首发抑郁症患者海马质子磁共振波谱成像研究

目的:探讨首发抑郁症患者海马的磁共振质子波谱(1HMRS)特点.方法:应用1HMRS成像技术检测21例未用药首发抑郁症患者和14例健康志愿者海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,计算NAA/Cr和Cho/Cr比值.结果:首发抑郁症患者组双侧海马NAA/Cr比值低于对照组,差异有统计学意义(右侧:0.88±0.29/1.37±0.51,P=0.004;左侧:0.76±0.33/1.40±0.99,P=0.034);Cho/Cr比值两组间无统计学差异(P＞0.05);双侧海马NAA/Cr和Cho/Cr与抑郁严重度无相关性(P＞0.05).结论:首发抑郁症患者可能存在双侧海马神经元活力和功能下降.     

皮质下缺血性脑血管病的磁共振波谱研究

目的:检测皮质下缺血性脑血管病(SIVD)患者和正常对照组不同脑区脑组织的代谢水平,探讨其与认知功能损害的关系。方法:采用多体素磁共振波谱(1 H-MRS)技术评测SIVD患者(SIVD组,n=32例)和体检健康人(对照组,n=21)额叶及顶叶皮质、白质的代谢物N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr);计算有关比值NAA/Cr、Cho/Cr,分析有无认知功能损害SIVD患者上述比值的变化。结果:(1)SIVD组额叶皮质、白质及顶叶皮质、白质各体素NAA/Cr比值明显低于对照组(P0.01);(2)SIVD组顶叶皮质及白质的Cho/Cr比值明显高于对照组(P0.01);(3)SIVD组有认知功能损害患者的额叶皮质和顶叶皮质、白质NAA/Cr比值显著低于无认知功能损害者(P值分别0.01、0.01、0.05),Cho/Cr比值的两者间差异无统计学意义(P0.05)。结论:SIVD患者脑组织存在NAA/Cr、Cho/Cr比值改变,且额叶皮质和顶叶皮质、白质NAA/Cr的下降与认知损害有关。     

阴性和阳性症状为主型精神分裂症患者脑部质子波谱与症状相关性

目的探讨阴性和阳性症状为主型的精神分裂症患者脑部磁共振质子波谱(1H-MRS)与临床症状之间的相关性。方法对住院诊治的89例精神分裂症患者采用阳性与阴性症状量表(PANSS)评定症状,用1H-MRS测定患者前额叶及丘脑生化代谢物N-乙酰基天门冬氨酸(NAA)、肌酸复合物(Cr),计算NAA/Cr值。结果阴性组阴性症状(29.03±7.13)分、阳性症状(20.43±4.46)分、一般病理(40.21±5.43)分、总分(90.24±8.87)分;阳性组阴性症状(20.12±3.64)分、阳性症状(30.31±3.55)分、一般病理(40.76±5.54)分、总分(89.98±9.23)分,两组患者阴性症状及阳性症状分值之间比较存在显著性差异(P0.05);NAA/Cr值阴性组前额叶左侧(1.34±0.35)、右侧(1.38±0.37),丘脑左侧(1.45±0.36)、右侧(1.46±0.37);阳性组前额叶左侧(1.37±0.36)、右侧(1.40±0.37),丘脑左侧(1.49±0.36)、右侧(1.64±0.39),丘脑右侧NAA/Cr值在两组间比较存在显著性差异(P0.05);阴性组患者左侧前额叶NAA/Cr值与PANSS总分、阴性症状总分之间均具有负相关(r=-0.34,-0.36;P0.05),阳性组患者左侧前额叶NAA/Cr值与PANSS总分之间具有负相关(r=-0.35,P0.05)。结论精神分裂症阳性与阴性为主型的患者前额叶及丘脑均存在NAA/Cr值变化,前额叶NAA/Cr值与阴性症状的严重程度密切相关。     

创伤后应激障碍患者海马容积与磁共振波谱的研究

目的探讨创伤后应激障碍患者海马容积与氢质子波谱(1H-MRS)的相关性。方法对50例急性型创伤后应激障碍患者和50例健康志愿者行磁共振海马容积测量和磁共振波谱检查,采用相除法标准化海马容积与N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)的比值对照分析。结果急性型创伤后应激障碍患者海马容积不同程度缩小,其中31例急性型创伤后应激障碍者海马容积明显缩小,与对照组比较差异有统计学意义(P<0.05)。创伤后应激障碍患者NAA峰高度降低、Cho峰增高,NAA/Cr比值不同程度减小、Cho/Cr值增高,31例重度患者NAA/Cr值明显减小,与对照组比较具有显著性差异(P<0.01);Cho/Cr值增高差异无统计学意义(P>0.05)。急性型创伤后应激障碍患者海马容积缩小程度与NAA/Cr降低幅度呈正相关。结论急性型创伤后应激障碍患者海马容积缩小、NAA丢失严重,提示神经递质N-乙酰天冬氨酸-谷氨酸在创伤后应激障碍发展中起重要作用。     

