3T MR功能成像评价肝纤维化的临床应用研究
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摘要
研究背景
肝纤维化是肝脏对各种原因所致肝损伤的创伤修复反应,表现为肝内纤维结缔组织增生与沉积。引起肝纤维化的病因很多,在我国,病毒性肝炎是其主要病因。研究发现,肝纤维化经有效治疗是可以逆转的,但若病因持续存在,最终必然发展成为不可逆的肝硬化。因此,在肝硬化之前能早期诊断并及时干预,对于减缓肝纤维化的进程至关重要。慢性肝炎发展至肝硬化,经历疾病的不同阶段,而不同阶段决定了临床不同的处理方法。所以,基于临床治疗干预及预后随访的需要,有必要对慢性肝炎病人肝纤维化程度及炎症活动度进行评估。
目前评估肝纤维化病变程度的金标准是肝脏穿刺活检的组织病理学检查,但其缺点是有创且存在取样误差,因此,临床迫切需要一种非侵袭性、可定量评价肝纤维化、准确性较高的诊断方法。MRI因为无创、无辐射、软组织分辨率高,尤其是MR功能成像技术的发展,为肝纤维化的无创诊断研究提供了契机。国内外一些学者使用不同的功能成像方法对肝纤维化及肝硬化进行研究,取得了初步成果,但相关结论还存在争议。另外,关于哪一种成像方法更敏感、更准确、更实用,尚无这方面的报导。基于以上现状,借助3.0T磁共振这样一个先进工具,本研究拟采用弥散加权成像(diffusion weight imaging,DWI)、动态增强(dynamic contrast-enhanced,DCE)、磁化传递成像(magnitization transferimaging,MTI)及T2mapping等功能成像方法对肝纤维化程度进行评估,以筛选出诊断准确性较高、实用性较强的成像方法,为肝纤维化的临床治疗及随访监测提供有益的参考。
第一部分弥散加权成像参数优化及评价肝纤维化的临床应用研究
研究目的
优化3T MR肝脏DWI成像的技术参数,分析ADC值与肝纤维化程度和炎症活动度的相关性,并探讨其诊断肝脏纤维化程度及炎症活动度的效力。
材料与方法
1.研究对象
纳入本研究分析共64例,按肝纤维化分期分6组:S0(14例)、S1(9例)、S2(14例)、S3(7例)、S4(3例)、肝硬化(17例);按炎症分级共47例分5组:G0(14例)、G1(2例)、G2(11例)、G3(16例)、G4(4例)。
2.仪器及设备
采用GE Signa Excite 3.0T超导型核磁共振扫描仪,8通道相控阵腹部表面线圈。GEADW4.3图形工作站。
3.检查方法及参数
所有被检查者需空腹4h以上,均采用深吸气吐气后屏息扫描。DWI扫描采用单次激发EPI序列联合ASSET技术,ASSET因子为2.0Ph。DWI成像前先行ASSET校准扫描,扫描范围自胸部中段至下腹。DWI弥散梯度因子(b)值分别取300、600、800、1000s/mm~2。TR/TE:1500/46.7～59.2,NEX＝4,层厚8mm,层间距2mm,矩阵128×128,FOV 38×38cm。
其中18例检查者行DWI成像时,保持其他成像参数不变,扩散方向数分别选取S/I(弥散梯度施加在z轴方向)和ALL(弥散梯度施加在x、y、z三个正交方向)模式。其余检查者行DWI成像时,扩散方向数均为ALL,其他成像参数不变。
4.图像后处理及分析
使用GE ADW4.3工作站Functool软件包的弥散分析软件进行图像后处理及测量。
从肝脏DWI图像形态学观察、SNR及相应ADC值三个方面比较两种弥散梯度方向施加模式下所得图像的差别。用5个指标对DWI图像质量进行形态学评价,即肝内管道边界是否清晰、有无磁敏感伪影、肝实质信号是否均匀细腻、肝左叶是否较好显示、背景噪声多少,并将其分优、良、差三个等级赋予2、1、0三个分值。DWI图像SNR,采用公式SNR＝SI_(liver)/SD_(noise)计算,在DWI图像肝右叶后段放置ROI,面积约为1.6cm~2,获取信号强度值(SI_(liver)),同时在图像左外侧背景噪声上放置ROI,获取噪声信号强度的标准差(SD_(noise))。对于两种梯度方向模式所得图像SNR的比较,要保证两种模式下ROI放置位置一致。
肝脏ADC值测量选取肝门及其上下共三个层面,每个层面肝右后叶选取3个ROI,取9个ROI所测得ADC值的平均值。ROI的放置应注意避开肝内大的血管和胆道。
评价ADC值测量的可重复性。对正常组中13名检查者的DWI成像原始数据,进行两次后处理,计算平均ADC值,比较两次测量的ADC值差别。
5.统计学分析
采用SPSS 11.5统计软件包,各测量参数用均数±标准差表示,P＜0.05认为有统计学意义。
运用配对秩和检验比较两种弥散梯度方向施加模式所得DWI图像质量的评分,用配对t检验比较两种梯度方向施加模式DWI图像的信噪比(SNR)及肝脏ADC值的差别。用Spearman相关分析法探讨DWI图像信号强度、信噪比及ADC值与b值的关系。同一原始数据两次后处理所得ADC值差别,亦采用配对t检验。
运用Spearman相关分析法探讨肝脏ADC值和肝纤维化程度、肝炎活动度之间的相关性。运用单因素方差分析法(One-way ANOVA)比较各b值条件下ADC值在不同程度肝纤维化、肝炎活动度的差异,并用LSD法进行多重比较。运用受试者工作曲线(ROC曲线)评价ADC值诊断S≥1、S≥2、S≥3、肝硬化及G≥2、G≥3的效能。
结果
1.DWI方法学
DWI成像时弥散梯度方向选取ALL模式所获DWI图像的图像质量在各b值条件下均明显优于S/I模式(P＜0.05);前者的图像SNR较后者略高,在b取300、800s/mm2时差异显著(P＜0.05);相应的ADC值也同样是前者高于后者,在b＝600和800 s/mm2时差异有统计学意义(P＜0.05)。
b值与DWI图像信号强度、信噪比及ADC值均呈显著负相关关系(P＜0.001,r为-0.811～-0.882),DWI图像信噪比、信号强度与ADC值存在显著相关关系(P＜0.001,r为0.811～0.817)。
依据ROI的选取标准,对同一DWI原始数据进行两次ADC值测量,测量结果差别无统计学意义(P＞0.05)。
2.ADC值与肝纤维化程度的相关性及其评估肝纤维化程度的效力
各b值条件下,ADC值与肝纤维化程度均存在显著负相关关系(P＜0.001),尤其在b＝600 s/mm~2和800 s/mm~2时相关关系较为密切(r＞0.5)。4个b值条件下ADC值在不同程度肝纤维化组间的差别均有统计学意义(P＜0.01)。多重比较,在b＝300 s/mm~2时,正常组与S2、S3、肝硬化组及S1组与肝硬化组间差异有统计学意义(P＜0.05);b＝600 s/mm~2、800 s/mm~2时,正常组除与S1组差异不显著外,与其他各组间差异均有统计学意义(P＜0.01),S1与S3组、S1与肝硬化组、S2与肝硬化组差异亦均有统计学意义(P＜0.05);b＝1000 s/mm~2时,正常组与S3、肝硬化组差异显著(P＜0.05),S1与S3、S1与肝硬化组、S2与肝硬化组间差异均有统计学意义(P＜0.05)。
ROC曲线分析显示,b取300、600、800、1000s/mm~2时,ADC值诊断S≥1的曲线下面积分别为0.733、0.844、0.793、0.694;诊断S≥2的曲线下面积分别为0.748、0.835、0.820、0.775:诊断S≥3的曲线下面积分别为0.748、0.855、0.840、0.791;诊断肝硬化的曲线下面积为0.748、0.824、0.812、0.761,各b值下曲线下面积的95%置信区间有交叉。诊断不同纤维化程度时均为b＝600s/mm~2时曲线下面积最大,其次为b＝800s/mm~2时。b取600s/mm~2时,以ADC值≤1.453×10~(-3)mm2/s为标准,诊断S≥1的灵敏度为75%,特异度为73.9%;取1.453×10~(-3)mm~2/s为诊断界值,ADC诊断S≥2的灵敏度为80.5%,特异度为73.9%;以ADC值≤1.414×10~(-3)mm~2/s为标准,诊断S≥3的灵敏度为81.5%,特异度为73%;以ADC值≤1.339×10~(-3)mm~2/s为标准,诊断肝硬化的准确性为82.4%,灵敏度70.6%,特异度87.2%。
3.ADC值与肝炎活动度的相关性及其评价肝炎活动度的效力
ADC值与肝炎活动度呈显著负相关关系(P＜0.05),同样在b＝600 s/mm~2和800 s/mm~2时相关关系较为密切(r＞0.5)。在b取600、800 s/mm~2时ADC值在不同程度炎症分级间的差异有统计学意义(P＜0.05)。进一步多重比较,b＝600s/mm~2时,正常组和轻、中、重度炎症组间比较均有统计学意义(P＜0.05),轻度炎症与重度炎症组间差异亦显著(P＜0.05)。b＝800 s/mm~2时,正常组和中度、重度炎症组间差异显著(P＜0.01),轻度与重度炎症组间差异有统计学意义(P＜0.01)。ROC曲线分析结果显示,各b值条件下,ADC值预测G≥2、G≥3均有统计学意义(P＜0.05),并且前者的AUC均略小于后者。4个b值下,ADC诊断G≥2的AUC分别为0.712、0.783、0.772、0.704,诊断G≥3的AUC分别为0.701、0.786、0.782、0.704。当b取600 s/mm~2时,以ADC值≤1.453×10~(-3)mm~2/s为标准,诊断G≥2的灵敏度为75%,特异度为73.9%;以ADC值≤1.433×10~(-3)mm~2/s为标准,诊断G≥3的灵敏度为71.4%,特异度为73.1%。
结论
1.在进行肝脏DWI成像时,采用同时3个正交方向施加弥散敏感梯度较为稳妥,可以获得较好的DWI成像质量及较为准确的ADC值。
2.肝脏ADC值与肝纤维化程度及肝炎活动度均呈显著负相关关系,ADC值是较有意义的评价指标。ADC值诊断不同程度纤维化时均具有一定的准确性,评价中度以上程度纤维化的准确性相对较高。
3.4个b值条件下,ADC值评价肝纤维化程度及肝炎活动度的效能无统计学差别,但b＝600 s/mm~2时,诊断准确性最高,同时又可获得较好的DWI成像质量,是肝脏DWI成像的最佳b值。
4.DWI成像无创,技术操作简单,ADC值测量可重复性较好,可以为临床肝炎、肝纤维化的早期诊断和治疗随访提供一定的参考指标。
第二部分MRI全肝动态增强扫描评价肝纤维化的临床应用研究
研究目的
利用LAVA技术设计多时相全肝动态增强扫描程序,探讨肝纤维化、肝硬化的血流动力学变化特点,评价动态增强扫描在诊断肝纤维化程度的价值。
材料与方法
1.研究对象
纳入本研究分析共31例,按纤维化程度分4组:正常组(S0期9例)、轻度纤维化组(S1期1例、S2期2例)、中重度纤维化组(S3期1例、S4期3例)、肝硬化组15例。
2.仪器设备与药品
磁共振扫描仪、表面线圈及图形工作站同前。使用全自动双筒压力注射器及顺磁性对比剂Gd-DTPA。
3.检查方法及参数
