11C-匹兹堡复合物B正电子发射断层摄影术脑显像在阿尔茨海默病早期诊断中的临床应用

目的 探讨N-甲基[11C]2-(4'-甲基氨基苯基-6-羟基苯并噻唑){N-methyl[11C]2-(4'-methylaminophenyl-6-Hydroxybenzathiazole),11C-PIB}PET脑显像在阿尔茨海默病(AD)早期诊断中的价值.方法 分别对6例AD患者、7例轻度认知功能障碍(MCI)患者及6名智能正常的老年对照者(NC)进行临床诊断、资料收集及11C-PIB PET脑显像,并对5、25和45 min PET图像进行分析.结果 视觉分析:AD患者3个时段放射性清除情况与NC组有明显不同,药物注射45 min后脑内放射性清除较NC组明显减低;MCI组图像呈不均一改变,与AD、NC组均有重叠.统计分析:3组受试者各脑区与小脑45 min标准吸收值(SUV)比值示:AD组顶叶、额叶、颞叶、枕叶及海马比值分别为1.91±0.21、2.09±0.41、1.92±0.35、1.66±0.41、1.55±0.28,高于NC组的1.48±0.53、1.57±0.64、1.36±0.53、1.27±0.40、1.17±0.33,差异具有统计学意义(t值分别为8.114、5.620、5.705、3.650、2.866,P值分别为0.0001、0.0002、0.0002、0.0045和0.0170),MCI组顶叶、额叶、颞叶、枕叶及海马的比值分别为1.48±0.53、1.57±0.64、l_36±0.53、1.27±0.40、1.17±0.33,均高于相应NC组,但差异无统计学意义.结论 11C-PIB PET脑显像能够鉴别早期AD患者与Nc,并对MCI患者有一定预测价值.     

Relationship between attentional performance and corpus callosum morphometry in patients with Alzheimer's disease

There has been considerable interest in cognitive deficits associated with Alzheimer's disease (AD) and relationships between these impairments and specific cortical atrophies. Two previous studies [Neuropsychologia 28 (1990) 1197; Dementia 3 (1992) 350] have found that AD patients exhibit significant impairments in the attentional ID/ED set-shifting tasks of the CANTAB battery which involved attentional shifting abilities. But, at present, no study has examined the neural bases of these abilities in AD patients. In the present study, the relationship between performances on this attentional test and morphometry of the anterior and posterior corpus callosum is examined in AD patients in the mild to moderate stages of the disease (n=30, mean age=74.1+/-4.9 years, mean MMSE score=23.9+/-2.6). A control group is constituted (n=20, mean age=73.15+/-5.5 years) for comparison of cerebral measurements. The stepwise multiple regression analysis indicates that the relative contribution for the total callosal and the anterior CC areas of the simple discrimination subtest is significantly positive whereas for the posterior callosal areas the relative contribution of the more complex subtest is significantly positive. AD patients from the subgroup "low", who failed to do the nine subtests of the attentional set-shifting tasks, exhibit smaller callosal areas than control subjects. There is no significant difference for all callosal measurements between AD patients from the subgroup "high", who completely succeeded the test, and control subjects. Our findings suggest that the anterior corpus callosum would be related to attentional shifting abilities in AD patients. Moreover, these patients with probable AD seem heterogeneous for performances in the attentional test of the CANTAB and for callosal atrophies.     

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.     

Magnetic resonance and positron emission tomography changes during the clinical progression of Rasmussen encephalitis.

The authors describe serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies in a patient with pathologically confirmed Rasmussen Encephalitis (RE). Results of initial PET and MRI studies were normal. Subsequent studies showed involvement of the percentral and postcentral gyri and the putamen on PET, and the precentral and postcentral gyri on MRI. Coregistration of PET and MR images showed good correlation between the precentral and postcentral gyri involvement. However, subcortical involvement occurred earlier on PET than on MRI. The authors demonstrate the evolution of changes on PET and MR images in a patient with RE. Despite early pathologic confirmation of RE, there were no definite structural or functional imaging changes on PET or MRI until 3 years after symptom onset. These findings demonstrate the variability of imaging changes in RE, and the need to carefully correlate electro-physiologic and clinical findings to confirm the diagnosis of RE.     

Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using 15O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets

Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous ¹⁵O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq ¹⁵O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and −0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq ¹⁵O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion.     

