脑内阿片受体PET成像及其在痛与镇痛研究中的应用

脑内阿片受体在痛与镇痛中的作用机制一直是神经科学领域研究热点之一。正电子发射体层扫描(positron emission tomography,PET)是目前在体定量检测脑内相关分子参与神经信号转导的唯一途径。本文在简要回顾阿片受体和内源性阿片肽的发现、生理功能及其脑内分布的基础上,对已应用或有望应用于人体的阿片受体选择性和非选择性示踪剂及其在PET成像中的应用进行介绍,并对阿片成像结果所反映的神经机制进行解读。鉴于脑内阿片受体在介导痛与镇痛中的重要作用,文中着重就近年来有关痛与镇痛的脑内阿片受体PET成像研究进展予以综述。     

PET/CT影像技术在神经退行性疾病动物模型研究中的应用

PET和CT影像技术是肿瘤、痴呆症、心脑血管病等的重要临床诊断技术,近年发展的小动物PET/CT成为对人类疾病动物模型,尤其是小动物模型进行比较医学研究的最新工具,能够活体无创的、动态的、定量的从分子水平观察动物的生理生化变化,进行代谢显像、受体显像、基因表达显像等。已经广泛应用于对神经退行性疾病的研究中.本文介绍了近年来一些小动物PET/CT在退行性疾病的研究中的最新应用。     

增强CT和18F-FDG PET/CT在胃癌术前分期评估中的临床价值比较

目的:对比评估增强计算机断层扫描(contrast enhancement computed tomography,CECT)和~(18)F-FDG正电子发射计算机断层扫描(positron emission tomography/computed tomography,PET/CT)在胃癌术前分期中的临床应用价值。方法:回顾性分析经病理证实的胃癌患者的术前CECT(27例)及~(18)F-FDG PET/CT(39例)图像,于两种影像学手段下,双盲法判定每位患者胃癌的TNM分期,然后分别计算每种影像学方法在胃癌术前分期中的敏感性、特异性、阳性预测值、阴性预测值和准确性。两种影像学方法的差异比较采用Pearson卡方检验。结果:CECT和~(18)F-FDG PET/CT诊断胃癌T分期的敏感性、阳性预测值和准确性分别是100.00%、72.73%、59.26%和100.00%、90.91%、76.92%;CECT和~(18)F-FDG PET/CT诊断胃癌N分期的敏感性、特异性、阳性预测值、阴性预测值和准确性分别是75.00%、71.43%、88.24%、50.00%、74.07%和42.86%、92.00%、75.00%、74.19%、35.90%。结论:CECT和~(18)F-FDG PET/CT均可用于胃癌术前分期的预估,尤其在N分期方面,CECT的敏感性和准确性高于~(18)F-FDG PET/CT。     

多巴胺神经系统显像分子探针研究

多巴胺神经系统在神经退行性疾病和精神紊乱中充当了主要角色,比如帕金森病、亨廷顿病、迟发性运动障碍、精神分裂症。以多巴胺能神经系统为靶点的PET显像可以了解多巴胺合成、受体密度和状态改变,为神经系统疾病的早期诊断、疗效监测、发病机制以及脑认知功能的研究等方面提供客观、科学的观察手段。本文综述了以多巴胺受体、多巴胺转运体及囊泡单胺转运体为靶点的PET显像剂的研究进展。     

不同放射剂量CT在早期非小细胞肺癌中筛检价值对比

摘要 目的：探讨与对比不同放射剂量计算机断层扫描(Computed Tomography,CT)在早期非小细胞肺癌中筛检价值。方法：2020年1月到2020年12月选择在本院经病理确诊为肺内磨玻璃样结节患者98例作为研究对象,所有患者都给予常规剂量正电子发射计算机断层扫描(Positron emission tomography,PET)/CT检查与低剂量PET/CT检查,记录成像特征、辐射剂量并判定筛检价值。结果：低剂量PET/CT对肺部增厚、边界不规则、钙化、囊变的检出率高于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT的图像质量优良率为98.0 %和96.9 %,对比差异无统计学意义(P>0.05)。低剂量PET/CT的有效放射剂量、剂量长度乘积低于常规剂量PET/CT(P<0.05)。低剂量PET/CT的最大标准摄取值(maximum standardized uptake value,SUVmax)值低于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT分别筛检非小细胞肺癌51例与37例,筛检敏感性分别为98.1 %和69.2 %,特异性分别为100.0 %和97.8 %。结论：低放射剂量PET/CT在肺结节中的应用不会影响图像质量,且能降低辐射剂量,提高对早期非小细胞肺癌患者的筛检效果。     

