【作者】 赵军；

【导师】 张雪林；

【作者基本信息】 南方医科大学 ， 影像医学与核医学， 2009， 博士

【摘要】 【研究目的】1.通过对一组健康新生儿常规MRI（T1WI、T2WI）检查与2D-¹H MRS分析,探讨健康新生儿的波谱成像方法。2.通过对该组健康新生儿做常规MRI（T1WI、T2WI）检查与2D-¹H MRS分析,探讨健康新生儿的波谱表现。3.通过对一组临床确诊为新生儿缺氧缺血性脑损伤的患儿进行常规MRI及2D-¹HMRS的检查,探讨足月、早产新生儿缺氧缺血性脑损伤的影像、波谱表现。4.通过对该组临床确诊为新生儿缺氧缺血性脑损伤的患儿进行临床贝利评分随访,总结常规MRI、2D-¹H MRS检查结果对新生儿缺氧缺血性脑损伤的愈后判断研究。【材料与方法】1、研究对象健康新生儿来源对从2008年08月08日至2009年03月08日期间在南方医科大学南方医院影像中心志愿接受检查的5例健康新生儿做常规MRI（T1WI、T2WI）与2D-¹HMRS分析检查,最后分析其影像资料。新生儿HIBD的来源对从2008年08月08日至2009年03月08日期间在南方医科大学南方医院影像中心志愿接受检查的45例足月新生儿和18例早产新生儿做常规MRI（T1WI、T2WI）与2D-¹H MRS分析检查,最后分析其影像资料。预后患儿来源对从2008年08月08日至2009年03月08日期间在南方医科大学南方医院确诊患有HIBD并住院治疗,还在影像中心志愿接受MRS检查;患儿出院后在规定的时间来复查BSID;共43例。2、设备与参数设置2.1设备2.1.1磁共振扫描仪:采用GE公司生产的Signa ExciteⅡ3.0T超导型核磁共振扫描设备进行检查。2.1.2线圈:采用常规MRI扫描使用头部八通道线圈,由自旋回波（SE）序列和快速自旋回波（FSE）序列获得T1、T2加权像（T1WI、T2WI）。磁共振波谱扫描采用头颅专用单通道正交线圈,二维多体素（2D-multi-voxel）点分辨波谱（PRESS）成像序列,于T1WI或T2WI平扫的纯轴位上进行波谱定位。定位完毕后先行预扫描,显示自动匀场达到半高线宽（FWHM）98%以上方开始正式进行波谱扫描,扫描时间大约5分钟。2.1.3支架:采用自制支架,大小为40cm×30cm×20cm的软质慢弹海绵,中间挖凹。检查时将婴儿头部固定在海绵中间。2.1.4图形工作站:GE公司提供的AW4.3工作站,其内配备有对MRS图像及数据资料进行处理的Functool软件。2.1.5图像存储与传输:采用经纬PACS（JW-PACS）（Picture Archiving andCommuniations System）系统,即图像存储与传输系统。2.2、扫描参数设置2.2.1常规MRI扫描:使用头部八通道线圈,由自旋回波（SE）序列和快速自旋回波（FSE）序列获得T1、T2加权像（T1WI、T2WI）,扫描参数如下:T1WI（TR/TE,600/16ms）,T2WI（TR/TE,5100/138ms）,层厚5-8mm,层间距1.5mm,FOV 24×18mm,矩阵512×288。2.2.3磁共振波谱扫描:主要采用两种脉冲序列成像,激励回波（STEAM）法及点分辨率（PRESS）法。成像的方式是二维采集。本文主要从脉冲序列、扫描、后处理三方面介绍波谱成像扫描技术。三维波谱后处理分析与二维波谱的分析基本一样。3、婴儿麻醉:3.1药品3.1.1苯巴比妥钠注射液（Sodium Phenobarbital Injection）药理毒理与药代动力学:本品为无色澄明液体。本品对中枢神经系统有广泛抑制作用,随用量增加而产生镇静、催眠和抗惊厥效应,大剂量时产生麻醉作用,作用机制现认为主要与阻断脑干网状结构上行激活系统有关。注射后0.5～1小时起效,2～18小时血药浓度达峰值,分布于体内组织和体液中,脑组织内浓度高,其次为骨骼肌内,进入脑组织的速度较慢,能通过胎盘,血液中本品的40%与血浆蛋白结合。半衰期(T_1/2)成人为48～144小时,小儿为40～70小时,肝、肾功能不全时半衰期(T_1/2)延长。约65%在肝脏代谢,转化为羟基苯巴比妥,大部分与葡萄糖醛酸或硫酸盐结合,而后经肾随尿排出;27～50%以原形从尿中排出,部分在肾小管重吸收,使其作用时间延长。用法用量:麻醉前给药术前0.5～1小时肌内注射100～200mg。儿童用药:肌内注射:抗惊厥,按体重一次3～5mg/kg。规格:1ml:0.1g;安瓿1ml×10支生产企业:天津金耀氨基酸有限公司;批准文号-国药准字H12020381;3.1.2水合氯醛（Chloral Hydrate）备用,以防止婴儿检查中苏醒药理毒理与药代动力学:本品为催眠药、抗惊厥药。催眠剂量30分钟内即可诱导入睡,催眠作用温和,不缩短REMS睡眠时间,无明显后遗作用。催眠机理可能与巴比妥类相似,引起近似生理性睡眠,无明显副作用。较大剂量有抗惊厥作用,可用于小儿高热、破伤风及了癎引起的惊厥。大剂量可引起昏迷和麻醉。抑制延髓呼吸及血管运动中枢,导致死亡。曾作为基础麻醉的辅助用药,现已极少应用。消化道或直肠给药均能迅速吸收,1小时达高峰,维持4～8小时。脂溶性高,易通过血脑屏障,分布全身各组织。血浆T_1/2为7～10小时。在肝脏迅速代谢成为具有活性的三氯乙醇。三氯乙醇的蛋白结合率为35～40%,三氯乙醇T_1/2约为4～6小时。口服水合氯醛30分钟内即能入睡,持续时间为4～8小时。三氯乙醇进一步与葡糖醛酸结合而失活,经肾脏排出,无滞后作用与蓄积性。本药可通过胎盘和分泌入乳汁。用法与用量:小儿常用量:催眠,一次按体重50mg/kg或按体表面积1.5g/m²,睡前服用,一次最大限量为1g;也可按体重16.7mg/kg或按体表面积500mg/m²,每日3次。镇静,一次按体重8mg/kg或按体表面积250mg/m²,最大限量为500mg,每日3次,饭后服用。灌肠,每次按体重25mg/kg。极量每次为1g。生产企业:南方医科大学南方医院;水合氯醛溶液10%洁芙柔消毒凝胶擦手后可触及婴儿。4、感兴趣区（Region of interest,ROI）的选择:矢旁血供分布:三支脑动脉（大脑前动脉ACA、大脑中动脉MCA、大脑后动脉PCA）分布区红色区域为分水岭区灌注不足时容易发生脑缺血;所以选择此处为主要感兴趣区。5、统计学处理将测得数据按婴儿胎龄及ROI采集位置归类输入SPSS13.0统计软件包后,分别计算出基底节区域各代谢物比值的平均值,用均数±标准差（±SD）形式表示。各个代谢物Cho、Cr、NAA、Cr+Cho、Cho/Cr、Cho/NAA、NAA/Cho、NAA/Cr、Cr/NAA、MI、Lip、Lac值,以均数±标准差（x±SD）的形式表示。（1）比较基底节区左右各代谢物比值有无统计学差异;（2）比较基底节区左右之间各代谢物比值有无统计学差异;经检验,各组数据均符合正态分布。HIBD患儿分组后:轻中、重度分别与MRS结果对照,采用LSD多重循环两两比较。贝利评分按原始分分4组后分别与MRS各结果对照,比较采用配对t检验。左右感兴趣之间的比较采用独立样本t检验。检验水准a值取0.05。【结果】正常新生儿波谱代谢物的主要病、生理意义及表现:波谱代谢物大的共振峰主要包括:1 Cho主要包括磷酸胆碱和磷酸乙酰胆碱,共振峰位于3.2ppm。正常情况下是¹H-MRS的第1高波峰。Cho与细胞膜磷脂的分解和合成有关,参与细胞膜的构成。Cho峰增高,与细胞分裂增殖活跃及细胞膜代谢异常增高有关,脱髓鞘可引起胆碱增高。2 NAA N-乙酰天门冬氨酸,位于2.0ppm,在正常¹H-MRS中NNA是第二高的峰。NAA主要存在于神经元及其轴索,被认为是神经元的内标志物,NAA的降低反映了神经元的丧失或其量的代谢障碍。3 Cr主要包括肌酸和磷酸肌酸,与能量代谢有关,共振峰见于3.0ppm,是¹H-MRS第3高波峰。4乳酸（Lac）正常情况下测不到,共振峰见于1.3ppm和4.1ppm,为双尖峰。是无氧糖酵解的产物,机体缺氧缺血时可引起乳酸盐的蓄积,对HIBD的诊断有重要意义。5肌醇（MI）共振峰见于3.5ppm。具有调节渗透压、营养细胞、抗氧化及生成表面活性物质等作用。机器的性能指标及序列参数与波谱扫描技术:从上面论述可见,要想得到精确的波谱分析结果,必须要注意的几个要点是:a.解剖定位图必须是垂直位;b.波谱定位至关重要;c.建议使用VSS;d.匀场是波谱扫描的关键;e.每次扫描钱都要做自动预扫描（auto prescan）,观察线宽值及水抑制值。MRI:对新生儿是较敏感的影像检查方法;优点:常规MRI（灰质、皮质、深部核团）损伤T1WI高信号;根据损伤时间、病理改变（出血、胶质增生）T2WI信号是变化的;自质损伤因缺血;脑水肿在T1WI为低信号,T2WI高信号;MRS（波谱）:提供粗略的脑组织生化分析,Lac、Cho、Cr、NAA的峰值潜在预测HIBD的预后:有文献MRS对HIBD在24小时内比DWI敏感。5例正常新生儿均可以显示NAA、Cr、Cho、波峰高耸,MI峰略低,Lac、Lip峰低平或者测不出,波峰由高到低的顺序是Cho、NAA、Cr、MI、Lac、Lip;值为Cr+Cho:19551.33±4210、Cho/Cr:1.17±0.52、Cho/NAA:1.47±0.22、NAA/Cho:1.61±0.19、NAA/Cr:1.73±0.45、Cr/NAA:1.0135±0.24。MRS能定量分析组织化学成份和结构,可活体研究新生儿脑的生化代谢过程,提供关于细胞能量代谢、细胞膜崩解、神经元功能及选择性神经递质活动等信息。MRS常用的检查方法有激励回波法（STEAM）和点分辨法（PRESS）。