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.

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.

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.

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.

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.

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.

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.

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.

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.

Neuronal degeneration in the hippocampus and dorsolateral prefrontal cortex in depressive disorder Correlation between ~1H-MRS and Minnesota Multiphasic Personality Inventory

Previous studies using magnetic resonance imaging（MRI）and functional MRI to study depression have primarily focused on proton magnetic resonance spectroscopy（1H-MRS）appearance in various areas of the brain and volume measurements in the limbic system.However,results have not been consistent.To the best of our knowledge,very little is known about the relationship between 1H-MRS appearance and depression inventory.In the present study,the relationship between 1H-MRS appearance in depressive patients and Minnesota Multiphasic Personality Inventory-2 scale was analyzed.MRI and 1H-MRS exhibited widened sulci and cisterns,as well as an absence of abnormal signals in depressive patients.In addition,N-acetyl aspartate/total creatine ratios in bilateral hippocampi and dorsolateral prefrontal cortex were significantly less in depressive patients than in control subjects（P 〈 0.01）.In contrast,choline-containing compounds/total creatine ratios in the dorsolateral prefrontal cortex were significantly greater in depressive patients than in control subjects（P 〈 0.01）.These ratios significantly and positively correlated with patient total depression scores as assessed using the Minnesota Multiphasic Personality Inventory-2 scale（r=0.934 7,0.878 7,P 〈 0.01）.These results suggested that 1H-MRS could be used to reveal a reduced number of neurons in the hippocampus and dorsolateral prefrontal cortex,as well as altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex,in patients with depressive disorder.Abnormal mechanisms partially reflected severity of depressive disorder.

MRI and ~1H-MRS detects volumetric and metabolic abnormalities of hippocampal sclerosis in temporal lobe epilepsy

Objective：To further investigate the ability of MRI and ^1H-MRS techniques for presurgical evaluation of hippocampal sclerosis. Methods：MRI and ^1H-MRS were performed on 30 healthy subjects to determine the confidence levels. Eight patients who were pathologically confirmed hippocampal sclerosis were then studied using the same protocols. The difference of hippocampal formation （DHF） was used to determine atrophy of hippocampus. Areas under the peak of N-acetylaspartate（NAA） ,Creatine（Cr） and Choline （Cho） were measured, and the ratios of NAA/Cr, Cho/Cr, and NAA/Cr＋Cho were calculated. NAA/Cr＋Cho value was applied to localize the seizure focus. Results：Two patients showed hippocampal atrophy according to DHF value. NAA/Cr ratio decreased significantly in ipsilateral hippocampus compared to that in contralateral hippocampus and control subjects（P 〈 0.01）. Cho/Cr value increased in both ipsi- and contralateral hippocampus in comparison with that in control subjects（P〈 0.01）. NAA/Cr＋Cho ratio, however, significantly reduced in both ipsi-and contralateral hippocampus（P〈 0.01） with lowest NAA/Cr＋Cho ratio in seizure foci. Six patients could be lateralized by reduced and/or asymmetric NAA/Cr＋Cho value. Conclusion：^1H-MRS should be a promising diagnostic tool to detect neuron abnormality, ^1H-MRS and MRI complement each other in presurgical lateralization of epileptogenic lesion in epilepsy patients.

Effects of moxibustion and acupuncture at Zusanli(ST 36) and Zhongwan(CV 12) on chronic atrophic gastritis in rats

OBJECTIVE:To evaluate the effects of moxibustion and acupuncture of Zusanli(ST 36)and Zhongwan(CV 12)acupoints on chronic atrophic gastritis(CAG)in rats,and to study the mechanisms behind their actions.METHODS:Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40%ethanol combined with free drinking of N-methyl-N′-nitro-N-nitrosoguanidine and irregular feeding for 12 weeks,followed by daily treatment with moxibustion or acupuncture for 2 weeks.Histopathologic examination,Western blotting of cytokines[epidermal growth factor(EGF),EGF receptor(EGFR),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK)],and1 H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment.RESULTS:Moxibustion and acupuncture at Zusanli(ST 36)and Zhongwan(CV 12)each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK.Only moxibustion treatment regulated the expression of EGF and EGFR.Metabolites that were increased in gastric tissue by CAG induction(alanine,nicotinamide adenine dinucleotide phosphate,uracil DNA glycosylase,lactate,glycerol and adenosine)were restored to normal levels after moxibustion treatment;acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol.CONCLUSION:Our findings suggest that moxibustion or acupuncture at Zusanli(ST 36)and Zhongwan(CV 12)can significantly improve the condition of CAG in rats.These treatments exert their effects on CAG through different mechanisms.

Performance of brain MRI of a two generation father-and-son family with long-term smoking caffeinum natrio benzoicum

Since the 1970s, some people in north, northeast,northwest areas began to smoke caffeinum natrio benzoicum （CNB） and started to abuse CNB. As a common ingredient that can be found in drugs or drinks,many studies on the safety of CNB have been investigated, but no one has shown significant abnormality in the brain of a CNB abuser by using neuroimaging. In our study, three subjects from of a two generation father-and-son family with long-term smoking CNB were enrolled. Combining with the clinical data and taking the cocaine animal trial model and toxicology as the reference, we wanted to observe the performance of brain MRI and MRS of patients with long-term smoking CNB.