动态增强扫描采用LAVA序列联合ASSET技术,ASSET因子取2.5Ph,TR/TE为2.8ms/1.2ms,带宽125KHz,重建层厚为2.7mm,8s完成一次72层全肝容积扫描。高压注射器经肘静脉团注0.2mmol/kg的Gd-DTPA,注射速率为4ml/s,随即以4 ml/s的速率注射21ml生理盐水冲管。注射对比剂的同时开始扫描,共扫描4期,每期连续3个时相,每个时相扫描时间8s,总扫描时间约160s。均采用屏息下扫描,每期扫描结束后嘱病人自由呼吸,3次间歇时间依次为5s、15s、30s,每期扫描屏息口令耗时约5s。
4.图像后处理及分析
原始数据使用Functool软件包SER软件进行处理,分别在腹主动脉、门静脉、肝脏实质、脾脏选取ROI,自动生成时间信号曲线(time signal intensity curve,TIC)。记录各ROI的TIC的信号强度峰值(SI_p)、基线信号强度值(SI_0)、达峰时间(time to peak,TTP),并计算各TIC的峰高、信号上升最大斜率(maximumslope of increase,MSI)和信号下降最大斜率(maximum slope of decrease,MSD),计算公式为:MSI/MSD＝(SI_2-SI_1)/t,SI_2和SI_1分别指曲线上升段或下降段信号强度变化最大的两个相邻扫描时相的信号强度,t为两个相邻时相的时间差。我们把扫描的1～3个时相归为动脉期、4～6个时相归为门静脉期,分别计算两期肝MSI及动脉期脾MSI。
5.统计学分析
统计学分析采用SPSS 11.5软件包,P＜0.05认为有统计学意义。
运用Spearman相关分析法评价TIC量化参数与肝纤维化程度的相关性;运用单向方差分析法比较各参数在不同程度纤维化组的差别;运用ROC曲线分析TIC参数诊断肝纤维化程度的效力。
结果
1.门静脉、肝脏、脾脏的峰高与纤维化程度呈显著负相关关系(P＜0.01),达峰时间与纤维化程度呈显著正相关关系(P＜0.01),门脉MSI、动脉期肝MSI、门脉期肝MSI、肝MSD、脾MSI、脾MSD均与纤维化程度呈显著负相关关系(P＜0.01)。
2.门静脉TIC的峰高、达峰时间及MSI在不同程度纤维化组间的差异有统计学意义(P＜0.05)。肝脏TIC的达峰时间、峰高、动脉期MSI、门静脉期MSI及MSD在各组间差异均显著(P＜0.05)。脾脏TIC的峰高、达峰时间、动脉期MSI及MSD在不同程度纤维化组间差异亦均显著(P＜0.01)。
3.ROC曲线分析结果显示,诊断S≥1时,TIC参数中有诊断意义的指标为门静脉期肝MSI、动脉期脾MSI、脾MSD,曲线下面积依次为0.747、0.738、0.783;诊断S≥3时,所有的速率指标均有诊断意义(P＜0.05),曲线下面积为0.728-0.877,由小到大依次为动脉期肝MSI、门静脉MSI、门静脉期肝MSI、肝MSD、动脉期脾MSI、脾MSD;诊断肝硬化时,所有的斜率指标均有诊断意义(P＜0.05),曲线下面积为0.742～0.821(表2.10,图2-9),AUC由小到大对应的参数依次为门静脉期肝MSI、肝MSD、动脉期肝MSI、门静脉MSI、动脉期脾MSI、脾MSD,其中脾MSD及动脉期脾MSI曲线下面积最大。
结论
1.动态增强TIC参数与肝纤维化程度有中等程度的相关关系,TIC量化参数在一定程度上可以判断肝纤维化的病变程度,但对判断有无纤维化(S≥1)的作用有限,对中度以上(S≥3)纤维化和肝硬化的诊断准确性较高。
2.诊断不同程度肝纤维化,脾脏的TIC参数都表现出较高的诊断准确性,说明对脾脏血流动力学的观察是有必要的。多个TIC指标联合分析,有助于对病变程度的判断。
3.建立了基于LAVA技术的全肝动态增强成像的一站式检查方法,即单次检查可同时评价病变的形态学、血流动力学变化,不失为一种实用的无创评价肝纤维化的功能成像方法。
第三部分磁化传递、T2mapping技术评价肝纤维化的临床应用研究
研究目的
采用MTI及T2mapping技术,评价MTR值、T2值与肝纤维化程度及炎症活动度的相关性,探讨其评价肝纤维化的价值。
材料与方法
1.研究对象
行MTI并最终纳入分析的共65例,按纤维化分期分6组:S0(n＝13)、S1(n＝8)、S2(n＝15)、S3(n＝7)、S4(n＝3)、肝硬化(n＝19);按炎症分级分4组:正常组(G0期13例)、轻度炎症组(G1期1例、G2期11例)、中度炎症组(G3期17例)、重度炎症组(G4期4例)。
行T2mapping并最终纳入分析的共55例,按纤维化分期分6组:S0(n＝10)、S1(n＝7)、S2(n＝16)、S3(n＝5)、S4(n＝3)、肝硬化(n＝14);按炎症分级分4组:正常组(G0期10例)、轻度炎症组(G1期1例、G2期11例)、中度炎症组(G3期16例)、重度炎症组(G4期3例)。
2.仪器与设备
同第一部分。
3.检查方法及参数
所有检查者需空腹4h以上。
MTI采用SPGR序列,分别在施加磁化传递脉冲前后进行扫描,TR/TE为76ms/4ms,翻转角15度,层厚6mm,层间隔2mm,矩阵192×192,FOV为38×38cm,采样带宽31.3KHz。MT脉冲偏移频率为1200Hz,有效翻转角670度,脉冲持续时间8s。采用深吸气吐气后屏息扫描,扫描层面定位于肝门水平,扫描两层,扫描时间17s。
T2map采用反转恢复快速自旋回波技术,同时采用呼吸触发。8个回波,TE分别为22.6ms、33.9ms、45.2 ms、56.6 ms、67.9 ms、79.2 ms、90.5 ms、101.8 ms,TR为3750ms,NEX为1,FOV为40×40cm,采样带宽15.63KHz,层厚8mm,层间隔2mm,最大层数为20层,进行全肝成像,扫描时间7分8秒。
4.图像后处理及分析
MTI原始数据使用Functool软件包内的磁化传递分析软件进行处理,给出MTR值计算方式,自动生成MTR伪彩图。MTR值计算方式为“(施加脉冲序列—未施加脉冲序列)/施加脉冲序列”。分别于两个层面上肝右叶后段放置3个圆形ROI获取相应的MTR值,取其平均值。ROI的放置需注意避开大血管及器官边缘。
T2mapping原始数据使用Functool软件包的T2mapping分析软件,可直接得到T2值伪彩图,图中每个像素值的高低代表组织T2值。取连续5个层面肝右叶后段放置圆形ROI,每层放置3个,直径1.8mm~2,取平均值。ROI放置应注意避开大血管。
5.统计学分析
采用SPSS 11.5软件包进行统计学分析,P＜0.05认为差异有统计学意义。
运用Spearman相关分析法探讨肝脏MTR值、T2值与肝纤维化程度及炎症活动度的相关性。运用ROC曲线分析MTR值用于诊断肝纤维化程度的效能。
结果
1.MTR值与纤维化程度及炎症活动度之间有显著正相关关系(P＜0.05),但相关关系并不密切,相关系数r分别为0.343、0.347。ROC曲线分析结果表明,MTR值用于判断肝纤维化程度有意义(P＜0.05),但准确性不高,诊断S≥1、S≥2、S≥3及肝硬化的曲线下面积分别为0.692、0.683、0.667、0.669。MTR值用于判断肝炎活动度无统计学意义(P＞0.05)。
2.T2值与肝纤维化程度及炎症活动度之间无显著相关关系(P＞0.05)。
结论
1.MTR值与肝纤维化程度及炎症活动度有轻度正相关关系,MTR值可以用于评价肝纤维化程度,但诊断准确性不高。
2.T2值与肝纤维化程度及炎症活动度无明显相关关系,在定量评价纤维化方面价值不大。
第四部分DWI与动态增强成像评价肝纤维化的优势比较
研究目的
比较肝脏DWI成像与动态增强成像诊断肝纤维化程度的效能。
材料与方法
仪器与药品、检查方法及图像分析方法均同第一、二部分。
对同时行DWI和动态增强成像的共23例(S0期8例,S1期1例,S2期3例,S3期1例,S4期2例,肝硬化8例)进行分析。用ROC曲线比较ADC值与TIC斜率指标在诊断S≥1、S≥3及肝硬化的效能。
结果
ROC曲线分析结果显示,在诊断S≥1时,ADC值作为诊断指标有统计学意义(P＜0.01),AUC为0.925,而TIC斜率指标无统计学意义(P＞0.05);在诊断S≥3时TIC斜率指标及ADC值均有诊断意义(P＜0.05),ADC值曲线下面积为0.932,TIC参数曲线下面积为0.803～0.871;诊断肝硬化时,两指标亦均有诊断意义(P＜0.05),ADC值的AUC为0.933,TIC参数曲线下面积为0.770～0.816。ADC值作为诊断指标的曲线下面积较大,但两种方法曲线下面积95%可信区间有交叉。
结论
1.在诊断有无肝纤维化时,动态增强TIC斜率参数不是较有意义的诊断指标,而ADC值有相对较高的准确性;在诊断中度以上纤维化时,两种方法诊断效力相当,但ADC值的诊断准确性较高。
2.从临床应用角度来看,两种诊断方法各有优势,需结合病情需要和病人意愿灵活选择。
Background
Liver fibrosis is the wound-healing response to various liver damage,in the form of a progressive accumulation of fibrosis.It alters the tissue structure and function of liver,leading to cirrhosis and liver failure.Many causes can induce hepatic fibrosis.In our country,however,chronic viral infection is the main cause.It is reported in some researches that liver fibrosis can be reversed through effective treatment;but if the cause stays on,it would develop into liver cirrhosis.So,early detection of liver fibrosis and cirrhosis has important clinical implications for the determination of antiviral treatment options and patient prognosis.Chronic liver diseases progress through different histological stages to final cirrhosis,and histological stages serve as a key predictor in the clinical management of patients with chronic hepatitis.Thus,the diagnosis of the stage of liver fibrosis and the grade of inflammation in patients with chronic hepatitis is essential for therapeutic and prognostic evaluation.
