1H MR Spectroscopy of the Brain in HIV-1-Seropositive Subjects: Evidence for Diffuse Metabolic Abnormalities

PURPOSE: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process.MATERIALS and METHODS: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T. Nine patients were classified as being neuropsychiatrically unimpaired and six as having HIV-1-associated dementia on the basis of a full neuropsychological examination. Spectra were analysed from multiple voxels located in the fronto-parietal cortex and white matter at the level of centrum semiovale.RESULTS: A significant reduction in mean peak area ratios of NAA/Cr (p<0.005 in the grey matter, p<0.01 in the white matter) and an elevation in mean Cho/Cr (p<0.005 in both grey matter and white matter) were observed in patients with HIV-1-associated dementia when compared to healthy volunteers. No significant metabolite abnormalities were detected in the neuropsychiatrically unimpaired group, although there was a similar trend in the metabolite ratios. The changes in metabolite ratios were of the same order of magnitude in the cortical grey matter and subcortical white matter as in the deeper white matter in all patients. There were also no significant regional variations in mean metabolite ratios between right and left hemispheres or anterior and posterior voxels at the level of the brain studied. There were no abnormalities in Glx/Cr in any spectra analysed from either patient group.CONCLUSION: The absence of significant regional variation in metabolite ratios at the level of the centrum semiovale provides some evidence that abnormalities of cerebral metabolites in HIV-infected patients may be part of a diffuse process.     

In vivo1H magnetic resonance spectroscopy‐derived metabolite variations between acute‐on‐chronic liver failure and acute liver failure

Background and Aims: Acute‐on‐chronic liver failure (ACLF), acute liver failure (ALF) and chronic liver disease (CLD) are common forms of liver failure and present with similar clinical profiles. The aim of this study was to compare brain metabolite alterations in all the three groups of patients with controls, using in vivo proton magnetic resonance spectroscopy (MRS), and to look for any significant differences in metabolites that may help in differentiating between these three conditions. Methods: Nine patients with ACLF, 10 with ALF, 10 patients with CLD and 10 age‐matched controls were studied. The relative concentrations of N‐acetylaspartate (NAA), choline (Cho), glutamine/glutamate (Glx) and myoinositol (mI) with respect to creatine (Cr) were measured. Results: ACLF (3.07±0.72), ALF (4.39±1.25) and CLD (3.15±0.69) patients exhibited significantly increased Glx/Cr ratios compared with controls (2.14±0.42). The NAA/Cr ratio was significantly decreased in both ACLF (mean=0.84±0.28) and CLD (mean=0.97±0.21) patients as compared with that in controls (mean=1.24±0.20). No significant difference among ALF, ACLF and CLD patients was noted in the Cho/Cr ratios. ACLF patients showed significantly lower mI/Cr and Glx/Cr ratios compared with the ALF group. Conclusion: In vivo proton MRS‐derived cerebral metabolite alterations in hepatic encephalopathy owing to ALF are significantly different from the one owing to ACLF and CLD; these may be due to the differences in the pathogenesis of these two overlapping clinical conditions.     

