MR血管成像及血流分析技术对纤维化肝脏血管的形态与血流动力学评价
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摘要
研究背景与目的：
肝硬化是一种复杂的病理生理变化,由于纤维化的持续发展,组织塌陷,导致肝脏血流减少,严重影响肝脏的微循环系统,导致肝脏血流减低、肝脏功能损伤、门静脉高压,加速肝脏再生进程。同时由于肝脏强大的代偿机制,往往直到肝硬变的晚期阶段才能够做出明确诊断,而且对肝脏实际功能的评价缺乏相对准确定量的方法。影像学诊断方法在诊断肝硬化观察肝脏整体变化特点上具有强大优势,例如,肝脏边缘呈波浪状、肝脏体积缩小、尾状叶增大、脾大、肝裂增宽、肝实质不均质强化、胆囊窝增宽等。在工作中我们注意到肝硬化肝脏静脉管径明显变细,且部分超声影像学研究也发现这样特点,但未对其进行量化研究。对比剂增强MR快速血管成像技术能够相对准确客观的对血管的形态、管径作出评价。肝脏具有双重血供,即肝动脉和门静脉,肝内纤维化导致肝脏血流动力学的改变,肝窦循环阻力增加,使来自于门静脉的血流减少,减少的门脉血供由增加的肝动脉循环有所补偿,门静脉血流的减少与肝动脉血流的增加受到肝纤维化进程的影响,且门静脉血流变化与肝脏的消化功能有一定的关系。本研究利用磁共振血管成像及血流定量技术,对不同病理分期的纤维化肝脏及正常肝脏进行对比,探讨较大的血管能否因为肝脏的纤维化而发生形态学上的变化,利用MR血流定量软件计算评价入肝血流：即门静脉及肝动脉血流分配关系,以期对进展期肝纤维化患者肝脏功能进行评价。
材料与方法：
本研究分两部分进行。所有入选病例行磁共振检查的时间与肝脏病理检查时间间隔不超过30天。第一部分2008年9月至2009年12月经手术或肝穿刺活检病理证实的肝纤维化病人64例,其中男51例,女13例,年龄23-58岁,平均年龄38.5±10.6岁。选择临床无肝脏疾病或肝脏损害史及近1月内无用药史的健康志愿者10例,其中男6例,女4例,年龄22-37岁,平均年龄25.9±4.8岁。
将肝纤维化病人64例及健康志愿者10例根据病理及临床结果分为肝纤维化S1组、S2组、S3组、S4组及正常对照组(C),分别进行进行动态门静脉及肝动脉血流量分析,包括禁饮食6小时后空腹时及进餐(758KJ)后3分钟至1小时(间隔3分钟,重复扫描),测量平面选择垂直门静脉主干距门静脉分叉1-2cm处及同平面肝动脉。测量形态学指标：门静脉主干的宽度、脾脏的长度和厚度、胆囊壁厚度,计算肝脏体积；于餐前及餐后动态测量血流指标：空腹及餐后每3分钟门静脉的平均血流速度Vp、空腹及餐后每3分钟肝动脉的平均血流速度Va、空腹及餐后每3分钟门静脉的平均血流流量(Fp)、空腹及餐后每3分钟肝动脉的平均血流流量(Fa)、餐后门静脉血流峰值(Fpp)、餐后门静脉峰值时间(Tpp)、餐后门静脉峰值时间对应的肝动脉血流量(Fap)、门静脉血流增长率(Rpi)、餐后45分钟及60分钟门静脉血流下降率(Rpd45, Rpd60)、肝动脉补偿率Rac、空腹状态下入肝血流分布Dlb、心动周期内肝动脉收缩期血流峰值速度Vas、心动周期内肝动脉舒张末期血流速度Vad、Vas／Vad、肝动脉搏动指数PI、肝动脉阻力指数RI。
第二部分回顾性分析了某肝脏移植中心2002年1月至2006年3月所有拟进行肝移植的肝硬化病人及2008年9月至2009年12月经手术或肝穿刺活检病理证实的肝纤维化病人共127例,其中男91例,女36例,年龄21-72岁,平均年龄57.9±8.7岁；同期拟作为肝脏供体的正常人85例,其中男43例,女42例,年龄21-58岁,平均年龄38.9±10.4岁。
所有病例均采用动态增强扫描,常规检查序列包括三平面定位序列、轴位FSE T2WI、轴位脂肪抑制LAVA/FAME序列。采用LAVE／FAME序列分别在注射造影剂之前、开始注射造影剂后15秒、1分钟、3分钟、5分钟进行动态数据采集。所有3D对比增强MR图像由3名高年资放射科医师分别独立在ADW4.1工作站(Advantage Window, GE Medical System)上进行测量,所有结果取平均值。测量指标包括肝左、中、右静脉、肠系膜上静脉、脾静脉、门静脉主干、门静脉左支、门静脉右前支、门静脉左前支、腹腔干动脉、肝固有动脉、左肾静脉及右肾静脉。所有测量均在轴位图像上进行。肝静脉测量选择静脉根部靠近下腔静脉处；肠系膜上静脉、脾静脉测量选择门静脉汇合之前约1cm处,但在各自分支静脉汇合之后；腹腔干动脉、肝固有动脉测量选择主干较清晰层面。左、右肾静脉的测量点位于下腔静脉入口前1cm。将测量值分为肝纤维化S1组、S2组、S3组、S4组和正常对照组(C)进行比较。
结果：
1.门静脉及肝动脉血流量分析结果
根据测量数据,描绘餐前及餐后门静脉及肝动脉平均流速随时间变化曲线(Vmean-Time)、餐前及餐后门静脉血流量随时间变化曲线(Flow-Time)、餐前及餐后门静脉面积随时间变化曲线(Area-Time)、肝动脉RI-Time曲线及PI-Time曲线。
①5组间门静脉及肝动脉血流量的比较
空腹时门静脉血流流量随肝脏纤维化程度增高呈递增趋势,S4组门静脉血流空腹值(Fp0)明显高于其他各组(p<0.05),S3组空腹门静脉血流量有升高趋势,但尚无统计学意义；进餐后,各组门静脉血流均较餐前提高,但门静脉血流流量的峰值(Fpp)随肝脏纤维化程度增加呈递减趋势,其中S3、S4组显著低于其他三组(p<0.05),其峰值血流量较餐前血流量增长率(Rpi)分别为S1组87%、S2组74%、S3组57%、S4组45%及正常对照组(C)90%,其中S3组、S4组较C组门静脉血流增加幅度显著降低(p<0.05)。ROC分析,当Fp0>15.2ml／s时,肝脏纤维化程度达stage 3期以上的敏感度85%,特异度85%；当Fp0>16.2ml／s时,特异度达98%,相应敏感度为42%。当Fpp<25.9ml／s时肝脏纤维化程度达stage 3期以上的敏感度85%,特异度70%,当Fpp<22.8ml／s时,特异度达98%,相应敏感度为73%。
门静脉血流到达峰值后开始下降,S3组的Rpd60值及S4组的Rpd45、Rpd60值明显低于其他各组(p<0.05)。门静脉血流流量到达峰值的时间随肝纤维化程度增高有延长的趋势,其中S4组明显晚于其他4组(p=0.03)
空腹时,S2、S3、S4组肝动脉血流略高于S1组和对照组,但无统计学差异(p>0.05)；各组肝动脉平均血流在餐后均呈递减趋势,在门静脉血流到达峰值时接近低值,五组间肝动脉血流流量在餐前、餐后无显著差异(p>0.05),五组肝动脉血流补偿率(Rac)值彼此接近(p>0.05)。
S4组肝脏体积明显小于对照组和其他肝纤维化组,根据肝脏体积计算入肝血流分布(Dlb)在S4组明显高于其他各组(p<0.01)。
②5组间门静脉及肝动脉平均流速的比较
空腹状态下,C组门静脉平均流速(8.0±2.1cm／s)略高于其他肝纤维化四组(S1：6.9±2.3 cm／s,S2：7.0±2.7 cm／s,S3：7.5±2.7 cm／s,S4：7.6±2.4 cm／s),但无统计学差异(p>0.05)；5组试验者在进食标准餐后,门静脉平均流速均较餐前提高,各组峰值流速较餐前平均流速增长率分别为S1组84%、S2组98%、S3组45%、S4组24%及正常对照组(C)54%；到达峰值流速的平均峰值时间随肝纤维化程度增高有延长趋势,其中S4组明显晚于其他四组(p<0.01)。
各组肝动脉平均流速在餐后均呈递减趋势,到达低值后又缓慢上升,肝硬化S4组的平均流速值略高于正常对照组,但无明显统计学差异(p>0.05)。
③5组间门静脉管径的比较
禁食状态下,组间门静脉管径差异明显,S4组门静脉主干管径较对照组明显增大(p<0.01)；5组试验者在进食标准餐后,门静脉管径均较餐前增大(图5),其门静脉最大面积较餐前增长率分别为S1组24%、S2组24%、S3组17%、S4组14%及正常对照组(C)29%,S4组较对照组有显著性差异(p<0.05)。
④5组间肝动脉PI及RI的比较
5组试验者在进食标准餐前,S4组PI及RI值均高于正常对照组(p<0.05)；5组试验者在进食标准餐后,肝动脉PI值和RI值均较餐前提高,但增加幅度不同。餐后30分钟时PI增长幅度分别为S1组350%、S2组358%、S3组347%、S4组146%及正常对照组(C)370%,其中S4组较C组有显著性差异(p<0.01)；RI增长幅度分别为S1组54%、S2组49%、S3组20%、S4组18%及C组58%,其中S3组、S4组较C组有显著性差异(p<0.01)。2.肝内大血管形态学比较结果
肝纤维化组肝右、中、左静脉平均管径分别为S 1(9.8mm、7.2mm、9.2 mm)、S2(9.2mm、7.5mm、9 mm)、S3(8 mm、7mm、6 mm)、S4(4.9mm、4.5mm、5.0mm),正常对照组肝右、中、左静脉平均管径分别为9.9mm、7.6mm、8.9 mm,其中S4组与正常对照组数据存在明显统计学差异(p<<0.001),与肝硬化呈负相关(r=-0.7,-0.6,-0.6,p<0.001)。肝右静脉直径<5mm诊断为肝硬化的敏感度为57%、特异度为99%。肝纤维化S4组门静脉主干、门静脉左支、门静脉右前支、门静脉右后支平均管径分别为14mm、10.6mm、6.5 mm、6.2 mm,正常对照组门静脉主干、门静脉左支、门静脉右前支、门静脉右后支平均管径分别为12 mm、10mm、8.4 mm、7.6 mm,二组比较除门静脉左支外,均存在统计学差异(p<0.001),排除脐静脉侧支开放因素,门静脉左支管径在肝硬化组略小于正常对照组,但二者没有统计学差异(p=0.2)；肝纤维化四组肝固有动脉管径平均值分别为S1(4.0±1.1mm)、S2(4.1±1.3mm)、S3(4.2±1.5mm)、S4(4.1±1.5mm),正常对照组肝固有动脉管径平均值4.0±1.1mm,各组之间没有明显统计学差异(p>0.05)。
结论及意义：
1.肝脏血管形态发生如下改变：肝静脉管径变窄、门静脉主干增宽,而肝内门静脉分支管径变窄,均提示肝硬化。肝右静脉直径小于5mm时,若不伴有副肝静脉的存在,高度提示肝硬化的病理改变。肝固有动脉管径受肝纤维化影响不明显。
2.在入肝血流门静脉与肝动脉之间存在肝动脉缓冲机制,但肝动脉缓冲能力有限,当肝脏纤维化进展到S3期以上时,肝动脉也不能代偿性满足肝脏的需要,从而产生肝功能异常；
3.在正常人群及肝纤维化病人中,门静脉的血流速度、血流量受食物影响显著,分别在30分钟前后到达门静脉血流的峰值；在门静脉血流增加的同时,肝动脉血流有降低趋势,但进食对肝动脉血流的影响不大；
4.肝纤维化程度达S3期及以上时,门静脉流速未出现明显变化,但门静脉管径增粗,空腹门静脉血流呈增加趋势,体现了门静脉血管自身的调节机制；门静脉受食物影响达峰值流速和峰值血流的时间延迟,餐前及餐后门静脉管径增粗幅度减低,提示门静脉血管本身的代偿机制受限,门静脉入肝血流受阻,出现门静脉高压可能增大；
5.肝纤维化程度达S3期及以上时,空腹肝动脉PI及RI值明显高于轻度纤维化病人及正常对照组,但在餐后,二值增大的幅度却明显减低,说明肝纤维化病人肝动脉的缓冲能力比正常人减低；
6.肝纤维化S3期以上的病人肝脏消化功能受到肝内病理改变的影响显著,经过硬化肝脏的无效血流增加,通过MR Q-Flow技术测量门静脉血流,当空腹血流高于16.2ml／s,进餐后峰值血流低于22.8ml／s时,肝脏纤维化程度达S3期以上的特异度达98%。
7.肝纤维化S3期以上的病人肝脏血管形态及血流动力学受到肝内病理改变影响显著,应用MR可以对肝硬化进行早期判断,并对早期诊断门静脉高压具有显著优势。
Background and purposes:
