阳性症状为主型精神分裂症首次发病患者前额叶和海马磁共振质子波谱成像研究

目的 探讨阳性症状为主型精神分裂症首次发病患者前额叶和海马的磁共振质子波谱(1H-MRS)变化特点,为其病因学探讨提供线索.方法 对22例首次发病精神分裂症阳性症状为主型患者(患者组)和11名年龄、性别、受教育时间均匹配的正常对照者(对照组),应用2D 1H-MRS成像技术检测2组双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,分别计算NAA/Cr和Cho/Cr的比值;采用配对t检验、独立样本t检验进行统计分析.结果 (1)患者组左侧额叶白质NAA/Cr和Cho/Cr分别为(1.63±0.30)和(1.23±0.26),均低于对照组[(2.10±0.30)、(1.54±0.25)],右侧额叶白质NAA/Cr(1.70±0.34)低于对照组(1.97±0.34),差异有统计学意义(P<0.01和P<0.05);(2)双侧前扣带回皮质NAA/Cr、Cho/Cr值与对照组差异无统计学意义(P>0.05);(3)患者组右侧海马NAA/Cr(1.59±0.27)高于对照组(1.24±0.17),差异有统计学意义(P<0.01);(4)对照组内左侧额叶白质Cho/Cr(1.54±0.25)高于右侧(1.35±0.18),左侧海马NAA/Cr(1.45±0.28)高于右侧(1.24±0.17),差异均有统计学意义(P<0.05);(5)患者组内左侧海马NAA/Cr和Cho/Cr分别为(1.43±0.27)和(1.39±0.38),均低于右侧[(1.59±0.27)、(1.56±0.39)],差异有统计学意义(P<0.05).结论 首发精神分裂症阳性症状为主型患者的1H-MRS代谢物与正常人存在差异,提示阳性症状为主型患者存在双侧前额叶白质、海马的神经功能障碍.

Abstract：

Objective To identify the possible alteration of brain functioning in prefrontal lobes and hippocampus in the first-episode positive symptoms of schizophrenia using proton magnetic resonance spectroscopy (1H-MRS). Methods 1H-MRS was performed on prefrontal white matter, anterior cingulated cortex and hippocampus in 22 patients and 11 age-, sex-, and education-matched right-handed healthy controls. The ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr were calculated. Results The NAA/Cr and Cho/Cr ratios in the left prefrontal white matter in patients were lower than that in normal controls (patients, NAA/Cr 1. 63 ±0. 30; Cho/Cr 1. 23 ±0. 26; controls, NAA/Cr 2. 10 ±0. 30; Cho/Cr 1. 54 ± 0. 25, P<0. 01) , and NAA/Cr in the right prefrontal white matter was lower in patients than in controls (patients 1. 70 ± 0. 34; controls 1. 97 ± 0. 34, P<0. 05). There were no significant difference in NAA/Cr, Cho/Cr for the bilateral anterior cingulated cortex between patients and controls (P>0. 05). The ratio of NAA/Cr in the right hippocampus was significantly higher in patients than that in controls (patients 1. 59 ± 0. 27; controls 1. 24 ± 0. 17, P<0. 01). In addition, in healthy controls,Cho/Cr was significantly higher in the left prefrontal white matter than in the right (left 1. 54 ± 0. 25; right 1. 35 ±0. 18, P<0. 05) , and NAA/Cr in the left hippocampus was significantly higher than in the right (left 1. 45 ± 0. 28; right 1. 24 ± 0. 17, P<0. 05). While NAA/Cr and Cho/Cr in the left hippocampus were significantly lower than in the right hippocampus in schizophrenia patients (left, NAA/Cr 1.43 ± 0. 27;Cho/Cr 1.39 ±0.38; right, NAA/Cr 1.59 ±0.27; Cho/Cr 1.56 ±0.39, P<0.05). Conclusion There is the significant difference of manifestation of 1H-MRS between schizophrenia patients with positive symptoms and normal controls, which reflects neuronal dysfunction in the prefrontal lobes and hippocampus.     

