PET和TCD对阿耳茨海默病早期诊断的研究

目的 利用正电子发射计算机断层扫描（ｐｏｓｉｔｒｏｎ ｅｍｉｓｓｉｏｎ ｔｏｍｏｇｒａｐｈｙ,ＰＥＴ）和经颅多普勒超声（ｔｒａｎｓｃｒａｎｉａｌ ｄｏｐｐｌｅｒ,ＴＣＤ）相结合的方法探讨阿耳茨海默病（Ａｌｚｈｅｉｍｅｒ’ｓ ｄｉｓｅａｓｅ,ＡＤ）的早期诊断,以及ＡＤ与脑血液供应之间的关系。方法 ２０例可疑ＡＤ患者和２０例正常对照行ＰＥＴ、ＴＣＤ以及临床神经心理量表检查,对局部脑区葡萄糖代谢率（ｒｅ     

Amyloid imaging in Alzheimer's disease

Alzheimer's disease (AD) is a complex neurodegenerative disorder of which the exact cause is still not known. There has, however, been remarkable progress in the understanding of the pathophysiological events that underlie the disease with a focus on amyloid formation. We do not know yet if amyloid is the most crucial target for an effective therapy in AD. The new amyloid PET imaging tracer ligands offer possibilities for measuring fibrillar beta amyloid (Abeta) in the brain and for studying the time course of amyloid in the brain. This opens up new possibilities for early diagnosis as well as new tools for monitoring anti-amyloid therapy in AD.     

阿尔茨海默病^18F-AV45 PET脑显像的操作技术和临床应用

^18F-florbetapir(AV45)正电子发射断层成像(PET)脑显像作为阿尔茨海默病早期诊断的一类无创性影像学手段,目前在国内已经逐渐被认可。规范的检查流程、检查技术、图像解读及报告书写将有助于获得高质量的图像和准确的定量分析数据。因此,在参考国内外相关指南并结合国内现状及实际操作经验的基础上,我们介绍了^18F-AV45 PET脑显像的操作技术和临床应用的相关内容,以更好地促进国内^18F-AV45 PET脑显像检查的规范开展和临床应用研究的推广,为患者提供准确的影像诊断服务。     

Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET study

Weight loss is a common problem in patients with Alzheimer's disease (AD) and this might be associated with an increased risk for mortality. Recent evidences have suggested that certain brain dysfunctions may result in impaired nutritional status in AD patients. However, the mechanism of body weight loss in AD remains enigmatic. To investigate a possible association between low body weight and regional brain dysfunction, the authors conducted the correlational analysis of body mass index (BMI) with regional brain glucose metabolism using positron emission tomography (PET) and [¹⁸F]fluorodeoxyglucose (FDG). Twenty-seven patients with probable AD were divided into two groups: the low BMI group and the normal BMI group. Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region. Comparisons were made of regional brain metabolic ratios between the low BMI group and the normal BMI group. Correlations of the glucose metabolic ratio with BMI were also assessed in all patients with AD. In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group, whereas no significant differences were found in all the other brain regions. Furthermore, regional glucose metabolism in the ACC had a significant and positive correlation with BMI (r=.450, P=.018). After adjustment for age, gender and disease duration, regional glucose metabolism in the ACC was independently associated with BMI. Our findings suggest that the ACC may be preferentially involved in the regulation of nutritional status in AD patients, and provides a new insight into developing strategies for prevention and treatment of undernutritional demented patients.     

The cerebral localization of neuropsychological impairment in Alzheimer's disease: a SPECT study

Summary Twenty-three patients with a clinical diagnosis of Alzheimer's disease were examined with a set of neuropsychological tests and with ^99mTc-hexamethyl-propyleneamineoxime (HMPAO) single photon emission computed tomography (SPECT). Correlations between test results and indices of regional HMPAO distribution were analysed by multidimensional scaling (MDS). Test results covaried positively with relative HMPAO uptake of frontal, inferior parietal and superior temporal regions but not, or in a negative way, with the remainder of the regions. When only positive correlations were analysed, MDS suggested two dimensions of organization: one was related to a dichotomy between frontal and temporo-parietal regions. The relationship of test results to this dimension was largely consistent with common neuropsychological knowledge. A second, less stringent dimension of organization opposed right and left hemisphere regions. The ordering of test results with respect to this dimension was only partly consistent with what is known about the lateralization of neuropsychological deficits from the study of localized brain lesions. The possibility is considered that these inconsistencies may reflect the effect of disproportionally severe involvement of extended cortical systems which modulates the sequels of localized brain damage.     