测定的代谢产物包括以下几种:N-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌酸（Cr）、肌醇（MI）、乳酸（Lac）。NAA是神经元的内标记物,位于2.0ppm处,在足月新生儿中是第二高波峰,仅次于Cho峰,出生后随着年龄的增长及神经元成熟,NAA峰逐渐升高,至6个月时NAA已跃升为最显著的波峰。Cho峰包括自由胆碱、磷酸胆碱及磷脂酰胆碱,参与磷脂代谢。正常足月新生儿Cho峰为最高峰,位于3.2ppm处,定量研究发现新生儿脑Cho含量较成人高,出生后数月随着髓鞘化的加速完成,Cho含量开始下降。Cr反映组织能量利用的潜力,在HIBD时相对稳定,故常作为其它代谢物的参考。Lac是糖酵解的终产物,位于1.33ppm处,它的出现提示有氧呼吸不再有效进行,正常新生儿Lac峰较低平。新生儿缺氧缺血性脑损伤（HIBD）的MRS表现:MRS能早期检测新生儿缺氧缺血性脑损伤（HIBD）,急性缺氧缺血后6h即可在基底节、丘脑及双侧额叶白质内检测到Lac峰升高。众多研究表明HIBD患儿与正常者有明显不同,即在1.3ppm处出现双峰状乳酸波,是由于无氧酵解增加所致,如果乳酸含量在较低水平,几周后由于局部代谢或氧的供给增加,脑内乳酸含量可逐步恢复到正常水平;若乳酸含量超过某一临界值,持续升高,引起细胞酸中毒并导致神经元的不可逆损伤,出现NAA含量下降。统计结果表明Lac/Cr及NAA/Cr比值在HIBD组与正常新生儿有明显差异,HIBD组Lac/Cr比值明显升高,NAA/Cr比值明显降低,且Lac/NAA及NAA/cho比值可用于评价HIBD预后。Juliet认为Lac/NAA比值＞0.5,Floris认为NAA/cho比值＜0.8,则预后不良,可出现神经发育损害。我们通过对临床确诊为HIBD患儿进行研究,按HIE轻、中、重度分级,轻度者比值为0.5～1.0,中度为1.0～2.0,重度者＞2.0以上。通过临床随访结果发现MRS与MRI及随访结果密切相关,表明MRS分度及MRI分度对HIBD预后的评价有重要价值。其它表现MI升高提示伴胶质增生及髓鞘化不良。MRS与智力发展指数关系:其受多种因素影响,智力发展指数的相关分析表明,在智力发展指数显著相关的4个变量中,LAC与智力发展指数的相关性最高（r=0.355 89,P=0.000 1）,有关早产儿的研究也证实了这一点。NAA是它的一个方面,比值与儿童智力发展之间的相关研究结果虽然不尽相同,但一般认为相关系数为低到中度水平,高评分的儿童智力发展水平高,但在不同年龄阶段并不一致,在2个月以前相关性很小,3个月之间开始出现相关,远期几个月以后相关明显也与之相符。对婴幼儿来说,完善的早期治疗对中枢神经系统的发育和成熟有着至关重要的作用。本研究结果显示,医疗干预越多,其智力发展指数也越高,与相关研究一致。另外,家庭的父母对精神与运动操作有明显影响。对HIBD在儿童生长发育过程中重要性认识要不断深入。因此,需要高度重视婴幼儿期的HIBD评分情况。孕周影响智力发展指数的原因可能是孕周从某一方面来说预示着婴幼儿出生时的成熟程度,特别是大脑神经系统发育作为婴幼儿发展的一个起点,尤其在小婴儿对智力发展指数影响更明显。MRS与运动发展指数关系:早期的预示作用运动发展指数的相关分析显示,与运动发展指数显著相关的有:医疗干预、早期诊断和孕周;运动发展指数的单因素方差分析表明,妊娠期用药史本组资料显示,婴幼儿的精神运动发展指数亦不同;结果与智力发展指数的影响因素相近。儿童的动作和对身体的控制能力使他们能够灵活地适应新的、多变的环境,如婴幼儿操作技巧的发展促进了其他各种基本智能过程的发展和应用,此时智力与运动量表的计分之间有很高的正相关。其临床意义在于运动功能失调可作为神经损伤的早期征象。【结论】1.正常新生儿MRS检查方法:波谱扫描:常规线圈扫描T1WI、T2WI、T2FLAIR图像;采用头颅专用单通道正交线圈,二维多体素（2D-multi-voxel）点分辨波谱（PRESS）成像序列,TR/TE:1000ms/144ms,频率编码设定为16,频率编码方向A/P,体素厚度（voxelthickness）10mm,层间距20mm,NEX 1,FOV 18mm×18mm。于T1WI或T2WI平扫的纯轴位上进行波谱定位,波谱扫描野（VOI）大小根据病变情况而定,应包括婴儿双侧基底节区及半卵圆中心区域,避免包括颅骨、头皮脂肪、含气窦腔等影响波谱成像质量的组织。定位完毕后先行预扫描,显示自动匀场达到半高线宽（FWHM）98%以上方开始正式进行波谱扫描,扫描时间大约5分钟。图像后处理:采用GE公司3.0T磁共振随机配置的分析软件包“FuncTool”自动对波谱扫描获得的化学频率图进行基线校正、频率翻转、回顾性体素转移等后处理后,在后处理工作站上可同时获得四种图形,即化学位移图（ChemicalShift Image,CSI）、波谱图（Spectrum,SI）、代谢图（MetabolicImages,MI）以及代谢与解剖图之叠加图（AI+MI,简称“代—解图”）。本设备预先设定的一个体素大小为机器推荐值31.6mm。于“代谢-解剖叠加图（AI+MI）”上放置两个感兴趣区（ROI）,分别位于基底节区域（ROI-1）、半卵圆中心区域（ROI-2）,后处理软件自动获得VOI内所有体素的位置、数量及各个体素内的波谱信息。在后处理时,根据选择的范围情况在“代-解图”上设定1-4个体素整合而成的方框作为感兴趣区（ROI）大小,感兴趣区大小一般由1-4个体素组成。在“代-解”图上观察各代谢物的浓度分布,在相应波谱图（SI）上观察各感兴趣区的波峰表现。同时,图形分析软件自动识别并计算各代谢物峰下面积代表其浓度,并自动计算各代谢物间的相对比值。在“代-解图”上观察各代谢物的伪彩浓度分布,在各ROI对应波谱图（Spectrum,SI）上观察代谢物的波峰高低情况,横轴代表各代谢物的化学位移位置,单位以ppm表示（ppm位置如表1所示）,纵轴代表各代谢物的波峰情况。同时,图形工作站及有关分析软件自动识别并计算相应ROI内的N一乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌酸（Cr）、乳酸（Lac）和脂质（Lip）等代谢物的峰下面积,所得数值代表各物质的浓度,并自动计算出各代谢物之间的相对比值。本研究中所有病人的MR及MRS资料诊断时经三名有经验的影像科医生共同进行阅片、图像后处理及数据测量,记录各ROI的Cho、Cr、NAA、Cr+Cho、Cho/Cr、Cho/NAA、NAA/Cho、NAA/Cr、Cr/NAA、MI、Lip、Lac代谢物值和相对比值,同时记录Lip峰或Lac峰在各组内分别出现的例数。2.正常新生儿MRS表现:5例正常新生儿均可以显示NAA、Cr、Ch、波峰高耸,MI峰略低,LAC、LIP峰低平或者测不出,波峰由高到低的顺序是Ch、NAA、Cr、MI、LAC、LIP;值为Cr+Cho:19551.33±4210、Cho/Cr:1.17±0.52、Cho/NAA:1.47±0.22、NAA/Cho:1.61±0.19、NAA/Cr:1.73±0.45、Cr/NAA:1.0135±0.24。准确测量体内代谢物对治疗效果及其他目的的分析研究起很重要作用。所测得的代谢物值和真实代谢物值还是有差别的;不能代表实际值。比如乳酸易受脂类分子及巨分子的影响而比实际值要高,肌醇则由于在体内本身含量很低难于测量或比实际值要小,用PRESS序列不能有效区分N-乙酰基及别的含N-乙酰基基团的氨基酸,所以活体MRS能测量的N-乙酰天冬氨酸值明显高于高效液相色谱测量的N-乙酰天冬氨酸值。MRS能检测出脑内各个具体的代谢物质水平,从定量的角度反映出更多的生化指标变化。也是目前能够进行活体组织内化学物质无创性检测的唯一方法,在很多疾病的发生和发展过程中,代谢改变往往早于形态学改变,因此充分认识MRS所能提供的代谢信息可以充分有助于疾病的早期诊断。MRS在新生儿HIBD中的表现:在MRS与HIBD研究中:所测量的各个指标中,经过统计分析可以明确的看到:Cho、MI、Lip、Lac、Cr+Cho、Cho/Cr、Cho/NAA、Cr/NAA这几个指标都是随着HIBD的加重而上升的;另外NAA、NAA/Cho、NAA/Cr与HIBD成负相关;Cr在统计学中P＞0.01;认为统计学意义不大,其值一直变化不大,看做是MRS的参照波;另外胎龄的大小在本次研究中我们认为与HIBD的关系不大;对新生儿HIBD的评价MRI具有许多其它检查方法无可比拟的优越性,能更准确地反映脑内病变的部位、范围、性质及与周围结构的关系,MRS能检测出脑内各个具体的代谢物质水平,从定量的角度反映出更多的生化指标。磁共振MRS技术可以预测HIBD患儿的预后,并且通过此次对比评估,发现MRS的代谢物值可以很直接的反应患儿预后,在此基础上应用适合的医疗干预,HIBD评分反映的值与MRS基本一致;MRS与贝利评分对照研究表明:Lac的升高说明脑内乳酸的升高,在本次研究中表明:Lac峰越高的在愈后越差,其次NAA、Cr+Cho、Cho/Cr、Cho/NAA、NAA/Cho、NAA/Cr、Cr/NAA都可以评价预后,但是以NAA、Lac、NAA/Cho、NAA/Cr相关性最大;随着磁共振MRS检查的普及,BSID和MRS技术可广泛推广,从而尽早筛查出HIBD病人,解决其早期诊断的问题。并为新生儿认知、运动障碍监测和治疗干预的疗效观察提供手段,推动HIBD治疗及各项研究的深入,最终提高部分人群的生活质量。但是多种影像技术（DWI、PWI）的联合应用将更深入地揭示新生儿HIBD脑损伤的影像学病理基础,能早期准确的诊断病变及病情严重程度并准确判断评估预后,寻求出最佳的康复治疗方案具有重要的临床价值。更多还原