MR化学位移成像脑代谢物改变与肝硬化的临床相关性

目的 利用磁共振波谱分析（MRS）评价肝硬化患者脑代谢物的异常变化及其与Child-Pugh分级和肝功能指标的相关性。方法 应用3．0T磁共振对52例乙型肝炎肝硬化患者（Child A级20例、Child B级14例、Child C级18例）及15例慢性乙型肝炎患者进行磁共振波谱分析,计算脑代谢物Cho（胆碱）、mI（肌醇）、NAA（N-乙酰天门冬氨酸）、Cr（肌酸）和GLX6（谷氨酰胺复合物）峰下面积、脑代谢物峰下面积与Cr比值（NAA／Cr、Cho／Cr、ml／Cr、Glx6／ml）。结果 Child-Pugh A级患者与对照组mI、GLX6比较,差异有统计学意义,Child-Pugh B级与Child-Pugh A级Cho、mI、GLX6比较,差异有统计学意义（P〈0．01）,Child-Pugh C级与Child-Pugh B级Cho、mI比较,差异有统计学意义（P〈0．01或P〈0．05）;Child-Pugh A级与对照组ml／Cr、Glx6/Cr比较,差异有统计学意义（P〈0．01）,Child-Pugh B级与Child-Pugh A级Cho／Cr、ml／Cr、Glx6/Cr比较,差异有统计学意义（P〈0．01或P〈0．05）,Child-Pugh C级与Child-Pugh B级Cho／Cr、ml／Cr比较,差异有统计学意义（P〈0．05）;肝陛脑病与无肝性脑病患者脑代谢物峰下面积比值（Cho／Cr、ml／Cr、G1x6/Cr）比较,差异有统计学意义（P〈0．01）;Child-Pugh分级与Glx6/Cr呈正相关,与Cho／Cr、ml／Cr呈负相关;肝硬化患者TBIL、PT与Cho／Cr、ml／Cr呈负相关,与Glx6/Cr呈正相关。ALB与Cho／Cr、ml／Cr呈正相关,与Glx6/Cr呈负相关。AIJT与NAMCr、Cho／Cr、ml／Cr、Glx6/Cr无明显相关性。结论 肝硬化及肝性脑病患者存在脑代谢物浓度异常改变,它可作为肝硬化和肝性脑病早期诊断及程度评价的一项指标。     

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure

Background and Aim:  Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors.
Methods:  Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions.
Results:  Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study.
Conclusions:  We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.     

Brain proton magnetic spectroscopy in long-term treatment of Wilson’s disease patients

We reported the brain proton magnetic resonance spectroscopy (MRS) findings in 27 Wilson’s disease (WD) patients treated more than 6 years in neurological (nWD) and hepatic (hWD) subgroups. We investigated four hWD patients, with no improvement and eight with marked improvement; and eight nWD patients with marked improvement and seven with no improvement of clinical status. In nWD patients with improvement the MRS showed significantly higher Cho/Cr, Glx/Cr ratios levels. In hWD patients with no improvement the lower Cho/Cr and in nWD significantly lower NAA/Cr and higher Cho/Cr and Lip/Cr ratios were detected. In nWD patients with improvement the spectroscopic pattern, can be related to gliosis. In patients with no neurological improvement a persistent neuronal dysfunction can occur, perhaps as a result of copper or iron deposition.     

Brain proton magnetic spectroscopy in long-term treatment of Wilson’s disease patients

We reported the brain proton magnetic resonance spectroscopy (MRS) findings in 27 Wilson’s disease (WD) patients treated more than 6 years in neurological (nWD) and hepatic (hWD) subgroups. We investigated 4 hWD patients, with no improvement and 8 with marked improvement; and 8 nWD patients with marked improvement and 7 with no improvement of clinical status. In nWD patients with improvement the MRS showed significantly higher Cho/Cr, Glx/Cr ratios levels. In hWD patients with no improvement the lower Cho/Cr and in nWD significantly lower NAA/Cr and higher Cho/Cr and Lip/Cr ratios were detected. In nWD patients with improvement the spectroscopic pattern, can be related to gliosis. In patients with no neurological improvement a persistent neuronal dysfunction can occur, perhaps as a result of copper or iron deposition.     

Localized proton magnetic resonance spectroscopy of the cerebellum in detoxifying alcoholics