Sleep and quantitative EEG in neurodegenerative disorders

This paper reviews current knowledge on sleep problems, sleep architecture changes and quantitative EEG alteration brought on by various neurodegenerative diseases, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), REM sleep behavior disorder (RBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy MSA, Huntington's disease and Creutzfeldt-Jakob disease, in comparison to normal aging. The study of sleep variables and that of the spectral composition of the EEG can provide valuable information for understanding the pathophysiology and for assisting the diagnosis of neurodegenerative diseases.     

EEG changes during long-term treatment with donepezil in Alzheimer's disease patients

Summary. In this pilot study, we examined the long-term treatment effect of donepezil on the quantitative EEG (qEEG) in 12 Alzheimer's disease patients. The qEEGs of the mean absolute and relative amplitudes of betal, alpha, theta and delta activities were obtained at baseline and during donepezil treatment. Comparisons of awake qEEG prior to and during treatment were performed using a 2-way analysis of variance (ANOVA) with repeated measures. In patients with mild dementia (n = 5), the qEEG analysis showed a significant reduction of the mean absolute theta activity (p = 0.05) by donepezil, particularly in frontal and temporo-parietal areas. In patients with moderate/severe dementia (n = 7), a significant decrease in the mean absolute beta 1 activity (p = 0.02), particularly in the frontal and occipital areas may be attributed to disease progression which was not counteracted by the long-term treatment. The differences in qEEG in patients with different stages of dementia under donepezil treatment may be related to different compensatory capacities due to structural and functional brain disturbances. Received January 27, 2001; accepted June 8, 2001     

Quantitative EEG changes in non-demented Parkinson's disease patients before and during L-dopa therapy

Nineteen non-demented Parkinson's disease patients have been studied before and during L-dopa therapy by quantitative EEG performed at rest with eyes closed (EC) and during attentive (BR) and cognitive (FIX) tasks. The data have been compared by ANOVA analysis with those of 22 age-matched healthy subjects. In all three conditions a significant increase of the mean δ power as well as a decrease of β1 power was observed in patients before therapy. Abnormal high δ values were observed in 10 out of 19 patients. L-Dopa therapy did not modify this EEG pattern. After therapy, however, a significant decrease of reactivity to BR and FIX was observed in patients compared to normal subjects. These data confirmed the presence of an EEG synchronization (increase of slow activity and decrease of fast activity) in non-demented Parkinson's disease patients. This pattern, similar to that of subjects with Alzheimer-type dementia, might indicate an intellectual impairment at sub-clinical level. A non-dopaminergic mechanism could be responsible for this impairment     

Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease

Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response.     

Sequential PET studies in neuro-behcet's syndrome

Summary A case of neuro-Behcet's syndrome is presented with sequential positron emission tomography (PET) studies. Regional cerebral blood flow (rCBF) and oxygen consumption (rCMRO₂) were decreased in the brain lesion; however, on follow-up studies 3 months after steroid therapy rCBF and rCMRO₂ had increased in the lesion, which demonstrated the reversibility of this disease. Such monitored improvement may accurately reflect the early stage of the disease and its response to steroid therapy.     

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease.

BACKGROUND: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns. OBJECTIVE: The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism. METHODS: We investigated healthy control subjects and patients with varying degrees of cognitive dysfunction and varying GluM patterns by applying [18F]FDG PET and EEG. RESULTS: We demonstrated that the localization of intracerebral generators of EEG correlates with spatial indices of GluM. CONCLUSION: These results indicates that EEG provides similar spatial information about brain function as GluM-PET. Since EEG is a non-invasive technique, which is more widely available and can be repeated more often than PET, this may have important implications both for neuropsychiatric research and for clinical diagnosis. However, further studies are required to determine whether equivalent EEG dipole generators can yield a diagnostic specificity and sensitivity similar to that of GluM-PET.     