【Abstract】 [Objectives]1.By a group of healthy newborns conventional MRI(T1WI,T2WI)inspection and analysis of 2D-1H MRS to examine the health of newborns method of spectral imaging.2.The health of newborns through the group a regular MRI(T1WI,T2WI) inspection and analysis of 2D-1H MRS to explore the spectral performance of the health of newborns.3.The adoption of a clinical diagnosis of hypoxic-ischemic brain injury in children with conventional MRI and 2D-1H MRS examination to explore the full-term and premature newborns with hypoxic-ischemic brain injury in the performance image.4.Through the clinical diagnosis of hypoxic-ischemic brain injury in children with clinical follow-up,sum up conventional MRI and 2D-1H MRS findings of neonatal hypoxic-ischemic brain injury after more research to determine.[Materials and Methods]1,studySource neonatal healthFrom August 8,2008 to March 2009 period 08 in the South Medical Imaging Center,Nanfang Hospital,Volunteers of five cases examined the health of newborns do conventional MRI(T1WI,T2WI)and 2D-1H MRS analysis of inspection,the final analyze the image data.The source of neonatal HIBDFrom August 8,2008 to March 2009 period 08 in the South Medical Imaging Center,Nanfang Hospital,volunteers checked 45 cases of the 18 cases of full-term newborn and premature newborns do conventional MRI(T1WI,T2WI)and 2D-1H MRS analysis of inspection,the final analysis of its image data.Prognosis of children with sourceFrom August 8,2008 to March 2009 period in the South 08 South Medical University Hospital and diagnosed with HIBD hospitalization,imaging centers also accept voluntary MRS examination;patients after discharge from hospital in time to review the provisions of the BSID;a total of 43 cases.2,equipment settings and parameters2.1 Equipment2.1.1 magnetic resonance scanner:the use of GE produced Signa ExciteⅡ3.0T superconductive magnetic resonance imaging equipment to be checked.2.1.2 coils:the use of conventional MRI scans of eight-channel head coil,by the spin-echo(SE)sequences and fast spin echo(FSE)sequence was T1, T2-weighted images(T1WI,T2WI).Scanned using magnetic resonance spectroscopy dedicated single-channel quadrature head coil,multi-voxel two-dimensional(2D-multi-voxel)point-resolved spectroscopy(PRESS)imaging sequence,in plain T1WI or T2WI pure axial position on the spectrum. Pre-positioning after the first scan,indicating semi-automatic shimming to achieve high linewidth(FWHM)98%or more to the beginning of formal spectral scanning, scan time of approximately 5 minutes. 2.1.3 stent:a self-made stent,the size of 40cm×30cm×20cm behind the soft sea shells,the middle of Au-dug.Check the infant head fixed in the middle of the sea.2.1.4 Workstation:GE workstations provided AW4.2,with its images and data to the MRS data processing software Functool.2.1.5 Picture Archiving and transmission:the use of latitude and longitude PACS(JW-PACS)(Picture Archiving and Communiations System)system,that is, picture archiving and communication system.2.2,scan parameters2.2.1 Conventional MRI scanning:the use of eight-channel head coil,by the spin-echo(SE)sequences and fast spin echo(FSE)sequence was T1,T2-weighted images(T1 WI,T2WI),scan parameters are as follows:T1WI(TR/TE,600/16ms), T2WI(TR/TE,5100/138ms),slice thickness 5-8mm,layer spacing of 1.5mm,FOV 24×18mm,matrix 512×288.2.2.3 Magnetic Resonance Spectroscopy Scanning:Mainly two kinds of imaging pulse sequence,STEAM and PRESS.Imaging single Su-way,two-dimensional,three-dimensional acquisition.This article from the pulse sequence,scanning,post-processing to introduce three spectral imaging scanning technology.Post-processing of three-dimensional spectral analysis: three-dimensional spectral analysis and post-processing of two-dimensional spectral analysis of exactly the same as basic.3,infant anesthesia:3.1 Drugs3.1.1 Phenobarbital sodium injection(Sodium Phenobarbital Injection)Pharmaco-toxicological and pharmacokinetics:This product is a colorless liquid clarity.This product has a wide range of central