阿尔茨海默病和血管性痴呆氢质子磁共振波谱研究

痴呆是一种获得性、持续性智能损害综合征,老年期痴呆主要包括阿尔茨海默病(Alzheimer disease,AD)和血管性痴呆(Vascular dementia,VD).AD是老年人最常见的痴呆类型,根据尸检病理研究,60%～70%的痴呆为此种类型[1].VD是第二大常见痴呆类型,约占痴呆类型的10%～20%[2],AD和VD病理过程不完全相同,但临床表现、危险因素、病理学所见、影像学特征存在一定程度的重叠[3],在临床上难以准确区分,鉴别诊断的困难长期存在.     

The hippocampus in patients treated with electroconvulsive therapy: a proton magnetic resonance spectroscopic imaging study

BACKGROUND: We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT-induced memory deterioration was associated with neuronal loss in the hippocampus, the N-acetylaspartate signal would decrease after ECT and any increased membrane turnover would result in an increase in the signal from choline-containing compounds. METHODS: Seventeen patients received complete courses of ECT, during which repeated proton magnetic resonance spectroscopic imaging studies of the hippocampal region were performed. Individual changes during the course of ECT were compared with values obtained in 24 healthy control subjects and 6 patients remitted from major depression without ECT. RESULTS: No changes in the hippocampal N-acetylaspartate signals were detected after ECT. A significant mean increase of 16% of the signal from choline-containing compounds after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT application (14 of 17 patients), the increase in the choline-containing compound signal was observed bilaterally. Lactate or elevated lipid signals were not detected. All patients showed clinical amelioration of depression after ECT. CONCLUSIONS: Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal. Compared with an age-matched control group, the choline-containing compounds signal in patients with a major depressive episode was significantly lower than normal, before ECT and normalized during ECT.     

Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer disease

CONTEXT: The staging of Alzheimer disease (AD) dementia could be improved by a neurometabolic analysis using magnetic resonance spectroscopy. OBJECTIVE: To examine the correlation between regional cerebral metabolic alterations measured by proton magnetic resonance spectroscopy and neuropsychological dysfunctions in patients with early AD. DESIGN: A case-control study. SETTING: University hospital neurology clinic and radiology department. PARTICIPANTS: A cohort of 14 patients with mild AD and 14 control subjects paired for age and sex. INTERVENTIONS: Single-voxel proton magnetic resonance spectroscopic brain examination (60 minutes) and a comprehensive battery of psychometric tests (2 hours). MAIN OUTCOME MEASURES: Metabolite ratios relative to unsuppressed water were calculated for magnetic resonance spectroscopic metabolites (N-acetylaspartate, choline, creatine-phosphocreatine, and myo-inositol) in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs), and frontal cortices of both hemispheres. Correlations were examined between metabolic changes in an area and psychometric scores of its known regional function: MTL and verbal memory, PTC and language and visuoconstructional abilities, and frontal cortices and executive functions. RESULTS: A significant reduction of N-acetylaspartate/water (H2O) in the left MTL and of choline/H2O in both MTLs, as well as a significant increase of myo-inositol/H2O in the right PTC were observed. Metabolic alterations in the left MTL were correlated with a loss of verbal memory, in the left PTC with language impairment, and in the right PTC with a loss of visuoconstructional abilities in the group with AD. CONCLUSION: These findings are consistent with regional distribution of neuropathologic changes and cognitive symptoms characterizing early phases of AD, and with the pattern of lateralization of normal brain function.     

抑郁症首次发病患者海马磁共振质子波谱成像的研究

目的 探讨抑郁症首次发病患者海马的磁共振质子波谱(1H-MRS)代谢物质的变化.方法 对99例首次发病的抑郁症患者和26例健康对照组行磁共振常规扫描及1H-MRS检查,测量双侧海马N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)和肌酸(Cr)三种代谢物质,计算NAA/Cr和Cho/Cr比值.结果 抑郁症患者海马NAA/Cr左右侧比值(1.23±0.16;1.16±0.16)低于对照组NAA/Cr左右侧比值(1.38±0.23;1.31±0.26),差异有显著性(P<0.05);抑郁症患者海马体部Cho/Cr左右侧比值(1.19±0.14;1.18±0.12)高于对照组Cho/Cr左右侧比值(1.14±0.12;1.11±0.14),差异有显著性(P<0.05).对照组左右侧NAA/Cr和Cho/Cr比较差异无显著性(P>0.05).抑郁症组右侧NAA/Cr低于左侧,差异显著(P<0.05);左侧Cho/Cr高于右侧,差异不明显(P>0.05).结论 抑郁症患者可能存在双侧海马神经细胞代谢功能障碍,右侧神经细胞功能障碍较左侧明显.     

