肝脏MR动态增强扫描:Gd-EOB-DTPA与Gd-DTPA的个体内对照研究

吴静云,王可,郭小超,王霄英

·LI-RADS临床应用研究专题·

肝脏MR动态增强扫描:Gd-EOB-DTPA与Gd-DTPA的个体内对照研究

吴静云,王可,郭小超,王霄英

目的:比较钆塞酸二钠(Gd-EOB-DTPA)及钆喷酸葡胺(Gd-DTPA)肝脏M R动态增强扫描腹腔脏器及血管的强化特点,重点比较Gd-EOB-DTPA移行期与Gd-DTPA平衡期的图像特点。方法:本研究为前瞻性、个体内随机对照研究。25例病理证实为原发直肠癌或结肠癌、怀疑肝转移的患者,3天内行2次肝脏M R动态增强检查,分别使用Gd-EOB-DTPA及Gd-DTPA两种对比剂。动态增强扫描的序列相同,包括平扫、动脉期、门静脉期、平衡期(Gd-DTPA)/移行期(Gd-EOB-DTPA)。图像客观评估中,测量各期相图像上血管及肝脾实质的信号强度。以椎旁肌肉的信号为参考,计算相对信号强度(RS)并比较两组间的差异,以及不同期相时肝实质RS的差异。主观评估:读片者主观评价增强扫描各期相图像上,主动脉、门静脉及肝静脉与肝实质的相对信号强度。结果:肝实质的RS:在动脉期Gd-DTPA组明显高于Gd-EOB-DTPA组(t=3.006,P=0.005);在门静脉期及平衡期/移行期,两组检查的差异无统计学意义(t=1.788,P=0.086; t=0.781,P=0.442)。Gd-EOB-DTPA检查时,门静脉期肝实质RS明显高于动脉期(t=-3.014,P=0.006),移行期RS与门静脉期的差异无统计学意义。Gd-DTPA检查时,平衡期肝实质RS明显低于门静脉期(t=5.827,P=0.000)。主观评估:Gd-DTPA增强扫描平衡期图像上所有患者的主动脉、门静脉、肝静脉均为高信号(100%);Gd-EOB-DTPA增强扫描移行期图像上主动脉、门静脉、肝静脉均以低或等信号为主(84%,92%,92%)。结论:Gd-EOB-DTPA动态增强M R检查,肝脏实质在门静脉期及移行期呈持续强化,其移行期的图像特征与Gd-DTPA平衡期的图像特征有明显不同,在影像诊断时应予以关注。

动态增强扫描;磁共振成像;肝脏;对比剂

MRI具有良好的软组织对比,已广泛应用于肝脏检查,T2WI和DWI对病灶的检出效能较高[1],联合使用动态增强扫描则可进一步提高检出和定性诊断的效能。临床肝脏M R增强检查中主要使用非特异性细胞外间隙对比剂——Gd-DTPA,但近年来肝脏特异性对比剂的使用越来越广泛[2-3],以Gd-EOB-DTPA (商品名Primovist,普美显)为代表。由于肝脏特异性对比剂的代谢途径与非特异性细胞外间隙对比剂不同,在增强扫描不同期相采集的图像特征也有差别。本文研究了同一组患者在行Gd-DTPA和Gd-EOBDTPA增强扫描时的图像特征方面的差别。

材料与方法

本研究为前瞻性研究。经医院伦理委员会批准,所有患者检查前了解并签署知情同意书。病例入组标准:确诊为直肠癌或结肠癌且怀疑有肝转移瘤的患者;肝肾功能正常;3天内分别进行Gd-DTPA及Gd-EOB-DTPA肝脏动态增强MR检查(两种增强扫描的次序由随机数字表确定)。排除标准:有MR检查或者含钆对比剂禁忌证的患者。2013年2月-2015年11月共纳入25例受试者,其中男17例,女8例,年龄34～79岁,平均60.4岁。