Liver cirrhosis is a major cause of morbidity and mortality for the patient with liver disease. Alcohol is the leading cause of liver cirrhosis in the western world. In China, cirrhosis is most commonly caused by hepatitis especially hepatitis B. In the end stage of the entity, due to the portal hypertension, it is associated with complicatied and debilitating clinical conditions. The more the disease progresses, the less blood flow to the liver, the worse the liver function will be. However, most patients with cirrhosis are asymptomatic due to the compensatory capacity of the liver. It is difficult to make an early diagnosis. Clinically quantitative analysis of liver function is still difficult. Imaging has advantage in diagnosis of cirrhosis. Well known imaging features of liver cirrhosis include nodularity, volume reduction, caudate lobe enlargement, splenomegaly, heterogeneous enhancement, decreased right to left lobe volume ratio, varices and ascites. We have noticed that on high resolution dynamic gadolinium enhanced MRI cirrhotic liver commonly have small hepatic veins even when other imaging features of cirrhosis are not present, but there was no quantitative analysis on it. There is a dual blood supply of the liver, i.e. hepatic artery and portal vein. Liver fibrosis induces hepatic hemodynamic changes. Increased resistance of hepatic sinus circulation causes reduced portal flow. Hepatic arterial blood flow changes so as to buffer the impact of portal flow alterations on total hepatic blood flow, thus tending to regulate total hepatic flow at a constant level. It seems that precession of liver fibrosis influent this mechanism. The purpose of the study is to investgate the morphologic change of the vessels due to the cirrhotic liver and to evaluate the relationship between the portal flow and hepatic arterial flow using MR Q-Flow analysis software.
Material and methods:
The medical ethics committee of our institution approval this study and written informed consent was obtained from all subjects prior to the exam.
This study included two parts, and the interval time between pathologic diagnosis and MR Scaning and liver biopsy or surgical operation on all cases was less than 30 days.
Firstly,64 patients (male:female 51:13) with hepatic fibrosis confirmed by biopsy or surgically and pathologicallyfrom September 2008 to December 2009, and 10 healthy volunteers (male:female 6:4).
All 64 patients were divided into 4 groups based on the severity of the liver fibrosis namely S1, S2, S3 and S4. All subjects were examined after 6 hours fast, and then exams were repeated in every 3 minutes for 60 minutes postprandially. Portal flow was measured at the level of main portal vein 1-2cm to the bification. Portal vein caliber, length and thickness of spleen and wall thickness of the gallbladder were also measured as morphologic index and liver volume was calculated as well. Data processing was acquired on the workstation, Mean Velocity of Portal Vein(Vp), Mean Velocity of Hepatic Artery(Va), Mean Flux of Portal Vein (Fp), Mean Flux of Hepatic Artery (Fa), Peak Flux of Portal Vein (Fpp), Time of Fpp(Tpp), Flux of Hepatic Artery at Tpp(Fap), Rate of Increase of Portal Flux(Rpi),Rate of Descend of Portal Flux(Rpd), Rate of Arterial Compensation(Rac), Distribution of Liver Blood Inflow(Dlb), Peak Systolic Arterial Flow Velocity(Vas), End Diastolic Flow Velocity(Vad), Hepatic Pulse Index(PI) and Resistance Index(RI) were measured and calculated.
Secondly,85 healthy liver donors (male:female 43:42) and 127 patients (male: female 91:36)with biopsy proven cirrhosis or fibrosis were selected retrospectively from the records of the Center for Liver Disease and Transplantation from January 2002 to March 2006 and from September 2008 to December 2009.
All subjects underwent dynamic gadolinium-enhanced 3D MR at 1.5 T/3.0T including FSE T2WI, dynamic 3D spoiled gradient echo imaging with fat suppression. Portal veins, hepatic veins, inferior vena cava, renal vein, superior mesenteric vein and splenic vein diameters as well as caudate lobe dimensions/volume, right lobe width, right and left lobe volume, spleen volume, gallbladder wall and colon wall thickness, presence of splenorenal shunt and recanalized umbilical veins were determined independently by three radiologists. The data from each of the three reviewers were averaged to obtain the final measurement results.
Results:
1 Portal and hepatic arterial flow analysis
1.1 The flow volume of portal vein/hepatic artery
Mean values of portal flow volume in 5 groups were all raised postprandially. It was 87% in group S1,74% in group S2,57% in group S3,45% in group S4 and 90% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). When FpO>15.2ml/s, there was a sensitivity 85% and specificity 85% to diagnose liver fibrosis at stage3 or above, and the FpO cutoff flow rate of more than 16.2ml/s has a specificity of 98% and sensitivity of 42%. When Fpp<25.9ml/s, there was a sensitivity 85% and specificity 70% to diagnose liver fibrosis at stage3 or above, and the Fpp cutoff flow rate of lesss than 22.8ml/s has a specificity of 98% and sensitivity of 73%. There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was no difference for mean flow volume values of hepatic artery among all groups at fasting conditions (p>0.05). The hepatic arterial flow volume decreased postprandially, but without significant difference among all groups (p>0.05).
1.2 Mean velocity of portal vein/hepatic artery
Mean values of portal flow velocity in 5 groups were all raised postprandially, and it was 84% in group S1,98% in group S2,45% in group S3,24% in group S4 and 54% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was a depressive trend of mean velocity values of hepatic artery in all groups postprandially. There was no significantly difference comparing hepatic arterial flow velocity values before and after a stantardized meal among fibrosis groups and control group (p>0.05).
