Pcr+Cr) ,NAA/ (Pcr+Cr) at6 0 m in had significant difference with that at5 0 min(P<0 .0 5 ) .The ratio of L ac/ (Pcr+Cr) began to decrease at4 0 min from initial in- crease of L ac in both A and B groups.MR proton spectrum analysis was a non- invasive,directand com prehensive tool for the study of cellular metabolism and the status of the biochemical energy in acute ischem ia stroke.

Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery

Background Reliable early prediction response to therapy and time-to-progression （TTP） remain an important goal of high-grade gliomas （HGGs） research. Proton magnetic resonance spectroscopy （1H-MRS） has been applied with variable success in clinical application, and we hypothesize that 1H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy （RT） after surgery. Methods 1H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine （Lip/Cr） and myo-inositol/creatine （ml/Cr） were determined in the solid tumor. RT response was classified as follows： complete resolution （CR）, partial response （PR）, stable disease （SD）, and progressive disease （PD） by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, ml/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. Results Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score （KPS）. The correlation between the ratios of lipid/Cr and TTP was significant （r=0.894, P=0.000）, and between the ratios of ml/Cr and TTP was also significant （r=0.891, P=-0.000）. As predicted, RT response correlated significantly with TTP （r=0.59, P=0.002）： median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR. Conclusion The ratios of Lip/Cr and ml/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

Long-term Brain Tissue Monitoring after Semi-brain Irradiation in Rats Using Proton Magnetic Resonance Spectroscopy： A Preliminary Study In vivo

Background： In head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been tillly understood, while the alternations could be sensitively detected by proton （~H） nuclear magnetic resonance spectroscopy （MRS）. In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term tbllow-up after radiation treatment using MRS m vivo. Methods： A total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain （field size： 1.0 cm x 2.0 cm; anterior limit： binocular posterior inner canthus connection; posterior limit： external acoustic meatus connection; internal limit： sagittal suture）. Conventional magnetic resonance imaging and single-voxel H-MRS were performed at different time points （in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation） to investigate the alternations in irradiation field. N-acetylaspartate/choline （NAA/ChoL NAA/creatinine （Cr）, and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test. Results： Significant changes in the ratios of NAA/Cho （F = 57.37, P 〈 0.001）, NAA/Cr （F = 54.49, P 〈 0.001） and Cho/Cr （F = 9.78, P = 0.005） between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were 〈, significant differences in NAA/Cho （F = 9.17, P 〈 0.001 ） and NAA/Cr （F = 13.04, P 〈 0.001 ） ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides. Conclusions： MRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.

Specific Patterns of Spinal Metabolite Ratio Underlying a-Me-5-HTevoked Pruritus Compared with Compound 48/80 Based on Proton Nuclear Magnetic Resonance Spectroscopy

Summary:Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord.We investigated pruritus behavioral testing in three groups of young adult male C57B1/6 mice,including one group treated with normal saline,while the other groups intradermally injected with a-Me-5-HT(histamine-independent pruritogen),compound 48/80(histaminedependent pruritogen)at the nape skin of the neck,respectively.Proton nuclear magnetic resonance spectroscopy(MRS)was used to compare spinal metabolites from the vertebral cervical among three groups,and to study the association of spinal metabolite ratio and pruritus intensity.The MRS-measured N-acetylaspartate-to-myoinositol ratio(NAA/Ins)was significantly correlated with the number of scratches between normal saline group and 48/80 group or a-Me-5-HT group(both P<0.0001),indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen.There was significant difference in Glu/Ins between normal saline group and 48/80 group(P=0.017),indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen,while GABA/Ins was highly significantly different between normal saline group and a-Me-5-HT group(P=0.008),suggesting that GABA/Ins may be a surrogate marker of histamineindependent pruritogen.MRS may reflect the extent of pruritus intensity elicited by a-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches,and above potential markers need to be further validated in pre-clinical and clinical treatment trials.

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.

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.

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.

A Preliminary Urinary Metabolomics Study of Sprague-Dawley Rats after Short‑term Ketamine Administration by Proton Nuclear Magnetic Resonance Spectroscopy

Drug abuse has become a global problem.The mass spectrometry‑based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied,but to the best of our knowledge,metabolomic studies of ketamine abuse based on nuclear magnetic resonance(NMR)spectroscopy are still lacking.In this study,twenty Sprague–Dawley rats were randomly assigned into two groups:a control group(n=10)and a ketamine group(n=10).The animals in the ketamine group received intraperitoneal injections of ketamine twice daily at 12‑h intervals at progressively increasing doses over a period of 9 days,while the control group received an equal volume of saline.The urine samples were collected for 24 h at days 0,1,3,5,7,and 9 for the metabolomics study.The metabolic changes in urine after short‑term ketamine administration were analyzed by proton NMR coupled with multivariate statistical analysis.The results indicated that short‑term ketamine exposure led to significant alterations of the metabolites in the urine of the rats.Specifically,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,acetoacetic acid,acetylglycine,creatine,sarcosine,dimethylglycine,glycine,and theobromine were significantly increased in the urine.Significant changes were also found in metabolites related to antioxidant and energy metabolism,including acetoacetic acid,succinate,1,3,7‑trimethyluric acid,1,3‑dimethyluric acid,creatine,and taurine.Our findings indicated that short‑term ketamine administration leads to disorder of energy metabolism and oxidative stress.In addition,the modified metabolites identified could serve as the new biological markers and potential biological indices reflecting the underlying mechanism of ketamine abuse.

Hippocampal and thalamic neuronal metabolism in a putative rat model of schizophrenia°

The transcription factor early growth response protein 3 （EGR3） is involved in schizophrenia. We developed a putative rat model of schizophrenia by transfecting lentiviral particles carrying the Egr3 gene into bilateral hippocampal dentate gyrus. We assessed spatial working memory using the Morris water maze test, and neuronal metabolite levels in bilateral hippocampus and thalamus were determined by 3.0 T proton magnetic resonance spectroscopy. Choline content was significantly greater in the hippocampus after transfection, while N-acetylaspartate and the ratio of N-acetylaspartate to creatine/phosphocreatine in the thalamus were lower than in controls. This study is the first to report evaluation of brain metabolites using 3,0 T proton magnetic resonance spectroscopy in rats transfected with Egr3, and reveals metabolic abnormalities in the hippocampus and thalamus in this putative model of schizophrenia.