使用GE Discovery HD750 3.0 TM R仪和体部相控阵线圈。动态增强扫描采用脂肪抑制3D LAVA (GRET1WI)序列。两种对比增强均采集4个期相,包括平扫、动脉期(延迟时间30s)、门静脉期(60s)、平衡期/移行期(180s)。Gd-EOB-DTPA增强扫描增加2个期相的延时扫描[延迟时间15、20 min(肝胆期)],横轴面及冠状面采集。

图像客观评估中,测量各期图像上血管及脏器的信号强度,包括主动脉、下腔静脉、门静脉、肝静脉、肝和脾实质。以椎旁肌肉的信号为参考,按照公式(1)计算上述结构在不同对比增强各期相时的相对信号强度(relative signal intensity,RS):

主观评估:读片者主观评价与肝脏实质相比各大血管结构的相对信号强度。

两组间及同一组内不同期相间客观评价指标(RS)的比较,使用配对t检验。主观评估指标的比较,使用卡方检验。P＜0.05为差异有统计学意义。

结 果

1.客观评估

两组增强扫描各期图像上肝脾实质及上腹部大血管的RS测量结果及比较见表1、图1～3。两组MR增强检查中,平扫图像上肝脾实质及血管结构的RS值的差异无统计学意义(P＞0.05)。动脉期时,Gd-DTPA增强扫描图像上下腔静脉、门静脉、肝静脉、肝脾实质的RS值均高于Gd-EOB-DTPA增强扫描,两组间的差异有统计学意义(P＜0.05);门静脉期时, Gd-DTPA增强扫描图像上主动脉、下腔静脉、门静脉、肝静脉和脾脏实质的RS值均高于Gd-EOB-DTPA增强扫描,两组间的差异具有统计学意义(P＜0.05);平衡期时,Gd-DTPA增强扫描图像上主动脉、下腔静脉、门静脉、肝静脉和脾脏实质的RS均高于Gd-EOB-DTPA移行期图像,两组间的差异具有统计学意义(P＜0.05)。门静脉期及平衡期/移行期,两组间肝脏实质RS值的差异无统计学意义(P＞0.05)。

同一组检查中肝脏实质不同期相的RS(图4): Gd-DTPA动态增强扫描过程中,动脉期肝实质的RS值较平扫有显著增高(t=4.657,P=0.000),但与门静脉期比较差异无统计学意义(t=-1.892,P= 0.070),平衡期肝脏实质的RS值较门静脉期有显著降低(t=5.827,P=0.000);Gd-EOB-DTPA动态增强扫描过程中,门静脉期肝实质的RS值与动脉期比较有显著增高(t=-3.014,P=0.006),但与移行期

比较差异无统计学意义(t=1.310,P=0.203)。

表1 两组MR增强检查各期相图像上各结构的RS值

2.主观评估

两组增强扫描各期相图像上(图5),主动脉、门静脉和肝静脉的相对信号强度(与肝脏实质相比)的主观评估结果见表2。

表2 各期相图像上大血管的相对信号强度的主观评估结果 (例)

Gd-DTPA动态增强扫描过程中,平衡期时全部病例的主动脉、门静脉和肝静脉均为高信号(100%); Gd-EOB-DTPA动态增强扫描过程中,移行期时主动脉、门静脉和肝静脉均以低信号～等信号为主(分别占84%、92%和92%)。

讨 论

Gd-EOB-DTPA是肝脏特异性对比剂,可被肝细胞摄取,并经胆管排泄[2,3]。团注Gd-EOB-DTPA后约20 min,肝实质的强化达到峰值。多项研究发现Gd-EOB-DTPA与Gd-DTPA动态增强检查中,血管及脏器的强化特征不一致[4],影像诊断的思路和诊断标准也应有所不同。本文采用自身对照的方法,研究同一组患者在短期内分别注射Gd-DTPA和Gd-EOBDTPA行动态增强M R检查,不同期相图像上腹部脏器及大血管强化的差异。

