張澍杰，饒圣祥，陳錦，李軔晨，陳財(cái)忠，曾蒙蘇

·腹部影像學(xué)·

Gd-EOB-DTPA與Gd-DTPA增強(qiáng)MR對(duì)肝硬化患者肝血管和肝實(shí)質(zhì)增強(qiáng)效果的自身對(duì)照研究

張澍杰，饒圣祥，陳錦，李軔晨，陳財(cái)忠，曾蒙蘇

目的自身對(duì)照比較Gd-EOB-DTPA與Gd-DTPA增強(qiáng)MR對(duì)肝硬化患者的肝動(dòng)脈、門靜脈和肝實(shí)質(zhì)強(qiáng)化效果的差異。方法回顧性分析35例肝硬化患者的Gd-EOB-DTPA與Gd-DTPA增強(qiáng)MR圖像，計(jì)算肝總動(dòng)脈、門靜脈和肝實(shí)質(zhì)的強(qiáng)化比率(PE)和肝總動(dòng)脈、門靜脈與肝實(shí)質(zhì)的相對(duì)對(duì)比度(RC)，并統(tǒng)計(jì)是否存在差異。結(jié)果Gd-EOB-DTPA增強(qiáng)MR肝總動(dòng)脈、門靜脈的平均PE明顯低于Gd-DTPA(P<0.05)。Gd-EOB-DTPA的門脈期肝實(shí)質(zhì)的平均PE明顯低于Gd-DTPA(P<0.05)而動(dòng)脈期肝實(shí)質(zhì)的PE值無(wú)明顯差異(P=0.1010)。肝總動(dòng)脈、門靜脈與肝實(shí)質(zhì)的RC值Gd-DTPA增強(qiáng)MR略高于Gd-EOB-DTPA，但是無(wú)明顯統(tǒng)計(jì)學(xué)差異(P分別為0.3421和0.2389)。結(jié)論肝硬化患者Gd-EOB-DTPA增強(qiáng)MR的肝血管和肝實(shí)質(zhì)效果低于Gd-DTPA,Gd-EOB-DTPA的劑量需要進(jìn)一步調(diào)整。

磁共振成像；肝硬化；對(duì)比劑；對(duì)照研究

Gd-EOB-DTPA(gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid)是肝臟新型的特異性對(duì)比劑，已開(kāi)始應(yīng)用于臨床并顯示其優(yōu)越性。目前研究表明Gd-EOB-DTPA不僅對(duì)提高肝臟局灶性病變的檢出、診斷與鑒別診斷的能力[1-3]，而且對(duì)判斷肝癌的發(fā)展、侵襲性及預(yù)后的判斷有重要的臨床應(yīng)用價(jià)值[4-5]。但是對(duì)于Gd-EOB-DTPA對(duì)肝動(dòng)脈、門靜脈的強(qiáng)化程度報(bào)道較少而且局限性于動(dòng)物實(shí)驗(yàn)和健康正常人[6-7]，因此本研究的目的在于自身對(duì)照比較Gd-EOB-DTPA與Gd-DTPA (gadolinium diethylenetriamine pentaacetic acid)增強(qiáng)MR對(duì)肝硬化患者的肝動(dòng)脈、門靜脈及肝實(shí)質(zhì)的強(qiáng)化效果。

材料與方法

1.臨床資料

回顧性分析復(fù)旦大學(xué)附屬中山醫(yī)院2011年9月-2012年12月的肝硬化患者的MRI資料，納入標(biāo)準(zhǔn)：①患者行兩次上腹部增強(qiáng)MR，對(duì)比劑分別為Gd-DTPA(Magnevist，Bayer Schering Pharma，0.5 mol/L)和Gd-EOB-DTPA(Primovist，Bayer Schering Pharma,0.25 mol/L)；②兩次檢查間隔≤15 d；③兩次檢查均在同1臺(tái)MR儀進(jìn)行檢查；④MRI圖像沒(méi)有明顯的呼吸運(yùn)動(dòng)偽影；⑤肝硬化通過(guò)影像學(xué)診斷[8]、病理證實(shí)或臨床標(biāo)準(zhǔn)診斷。排除標(biāo)準(zhǔn)：患者經(jīng)過(guò)動(dòng)脈栓塞或手術(shù)等治療。

