【作者】 史源；

【导师】 李廷玉；

【作者基本信息】 重庆医科大学 ， 儿科学， 2010， 博士

【摘要】 背景正电子发射断层显像（position emission tomography, PET）利用正电子发射体标记的药物为示踪剂,以解剖图象方式、从分子水平显示机体及病灶组织细胞的代谢、功能、血流、细胞增殖和受体分布等状况,为临床提供更多生理和病理方面的诊断信息,尤其在中枢神经系统疾病的诊断方面具有独特的优势,是近年应用临床的新的影像诊断技术,已较广泛应用成人临床,但在儿童应用甚少。新生儿脑功能发育、损伤以及修复的过程一直是新生儿学以及神经科学的重要研究内容,利用PET对新生儿脑功能发育和损伤进行研究,并在此基础上建立相应的诊断标准,将大大提高新生儿脑发育和损伤相关疾病的诊断水平。18氟脱氧葡萄糖（18F-fluorodeoxyglucose, 18F-FDG）是临床最常用的PET显像测定脑葡萄糖代谢的显像剂,应用PET显像测定脑葡萄糖代谢,尤其是在不同胎龄新生儿及新生儿缺氧缺血性脑病（hypoxic-ischemic encephalopathy, HIE）中的应用,目前国外的研究甚少,国内则未见报道。目的对不同胎龄新生儿及新生HIE患儿应用¹⁸F-FDG PET测定脑葡萄糖代谢,探讨PET测定脑葡萄糖代谢在不同胎龄新生儿中的变化及新生儿HIE中的临床应用价值。方法研究对象包括不同胎龄新生儿及新生儿HIE患儿,共计67例,其中7例因各种原因导致PET数据采集失败未纳入统计,失败原因包括注射部位不当、注射剂量偏小、新生儿哭闹、活动导致PET数据采集失败等。其余60例新生儿纳入统计。其中,不同胎龄新生儿36例,包括≤32wk 4例,33-34wk 5例,35-36wk 12例,≥37wk15例;新生儿HIE患儿24例,其中,轻度13例,中度7例,中度4例。以RDSⅢ型回旋加速器获得¹⁸F后,通过自动化学合成装置制备¹⁸F-FDG溶液,在注射0.1mCi /kg ¹⁸F-FDG后应用PET成像仪采集数据,并通过测定新生儿脑不同部位的标准摄取值（standardized uptake values, SUV）进行脑葡萄糖代谢半定量分析。结果比较不同胎龄新生儿¹⁸F-FDG PET脑显像,可见随着胎龄的成熟,新生儿脑葡萄糖活性呈现逐步增高的趋势,结构也变得较为清晰,尤其以胎龄达到足月新生儿标准（≥37wk）后更为显著。不同胎龄新生儿脑¹⁸F-FDG PET显像的结果显示:其葡萄糖代谢活性在大脑皮层普遍较低,在丘脑则较高,其次为小脑、感觉运动皮质、基底节。胎龄≥37wk的足月新生儿,其不同部位的葡萄糖代谢活性较胎龄<32wk的早产儿显著增高（p<0.01）。新生儿HIE患儿脑存在明显葡萄糖代谢异常,主要表现为:大脑皮层18 F-FDG摄取量不一致,如损伤一侧明显低于对侧,或某区域低于其他区域,或全脑葡萄糖代谢偏低,尤其是皮层下白质、丘脑、基底节等部位最为明显。与胎龄≥37wk的足月新生儿相比,HIE患儿¹⁸F-FDG PET脑显像在所有测定的脑组织均呈现低代谢状况（p<0.05）,而且,病情越重越为明显,HIE患儿重度HIE患儿脑葡萄糖代谢较轻、中度HIE患儿显著降低（p<0.05）。结论随着胎龄的成熟,新生儿脑葡萄糖活性呈现逐步增高的趋势,结构也变得较为清晰,尤其以胎龄达到足月新生儿标准（≥37wk）后更为显著。新生儿HIE患儿PET脑显像存在明显¹⁸F-FDG代谢异常,新生儿HIE的¹⁸F-FDG PET脑显像特征为:1)大脑皮层¹⁸F-FDG摄取量不一致,如损伤一侧明显低于对侧,或某区域低于其他区域;2)全脑葡萄糖代谢偏低。应用¹⁸F-FDG PET测定脑葡萄糖代谢为研究新生儿脑发育和损伤提供了新的方法,其临床意义值得进一步研究。更多还原

