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新生儿缺血缺氧性脑病(hypoxic-ischemic encephalopathy,HIE)是指各种围产期窒息引起的部分或完全缺氧、脑血流减少或暂停而导致胎儿或新生儿脑损伤,是导致儿童精神运动发育迟缓的主要原因之一[1]。在婴儿早期大脑尚未出现明显形态结构的改变时,采用CT、MRI等传统影像学检查可能出现漏诊或误诊,对HIE的早期诊断、临床分度及治疗后评估作用有限。出生后新生儿大脑利用葡萄糖供能的能力增强[2],18F-FDG是临床上最常用的正电子放射性显像剂,作为葡萄糖类似物,能准确反映大脑组织的葡萄糖代谢水平。PET/CT是当代核医学领域最先进的检查设备之一,在中枢神经系统疾病的诊断方面具有独特的优势[3]。18F-FDG PET/CT脑显像在足月新生儿HIE中的应用目前国内外的研究甚少。本研究应用18F-FDG PET/CT脑显像对足月新生儿HIE临床分度及治疗反应进行评估,现将结果报道如下。
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选取2012年5月至2014年10月在我院核医学科行18F-FDG PET/CT脑显像的新生儿共76例。研究获得我院医学伦理委员会批准,经其父母或法定监护人知情同意后行18F-FDG PET/CT脑显像检查。HIE患儿入选标准:(1)胎龄≥37周的足月新生儿,满足由中华医学会儿科学会新生儿组制定的足月儿HIE诊断及分度标准;(2)初次18F-FDG PET/CT脑显像在出生后2 d内进行,初次显像前患儿未接受抗惊厥药物治疗,在抗HIE治疗7 d后再次进行了18F-FDG PET/CT脑显像复查,治疗方法根据患儿的病情不同包括:3项维持疗法(①维持良好的通气、换气功能;②维持血糖在正常水平;③维持周身脏器足够的血液灌流,使心率和血压保持在正常范围)、3项对症治疗(①控制惊厥;②降低颅内压;③消除脑干症状)及亚低温疗法(降低脑温2℃~4℃)。最终有34例HIE足月新生儿入选,男18例、女16例,其中包括轻度16例、中度11例、重度7例。34例新生儿均排除电解质紊乱、颅内出血和产伤等原因引起的抽搐,以及宫内感染、遗传代谢性疾病和其他先天性疾病所引起的脑损伤。同期收集10名足月健康新生儿作为对照,其中男4名、女6名。所有受检新生儿的临床一般资料见表 1,健康新生儿与HIE轻、中、重度患儿的性别构成、胎龄及初次显像时体重之间的差异无统计学意义。
组别 例数 性别(男/女) 胎龄(周) 初次显像时
体重(g)健康新生儿 10 4/6 38.25±3.57 3654.84±572.56 HIE患儿 轻度 16 9/7 37.75±4.42 3393.23±704.57 中度 11 5/6 37.83±3.81 3483.85±294.87 重度 7 4/3 38.18±3.27 3474.38±638.64 表中,HIE:缺血缺氧性脑病。 表 1 健康新生儿及HIE患儿的一般临床资料
Table 1. The general clinical data of healthy neonates and HIE infants
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新生儿18F-FDG PET/CT脑显像采用荷兰Philips公司GEMINI TF PET/CT仪。18F-FDG由德国Siemens公司的eclipse HP/RD回旋加速器及自动合成系统生产,合成效率>60%,放化纯度>95%。检查前患儿均停止喂奶1~2 h,其间可喂以白开水,静脉注射18F-FDG 3.7 MBq/kg后约40 min,在患儿入睡期间行PET/CT脑显像,如患儿未能自行入睡,按8 mg/kg用量予以注射用苯巴比妥钠镇静、催眠。新生儿取仰卧位,用温暖毛毯包裹。先行低剂量头颅CT定位扫描,扫描范围从颅顶至颅底,扫描条件采用420 mAs、120 kV。PET数据采用三维采集模式,矩阵128×128、Hann滤波、放大2.5倍、半高宽为5。机器自动利用CT数据对PET图像进行衰减校正,并进行图像重建和融合。
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由两位分别具有10年以上放射诊断工作经验和核医学工作经验的正高级职称医师共同对CT、PET及融合图像进行阅片。测定患儿大脑双侧感觉运动皮质区、额叶、颞叶、枕叶、丘脑、基底节、脑干及小脑区脑组织SUVmax。
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采用Microsoft Excel和SPSS 13.0软件分析,计量资料以均数±标准差表示,数据保留小数点后两位有效数字,检验方法采用多组均数比较方差分析、多个构成比X2检验,P<0.05表示差异具有统计学意义。