Gd-EOB-DTPA同时具有细胞外对比剂及肝脏特

异性对比剂的特点,经静脉注射后约50%的Gd-EOBDTPA经肾脏排泄,50%经胆管排泄。关于Gd-EOBDTPA动态增强MRI是否具有Gd-DTPA动态增强MRI同样的血管及组织强化效果,既往的研究比较少,结果也不一致。有几项在1.5 TMR设备上进行的Gd-EOB-DTPA与细胞外含钆对比剂(钆布醇)的研究,认为Gd-EOB-DTPA与传统对比剂的血管强化效果没有差别[5-7]。Fujinaga等[8]研究者在3.0 TMR设备上对17例受试者进行自身对照研究,比较Gd-EOB-DTPA与Gd-DTPA动态增强MRI上脏器及血管的强化特点,结论与本研究类似,Gd-EOB-DTPA增强扫描时血管强化程度低于Gd-DTPA。

本研究采用自身对照的方法,探讨了Gd-EOBDTPA与Gd-DTPA动态增强检查脏器及血管强化特点的差异。Gd-EOB-DTPA动态增强M R检查,除门静脉期及平衡期的肝脏实质外,动脉期肝脏实质、动态增强各期血管及脾脏的强化程度均低于Gd-DTPA动态增强扫描,这可能与Gd-EOB-DTPA注射剂量小有关[9]。Gd-EOB-DTPA的临床常用剂量是Gd-DTPA的一半(0.1 mL/kg vs 0.2 mL/kg),钆含量为Gd-DTPA的25%(0.025 mmol/kg vs 0.1 mmol/kg)。尽管Gd-EOB-DTPA具有较高的T1弛豫率[5,10],但由于注射剂量小,因此在动态增强扫描早期(3分钟以内)相对于传统的细胞外含钆对比剂,脏器和血管的强化程度相对较低。此外,有研究发现Gd-EOB-DTPA动态增强扫描时动脉期出现严重运动伪影的概率较传统含钆对比剂高,发生率约10.7%～18.0%[11-13]。这种伪影的存在影响动脉期图像质量,目前尚不清楚原因。

门静脉期及平衡期/移行期,肝脏的相对信号强度在Gd-EOB-DTPA及Gd-DTPA动态增强MR检查中的差异无统计学意义。这与Kuhn等[6]比较Gd-EOB-DTPA及传统细胞外含钆对比剂(钆布醇)的结果类似。其它研究发现,Gd-EOB-DTPA动态增强扫描移行期图像上肝脏强化程度明显高于Gd-DTPA,认为移行期时因肝细胞摄取Gd-EOB-DTPA,因此其强化高于Gd-DTPA[8]。本研究与其结果不一致,可能是因为平衡期的时相选取不一致。但本研究经过纵向比较发现,Gd-EOB-DTPA检查中,肝脏实质在门静脉期的强化程度显著高于动脉期,这与肝脏本身的血供特点有关(肝脏主要由门静脉供血,因此门静脉期强化程度高于动脉期);移行期强化程度未见显著下降,这可能与肝细胞摄取对比剂有关。在Gd-DTPA检查中,肝脏实质在门静脉期强化程度与动脉期的差异无统计学意义,但绝对值是上升的,这可能与本研究样本量小、测量过程存在误差有关;平衡期时Gd-DTPA不能被肝细胞摄取,因此肝实质强化程度明显下降。

Gd-EOB-DTPA与传统的细胞外对比剂不同,没有纯粹的平衡期,与之对应的时相定义为移行期(transitional phase),约为注射对比剂后120～300s,表示对比剂从细胞外向细胞内移行的时期,与肝胆期重叠。移行期的概念在2010年由欧洲放射学会明确提出,很快就被业内广泛接受和使用[14-15]。移行期与平衡期这两个概念有本质的差别:注射Gd-DTPA后3分钟时的肝脏信号,取决于血池和细胞外间隙的对比剂滞留情况;而Gd-EOB-DTPA增强后90～180s时的肝脏信号,还受到了肝细胞摄取对比剂这一因素的影响,肝脏实质呈高信号。对移行期肝脏信号特点的产生机制目前还并未完全阐明,在这一时期,肝脏内的"低"信号区域可能是由于肝脏实质高强化的衬托造成的,而并非传统意义上的少血供性低强化[14,16]。以肝静脉为例,在主观评估中发现,Gd-EOB-DTPA增强扫描移行期图像伤肝静脉表现为"低"信号,而Gd-DTPA增强扫描平衡期图像上肝静脉表现为"高"信号。这种移行期与平衡期图像的差异,应引起足够的重视,在分析移行期图像中"低"信号病灶时,其图像分析的思路与常规增强扫描不同。