nervous system inhibition, with the resulting increase in the amount of sedative,hypnotic and anti-convulsive effect,when high-dose anesthetic effects,it is considered the main mechanism of the brain stem reticular formation and the blocking up of the activation system.Injection of 0.5～1 hour after the onset,2～18 hours of peak plasma concentration, distribution in tissue and body fluids with high concentrations of brain tissue, followed by skeletal muscle,the brain tissue to enter the slow through the placenta blood in 40 percent of the goods with the plasma protein binding.Half-life(t1/2) adults for the 48～144 hours,in children 40 to 70 hours,liver,renal insufficiency when the half-life(t1/2)to extend.About 65%of metabolism in the liver and converted to a p-barbital,most with glucuronic acid or sulfate-binding,and then discharged by the kidneys with the urine;27～50%of urine discharged from the prototype,some in the tubular reabsorption to the role of time.Usage and dosage:Preoperative administration of anesthesia prior to 0.5～1 hour and intramuscular injection of 100～200mg.Medication for children: Intramuscular injection:anticonvulsant,according to the weight the first 3～5mg/kg. Specifications:1ml:0.1g;ampoule 1ml×10 supportManufacturing enterprises:Tianjin Amino Acid Co.,Ltd.Jin-Yao;Approval Number-State H12020381;3.1.2 Chloral Hydrate(Chloral Hydrate)available for inspection to prevent the baby to wake upPharmaco-toxicological and pharmacokinetics:This product is hypnotic, anticonvulsant drugs.Dose within 30 minutes of hypnosis can be induced to sleep, and hypnotic effects of moderate,non-REMS shortened sleep time,no significant residual effect.Mechanism may be related to hypnotic barbiturates is similar to approximate the physiological cause of sleep,after no significant role.Larger doses have anticonvulsant effect,can be used for children with high fever,tetanus and sub-epileptic seizures caused.Large doses can cause coma and anesthesia.Inhibit the medullary respiratory and vasomotor center,leading to death.As the basis of anesthesia-assisted medication,has been very little application.Digestive tract or rectal administration can be quickly absorbed,1 hour,peaked at 4 to 8 hours to maintain.High-fat-soluble,easily through the blood-brain barrier,the distribution of the whole body of the organization.Plasma T1/2 for 7 to 10 hours a day.Rapid metabolism in the liver activity of triclosan into ethanol.Trichloro ethanol protein binding rate of 35～40%,trichloro ethanol T1/2 of approximately 4 to 6 hours. Oral chloral hydrate 30 minutes can go to sleep,duration of 4～8 hours.Trichloro ethanol further glucuronic acid binding and inactivation by the kidneys from,no hysteresis and accumulation.The drug through the placenta and secreted into the milk.Usage and consumption:the amount used in children:hypnosis,one by 50mg/kg body weight or body surface area 1.5g/m2,taken before going to bed, limited to a maximum 1g;also can be 16.7mg/kg body weight or body surface area 500mg/m2,3 times a day.Sedation,a 8mg/kg according to the weight or body surface area 250mg/m2,maximum limits for 500mg,3 times a day after meal. Enema,according to the weight of each 25mg/kg.Maximum dose for each 1g.Manufacturing enterprises:Nanfang Hospital,Southern Medical University; solution of chloral hydrate 10%4,the choice of regions of interest:Arrow next to the blood supply of distribution:the three cerebral artery(ACA ACA,middle cerebral artery MCA,posterior cerebral artery PCA)distribution area of red region hypoperfusion as the watershed areas are susceptible to cerebral ischemia;so I chose here as the main sense of interest in the district.5,statistical Data will be measured by infant gestational age and the location of ROI Acquisition classified SPSS13.0 Statistical Package for the importation,the basal ganglia were calculated and semi-oval center region of the average ratio of metabolites,with mean±standard deviation(±SD)form.Various metabolites Ch, Cr,NAA,Cr+Ch,Ch/Cr,Ch/NAA,NAA/Ch,NAA/Cr,Cr/NAA,MI,LIP, LAC value to mean±standard deviation(x±SD)of the form.