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不论是健康新生儿还是HIE患儿,丘脑、基底节、脑干及小脑葡萄糖代谢水平均普遍较大脑皮层各叶脑组织高,而在大脑皮层脑组织中,感觉运动皮质区代谢较高。健康新生儿组各脑组织区葡萄糖代谢水平(图 1)均显著高于HIE轻、中、重度组(表 2)。不同病情的HIE患儿中,轻度HIE患儿除脑干之外(t=1.4893,P>0.05),感觉运动皮质区、额叶、颞叶、枕叶、基底节、丘脑及小脑的葡萄糖代谢水平均显著高于中度HIE患儿(t=3.9192、3.2603、5.2501、4.1415、2.4454、2.7070、2.4646,P均<0.05),轻度HIE患儿各脑部位区葡萄糖代谢水平均显著高于重度HIE患儿(t=5.5062、5.5654、5.9370、4.8875、8.8283、6.7671、8.5161、4.7074,P均<0.05),中度HIE患儿与重度HIE患儿各脑部位区比较,除枕叶差异无统计学意义外(t=1.6876,P>0.05),其余部位均高于重度HIE患儿相应脑部位区(t=3.8967、5.5654、2.5880、3.8856、3.7778、6.9660、4.0630,P均<0.05)(表 2)。健康新生儿及不同程度HIE患儿脑葡萄糖代谢比较结果可见,HIE程度越重,患儿脑各部位区葡萄糖代谢水平呈现逐步降低的趋势(图 2~图 4)。
组别 感觉运动皮质区 额叶 颞叶 枕叶 基底节 丘脑 脑干 小脑 健康新生儿 1.98±0.43 1.68±0.34 1.62±0.28 1.74±0.35 2.23±0.52 2.56±0.62 2.18±0.30 2.12±0.41 HIE患儿 轻度 1.26±0.31
(t=4.9652)1.14±0.27
(t=4.4924)1.22±0.34
(t=3.1122)1.17±0.36
(t=3.9687)1.18±0.19
(t=7.3980)1.42±0.28
(t=6.4347)1.27±0.24
(t=8.5475)1.35±0.37
(t=4.9551)中度 0.86±0.16
(t=8.0634)0.81±0.24
(t=6.8266)0.63±0.18
(t=9.7333)0.65±0.25
(t=8.2733)0.95±0.30
(t=6.9938)1.11±0.31
(t=6.8800)1.13±0.24
(t=8.8975)1.05±0.19
(t=7.7978)重度 0.59±0.11
(t=8.2893)0.53±0.15
(t=8.3363)0.39±0.21
(t=9.8139)0.47±0.16
(t=8.9055)0.48±0.13
(t=8.6381)0.57±0.27
(t=7.9224)0.47±0.08
(t=14.590)0.62±0.26
(t=8.5109)表中,HIE:缺血缺氧性脑病;括号中t值为HIE患儿与健康新生儿各脑组织区比较的结果,P均 < 0.05。 表 2 健康新生儿及不同程度HIE患儿脑组织SUVmax比较
Table 2. The comparison of SUVmax between healthy neonates and infants with different degree of HIE
图 2 轻度缺血缺氧性脑病患儿18F-FDG PET/CT脑显像图
Figure 2. 18F-FDG PET/CT brain imaging of infant with mild hypoxic-ischemic encephalopathy
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根据2.1节中健康新生儿组及不同程度HIE患儿组平均SUVmax情况,笔者自定义公式:x=(HIE患儿脑某部位SUVmax-健康新生儿相应部位平均SUVmax)/健康新生儿相应部位平均SUVmax×100%;并定义感觉运动皮质区、额叶、颞叶、枕叶、丘脑、基底节、脑干及小脑8个脑部位中,若有其中5个及以上部位的x≥10%为代谢高于正常,-10%≤x<10%为代谢基本正常,-30%≤x<-10%为代谢轻度降低,-50%≤x<-30%为代谢中度降低,x<-50%为代谢重度降低。分别测定34例HIE患儿治疗前后大脑各部位SUVmax,得到其治疗前后脑组织葡萄糖代谢情况例数及构成比分布(表 3)。比较治疗前后HIE患儿脑葡萄糖代谢情况,结果显示治疗后脑葡萄糖代谢水平显著高于治疗前(x2=32.30,P<0.05)。
显像时间 高于正常 基本正常 轻度降低 中度降低 重度降低 治疗前 0(0%) 0(0%) 2(5.88%) 18(52.94%) 14(41.18%) 治疗后 4(11.76%) 11(32.35%) 9(26.47%) 8(23.53%) 2(5.88%) 表 3 缺血缺氧性脑病患儿治疗前后脑组织SUVmax变化情况[例(%)]