1.3 The cross section area of portal veins
At the fasting state, main portal vein's cross section area in group S3 and S4 were larger than other groups(p<0.01). After meal, the portal veins'cross section areas were all increased in 5 groups, and the increased rates were 24% in S1,24% in S2, 17% in S3,14% in S4 and 29% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).
1.4 PI and RI of the hepatic artery
After a standardized meal, the hepatic arteries' PI and RI values were all increased in 5 groups, and the increase rates of PI were 350% in S1,358% in S2, 347% in S3,146% in S4 and 370% in C respectively. There was significantly difference between S4 and C (p<0.01). The increase rates of RI were 54% in S1,49% in S2,20% in S3,18% in S4 and 58% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).
2. Changes of the major vessels of the liver
Hepatic veins in 4 fibrotic liver groups were 9.8mm、7.2mm、9.2 mm in S1, 9.2mm、7.5mm、9 mm in S2 group,8mm、7mm、6 mm in S3 group and 4.9mm、4.5mm、5.0mm in S4 group for right, middle and left compared to 9.9,7.6 and 8.9 mm in C group. Hepatic veins were significantly smaller in S4 compared to group C(p<< 0.001) and were negatively correlated with cirrhosis (r=-0.7,-0.6 and -0.6 respectively, p< 0.001). A right hepatic vein diameter< 5mm diagnosed cirrhosis with sensitivity= 57% but specificity=99%. Right portal veins were smaller in cirrhotic patients (group S4) measuring 6.4 mm (anterior) and 6.2 (posterior) mm, compared to 8.4 and 7.6 mm (p<< 0.001) in group C in spite of higher portal pressure in patients with cirrhosis. Left portal vein was only smaller in cirrhotic patients without recanalized umbilical vein. Mean caliber of proper hepatic artery were S1 (4.0±.1mm), S2(4.1±1.3mm), S3(4.2±1.5mm)and S4(4.1±1.5mm) respectively, and there was no significant difference compared to C(4.0±1.1mm) (p>0.05).
Conclusions:
1. Hepatic veins'diameter reduction inversely correlates with cirrhosis and may help diagnose cirrhosis when other imaging features of cirrhosis are absent. A right hepatic vein less than 5 mm in diameter on cross-sectional imaging should raise a high suspicion for cirrhosis when there are no large accessory right hepatic veins. There was no obvious change on hepatic arterial caliber when liver fibrosis happened.
2. Hepatic arterial buffer response was proved. If liver fibrosis was more severe than fibrosis of stage 3, this buffer response couldnot meet the requirement of liver function.
3. Portal blood flow velocity and volume are significantly influenced increasingly by food no matter with or without liver fibrosis, and reached the peak values around 30 minutes after meal. Hepatic arterial flow which was not correlated with meal decreased along with portal flow increasing.
4. When the severity of liver fibrosis is more than stage 3, the cross section area of main portal vein increases compensatively in order to increase the portal blood flow, which was the self-regulatory response of portal vein.The followings may suggest the block of portal flow as well as portal hypertension:delay when portal flow velocity and volume reach to the peak value postprandially, postprandial cross section area of portal vein increases unconspicuously
5. Fasting hepatic artery's PI and RI of fibrotic liver with stage 3-4 are significantly higher than normal liver and fibrotic liver with stage 1-2, but increase rate of PI and RI for stage 3-4 fibrotic liver postprandial comparing to fasting are significantly lower than other stages and normal liver. It is suggested that hepatic artery's buffer ablility is weaker in severe fibrotic liver than in the normal.
6. When the severity of liver fibrosis is more than stage 3, invalid blood flow through the fibrotic liver increases and the function disorder of severe fibrotic liver will occur. The FpO cutoff flow rate of more than 16.2ml/s and the Fpp cutoff flow rate of lesss than 22.8ml/s have a specificity of 98% for liver fibrosis diagnosis of stage3-4.
7. Liver vascular morphology and hemodynamic are related to pathologic change of fibrosis. MR techniques may help to dignose liver fibrosis and portal hypertension in early stage.
肝硬化是一种复杂的病理生理变化,由于纤维化的持续发展,组织塌陷,导致肝脏血流减少,严重影响肝脏的微循环系统,导致肝脏血流减低、肝脏功能损伤、门静脉高压,加速肝脏再生进程。同时由于肝脏强大的代偿机制,往往直到肝硬变的晚期阶段才能够做出明确诊断,而且对肝脏实际功能的评价缺乏相对准确定量的方法。影像学诊断方法在诊断肝硬化观察肝脏整体变化特点上具有强大优势,例如,肝脏边缘呈波浪状、肝脏体积缩小、尾状叶增大、脾大、肝裂增宽、肝实质不均质强化、胆囊窝增宽等。在工作中我们注意到肝硬化肝脏静脉管径明显变细,且部分超声影像学研究也发现这样特点,但未对其进行量化研究。对比剂增强MR快速血管成像技术能够相对准确客观的对血管的形态、管径作出评价。肝脏具有双重血供,即肝动脉和门静脉,肝内纤维化导致肝脏血流动力学的改变,肝窦循环阻力增加,使来自于门静脉的血流减少,减少的门脉血供由增加的肝动脉循环有所补偿,门静脉血流的减少与肝动脉血流的增加受到肝纤维化进程的影响,且门静脉血流变化与肝脏的消化功能有一定的关系。本研究利用磁共振血管成像及血流定量技术,对不同病理分期的纤维化肝脏及正常肝脏进行对比,探讨较大的血管能否因为肝脏的纤维化而发生形态学上的变化,利用MR血流定量软件计算评价入肝血流：即门静脉及肝动脉血流分配关系,以期对进展期肝纤维化患者肝脏功能进行评价。
材料与方法：
本研究分两部分进行。所有入选病例行磁共振检查的时间与肝脏病理检查时间间隔不超过30天。第一部分2008年9月至2009年12月经手术或肝穿刺活检病理证实的肝纤维化病人64例,其中男51例,女13例,年龄23-58岁,平均年龄38.5±10.6岁。选择临床无肝脏疾病或肝脏损害史及近1月内无用药史的健康志愿者10例,其中男6例,女4例,年龄22-37岁,平均年龄25.9±4.8岁。
将肝纤维化病人64例及健康志愿者10例根据病理及临床结果分为肝纤维化S1组、S2组、S3组、S4组及正常对照组(C),分别进行进行动态门静脉及肝动脉血流量分析,包括禁饮食6小时后空腹时及进餐(758KJ)后3分钟至1小时(间隔3分钟,重复扫描),测量平面选择垂直门静脉主干距门静脉分叉1-2cm处及同平面肝动脉。测量形态学指标：门静脉主干的宽度、脾脏的长度和厚度、胆囊壁厚度,计算肝脏体积；于餐前及餐后动态测量血流指标：空腹及餐后每3分钟门静脉的平均血流速度Vp、空腹及餐后每3分钟肝动脉的平均血流速度Va、空腹及餐后每3分钟门静脉的平均血流流量(Fp)、空腹及餐后每3分钟肝动脉的平均血流流量(Fa)、餐后门静脉血流峰值(Fpp)、餐后门静脉峰值时间(Tpp)、餐后门静脉峰值时间对应的肝动脉血流量(Fap)、门静脉血流增长率(Rpi)、餐后45分钟及60分钟门静脉血流下降率(Rpd45, Rpd60)、肝动脉补偿率Rac、空腹状态下入肝血流分布Dlb、心动周期内肝动脉收缩期血流峰值速度Vas、心动周期内肝动脉舒张末期血流速度Vad、Vas／Vad、肝动脉搏动指数PI、肝动脉阻力指数RI。
第二部分回顾性分析了某肝脏移植中心2002年1月至2006年3月所有拟进行肝移植的肝硬化病人及2008年9月至2009年12月经手术或肝穿刺活检病理证实的肝纤维化病人共127例,其中男91例,女36例,年龄21-72岁,平均年龄57.9±8.7岁；同期拟作为肝脏供体的正常人85例,其中男43例,女42例,年龄21-58岁,平均年龄38.9±10.4岁。