Diagnosing Alzheimer's disease in elderly,mildly demented patients: the impact of routine single photon emission computed tomography

Based on the observation of bilateral temporoparietal hypoperfusion in Alzheimer's disease (AD), single photon emission computed tomography (SPECT) is advocated by some as a powerful diagnostic tool in the evaluation of demented patients. We studied whether routine brain SPECT in elderly, mildly demented outpatients increases the a priori diagnostic sensitivity and specificity of a careful clinical examination.^99mTc-HMPAO SPECT imaging was performed in 110 patients for a first evaluation for dementia. A semiquantitative measure of temporoparietal (TP) perfusion was calculated as the ratio of the activity in the temporoparietal cortex to activity in the cerebellum. A diagnosis of probable AD according to the McKhann criteria was made in 68 patients (mean age of 79.3 years) based on the results of a clinical examination, ancillary investigations and a 6-month follow-up. TP perfusion was significantly lower in AD patients than in 18 age-matched, non-demented controls. However, at a specificity of 89%, sensitivity was only 43% for detecting probable AD. The clinicians judged that SPECT had contributed to the final diagnosis in only 8% of the demented patients investigated. Routine brain SPECT in elderly, mildly demented outpatients does not contribute substantially to diagnostic accuracy after a careful clinical examination using current diagnostic criteria. Clinical guidelines have to be developed for the use of SPECT in patients with (suspected) dementia.     

PET与发作间期癫痫灶定位

我们用￣~(１８)Ｆ－ＦＤＧ－ＰＢＴ显像对１２６例癫痫患者进行了发作间期癫痫灶定位，男８１例，女４５例，年龄２～５６岁，其中１１０例（８７．３％）在ＰＥＴ上可发现明显相对低代谢区，而ＭＲＩ或ＣＴ仅３２例发现异常，头皮ＥＥＧ有１０２例异常，但无明确定位价值。我们认为，￣１８Ｆ－ＦＤＧ－ＰＥＴ可通过观察脑组织内的葡萄糖代谢而进行癫痫灶定位，是无创伤性癫痫灶定位的最佳方法。     

Disease-related and drug-induced changes in dopamine transporter expression might undermine the reliability of imaging studies of disease progression in Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder. Standard therapeutic interventions are aimed at replenishment of empty dopamine stores with levodopa or substitution with dopamine receptor agonists. However, in the long term this symptomatic therapy fails. Currently, various neuroprotective agents are being developed, with the intention to slow down the degeneration of dopaminergic neurons. In this context, the early identification of persons at risk to develop the disease as well as the assessment of the effectiveness of putative neuroprotective agents, are critical issues. Dopamine transporter (DAT) scintigraphy with single photon emission computed tomography (SPECT) has been used to assess the dopaminergic function in PD. Initial studies with several radioligands show significant loss of DAT binding in PD patients as compared to controls. In this paper we review the evidence on the utility of DAT imaging with SPECT in early PD detection as well as in monitoring neurprotection.     

PET对癫痫致痫区定位的研究进展

正电子发射型计算机断层显像（Positron Emission Computed Tomography ,PET ）是一种探测放射性示踪剂在体内分布及动态变化情况的显像技术,在神经功能影像学检查方法中,PET 目前被认为是癫痫外科术前评估的最佳无创性功能性影像检查方法［1］。 PET 利用不同种类的示踪剂,来探究脑组织葡萄糖代谢、氧代谢、脑血流灌注、神经受体分布、生化和蛋白合成等方面的变化,尤其对于结构影像学检查阴性的癫痫患者有很大的定位诊断价值［2－3］。     

Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer''s disease

Patterns of cerebral metabolic correlations were compared between 21 Alzheimer's disease patients and 21 healthy age-matched controls in the resting state. Cerebral metabolic rates for glucose were determined by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. Partial correlation coefficients, controlling for whole brain glucose metabolism, were evaluated between pairs of regional glucose metabolic rates in 59 brain regions. Reliable correlation coefficients were obtained with the 'jackknife' and 'bootstrap' statistical procedures. Compared with healthy controls, the Alzheimer patients had significantly fewer reliable partial correlation coefficients between frontal and parietal lobe regions, and more reliable correlations between the cerebellum and temporal lobe. The number of reliable correlations between many bilaterally symmetric brain regions was reduced in the Alzheimer patients, as compared with controls. These results suggest that in the early stages of Alzheimer's disease there is a breakdown of the organized functional activity between the two cerebral hemispheres, and between parietal and frontal lobe structures.     