Functional imaging with positron emission tomography in multiple system atrophy

Summary. Although the current guidelines for the clinical diagnosis of multiple system atrophy (MSA) do not require structural or functional brain imaging, investigations utilizing positron emission tomography (PET) have been helpful diagnostically in differentiating between MSA and primary autonomic failure; idiopathic Parkinson’s disease; and sporadic olivopontocerebellar atrophy. These investigations have demonstrated different patterns of cerebral glucose utilization and of nigrostriatal projection abnormalities among these disorders and between the cerebellar and parkinsonian forms of MSA. Most of the studies have focused upon patients with well-established disease and none have examined the utility of PET imaging in early stage patients with follow-up of clinical course and autopsy verification to ensure accuracy of diagnosis and to determine the sensitivity and specificity of PET techniques for diagnosis. Recent PET studies have revealed denervation of myocardial post-ganglionic sympathetic neurons in some MSA patients, indicating that this disorder can affect the peripheral autonomic as well as the central nervous system. Investigations utilizing ligands to quantify central nervous system dopaminergic and cholinergic terminals have begun to provide insight into the neurochemical disorders that may underlie two of the sleep disturbances common in MSA, rapid eye movement sleep behavior disorder and obstructive sleep apnea.     

Amyloid imaging in Alzheimer's disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography

Background Amyloid imaging provides in vivo detection of the fibrillar amyloid-β (Aβ) plaques of Alzheimer's disease (AD). The positron emission tomography (PET) ligand, Pittsburgh Compound-B (PiB-C11), is the most well studied amyloid imaging agent, but the short half-life of carbon-11 limits its clinical viability. Florbetapir-F18 recently demonstrated in vivo correlation with postmortem Aβ histopathology, but has not been directly compared with PiB-C11. Methods Fourteen cognitively normal adults and 12 AD patients underwent PiB-C11 and florbetapir-F18 PET scans within a 28-day period. Results Both ligands displayed highly significant group discrimination and correlation of regional uptake. Conclusion These data support the hypothesis that florbetapir-F18 provides comparable information with PiB-C11.     

Brain dopaminergic mechanisms in Parkinson's disease evaluated by positron emission tomography

Abstract– The meso-striatal dopamine neurons, essential for the automated control of movements, are primarily affected in patients with P.D. Direct study of the role of this pathway in states of disease has not been possible until recently and the application of PET for the in vivo investigation of dopaminergic mechanisms may serve to demonstrate the potential of the technique.
One basic idea has been to work out methods to investigate multiple aspects of dopaminergic function, i.e. presynaptic mechanisms such as re-uptake sites and synthesis of neurotransmitter as well as postsynaptic such as receptor properties. Furthermore, efforts have been made to evaluate dopamine degradating enzymes. Preclinical PET-investigations have regularly been performed in Rhesus monkeys and the hemiparkinsonian model produced by infusing MPTP into one internal carotid artery has been of great value to characterize new ¹¹C-labelled tracers. Today ¹¹C–(+)-nomifensine is used to give a measure of dopamine re-uptake sites, probably reflecting nerve terminals. ¹¹C-labelled L-dopa has now been introduced and can be expected to replace ¹⁸F-L-fluorodopa as a physiological tracer for precursor transport and transmitter synthesis. Several ligands are available for the quantitation of dopamine receptors – ¹¹C-N-methylspiperone and ¹¹C-raclopride have been used in our studies. ¹¹C-L-selegiline and its "inactive'D-form have been used in clinical PET-studies aimed to evaluate the enzyme MAO-B. A summary of in vivo information of dopaminergic mechanisms in P.D. obtained using the above-mentioned tracers and PET is presented.     