An increased daily alcohol consumption results in neurological symptoms and morphological central nervous system changes, e.g. shrinkage of the frontal lobes and the cerebellar vermis. Brain shrinkage can be due to neuronal loss, gliosis, or alterations of (cell) membrane constitutes/myelin. Neuronal, glial, and metabolic changes can be measured in vivo with proton magnetic resonance spectroscopy. A total of 11 alcoholics and 10 age-matched volunteers were examined by magnetic resonance imaging and localized magnetic resonance spectroscopy at an echo time of 135 and 5 msec. Peak integral values were calculated for N-acetylaspartate (NAA), choline (Cho), myo-inositol (ml), glutamate/glutamine (Glx), and normalized to phosphocreatine/creatine (Cr). Patients had a significant shrinkage of the cerebellar vermis. NAA/Cr and Cho/Cr ratios were reduced in both sequences, but the NAA/Cr reduction was only significant in long echo time, although the Cho/Cr reduction was significant in short echo time. The ml/Cr and Glx/Cr ratios did not show any significant difference between volunteers and patients. The decrease of NAA/Cr in alcohol dependent patients is consistent with neuronal loss. The Cho/Cr decrease and an unchanged ml/Cr may reflect cell membrane modification or myelin alterations in alcohol-dependent patients. These changes lead to brain shrinkage, although hydration effects and gliosis are less likely.     

Evaluation of metabolite changes in visual cortex in diabetic retinopathy by MR-spectroscopy

PurposeTo evaluate metabolite changes in the visual cortex of diabetic patients with nonproliferative or proliferative diabetic retinopathy by Magnetic Resonance Spectroscopy (MRS).Materials and Methods15 normal subjects (group 1), 15 patients with diabetes who did not have diabetic retinopathy (group 2), 15 patients with nonproliferative diabetic retinopathy (NPDR) (group 3), and 15 patients with proliferative diabetic retinopathy (PDR) (group 4) were included in the study. Furthermore, diabetic patients were divided into two groups according to HbA1c levels (Group A: 20 patients, HbA1c < 8%; Group B: 20 patients, HbA1c > 8%). In all cases' left visual cortex, amounts of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) were measured by MRS. NAA/Cr, Cho/Cr, and NAA/Cho ratios were calculated. Furthermore, all cases' complete blood count (CBC) and biochemical parameters were evaluated.ResultsThere was no statistically significant difference for NAA/Cr, Cho/Cr, and NAA/Cho ratios between groups 1, 2, 3, and 4 (P > 0.05). However there was a statistically significant difference for NAA/Cr and NAA/Cho ratios between groups A and B (P < 0.05). There was no statistically significant difference for Cho/Cr ratio between groups A and B (P > 0.05).ConclusionAlthough NAA/Cr and NAA/Cho ratios decrease in the visual cortex while diabetic retinopathy progresses, these decreases are not statistically significant. While HbA1c levels increase, the NAA concentration decreases in the visual cortex which indicates neuronal loss. The metabolite changes in the visual cortex are associated with acute events rather than chronic.     

正常人颞叶质子磁共振波谱研究

目的 运用质子磁共振波谱（^1H—MRS）研究年龄对正常人颞叶脑组织代谢物浓度的影响。方法 将80例健康人分为4个不同年龄组并对双侧颞叶进行^1H—MRS检测，对比分析不同年龄组的颞叶N-乙酰基天门冬氨酸（NAA）／肌酸复合物（Cr）和含胆碱化合物（Cho）／Cr比值的变化。结果 随着年龄的增长，在≤50岁年龄段颞叶的NAA／Cr和Cho／Cr比值无明显改变（P〉0．05），但在〉50岁年龄段颞叶的NAA／Cr比值逐渐降低（P〈0．05）、Cho／Cr比值逐渐增高（P〈0．05）。结论 ^1H-MRS是一种可以为正常人颞叶与年龄相关的代谢物浓度改变提供有价值信息的无创技术。     

Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus

The aim of this study was to investigate possible metabolic alterations in cerebral tissues on magnetic resonance spectroscopy (MRS) in patients with impaired glucose tolerance (IGT) and with type 2 diabetes mellitus (T2-DM). Twenty-five patients with T2-DM, 13 patients with IGT, and 14 healthy volunteers were included. Single-voxel spectroscopy (TR: 2000 ms, TE: 31 ms) was performed in all subjects. Voxels were placed in the frontal cortex, thalamus, and parietal white matter. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and myo-inositol (MI)/Cr ratios were calculated. Frontal cortical Cho/Cr ratios were increased in patients with IGT compared to control subjects. Parietal white matter Cho/Cr ratios were significantly higher in patients with IGT when compared to patients with T2-DM. In the diabetic group, frontal cortical MI/Cr ratios were increased, and parietal white matter Cho/Cr ratios were decreased when compared to the control group. Frontal cortical NAA/Cr and Cho/Cr ratios and parietal white matter Cho/Cr ratios were decreased in diabetic patients with poor glycemic control (A1C>10%). A1C levels were inversely correlated with frontal cortical NAA/Cr and Cho/Cr ratios and with parietal white matter Cho/Cr ratios. T2-DM and IGT may cause subtle cerebral metabolic changes, and these changes may be shown with MRS. Increased Cho/Cr ratios may suggest dynamic change in membrane turnover in patients with IGT. Diabetic patients with poor glycemic control may be associated with neuronal dysfunction/damage in brain in accordance with A1C levels and, in some, extend with insulin resistance.     

盐酸多奈哌齐干预血管性痴呆患者后的磁共振波谱分析

目的 利用氢质子磁共振波谱分析(1 H-magnetic resonance spectroscopy,1 H-MRS)技术研究脑卒中后血管性痴呆(vascular dementia,VD)患者颞叶海马区细胞代谢水平及给予盐酸多奈哌齐后,细胞代谢水平的改变及其与临床症状的关系.方法 脑卒中VD组18例,男性16例,女性2例,平均年龄(76.9±2.7)岁,符合痴呆的《神经病诊断和统计手册》第4版(DSM-Ⅳ)诊断标准;脑卒中非VD组13例,男性11例,女性2例,平均年龄(76.2±3.6)岁;正常对照组来源于门诊就诊者,共14例,男性12例,女性2例,平均年龄(75.1±2.4)岁.所有入组者均行简易精神状态量表(MMSE)、日常生活活动能力量表(ADL)、汉密尔顿抑郁量表(HAMD)评分以及1H-MRS检测患者双侧颞叶海马区细胞代谢水平.脑卒中VD组在盐酸多奈哌齐治疗6个月后复查MMSE评分及1H-MRS检查.结果 脑卒中VD组患者双侧颞叶海马区N-乙酰天门冬氨酸盐(NAA)/肌酸(Cr)比值较正常对照组及脑卒中非VD组均有显著下降(F=4.23、4.98,均P＜0.05);而双侧胆碱复合物(Cho)/Cr比值较正常对照组显著升高(P=0.005、0.010),较脑卒中非VD组左侧有显著升高(P=0.038),但右侧差异无统计学意义(P=0.066).脑卒中非VD组NAA/Cr比值及Cho/Cr比值较正常对照组虽有变化,但差异无统计学意义.脑卒中VD组MMSE评分与双侧颞叶海马区NAA/Cr及Cho/Cr比值有相关性,且MMSE分数越低,NAA/Cr比值越低,而Cho/Cr比值则越高.应用盐酸多奈哌齐干预治疗脑卒中VD组患者6个月后,患者MMSE及ADL评分均有显著提高(均P＜0.05);双侧颞叶海马区NAA/Cr比值无明显改善(t=-2.02、-2.04,均P＞0.05),而双侧颞叶海马区Cho/Cr比值有显著下降(t=2.86、2.23,均P＜0.05).结论 1 H-MRS技术可能有助于早发现脑卒中后血管性痴呆;盐酸多奈哌齐可通过调整脑内胆碱能系统,改善血管性痴呆患者的认知功能.     