The gold standard in assessing fibrosis is still represented by liver biopsy, despite the invasiveness of the procedure and the likelihood of sampling errors. Therefore it is an urgent need to search for a noninvasive diagnosis method to quantify liver fibrosis.MRI has become an increasingly important imaging modality for the investigation of patients with chronic liver disease.Some functional imaging methods have been investigated for this purpose,but their clinical role remains undefined.To our knowledge,however,the comparison among these methods in the diagnosis of liver fibrosis has not been reported.Thus,the purpose of our study is to prospectively evaluate the sensitivity and specificity of various functional imaging methods by using 3.0 T MR in the diagnosis of liver fibrosis(such as DWI,Dynamic contrast-enhanced MRI,MTI and T2mapping),in order to choose reasonably in clinical work.
Part One:Clinical Study of Diffusion-weighted MR Imaging in Evaluating Liver Fibrosis
Objective
The purpose of this study is to optimize the technical parameters of diffusion-weighted MRI in liver with 3T MR scanner and to evaluate its ability for evaluating of liver fibrosis quantificativly.
Materials and Methods
1.Subjects
A total of 64 cases were incorporated into this study and were divided into 6 groups according to the stage of liver fibrosis:S0(14 cases),S1(9 cases),S2(14 cases),S3(7 cases),S4(3 cases),liver cirrhosis(17 cases).A total of 46 cases were divided into 5 groups according to the grade of inflammation:G0(14 cases),G1(2 cases),G2(11 cases),G3(16 cases),G4(4 cases).
2.Instruments and equipment
DWI of the liver was performed on a GE Signa Excite 3.0-T superconductive MRI scanners with an eight-element phased-array superficial coil.
3.Examination methods and parameters
The patients and control subjects were asked to fast for 4 hours before the study. Breathhold diffusion-weighted imaging of the liver was performed,using single shot echo-planar imaging sequences in conjunction with parallel imaging with an acceleration factor of 2.0Ph.ASSET correction scan was performed before DWI imaging with scan range from the middle chest to the lower abdomen.Four breath-hold acquisitions were obtained in the same liver location at b values of 0-300,0-600,0-800 and 0-1000s/mm~2.The following parameters were used: TR/TE＝1500/46.7～59.2ms,NEX＝4,slice thickness＝8mm;gap＝2mm;matrix＝128×128,field of view＝38×38cm.
First of all,18 healthy volunteers were imaged twice under each b value with diffusion gradient applied along the section-select direction(S/I) and in three orthogonal directions(All).The rest of examinees were imaged with“ALL”model with other imaging parameters invariably.
4.Data processing and data analysis
Diffusion analysis software package on a workstation(GE ADW4.3) was used to obtain ADC maps for each b value.The quality of DWI images obtained from two patterns of diffusion gradient directions was evaluated by 5 indicatrixs as follows: Whether the intrahepatic pipe has a clear border;Whether the magnetic artifacts were sensitive,Whether the signal of liver parenchyma is homogeneous and fine,whether the left lobe of liver shows better,and how much the background noise is.Three scores(2,1,0) were given,representing respectively three levels as excellent,good, bad.Signal intensity(SI) was measured on the images recorded in a homogeneous circular(area,1.3cm2) at the right posterior lobe of the liver and the noise of background.Signal to noise ratios(SNR) of liver on DWI were calculated:SNR＝SI/SDnoise,in which SDnoise is the standard deviation of the background noise. During the process,great care needed to be taken to ensure the consistency of ROI placement at different diffusion gradient directions.ROIs were placed in areas that were as similar as possible to the areas assessed in two patterns.
Quantitative ADC maps were derived automatically on a voxel-by-voxel basis by using software.Three regions of interest(ROIs) were placed in the posterior right hepatic lobe per slice(mean size＝1.3 cm) on three consecutive slices to measure liver ADC values.Care was taken to exclude vessels and bile duct.The final ADC per subject used for analysis was the average of nine measurements.
With method mentioned above,the ADC values were measured twice by examining the b value of the DWI images of 13 examinees.Differences were then compared.
5.Statistical analysis
SPSS 11.5 statistical software was used for analysis.All values were expressed as mean±standard deviation.For all tests used,A p value＜0.05 was considered statistically significant.
The paired Kruskal-Wallis test was used to compare the images' quality score obtained with two Pattern that diffusion gradient directions were applied.The paired T test was used to compare the difference of SNR and the ADC value of the two DWI images with two patterns.The Spearman correlation analysis was used to study the relevance between the b value and signal strength,signal to noise ratio and ADC value on DWI images.The paired T test compared the ADC values measured two times from the same patients.
The Spearman rank correlation test was used to assess the correlation between liver ADC and stage of fibrosis and grade of inflammation.One-way ANOVA test was used to compare the difference of ADC value among fibrosis stage and inflammation grade under the conditions of different b values,and LSD method was used to perform multiple comparisons.Receiver operating characteristic analysis was used to assess the performance of ADC in prediction of the presence of stage 1 or greater,stage 2 or greater,stage 3 or greater of liver fibrosis and grade 2 or greater, grade 3 or greater of inflammatory activity.
Result
1.DWI Methodology
DWI image quality obtained with diffusion gradient applied in three orthogonal direction was significantly better than that obtained with diffusion gradient applied along the section-select direction(P＜0.05) at each b values.The SNR of the image with“all”pattern tended to be higher than those with“S/I”pattern and the difference was significant(P＜0.05) at b＝300,800 s/mm2.ADC value tended to be higher than the S/I image and the difference was significant at b＝600,800 s/mm2(P＜0.05).
There was negative correlation between b value and signal strength,SNR and ADC values of DWI images(P＜0.01).
There were no significant differences between ADC values measured two times based on the ROI selection criteria(P＞0.05).
2.ADC Values and Fibrosis Stage
There was moderate but significant negative correlation between ADC and fibrosis stage.The best correlation was observed for the ADC at b values 600 and 800 s/mm~2(r＞0.5).
There was a decreasing trend in hepatic ADC with increasing degree of fibrosis. There were significant differences among different fibrosis stages at each b values(P＜0.01).In multiple comparisons,there were no significant difference between S0 and S1 for all b values and there were significant differences between stage 0 and stage 2-4(P＜0.05).In addition,there were significant differences between stage 1 and stage 3 fibrosis,stage 1 and cirrhosis for b value of 800～1000 s/mm~2,between stage 1 and stage 2 and cirrhosis for a b value of 600～800 s/mm~2.
Using ROC analysis,we found hepatic ADC to be a significant predictor of stage 1 or greater fibrosis with an AUC of 0.733,0.844,0.793,0.694 at b value of 300,600,800,1000s/mm~2.AUC were 0.748,0.835,0.820,0.775 when hepatic ADC was used to predict S≥2 and were 0.748,0.855,0.840,0.791 respectively when hepatic ADC was used to predict S≥3.The largest AUC was observed at b value of 600s/mm~2 and followed at b value of 800s/mm~2.At b value of 600s/mm~2,the diagnosis of S≥1 accuracy of ADC values was 84.4%.
When assuming ADC values＜1.453×10~(-3)mm~2/s as the standard,the sensitivity was 75%and specificity 73.9%;the diagnosis of S≥2 accuracy was 83.5%,When assuming ADC＜1.453×10~(-3)mm~2/s for the diagnosis of community value,the sensitivity was 80.5%and specificity 73.9%;predicted moderate and above fibrosis (S3 or grater) for the area under the curve was 0.855,when assuming ADC value≤1.414×10~(-3)mm~2/s as the standard,sensitivity was 81.5%,specificity was 73%.
3.ADC Values and Inflammation Grade
There was a decreasing trend in hepatic ADC with increasing degree of inflammation.The correlation between ADC and inflammation grade(P＜0.05) varied from weak to moderate.There were a significant difference at b values of 600,800 s/mm~2 among different degree inflammation(P＜0.05).Using ROC analysis,we found ADC to be a significant predictor of grade 2 or greater inflammation with an AUC of 0.783,0.832 respectively(b＝600,800 s/mm~2) and to be a significant predictor of grade 3 or greater inflammation with an AUC of 0.786,0.782 respectively.For prediction of great 2 or greater inflammation at b values of 600 s/mm~2,we found an AUC of 0.783 with a sensitivity of 75%,specificity of 73.9%for a hepatic ADC of 1.453×10~(-3)mm~2/s or less.For prediction of great 3 or greater inflammation at b values of 800 s/mm~2,we found an AUC of 0.783 with a sensitivity of 75%,specificity of 73.9%for a hepatic ADC of 1.433×10~(-3)mm~2/s or less.
Conclusions
1.When conducting liver DWI,the selection of diffusion-sensitive gradient direction has a certain impact on image quality and ADC value measured.In this study,diffusion-sensitive gradient were applied in three orthogonal directions,a better image quality and stability of the ADC value were obtained.
2.There was negative correlation between ADC and fibrosis stage,inflammation grade.ADC values have a certain contribution to the evaluation of the stage of hepatic fibrosis and inflammatory activity.The former presents a higher accuracy.
3.The diagnosis performance of ADC values in predicting the stage of liver fibrosis was at the b of 600 s/mm~2.