Multislice proton magnetic resonance spectroscopic imaging in X-linked adrenoleukodystrophy

Multislice proton magnetic resonance spectroscopic imaging permits metabolic analysis of brain tissue in vivo by data acquisition in four oblique axial slices, each 15-mm thick and divided into 0.8-ml single-volume elements. We applied this technique to the systematic study of 25 patients with adrenoleukodystrophy: 3 with the severe childhood or adult cerebral form of the disease, 5 with adrenomyeloneuropathy, 12 with no demonstrable neurological involvement, and 5 women heterozygous for adrenoleukodystrophy who had some degree of neurological disability. Abnormalities on magnetic resonance spectroscopic imaging included a reduction in N-acetyl aspartate, an increase in cholin-containing compounds, and at times, an increase in lactate. Five patients showed abnormalities in the presence of normal-appearing magnetic resonance images, and in 8 other patients the alterations on spectroscopic images were more severe than those demonstrable by magnetic resonance imaging. Correlation with clinical course suggests that an increase in the choline-containing compounds is associated with an active demyelinative process, whereas such compounds are not elevated in lesions that are stable. We conclude that magnetic resonance spectroscopic imaging is a more sensitive indicator of early neurological involvement thatn is magnetic resonance imaging, and that the character of abnormalities detected by the former technique may serve as a gauge of the degree of activity of the demyelinating process and as a guide to the selection and evaluation of therapeutic approaches.     

Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis detected by proton magnetic resonance spectroscopic imaging

Riluzole prolongs survival in amyotrophic lateral sclerosis. The temporal and spatial profile of its effect on the brain is unknown. We used proton magnetic resonance spectroscopic imaging to evaluate the neuronal response to 1 day of riluzole treatment in motor and non-motor regions of the brain. In 10 patients the N-acetylaspartate/total creatine (NAA/Cr) ratio increased in the precentral gyrus and supplementary motor area, but not in the post-central gyrus or parietal lobe. Improvement in cortical neuronal metabolic function in the motor cortex occurs early with riluzole treatment.     

Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration

Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N- acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substan- tial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.     

Measuring N-acetylaspartate synthesis in vivo using proton magnetic resonance spectroscopy

N-Acetylaspartate (NAA) is an important marker of neuronal function and viability that can be measured using magnetic resonance spectroscopy (MRS). In this paper, we proposed a method to measure NAA synthesis using proton MRS with infusion of uniformly (13)C-labeled glucose, and demonstrated its feasibility in an in vivo study of the rat brain. The rate of (13)C-label incorporation into the acetyl group of NAA was measured using a localized, long echo-time proton MRS method. Signals from the (13)C satellites of the main NAA methyl protons at 2.02 ppm were continuously monitored for 10h. Quantification of the data based on a linear kinetic model showed that NAA synthesis rate in isoflurane-anesthetized rats was 0.19+/-0.02 micromol/g/h (mean+/-standard deviation, n=12).     

青少年首次发病精神分裂症患者前额叶和海马磁共振质子波谱成像的研究

目的探讨青少年首次发病（以下简称首发）精神分裂症患者前额叶、海马的磁共振质子波谱（^1H—MRS）变化特点。方法对21例青少年（13—17岁）首发精神分裂症患者（患者组）和20名（14～17岁）年龄、性别、受教育时间均匹配的正常对照者（对照组），应用^1H—MRS成像技术检测两组前额叶、海乌N-乙酰天门冬氨酸（NAA）、肌碱（Cho）、肌酸（Cr）3种代谢物，计算NAA／Cr和Cho／Cr比值。采用t检验进行分析。结果（1）患者组左侧前额叶NAA／Cr（1．56±0．81）低于对照组（2．09±0．81），右侧前额叶NAA／Cr（1．84±0．42）低于对照组（2．58±0．83），右侧前额叶Cho／Cr（1．25±0．17）也低于对照组（1．51±0．38），差异有统计学意义（P〈0．05和P〈0．01）。（2）患者组左侧海马NAA／Cr（1．33±0．34）低于对照组（1．64±0．56），差异有统计学意义（P〈0．05）。结论青少年首发精神分裂症患者存在双侧前额叶、左侧海弓神经元完整性和功能障碍，同时可能提示右侧前额叶神经厄能黾需要降低及神经胶质细胞的密度或功能完整性受损。     

Thalamic involvement in neurofibromatosis type 1: evaluation with proton magnetic resonance spectroscopic imaging

Neurofibromatosis type 1 is a common autosomal dominant disorder associated with learning disabilities. In addition to gliomas and other tumors, T2 hyperintense lesions (unidentified bright objects or UBOs) are frequently found in the globus pallidus, cerebellum, and white matter regions. To better characterize supratentorial UBO functional significance, we studied by quantitative magnetic resonance spectroscopic imaging (MRSI) 9 male subjects with neurofibromatosis type 1 (age, 6-19 years) and 9 age-matched and sex-matched controls. Maps of the anatomical distribution of the metabolites choline (Cho), N-acetylaspartate (NAA), and creatine were calculated in four axial 15-mm slices. Absolute metabolite concentrations within UBOs, unaffected globus pallidus, and thalami demonstrated an age-related pattern, characterized by elevated Cho and relatively preserved NAA in younger subjects (<10 years) and reduced NAA and normal Cho in older subjects. These changes were found in both UBOs and thalami but were only significant for NAA, NAA/creatine, and NAA/Cho in the latter region. Decreases in NAA ratios were most severe in the thalami of subjects with UBOs in the globus pallidus, whereas UBOs showed similar but milder abnormalities than those in the thalamus. We speculate that the MRSI metabolic abnormality may represent a more generalized phenomenon, without a T2 signal counterpart in the affected brain regions. Based on the neuropathological study by DiPaolo and colleagues (1995), we postulate that Cho elevations reflect increased myelin turnover in areas of intramyelinic edema, which is followed by neuropil injury (reduced NAA). Temporal progression and behavioral correlates of these MRSI changes deserve further exploration.     