首发抑郁症患者海马容积与磁共振波谱的研究

目的:探讨抑郁症患者海马容积与氢质子波谱(1H-MRS)的相关性。方法:对50例首发抑郁症患者和50例健康志愿者行磁共振海马容积测量和磁共振波谱检查,将采用相除法标准化海马容积与N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)的比值对照分析。结果:抑郁症患者海马容积不同程度缩小,其中31例重度抑郁症者海马容积明显缩小。抑郁症患者NAA峰高度降低、Cho峰增高,NAA/Cr比值不同程度减小、Cho/Cr值增高,31例重度患者NAA/Cr值明显减小;重度抑郁症患者海马容积缩小与NAA/Cr降低幅度呈正相关。结论:重度抑郁症患者海马容积缩小、NAA丢失严重,提示神经递质N-乙酰天门冬氨酸-谷氨酸在抑郁症发展中起重要作用。     

磁共振波谱评价大脑半球代谢物的偏侧优势

为了利用无创性的磁共振波谱成像技术研究大脑半球代谢物的非对称性,本研究对56例正常成年人行磁共振波谱成像,主要对双侧大脑半球的4个解剖区域:额叶、颞叶、枕叶及顶叶的代谢物天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)进行测量,并以Cr为内参照物比较NAA和Cho相对含量(NAA/Cr、Cho/Cr)的侧别差异。结果表明:双侧额叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异;在双侧颞叶之间,这2种比值均存在显著性差异;双侧枕叶之间Cho/Cr存在显著性差异,而NAA/Cr无显著性差异;双侧顶叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异。本研究结果提示双侧大脑半球的代谢物存在偏侧优势。     

视觉诱发电位和1H磁共振波谱在枕叶癫的应用价值

目的：通过对枕叶癫痫患者进行视觉诱发电位（PVEP）和氢质子波谱分析（1HMRS）检查，分析二者在枕叶癫痫的应用价值。方法：19例患者进行PVEP、1HMRS和MRI检查。VEP检查分析其P100潜伏期和波幅；1HMRs测量双侧枕叶N-乙酰天门冬氨酸（NAA）、肌酸（Cr）和胆碱（Cho），得出NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）的比值。选取年龄相应的健康人15例作为对照组，同样进行PVEP和1HMRS检查。分析患者组与对照组的P100潜伏期和波幅、NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）比值的差异；分析P100潜伏期与NAA／（Cr＋Cho）比值的相关关系。结果：患者组NAA／Cr、NAA／Cho和NAA／（cr＋Cho）的比值与对照组比较有显著差异；P100潜伏期和波幅与对照组比较有显著差异；P100潜伏期延长与NAA／（Cr＋Cho）比值降低呈负相关。结论：PVEP和1HMRS检查联合应用可以提高枕叶癫痫诊断的可靠性，还可帮助定位，为MRI无可见病灶者行外科治疗提供依据；1HMRS在枕叶癫痫定位诊断方面较MRI更敏感；PVEP和1HMRS检查有较高的一致性。     

视觉诱发电位和1H磁共振波谱在枕叶癫痫的应用价值

目的：通过对枕叶癫痫患者进行视觉诱发电位（PVEP）和氢质子波谱分析（1HMRS）检查，分析二者在枕叶癫痫的应用价值。方法：19例患者进行PVEP、1HMRS和MRI检查。VEP检查分析其P100潜伏期和波幅；1HMRs测量双侧枕叶N-乙酰天门冬氨酸（NAA）、肌酸（Cr）和胆碱（Cho），得出NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）的比值。选取年龄相应的健康人15例作为对照组，同样进行PVEP和1HMRS检查。分析患者组与对照组的P100潜伏期和波幅、NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）比值的差异；分析P100潜伏期与NAA／（Cr＋Cho）比值的相关关系。结果：患者组NAA／Cr、NAA／Cho和NAA／（cr＋Cho）的比值与对照组比较有显著差异；P100潜伏期和波幅与对照组比较有显著差异；P100潜伏期延长与NAA／（Cr＋Cho）比值降低呈负相关。结论：PVEP和1HMRS检查联合应用可以提高枕叶癫痫诊断的可靠性，还可帮助定位，为MRI无可见病灶者行外科治疗提供依据；1HMRS在枕叶癫痫定位诊断方面较MRI更敏感；PVEP和1HMRS检查有较高的一致性。     