2.檢查方法

采用1.5T MRI掃描儀(Magnetom Area,Siemens AG)，檢查前禁食6 h，動(dòng)態(tài)增強(qiáng)掃描序列采用3D-T1WI三維屏氣容積內(nèi)插法(volume interpolated breathhold examination,VIBE)抑脂序列，掃描參數(shù)如下：TR 3.47 ms，TE 1.36 ms，翻轉(zhuǎn)角10°，矩陣320×195，視野(380～400)mm×(300～324)mm，層厚3 mm，層間距21.6 mm，1次信號(hào)采集，帶寬400 Hz/px。應(yīng)用全面自動(dòng)校準(zhǔn)部分并行采集(generalized autocalibrating partially parallel acquisitions,GRAPPA)技術(shù)，加速因子為2。對(duì)比劑Gd-DTPA和Gd-EOB-DTPA的用量分別為0.1 mmol/kg和0.025 mmol/kg，采用手推注射，注射流率約1～2 mL/s，注射完畢后以相同流率注射20 mL生理鹽水。動(dòng)脈期掃描采用監(jiān)測(cè)降主動(dòng)脈，當(dāng)對(duì)比劑到達(dá)時(shí)自動(dòng)觸發(fā)掃描，門靜脈期、平衡期分別與動(dòng)脈期間隔14和90 s。Gd-EOB-DTPA增強(qiáng)掃描額外加掃肝膽特異期(延遲20 min)。

3.圖像分析

所有圖像都在Siemens Leonardo工作站上進(jìn)行分析，由1位有經(jīng)驗(yàn)的放射科醫(yī)生測(cè)量肝臟平掃、動(dòng)脈期和門脈期的肝總動(dòng)脈、門靜脈和肝實(shí)質(zhì)的信號(hào)值。肝總動(dòng)脈、肝門靜脈測(cè)量測(cè)量時(shí)興趣區(qū)(regions of interest，ROI)取圓形或卵圓形，置于血管的中心，門靜脈測(cè)量選取左右門靜脈匯合層面，肝實(shí)質(zhì)測(cè)量選取肝門層面，盡量避開(kāi)大血管和膽道。然后計(jì)算以下參數(shù)：①肝動(dòng)脈、門靜脈和肝實(shí)質(zhì)的強(qiáng)化率PE(percentage enhancement)=(SIpost-SIpre)/SIpre，SIpre和SIpost分別代表增強(qiáng)前后的信號(hào)值；②計(jì)算肝總動(dòng)脈、門靜脈與肝實(shí)質(zhì)的相對(duì)對(duì)比度RC(relative contrast)=(SI tissue A-SI tissue B)/SI tissue A，tissue A的信號(hào)值高于tissue B[9]。

4.統(tǒng)計(jì)學(xué)方法

Gd-EOB-DTPA與Gd-DTPA增強(qiáng)MR的肝總動(dòng)脈、門靜脈和肝實(shí)質(zhì)的PE以及門靜脈與肝實(shí)質(zhì)的RC值采用配對(duì)t檢驗(yàn)。由于Gd-DTPA增強(qiáng)MR的肝總動(dòng)脈與肝實(shí)質(zhì)的RC值不服從正態(tài)分布，因此肝總動(dòng)脈與肝實(shí)質(zhì)的RC值采用非參數(shù)檢驗(yàn)Wilcoxon符號(hào)秩和檢驗(yàn)比較。利用MedCalc軟件進(jìn)行統(tǒng)計(jì)分析，以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

結(jié)果

1.入選患者的基線特征

總共35患者入選，其中男24例，女11例，年齡36～64歲，中位年齡54歲。兩次MRI檢查間隔中位時(shí)間為6 d(2～14 d)。35例中12例(34.29%，12/35)患者血AFP升高(>20 ng/ml)。所有患者均因肝癌行MRI檢查，其中23例行手術(shù)切除，12例行射頻治療前穿刺證實(shí)。肝硬化診斷23例由手術(shù)證實(shí)，其余病理通過(guò)影像或臨床診斷。肝硬化原因有乙肝(n=33和不明原因(n=2)。根據(jù)Child-Pugh分級(jí)，A級(jí)31例，B級(jí)4例。