所有病例均采用动态增强扫描,常规检查序列包括三平面定位序列、轴位FSE T2WI、轴位脂肪抑制LAVA/FAME序列。采用LAVE／FAME序列分别在注射造影剂之前、开始注射造影剂后15秒、1分钟、3分钟、5分钟进行动态数据采集。所有3D对比增强MR图像由3名高年资放射科医师分别独立在ADW4.1工作站(Advantage Window, GE Medical System)上进行测量,所有结果取平均值。测量指标包括肝左、中、右静脉、肠系膜上静脉、脾静脉、门静脉主干、门静脉左支、门静脉右前支、门静脉左前支、腹腔干动脉、肝固有动脉、左肾静脉及右肾静脉。所有测量均在轴位图像上进行。肝静脉测量选择静脉根部靠近下腔静脉处；肠系膜上静脉、脾静脉测量选择门静脉汇合之前约1cm处,但在各自分支静脉汇合之后；腹腔干动脉、肝固有动脉测量选择主干较清晰层面。左、右肾静脉的测量点位于下腔静脉入口前1cm。将测量值分为肝纤维化S1组、S2组、S3组、S4组和正常对照组(C)进行比较。
结果：
1.门静脉及肝动脉血流量分析结果
根据测量数据,描绘餐前及餐后门静脉及肝动脉平均流速随时间变化曲线(Vmean-Time)、餐前及餐后门静脉血流量随时间变化曲线(Flow-Time)、餐前及餐后门静脉面积随时间变化曲线(Area-Time)、肝动脉RI-Time曲线及PI-Time曲线。
①5组间门静脉及肝动脉血流量的比较
空腹时门静脉血流流量随肝脏纤维化程度增高呈递增趋势,S4组门静脉血流空腹值(Fp0)明显高于其他各组(p<0.05),S3组空腹门静脉血流量有升高趋势,但尚无统计学意义；进餐后,各组门静脉血流均较餐前提高,但门静脉血流流量的峰值(Fpp)随肝脏纤维化程度增加呈递减趋势,其中S3、S4组显著低于其他三组(p<0.05),其峰值血流量较餐前血流量增长率(Rpi)分别为S1组87%、S2组74%、S3组57%、S4组45%及正常对照组(C)90%,其中S3组、S4组较C组门静脉血流增加幅度显著降低(p<0.05)。ROC分析,当Fp0>15.2ml／s时,肝脏纤维化程度达stage 3期以上的敏感度85%,特异度85%；当Fp0>16.2ml／s时,特异度达98%,相应敏感度为42%。当Fpp<25.9ml／s时肝脏纤维化程度达stage 3期以上的敏感度85%,特异度70%,当Fpp<22.8ml／s时,特异度达98%,相应敏感度为73%。
门静脉血流到达峰值后开始下降,S3组的Rpd60值及S4组的Rpd45、Rpd60值明显低于其他各组(p<0.05)。门静脉血流流量到达峰值的时间随肝纤维化程度增高有延长的趋势,其中S4组明显晚于其他4组(p=0.03)
空腹时,S2、S3、S4组肝动脉血流略高于S1组和对照组,但无统计学差异(p>0.05)；各组肝动脉平均血流在餐后均呈递减趋势,在门静脉血流到达峰值时接近低值,五组间肝动脉血流流量在餐前、餐后无显著差异(p>0.05),五组肝动脉血流补偿率(Rac)值彼此接近(p>0.05)。
S4组肝脏体积明显小于对照组和其他肝纤维化组,根据肝脏体积计算入肝血流分布(Dlb)在S4组明显高于其他各组(p<0.01)。
②5组间门静脉及肝动脉平均流速的比较
空腹状态下,C组门静脉平均流速(8.0±2.1cm／s)略高于其他肝纤维化四组(S1：6.9±2.3 cm／s,S2：7.0±2.7 cm／s,S3：7.5±2.7 cm／s,S4：7.6±2.4 cm／s),但无统计学差异(p>0.05)；5组试验者在进食标准餐后,门静脉平均流速均较餐前提高,各组峰值流速较餐前平均流速增长率分别为S1组84%、S2组98%、S3组45%、S4组24%及正常对照组(C)54%；到达峰值流速的平均峰值时间随肝纤维化程度增高有延长趋势,其中S4组明显晚于其他四组(p<0.01)。
各组肝动脉平均流速在餐后均呈递减趋势,到达低值后又缓慢上升,肝硬化S4组的平均流速值略高于正常对照组,但无明显统计学差异(p>0.05)。
③5组间门静脉管径的比较
禁食状态下,组间门静脉管径差异明显,S4组门静脉主干管径较对照组明显增大(p<0.01)；5组试验者在进食标准餐后,门静脉管径均较餐前增大(图5),其门静脉最大面积较餐前增长率分别为S1组24%、S2组24%、S3组17%、S4组14%及正常对照组(C)29%,S4组较对照组有显著性差异(p<0.05)。
④5组间肝动脉PI及RI的比较
5组试验者在进食标准餐前,S4组PI及RI值均高于正常对照组(p<0.05)；5组试验者在进食标准餐后,肝动脉PI值和RI值均较餐前提高,但增加幅度不同。餐后30分钟时PI增长幅度分别为S1组350%、S2组358%、S3组347%、S4组146%及正常对照组(C)370%,其中S4组较C组有显著性差异(p<0.01)；RI增长幅度分别为S1组54%、S2组49%、S3组20%、S4组18%及C组58%,其中S3组、S4组较C组有显著性差异(p<0.01)。2.肝内大血管形态学比较结果
肝纤维化组肝右、中、左静脉平均管径分别为S 1(9.8mm、7.2mm、9.2 mm)、S2(9.2mm、7.5mm、9 mm)、S3(8 mm、7mm、6 mm)、S4(4.9mm、4.5mm、5.0mm),正常对照组肝右、中、左静脉平均管径分别为9.9mm、7.6mm、8.9 mm,其中S4组与正常对照组数据存在明显统计学差异(p<<0.001),与肝硬化呈负相关(r=-0.7,-0.6,-0.6,p<0.001)。肝右静脉直径<5mm诊断为肝硬化的敏感度为57%、特异度为99%。肝纤维化S4组门静脉主干、门静脉左支、门静脉右前支、门静脉右后支平均管径分别为14mm、10.6mm、6.5 mm、6.2 mm,正常对照组门静脉主干、门静脉左支、门静脉右前支、门静脉右后支平均管径分别为12 mm、10mm、8.4 mm、7.6 mm,二组比较除门静脉左支外,均存在统计学差异(p<0.001),排除脐静脉侧支开放因素,门静脉左支管径在肝硬化组略小于正常对照组,但二者没有统计学差异(p=0.2)；肝纤维化四组肝固有动脉管径平均值分别为S1(4.0±1.1mm)、S2(4.1±1.3mm)、S3(4.2±1.5mm)、S4(4.1±1.5mm),正常对照组肝固有动脉管径平均值4.0±1.1mm,各组之间没有明显统计学差异(p>0.05)。
结论及意义：
1.肝脏血管形态发生如下改变：肝静脉管径变窄、门静脉主干增宽,而肝内门静脉分支管径变窄,均提示肝硬化。肝右静脉直径小于5mm时,若不伴有副肝静脉的存在,高度提示肝硬化的病理改变。肝固有动脉管径受肝纤维化影响不明显。
2.在入肝血流门静脉与肝动脉之间存在肝动脉缓冲机制,但肝动脉缓冲能力有限,当肝脏纤维化进展到S3期以上时,肝动脉也不能代偿性满足肝脏的需要,从而产生肝功能异常；
3.在正常人群及肝纤维化病人中,门静脉的血流速度、血流量受食物影响显著,分别在30分钟前后到达门静脉血流的峰值；在门静脉血流增加的同时,肝动脉血流有降低趋势,但进食对肝动脉血流的影响不大；
4.肝纤维化程度达S3期及以上时,门静脉流速未出现明显变化,但门静脉管径增粗,空腹门静脉血流呈增加趋势,体现了门静脉血管自身的调节机制；门静脉受食物影响达峰值流速和峰值血流的时间延迟,餐前及餐后门静脉管径增粗幅度减低,提示门静脉血管本身的代偿机制受限,门静脉入肝血流受阻,出现门静脉高压可能增大；
5.肝纤维化程度达S3期及以上时,空腹肝动脉PI及RI值明显高于轻度纤维化病人及正常对照组,但在餐后,二值增大的幅度却明显减低,说明肝纤维化病人肝动脉的缓冲能力比正常人减低；
6.肝纤维化S3期以上的病人肝脏消化功能受到肝内病理改变的影响显著,经过硬化肝脏的无效血流增加,通过MR Q-Flow技术测量门静脉血流,当空腹血流高于16.2ml／s,进餐后峰值血流低于22.8ml／s时,肝脏纤维化程度达S3期以上的特异度达98%。
7.肝纤维化S3期以上的病人肝脏血管形态及血流动力学受到肝内病理改变影响显著,应用MR可以对肝硬化进行早期判断,并对早期诊断门静脉高压具有显著优势。
Background and purposes:
Liver cirrhosis is a major cause of morbidity and mortality for the patient with liver disease. Alcohol is the leading cause of liver cirrhosis in the western world. In China, cirrhosis is most commonly caused by hepatitis especially hepatitis B. In the end stage of the entity, due to the portal hypertension, it is associated with complicatied and debilitating clinical conditions. The more the disease progresses, the less blood flow to the liver, the worse the liver function will be. However, most patients with cirrhosis are asymptomatic due to the compensatory capacity of the liver. It is difficult to make an early diagnosis. Clinically quantitative analysis of liver function is still difficult. Imaging has advantage in diagnosis of cirrhosis. Well known imaging features of liver cirrhosis include nodularity, volume reduction, caudate lobe enlargement, splenomegaly, heterogeneous enhancement, decreased right to left lobe volume ratio, varices and ascites. We have noticed that on high resolution dynamic gadolinium enhanced MRI cirrhotic liver commonly have small hepatic veins even when other imaging features of cirrhosis are not present, but there was no quantitative analysis on it. There is a dual blood supply of the liver, i.e. hepatic artery and portal vein. Liver fibrosis induces hepatic hemodynamic changes. Increased resistance of hepatic sinus circulation causes reduced portal flow. Hepatic arterial blood flow changes so as to buffer the impact of portal flow alterations on total hepatic blood flow, thus tending to regulate total hepatic flow at a constant level. It seems that precession of liver fibrosis influent this mechanism. The purpose of the study is to investgate the morphologic change of the vessels due to the cirrhotic liver and to evaluate the relationship between the portal flow and hepatic arterial flow using MR Q-Flow analysis software.
Material and methods:
The medical ethics committee of our institution approval this study and written informed consent was obtained from all subjects prior to the exam.