Application of proton magnetic resonance spectroscopy on substantia nigra metabolites in Parkinson’s disease

This study investigates changes in substantia nigra metabolites in Parkinson’s disease (PD) using proton magnetic resonance spectroscopy (¹H- MRS). Thirty patients with asymmetric PD and 20 normal controls were included in this study. Substantia nigra metabolites were detected in all subjects using 3D-multimer ¹H-MRS with a 3.0 T MRI scanner. The relative ratios of NAA/Cr, NAA/Cho, NAA/(Cho + Cr) in the substantia nigra were compared between two sides of asymmetric PD patients as well as between PD patients and controls. Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were observed between PD patients and healthy controls (P?<?0.05) as well as between the ipsilateral and contralateral of affected extremity in PD patients (P?<?0.05). Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were also observed between patients with mild and severe PD. Thus, we found that ¹H-MRS can be used to detect substantia nigra metabolites in PD patients, which may be useful for early diagnosis and evaluation of PD.     

Thalamic neurometabolic alterations in tremulous Parkinson's disease: A preliminary proton MR spectroscopy study

IntroductionThe objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (¹H-MRS).MethodsFourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with ¹²³I-ioflupane, and a short-echo single-voxel ¹H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated.ResultsDAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls.ConclusionsThis study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that ¹H-MRS can help differentiate patients with tPD from those with rET.     

双相抑郁患者前额叶及海马磁共振质子波谱成像研究

目的探讨双相抑郁患者前额叶及海马磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)的代谢物变化特点,为其神经生物学研究提供线索。方法应用磁共振质子波谱成像技术检测26例双相抑郁患者(患者组)和26例单相抑郁患者及13例健康志愿者(对照组)双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(N-Acetylaspartate,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)3种代谢物,以Cr为参照物,分别计算双侧NAA/Cr和Cho/Cr比值。采用SPSS 13.0进行统计处理。结果患者组左侧前额叶白质NAA/Cr(1.65±0.31)低于对照组(2.37±0.36),左侧前额叶白质Cho/Cr(1.35±0.27)低于对照组(1.65±0.21),差异有统计学意义(P<0.05);右侧前额叶白质NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧前扣带回NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧海马NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组与单相抑郁组的双侧额叶白质、双侧前扣带回皮质、双侧海马NAA/Cr、Cho/Cr值差异均无统计学意义。结论双相抑郁患者可能存在左侧前额叶神经元功能下降和膜磷脂代谢异常,其代谢物特点存在偏侧化。     

An 1H-MRS framework predicts the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers

BackgroundAlzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (¹H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD.MethodsWe studied 75 subjects from the largest multigenerational pedigree in the world (∼5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two-dimensional ¹H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to ¹H-MRS data while controlling for age, educational level, and sex.ResultsWe found that (1) the combination of LPPGM Cho/Cr <0.165 and RPPGM Glx/Cr >1.54 fully excluded carriers; (2) LPPGM Cho/Cr >0.165, RPPGM Glx/Cr <1.54, and left parietal white mater NAA/Cr >1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr >1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%.ConclusionsBrain metabolites measured by ¹H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.     

The correlation between 1H-MR spectroscopy and clinical manifestation with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease. Cortical tubers are one of the standard intracranial hallmarks of TSC, they comprise subependymal hamartomas protruding into the ventricles, cortical and white matter hamartomas, and giant cell tumors. The clinical course of TSC varies from asymptomatic to severe, with epileptic seizures and psychomotor retardation. We discuss here the correlation between clinical manifestation and features on 1H-MR spectroscopy ( 1H-MRS) of the white matter involving cortical tubers in patients with TSC. Statistical analysis of the N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI)/creatinine (Cr) ratios between tubers and normal controls showed decreased NAA/Cr and increased mI/Cr ratios (P<0.05) in tubers, but no significance difference in Cho/Cr. The significance of the clinical appearance is associated with a decreased ratio of NAA/Cr in tubers with TSC. An elevated ratio of mI/Cr in tuber does not parallel the severity of the clinical features of TSC. These findings suggest that 1H-MRS may be useful for the evaluation of the clinical severity and prognostic diagnosis of TSC.     