卒中后抑郁患者海马磁共振氢质子波谱分析

目的 探讨卒中后抑郁患者海马氢质子磁共振波谱（1H-MRS）的特点.方法 以32例卒中后抑郁患者为研究组,30例脑卒中患者为病例对照组,30名正常人为正常对照组.三组在入组24 h内采用多体素1 H-MRS检测双侧海马N-乙酰基天门冬氨酸（NAA）、胆碱复合物（Cho）与肌酸复合物（Cr）,完成NAA/Cr值和Cho/Cr值的计算.结果 研究组左右侧海马NAA/Cr值均低于病例对照组和正常对照组,P均＜0.05;研究组左侧海马Cho/Cr值均高于病例对照组和正常对照组,P均＜0.05;右侧海马Cho/Cr值高于正常对照组（P＜0.05）,但与病例对照组比较,P＞0.05.重度抑郁组左右侧海马NAA/Cr值均低于轻度抑郁组,P均＜0.05;不同抑郁程度的双侧海马Cho/Cr值比较,P均＞0.05;研究组双侧海马NAA/Cr值与HAMD评分呈负相关（P均＜0.05）,而双侧海马Cho/Cr值与HAMD评分不存在相关关系（P＞0.05）.三组左右两侧海马各研究指标比较,P均＞0.05.结论 海马神经元代谢的异常可能是卒中后抑郁的神经生物学基础;卒中后抑郁患者、脑卒中患者和正常人脑部NAA、Cho可能并不存在侧化现象.     

MR imaging and spectroscopy of the basal ganglia in chronic liver disease: Correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra

The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T₁-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T₁-weighted spin echo (T₁ WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pugh's score (p<0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to BATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T₁WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T₁WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the brain observed in hepatic encephalopathy.     

The metabolic alterations within the normal appearing brain in patients with Hashimoto’s thyroiditis are correlated with hormonal changes

Hashimoto’s thyroiditis (HT) is the most common autoimmune disease in humans usually associated with subsequent hypothyroidism. The purpose of the study was to assess metabolic alterations within the normal appearing brain in subjects with HT using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations. Fifty-five HT patients (mean age 43.5 yrs) and 30 healthy controls (mean age 42.5 yrs) were examined with the use of a 1.5 T MR scanner. There were no signs of central nervous system involvement in the studied group. The MRS examinations were performed using the single voxel method. The voxels were placed in the left parietal white matter (PWM) and the posterior cingulate gyrus (PCG). The NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. The correlations between metabolite ratios and hormonal concentrations (TSH, fT3, fT4) as well as anti-TG and anti-TPO levels were also assessed. We found significantly (p?<?0.05) decreased NAA/Cr ratios in PCG and PWM in HT subjects compared to the control group. There were no other significant differences in metabolite ratios. We observed significant positive correlations between the NAA/Cr ratio in PCG as well as the PWM and fT3 level. There was also a significant negative correlation between the Cho/Cr ratio in the PCG and fT4 level. MRS could be a sensitive biomarker capable of depicting early cerebral metabolic disturbances associated with HT. Our findings may indicate the reduction of neuronal activity within the normal appearing brain in patients with HT as well as suggesting that there is a possible biological association between thyroid dysfunction and cerebral metabolic changes.

     

质子磁共振波谱评价颈内和大脑中动脉狭窄与闭塞的脑代谢研究

目的探讨质子磁共振波谱(1H-MRS)在单侧颈内动脉(ICA)和大脑中动脉(MCA)重度狭窄与闭塞中的应用价值。方法32例单侧ICA或MCA重度狭窄或闭塞患者(ICA18例,MCA14例)行1H-MRS检查,测量患侧和对侧大脑半球半卵圆中心N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)的波峰下面积,比较患侧和对侧各代谢物峰下面积比值NAA/Cho、NAA/Cr和Cho/Cr的差异,并观察有无乳酸(Lac)峰出现。结果1H-MRS显示患侧半卵圆中心的NAA/Cho、NAA/Cr低于对侧,差异有显著性意义(P<0.01),Cho/Cr高于对侧,差异有显著性意义(P<0.01),5例患者于患侧检测到Lac峰。结论1H-MRS能够早期发现ICA或MCA重度狭窄或闭塞患者缺血脑组织的代谢异常,从代谢产物角度评价脑缺血程度,对于早期治疗和判断预后具有重要价值。     

A Proton Magnetic Resonance Spectroscopy Study of the Striatum and Cerebral Cortex in Parkinson's Disease