Quantitative EEG asymmetry correlates with clinical severity in unilateral Sturge-Weber syndrome

PURPOSE: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder with vascular malformations of the skin, brain, and eye. SWS results in ischemic brain injury, seizures, and neurologic deficits. We hypothesized that a decrease in quantitative EEG (qEEG) power, on the affected side, correlates with clinical severity in subjects with SWS. METHODS: Fourteen subjects had 16-channel scalp EEG recordings. Data were analyzed using fast Fourier transform and calculation of power asymmetry. Blinded investigators assigned scores for clinical neurological status and qualitative assessment of MRI and EEG asymmetry. RESULTS: The majority of subjects demonstrated lower total power on the affected side, usually involving all four frequency bands (delta, theta, alpha, and beta). qEEG asymmetry correlated strongly with neurologic clinical severity scores and MRI asymmetry scores. qEEG data generally agreed with the MRI evidence of regional brain involvement. In MRI-qEEG comparisons that did not agree, decreased power on qEEG in a brain region not affected on MRI was more likely to occur in subjects with more severe neurologic deficits. CONCLUSIONS: qEEG provides an objective measure of EEG asymmetry that correlates with clinical status and brain asymmetry seen on MRI. These findings support the conclusion that qEEG reflects the degree and extent of brain involvement and dysfunction in SWS. qEEG may potentially be a useful tool for early diagnosis and monitoring of disease progression in SWS. qEEG may prove useful, in severely affected individuals with SWS, for determining regions of brain dysfunction.     

正电子断层显像技术在阿尔茨海默病中的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是老年人最常见的痴呆类型,为一种进行性神经系统变性疾病[1].其主要神经病理学特征包括神经元纤维缠结(neurofibrillary tangles,NET)、老年斑(senile plaque,Sp)的出现及神经元的减少.迄今为止,AD病因不明,缺乏客观的诊断及有效治疗方法.当AD患者出现临床症状时,往往已处于临床中期阶段,即中度AD,此时治疗效果较差,且很难逆转病情的进展,因此研究者们都在努力寻找早期诊断标记物及疾病修复疗法,结果发现正电子断层显像(PET)技术有望成为实现这个目标的重要手段.研究表明,PET技术可以被用于研究脑代谢变化、各种神经递质系统、炎症过程及蛋白质聚合物(尤其是淀粉样蛋白沉积物)[2].PET利用11C标记的匹兹堡复合物B(11C- PIB)和18F脱氧葡萄糖(18F- FDG)在体显像,可以了解脑内Aβ蛋白分布及葡萄糖代谢情况[3].本文将近年来PET影像技术在AD基础及临床方面的研究情况作一综述.     

18F-FCWAY and 18F-FDG PET in MRI-negative temporal lobe epilepsy

Background: Positron emission tomography (PET) with ¹⁸F‐fluorodeoxyglucose (FDG) shows widespread hypometabolism even in temporal lobe epilepsy (TLE) patients with mesial temporal foci. ¹⁸F‐trans‐4‐fluoro‐N‐2‐[4‐(2‐methoxyphenyl) piperazin‐1‐yl]ethyl‐N‐(2‐pyridyl)cyclohexane carboxamide (¹⁸F‐FCWAY) PET may show more specific 5‐HT_1A‐receptor binding reduction in seizure initiation than in propagation regions. ¹⁸FCWAY PET might be valuable for detecting epileptic foci, and distinguishing mesial from lateral temporal foci in MRI‐negative patients with TLE. Methods: We performed ¹⁸F‐FCWAY‐PET and ¹⁸F‐FDG‐PET in 12 MRI‐negative TLE patients who had had either surgery or subdural electrode recording, and 15 healthy volunteers. After partial volume correction for brain atrophy, free fraction‐corrected volume of distribution (V/f1) measurement and asymmetry indices (AIs) were computed. We compared ¹⁸F‐FCWAY‐PET and ¹⁸F‐FDG‐PET results with scalp video electroencephalography (EEG), invasive EEG, and surgical outcome. Results: Mean ¹⁸F‐FCWAY V/f1, compared with normal controls, was decreased significantly in fusiform gyrus, hippocampus, and parahippocampus ipsilateral to epileptic foci, and AIs were significantly greater in hippocampus, parahippocampus, fusiform gyrus, amygdala, and inferior temporal regions. Eleven patients had clearly lateralized epileptogenic zones. Nine had congruent, and two nonlateralized, ¹⁸F‐FCWAY PET. One patient with bitemporal seizure onset had nonlateralized ¹⁸F‐FCWAY‐PET. ¹⁸F‐FDG‐PET showed congruent hypometabolism in 7 of 11 EEG‐lateralized patients, bilateral hypometabolic regions in one, contralateral hypometabolism in one, as well as lateralized hypometabolism in the patient with bitemporal subdural seizure onset. Patients with mesial temporal foci tended to have lower superior and midtemporal ¹⁸F‐FCWAY V/f1 binding AI than those with lateral or diffuse foci. Conclusion: ¹⁸F‐FCWAY‐PET can detect reduced binding in patients with normal MRI, and may be more accurate than ¹⁸F‐FDG‐PET.