Proton magnetic resonance spectroscopy of normal appearing white matter in familial and sporadic multiple sclerosis

Objective To assess metabolite levels in normal–appearing white matter in sporadic and familial multiple sclerosis (MS). Methods Using H–MRS and applying one voxel measure we assessed NAA/Cho,NAA/Cr and Cho/Cr ratios in 26 patients with sporadic and in 25 with familial MS and compared them with healthy subjects. Results In both MS groups NAA/Cho and NAA/Cr ratio were significantly lower than in healthy individuals whereas Cho/Cr ratio was higher in MS patients. In sporadic MS patients NAA/Cho and NAA/Cr ratios were lower, although not significantly, than in familial cases. The Cho/Cr ratio was similar in both MS groups. Conclusion These results suggest that subtle differences in H–MRS measures corresponding to axonal rather than to myelin pathology might occur in sporadic and familial MS.     

Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal brain lesions in patients infected with HIV

OBJECTIVES—To evaluate the role of proton MRspectroscopy (¹H-MRS) in detecting metabolic changes indiffuse or focal lesions in the brain of patients infected with HIV.
METHODS—Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight withprogressive multifocal leukoencephalopathies (PMLs), and sevenwith lymphomas) and 22HIV seronegative neurologicalcontrols were examined with a combined MRI and¹H-MRStechnique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echosequence, TE 135 ms) were acquired by single voxel, localised on focallesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies andon the centrum semiovale of neurological controls. Choline (Cho),creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids wereevaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated.
RESULTS—A significant decrease in NAA/Cr andNAA/Cho ratios were found in all HIV diagnostic groups in comparisonwith neurological controls (p<0.003), suggesting neuronal or axonaldamage independent of brain lesion aetiology. However, the NAA/Cr ratiowas significantly lower in PML and lymphomas than in HIVencephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIVencephalopathies, lymphomas, and toxoplasmosis showed a significantincrease in the Cho/Cr ratio in comparison withneurological controls (p<0.03) without between groupdifferences. The presence of a lipid signal was more frequent inlymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher's test, p=0.00024).
CONCLUSION—¹H-MRS shows a highsensitivity in detecting brain involvement in HIV related diseases, buta poor specificity in differential diagnosis of HIV brain lesions.Nevertheless, the homogeneous metabolic pattern that characterises PMLsuggests the usefulness of ¹H-MRS as an adjunct to MRI indifferentiating CNS white matter lesions, such as HIV encephalopathies,from PML.

     

磁共振波谱检测肌萎缩侧索硬化的上运动神经元损害

目的探讨质子磁共振波谱(proton magnetic resonance spectroscopy,1 H-MRS)检测肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)的上运动神经元损害(upper motor neuron,UMN)的特点和诊断准确性。方法收集ALS患者31例和健康对照32名,采用1 H-MRS检测脑中央前回皮质下、内囊后肢和大脑脚感兴趣区代谢产物N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)的水平,计算NAA/Cr、NAA/(Cho+Cr)、Cho/Cr比值,采用受试者工作特征(receiver operating characteristic,ROC)曲线分析1 H-MRS对ALS患者UMN损害的诊断价值。结果 ALS患者各锥体束走行部位和部位组合的NAA/Cr和NAA/(Cho+Cr)较对照组显著降低(P0.05)。NAA比值预测ALS的UMN损害的ROC曲线下面积(area under the curve,AUC)为0.67~0.91,其中内囊后肢、大脑脚两部位的平均NAA/(Cho+Cr)和三部位的平均NAA/(Cho+Cr)的AUC、灵敏度、特异度分别为0.91、0.828、0.906和0.90、0.769、0.875。结论 1 H-MRS可检出ALS患者锥体束走行的生化代谢异常,是评估ALS的UMN损害的客观影像学指标,其诊断准确性中等,多水平检测和综合指标的选择有助于提高其诊断效力。     