Animal studies have suggested an increased striatal glutamate activity in Parkinson's disease models, although this has not been substantiated in magnetic resonance spectroscopy studies in patients. Our initial aim was to assess glutamate and glutamine levels in the striatum of patients with idiopathic Parkinson's disease, using multivoxel proton magnetic resonance spectroscopy techniques. Since data were collected from other areas of the brain without a priori selection, information on the cortex was also obtained. Twelve healthy volunteers, seven dyskinetic and five non-dyskinetic patients were studied. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx) and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr) were calculated. Spectra were analysed from the corpus striatum, the occipital cortex and the temporo-parietal cortex. The median Glx/Cr ratio was unaltered in the striatal spectra of Parkinson's disease patients compared to healthy controls. However, the more severely affected patients had significantly reduced NAx/Cr ratios in spectra localised to the temporo-parietal cortex, compared to healthy controls. Furthermore, the entire patient population had significantly reduced Cho/Cr ratios in spectra from the temporo-parietal cortex, compared to the reference population. We found no evidence of increased striatal glutamate in either dyskinetic or non-dyskinetic Parkinson's disease. However, the low NAx/Cr and Cho/Cr ratios in the temporo-parietal cortex may indicate the presence of subclinical cortical dysfunction.     

Detection of subclinical and overt hepatic encephalopathy and treatment control after L-ornithine-L-aspartate medication by magnetic resonance spectroscopy ((1)H-MRS)

Hepatic encephalopathy (HE) is a common problem in liver cirrhosis and is associated with typical changes of cerebral metabolite pattern observed by proton magnetic resonance spectroscopy (MRS). In HE, a reduction of the cerebral myo-inositol (mI) and choline (Cho) and an increase of glutamine/glutamate (Glx) can typically be detected with this method. In the present study MRS was used to assess prospectively specific parameters of cerebral metabolism before and after 6 days of treatment with a low-protein diet and with L-ornithine-L-aspartate (LOLA). 6 patients with liver cirrhosis were included in this pilot study. According to standardized neuropsychological tests overt HE or subclinical HE was detected in all patients. All patients received a low-protein diet (< 60 g/d) and were treated additionally with LOLA (20 g QD i. v.). MRS examinations were done before and after 6 days of treatment and the results were compared with those of healthy volunteers. Before treatment mI/Cr ratios in the grey matter were reduced significantly in cirrhotic patients as compared to healthy volunteers (0.30 +/- 0.22 vs. 0.68 +/- 0.11; P = 0.028). In addition, patients showed a (non-significant) reduction of the Cho/Cr-ratio (0.19 +/- 0.03 vs. 0.25 +/- 0.02; P = 0.17) and an elevated Glx/Cr-ratio (1.84 +/- 0.63 vs. 1.29 +/- 0.31; P = 0.05). After 6 days of treatment a significant increase of the Cho/Cr ratio (0.23 +/- 0.03 vs. 0.19 +/- 0.03; P = 0.028) was detectable and 5 of the 6 patients showed a (not significant) decrease of the elevated Glx/Cr ratios. After cessation of treatment an improvement in neuropsychological tests as shown by number-connection testing (P = 0.046) as well as a decrease of elevated pre-treatment ammonia blood levels were noted. These findings, however, did not correlate with the Child-Pugh classification or evidence of clinical/subclinical HE. Using (1)H-MRS it is possible to observe a specific pattern of cerebral metabolites in patients with overt and subclinical HE. In this pilot study a fast change of cerebral metabolite pattern after specific therapy of HE with LOLA was detected. Therefore, future studies with larger patient groups are needed to establish (1)H-MRS as an objective method for detection and treatment control in overt and subclinical HE, especially when compared to commonly used parameters such as ammonia levels or standardized neuropsychological tests.     