(1)Comparison of basal ganglia metabolite ratio about whether the statistical difference;(2) Comparison of semi-oval around the central area of the metabolite ratios between any statistical difference;by test data in each group are in line with normal distribution.Comparison between the two groups interested in using one-way ANOVA,a significant difference in the overall circumstances,the use of LSD multiple comparison cycle 22.Region of interest with the group comparisons using paired t test.Interested in comparisons between about using independent samples t test.Test standard a value of 0.05 check.[Results]Large spectrum of metabolite resonance peaks include:1 NAA N-acetyl aspartate,at 2.0ppm,in the 1H-MRS in normal NNA is the second-highest peak.NAA mainly in neurons and their axon is seen within neuronal marker,NAA reduction reflects the loss of neurons or the volume of metabolism.2 Cho mainly phosphocholine and phosphate acetylcholine,the resonance peak at 3.2ppm.Under normal circumstances is a 1H-MRS of the No.1 high peaks.Cho and membrane phospholipid breakdown and synthesis,and to participate in the composition of cell membranes.Cho peak increased with active cell division and cell proliferation increase in metabolic abnormalities,and increased choline can cause demyelination. 3 Cr include creatine and creatine phosphate,and energy metabolism,and the resonance peak at 3.0ppm,is a 1H-MRS of high peak No.3.4 lactic acid(Lac)measured less than under normal circumstances,the resonance peak at 1.3ppm and 4.1ppm,double peak.Is a product of anaerobic glycolysis,the body can cause hypoxic-ischemic lactate accumulation,the diagnosis of HIBD significance.5 inositol(MI)resonance peak at 3.5ppm.With regulation of osmotic pressure, nutrition cells,anti-oxidation and generation,such as the role of surfactant.Performance machine and sequence parameters and spectral scanning technology:Can be seen from the above discussion,in order to obtain accurate spectral analysis results,it is necessary to pay attention to several key points are:a.anatomical location map must be vertical;b.positioning essential spectrum;c.recommend the use of VSS;d.spectral scanning shimming is the key;e.money each scan to be done auto prescan,observed linewidth value and the value of water suppression.MRI:the newborn is more sensitive to the imaging method;benefits: Conventional MRI gray matter(cortex,deep nuclei)injury in the high-signal T1-WI; based on injury time,pathological changes(hemorrhage,gliosis)T2-WI signal is changing;white matter damage due to ischemia,cerebral edema in the lower T1-WI signal,T2-WI signal;MRS(spectroscopy):to provide a rough and biochemical analysis of brain tissue,lactic acid,choline,creatine,NAA’s HIE peak potential prognostic prediction:A literature-MRS of HIE within 24 hours sensitive than DWI.5 cases of normal neonates may show NAA,Cr,Ch,towering peaks,MI peak is slightly lower,LAC,LIP measured peak or not the low,the peak of the order of high to low Ch,NAA,Cr,MI,LAC,LIP;ratio of Cr+Ch:19551.33±4210,Ch/Cr: 1.17±0.52,Ch/NAA:1.47±0.22,NAA/Ch:1.61±0.19,NAA/Cr:1.73±0.45, Cr/NAA:1.0135±0.24.MRS organizations to quantitative analysis of chemical composition and structure of neonatal brain in vivo study of the biochemical metabolic process and provide information on cellular energy metabolism,cell membrane collapse of neuronal function and neurotransmitter activities such as selective information[18～22].MRS examination method commonly used incentive echo(STEAM)and point-resolved method(PRESS).Determination of metabolites,including the following:N2 acetyl aspartate(NAA),choline(Cho),creatine plus phosphocreatine (Cr+PCr),inositol(MI),lactate(Lac)and the Valley glutamine and glutamate complex(Glu/Gln).NAA is a neuronal marker within,at 2.0ppm Department,in full-term newborn is the second-highest peak,after Cho peak with age after birth, growth and mature neurons,NAA peak gradually increased,6 months to NAA has risen to the most significant peaks.Cho peak,including free choline,phosphocholine and phosphatidylcholine,involved