This study included two parts, and the interval time between pathologic diagnosis and MR Scaning and liver biopsy or surgical operation on all cases was less than 30 days.
Firstly,64 patients (male:female 51:13) with hepatic fibrosis confirmed by biopsy or surgically and pathologicallyfrom September 2008 to December 2009, and 10 healthy volunteers (male:female 6:4).
All 64 patients were divided into 4 groups based on the severity of the liver fibrosis namely S1, S2, S3 and S4. All subjects were examined after 6 hours fast, and then exams were repeated in every 3 minutes for 60 minutes postprandially. Portal flow was measured at the level of main portal vein 1-2cm to the bification. Portal vein caliber, length and thickness of spleen and wall thickness of the gallbladder were also measured as morphologic index and liver volume was calculated as well. Data processing was acquired on the workstation, Mean Velocity of Portal Vein(Vp), Mean Velocity of Hepatic Artery(Va), Mean Flux of Portal Vein (Fp), Mean Flux of Hepatic Artery (Fa), Peak Flux of Portal Vein (Fpp), Time of Fpp(Tpp), Flux of Hepatic Artery at Tpp(Fap), Rate of Increase of Portal Flux(Rpi),Rate of Descend of Portal Flux(Rpd), Rate of Arterial Compensation(Rac), Distribution of Liver Blood Inflow(Dlb), Peak Systolic Arterial Flow Velocity(Vas), End Diastolic Flow Velocity(Vad), Hepatic Pulse Index(PI) and Resistance Index(RI) were measured and calculated.
Secondly,85 healthy liver donors (male:female 43:42) and 127 patients (male: female 91:36)with biopsy proven cirrhosis or fibrosis were selected retrospectively from the records of the Center for Liver Disease and Transplantation from January 2002 to March 2006 and from September 2008 to December 2009.
All subjects underwent dynamic gadolinium-enhanced 3D MR at 1.5 T/3.0T including FSE T2WI, dynamic 3D spoiled gradient echo imaging with fat suppression. Portal veins, hepatic veins, inferior vena cava, renal vein, superior mesenteric vein and splenic vein diameters as well as caudate lobe dimensions/volume, right lobe width, right and left lobe volume, spleen volume, gallbladder wall and colon wall thickness, presence of splenorenal shunt and recanalized umbilical veins were determined independently by three radiologists. The data from each of the three reviewers were averaged to obtain the final measurement results.
Results:
1 Portal and hepatic arterial flow analysis
1.1 The flow volume of portal vein/hepatic artery
Mean values of portal flow volume in 5 groups were all raised postprandially. It was 87% in group S1,74% in group S2,57% in group S3,45% in group S4 and 90% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). When FpO>15.2ml/s, there was a sensitivity 85% and specificity 85% to diagnose liver fibrosis at stage3 or above, and the FpO cutoff flow rate of more than 16.2ml/s has a specificity of 98% and sensitivity of 42%. When Fpp<25.9ml/s, there was a sensitivity 85% and specificity 70% to diagnose liver fibrosis at stage3 or above, and the Fpp cutoff flow rate of lesss than 22.8ml/s has a specificity of 98% and sensitivity of 73%. There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was no difference for mean flow volume values of hepatic artery among all groups at fasting conditions (p>0.05). The hepatic arterial flow volume decreased postprandially, but without significant difference among all groups (p>0.05).
1.2 Mean velocity of portal vein/hepatic artery
Mean values of portal flow velocity in 5 groups were all raised postprandially, and it was 84% in group S1,98% in group S2,45% in group S3,24% in group S4 and 54% in group C respectively. There was significantly difference between S3/S4 and C (p<0.01). There was a delay of peak time when the mean velocity values reached the top point along with severity of liver fibrosis, especially in group S4 (p<0.01). There was a depressive trend of mean velocity values of hepatic artery in all groups postprandially. There was no significantly difference comparing hepatic arterial flow velocity values before and after a stantardized meal among fibrosis groups and control group (p>0.05).
1.3 The cross section area of portal veins
At the fasting state, main portal vein's cross section area in group S3 and S4 were larger than other groups(p<0.01). After meal, the portal veins'cross section areas were all increased in 5 groups, and the increased rates were 24% in S1,24% in S2, 17% in S3,14% in S4 and 29% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).
1.4 PI and RI of the hepatic artery
After a standardized meal, the hepatic arteries' PI and RI values were all increased in 5 groups, and the increase rates of PI were 350% in S1,358% in S2, 347% in S3,146% in S4 and 370% in C respectively. There was significantly difference between S4 and C (p<0.01). The increase rates of RI were 54% in S1,49% in S2,20% in S3,18% in S4 and 58% in C respectively. There was significantly difference between S3/S4 and C (p<0.01).
2. Changes of the major vessels of the liver
Hepatic veins in 4 fibrotic liver groups were 9.8mm、7.2mm、9.2 mm in S1, 9.2mm、7.5mm、9 mm in S2 group,8mm、7mm、6 mm in S3 group and 4.9mm、4.5mm、5.0mm in S4 group for right, middle and left compared to 9.9,7.6 and 8.9 mm in C group. Hepatic veins were significantly smaller in S4 compared to group C(p<< 0.001) and were negatively correlated with cirrhosis (r=-0.7,-0.6 and -0.6 respectively, p< 0.001). A right hepatic vein diameter< 5mm diagnosed cirrhosis with sensitivity= 57% but specificity=99%. Right portal veins were smaller in cirrhotic patients (group S4) measuring 6.4 mm (anterior) and 6.2 (posterior) mm, compared to 8.4 and 7.6 mm (p<< 0.001) in group C in spite of higher portal pressure in patients with cirrhosis. Left portal vein was only smaller in cirrhotic patients without recanalized umbilical vein. Mean caliber of proper hepatic artery were S1 (4.0±.1mm), S2(4.1±1.3mm), S3(4.2±1.5mm)and S4(4.1±1.5mm) respectively, and there was no significant difference compared to C(4.0±1.1mm) (p>0.05).
Conclusions:
1. Hepatic veins'diameter reduction inversely correlates with cirrhosis and may help diagnose cirrhosis when other imaging features of cirrhosis are absent. A right hepatic vein less than 5 mm in diameter on cross-sectional imaging should raise a high suspicion for cirrhosis when there are no large accessory right hepatic veins. There was no obvious change on hepatic arterial caliber when liver fibrosis happened.
2. Hepatic arterial buffer response was proved. If liver fibrosis was more severe than fibrosis of stage 3, this buffer response couldnot meet the requirement of liver function.
3. Portal blood flow velocity and volume are significantly influenced increasingly by food no matter with or without liver fibrosis, and reached the peak values around 30 minutes after meal. Hepatic arterial flow which was not correlated with meal decreased along with portal flow increasing.
4. When the severity of liver fibrosis is more than stage 3, the cross section area of main portal vein increases compensatively in order to increase the portal blood flow, which was the self-regulatory response of portal vein.The followings may suggest the block of portal flow as well as portal hypertension:delay when portal flow velocity and volume reach to the peak value postprandially, postprandial cross section area of portal vein increases unconspicuously
5. Fasting hepatic artery's PI and RI of fibrotic liver with stage 3-4 are significantly higher than normal liver and fibrotic liver with stage 1-2, but increase rate of PI and RI for stage 3-4 fibrotic liver postprandial comparing to fasting are significantly lower than other stages and normal liver. It is suggested that hepatic artery's buffer ablility is weaker in severe fibrotic liver than in the normal.
6. When the severity of liver fibrosis is more than stage 3, invalid blood flow through the fibrotic liver increases and the function disorder of severe fibrotic liver will occur. The FpO cutoff flow rate of more than 16.2ml/s and the Fpp cutoff flow rate of lesss than 22.8ml/s have a specificity of 98% for liver fibrosis diagnosis of stage3-4.
7. Liver vascular morphology and hemodynamic are related to pathologic change of fibrosis. MR techniques may help to dignose liver fibrosis and portal hypertension in early stage.
引文
1. Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier M. Comparison of fibrosis progression in chronic liver disease. J Hepatol 2003; 38:257-265.
2. Khan F, Peltekian KM, Peterson TC. Effect of Interferon-Alpha, Ribavirin, Pentoxifylline, and Interleukin-18 Antibody on Hepatitis C Sera-Stimulated Hepatic Stellate Cell Proliferation. Journal of Interferon & Cytokine Research 2008; 28:643-652.
3. Groszmann RJ, Atterbury CE. The pathophysiology of portal hypertension:a basis for classification. Semin Liver Dis 1982; 2:177-186.
4. Child C, Turcotte J. Surgery and portal hypertension 1964:50-64.
5. Pugh R, Murray-Lyon I, Dawson J, Pietroni M, Williams R. Transection of the esophagus for bleeding esophageal varices. The British Journal of Surgery 1973; 60:646-649.
6. Kamath PS, Kim WR. The model for end-stage liver disease(MELD). Hepatology 2007; 45:797-805.
7. Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Roberto J G. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol 2006; 290:980-987.
8. Olga OZ, Nikolai DY. Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis:alternatives or complements? Current Pharmaceutical Biotechnology 2003; 4:195-209.
9. Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 1986; 2:165-173.
10. Poniachik J, Bernstein D, Reddy K, et al. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc 1996; 43:568-571.
11. Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis:accuracy of US for detection—analysis of 300 cases. Radiology 2003; 227:89-94.