4.DWI imaging is a non-invasive technology and could be operated easily,and ADC value measurement has better reproducibility.DWI could provide a reference in early diagnosis,treatment and follow-ups for chronic patients.
Part Two Application Study of Dynamic Contrast-Enhanced MRI of Whole Liver in Evaluating Liver Fibrosis
Objective
To analyze the homodynamic changes of liver fibrosis by using enhanced dynamic MRI;to investigate the role of Dynamic Contrast-Enhanced MRI in evaluating liver fibrosis.
Materials and Methods
1.Subjects
Thirty-one consecutive patients were prospectively enrolled in this study.They are divided into 4 groups according to the stages of fibrosis:normal group(SO 9 cases),mild fibrosis group(S1 1 case,S2 2 cases),moderate to severe fibrosis group (S3 1 case,S4 3 cases),15 cases of liver cirrhosis group.
2.Equipment and contrast medium
Magnetic resonance scanner and the surface coil were the same as used in Part One.Gd-DTPA(Dimeglnmine Gadopentetate Injection,Kangchen,China) was injected as paramagnetic contrast medium with high pressure injection(Ulrich corp).
3.Examination Technique
Whole-liver enhanced dynamic MR imaging was performed by using a liver acceleration volume acqui-sition technique in Axial plane.Phase-accelerating factor was 2.5Ph.The following imaging parameters were used:2.8/1.2(repetition time msec/echo time msec),5.4-cm slice thickness resulting in an interpolated 2.7-mm section thickness,and 125 Hz bandwidth.The starting time of acquisition of dynamic contrast-enhanced images was synchronized with the start ofⅣbolus administration of 0.1 mmol/kg of gadopentetate dimeglumine followed by a 20ml saline flush injected at a rate of 4 ml/sec with an MR-compatible power injector.A total of four scanning were conducted,each including three phases,and each phase lasted 8s,the total scan time totaled approximately 160s.Patients were requested to hold their breath for 24s thrice.The first breath-holding was started simultaneously with administration of gadopentetate dimeglumine and the interval between breath-holding periods was 10,20,35sec,respectively.
4.Image Analysis
The images were transferred to GE ADW4.3 workstation and were analyzed using the SER software of Functool software package.Regions of interest(ROIs) were drawn manually on the main portal vein,the proximal abdominal aorta,right lobe areas of the liver and spleen.Time-signal intensity curve(TIC) generated automatically.Signal intensity curve peak(Sip),the baseline signal intensity value (SI_0) and peak time(time to peak,TTP) were recorded and peak height of the TIC, the largest increase in the slope of the signal(maximum slope of increase,MSI) and signal the largest drop in the slope(maximum slope of decrease,MSD) were calculated.MSI was calculated as follows:MSI/MSD＝(SI_2-SI_1) / t,where“SI_2”and“SI_1”is the signal intensity at the point of biggest signal intensity changes in two adjacent phase on an increase or decrease section of TIC,and“t”is the interval time of two adjacent phase.The 1 to 3 phases were defined as the hepatic artery phase,and 4～6 phase were defined as the portal vein-phase.
5.Statistical Analysis
Statistical software(SPSS,version 11.5) was used for all statistical computations. For all tests used,A p value＜0.05 was considered statistically significant.
The Spearman rank correlation test was used to assess the correlation between TIC parameters and stage of fibrosis and grade of inflammation.One-way ANOVA test was used to compare the difference of TIC parameters among fibrosis stage and inflammation grade and LSD method was used to perform multiple comparisons. Receiver operating characteristic(ROC) curve analyses were conducted to evaluate the utility of the TIC parameters for the prediction of fibrosis stage≥1,≥2,and≥3, and for the prediction of inflammation grade≥2.
Results
1.There was moderate but significant negative correlation between the peak height of portal vein,liver,spleen and fibrosis stage(P＜0.01).There was significant positive correlation between the peak time and fibrosis stage(P＜0.01).There was significant negative correlation between portal MSI,hepatic arterial phase,MSI, hepatic portal venous phase MSI,liver MSD,spleen MSI,spleen MSD and fibrosis stage(P＜0.01).However,There was no significant correlation between TIC parameters and the degree of stage of inflammation,only spleen peak height has a negative correlation with it(P＜0.01).
2.There was a significant difference among patients who have different degrees of liver fibrosis((P＜0.05)) in peak height,TTP and MSI of portal vein.There was a significant difference among patients who have different degrees of liver fibrosis in TIC Parameters of liver and spleen(P＜0.05).
3.Receiver operating characteristic analysis showed that the relative good estimated parameters used to predict S≥1 were liver MSI of Portal venous phase,spleen MSI of Arterial phase,spleen MSD(area under the receiver operating characteristic curve,0.747,0.738,0.783,respectively).For prediction of stage lor greater fibrosis with MSD of spleen,we found an AUC of 0.783 with a sensitivity of 81.8%,specificity of 77.8%(MSD≤11.475).All TIC parameters were significante when to diagnosis S≥3(P＜0.05).The estimated paramerers were as follows:liver MSI of arterial phase,the portal vein MSI,liver MSI of portal venous phase,liver MSD,splenic MSI of arterial phase,splenic MSD with area under the curve 0.728～0.877.For prediction of stage 3or greater fibrosis with MSD of spleen,we found an AUC of 0.877 with a sensitivity of 96.7%,specificity of 83.3%(MSD≤11.475).
Conclusion
1.There was moderate correlation between TIC parameters and stage of liver fibrosis.TIC paramerers can be used to predict advanced liver fibrosis stage.
2.The significant indicators of TIC was spleen MSD,splenic MSI,liver MSD, MSI of hepatic portal venous phase and portal vein MSI followed by AUC descending.It is necessary to observe the hemodynamics of the spleen.
3.Multiphase dynamic contrast-enhanced MRI with coverage of the entire liver could be used to evaluate the hemodynamic changes in liver,while satisfying the need of morphological observation,and it would be regarded as a practical non-invasive functional imaging method in evaluating hepatic fibrosis.
Part Three Magnetization transfer,T2 Mapping Technology in the Diagnosis of Liver Fibrosis
Objective
To evaluate the relevance between MTR values,T2 values and stage of liver fibrosis,grade of inflammatory and to explore the value of MTI and T2mapping technology to predict liver fibrosis.
Materials and Methods
1.Subjects
A total of 65 cases in which the subjects had done MTI and were incorporated into the analysis eventually.They were divided into 6 groups according to the degree of fibrosis:S0(n＝13),S1(n＝8),S2(n＝15),S3(n＝7),S4(n＝3),liver cirrhosis (n＝19);and were divided into 4 groups by degree of inflammation:normal group (G0 period of 13 cases),mild inflammation group(1 case G1,G2 of 11),moderate inflammation group(G3 of 16 cases),severe inflammation(G4 of 4 cases).
A total of 55 cases in which the subjects had done T2mapping imaging were incorporated into the analysis eventually and divided into 6 groups according to the stage of fibrosis:S0(n＝10),S1(n＝7),S2(n＝16),S3(n＝5),S4(n＝3),cirrhosis (n＝14).They were divided into 4 groups according to the grade of inflammation: normal group(G0 period of 10 cases),mild inflammation group(1 case G1,G2 of 11), moderate inflammation group(G3 period of 16 cases),severe inflammation(G4 of 3 cases).
2.Apparatus and Equipment
The same with the Part One.
3.Methods and Parameters
The patients and controlled subjects were asked to fast for 4 hours before the study.MTI was performed using SPGR sequence shaped MT saturation pulse.The parameters of SPGR were as follows:TR/TE:76ms/4ms,flip angle:15 degrees,slice thickness:6mm and layer spacing 2mm,matrix 192×192,FOV38×38cm,the receiver bandwidth was 31.3KHz.MT pulse was performed with offset frequency 1200Hz,the effective flip angle 670°and pulse duration 8s.The scanning of the bottom two layers of hilar level position is conducted with the subjects holding breath after expiration.The whole scanning process takes 17s.
Inversion recovery fast spin-echo techniques and respiratory triggering technique were used to conduct T2mapping image.T2mapping were acquired using a preparatory time of 35.4 msec followed by an echo train length(ETL) of 8(22.6,33.9,45.2,56.6,67.9,79.2,90.5,101.8ms).FOV:40×40cm,receiver bandwidth: 15.63KHz,slice thickness of 8mm,layer spacing of 2mm,20 slices were acquired using one acquire.Scan time was 7 minutes and 8 seconds.
4.Post-Processing & Analysis of Images
MTI imaging data were analyzed by the magnetization transfer analysis software package.ROI was placed in the right posterior lobe of liver with large blood vessels and edge of organs excluded.MTR value was calculated as(pulse sequence imposed -is not imposed pulse sequences)/pulse sequence imposed.MTR value was obtained automatically by using the software.
T2 color map would be obtained by using T2map analysis software within the Functool package tool package.Each pixel value level in the color map represented T2 relaxation values(RV) respectively.The ROIs(area＝1.8mm2) were chosen in the right posterior lobe of the liver of continual 5layers and the average of all ROIs was calculated.
5.Statistical Analysis
Statistical software(SPSS,version 11.5) was used for all statistical computations. For all tests used,A p value＜0.05 was considered statistically significant.
Spearman correlation analysis was used to study the correlation between liver magnetization transfer ratio(MTR),T2 values and the stage of liver fibrosis,grade of inflammation.Receiver operating characteristic(ROC) curve analyses were conducted to evaluate the utility of the MTR value for the prediction of fibrosis stage≥1,≥2,and≥3.
Results
1.There was mild but significant positive correlation between MTR value and the stage of liver fibrosis,the grade of inflammation(P＜0.05,r＝0.343,0.347). Receiver operating characteristic analysis showed that the MTR value could be used to diagnosis liver fibrosis but had poor accuracy.The AUC were 0.692,0.683,0.667 respectively when MTR value was used to predict S≥1,S≥2 and S≥3.However, MTR value was not a statistical significance parameter in predicting the grade of inflammation(P＞0.05).
2.There was no significant correlation between T2 relaxation value and the stage of liver fibrosis,the grade of inflammation(P＞0.05)
Conclusion
1.There is a positive correlation between MTR value and the stage of hepatic fibrosis and grade of inflammation.MTR values can be used to predict the stage of hepatic fibrosis,but the diagnostic accuracy is not high.
2.T2mapping with respiratory triggering technique can be used to obtain the T2 relaxation value of the entire liver.But There was no significant correlation between T2 relaxation value and the stage of liver fibrosis,the grade of inflammation.