【Abstract】 BackgroundPET （position emission tomography） is a noninvasive measurement of the levels of radiopharmaceuticals labeled with positron emitters, which can provide anatomically physiological and pathophysiological information on metabolism, function, blood supply, cell proliferation, and distribution of receptor of organs and tissues from molecular level. The most frequently used tracer for the assessment of tissue glucose metabolism is ¹⁸F-fluorodeoxyglucose(¹⁸F-FDG). PET has been widely used in a lot of cerebral diseases in adults. Only a few pediatric and even fewer neonatal PET studies have been presented so far. The measurement, however, of the cerebral glucose metabolism is important to study the physiology and pathophysiology of the developing brain in preterm, term infants, and in neonatal patients suffering from hypoxic-ischemic encephalopathy （HIE）.ObjectiveTo study the clinical value of cerebral glucose metabolism measure by ¹⁸F-fluorodeoxyglucose ¹⁸F-FDG PET in preterm, term newborn infants and neonatal hypoxic-ischemic encephalopathy （HIE）.Methods To measure the cerebral glucose metabolism by ¹⁸F-FDG PET imaging in 67 newborn infants. Seven neonates were excluded due to failure of data collection by PET, which caused by inadequate of administration of ¹⁸F-FDG, low dose of ¹⁸F-FDG , and crying or movement of the infants during PET course. Sixty infants were included in the study. Among them, 36 preterm and term infants without any sign of brain injury were divided into 4 groups, including≤32wk （n=4）, 33-34wk （n=5）, 35-36wk （n=12）, and≥37wk group （n=15）, and the other 24 newborn infants suffering from HIE were divided into 3 groups, including mild HIE （n=13）, medium HIE （n=7）, and severe HIE group （n=4）.¹⁸F was obtained by RDSⅢCyclotron, and then, ¹⁸F-FDG was produced by Chemistry Process Control Unit. The data was collected by PET instrument after administration of 0.1mCi /kg ¹⁸F-FDG in the newborns, and standardized uptake values （SUV） were calculated to estimate the cerebral glucose metabolism.ResultsThe cerebral glucose metabolism was found to have a trend to be increased, and the structure of brain ¹⁸F-FDG PET imaging to be clear with the increase of gestational age, especially when the gestational age was older than 37wk.The brain ¹⁸F-FDG PET imaging in different gestational age showed that the uptake of ¹⁸F-FDG was relatively higher in thalamus, cerebellum, sensorimotor cortex and basal ganglia, where as relatively lower in cerebral cortex. The uptakes of ¹⁸F-FDG in≥37wk group were found to be significantly higher than those in≤32wk group （p<0.01）.The cerebral glucose metabolism was significantly changed in neonatal HIE as measured by ¹⁸F-FDG PET. The cerebral uptake of ¹⁸F-FDG was either unbalanced bilaterally or relatively low in all sites especially in subcortical alba, thalamus, basal ganglia in HIE patients. Moreover, The uptakes of ¹⁸F-FDG in severe HIE patients were found to be significantly lower than those in mild and medium HIE patients（p<0.05 respectively）.Conclusions1. The uptakes of ¹⁸F-FDG in≥37wk term infants were significantly higher than those in≤32wk preterm infants.2. The cerebral uptake of ¹⁸F-FDG was either unbalanced bilaterally or relatively low in all regions or some places as compared with other areas of the brain in neonatal patients with HIE.3. Cerebral glucose metabolism measured by ¹⁸F-FDG PET might be a useful tool for estimating the brain development and injury in newborn infants, and its clinical values need further investigating.更多还原