12. Ito K, G.Mitchell D. Imaging Diagnosis of Cirrhosis and Chronic Hepatitis. Intervirology 2004; 47:134-143.
13. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: simple MR imaging sign of cirrhosis. Radiology 1999; 211:723-726.
14. Verma SK, Mitchell DG, Bergin D, et al. Dilated cisternae chyli:a sign of uncompensated cirrhosis at MR imaging. Abdom Imaging 2008.
15. Mortele KJ, Ros PR. MR imaging in chronic hepatitis and cirrhosis. Semin Ultrasound CT MR 2002; 23:79-100.
16. Gualdi GF, Volpe A, Polettini E, Ceroni AM, Pirolli FM, Casciani E. [The role of magnetic resonance in the evaluation of diffuse liver diseases]. Clin Ter 1994; 144:539-544.
17. Kudo M, Zheng RQ, Ryang KS, et al. Diagnostic accuracy of imaging for liver cirrhosis compared to histologically proven liver cirrhosis. A multicenter collaborative study. Intervirology 2008; 51:17-26.
18. Tatsumia C, Kudoa M, Ueshimaa K, et al. Noninvasive evaluation of hepatic fibrosis using serum fibrotic markers, transient elastography (FibroScan) and real-time tissue elastography. Intervirology 2008; 51:27-33.
19. Lim AKP, Taylor-Robinson SD, Patel N, et al. Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitisC. Gut 2005; 54:128-133.
20. Faria S, Ganesan K, Mwangi I, et al. MR imaging of liver fibrosis:current state of the art. Radiographics 2009; 29:1615-1635.
21. Taouli B, Koh D. Diffusion-weighted MR imaging of the liver. Radiology 2010; 254:47-66.
22. Rouviere O, Yin M, Dresner M, et al. MR elastography of the liver: preliminary results. Radiology 2006; 240:440-448.
23. Huwart L, Salameh N, Ter Beek L, et al. MR elastography of liver fibrosis: preliminary results comparing spin-echo and echo-planar imaging. Eur Radiol 2008; in press.
24. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41:48-54.
25. Macarini L, Marini S, Milillo P, Vinci R, Ettorre G Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver:utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution
alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions. Radiol Med (Torino) 2006; 111:1087-1102.
26. Zeh H, Choyke P, Alexander H, et al. Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases. Journal of computer assisted tomography 1999; 23:664-669.
27. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Beers BEV. Hepatic flow parameters measured with MR Imaging and Doppler US:Correlations with degree of cirrhosis and portal hypertension. Radiology 2003; 229:409-414.
28. Alvarez D, Mastai R, Lennie A, Soifer G, Levi D, Terg R. Noninvasive measurement of portal venous blood flow in patients with cirrhosis:effects of physiological and pharmacological stimuli. Dig Dis Sci 1991; 36:82-86.
29. Burkart DJ, Johnson CD, Morton MJ, Wolf RL, Ehman RL. Volumetric flow rates in the portal venous system:Measurement with cine Phase-Contrast MR Imaging. Am J Roentgenol 1992; 160:1113-1118.
30. Lautt W. Relationship between hepatic blood flow and overall metabolism:the hepatic arterial buffer response. Federation Proceedings 1983; 42:1662-1666.
1. Sacerdoti D, Merkel C, Bolognesi M, Amodio P, Angeli P, Gatta A. Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gastroenterology 1995; 108:1152-1158.
2. Bosch J, Garcia-Pagan J. Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000; 32:141-156.
3. Denys A, Menu Y. Portal and splanchnic blood flow measurements in vivo: US Doppler or MR angiography. J Hepatol 1997; 26:437-438.
4. Kok T, Jagt Evd, Haagsma E, Bijleveld C, Jansen P, Boeve W. The value of Doppler ultrasound in cirrhosis and portal hypertension. Scand J Gastroenterol Suppl 1999; 230:82-88.
5. Lautt W. Relationship between hepatic blood flow and overall metabolism:the hepatic arterial buffer response. Federation Proceedings 1983; 42:1662-1666.
6. Scheuer PJ. Classification of chronic viral hepatitis:a need for reassessment. J Hepatol 1991; 13:372-374.
7. Child C, Turcotte J. Surgery and portal hypertension 1964:50-64.
8. Pugh R, Murray-Lyon I, Dawson J, Pietroni M, Williams R. Transection of the esophagus for bleeding esophageal varices. The British Journal of Surgery 1973; 60:646-649.
9. Burkart DJ, Johnson CD, Morton MJ, Wolf RL, Ehman RL. Volumetric flow rates in the portal venous system:Measurement with cine Phase-Contrast MR Imaging. Am J Roentgenol 1992; 160:1113-1118.
10. Wolf RL, Ehman RL, Riederer SJ, Rossman PJ. Analysis of systematic and random error in MR volumetric flow measurements. Magnetic Resonance in Medicine 1993; 30.
11. Hiatt JR, Gabbay J, Busuttil RW. Surgical anatomy of the hepatic arteries in 1000 cases. Annals of Surgery 1994; 220:50-52.
12. Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited:Digital subtraction angiography performed in 600 patients. Radiology 2002; 224:542-547.
13. Kopka L, Rodenwaldt J, Vosshenrich R, et al. Hepatic blood supply: comparison of optimized dual phase contrast-enhanced three-dimensional MR angiography and digital subtraction angiography. Radiology 1999; 211:51-58.
14. Zeh H, Choyke P, Alexander H, et al. Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases. Journal of computer assisted tomography 1999; 23:664-669.
15. Nelson T, Pollak R, Jonasson O, Abcarian H. Anatomic variants of the celiac, superior mesenteric and inferior mesenteric arteries and their clinical relevance. Clin Anat 1988; 1:75-91.
16. Taourel P, Blanc P, Dauzat M, et al. Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis:relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology 1999; 28:932-936.
17. Host U, Kelbaek H, Rasmusen H, et al. Haemodynamic effects of eating:the role of meal composition. Clin Sci (Lond) 1996; 90:269-276.
18. Qamar M, Read A, Mountford R, Skidmore R, Wells P. Effects of carohydrate, fat and protein on superior mesenteric artery blood flow in man. Gut 1984; 25:1154.
19. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Beers BEV. Hepatic flow parameters measured with MR Imaging and Doppler US:Correlations with degree of cirrhosis and portal hypertension. Radiology 2003; 229:409-414.
20. Numata k, Tanaka K, Kiba T, Mitsui K, Saito S, Sekihara H. Hemodynamic changes in hepatic artery after glucose ingestion in healthy subjects and patients with cirrhosis. J Clin Ultrosound 1998; 26:137-142.
21. Zhou X-p, Lu T, Wei Y-g, Chen X-z. Liver volume variation in patients with virus-induced cirrhosis:Findings on MDCT. Am J Roentgenol 2007; 189:153-159.
22. Riehl J, Bongartz D, Nguyen H, Sieberth H. Spontaneous portasystemic shunt in liver cirrhosis:imaging with color-coded duplex ultrasonography. Ultraschall Med 1997; 18:272-276.
1. Singh GK, Hoyert DL. Social epidemiology of chronic liver disease and cirrhosis mortality in the United States,1935-1997:trends and differentials by ethnicity, socioeconomic status, and alcohol consumption. Hum Biol 2000; 72:801-820.
2. Ueno Y, Moriyama M, Uchida T, Arakawa Y. Irregular regeneration of hepatocytes is an important factor in the hepatocarcinogenesis of liver disease. Hepatology 2001; 33:357-362.
3. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: simple MR imaging sign of cirrhosis. Radiology 1999; 211:723-726.
4. Verma SK, Mitchell DG, Bergin D, et al. Dilated cisternae chyli:a sign of uncompensated cirrhosis at MR imaging. Abdom Imaging 2008.
5. Gualdi GF, Volpe A, Polettini E, Ceroni AM, Pirolli FM, Casciani E. [The role of magnetic resonance in the evaluation of diffuse liver diseases]. Clin Ter 1994; 144:539-544.
6. John OD, Chaan N, Susan C, Patricia F, Roger W. Diagnostic value of Doppler assessment of the hepatic and portal vessels and ultrasound of the spleen in liver disease. Eur J Gastroenterol Hepatol 2004; 16:147-155.
7. Scheuer PJ. Classification of chronic viral hepatitis:a need for reassessment. J Hepatol 1991; 13:372-374.
8. Piccinino F, Sagnelli E, Pasquale G, Giusti G Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 1986; 2:165-173.
9. Poniachik J, Bernstein D, Reddy K, et al. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc 1996; 43:568-571.
10. Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis:accuracy of US for detection—analysis of 300 cases. Radiology 2003; 227:89-94.
11. Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests. Clin Chim Acta 2007; 381:107-113.
12. Stauber RE, Lackner C. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C. World J Gastroenterol 2007; 13:4287-4294.
13. Kamei T, Asou M, Taki K, et al. Evaluation of the degree of severity in liver cirrhosis by computed tomography. Radiat Med 1985; 3:197-203.
14. Numminen K, Tervahartiala P, Halavaara J, Isoniemi H, Hockerstedt K. Non-invasive diagnosis of liver cirrhosis:magnetic resonance imaging presents special features. Scand J Gastroenterol 2005; 40:76-82.
15. Ito K, Mitchell DG, Kim MJ, Awaya H, Koike S, Matsunaga N. Right posterior hepatic notch sign:a simple diagnostic MR finding of cirrhosis. J Magn Reson Imaging 2003; 18:561-566.