PartⅣComparison of Diagnosis Effects on Liver Fibrosis Between DWI and Enhanced Dynamic MRI
Objective
To compare the effectiveness of DWI and enhanced dynamic MRI in evaluating liver fibrosis.
Materials and Methods
A total of 23 patients(S0 8 cases,S1 1 cases,S2 3 cases,S3 1 cases,S4 2 cases, liver cirrhosis 8 cases) who underwent DWI and enhanced dynamic MRI imaging at the same time.ROC curve was used to compare the effect of TIC parameters and ADC value in diagnosing the stage of liver fibrosis.
Results
Using ROC analysis,we found the TIC parameter was not a significant predictor of stage 1 or greater fibrosis,however,hepatic ADC worked as a good predictor with larger AUC(0.925).TIC parameter and ADC values were both significant predictors of stage 3 or greater fibrosis,however,ADC values were still having largest area under the curve of more than 0.9.The AUC of TIC parameters were 0.765～0.871.
Conclusion
DWI method is simple without using contrast agent and its diagnosis effect is higher than TIC parameters of enhanced dynamic MRI -- especially in the diagnosis of mild liver fibrosis.However,each method has its own privilege,so the application should be based on the clinical work and the actual need of patients.
肝纤维化是肝脏对各种原因所致肝损伤的创伤修复反应,表现为肝内纤维结缔组织增生与沉积。引起肝纤维化的病因很多,在我国,病毒性肝炎是其主要病因。研究发现,肝纤维化经有效治疗是可以逆转的,但若病因持续存在,最终必然发展成为不可逆的肝硬化。因此,在肝硬化之前能早期诊断并及时干预,对于减缓肝纤维化的进程至关重要。慢性肝炎发展至肝硬化,经历疾病的不同阶段,而不同阶段决定了临床不同的处理方法。所以,基于临床治疗干预及预后随访的需要,有必要对慢性肝炎病人肝纤维化程度及炎症活动度进行评估。
目前评估肝纤维化病变程度的金标准是肝脏穿刺活检的组织病理学检查,但其缺点是有创且存在取样误差,因此,临床迫切需要一种非侵袭性、可定量评价肝纤维化、准确性较高的诊断方法。MRI因为无创、无辐射、软组织分辨率高,尤其是MR功能成像技术的发展,为肝纤维化的无创诊断研究提供了契机。国内外一些学者使用不同的功能成像方法对肝纤维化及肝硬化进行研究,取得了初步成果,但相关结论还存在争议。另外,关于哪一种成像方法更敏感、更准确、更实用,尚无这方面的报导。基于以上现状,借助3.0T磁共振这样一个先进工具,本研究拟采用弥散加权成像(diffusion weight imaging,DWI)、动态增强(dynamic contrast-enhanced,DCE)、磁化传递成像(magnitization transferimaging,MTI)及T2mapping等功能成像方法对肝纤维化程度进行评估,以筛选出诊断准确性较高、实用性较强的成像方法,为肝纤维化的临床治疗及随访监测提供有益的参考。
第一部分弥散加权成像参数优化及评价肝纤维化的临床应用研究
研究目的
优化3T MR肝脏DWI成像的技术参数,分析ADC值与肝纤维化程度和炎症活动度的相关性,并探讨其诊断肝脏纤维化程度及炎症活动度的效力。
材料与方法
1.研究对象
纳入本研究分析共64例,按肝纤维化分期分6组:S0(14例)、S1(9例)、S2(14例)、S3(7例)、S4(3例)、肝硬化(17例);按炎症分级共47例分5组:G0(14例)、G1(2例)、G2(11例)、G3(16例)、G4(4例)。
2.仪器及设备
采用GE Signa Excite 3.0T超导型核磁共振扫描仪,8通道相控阵腹部表面线圈。GEADW4.3图形工作站。
3.检查方法及参数
所有被检查者需空腹4h以上,均采用深吸气吐气后屏息扫描。DWI扫描采用单次激发EPI序列联合ASSET技术,ASSET因子为2.0Ph。DWI成像前先行ASSET校准扫描,扫描范围自胸部中段至下腹。DWI弥散梯度因子(b)值分别取300、600、800、1000s/mm~2。TR/TE:1500/46.7～59.2,NEX＝4,层厚8mm,层间距2mm,矩阵128×128,FOV 38×38cm。
其中18例检查者行DWI成像时,保持其他成像参数不变,扩散方向数分别选取S/I(弥散梯度施加在z轴方向)和ALL(弥散梯度施加在x、y、z三个正交方向)模式。其余检查者行DWI成像时,扩散方向数均为ALL,其他成像参数不变。
4.图像后处理及分析
使用GE ADW4.3工作站Functool软件包的弥散分析软件进行图像后处理及测量。
从肝脏DWI图像形态学观察、SNR及相应ADC值三个方面比较两种弥散梯度方向施加模式下所得图像的差别。用5个指标对DWI图像质量进行形态学评价,即肝内管道边界是否清晰、有无磁敏感伪影、肝实质信号是否均匀细腻、肝左叶是否较好显示、背景噪声多少,并将其分优、良、差三个等级赋予2、1、0三个分值。DWI图像SNR,采用公式SNR＝SI_(liver)/SD_(noise)计算,在DWI图像肝右叶后段放置ROI,面积约为1.6cm~2,获取信号强度值(SI_(liver)),同时在图像左外侧背景噪声上放置ROI,获取噪声信号强度的标准差(SD_(noise))。对于两种梯度方向模式所得图像SNR的比较,要保证两种模式下ROI放置位置一致。
肝脏ADC值测量选取肝门及其上下共三个层面,每个层面肝右后叶选取3个ROI,取9个ROI所测得ADC值的平均值。ROI的放置应注意避开肝内大的血管和胆道。
评价ADC值测量的可重复性。对正常组中13名检查者的DWI成像原始数据,进行两次后处理,计算平均ADC值,比较两次测量的ADC值差别。
5.统计学分析
采用SPSS 11.5统计软件包,各测量参数用均数±标准差表示,P＜0.05认为有统计学意义。
运用配对秩和检验比较两种弥散梯度方向施加模式所得DWI图像质量的评分,用配对t检验比较两种梯度方向施加模式DWI图像的信噪比(SNR)及肝脏ADC值的差别。用Spearman相关分析法探讨DWI图像信号强度、信噪比及ADC值与b值的关系。同一原始数据两次后处理所得ADC值差别,亦采用配对t检验。
运用Spearman相关分析法探讨肝脏ADC值和肝纤维化程度、肝炎活动度之间的相关性。运用单因素方差分析法(One-way ANOVA)比较各b值条件下ADC值在不同程度肝纤维化、肝炎活动度的差异,并用LSD法进行多重比较。运用受试者工作曲线(ROC曲线)评价ADC值诊断S≥1、S≥2、S≥3、肝硬化及G≥2、G≥3的效能。
结果
1.DWI方法学
DWI成像时弥散梯度方向选取ALL模式所获DWI图像的图像质量在各b值条件下均明显优于S/I模式(P＜0.05);前者的图像SNR较后者略高,在b取300、800s/mm2时差异显著(P＜0.05);相应的ADC值也同样是前者高于后者,在b＝600和800 s/mm2时差异有统计学意义(P＜0.05)。
b值与DWI图像信号强度、信噪比及ADC值均呈显著负相关关系(P＜0.001,r为-0.811～-0.882),DWI图像信噪比、信号强度与ADC值存在显著相关关系(P＜0.001,r为0.811～0.817)。
依据ROI的选取标准,对同一DWI原始数据进行两次ADC值测量,测量结果差别无统计学意义(P＞0.05)。
2.ADC值与肝纤维化程度的相关性及其评估肝纤维化程度的效力
各b值条件下,ADC值与肝纤维化程度均存在显著负相关关系(P＜0.001),尤其在b＝600 s/mm~2和800 s/mm~2时相关关系较为密切(r＞0.5)。4个b值条件下ADC值在不同程度肝纤维化组间的差别均有统计学意义(P＜0.01)。多重比较,在b＝300 s/mm~2时,正常组与S2、S3、肝硬化组及S1组与肝硬化组间差异有统计学意义(P＜0.05);b＝600 s/mm~2、800 s/mm~2时,正常组除与S1组差异不显著外,与其他各组间差异均有统计学意义(P＜0.01),S1与S3组、S1与肝硬化组、S2与肝硬化组差异亦均有统计学意义(P＜0.05);b＝1000 s/mm~2时,正常组与S3、肝硬化组差异显著(P＜0.05),S1与S3、S1与肝硬化组、S2与肝硬化组间差异均有统计学意义(P＜0.05)。
ROC曲线分析显示,b取300、600、800、1000s/mm~2时,ADC值诊断S≥1的曲线下面积分别为0.733、0.844、0.793、0.694;诊断S≥2的曲线下面积分别为0.748、0.835、0.820、0.775:诊断S≥3的曲线下面积分别为0.748、0.855、0.840、0.791;诊断肝硬化的曲线下面积为0.748、0.824、0.812、0.761,各b值下曲线下面积的95%置信区间有交叉。诊断不同纤维化程度时均为b＝600s/mm~2时曲线下面积最大,其次为b＝800s/mm~2时。b取600s/mm~2时,以ADC值≤1.453×10~(-3)mm2/s为标准,诊断S≥1的灵敏度为75%,特异度为73.9%;取1.453×10~(-3)mm~2/s为诊断界值,ADC诊断S≥2的灵敏度为80.5%,特异度为73.9%;以ADC值≤1.414×10~(-3)mm~2/s为标准,诊断S≥3的灵敏度为81.5%,特异度为73%;以ADC值≤1.339×10~(-3)mm~2/s为标准,诊断肝硬化的准确性为82.4%,灵敏度70.6%,特异度87.2%。
3.ADC值与肝炎活动度的相关性及其评价肝炎活动度的效力
ADC值与肝炎活动度呈显著负相关关系(P＜0.05),同样在b＝600 s/mm~2和800 s/mm~2时相关关系较为密切(r＞0.5)。在b取600、800 s/mm~2时ADC值在不同程度炎症分级间的差异有统计学意义(P＜0.05)。进一步多重比较,b＝600s/mm~2时,正常组和轻、中、重度炎症组间比较均有统计学意义(P＜0.05),轻度炎症与重度炎症组间差异亦显著(P＜0.05)。b＝800 s/mm~2时,正常组和中度、重度炎症组间差异显著(P＜0.01),轻度与重度炎症组间差异有统计学意义(P＜0.01)。ROC曲线分析结果显示,各b值条件下,ADC值预测G≥2、G≥3均有统计学意义(P＜0.05),并且前者的AUC均略小于后者。4个b值下,ADC诊断G≥2的AUC分别为0.712、0.783、0.772、0.704,诊断G≥3的AUC分别为0.701、0.786、0.782、0.704。当b取600 s/mm~2时,以ADC值≤1.453×10~(-3)mm~2/s为标准,诊断G≥2的灵敏度为75%,特异度为73.9%;以ADC值≤1.433×10~(-3)mm~2/s为标准,诊断G≥3的灵敏度为71.4%,特异度为73.1%。
结论
1.在进行肝脏DWI成像时,采用同时3个正交方向施加弥散敏感梯度较为稳妥,可以获得较好的DWI成像质量及较为准确的ADC值。
