Identification of abnormal neuronal metabolism outside the seizure focus in temporal lobe epilepsy

PURPOSE: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) magnetic resonance imaging (MRI) evidence for mesial-temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1H magnetic resonance spectroscopic imaging (MRSI). METHODS: MRSI in combination with tissue segmentation was performed on 14 TLE-MTS and seven TLE-no and 12 age-matched controls. In controls, N-acetylaspartate/(creatine + choline) [NAA/(Cr+Cho)] of all voxels of a given lobe was expressed as a function of white matter content to determine the 95% prediction interval for any additional voxel of a given tissue composition. Voxels with NAA/(Cr+Cho) below the lower limit of the 95% prediction interval were defined as "pathological" in patients and controls. Z-scores were used to identify regions with a higher percentage of pathological voxels than those in controls. Results: Reduced NAA/(Cr+Cho) was found in ipsilateral temporal and parietal lobes and bilaterally in insula and frontal lobes. Temporal abnormalities identified the epileptogenic focus in 70% in TLE-MTS and 83% of TLE-no. Extratemporal abnormalities identified the epileptogenic focus in 78% of TLE-MTS but in only 17% of TLE-no. Conclusions: TLE is associated with extrahippocampal reductions of NAA/(Cr+Cho) in several lobes consistent with those brain areas involved in seizure spread. Temporal and extratemporal NAA/(Cr+Cho) reductions might be helpful for focus lateralization.     

Parietal white matter abnormalities in obsessive-compulsive disorder: a magnetic resonance spectroscopy study at 3-Tesla

OBJECTIVE: To identify a neurochemical basis for the hypothesis that an aberrant cortico-subcortical circuit underlies obsessive-compulsive disorder (OCD). The white matter was also investigated because of recent research which suggests the altered connectivity of axons. METHOD: Using 3-Tesla magnetic resonance spectroscopy, the relative concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) to creatine/phosphocreatine (Cr) were measured in the anterior cingulate, basal ganglia, thalamus, frontal and parietal white matter of 12 OCD patients, and 32 control subjects. RESULTS: The mean concentration of Cho/Cr was significantly higher in the patients than in the controls, but only in the parietal white matter, while no significant group differences in NAA/Cr were observed in any of the brain regions. Parietal Cho/Cr correlated positively with the severity of OCD symptoms. CONCLUSION: This finding provides indirect evidence for the parietal white matter involvement in OCD, thus suggesting a change in the phospholipids of myelinated axons and/or glia cells.     

Proton spectroscopic imaging shows abnormalities in glial and neuronal cell pools in frontal lobe epilepsy

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. METHODS: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. RESULTS: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. CONCLUSIONS: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a "noninvasive biopsy" in epileptogenic lesions.     

Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study.

BACKGROUND: Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). METHODS: Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. RESULTS: Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. CONCLUSIONS: These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism.     

Detection of metabolites in the white matter of frontal lobes and hippocampus with proton in first-episode treatment-naïve schizophrenia patients

Aim: This study aimed to investigate the changes of the metabolites in the white matter of frontal lobes and hippocampus in schizophrenia by using proton magnetic resonance spectroscopy (¹H‐MRS). Methods: Sixty‐three first‐episode treatment‐naïve schizophrenia (FES) patients and 63 age‐, gender‐ and education level‐matched healthy controls were recruited. The relative levels of metabolites including N‐acetylaspartate (NAA), choline‐containing compounds (Cho), (Cr) and myo‐inositol (MI) were detected with ¹H‐MRS, and the laterality index (Li) was calculated. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale. Results: Compared with controls, FES patients did not show significant differences in all metabolites. The severity of positive symptoms was negatively correlated with the NAA/Cho in the white matter of the left frontal lobe and positively correlated with the Cho/Cr in the right white matter of frontal lobes. A negative correlation was observed between the severity of negative symptoms and the NAA/Cr in the white matter of bilateral frontal lobes. No difference was shown in the Li of metabolites between FES patients and controls. Conclusions: The metabolites such as NAA, Cho and MI in white matter of frontal lobes and hippocampus were not significantly altered in FES patients. The lower axonal integrity/number (NAA concentration) may be associated with more severe negative symptoms, and dysmetabolism in process of myelination in the white matter of frontal lobes associated with more severe positive symptoms.     

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.     

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.     

Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging

Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD.     

老年抑郁症患者脑磁共振波谱成像研究

目的 应用磁共振波谱成像(MRS)研究老年抑郁症患者脑内神经环路物质代谢异常,探讨其发病机制.方法 对23例老年抑郁症患者(抑郁症组)及18名老年健康志愿者(正常对照组)行常规磁共振及三维磁共振氢质子波谱(<'1>H-MRS)检查,测量双侧额叶背外侧白质、前部扣带回皮质、杏仁核、海马、丘脑的N-乙酰天门冬氨酸(N从)、胆碱(Cho)与肌酸(Cr)的比值,对两组各部位的比值分别进行独立样本t检验.结果 (1)抑郁症组额叶背外侧白质(2.28±0.32)、前部扣带回皮质(2.19 ±0.39)、杏仁核(1.95 ±0.22)、海马的Cho/Cr比值(2.38 ±0.30)均高于正常对照组(分别为1.88 ±0.40、1.68±0.30、1.66±0.24、2.00±0.34),差异有统计学意义(P＜0.01～0.05);而丘脑Cho/Cr比值与对照组的差异无统计学意义(P＞0.05).(2)抑郁症组前部扣带回皮质(2.08 ±0.26)、杏仁核(2.20 ±0.27)、海马的NAA/Cr比值(2.10 ±0.27)低于正常对照组(分别为2.58 ±0.35、2.52±0.22、2.44±0.24),差异有统计学意义(P＜0.01～0.05);而额叶背外侧白质及丘脑未见明显变化(P＞0.05).结论 老年抑郁症患者额叶背外侧白质、前部扣带回皮质、杏仁核、海马的Cho/Cr比值明显高于对照组,提示边缘系统-皮质-纹状体-苍白球-丘脑环路的功能受到影响,该神经环路在老年抑郁症发病机制中可能起一定作用.     