16. Martinez-Noguera A, Montserrat E, Torrubia S, Villalba J. Doppler in hepatic cirrhosis and chronic hepatitis. Semin Ultrasound CT MR 2002; 23:19-36.
17. Di Lelio A, Cestari C, Lomazzi A, Beretta L. Cirrhosis:diagnosis with sonographic study of the liver surface. Radiology 1989; 172:389-392.
18. Tchelepi H, Ralls P, Radin R, Grant E. Sonography of diffuse liver disease. J Ultrasound Med 2002; 21:1023-1032.
19. Awaya H, Mitchell D, Kamishima T, Holland G, Ito K, Matsumoto T. Cirrhosis: modified caudate-right lobe ratio. Radiology 2002; 224:769-774.
20. Kudo M, Zheng RQ, Ryang KS, et al. Diagnostic accuracy of imaging for liver cirrhosis compared to histologically proven liver cirrhosis. A multicenter collaborative study. Intervirology 2008; 51:17-26.
21. Chiu K-C, Sheu B-S, Chuang C-H. Portal Venous Flow Pattern as a Useful Tool for Predicting Esophageal Varix Bleeding in Cirrhotic Patients. Digestive Diseases and Sciences 2005; 50:1170-1174.
22. Henriksson L, Hedman A, Johansson R, Lindstr?m K. Ultrasound assessment of liver veins in congestive heart failure. Acta Radiol Diagn (Stockh) 1982; 23:361-363.
23. Strasberg SM. Nomenclature of hepatic anatomy and resections:a review of the Brisbane 2000 system. Journal of Hepato-Biliary-Pancreatic Surgery 2005; 12:351-355.
24. De Cecchis L, Hribernik M, Ravnik D, Gadzijev E. Anatomic variations in the pattern of the right hepatic veins:possibilities for type classification. J Anat 2000; 197:487-493.
25. Cheng YF, Huang TL, Chen CL, Chen TY, Huang CC, Ko SF. Variations of the middle and inferior right hepatic vein:application in hepatectomy. Journal of Clinical Ultrosound 1997; 25:175-182.
26. Couinaud C. Controlled Hepatectomies and Exposure of the Intrahepatic Bile Ducts:Anatomical and Technical Study. Paris, France:C Couinaud,1981.
27. Nakamura S, Tsuzuki T. Surgical anatomy of the hepatic veins and the inferior vena cava. Surg Gynecol Obstet 1981; 152:43-50.
28. de Oliveira IR, Widman A, Fukushima JT, Saad WA, Gama-Rodrigues JJ, Cerri GG Doppler ultrasonography evaluation of paraumbilical vein and portal hypertension. J Radiol 2001; 82:1627-1631.
29. Riehl J, Bongartz D, Nguyen H, Sieberth H. Spontaneous portasystemic shunt in liver cirrhosis:imaging with color-coded duplex ultrasonography. Ultraschall Med 1997; 18:272-276.
30. Burchell A, Panke W, Moreno A, Rousselot L. The patent umbilical vein in portal hypertension. Surg Gynecol Obstet 1970; 130:77-86.
31. Aagaard J, Jensen L, S?rensen T, Christensen U, Burcharth F. Recanalized umbilical vein in portal hypertension. AJR Am J Roentgenol 1982; 139:1107-1110.
32. Lee S, Moon D, Ahn C, et al. Ligation of left renal vein for large spontaneous splenorenal shunt to prevent portal flow steal in adult living donor liver transplantation. Transpl Int 2007; 20:45-50.
33. Rouviere O, Yin M, Dresner M, et al. MR elastography of the liver: preliminary results. Radiology 2006; 240:440-448.
34. Huwart L, Salameh N, Ter Beek L, et al. MR elastography of liver fibrosis: preliminary results comparing spin-echo and echo-planar imaging. Eur Radiol 2008; in press.
35. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41:48-54.
36. Macarini L, Marini S, Milillo P, Vinci R, Ettorre G. Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver:utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions. Radiol Med (Torino) 2006; 111:1087-1102.
2. Khan F, Peltekian KM, Peterson TC. Effect of Interferon-Alpha, Ribavirin, Pentoxifylline, and Interleukin-18 Antibody on Hepatitis C Sera-Stimulated Hepatic Stellate Cell Proliferation. Journal of Interferon & Cytokine Research 2008; 28:643-652.
3. Groszmann RJ, Atterbury CE. The pathophysiology of portal hypertension:a basis for classification. Semin Liver Dis 1982; 2:177-186.
4. Child C, Turcotte J. Surgery and portal hypertension 1964:50-64.
5. Pugh R, Murray-Lyon I, Dawson J, Pietroni M, Williams R. Transection of the esophagus for bleeding esophageal varices. The British Journal of Surgery 1973; 60:646-649.
6. Kamath PS, Kim WR. The model for end-stage liver disease(MELD). Hepatology 2007; 45:797-805.
7. Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Roberto J G. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol 2006; 290:980-987.
8. Olga OZ, Nikolai DY. Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis:alternatives or complements? Current Pharmaceutical Biotechnology 2003; 4:195-209.
9. Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 1986; 2:165-173.
10. Poniachik J, Bernstein D, Reddy K, et al. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc 1996; 43:568-571.
11. Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis:accuracy of US for detection—analysis of 300 cases. Radiology 2003; 227:89-94.
12. Ito K, G.Mitchell D. Imaging Diagnosis of Cirrhosis and Chronic Hepatitis. Intervirology 2004; 47:134-143.
13. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: simple MR imaging sign of cirrhosis. Radiology 1999; 211:723-726.
14. Verma SK, Mitchell DG, Bergin D, et al. Dilated cisternae chyli:a sign of uncompensated cirrhosis at MR imaging. Abdom Imaging 2008.
15. Mortele KJ, Ros PR. MR imaging in chronic hepatitis and cirrhosis. Semin Ultrasound CT MR 2002; 23:79-100.
16. Gualdi GF, Volpe A, Polettini E, Ceroni AM, Pirolli FM, Casciani E. [The role of magnetic resonance in the evaluation of diffuse liver diseases]. Clin Ter 1994; 144:539-544.
17. Kudo M, Zheng RQ, Ryang KS, et al. Diagnostic accuracy of imaging for liver cirrhosis compared to histologically proven liver cirrhosis. A multicenter collaborative study. Intervirology 2008; 51:17-26.
18. Tatsumia C, Kudoa M, Ueshimaa K, et al. Noninvasive evaluation of hepatic fibrosis using serum fibrotic markers, transient elastography (FibroScan) and real-time tissue elastography. Intervirology 2008; 51:27-33.
19. Lim AKP, Taylor-Robinson SD, Patel N, et al. Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitisC. Gut 2005; 54:128-133.
20. Faria S, Ganesan K, Mwangi I, et al. MR imaging of liver fibrosis:current state of the art. Radiographics 2009; 29:1615-1635.
21. Taouli B, Koh D. Diffusion-weighted MR imaging of the liver. Radiology 2010; 254:47-66.
22. Rouviere O, Yin M, Dresner M, et al. MR elastography of the liver: preliminary results. Radiology 2006; 240:440-448.
23. Huwart L, Salameh N, Ter Beek L, et al. MR elastography of liver fibrosis: preliminary results comparing spin-echo and echo-planar imaging. Eur Radiol 2008; in press.
24. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41:48-54.
25. Macarini L, Marini S, Milillo P, Vinci R, Ettorre G Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver:utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution
alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions. Radiol Med (Torino) 2006; 111:1087-1102.
26. Zeh H, Choyke P, Alexander H, et al. Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases. Journal of computer assisted tomography 1999; 23:664-669.
27. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Beers BEV. Hepatic flow parameters measured with MR Imaging and Doppler US:Correlations with degree of cirrhosis and portal hypertension. Radiology 2003; 229:409-414.
28. Alvarez D, Mastai R, Lennie A, Soifer G, Levi D, Terg R. Noninvasive measurement of portal venous blood flow in patients with cirrhosis:effects of physiological and pharmacological stimuli. Dig Dis Sci 1991; 36:82-86.
29. Burkart DJ, Johnson CD, Morton MJ, Wolf RL, Ehman RL. Volumetric flow rates in the portal venous system:Measurement with cine Phase-Contrast MR Imaging. Am J Roentgenol 1992; 160:1113-1118.
30. Lautt W. Relationship between hepatic blood flow and overall metabolism:the hepatic arterial buffer response. Federation Proceedings 1983; 42:1662-1666.
1. Sacerdoti D, Merkel C, Bolognesi M, Amodio P, Angeli P, Gatta A. Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gastroenterology 1995; 108:1152-1158.
2. Bosch J, Garcia-Pagan J. Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000; 32:141-156.
3. Denys A, Menu Y. Portal and splanchnic blood flow measurements in vivo: US Doppler or MR angiography. J Hepatol 1997; 26:437-438.
4. Kok T, Jagt Evd, Haagsma E, Bijleveld C, Jansen P, Boeve W. The value of Doppler ultrasound in cirrhosis and portal hypertension. Scand J Gastroenterol Suppl 1999; 230:82-88.
5. Lautt W. Relationship between hepatic blood flow and overall metabolism:the hepatic arterial buffer response. Federation Proceedings 1983; 42:1662-1666.