Serial proton magnetic resonance spectroscopic imaging,contrast-enhanced magnetic resonance imaging,and quantitative lesion volumetry in multiple sclerosis

Serial magnetic resonnce (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast-enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N-acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI-defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.     

Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging

Pathologically defined abnormalities in the cortical gray matter (GM) are well described in multiple sclerosis (MS) but are infrequently seen by conventional magnetic resonance imaging (MRI). We systematically evaluated 52 relapsing-remitting MS patients and 20 normal volunteers with high resolution MRI and short echo proton magnetic resonance spectroscopic imaging (MRSI). Individual tissue contributions to the spectroscopic voxels were estimated based on MRI that incorporated both CSF suppression and magnetization transfer, or double inversion images in which both CSF and GM were suppressed. Strong resonances in the 0.8 to 1.5 p.p.m. spectral region were observed in 13 MS patients. Image segmentation based on the MRI characteristics of tissues contributing to the spectroscopic voxels showed that these additional peaks originated mainly from GM. The presence of these additional peaks suggests that the normal appearance GM on MRI, is biochemically abnormal in a substantial proportion of relapsing-remitting MS patients.     

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.     

Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease

OBJECTIVES—10 patientswith Niemann-Pick disease type C (NP-C) were studied by proton magneticresonance spectroscopic imaging (¹H-MRSI) to assess thebiochemical pathology of the brain and to determine whether this methodcan be useful to clinically evaluate these patients.
METHODS—¹H-MRSIpermits the simultaneous measurement of N-acetyl aspartate (NA),compounds containing choline (Cho), creatine plus phosphocreatine(Cre), and lactate (Lac) signal intensities from four 15 mm slicesdivided into 0.84 ml single volume elements. Spectroscopic voxels wereidentified from seven regions of interest.
RESULTS—In patientswith NP-C, NA/Cre was significantly decreased in the frontal andparietal cortices, centrum semiovale, and caudate nucleus; Cho/Cre wassignificantly increased in the frontal cortex and centrum semiovale.Significant correlations were found between clinical staging scalescores and ¹H-MRSI abnormalities.
CONCLUSION—¹H-MRSIshowed diffuse brain involvement in patients with NP-C consistent withthe pathological features of the disease. ¹H-MRSI is anobjective and sensitive tool to neurologically evaluate patients withNP-C.

     

Proton magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy

Proton magnetic resonance spectroscopic imaging (¹H MRSI) has demonstrated decreased N-acetyl compounds (NA) in the epileptogenic hippocampus in patients with temporal lobe epilepsy. We studied 8 patients with frontal lobe epilepsy and found mean NA/creatine (Cr) in the epileptogenic frontal lobe decreased by 27% compared with that of the contralateral homologous region (1.81 ±0.36 vs 2.49 ± 0.60, p < 0.008). In every patient, NA/Cr was decreased in the epileptogenic region by at least 5%. These findings suggest that ¹H MRSI may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.     

Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 ± 0.05 vs 7.00 ± 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 ± 6.0 vs 23.0 ± 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.     

难治性抑郁症患者海马代谢的磁共振质子波谱研究

目的 探讨难治性抑郁症患者双侧海马磁共振质子波谱(1H-MRS)的代谢特点.方法 运用1H-MRS成像系统检测16例难治性抑郁症患者(患者组)和16名健康对照者(对照组)双侧海马的N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)、肌醇(mI)及肌酸(Cr)4种代谢产物,分别计算双侧NAA/Cr、Cho/Cr及mI/Cr.采用配对t检验、独立样本t检验及偏相关分析进行统计处理.结果 对照组左侧海马NAA/Cr(1.43±0.19),明显高于右侧(1.21±0.10),P＜0.01.患者组双侧海马NAA/Cr的差异无统计学意义(P＞0.05),右侧海马NAA/Cr(1.44±0.31),明显高于对照组(1.21±0.10),P＜0.01.未发现患者组海马的任何代谢指标与病程及汉密尔顿抑郁量表(17项)评分的相关性(P＞0.05).结论 难治性抑郁症患者右侧海马代谢增强,双侧海马NAA/Cr不对称性消失.     

Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging

We used spin-echo magnetic resonance imaging and prton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed signficant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolities, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate–choline ration) and creatine-containing metabolities (N-acetylaspartate–creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate–choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline–N-acetylaspartate ratios with the N-acetylaspartate–creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.