多体素H-MRS在脑胶质瘤术前评价中的应用

目的运用多体素二维磁共振波谱法（H-MRS）分析脑胶质瘤周围区域。H-MRS代谢物改变特点,评价H-MRS在脑胶质瘤术前的应用价值。方法收集经手术及病理证实的28例胶质瘤患者,所有患者在术前均行磁共振头颅常规检查和。H-MRS检查。分别测量不同区域的N-乙酰天门冬氨酸（NAA）、肌酸（Cr）、胆碱（Cho）峰下面积,计算出NAA／Cr、Cho／Cr及NAA／Cho比值,并进行统计学分析。结果低／高级别胶质瘤肿瘤组织和对侧正常脑组织的NAA／Cr、Cho／Cr及NAA／Cho比值存在显著性差异;低／高级别胶质瘤肿瘤组织和远瘤周区域的NAA／Cr、Cho／Cr及NAA／Cho比值存在显著性差异;低级别胶质瘤远瘤周区域和对侧正常脑组织的NAA／Cho比值存在显著性差异,NAA／Cr、Cho／Cr比值不存在显著性差异;高级别胶质瘤远瘤周区域和对侧正常脑组织的Cho／Cr、NAA／Cho比值存在显著性差异,但NAA／Cr比值不存在显著性差异。结论多体素H-MRS可帮助临床医生在术前评价胶质瘤的浸润范围,并制定最佳的治疗方案。     

氟西汀对脑卒中后抑郁患者海马磁共振氢质子波谱影响的研究

目的探讨氟西汀对脑卒中后抑郁患者海马氢质子磁共振波谱(~1 H-MRS)影响的特点。方法以60例脑卒中后抑郁患者为研究组,研究组给予氟西汀抗抑郁治疗8周,以62名脑卒中患者为对照组。采用~1 H-MRS检测脑卒中后抑郁患者(研究组)治疗前后及脑卒中患者(对照组)双侧海马的N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),以NAA/Cr值和Cho/Cr值进行统计分析。结果研究组治疗前后左右侧海马NAA/Cr值(分别为1.22±0.31和1.19±0.42,1.46±0.35和1.43±0.41)均低于对照组(分别为1.69±0.33和1.66±0.47),差异有统计学意义(均P0.05);研究组治疗前后左右侧海马Cho/Cr值(分别为1.58±0.39和1.59±0.46,1.55±0.43和1.53±0.42)高于对照组(分别为1.26±0.42和1.31±0.47),差异有统计学意义(均P0.05);研究组治疗后左右侧海马NAA/Cr值(分别为1.46±0.35和1.43±0.41)均高于治疗前(分别为1.22±0.31和1.19±0.42),差异有统计学意义(均P0.05)。结论氟西汀可能改变脑卒中后抑郁患者海马神经元的代谢异常。     

Brain metabolites in definite amyotrophic lateral sclerosis

Abstract Biomarkers beyond clinical assessment are needed in patients who suffer from amyotrophic lateral sclerosis (ALS). Here, single-voxel proton magnetic resonance spectroscopy (¹H MRS) of the gray matter of the motor cortex and the white matter including the pyramidal tracts was used to investigate concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, glutamate, and glutamine in patients with definite ALS in a longitudinal design (three measurements at study inclusion, after 3 and 6 months). A volume-corrected analysis of gray and white matter fractions within the volumes of interest (VOI) was performed for the identification of the absolute metabolite concentrations. The patient group showed a significant decline of the compound NAA over time in the motor cortex areas both of the clinically more and less affected hemisphere between first measurement and month 6 and for the less affected side additionally between first measurement and month 3. For the NAA/(Cr + Cho) ratio, significant decline in the less affected hemisphere was observed from the first measurement to month 3 and to month 6 as well as from month 3 to month 6. In contrast, neither NAA nor the NAA/(Cr + Cho) ratios in the white matter areas showed any significant alterations. All other compounds showed no significant changes over time. In summary, the longitudinal changes of cortical metabolite concentrations in the course of ALS could be assessed by optimized ¹H MRS techniques at group level, so that ¹H MRS parameters, in particular volume-corrected values of NAA in the clinically less affected hemisphere, seem to have the potential to serve as a surrogate marker for monitoring ALS disease progression.     