圖1 a)肝動(dòng)脈、門靜脈的強(qiáng)化率的中位數(shù)和四分位數(shù)間距范圍的箱式圖；b)肝動(dòng)脈、門靜脈與肝臟的對(duì)比度的中位數(shù)和四分位數(shù)間距范圍的箱式圖；c)肝實(shí)質(zhì)的強(qiáng)化率的中位數(shù)和四分位數(shù)間距范圍的箱式圖。(HA代表肝動(dòng)脈，PV代表門靜脈，AP代表動(dòng)脈期，PP代表門脈期)。

2.定量分析

Gd-EOB-DTPA與Gd-DTPA增強(qiáng)MR的肝總動(dòng)脈、門靜脈和肝實(shí)質(zhì)的PE以及肝總動(dòng)脈、門靜脈與肝實(shí)質(zhì)的RC值的結(jié)果分布見(jiàn)箱式圖1和圖2。動(dòng)脈期Gd-DTPA增強(qiáng)MRI肝總動(dòng)脈的平均強(qiáng)化率PE明顯高于Gd-EOB-DTPA，差異有統(tǒng)計(jì)學(xué)意義(4.4064 vs 2.9242，t=-5.794，P<0.0001，圖1a)；而Gd-DTPA增強(qiáng)MRI肝實(shí)質(zhì)的平均強(qiáng)化率高于Gd-EOB-DTPA增強(qiáng)，但差異無(wú)統(tǒng)計(jì)學(xué)意義(0.1903 vs 0.1248，t=1.686，P=0.1010，圖1c)。門脈期Gd-DTPA增強(qiáng)MR門靜脈和肝實(shí)質(zhì)的平均強(qiáng)化率PE均明顯高于Gd-EOB-DTPA，差異有統(tǒng)計(jì)學(xué)意義(門靜脈：4.0841 vs 2.6409，t=-5.206，P<0.0001，圖1a；肝實(shí)質(zhì)：0.5198 vs 0.8598，t=-7.725，P<0.0001，圖1c)。Gd-DTPA增強(qiáng)肝總動(dòng)脈、門靜脈與肝實(shí)質(zhì)的RC值略高于Gd-EOB-DTPA增強(qiáng)(圖2)，但差異無(wú)統(tǒng)計(jì)學(xué)意義(肝總動(dòng)脈與肝實(shí)質(zhì)的RC值：0.5733 vs 0.5550，Z=-5.950，P=0.3421；門靜脈與肝實(shí)質(zhì)的RC值：0.3219 vs 0.2963，t=-1.199，P=0.2389,圖1b)。

圖2 肝硬化，肝癌。a)Gd-EOB-DTPA增強(qiáng)動(dòng)脈期示肝動(dòng)脈和門靜脈(直箭)及肝左葉肝癌病灶(彎箭)；b)Gd-EOB-DTPA增強(qiáng)門脈期示肝動(dòng)脈和門靜脈(箭)及肝左葉肝癌病灶；c)Gd-DTPA增強(qiáng)動(dòng)脈期示肝動(dòng)脈和門靜脈(箭)高于Gd-EOB-DTPA增強(qiáng)；d)Gd-DTPA增強(qiáng)門脈期示肝動(dòng)脈和門靜脈(箭)強(qiáng)化程度高于Gd-EOB-DTPA增強(qiáng)。