18F-FDG PET 和治疗量131I 全身扫描对分化型甲 状腺癌根治术后转移灶检测的临床价值评估

目的:探讨18F-FDG PET显像和131I-全身扫描(131I-WBS)SPECT显像对分化型甲状腺癌(DTC)术后转移灶的临床诊断价值。方法:对57例外科术后拟行131I治疗的DTC患者行18F-FDG PET全身显像和131I-WBS扫描,观察和记录在糖代谢和碘代谢中DTC转移灶的定位及数量变化,并同时测定甲状腺球蛋白(Tg),促甲状腺激素释放激素(TSH)等实验室检查项目。结果:57例DTC患者18F-FDG PET显像发现真阳性20例、假阳性3例、真阴性31例、假阴性3例,其灵敏度为87.0%,特异性为91.2%。而131I-WBS扫描发现真阳性13例、假阳性2例、真阴性34例、假阴性8例,其灵敏度为61.9%,特异性为94.4%。PET显像和131I-WBS扫描共检出阳性病灶73个,其中淋巴结32个,肺5个,纵隔6个,骨26个,其他部位4个。PET显像发现43个阳性病灶(58.9%),而131I-WBS检出30个(41.1%)。当Tg水平>10μg/L时,随着Tg在血清含量的增高,两种显像方法的对DTC转移灶的阳性检出率亦随之升高。结论:两种检查对DTC术后转移灶的监测和131I的治疗具有良好的互补性,18F-FDG PET显像在Tg阳性和131I-WBS阴性的患者的转移灶检出上更具有优势,有重要的临床指导意义。     

18F-FDG PET和治疗量131I全身扫描对分化型甲状腺癌根治术后转移灶检测的临床价值评估

目的：探讨18F-FDG PET显像和131I-全身扫描（131I-WBS）SPECT显像对分化型甲状腺癌（DTC）术后转移灶的临床诊断价值。方法：对57例外科术后拟行131I治疗的DTC患者行18F-FDG PET全身显像和131I-WBS扫描,观察和记录在糖代谢和碘代谢中DTC转移灶的定位及数量变化,并同时测定甲状腺球蛋白（Tg）,促甲状腺激素释放激素（TSH）等实验室检查项目。结果：57例DTC患者18F-FDG PET显像发现真阳性20例、假阳性3例、真阴性31例、假阴性3例,其灵敏度为87.0%,特异性为91.2%。而131I-WBS扫描发现真阳性13例、假阳性2例、真阴性34例、假阴性8例,其灵敏度为61.9%,特异性为94.4%。PET显像和131I-WBS扫描共检出阳性病灶73个,其中淋巴结32个,肺5个,纵隔6个,骨26个,其他部位4个。PET显像发现43个阳性病灶（58.9%）,而131I-WBS检出30个（41.1%）。当Tg水平〉10μg/L时,随着Tg在血清含量的增高,两种显像方法的对DTC转移灶的阳性检出率亦随之升高。结论：两种检查对DTC术后转移灶的监测和131I的治疗具有良好的互补性,18F-FDG PET显像在Tg阳性和131I-WBS阴性的患者的转移灶检出上更具有优势,有重要的临床指导意义。     

美研制出新成像技术帮助检测癌症

美国宾夕法尼亚大学研究人员最近将计算机轴向断层扫描技术（CAT）和正电子发射断层显像技术（PET）相结合,研制出了一种新的成像技术,采用新技术可以更准确地检测癌症等疾病。     