Proton magnetic resonance spectroscopy (H-MRS) of the thalamus in schizophrenia

This study applied ¹H-MRS in the thalamus of schizophrenic patients and healthy subjects.There were no differences in the metabolite ratios (NAA/Cr, Cho/Cr or mI/Cr) between the two groups. Relationships were noted between NAA/Cr and age in patients with a trend toward this correlation in controls, suggesting an effect of age on the metabolism of the thalamus.     

脑白质疏松症患者认知功能与海马代谢关系的研究

目的探讨脑白质疏松症患者认知损害与海马代谢间的关系。方法对108例性别、受教育程度和脑血管病危险因素相匹配且有记忆力减退主诉的患者进行神经心理学评价,通过氢质子磁共振波谱测量左侧海马区N-乙酰天冬氨酸/肌酸、肌醇/肌酸、胆碱复合物/肌酸,以及谷氨酸和谷氨酰胺复合物α峰/肌酸比值,以观察与记忆相关脑区的代谢物变化。结果脑白质疏松症组患者简易智能状态检查量表(24.00)和蒙特利尔认知评价量表(16.50)中位数评分低于对照组(27.00和21.00),组间差异有统计学意义(均P=0.000);其中以视觉执行能力(1.00:3.00)、注意力(4.00:5.00)、语言(1.00:2.00)、延迟回忆(0.00:2.00)等项评分降低最为显著(P<0.05或P<0.01)。韦氏记忆量表中文修订版进一步测验显示,脑白质疏松症组患者瞬时记忆(5.06±2.86)和短时记忆(32.76±13.31)评分均显著低于对照组[(7.68±4.41)和(46.95±1481)],且差异具有统计学意义(P<0.05或p<0.01);左侧海马区N-乙酰天冬氨酸、肌醇、胆碱复合物与肌酸比值测定,两组差异无统计学意义(P>0.05)。结论脑白质疏松症引起的认知损害主要表现为视觉执行能力、注意力、语言及记忆(瞬时记忆和短时记忆)显著降低,未发现这一改变与左侧海马代谢变化有关。     

Metabolic Changes in Neuronal Migration Disorders: Evaluation by Combined MRI and Proton MR Spectroscopy

PURPOSE: To assess the role of 1H-magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs). METHODS: We performed 1H-MRS studies on 17 brain NMD areas [five polymicrogyria, eight subcortical heterotopia, and four cortical dysplasia on magnetic resonance imaging (MRI)]. The study group consisted of 15 patients, all but one affected by partial epileptic seizures. Spectra were acquired from volumes of interest localized on NMDs and contralateral sides and compared with those obtained on gray and white matter of 18 neurologic controls. RESULTS: NMD lesions were characterized by lower N-acetylaspartate to creatine (NAA/Cr) and choline to Cr (Cho/Cr) ratios than those of the white (p = 0.002 and p = 0.004) and gray matter (p = 0.03 and p = 0.06) of neurologic controls. In addition, the normal-appearing contralateral sides to the NMD lesions showed a significant decrease of Cho/Cr ratio when compared with those of white (p = 0.003) and gray matter (p = 0.05) of neurologic controls. No relation was found between NAA/Cr decrease, EEG abnormalities, and NMD sides, or between NAA/Cr ratios, duration of epilepsy, and frequency of seizures. Lactate signal was detected in the spectra of four patients who had an epileptic seizure a short time before MR examination. CONCLUSIONS: NAA/Cr decrease may be related more to structural and functional alteration of the NMD sides than to epileptic activity in these lesions. Low Cho/Cr may be related to a more extensive diffuse hypomyelination than suggested by the MRI findings. An activation of anerobic glycolysis during and after seizures could account for the presence of lactate. These data confirm that H-MRS is an advanced technique that may provide useful biochemical information in vivo on neurobiologic processes underlying NMDs.     