in phospholipid metabolism.Normal full-term newborns peak Cho peak at 3.2ppm,the quantitative study found that Cho content in neonatal brain than adults,a few months after birth as to accelerate the completion of myelin,Cho content started to decline.Cr reflect the organization’s potential energy, relative stability in the HIE,故常as a reference for other metabolites.Lac is the end product of glycolysis,is located at 1.33ppm Department,which prompted the emergence of aerobic respiration is no longer valid,and the normal low level of neonatal Lac peak.Gln/Glu at 2.3～2.5ppm spectral range,was more than saw the two difficult to separate the complexes referred to as Glx.MRS to early detection of neonatal hypoxic-ischemic brain damage,acute 6h after hypoxia-ischemia can be in the basal ganglia,thalamus and bilateral prefrontal white matter detected elevated Lac peak.A large number of research shows that children with HIE were significantly different from normal,that is,two peaks appeared in the 1,3ppm wave-like lactic acid,is due to the increase in anaerobic glycolysis,if the lactic acid content at a relatively low level,a few weeks due to local metabolism or increase the supply of oxygen,lactic acid content of the brain can gradually return to normal levels;if the lactic acid content of more than a certain critical value, continues to rise,causing acidosis cells and lead to irreversible neuronal damage loss, there decreased NAA(Figure 5).Results show that the Lac/Cr and NAA/Cr ratio in the HIE group and there are significant differences in the normal newborn,HIE group of Lac/Cr ratio was significantly increased,NAA/Cr ratio decreased significantly,and Lac/NAA and NAA/cho ratio can be used to Evaluation of prognosis of HIE.However,the determination of these values as a result of experiments,the methodology and the different MR field strength and are very different.Juliet that Lac/NAA ratio＞0.5,Floris that NAA/cho ratio＜0.8,then a poor prognosis,neurodevelopmental damage can occur.Li-Ying Chen of 52 cases diagnosed as HIE large sample study of children,according to Lac/Cr ratio of the size of the HIE is divided into mild,moderate,severe,mildly De ratio is 0.5 to 1.0, moderate for 1.0～2.0,severe were＞2.0 and above.The results showed that clinical follow-up with MRI and MRS is closely related to follow-up results,indicating that sub-MRS and MRI graduated degrees of HIE has important prognostic value of evaluation.Other manifestations include elevated Glx caused as a result of hypoxic-ischemic neurotransmitter into the synaptic cleft caused by the release.MI increased with tips and myelination gliosis bad.Mental development indexThe influence of various factors,mental development index of the correlation analysis showed that the mental development index were significantly correlated in the four variables,LAC and intellectual development of the most relevant index(r= 0.355 89,P Second 0.000 1),Study of the premature infants also confirmed this point.NAA is one aspect of it,the ratio of children’s intellectual development and the correlation between the results,although not the same,but the correlation coefficient is generally believed that for low to moderate level,high-score of children with high levels of intellectual development,but in different age groups and inconsistent,2 months ago in the correlation is very small,between 3 months began to emerge related to the long-term after a few months in line with related significantly also.For infants and young children,the sound of early treatment of central nervous system development and maturation has a crucial role.The results of this study show that the more medical intervention,the mental development index was higher in line with related research.In addition,the Canadian Chamber of the spirit of the parents have a significant effect on movement operations.Of HIBD in the process of growth and development of children’s recognition of the importance of a deeper level.Therefore,infants and young children need to attach great importance to score situation HIBD period.The