轻度认知功能障碍患者正电子发射计算机体层摄影术和神经心理学测定的初步研究

目的　探讨轻度认知功能障碍患者脑葡萄糖代谢与神经心理学特点及其相互关系。方法　采用正电子发射体层摄影术 (PET)、简易智能状态测定 (MMSE)、韦克斯勒记忆量表测定 (WMS)和总体衰退量表 (GDS)测定 10例轻度认知功能障碍 (MCI)患者和 10名健康志愿者 (HC)。结果 (1)MCI组MMSE[(2 4.6± 2 2 )分 ]、WMS[(6 9.4± 10 .4)分 ]分值低于HC组 [分别为 (2 8.9± 1.1)分和 (93.1± 9.0 )分 ;P〈0 .0 1];(2 )MCI组左侧眶回、右侧颞叶中回和右侧壳核的局部脑葡萄糖代谢率 (rCMRglc)较HC组低 (P〈0 .0 5～ 0 .0 1) ;(3)将年龄、受教育年限、MMSE、WMS与不同脑区用18F标记的脱氧葡萄糖放射性比值进行相关分析显示 ,与年龄呈负相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :眶回、左侧额上回、左侧额下回、颞叶中回、颞叶下回、左侧顶叶、左侧中央前回、右侧中央后回、左颞叶内侧皮质、左侧海马回、左侧海马旁回、右侧前扣带回、后扣带回、左侧杏仁核等。与文化程度呈正相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :左侧颞叶下回、中央前回、左侧中央后回等 ;而右侧壳核则呈负相关。与MMSE呈正相关 (P〈0 .0 5或P〈0 .0 1)的脑区有 :额下回、左侧颞叶上回、颞叶中回、颞叶下回、左侧顶叶、左侧中央前回、中央后回、颞叶内侧皮     

Functional imaging of vegetative state applying single photon emission tomography and positron emission tomography

Nuclear medicine techniques, such as single photon emission tomography (SPECT) and positron emission tomography (PET) have been applied in patients in a vegetative state to investigate brain function in a non-invasive manner. Parameters investigated include glucose metabolism, perfusion at rest, variations of regional perfusion after stimulation, and benzodiazepine receptor density. Compared to controls, patients in a vegetative state show a substantial reduction of glucose metabolism and perfusion. While patients post-anoxia exhibit a rather homogenous cortical reduction of glucose metabolism, patients after head trauma often show severe cortical and sub-cortical reductions at the site of primary trauma. To distinguish reduced glucose metabolism due to neuronal inactivation from neuronal loss, flumazenil-PET, an indicator of benzodiazepine receptor density, could add valuable information on the extent of brain damage. Activation studies focus on the evaluation of residual brain network, looking for processing in secondary projection fields. So far the predictive strength concerning possible recovery for the individual patient is limited, and PET and SPECT are not routine procedures in the assessment of patients in a vegetative state.     

Cerebral mapping of apraxia in Alzheimer's disease by positron emission tomography

The ability to mimic skilled movements or to pantomime them in response to spoken command was compared with psychometric performance and with regional glucose utilization as estimated by [18F]fluorodeoxyglucose positron emission tomography in 17 right-handed patients with Alzheimer's disease and 6 age-matched normal subjects. Apraxia scores, both on tests to command and to imitation, were significantly lower in the Alzheimer patients. Imitation scores correlated best with performance on tests of visual--spatial ability and with cortical metabolism in the right parietal lobe; command scores related most closely with the results of tests reflecting verbal proficiency and with cortical metabolism in the left inferior hemisphere, especially frontally. Apraxia to command and imitation may thus reflect neuronal dysfunction in distinct cerebral regions in patients with Alzheimer's disease.     

Contribution of positron emission tomography to functional neuroimaging in Alzheimer's disease

When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.     