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.     

Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis

Abstract

Objective:

To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS).

Methods:

Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7.

Results:

Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r = ?0·56, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05).

Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), but not with EDSS at year 7.

Discussion:

Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.     

1H-MRS asymmetry changes in the anterior and posterior cingulate gyrus in patients with mild cognitive impairment and mild Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Amnestic mild cognitive impairment (aMCI) is often the prodromal stage to AD. Most patients with aMCI harbor the pathologic changes of AD and demonstrate transition to AD at a rate of 10%–15% per year. Patients with AD and aMCI experience progressive brain metabolite changes. Accumulating evidence indicates that the asymmetry changes of left and right brain happen in the early stage of AD. However, the features of asymmetry changes in both anterior cingulate gyrus (ACG) and posterior cingulate gyrus (PCG) are still unclear. Here, we examine the left–right asymmetry changes of metabolites in ACG and PCG. Fifteen cases of mild AD patients meeting criteria for probable AD of NINDS-ADRDA, thirteen cases of aMCI according to the Mayo Clinic Alzheimer's Disease Research Center criteria, and sixteen cases of age-matched normal controls (NC) received Proton magnetic resonance spectroscopy (¹H-MRS) for measurement of NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in the PCG and ACG bilaterally. We analyzed ¹H-MRS data by paired t-test to validate the left–right asymmetry of ¹H-MRS data in the PCG and ACG. In AD, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001) and the left and right PCG (P = 0.007). In aMCI, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001). In NC, there were no differences in the ratio value of metabolites NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr between the left and right ACG and PCG. Thus, the left–right asymmetry of mI/Cr in the ACG and PCG may be an important biological indicator of mild AD.     

Characterization of cerebral small vessel disease by proton spectroscopy and morphological magnetic resonance

This study sought to investigate whether clinical and neuropsychological impairment in cerebral small vessel disease (CSVD) can be evaluated by proton spectroscopy ((1)H-MRS) and structural magnetic resonance (MR) imaging. Sixteen patients with CSVD and 15 healthy age-matched controls participated in the study. In addition to spectroscopic and structural MR examination all patients underwent a comprehensive clinical and neuropsychological investigation. Significant differences in between patients and controls were revealed by (1)H-MRS in the parietal white matter: decreased metabolic ratios of N-acetyl aspartate to choline (NAA/Cho; patients: 1.37 +/- 0.17, control: 1.72 +/- 0.25, p < 0.001) and of N-acetyl aspartate to creatin (NAA/Cr; patients: 1.41 +/- 0.15, control: 1.66 +/- 0.2, p < 0.01) indicated a pathological state. Evaluation of spectroscopic and neuropsychological data revealed a close relation between attentional impairment, i.e. delayed cerebral transmission time and decreased NAA/Cho and NAA/Cr (r = 0.62, p = 0.014). In sum, (1)H-MRS allowed a clear discrimination between patients with CSVD and age-matched normal controls. Moreover, comparisons of (1)H-MRS and neuropsychological data suggested that NAA metabolic levels, and particularly the delay in cerebral transmission time, could be potential predictors of the severeness of attentional impairment.     

Proton magnetic resonance spectroscopy in parkinson's disease and atypical parkinsonian disorders

Proton magnetic resonance spectroscopy (¹H-MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple-system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age matched controls. The study assessed the level of N-acetylaspartate (NAA), creatine–phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. ¹H-MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.