磁共振波谱分析在颅脑胶质瘤分级中的应用研究

目的分析脑胶质瘤的氢质子磁共振波谱(proton magnetic resonance spectroscopy,~1H-MRS)表现及其临床意义;探讨脑胶质瘤的1H-MRS特点与其病理级别相关性。方法搜集经临床手术、病理证实的脑胶质瘤病例49例,按照WHO诊断标准分成两组:低级别脑胶质瘤组、高级别脑胶质瘤组。所有患者在术前行~1H-MRS检查,均在MR非增强成像的基础上获得。使用Philips Achieva 1.5T超导磁共振扫描仪,单体素或多体素扫描,点分辨法,检测不同区域代谢物变化。结果脑胶质瘤的~1H-MRS表现:肌酸(Cr)轻度下降,N-乙酰天门冬氨酸(NAA)显著下降,胆碱(Cho)显著增高。低、高级别脑胶质瘤的肿瘤组织与对侧正常脑组织的NAA、Cho、NAA/Cr、NAA/Cho值存在显著性差异(P0.05);低级别和高级别脑胶质瘤的肿瘤组织的NAA/Cr、NAA/Cho值存在显著性差异(P0.05)。脑胶质瘤的NAA/Cho、Cho/Cr、NAA/Cr值与病理级别相关,其中NAA/Cho和NAA/Cr值反映肿瘤级别较稳定;NAA/Cr、NAA/Cho值呈负相关关系,Cho/Cr值呈正相关关系。结论 :~1H-MRS结合MRI能提高脑胶质瘤术前诊断的准确性。~1H-MRS能对胶质瘤进行分级,反映胶质瘤代谢特性以及肿瘤生长潜能。     

原发性失眠患者大脑背外侧前额叶的异常静息态功能连接

目的:利用功能连接方法观察原发性失眠患者静息态下的背外侧前额叶的异常功能连接。方法:采集33 例原 发性失眠患者以及33 例年龄、性别和受教育程度相匹配的健康对照的功能磁共振图像,以背外侧前额叶为感兴趣区 域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常功能连接脑区与临床的量表分 数做相关分析。结果:与对照组相比,发现失眠患者左侧背外侧前额叶与左侧枕下回、右侧枕下回、右侧枕中回、右侧 颞叶、左侧额中回,左侧额下回以及右侧梭状回之间的功能连接增强（P<0.05,体素簇个数≥100,FDR校正）,与左侧前 扣带皮层、右侧海马旁回、右侧脑岛、右侧背外侧额上回、右侧顶上回、右侧中央后回以及右侧中央前回之间的功能连 接减弱（P<0.05,体素簇个数≥100,FDR校正）。并且左侧背外侧前额叶与左侧枕叶下回的功能连接值与睡眠状况自评 量表分数成正相关（P=0.035）。结论:原发性失眠患者背外侧前额叶与大脑多个脑区出现异常的功能连接,可能为理 解原发性失眠患者的神经机制提供一些新的影像学依据。     

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.     

1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients

BACKGROUND: Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo (1)H MRS NAA levels in the DLPFC of adult bipolar patients. METHODS: Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time 1H MRS session, which localized an 8 cm3 single-voxel in the left DLPFC using a STEAM sequence. RESULTS: No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p > 0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann-Whitney U-test, p < 0.05). LIMITATIONS: Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas. CONCLUSIONS: This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal 1H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.     

Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

BACKGROUND: Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation. METHOD: Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent. CONCLUSIONS: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.     

Dopaminergic control of working memory and its relevance to schizophrenia: a circuit dynamics perspective

This article argues how dopamine controls working memory and how the dysregulation of the dopaminergic system is related to schizophrenia. In the dorsolateral prefrontal cortex, which is the principal part of the working memory system, recurrent excitation is subtly balanced with intracortical inhibition. A potent controller of the dorsolateral prefrontal cortical circuit is the mesocortical dopaminergic system. To understand the characteristics of the dopaminergic control of working memory, the stability of the circuit dynamics under the influence of dopamine has been studied. Recent computational studies suggest that the hyperdopaminergic state is usually stable but the hypodopaminergic state tends to be unstable. The stability also depends on the efficacy of the glutamatergic transmission in the corticomesencephalic projections to dopamine neurons. When this cortical feedback is hypoglutamatergic, the circuit of the dorsolateral prefrontal cortex tends to be unstable, such that a slight increase in dopamine releasability causes a catastrophic jump of the dorsolateral prefrontal cortex activity from a low to a high level. This may account for the seemingly paradoxical overactivation of the dorsolateral prefrontal cortex observed in schizophrenic patients. Given that dopamine transmission is abnormal in the brains of patients with schizophrenia and working memory deficit is a core dysfunction in schizophrenia, the concept of circuit stability would be useful not only for understanding the mechanisms of working memory processing but for developing therapeutic strategies to enhance cognitive functions in schizophrenia.     