Table 3. Comparison of SUVmax between pre- and post-treatment hypoxic- ischemic encephalopathy infants[n(%)]
18F-FDG PET/CT脑显像在新生儿缺血缺氧性脑病诊断及治疗后评估中的临床研究
Clinical research on using 18F-FDG PET/CT brain imaging in the diagnosis of and therapeutic effect evaluation in neonatal hypoxic-ischemic encephalopathy
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摘要:
目的 应用18F-FDG PET/CT脑显像测定健康新生儿及缺氧缺血性脑病(HIE)患儿的脑葡萄糖代谢水平, 探讨18F-FDG PET/CT脑显像在HIE患儿严重程度分度及治疗后评估中的作用。 方法 研究对象包括健康新生儿10名和不同程度HIE患儿34例, 后者包括轻度16例、中度11例、重度7例, 注射18F-FDG后显像测定患儿大脑双侧感觉运动皮质区、额叶、颞叶、枕叶、丘脑、基底节、脑干及小脑区脑组织SUVmax, 观察治疗前不同程度HIE患儿各脑组织区葡萄糖代谢情况, 并与健康新生儿脑代谢情况进行比较;HIE患儿治疗后再次行18F-FDG PET/CT脑显像, 比较治疗前后HIE患儿各脑组织区SUVmax变化情况。 结果 对于健康新生儿及不同程度HIE患儿, 丘脑、基底节、脑干及小脑葡萄糖代谢水平均普遍较大脑皮层各叶脑组织高, 而在大脑皮层脑组织中, 感觉运动皮质区代谢较高。健康新生儿组各脑组织区葡萄糖代谢水平均显著高于HIE轻、中、重度组, 不同程度HIE患儿脑葡萄糖代谢比较可见, HIE程度越重, 患儿脑各部位葡萄糖代谢水平呈现逐步降低的趋势。不同程度HIE患儿治疗后各脑组织区葡萄糖代谢情况显著高于治疗前。 结论 18F-FDG PET/CT脑显像在HIE患儿严重程度分度及治疗后评估中具有较好的临床适用价值, 为新生儿脑损伤提供了新的方法, 其临床意义及对新生儿的辐射安全性值得进一步研究。 -
关键词:
- 缺血缺氧, 脑 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术 /
- 最大标准化摄取值
Abstract:Objective Cerebral glucose metabolism was measured using 18F-FDG PET/CT in healthy full-term neonates and infants exhibiting neonatal hypoxic-ischemic encephalopathy(HIE) to investigate the role of 18F-FDG PET/CT brain imaging in HIE diagnosis and in therapeutic effect evaluation in HIE. Methods Ten healthy full-term neonates and thirty-four term infants exhibiting different degrees of HIE (mild, n=16; moderate, n=11; and severe, n=7) were included in this research. The SUVmax were measured to determine the cerebral glucose metabolism in various brain anatomical regions, including bilateral sensorimotor cortex, frontal lobe, temporal lobe, occipital lobe, thalamus, basal ganglia, brain stem, and cerebellum. The cerebral glucose metabolism in healthy neonates and infants exhibiting different degrees of HIE was compared. The glucose metabolism pre- and post-treatment was also assessed using 18F-FDG PET/CT and then compared with each other. Results Results indicated