impact of mental development index of gestational age may be due to a terms of gestational age from infants and young children indicates that the degree of maturity at birth,especially the development of brain systems development in infants and young children as a starting point, especially in young infants on the mental development index an even greater impact.Psychomotor development indexThe role of early motor development index indicates the correlation analysis showed that significant movement-related development index are:medical intervention,early diagnosis and gestational age;sports development index of one-way ANOVA showed that the medication during pregnancy in this group show, the infant psychomotor development index is also different;results and the impact of intellectual development index similar factors.Children’s movements and the control of the body so that they can flexibly adapt to the new,ever-changing environment, such as infant and child development skills to promote a variety of other basic intelligence of the development and application of the process,when the mental and motor scale points between the high positive correlation.Its clinical significance of the motor function disorders can be used as early signs of nerve injury.[Conclusions]1.MRS normal neonatal examination:Spectrum Scanning:Scanning of conventional coils T1,T2,FLAIR image;the use of a dedicated single-channel quadrature head coil,multi-voxel two-dimensional (2D-multi-voxel)point-resolved spectroscopy(PRESS)imaging sequence,TR/TE: 1000ms/144ms,frequency encoding is set to 16,the frequency encoding direction of A/P,the thickness of voxel(voxel thickness)10mm,spacing 20mm,NEX 1, FOV 18mm×18mm.T1WI or T2WI in plain pure axial position on the spectrum, spectral scanning field(VOI)size of the case may be based on disease should include the infant with bilateral basal ganglia and semi-oval center region,to avoid including the skull,scalp fat,Gas image quality,such as the impact of the organizational spectrum.Pre-positioning after the first scan,indicating semi-automatic shimming to achieve high linewidth(FWHM)98%or more to the beginning of formal spectral scanning,scan time of approximately 5 minutes.Image post-processing:the use of GE Company 3.0T magnetic resonance analysis of a random configuration package“FuncTool”automatically scan spectrum of chemical frequency chart baseline correction,the frequency of reversal,a retrospective voxel-transfer post-processing after the post-processing workstations can simultaneously access four graphics,that is,chemical shift map(ChemicalShift Image,CSI),Spectral map(Spectrum,SI),metabolic map(Metabolic Images,MI), as well as metabolic and anatomical map of the overlay map(AI+MI,referred to as“-A Solution Map”)(see Figure 1).The device pre-set size of a voxel machines recommended 31.6mm.In the“metabolism-anatomical overlay map(AI+MI)”to place the two regions of interest(ROI),are located in the basal ganglia region (ROI-1),semi-oval center region(ROI-2),post-processing software automatically access to all VOI voxel location,the number of individual-endoperoxide and the spectral information(see Figure 1B,1C).In the post-processing,in accordance with the scope of choice in the“on behalf of-solution map”set from 1-4 individual Su-box integration as a region of interest(ROI)size,size of general interest to the individual by 1-4 Su-component.In the“on behalf of-solution”map to observe the distribution of metabolite concentrations,in the corresponding spectral map(SI)on regions of interest to observe the performance of the peak.At the same time, graphical analysis software automatically identify and calculate the area under the metabolite peak on behalf of its concentration,and automatic calculation of the relative metabolite ratios.In the“on behalf of-solution map”on the observation of the metabolite concentration of the pseudo-color distribution,the corresponding spectrum in the ROI map(Spectrum,SI)on the observation of the peak level of metabolites,the horizontal axis represent the chemical shifts of