X线、CT、SPECT、PET在评估小鼠的骨成像中的作用

目的利用各种影像诊断设备对正常小鼠的骨进行成像,观察其在小鼠骨成像中最佳成像参数。方法分别使用X线、CT、SPECT、PET对小鼠的骨进行拍摄成像。结果X线和CT均可以清楚地对小鼠的骨组织成像,而SPECT、PET由于其分辨率和特异性不高,成像较模糊。结论X线和CT检查对小鼠的骨成像明显,对小鼠疾病的观察有重要意义。而SPECT、PET对诊断小鼠的骨疾病意义不是很大。     

努力开发氨基酸在饲料工业中的应用

<正> 氨基酸是构成生物体蛋白质并同生命活动有关的最基本的物质,它在机体内具有特殊的生理功能,是生物体不可缺少的营养成份之一,对促进动物的生长发育起着重要的作用,对于开发氨基酸在饲料工业中的应用,促进我国畜牧业的发展有着十分重要的意义。     

Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men

Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAO A)—an enzyme metabolizing neurotransmitters—revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAO A levels (using PET and [¹¹C]clorgyline, a radiotracer with specificity for MAO A) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAO A activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAO A levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior.     

Poisson Noise Obscures Hypometabolic Lesions in PET

The technology of fluoro-deoxyglucose positron emission tomography (PET) has drastically increased our ability to visualize the metabolic process of numerous neurological diseases. The relationship between the methodological noise sources inherent to PET technology and the resulting noise in the reconstructed image is complex. In this study, we use Monte Carlo simulations to examine the effect of Poisson noise in the PET signal on the noise in reconstructed space for two pervasive reconstruction algorithms: the historical filtered back-projection (FBP) and the more modern expectation maximization (EM). We confirm previous observations that the image reconstructed with the FBP biases all intensity values toward the mean, likely due to spatial spreading of high intensity voxels. However, we demonstrate that in both algorithms the variance from high intensity voxels spreads to low intensity voxels and obliterates their signal to noise ratio. This finding has profound impacts on the clinical interpretation of hypometabolic lesions. Our results suggest that PET is relatively insensitive when it comes to detecting and quantifying changes in hypometabolic tissue. Further, the images reconstructed with EM visually match the original images more closely, but more detailed analysis reveals as much as a 40 percent decrease in the signal to noise ratio for high intensity voxels relative to the FBP. This suggests that even though the apparent spatial resolution of EM outperforms FBP, the signal to noise ratio of the intensity of each voxel may be higher in the FBP. Therefore, EM may be most appropriate for manual visualization of pathology, but FBP should be used when analyzing quantitative markers of the PET signal. This suggestion that different reconstruction algorithms should be used for quantification versus visualization represents a major paradigm shift in the analysis and interpretation of PET images.     

Neuropathological correlates of amyloid PET imaging in Down syndrome

Down syndrome (DS) results in an overproduction of amyloid‐β (Aβ) peptide associated with early onset of Alzheimer's disease (AD). DS cases have Aβ deposits detectable histologically as young as 12–30 years of age, primarily in the form of diffuse plaques, the type of early amyloid pathology also seen at pre‐clinical (i.e., pathological aging) and prodromal stages of sporadic late onset AD. In DS subjects aged >40 years, levels of cortical Aβ deposition are similar to those observed in late onset AD and in addition to diffuse plaques involve cored plaques associated with dystrophic neurites (neuritic plaques), which are of neuropathological diagnostic significance in AD. The purpose of this review is to summarize and discuss findings from amyloid PET imaging studies of DS in reference to postmortem amyloid‐based neuropathology. PET neuroimaging applied to subjects with DS has the potential to (a) track the natural progression of brain pathology, including the earliest stages of amyloid accumulation, and (b) determine whether amyloid PET biomarkers predict the onset of dementia. In addition, the question that is still incompletely understood and relevant to both applications is the ability of amyloid PET to detect Aβ deposits in their earliest form.     

Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner

Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate chair was constructed out of styrofoam and fixed to the head portion of the bed of a PET scanner. A lightly anaesthetised rhesus monkey was positioned in the chair in a sitting position and injected with the radiotracer. The styrofoam chair provided sufficient support for the monkey. The presence of the chair in the PET scanner caused negligible attenuation of radiation, allowing simultaneous acquisition of dynamic data from the subject's brain and heart. We conclude that a styrofoam primate chair is an ideal tool to measure blood and brain data from a rhesus monkey with PET. Invasiveness to the animal is reduced, as well as experimenter time.     

多方式认知功能成像研究进展

对大脑结构和功能的深入研究要求认知功能成像技术同时具有高时间分辨率和高空间分辨率.多方式认知功能成像通过不同成像技术fMRI/PET和EEG/MEG的结合,能够同时在空间定位和时间过程上研究大脑认知活动的动态过程.多方式认知功能成像已经被成功地应用于选择性注意、视觉通路、随意运动和语义加工等的研究,并揭示了相关大脑活动的空间和时间特征.今后的研究将进一步提高多方式认知功能成像的时空分辨率和准确性,以更深入地探索认知功能的神经机制.     

Impairment of nigrostriatal dopamine neurotransmission by manganese is mediated by pre-synaptic mechanism(s): implications to manganese-induced parkinsonism

The long-term consequences of chronic manganese (Mn) exposure on neurological health is a topic of great concern to occupationally-exposed workers and in populations exposed to moderate levels of Mn. We have performed a comprehensive assessment of Mn effects on dopamine (DA) synapse markers using positron emission tomography (PET) in the non-human primate brain. Young male Cynomolgus macaques were given weekly i.v. injections of 3.3-5.0 mg Mn/kg (n = 4), 5.0-6.7 mg Mn/kg (n = 5), or 8.3-10.0 mg Mn/kg (n = 3) for 7-59 weeks and received PET studies of various DA synapse markers before (baseline) and at one or two time points during the course of Mn exposure. We report that amphetamine-induced DA release measured by PET is markedly impaired in the striatum of Mn-exposed animals. The effect of Mn on DA release was present in the absence of changes in markers of dopamine terminal integrity determined in post-mortem brain tissue from the same animals. These findings provide compelling evidence that the effects of Mn on DA synapses in the striatum are mediated by inhibition of DA neurotransmission and are responsible for the motor deficits documented in these animals.     

Analyse texturale en TEP au FDG des cancers pulmonaires non à petites cellules de stade localement avancé : valeur pronostique de l’entropie

IntroductionIn the current context of personalized medicine, textural analysis promises to be an accurate approach of cancer prognosis. The lack of standardization and the multitude of textural indices limited radiomics studies reproducibility as an obstacle of introduction of textual analysis into clinical practice. Our study assessed the prognostic value of entropy in 18F-FDG PET/CT in locally advanced non-small cell lung cancer (NSCLC).MethodPatients who performed 18F-FDG PET/CT for lung cancer staging between September 2015 and April 2017 in 2 hospitals were included for conventional and textural PET parameters extraction. A retrospective analysis of patient was performed over 24 months to determine the progression-free survival and overall survival.ResultsForty-two patients were included. Progression-free survival was significantly correlated with entropy on multivariate regression (cut-off at 8.4) with a hazard ratio of 3.04 (95 % CI 1.13–8.16) (P = 0.03), as MTV (P < 0.001). Neither conventional PET parameters nor entropy was a significant association with overall survival.ConclusionThese results confirmed the external validity and robustness of FDG PET entropy as an independent prognostic factor of progression-free survival in patients with locally advanced NSCLC, in addition to Conventional PET.     

Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAOA enzyme in healthy men

Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAOA)—an enzyme metabolizing neurotransmitters—revealed that MAOA levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAOA levels (using PET and [¹¹C]clorgyline, a radiotracer with specificity for MAOA) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAOA activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAOA levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior.     

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain''s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which ¹¹C-AcAc and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of ¹¹C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of ¹¹C-AcAc and ¹⁸F-FDG brain uptake (cerebral metabolic rate; μmol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer''s and Parkinson''s diseases.