2型糖尿病合并轻度认知损害的正电子发射计算机断层扫描研究

目的 探讨2型糖尿病(DM)合并轻度认知损害( MCI)患者脑葡萄糖代谢特点.方法 应用18-氟代脱氧葡萄糖(18F-FDG)正电子发射计算机断层扫描(PET),对7例单纯DM患者(DM组)、6例DM合并MCI患者(DM+ MCI组)及10名正常对照者(对照组)脑葡萄糖代谢进行检测;采用简易精神状态检查量表(MMSE)、画钟试验(CDT)及临床痴呆评定量表(CDR)测定患者认知功能.结果 (1)认知功能:DM+ MCI组的MMSE得分[(24.67±0.82)分]显著低于对照组[(29.20± 0.79)分]及DM组(29.14±1.21)分](P均＜0.01),CDR得分[(0.58±0.20)分]显著高于对照组[(0.10±0.21)分]及DM组[(0.14±0.24)分](P均＜0.01),CDT得分与对照组及DM组间差异无统计学意义.(2)18F-FDG PET检查:与对照组比较,DM组左顶叶平均标准化摄取值(SUV)半定量比值降低(1.03 ±0.07比1.16 ±0.09,P＜0.05),DM+ MCI组左额叶(1.02±0.16比1.15 ±0.08)、右额叶(0.90±0.07比1.10±0.06)、扣带回(0.92 ±0.06比1.17±0.08)、左顶叶(0.94±0.12比1.16±0.09)、右顶叶(0.93 ±0.10比1.11 ±0.06)、左颞顶后叶(0.96±0.11比1.17 ±0.01)、右颞顶后叶(0.90±0.09比1.15 ±0.06)的SUV半定量比值均降低(P＜0.01);与DM组比较,DM+ MCI组左额叶(1.02±0.16比1.15 ±0.11)、右额叶(0.90±0.07比1.06±0.18)、扣带回(0.92 ±0.06比1.16± 0.08)、右顶叶(0.93±0.10比1.10±0.12)、左颞顶后叶(0.96±0.11比1.14 ±0.14)、右颞顶后叶(0.90±0.09比1.18±0.17)的SUV半定量比值降低(P＜0.01或P＜0.05).结论 2型糖尿病合并MCI患者的双侧额叶、扣带回、顶叶、颞顶后叶等多个脑区葡萄糖代谢均降低.     

Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography

Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.     

Predicting diagnosis and cognition with 18F-AV-1451 tau PET and structural MRI in Alzheimer's disease

Introduction

The relative importance of structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) to predict diagnosis and cognition in Alzheimer's disease (AD) is unclear.

Noninvasive estimation of the arterial input function in positron emission tomography imaging of cerebral blood flow

Positron emission tomography (PET) with ¹⁵O-labeled water can provide reliable measurement of cerebral blood flow (CBF). Quantification of CBF requires knowledge of the arterial input function (AIF), which is usually provided by arterial blood sampling. However, arterial sampling is invasive. Moreover, the blood generally is sampled at the wrist, which does not perfectly represent the AIF of the brain, because of the effects of delay and dispersion. We developed and validated a new noninvasive method to obtain the AIF directly by PET imaging of the internal carotid artery in a region of interest (ROI) defined by coregistered high-resolution magnetic resonance angiography. An ROI centered at the petrous portion of the internal carotid artery was defined, and the AIF was estimated simultaneously with whole brain blood flow. The image-derived AIF (IDAIF) method was validated against conventional arterial sampling. The IDAIF generated highly reproducible CBF estimations, generally in good agreement with the conventional technique.     

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease

BackgroundThe utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in Alzheimer’s disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG-PET.MethodsWe used a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched control subjects. Paired FDG-PET and ASL-MRI images from 19 control subjects and 15 AD patients were included for qualitative analysis, and paired images from 18 control subjects and 13 AD patients were suitable for quantitative analyses.ResultsThe combined imaging protocol was well tolerated. Both modalities revealed similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD after visual review by two expert readers. Interobserver agreement was better for FDG-PET (κ: 0.75, standard error: 0.12) than ASL-MRI (κ: 0.51, standard error: 0.15); intermodality agreement was moderate to strong (κ: 0.45–0.61); and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral fluorodeoxyglucose uptake (FDG-PET) or whole-brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under receiver operating characteristic curves of 0.90 for FDG-PET (95% confidence interval: 0.79–0.99) and 0.91 for ASL-MRI (95% confidence interval: 0.80–1.00).ConclusionsOur results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.     

Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18

At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC). We evaluated the effect of the different count normalization procedures on the accuracy of (18)F-FDG PET to detect AD-specific metabolic abnormalities (voxel-based group comparison) and to differentiate between patients and healthy subjects (ROI-based discriminant analysis) with regard to the degree of clinical deterioration. Metabolic reductions in groups of very mildly, mildly and moderate-to-severely affected patients appeared, respectively, 2.2, 2.6, and 2.7 times greater in spatial extent when tracer uptake was normalized to SMC rather than to CGM. The overall accuracy of discrimination was 94%, 91%, and 80% after normalization to SMC, CBL, and CGM, respectively. In general, normalization to SMC was somewhat superior to cerebellar normalization, allowing the detection of more pronounced metabolic deficits and the more accurate discrimination of patients from non-patients. Normalization to CGM should be used with great caution not only in advanced stages of dementia, but also in very mild AD cases.