metabolites location, unit ppm expressed in(ppm position as shown in table 1),on behalf of the longitudinal axis of the peaks and the situation of metabolites.At the same time, graphics workstations and the analysis software automatically identify and calculate the ROI of the corresponding N-acetyl aspartate(NAA),choline(Cho),creatine(Cr), lactate(Lac)and lipid(Lip),etc.under the metabolite peak area values from the representative of the concentration of the material and automatically calculated the relative metabolite ratios.In this study,all patients in the MR and MRS data at the time of diagnosis experienced by the three images together practitioners reading piece,image post-processing and data measurement,recording the ROI of the Ch,Cr, NAA,Cr+Ch,Ch/Cr,Ch/NAA,NAA/Ch,NAA/Cr,Cr/NAA,MI,LIP,LAC value and relative metabolite ratios,at the same time record peak Lip or Lac peak in the group respectively,the number of cases.2.Performance of normal newborns MRS:5 cases of normal neonates may show NAA,Cr,Ch,towering peaks,MI peak is slightly lower,LAC,LIP measured peak or not the low,the peak of the order of high to low Ch,NAA,Cr,MI,LAC,LIP;ratio of Cr+Ch:19551.33±4210,Ch/Cr: 1.17±0.52,Ch/NAA:1.47±0.22,NAA/Ch:1.61±0.19,NAA/Cr:1.73±0.45, Cr/NAA:1.0135±0.24.The accurate measurement of in vivo effects of metabolites on the treatment and other purposes of analysis play a very important role.Measured by value and the true metabolite metabolites or different values;can not represent the actual value. Susceptible to lipid molecules such as lactic acid and the effects of giant molecules is higher than the actual value,inositol in the body due to its low content of difficult to measure or smaller than the actual value,using PRESS sequence can not effectively distinguish between N-acetyl-and other containing N-acetyl amino acid Kiki mission,such as N-acetyl-aspartate salt,N-acetyl glutamic acid and N-acetyl group,or glutamic acid/glutamine resonance frequency,so in vivo MRS able to measure the value of N-acetyl-aspartate was significantly higher than high-performance liquid chromatography measurement of the value of N-acetyl aspartate.MRS can detect specific brain metabolites in various levels,from the perspective of quantitative biochemical indicators reflect the additional changes. Biopsy is also capable of chemical substances in non-invasive detection of the only way,in many diseases and the development process,metabolic changes often early in the morphological changes,so fully understand the MRS can provide metabolic information and the pros and cons of no doubt help the early diagnosis of disease.HIBD evaluation of neonatal MRI method has many other advantages of unparalleled,and can more accurately reflect the site of brain lesions,scope,nature and the relationship with the surrounding structures,MRS can detect the specific metabolism of the brain material level,from the perspective of quantitative biochemical indices reflect more.However,a variety of imaging(DWI,PWI)will be a joint application to reveal the depth of neonatal brain injury HIBD pathologic basis of imaging can be accurate diagnosis of early lesions and the severity of the disease and to determine accurately assess the prognosis for the best rehabilitation programs have important clinical value.MRS magnetic resonance technology can predict the prognosis of children with HIBD and assessment through the comparison and found that the value of MRS metabolites can be a direct response to children with the prognosis,again based on the application of appropriate medical intervention,HIBD score reflects the value of MRS basically the same;With the popularization of magnetic resonance MRS examination,BSID and promote the wider use of MRS technology to provide early screening of patients HIBD to address the issue of its early diagnosis.And neonatal awareness,monitoring and treatment of dyskinesia of the efficacy of intervention to provide a means to observe and promote the study of the treatment and HIBD depth,and ultimately improve the quality of life of some of the crowd.更多还原