Proton magnetic resonance spectroscopy in children with spastic diplegia

The objective of this prospective study was the application of proton magnetic resonance spectroscopy in children with spastic diplegia (SD) to determine the metabolite profile of SD children in the left basal ganglia, and to assess the relationship of this profile with motor and mental development. Patients with SD showed reduced ratios of N-acetylaspartate (NAA)/creatine (Cr), NAA/choline (Cho), NAA/myo-inositol (mI), Cho/NAA, Cho/Cr and Cho/mI in the basal ganglia compared to a well-matched control group. On the other hand, we noted increased Cr/NAA, Cr/Cho and mI/NAA ratios in the SD patients as compared with controls. NAA/mI ratios were positively correlated with the severity scale of cerebral palsy in SD children. There was also a significant correlation between Cr/NAA and mental retardation. Increased Cr/NAA, Cr/Cho and mI/NAA ratios in SD children may suggest the existence of the compensatory mechanisms in these patients. The NAA/mI ratio could be used as an additional marker of SD severity and Cr/NAA as a marker of the mental retardation.     

Attention-deficit disorder in adults with or without hyperactivity: where is the difference? A study in humans using short echo (1)H-magnetic resonance spectroscopy

The DSM-IV distinguishes three subtypes of attention deficit hyperactivity disorder: The predominantly inattentive subtype (ADD), the hyperactive-impulsive subtype (ADHD) and the combined subtype. We used short echo time (1)H-magnetic resonance spectroscopy (TE=30 ms, TR=3000 ms) for absolute quantification of neurometabolites using the LC model algorithm to investigate a possible metabolic neuropathology in adult patients with ADD and ADHD and compared their spectra with healthy controls (n=5 in each group). Spectra were acquired in the left dorsolateral prefrontal cortex and the left striatum. There was a significant group difference in N-acetylaspartate (NAA) concentration in the left dorsolateral prefrontal cortex distinguishing patients with the ADHD from patients with pure ADD and healthy controls. The absolute NAA concentration was significantly reduced only in the ADHD group. Since NAA-depletion reflects a state of neuronal dysfunction, this finding indicates evidence of subtle left prefrontal neuropathology in ADHD in adults.     

Comparisons of brain metabolites observed by HRMAS 1H NMR of intact tissue and solution 1H NMR of tissue extracts in SIV-infected macaques

The objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)H NMR of brain extracts of the same sample. Sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (MI), creatine (Cr), lactate (Lac), glutamate (Glu) and acetate (Ace). The ratios of the individual NMR peak areas of all metabolites relative to the creatine peak area were calculated. Linear regression analysis revealed significant correlations between measurements using the two methods. The strength of the correlations varied depending on the metabolite studied. We found highly significant correlations for NAA/Cr (r2 = 0.77; p < 0.0001), NAA + Ace/Cr (r2 = 0.73; p < 0.0001) and MI/Cr (r2 = 0.75; p < 0.0001). We observed somewhat less strong correlations for Glu/Cr (r2 = 0.54; p < 0.002) and Lac/Cr (r2 = 0.54; p < 0.002). There was a substantially weaker correlation for Cho/Cr (r2 = 0.32; p = 0.02). When plotting the metabolite ratios obtained by 1H HRMAS NMR of the intact tissue sample on the ordinate vs 1H NMR of the tissue extract on the abscissa, most metabolites exhibited a slope close to unity, and a positive intercept probably due to macromolecular contributions to the MAS spectra. The slope for Cho/Cr was substantially less than unity. Generally, samples from the frontal cortex showed a better correlation between intact and extracted tissue samples than putamen. This is most prominent in the cases of NAA/Cr and Cho/Cr. We conclude that both methods provide substantially the same information for most major brain metabolites, with the exception of the Cho resonance.     

低频重复经颅磁刺激治疗精神分裂症顽固性幻听的随机双盲对照研究

目的:初步探讨双背侧前额叶低频重复经颅磁刺激(rTMS)治疗精神分裂症顽固性幻听的疗效和安全性,并观察其副反应。方法:25例伴顽固性幻听的精神分裂症患者随机分为rTMS治疗组(N=12)和对照组(N=13),分别给予10次1HzrTMS真刺激和伪刺激治疗,治疗期间维持原有抗精神病药种类及剂量不变。采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评定临床症状,采用治疗中需处理的不良反应症状量表(Treatment Emergent Symptom Scale,TESS)等检查评估副反应。结果:25例患者均完成治疗,治疗组有效率高于对照组(75%vs.31%,P0.05)。未观察到明显副反应。结论:1Hz双背侧前额叶低频重复经颅磁刺激治疗精神分裂症顽固性幻听可能有效,且安全性好,值得进一步研究。