2.肝脏ADC值与肝纤维化程度及肝炎活动度均呈显著负相关关系,ADC值是较有意义的评价指标。ADC值诊断不同程度纤维化时均具有一定的准确性,评价中度以上程度纤维化的准确性相对较高。
3.4个b值条件下,ADC值评价肝纤维化程度及肝炎活动度的效能无统计学差别,但b＝600 s/mm~2时,诊断准确性最高,同时又可获得较好的DWI成像质量,是肝脏DWI成像的最佳b值。
4.DWI成像无创,技术操作简单,ADC值测量可重复性较好,可以为临床肝炎、肝纤维化的早期诊断和治疗随访提供一定的参考指标。
第二部分MRI全肝动态增强扫描评价肝纤维化的临床应用研究
研究目的
利用LAVA技术设计多时相全肝动态增强扫描程序,探讨肝纤维化、肝硬化的血流动力学变化特点,评价动态增强扫描在诊断肝纤维化程度的价值。
材料与方法
1.研究对象
纳入本研究分析共31例,按纤维化程度分4组:正常组(S0期9例)、轻度纤维化组(S1期1例、S2期2例)、中重度纤维化组(S3期1例、S4期3例)、肝硬化组15例。
2.仪器设备与药品
磁共振扫描仪、表面线圈及图形工作站同前。使用全自动双筒压力注射器及顺磁性对比剂Gd-DTPA。
3.检查方法及参数
动态增强扫描采用LAVA序列联合ASSET技术,ASSET因子取2.5Ph,TR/TE为2.8ms/1.2ms,带宽125KHz,重建层厚为2.7mm,8s完成一次72层全肝容积扫描。高压注射器经肘静脉团注0.2mmol/kg的Gd-DTPA,注射速率为4ml/s,随即以4 ml/s的速率注射21ml生理盐水冲管。注射对比剂的同时开始扫描,共扫描4期,每期连续3个时相,每个时相扫描时间8s,总扫描时间约160s。均采用屏息下扫描,每期扫描结束后嘱病人自由呼吸,3次间歇时间依次为5s、15s、30s,每期扫描屏息口令耗时约5s。
4.图像后处理及分析
原始数据使用Functool软件包SER软件进行处理,分别在腹主动脉、门静脉、肝脏实质、脾脏选取ROI,自动生成时间信号曲线(time signal intensity curve,TIC)。记录各ROI的TIC的信号强度峰值(SI_p)、基线信号强度值(SI_0)、达峰时间(time to peak,TTP),并计算各TIC的峰高、信号上升最大斜率(maximumslope of increase,MSI)和信号下降最大斜率(maximum slope of decrease,MSD),计算公式为:MSI/MSD＝(SI_2-SI_1)/t,SI_2和SI_1分别指曲线上升段或下降段信号强度变化最大的两个相邻扫描时相的信号强度,t为两个相邻时相的时间差。我们把扫描的1～3个时相归为动脉期、4～6个时相归为门静脉期,分别计算两期肝MSI及动脉期脾MSI。
5.统计学分析
统计学分析采用SPSS 11.5软件包,P＜0.05认为有统计学意义。
运用Spearman相关分析法评价TIC量化参数与肝纤维化程度的相关性;运用单向方差分析法比较各参数在不同程度纤维化组的差别;运用ROC曲线分析TIC参数诊断肝纤维化程度的效力。
结果
1.门静脉、肝脏、脾脏的峰高与纤维化程度呈显著负相关关系(P＜0.01),达峰时间与纤维化程度呈显著正相关关系(P＜0.01),门脉MSI、动脉期肝MSI、门脉期肝MSI、肝MSD、脾MSI、脾MSD均与纤维化程度呈显著负相关关系(P＜0.01)。
2.门静脉TIC的峰高、达峰时间及MSI在不同程度纤维化组间的差异有统计学意义(P＜0.05)。肝脏TIC的达峰时间、峰高、动脉期MSI、门静脉期MSI及MSD在各组间差异均显著(P＜0.05)。脾脏TIC的峰高、达峰时间、动脉期MSI及MSD在不同程度纤维化组间差异亦均显著(P＜0.01)。
3.ROC曲线分析结果显示,诊断S≥1时,TIC参数中有诊断意义的指标为门静脉期肝MSI、动脉期脾MSI、脾MSD,曲线下面积依次为0.747、0.738、0.783;诊断S≥3时,所有的速率指标均有诊断意义(P＜0.05),曲线下面积为0.728-0.877,由小到大依次为动脉期肝MSI、门静脉MSI、门静脉期肝MSI、肝MSD、动脉期脾MSI、脾MSD;诊断肝硬化时,所有的斜率指标均有诊断意义(P＜0.05),曲线下面积为0.742～0.821(表2.10,图2-9),AUC由小到大对应的参数依次为门静脉期肝MSI、肝MSD、动脉期肝MSI、门静脉MSI、动脉期脾MSI、脾MSD,其中脾MSD及动脉期脾MSI曲线下面积最大。
结论
1.动态增强TIC参数与肝纤维化程度有中等程度的相关关系,TIC量化参数在一定程度上可以判断肝纤维化的病变程度,但对判断有无纤维化(S≥1)的作用有限,对中度以上(S≥3)纤维化和肝硬化的诊断准确性较高。
2.诊断不同程度肝纤维化,脾脏的TIC参数都表现出较高的诊断准确性,说明对脾脏血流动力学的观察是有必要的。多个TIC指标联合分析,有助于对病变程度的判断。
3.建立了基于LAVA技术的全肝动态增强成像的一站式检查方法,即单次检查可同时评价病变的形态学、血流动力学变化,不失为一种实用的无创评价肝纤维化的功能成像方法。
第三部分磁化传递、T2mapping技术评价肝纤维化的临床应用研究
研究目的
采用MTI及T2mapping技术,评价MTR值、T2值与肝纤维化程度及炎症活动度的相关性,探讨其评价肝纤维化的价值。
材料与方法
1.研究对象
行MTI并最终纳入分析的共65例,按纤维化分期分6组:S0(n＝13)、S1(n＝8)、S2(n＝15)、S3(n＝7)、S4(n＝3)、肝硬化(n＝19);按炎症分级分4组:正常组(G0期13例)、轻度炎症组(G1期1例、G2期11例)、中度炎症组(G3期17例)、重度炎症组(G4期4例)。
行T2mapping并最终纳入分析的共55例,按纤维化分期分6组:S0(n＝10)、S1(n＝7)、S2(n＝16)、S3(n＝5)、S4(n＝3)、肝硬化(n＝14);按炎症分级分4组:正常组(G0期10例)、轻度炎症组(G1期1例、G2期11例)、中度炎症组(G3期16例)、重度炎症组(G4期3例)。
2.仪器与设备
同第一部分。
3.检查方法及参数
所有检查者需空腹4h以上。
MTI采用SPGR序列,分别在施加磁化传递脉冲前后进行扫描,TR/TE为76ms/4ms,翻转角15度,层厚6mm,层间隔2mm,矩阵192×192,FOV为38×38cm,采样带宽31.3KHz。MT脉冲偏移频率为1200Hz,有效翻转角670度,脉冲持续时间8s。采用深吸气吐气后屏息扫描,扫描层面定位于肝门水平,扫描两层,扫描时间17s。
T2map采用反转恢复快速自旋回波技术,同时采用呼吸触发。8个回波,TE分别为22.6ms、33.9ms、45.2 ms、56.6 ms、67.9 ms、79.2 ms、90.5 ms、101.8 ms,TR为3750ms,NEX为1,FOV为40×40cm,采样带宽15.63KHz,层厚8mm,层间隔2mm,最大层数为20层,进行全肝成像,扫描时间7分8秒。
4.图像后处理及分析
MTI原始数据使用Functool软件包内的磁化传递分析软件进行处理,给出MTR值计算方式,自动生成MTR伪彩图。MTR值计算方式为“(施加脉冲序列—未施加脉冲序列)/施加脉冲序列”。分别于两个层面上肝右叶后段放置3个圆形ROI获取相应的MTR值,取其平均值。ROI的放置需注意避开大血管及器官边缘。
T2mapping原始数据使用Functool软件包的T2mapping分析软件,可直接得到T2值伪彩图,图中每个像素值的高低代表组织T2值。取连续5个层面肝右叶后段放置圆形ROI,每层放置3个,直径1.8mm~2,取平均值。ROI放置应注意避开大血管。
5.统计学分析
采用SPSS 11.5软件包进行统计学分析,P＜0.05认为差异有统计学意义。
运用Spearman相关分析法探讨肝脏MTR值、T2值与肝纤维化程度及炎症活动度的相关性。运用ROC曲线分析MTR值用于诊断肝纤维化程度的效能。
结果
1.MTR值与纤维化程度及炎症活动度之间有显著正相关关系(P＜0.05),但相关关系并不密切,相关系数r分别为0.343、0.347。ROC曲线分析结果表明,MTR值用于判断肝纤维化程度有意义(P＜0.05),但准确性不高,诊断S≥1、S≥2、S≥3及肝硬化的曲线下面积分别为0.692、0.683、0.667、0.669。MTR值用于判断肝炎活动度无统计学意义(P＞0.05)。
2.T2值与肝纤维化程度及炎症活动度之间无显著相关关系(P＞0.05)。
结论
1.MTR值与肝纤维化程度及炎症活动度有轻度正相关关系,MTR值可以用于评价肝纤维化程度,但诊断准确性不高。
2.T2值与肝纤维化程度及炎症活动度无明显相关关系,在定量评价纤维化方面价值不大。
第四部分DWI与动态增强成像评价肝纤维化的优势比较
研究目的
比较肝脏DWI成像与动态增强成像诊断肝纤维化程度的效能。
材料与方法
仪器与药品、检查方法及图像分析方法均同第一、二部分。
对同时行DWI和动态增强成像的共23例(S0期8例,S1期1例,S2期3例,S3期1例,S4期2例,肝硬化8例)进行分析。用ROC曲线比较ADC值与TIC斜率指标在诊断S≥1、S≥3及肝硬化的效能。
结果
ROC曲线分析结果显示,在诊断S≥1时,ADC值作为诊断指标有统计学意义(P＜0.01),AUC为0.925,而TIC斜率指标无统计学意义(P＞0.05);在诊断S≥3时TIC斜率指标及ADC值均有诊断意义(P＜0.05),ADC值曲线下面积为0.932,TIC参数曲线下面积为0.803～0.871;诊断肝硬化时,两指标亦均有诊断意义(P＜0.05),ADC值的AUC为0.933,TIC参数曲线下面积为0.770～0.816。ADC值作为诊断指标的曲线下面积较大,但两种方法曲线下面积95%可信区间有交叉。
结论
1.在诊断有无肝纤维化时,动态增强TIC斜率参数不是较有意义的诊断指标,而ADC值有相对较高的准确性;在诊断中度以上纤维化时,两种方法诊断效力相当,但ADC值的诊断准确性较高。
2.从临床应用角度来看,两种诊断方法各有优势,需结合病情需要和病人意愿灵活选择。
Background
Liver fibrosis is the wound-healing response to various liver damage,in the form of a progressive accumulation of fibrosis.It alters the tissue structure and function of liver,leading to cirrhosis and liver failure.Many causes can induce hepatic fibrosis.In our country,however,chronic viral infection is the main cause.It is reported in some researches that liver fibrosis can be reversed through effective treatment;but if the cause stays on,it would develop into liver cirrhosis.So,early detection of liver fibrosis and cirrhosis has important clinical implications for the determination of antiviral treatment options and patient prognosis.Chronic liver diseases progress through different histological stages to final cirrhosis,and histological stages serve as a key predictor in the clinical management of patients with chronic hepatitis.Thus,the diagnosis of the stage of liver fibrosis and the grade of inflammation in patients with chronic hepatitis is essential for therapeutic and prognostic evaluation.