討論

本研究通過(guò)測(cè)量肝動(dòng)脈、門靜脈及肝實(shí)質(zhì)強(qiáng)化率評(píng)價(jià)血管及肝實(shí)質(zhì)的直接強(qiáng)化效果，筆者發(fā)現(xiàn)Gd-EOB-DTPA增強(qiáng)MRI的肝動(dòng)脈、門靜脈強(qiáng)化率明顯低于Gd-DTPA。以往對(duì)Gd-EOB-DTPA的研究大都著力于肝膽特異期對(duì)腫瘤的定性、檢出[1-5]，這主要由于定性、檢出是腫瘤評(píng)估的主要目的，臨床上很少因?yàn)閱渭冊(cè)u(píng)估血管而做MRI，但是評(píng)估血管的變異、門靜脈高壓以及腫瘤是否侵犯血管在臨床診療過(guò)程中也是非常重要的。Tamad等[7]通過(guò)健康人體研究發(fā)現(xiàn)Gd-EOB-DTPA增強(qiáng)MRI主動(dòng)脈、門靜脈的強(qiáng)化程度均低于Gd-DTPA。本研究發(fā)現(xiàn)肝硬化患者血管強(qiáng)化效果結(jié)果與Tamada等的研究的正常人結(jié)果相似，Gd-EOB-DTPA增強(qiáng)MRI肝動(dòng)脈、門靜脈強(qiáng)化程度低，主要原因Gd-EOB-DTPA的標(biāo)準(zhǔn)劑量是Gd-DTPA劑量的1/4(0.025 mmol/kg vs 0.1 mmol/kg)，而兩者在37℃時(shí)1.5T MR的弛豫率比值僅是的58.9% (Gd-EOB-DTPA vs Gd-DTPA:7.3 vs 4.3 L/mmol/s)[10]，但是Zench等[6]進(jìn)行動(dòng)物實(shí)驗(yàn)研究發(fā)現(xiàn)3D-T1WI(VIBE)動(dòng)脈掃描Gd-EOB-DTPA增強(qiáng)MR主動(dòng)脈強(qiáng)化最高值與Gd-DTPA無(wú)明顯差異，主要由于梯度回波VIBE序列在對(duì)比劑濃度很高時(shí)會(huì)飽和效應(yīng)所致(釓的溶液濃度高于5.0 mmol/L時(shí)出現(xiàn))[11]，但是本研究中未出現(xiàn)相應(yīng)結(jié)果，估計(jì)由于在人體內(nèi)血管內(nèi)釓不能達(dá)到足夠的濃度而出現(xiàn)飽和現(xiàn)象，因此在人體內(nèi)信號(hào)強(qiáng)度隨著釓濃度升高近似線性升高，因此推測(cè)應(yīng)用更高劑量可以提高動(dòng)脈期腫瘤、肝內(nèi)血管的強(qiáng)化效應(yīng)[2]。本研究另發(fā)現(xiàn)動(dòng)脈期和門靜脈肝實(shí)質(zhì)強(qiáng)化程度Gd-EOB-DTPA均低于Gd-DTPA，但只有門脈期差異才有統(tǒng)計(jì)學(xué)意義，可能由于肝實(shí)質(zhì)的血供中約1/4來(lái)自肝動(dòng)脈，約3/4來(lái)自門靜脈，所以動(dòng)脈期肝實(shí)質(zhì)內(nèi)釓的濃度相對(duì)較低，其引起的信號(hào)差別相對(duì)較小所致。

另一方面筆者發(fā)現(xiàn)肝動(dòng)脈和門靜脈與肝實(shí)質(zhì)的相對(duì)對(duì)比度沒(méi)有明顯差異，而相對(duì)對(duì)比度主要用于反映觀察圖像中血管的視覺(jué)效果[9]，此結(jié)果表明雖然Gd-EOB-DTPA增強(qiáng)MRI的血管強(qiáng)化程度降低了，但是血管與周圍肝實(shí)質(zhì)的對(duì)比度沒(méi)有明顯差異。其主要原因可能是由于血管和肝實(shí)質(zhì)的強(qiáng)化程度在Gd-EOB-DTPA增強(qiáng)MRI均下降，其比值變化不大，說(shuō)明血管與肝實(shí)質(zhì)內(nèi)走形的顯示所受的影響比較小，但是本研究只測(cè)量比較肝總動(dòng)脈和門靜脈主干大血管與肝實(shí)質(zhì)的對(duì)比度，而大血管強(qiáng)化程度不夠，可能會(huì)潛在影響血管細(xì)小分支和門脈管腔內(nèi)小栓子的顯示。目前提高Gd-EOB-DTPA增強(qiáng)的增強(qiáng)效果主要有以下方法：①優(yōu)化動(dòng)脈期的延遲時(shí)間，由于Gd-EOB-DTPA劑量少，動(dòng)脈期時(shí)間窗比較短，因此我們采用自動(dòng)監(jiān)測(cè)觸發(fā)掃描的方法以達(dá)到最佳的強(qiáng)化效果；②降低對(duì)比劑的注射流率，Zench等[6]動(dòng)物實(shí)驗(yàn)研究發(fā)現(xiàn)Gd-EOB-DTPA增強(qiáng)時(shí)注射流率1 mL/s的動(dòng)脈強(qiáng)化效果較2 mL/s好，但是目前國(guó)內(nèi)尚無(wú)專用高壓注射器，我們采用手動(dòng)推注，注射流率約1～2 mL/s；③對(duì)比劑的劑量的調(diào)整，通過(guò)本研究我們發(fā)現(xiàn)標(biāo)準(zhǔn)劑量的Gd-EOB-DTPA增強(qiáng)肝臟血管、肝臟實(shí)質(zhì)強(qiáng)化效果均低于Gd-DTPA，因此筆者同意Ringe等[12]的觀點(diǎn)即不管患者的體重多少，將瓶裝10 mL Gd-EOB-DTPA總劑量全部注射，有助于提高強(qiáng)化效果。對(duì)于是否進(jìn)一步提高對(duì)比劑的劑量，還需要進(jìn)一步臨床試驗(yàn)研究。