Brain metabolic alterations in adolescents and young adults with fetal alcohol spectrum disorders

BACKGROUND: Prenatal alcohol exposure affects brain structure and function. This study examined brain metabolism using magnetic resonance spectroscopy (MRS) and searched for regions of specific vulnerability in adolescents and young adults prenatally exposed to alcohol. METHODS: Ten adolescents and young adults with confirmed heavy prenatal alcohol exposure and a diagnosis within the fetal alcohol spectrum disorders (FASD) were included. Three of them had fetal alcohol syndrome (FAS), 3 had partial FAS (PFAS), and 4 had alcohol-related neurobehavioral disorder (ARND). The control group consisted of 10 adolescents matched for age, sex, head circumference, handedness, and body mass. Exclusionary criteria were learning disorders and prenatal alcohol exposure. Three-dimensional (1)H magnetic resonance spectroscopic imaging ((1)H MRSI) was performed in the cerebrum and cerebellum. Metabolite ratios N-acetylaspartate/choline (NAA/Cho), NAA/creatine (Cr) and Cho/Cr, and absolute metabolite intensities were calculated for several anatomic regions. RESULTS: In patients with FASD, lower NAA/Cho and/or NAA/Cr compared with controls were found in parietal and frontal cortices, frontal white matter, corpus callosum, thalamus, and cerebellar dentate nucleus. There was an increase in the absolute intensity of the glial markers Cho and Cr but no change in the neuronal marker NAA. CONCLUSIONS: Our results suggest that prenatal alcohol exposure alters brain metabolism in a long-standing or permanent manner in multiple brain areas. These changes are in accordance with previous findings from structural and functional studies. Metabolic alterations represent changes in the glial cell pool rather than in the neurons.     

抑郁大鼠海马区代谢指标的动态变化及意义

目的探讨大鼠抑郁模型海马区各项代谢指标的变化特征及动态变化规律。方法将40只SD大鼠随机分成对照组及抑郁组各20只,抑郁组利用孤养及慢性轻度不可预见性应激(CUMS)相结合的方法建立抑郁模型,共应激8周。实验前及每周末对各组海马进行3.0T超高场MRI扫描及磁共振质子波谱检测,指标包括N-乙酰天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)、谷氨酰胺和谷氨酸(Glx)、肌醇(MI)。结果与对照组相比,抑郁组左侧海马Glx/Cr值第3周开始下降、第4～8周基本维持恒定,右侧海马Glx/Cr值于第4周开始下降、第4～8周基本维持恒定(P<0.05);左侧海马Cho/Cr值于第4周升高、第5～8周升高更加明显,右侧海马Cho/Cr值于第6周升高、第7～8周升高更加明显(P<0.05);左侧海马MI/Cr值于第4周升高、第5～8周升高更加明显,右侧海马MI/Cr值于第6周升高、第7～8周升高更加明显(P<0.05);双侧海马NAA/Cr值未见明显差别。结论抑郁大鼠海马的代谢指标出现异常并呈一定规律性动态变化,此可能为构成抑郁症发病机制的神经生物学基础。     

基底神经节代谢物的质子磁共振波谱增龄变化

目的 探讨基底神经节代谢物N-乙酰天门冬氨酸/胆碱复合物(NAA/Cho)、N-乙酰天门冬氨酸/肌酸(NAA/Cr)和Cho/Cr浓度比值的增龄变化规律. 方法 选择20～87岁健康志愿者70例,男36例,女34例,分为20～40岁、41～59岁和60～87岁者三组,采用磁共振波谱的二维化学位移成像(2D chemical shift imaging,2D CSI)技术检测其大脑双侧豆状核,丘脑及尾状核的代谢物浓度,分析比较不同年龄组的基底神经节代谢物NAA/Cho、NAA/Cr、Cho/Cr浓度比值的变化.结果 双侧豆状核、尾状核、丘脑的NAA/Cho比值及双侧丘脑、右豆状核的NAA/Cr比值与年龄呈负相关(P<0.05),双豆状核的Cho/Cr比值与年龄呈正相关(P<0.05).不同年龄组的NAA/Cho、NAA/Cr、Cho/Cr比值之间差异亦有统计学意义(P<0.05). 结论 健康人的基底神经节代谢物浓度,随其年龄增长而发牛规律性变化,二维化学位移成像是一种检测基底神经节代谢物浓度的无创伤性的方法,是检测正常脑的生理性和病变脑的病理性代谢物浓度变化的重要手段之一.