The gold standard in assessing fibrosis is still represented by liver biopsy, despite the invasiveness of the procedure and the likelihood of sampling errors. Therefore it is an urgent need to search for a noninvasive diagnosis method to quantify liver fibrosis.MRI has become an increasingly important imaging modality for the investigation of patients with chronic liver disease.Some functional imaging methods have been investigated for this purpose,but their clinical role remains undefined.To our knowledge,however,the comparison among these methods in the diagnosis of liver fibrosis has not been reported.Thus,the purpose of our study is to prospectively evaluate the sensitivity and specificity of various functional imaging methods by using 3.0 T MR in the diagnosis of liver fibrosis(such as DWI,Dynamic contrast-enhanced MRI,MTI and T2mapping),in order to choose reasonably in clinical work.
Part One:Clinical Study of Diffusion-weighted MR Imaging in Evaluating Liver Fibrosis
Objective
The purpose of this study is to optimize the technical parameters of diffusion-weighted MRI in liver with 3T MR scanner and to evaluate its ability for evaluating of liver fibrosis quantificativly.
Materials and Methods
1.Subjects
A total of 64 cases were incorporated into this study and were divided into 6 groups according to the stage of liver fibrosis:S0(14 cases),S1(9 cases),S2(14 cases),S3(7 cases),S4(3 cases),liver cirrhosis(17 cases).A total of 46 cases were divided into 5 groups according to the grade of inflammation:G0(14 cases),G1(2 cases),G2(11 cases),G3(16 cases),G4(4 cases).
2.Instruments and equipment
DWI of the liver was performed on a GE Signa Excite 3.0-T superconductive MRI scanners with an eight-element phased-array superficial coil.
3.Examination methods and parameters
The patients and control subjects were asked to fast for 4 hours before the study. Breathhold diffusion-weighted imaging of the liver was performed,using single shot echo-planar imaging sequences in conjunction with parallel imaging with an acceleration factor of 2.0Ph.ASSET correction scan was performed before DWI imaging with scan range from the middle chest to the lower abdomen.Four breath-hold acquisitions were obtained in the same liver location at b values of 0-300,0-600,0-800 and 0-1000s/mm~2.The following parameters were used: TR/TE＝1500/46.7～59.2ms,NEX＝4,slice thickness＝8mm;gap＝2mm;matrix＝128×128,field of view＝38×38cm.
First of all,18 healthy volunteers were imaged twice under each b value with diffusion gradient applied along the section-select direction(S/I) and in three orthogonal directions(All).The rest of examinees were imaged with“ALL”model with other imaging parameters invariably.
4.Data processing and data analysis
Diffusion analysis software package on a workstation(GE ADW4.3) was used to obtain ADC maps for each b value.The quality of DWI images obtained from two patterns of diffusion gradient directions was evaluated by 5 indicatrixs as follows: Whether the intrahepatic pipe has a clear border;Whether the magnetic artifacts were sensitive,Whether the signal of liver parenchyma is homogeneous and fine,whether the left lobe of liver shows better,and how much the background noise is.Three scores(2,1,0) were given,representing respectively three levels as excellent,good, bad.Signal intensity(SI) was measured on the images recorded in a homogeneous circular(area,1.3cm2) at the right posterior lobe of the liver and the noise of background.Signal to noise ratios(SNR) of liver on DWI were calculated:SNR＝SI/SDnoise,in which SDnoise is the standard deviation of the background noise. During the process,great care needed to be taken to ensure the consistency of ROI placement at different diffusion gradient directions.ROIs were placed in areas that were as similar as possible to the areas assessed in two patterns.
Quantitative ADC maps were derived automatically on a voxel-by-voxel basis by using software.Three regions of interest(ROIs) were placed in the posterior right hepatic lobe per slice(mean size＝1.3 cm) on three consecutive slices to measure liver ADC values.Care was taken to exclude vessels and bile duct.The final ADC per subject used for analysis was the average of nine measurements.
With method mentioned above,the ADC values were measured twice by examining the b value of the DWI images of 13 examinees.Differences were then compared.
5.Statistical analysis
SPSS 11.5 statistical software was used for analysis.All values were expressed as mean±standard deviation.For all tests used,A p value＜0.05 was considered statistically significant.
The paired Kruskal-Wallis test was used to compare the images' quality score obtained with two Pattern that diffusion gradient directions were applied.The paired T test was used to compare the difference of SNR and the ADC value of the two DWI images with two patterns.The Spearman correlation analysis was used to study the relevance between the b value and signal strength,signal to noise ratio and ADC value on DWI images.The paired T test compared the ADC values measured two times from the same patients.
The Spearman rank correlation test was used to assess the correlation between liver ADC and stage of fibrosis and grade of inflammation.One-way ANOVA test was used to compare the difference of ADC value among fibrosis stage and inflammation grade under the conditions of different b values,and LSD method was used to perform multiple comparisons.Receiver operating characteristic analysis was used to assess the performance of ADC in prediction of the presence of stage 1 or greater,stage 2 or greater,stage 3 or greater of liver fibrosis and grade 2 or greater, grade 3 or greater of inflammatory activity.
Result
1.DWI Methodology
DWI image quality obtained with diffusion gradient applied in three orthogonal direction was significantly better than that obtained with diffusion gradient applied along the section-select direction(P＜0.05) at each b values.The SNR of the image with“all”pattern tended to be higher than those with“S/I”pattern and the difference was significant(P＜0.05) at b＝300,800 s/mm2.ADC value tended to be higher than the S/I image and the difference was significant at b＝600,800 s/mm2(P＜0.05).
There was negative correlation between b value and signal strength,SNR and ADC values of DWI images(P＜0.01).
There were no significant differences between ADC values measured two times based on the ROI selection criteria(P＞0.05).
2.ADC Values and Fibrosis Stage
There was moderate but significant negative correlation between ADC and fibrosis stage.The best correlation was observed for the ADC at b values 600 and 800 s/mm~2(r＞0.5).
There was a decreasing trend in hepatic ADC with increasing degree of fibrosis. There were significant differences among different fibrosis stages at each b values(P＜0.01).In multiple comparisons,there were no significant difference between S0 and S1 for all b values and there were significant differences between stage 0 and stage 2-4(P＜0.05).In addition,there were significant differences between stage 1 and stage 3 fibrosis,stage 1 and cirrhosis for b value of 800～1000 s/mm~2,between stage 1 and stage 2 and cirrhosis for a b value of 600～800 s/mm~2.
Using ROC analysis,we found hepatic ADC to be a significant predictor of stage 1 or greater fibrosis with an AUC of 0.733,0.844,0.793,0.694 at b value of 300,600,800,1000s/mm~2.AUC were 0.748,0.835,0.820,0.775 when hepatic ADC was used to predict S≥2 and were 0.748,0.855,0.840,0.791 respectively when hepatic ADC was used to predict S≥3.The largest AUC was observed at b value of 600s/mm~2 and followed at b value of 800s/mm~2.At b value of 600s/mm~2,the diagnosis of S≥1 accuracy of ADC values was 84.4%.
When assuming ADC values＜1.453×10~(-3)mm~2/s as the standard,the sensitivity was 75%and specificity 73.9%;the diagnosis of S≥2 accuracy was 83.5%,When assuming ADC＜1.453×10~(-3)mm~2/s for the diagnosis of community value,the sensitivity was 80.5%and specificity 73.9%;predicted moderate and above fibrosis (S3 or grater) for the area under the curve was 0.855,when assuming ADC value≤1.414×10~(-3)mm~2/s as the standard,sensitivity was 81.5%,specificity was 73%.