男性酒精依赖患者的威斯康星卡片分类测验及脑质子波谱动态研究

目的 通过磁共振质子波谱(1H-MRS)检测酒精依赖患者额叶代谢物质的变化,探讨酒精依赖所致认知障碍的神经生物学基础.方法 分别于戒酒前和戒酒1个月时应用1H-MRS技术,检测10例男性酒精依赖患者(患者组)的额叶氮-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)、肌酸(Cr)变化,并与10名正常对照者(对照组)进行比较;同时用威斯康星卡片分类测试(WCST)评定受试者的认知功能.结果 (1)戒酒前,患者组双侧前额叶灰质和白质NAA/Cr比值均低于对照组(P＜0.05),戒酒1个月时较戒酒前有好转(P=0.00),但仍低于对照组(P＜0.05);而Cho/Cr戒酒前后的差异元统计学意义(P＞0.05).(2)患者组戒酒前WCST中的完成分类数[(0.70±1.06)个]和概念化水平[(16.29±10.27)%]低于戒酒1个月时[分别为(3.80±2.15)个,(52.32±20.81)%],而错误应答数[(83.60±10.80)个]和持续性错误[(34.80±16.94)个]高于戒酒1个月时[分别为(42.80±21.06)个,(21.70±11.39)个;P＜0.05].(3)患者组戒酒前后右侧灰质NAA/Cr变化与WCST完成分类数的变化相关(r=0.7002,P＜0.05).结论 长期饮酒可导致酒精依赖患者前额叶代谢物浓度改变;其认知功能的损害,可能与酒精对前额叶代谢物浓度的影响有关.     

Regional myo-inositol concentration in mild cognitive impairment Using 1H magnetic resonance spectroscopic imaging

The goal was to assess regional patterns of metabolite abnormalities in mild cognitive impairment (MCI) and Alzheimer disease (AD) patients using proton magnetic resonance spectroscopy imaging at 1.5 Tesla. Fourteen MCI, 17 AD, and 16 healthy control (HC) subjects were studied. MCI was associated with higher myo-inositol (mIn) concentration in right parietal white matter compared with HC and lower mIn levels in frontal white matter compared with AD. AD was associated with higher mIn concentration in frontal and parietal white matter compared with HC. N-acetylaspartate (NAA) concentration of white matter was similar in all groups, whereas NAA concentration of gray matter showed a trend toward lower values in the right parietal lobe in AD compared with MCI and HC. A mIn increase in white matter in absence of significant NAA reduction suggests that mIn is a more robust and sensitive marker of white matter pathology in AD and MCI than NAA. Furthermore, the dissociation between mIn and NAA alterations in white matter could provide important information regarding the role of glial and neuronal damage in MCI and AD.     

Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.     

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.     

Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI

OBJECTIVE: To determine 1) the reproducibility of metabolite measurements by (1)H MRS in the motor cortex; 2) the extent to which (1)H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. METHODS: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice (1)H MRSI. (1)H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. RESULTS: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. CONCLUSION: Metabolite changes measured by (1)H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.     

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.     

Identification of the epileptogenic lobe in neocortical epilepsy with proton MR spectroscopic imaging

PURPOSE: The aim of this study was to evaluate the usefulness of multislice magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation for the identification of the epileptogenic focus in neocortical epilepsy (NE). METHODS: Twenty patients with NE (10 with MRI-visible malformations, 10 with normal MRI) and 19 controls were studied. In controls, N-acetylaspartate NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter, and thresholds were determined by calculating the 95% prediction intervals (PIs) for NAA/Cr and NAA/Cho. Voxels with NAA/Cr or NAA/Cho values less than the 95% PI were defined as "pathological." Z-scores were calculated. Depending on the magnitude of those z-scores, we used two different methods (score-localization or forced-localization) to identify in a given subject the lobe with the highest percentage of pathological voxels, which was supposed to represent the epileptogenic lobe. RESULTS: MRSI correctly identified the lobe containing the epileptogenic focus as defined by EEG in 65% of the NE patients. MRSI localization of the focus was correct in 70% of the patients with an MRI-visible malformation and in 60% of the patients with normal MRI. Of the patients, 15% had metabolically abnormal brain regions outside the epileptogenic lobe, and 35% of the patients had evidence for secondary hippocampal damage. CONCLUSIONS: MRSI may be helpful for the identification of the epileptogenic focus in NE patients, even in NE with normal MRI.     

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.     

Metabolite changes in early relapsing–remitting multiple sclerosis

Previous in vivo proton magnetic resonance spectroscopic imaging (¹H–MRSI) studies have found reduced levels of N–acetyl–aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal–appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by ¹H–MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N–acetyl–aspartyl–glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing–remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent ¹H–MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM.At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (–7%, p = 0.003), as well as in the CGM (–8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial ¹H–MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.     

Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.     

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 b