6. Scheuer PJ. Classification of chronic viral hepatitis:a need for reassessment. J Hepatol 1991; 13:372-374.
7. Child C, Turcotte J. Surgery and portal hypertension 1964:50-64.
8. Pugh R, Murray-Lyon I, Dawson J, Pietroni M, Williams R. Transection of the esophagus for bleeding esophageal varices. The British Journal of Surgery 1973; 60:646-649.
9. Burkart DJ, Johnson CD, Morton MJ, Wolf RL, Ehman RL. Volumetric flow rates in the portal venous system:Measurement with cine Phase-Contrast MR Imaging. Am J Roentgenol 1992; 160:1113-1118.
10. Wolf RL, Ehman RL, Riederer SJ, Rossman PJ. Analysis of systematic and random error in MR volumetric flow measurements. Magnetic Resonance in Medicine 1993; 30.
11. Hiatt JR, Gabbay J, Busuttil RW. Surgical anatomy of the hepatic arteries in 1000 cases. Annals of Surgery 1994; 220:50-52.
12. Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited:Digital subtraction angiography performed in 600 patients. Radiology 2002; 224:542-547.
13. Kopka L, Rodenwaldt J, Vosshenrich R, et al. Hepatic blood supply: comparison of optimized dual phase contrast-enhanced three-dimensional MR angiography and digital subtraction angiography. Radiology 1999; 211:51-58.
14. Zeh H, Choyke P, Alexander H, et al. Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases. Journal of computer assisted tomography 1999; 23:664-669.
15. Nelson T, Pollak R, Jonasson O, Abcarian H. Anatomic variants of the celiac, superior mesenteric and inferior mesenteric arteries and their clinical relevance. Clin Anat 1988; 1:75-91.
16. Taourel P, Blanc P, Dauzat M, et al. Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis:relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology 1999; 28:932-936.
17. Host U, Kelbaek H, Rasmusen H, et al. Haemodynamic effects of eating:the role of meal composition. Clin Sci (Lond) 1996; 90:269-276.
18. Qamar M, Read A, Mountford R, Skidmore R, Wells P. Effects of carohydrate, fat and protein on superior mesenteric artery blood flow in man. Gut 1984; 25:1154.
19. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Beers BEV. Hepatic flow parameters measured with MR Imaging and Doppler US:Correlations with degree of cirrhosis and portal hypertension. Radiology 2003; 229:409-414.
20. Numata k, Tanaka K, Kiba T, Mitsui K, Saito S, Sekihara H. Hemodynamic changes in hepatic artery after glucose ingestion in healthy subjects and patients with cirrhosis. J Clin Ultrosound 1998; 26:137-142.
21. Zhou X-p, Lu T, Wei Y-g, Chen X-z. Liver volume variation in patients with virus-induced cirrhosis:Findings on MDCT. Am J Roentgenol 2007; 189:153-159.
22. Riehl J, Bongartz D, Nguyen H, Sieberth H. Spontaneous portasystemic shunt in liver cirrhosis:imaging with color-coded duplex ultrasonography. Ultraschall Med 1997; 18:272-276.
1. Singh GK, Hoyert DL. Social epidemiology of chronic liver disease and cirrhosis mortality in the United States,1935-1997:trends and differentials by ethnicity, socioeconomic status, and alcohol consumption. Hum Biol 2000; 72:801-820.
2. Ueno Y, Moriyama M, Uchida T, Arakawa Y. Irregular regeneration of hepatocytes is an important factor in the hepatocarcinogenesis of liver disease. Hepatology 2001; 33:357-362.
3. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: simple MR imaging sign of cirrhosis. Radiology 1999; 211:723-726.
4. Verma SK, Mitchell DG, Bergin D, et al. Dilated cisternae chyli:a sign of uncompensated cirrhosis at MR imaging. Abdom Imaging 2008.
5. Gualdi GF, Volpe A, Polettini E, Ceroni AM, Pirolli FM, Casciani E. [The role of magnetic resonance in the evaluation of diffuse liver diseases]. Clin Ter 1994; 144:539-544.
6. John OD, Chaan N, Susan C, Patricia F, Roger W. Diagnostic value of Doppler assessment of the hepatic and portal vessels and ultrasound of the spleen in liver disease. Eur J Gastroenterol Hepatol 2004; 16:147-155.
7. Scheuer PJ. Classification of chronic viral hepatitis:a need for reassessment. J Hepatol 1991; 13:372-374.
8. Piccinino F, Sagnelli E, Pasquale G, Giusti G Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 1986; 2:165-173.
9. Poniachik J, Bernstein D, Reddy K, et al. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc 1996; 43:568-571.
10. Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis:accuracy of US for detection—analysis of 300 cases. Radiology 2003; 227:89-94.
11. Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests. Clin Chim Acta 2007; 381:107-113.
12. Stauber RE, Lackner C. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C. World J Gastroenterol 2007; 13:4287-4294.
13. Kamei T, Asou M, Taki K, et al. Evaluation of the degree of severity in liver cirrhosis by computed tomography. Radiat Med 1985; 3:197-203.
14. Numminen K, Tervahartiala P, Halavaara J, Isoniemi H, Hockerstedt K. Non-invasive diagnosis of liver cirrhosis:magnetic resonance imaging presents special features. Scand J Gastroenterol 2005; 40:76-82.
15. Ito K, Mitchell DG, Kim MJ, Awaya H, Koike S, Matsunaga N. Right posterior hepatic notch sign:a simple diagnostic MR finding of cirrhosis. J Magn Reson Imaging 2003; 18:561-566.
16. Martinez-Noguera A, Montserrat E, Torrubia S, Villalba J. Doppler in hepatic cirrhosis and chronic hepatitis. Semin Ultrasound CT MR 2002; 23:19-36.
17. Di Lelio A, Cestari C, Lomazzi A, Beretta L. Cirrhosis:diagnosis with sonographic study of the liver surface. Radiology 1989; 172:389-392.
18. Tchelepi H, Ralls P, Radin R, Grant E. Sonography of diffuse liver disease. J Ultrasound Med 2002; 21:1023-1032.
19. Awaya H, Mitchell D, Kamishima T, Holland G, Ito K, Matsumoto T. Cirrhosis: modified caudate-right lobe ratio. Radiology 2002; 224:769-774.
20. Kudo M, Zheng RQ, Ryang KS, et al. Diagnostic accuracy of imaging for liver cirrhosis compared to histologically proven liver cirrhosis. A multicenter collaborative study. Intervirology 2008; 51:17-26.
21. Chiu K-C, Sheu B-S, Chuang C-H. Portal Venous Flow Pattern as a Useful Tool for Predicting Esophageal Varix Bleeding in Cirrhotic Patients. Digestive Diseases and Sciences 2005; 50:1170-1174.
22. Henriksson L, Hedman A, Johansson R, Lindstr?m K. Ultrasound assessment of liver veins in congestive heart failure. Acta Radiol Diagn (Stockh) 1982; 23:361-363.
23. Strasberg SM. Nomenclature of hepatic anatomy and resections:a review of the Brisbane 2000 system. Journal of Hepato-Biliary-Pancreatic Surgery 2005; 12:351-355.
24. De Cecchis L, Hribernik M, Ravnik D, Gadzijev E. Anatomic variations in the pattern of the right hepatic veins:possibilities for type classification. J Anat 2000; 197:487-493.
25. Cheng YF, Huang TL, Chen CL, Chen TY, Huang CC, Ko SF. Variations of the middle and inferior right hepatic vein:application in hepatectomy. Journal of Clinical Ultrosound 1997; 25:175-182.
26. Couinaud C. Controlled Hepatectomies and Exposure of the Intrahepatic Bile Ducts:Anatomical and Technical Study. Paris, France:C Couinaud,1981.
27. Nakamura S, Tsuzuki T. Surgical anatomy of the hepatic veins and the inferior vena cava. Surg Gynecol Obstet 1981; 152:43-50.
28. de Oliveira IR, Widman A, Fukushima JT, Saad WA, Gama-Rodrigues JJ, Cerri GG Doppler ultrasonography evaluation of paraumbilical vein and portal hypertension. J Radiol 2001; 82:1627-1631.
29. Riehl J, Bongartz D, Nguyen H, Sieberth H. Spontaneous portasystemic shunt in liver cirrhosis:imaging with color-coded duplex ultrasonography. Ultraschall Med 1997; 18:272-276.
30. Burchell A, Panke W, Moreno A, Rousselot L. The patent umbilical vein in portal hypertension. Surg Gynecol Obstet 1970; 130:77-86.
31. Aagaard J, Jensen L, S?rensen T, Christensen U, Burcharth F. Recanalized umbilical vein in portal hypertension. AJR Am J Roentgenol 1982; 139:1107-1110.
32. Lee S, Moon D, Ahn C, et al. Ligation of left renal vein for large spontaneous splenorenal shunt to prevent portal flow steal in adult living donor liver transplantation. Transpl Int 2007; 20:45-50.
33. Rouviere O, Yin M, Dresner M, et al. MR elastography of the liver: preliminary results. Radiology 2006; 240:440-448.
34. Huwart L, Salameh N, Ter Beek L, et al. MR elastography of liver fibrosis: preliminary results comparing spin-echo and echo-planar imaging. Eur Radiol 2008; in press.
35. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41:48-54.
36. Macarini L, Marini S, Milillo P, Vinci R, Ettorre G. Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver:utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions. Radiol Med (Torino) 2006; 111:1087-1102.