that uptake in the major brain areas was significantly higher in healthy term newborns than in the neonatal HIE patients. Moreover, patients with severer HIE demonstrated lower cerebral glucose metabolism. Cerebral glucose metabolism in patients exhibiting different degrees of HIE was also significantly higher after treatment than before treatment. Conclusion 18F-FDG PET/CT brain imaging demonstrated a preferable clinical applicable value in the diagnosis and therapeutic effect evaluation of HIE patients and provides a new method for treatment of neonatal brain injury. The clinical value and neonatal radiation safety of this technique warrants further investigation. -
表 1 健康新生儿及HIE患儿的一般临床资料
Table 1. The general clinical data of healthy neonates and HIE infants
组别 例数 性别(男/女) 胎龄(周) 初次显像时
体重(g)健康新生儿 10 4/6 38.25±3.57 3654.84±572.56 HIE患儿 轻度 16 9/7 37.75±4.42 3393.23±704.57 中度 11 5/6 37.83±3.81 3483.85±294.87 重度 7 4/3 38.18±3.27 3474.38±638.64 表中,HIE:缺血缺氧性脑病。 表 2 健康新生儿及不同程度HIE患儿脑组织SUVmax比较
Table 2. The comparison of SUVmax between healthy neonates and infants with different degree of HIE
组别 感觉运动皮质区 额叶 颞叶 枕叶 基底节 丘脑 脑干 小脑 健康新生儿 1.98±0.43 1.68±0.34 1.62±0.28 1.74±0.35 2.23±0.52 2.56±0.62 2.18±0.30 2.12±0.41 HIE患儿 轻度 1.26±0.31
(t=4.9652)1.14±0.27
(t=4.4924)1.22±0.34
(t=3.1122)1.17±0.36
(t=3.9687)1.18±0.19
(t=7.3980)1.42±0.28
(t=6.4347)1.27±0.24
(t=8.5475)1.35±0.37
(t=4.9551)中度 0.86±0.16
(t=8.0634)0.81±0.24
(t=6.8266)0.63±0.18
(t=9.7333)0.65±0.25
(t=8.2733)0.95±0.30
(t=6.9938)1.11±0.31
(t=6.8800)1.13±0.24
(t=8.8975)1.05±0.19
(t=7.7978)重度 0.59±0.11
(t=8.2893)0.53±0.15
(t=8.3363)0.39±0.21
(t=9.8139)0.47±0.16
(t=8.9055)0.48±0.13
(t=8.6381)0.57±0.27
(t=7.9224)0.47±0.08
(t=14.590)0.62±0.26
(t=8.5109)表中,HIE:缺血缺氧性脑病;括号中t值为HIE患儿与健康新生儿各脑组织区比较的结果,P均 < 0.05。 表 3 缺血缺氧性脑病患儿治疗前后脑组织SUVmax变化情况[例(%)]
Table 3. Comparison of SUVmax between pre- and post-treatment hypoxic- ischemic encephalopathy infants[n(%)]
显像时间 高于正常 基本正常 轻度降低 中度降低 重度降低 治疗前 0(0%) 0(0%) 2(5.88%) 18(52.94%) 14(41.18%) 治疗后 4(11.76%) 11(32.35%) 9(26.47%) 8(23.53%) 2(5.88%) -
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