本研究较其它研究的优势是采用了自身对照的方法,但也存在不足之处:样本量较小,肝脏病灶性质单一,受试者为肝肾功能正常的人群。

综上所述,Gd-EOB-DTPA动态增强M R检查,肝脏实质在门静脉期及移行期信号持续增高,其移行期的图像特征与Gd-DTPA平衡期的图像特征有明显不同,在影像诊断时应予以关注。

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Comparison of gadoxetate disodium and gadopentetate dimeglumine in dynamic contrast-enhanced liver MRI:an intra-individual comparative study

WU Jing-yun,WANG Ke,GUO Xiao-chao,et al.Department of Radiology,Peking University First Hospital,Beijing 100034,P.R.China

Objective:To compare the imaging feature of dynamic contrast enhanced liver MR imaging by gadoxetate disodium(Gd-EOB-DTPA)and gadopentetate dimeglumine(Gd-DTPA).Methods:Twenty-five patients suspected of liver metastases from colorectal cancer underwent twice MR examinations on 3.0 T scanner using the contrast agent of Gd-EOBDTPA(0.05 mmol/kg)and Gd-DTPA(0.1 mmol/kg)respectively.Pre-and post-dynamic contrast enhanced images were acquired,including arterial phase(AP),portal venous phase(PP),equilibrium phase(EP for Gd-DTPA)/transitional phase (TP for Gd-EOB-DTPA).On images of all phases,signal intensity of abdominal organs(liver and spleen)and vessels(aorta,inferior vena cava,portal vein,hepatic vein)were measured,and signal intensity of paravertebral muscle was measured as reference.Relative signal intensity(RS)were calculated and compared between the two groups using the two types of contrast media.The image features of contrast enhanced images were also subjectively evaluated.Results:There was statistically significant difference in RS of liver on AP images between the two groups(t=3.006,P=0.005).There was no statistically significant difference in RS of liver on EP and TP images between the two groups.In Gd-EOB-DTPA group,liver RS on PP images was much higher than that on AP images(t=-3.014,P=0.006),and on TP images,liver RS was lower than that on PP images but without statistic difference.In Gd-DTPA group,liver RS was much lower on EP images than that on PP images(t=5.827,P=0.000).In subjective evaluation,aorta,portal vein and hepatic vein of all patients were hyperintense on EP images in Gd-DTPA group;whereas in Gd-EOB-DTPA group,aorta,portal vein and hepatic vein were mainly hypoor iso-intense images(84%,92%,92%).Conclusion:In Gd-EOB-DTPA dynamic contrast enhanced MRI,liver parenchyma was continuously enhanced during portal venous phase and transitional phase.The image features in equilibrium phase of Gd-DTPA enhanced scan are quite different from transitional phase of Gd-EOB-DTPA enhanced scan,which should be considered in diagnosis.

Dynamic contrast-enhancement scan;Magnetic resonance imaging;Liver;Contrast media

R445.2;R735.7

A

1000-0313(2016)04-0326-05

10.13609/j.cnki.1000-0313.2016.04.010

2016-02-02

2016-03-15)

100034 北京,北京大学第一医院医学影像科

吴静云(1985-),女,广西桂林人,博士,住院医师,主要从事泌尿生殖系统影像诊断和对比剂成像研究。

王霄英,E-mail:cjr.wangxiaoying@vip.163.com