本研究的不足之處主要有：首先，本研究為回顧性分析，存在選擇偏倚；其次，未計(jì)算肝血管和肝實(shí)質(zhì)的信噪比和對(duì)比噪聲比，有文獻(xiàn)報(bào)道并行采集技術(shù)可導(dǎo)致噪聲的空間分布不同[13]；最后，血管的分析未采用三維重組方法，由于本研究為回顧性，層厚為3 mm，三維重組血管圖像質(zhì)量較差。

綜上所述，肝硬化患者的Gd-EOB-DTPA增強(qiáng)MR的肝總動(dòng)脈和門靜脈的強(qiáng)化比率低于Gd-DTPA，但是與肝實(shí)質(zhì)的對(duì)比度無(wú)明顯差別；而Gd-EOB-DTPA增強(qiáng)MR肝實(shí)質(zhì)在門靜脈強(qiáng)化均明顯低于Gd-DTPA。筆者認(rèn)為肝硬化患者的Gd-EOB-DTPA增強(qiáng)MRI可能需要增加劑量才能達(dá)到Gd-DTPA增強(qiáng)的效果。

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ComparativestudyofusingGd-EOB-DTPAandGd-DTPAasMRcontrastagentforhepaticparenchymaandvesslesenhacementinthesamepatientwithcirrhosis

ZHANG Shu-jie,RAO Sheng-xiang,CHEN Cai-zhong,et al.

Department of Radiology,Zhongshan Hospital,Fudan University,and Shanghai Medical Imaging Institute,Shanghai 200032,P.R.China

Objective：To evaluate the differences of enhance effects of common hepatic artery (CHA),portal vein (PV)and hepatic parenchyma on dynamic contrast-enhanced (DCE)MRI by using gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)separately in the same cirrhotic patient.MethodsThe enhanced MR images of liver in 35 cirrhotic patients obtained by using Gd-EOB-DTPA and Gd-DTPA separately in the same patient were reviewed.The percentage enhancement (PE)of CHA,PV and hepatic parenchyma and the relative contrast (RC)between CHA,PV and hepatic parenchyma were calculated and analyzed statistically.ResultsThe mean PEs of CHA,PV were significantly lower for Gd-EOB-DTPA than Gd-DPTA (P<0.05).The mean PE of hepatic parenchyma at portal phase using Gd-EOB-DTPA was markedly lower than that using Gd-DPTA (P<0.05),whereas there was no significant difference of the mean PE of hepatic parenchyma at arterial phase (P=0.1010).The RC values of CHA,PV and hepatic parenchyma using Gd-DTPA was slightly higher than that using Gd-EOB-DTPA,yet with no significant statistic difference (P=0.3421 and 0.2389 respectively).ConclusionCompared with Gd-DTPA,the enhance effect of Gd-EOB-GTPA was lower in hepatic vessels and hepatic parenchyma in patients with cirrhosis,adjustment of the dosage of Gd-EOB-GTPA should be considered.

Magnetic resonance imaging; Liver cirrhosis; Contrast medium; Comparative study

200032 上海，中山醫(yī)院放射診斷科，上海市影像醫(yī)學(xué)研究所

張澍杰(1977-)，女，上海人，技師，主要從事腹部MR成像技術(shù)工作。

曾蒙蘇，zeng.mengsu@ zs-hospital.sh.cn

R445.2; R814.46; R657.31

A

1000-0313(2014)07-0814-04

10.13609/j.cnki.1000-0313.2014.07.020

2013-09-04

2013-12-20)