3.ADC Values and Inflammation Grade
There was a decreasing trend in hepatic ADC with increasing degree of inflammation.The correlation between ADC and inflammation grade(P＜0.05) varied from weak to moderate.There were a significant difference at b values of 600,800 s/mm~2 among different degree inflammation(P＜0.05).Using ROC analysis,we found ADC to be a significant predictor of grade 2 or greater inflammation with an AUC of 0.783,0.832 respectively(b＝600,800 s/mm~2) and to be a significant predictor of grade 3 or greater inflammation with an AUC of 0.786,0.782 respectively.For prediction of great 2 or greater inflammation at b values of 600 s/mm~2,we found an AUC of 0.783 with a sensitivity of 75%,specificity of 73.9%for a hepatic ADC of 1.453×10~(-3)mm~2/s or less.For prediction of great 3 or greater inflammation at b values of 800 s/mm~2,we found an AUC of 0.783 with a sensitivity of 75%,specificity of 73.9%for a hepatic ADC of 1.433×10~(-3)mm~2/s or less.
Conclusions
1.When conducting liver DWI,the selection of diffusion-sensitive gradient direction has a certain impact on image quality and ADC value measured.In this study,diffusion-sensitive gradient were applied in three orthogonal directions,a better image quality and stability of the ADC value were obtained.
2.There was negative correlation between ADC and fibrosis stage,inflammation grade.ADC values have a certain contribution to the evaluation of the stage of hepatic fibrosis and inflammatory activity.The former presents a higher accuracy.
3.The diagnosis performance of ADC values in predicting the stage of liver fibrosis was at the b of 600 s/mm~2.
4.DWI imaging is a non-invasive technology and could be operated easily,and ADC value measurement has better reproducibility.DWI could provide a reference in early diagnosis,treatment and follow-ups for chronic patients.
Part Two Application Study of Dynamic Contrast-Enhanced MRI of Whole Liver in Evaluating Liver Fibrosis
Objective
To analyze the homodynamic changes of liver fibrosis by using enhanced dynamic MRI;to investigate the role of Dynamic Contrast-Enhanced MRI in evaluating liver fibrosis.
Materials and Methods
1.Subjects
Thirty-one consecutive patients were prospectively enrolled in this study.They are divided into 4 groups according to the stages of fibrosis:normal group(SO 9 cases),mild fibrosis group(S1 1 case,S2 2 cases),moderate to severe fibrosis group (S3 1 case,S4 3 cases),15 cases of liver cirrhosis group.
2.Equipment and contrast medium
Magnetic resonance scanner and the surface coil were the same as used in Part One.Gd-DTPA(Dimeglnmine Gadopentetate Injection,Kangchen,China) was injected as paramagnetic contrast medium with high pressure injection(Ulrich corp).
3.Examination Technique
Whole-liver enhanced dynamic MR imaging was performed by using a liver acceleration volume acqui-sition technique in Axial plane.Phase-accelerating factor was 2.5Ph.The following imaging parameters were used:2.8/1.2(repetition time msec/echo time msec),5.4-cm slice thickness resulting in an interpolated 2.7-mm section thickness,and 125 Hz bandwidth.The starting time of acquisition of dynamic contrast-enhanced images was synchronized with the start ofⅣbolus administration of 0.1 mmol/kg of gadopentetate dimeglumine followed by a 20ml saline flush injected at a rate of 4 ml/sec with an MR-compatible power injector.A total of four scanning were conducted,each including three phases,and each phase lasted 8s,the total scan time totaled approximately 160s.Patients were requested to hold their breath for 24s thrice.The first breath-holding was started simultaneously with administration of gadopentetate dimeglumine and the interval between breath-holding periods was 10,20,35sec,respectively.
4.Image Analysis
The images were transferred to GE ADW4.3 workstation and were analyzed using the SER software of Functool software package.Regions of interest(ROIs) were drawn manually on the main portal vein,the proximal abdominal aorta,right lobe areas of the liver and spleen.Time-signal intensity curve(TIC) generated automatically.Signal intensity curve peak(Sip),the baseline signal intensity value (SI_0) and peak time(time to peak,TTP) were recorded and peak height of the TIC, the largest increase in the slope of the signal(maximum slope of increase,MSI) and signal the largest drop in the slope(maximum slope of decrease,MSD) were calculated.MSI was calculated as follows:MSI/MSD＝(SI_2-SI_1) / t,where“SI_2”and“SI_1”is the signal intensity at the point of biggest signal intensity changes in two adjacent phase on an increase or decrease section of TIC,and“t”is the interval time of two adjacent phase.The 1 to 3 phases were defined as the hepatic artery phase,and 4～6 phase were defined as the portal vein-phase.
5.Statistical Analysis
Statistical software(SPSS,version 11.5) was used for all statistical computations. For all tests used,A p value＜0.05 was considered statistically significant.
The Spearman rank correlation test was used to assess the correlation between TIC parameters and stage of fibrosis and grade of inflammation.One-way ANOVA test was used to compare the difference of TIC parameters among fibrosis stage and inflammation grade and LSD method was used to perform multiple comparisons. Receiver operating characteristic(ROC) curve analyses were conducted to evaluate the utility of the TIC parameters for the prediction of fibrosis stage≥1,≥2,and≥3, and for the prediction of inflammation grade≥2.
Results
1.There was moderate but significant negative correlation between the peak height of portal vein,liver,spleen and fibrosis stage(P＜0.01).There was significant positive correlation between the peak time and fibrosis stage(P＜0.01).There was significant negative correlation between portal MSI,hepatic arterial phase,MSI, hepatic portal venous phase MSI,liver MSD,spleen MSI,spleen MSD and fibrosis stage(P＜0.01).However,There was no significant correlation between TIC parameters and the degree of stage of inflammation,only spleen peak height has a negative correlation with it(P＜0.01).
2.There was a significant difference among patients who have different degrees of liver fibrosis((P＜0.05)) in peak height,TTP and MSI of portal vein.There was a significant difference among patients who have different degrees of liver fibrosis in TIC Parameters of liver and spleen(P＜0.05).
3.Receiver operating characteristic analysis showed that the relative good estimated parameters used to predict S≥1 were liver MSI of Portal venous phase,spleen MSI of Arterial phase,spleen MSD(area under the receiver operating characteristic curve,0.747,0.738,0.783,respectively).For prediction of stage lor greater fibrosis with MSD of spleen,we found an AUC of 0.783 with a sensitivity of 81.8%,specificity of 77.8%(MSD≤11.475).All TIC parameters were significante when to diagnosis S≥3(P＜0.05).The estimated paramerers were as follows:liver MSI of arterial phase,the portal vein MSI,liver MSI of portal venous phase,liver MSD,splenic MSI of arterial phase,splenic MSD with area under the curve 0.728～0.877.For prediction of stage 3or greater fibrosis with MSD of spleen,we found an AUC of 0.877 with a sensitivity of 96.7%,specificity of 83.3%(MSD≤11.475).
Conclusion
1.There was moderate correlation between TIC parameters and stage of liver fibrosis.TIC paramerers can be used to predict advanced liver fibrosis stage.
2.The significant indicators of TIC was spleen MSD,splenic MSI,liver MSD, MSI of hepatic portal venous phase and portal vein MSI followed by AUC descending.It is necessary to observe the hemodynamics of the spleen.
3.Multiphase dynamic contrast-enhanced MRI with coverage of the entire liver could be used to evaluate the hemodynamic changes in liver,while satisfying the need of morphological observation,and it would be regarded as a practical non-invasive functional imaging method in evaluating hepatic fibrosis.
Part Three Magnetization transfer,T2 Mapping Technology in the Diagnosis of Liver Fibrosis
Objective
To evaluate the relevance between MTR values,T2 values and stage of liver fibrosis,grade of inflammatory and to explore the value of MTI and T2mapping technology to predict liver fibrosis.
Materials and Methods
1.Subjects
A total of 65 cases in which the subjects had done MTI and were incorporated into the analysis eventually.They were divided into 6 groups according to the degree of fibrosis:S0(n＝13),S1(n＝8),S2(n＝15),S3(n＝7),S4(n＝3),liver cirrhosis (n＝19);and were divided into 4 groups by degree of inflammation:normal group (G0 period of 13 cases),mild inflammation group(1 case G1,G2 of 11),moderate inflammation group(G3 of 16 cases),severe inflammation(G4 of 4 cases).
A total of 55 cases in which the subjects had done T2mapping imaging were incorporated into the analysis eventually and divided into 6 groups according to the stage of fibrosis:S0(n＝10),S1(n＝7),S2(n＝16),S3(n＝5),S4(n＝3),cirrhosis (n＝14).They were divided into 4 groups according to the grade of inflammation: normal group(G0 period of 10 cases),mild inflammation group(1 case G1,G2 of 11), moderate inflammation group(G3 period of 16 cases),severe inflammation(G4 of 3 cases).
2.Apparatus and Equipment
The same with the Part One.
3.Methods and Parameters
The patients and controlled subjects were asked to fast for 4 hours before the study.MTI was performed using SPGR sequence shaped MT saturation pulse.The parameters of SPGR were as follows:TR/TE:76ms/4ms,flip angle:15 degrees,slice thickness:6mm and layer spacing 2mm,matrix 192×192,FOV38×38cm,the receiver bandwidth was 31.3KHz.MT pulse was performed with offset frequency 1200Hz,the effective flip angle 670°and pulse duration 8s.The scanning of the bottom two layers of hilar level position is conducted with the subjects holding breath after expiration.The whole scanning process takes 17s.
Inversion recovery fast spin-echo techniques and respiratory triggering technique were used to conduct T2mapping image.T2mapping were acquired using a preparatory time of 35.4 msec followed by an echo train length(ETL) of 8(22.6,33.9,45.2,56.6,67.9,79.2,90.5,101.8ms).FOV:40×40cm,receiver bandwidth: 15.63KHz,slice thickness of 8mm,layer spacing of 2mm,20 slices were acquired using one acquire.Scan time was 7 minutes and 8 seconds.
4.Post-Processing & Analysis of Images
MTI imaging data were analyzed by the magnetization transfer analysis software package.ROI was placed in the right posterior lobe of liver with large blood vessels and edge of organs excluded.MTR value was calculated as(pulse sequence imposed -is not imposed pulse sequences)/pulse sequence imposed.MTR value was obtained automatically by using the software.
T2 color map would be obtained by using T2map analysis software within the Functool package tool package.Each pixel value level in the color map represented T2 relaxation values(RV) respectively.The ROIs(area＝1.8mm2) were chosen in the right posterior lobe of the liver of continual 5layers and the average of all ROIs was calculated.
5.Statistical Analysis
Statistical software(SPSS,version 11.5) was used for all statistical computations. For all tests used,A p value＜0.05 was considered statistically significant.
Spearman correlation analysis was used to study the correlation between liver magnetization transfer ratio(MTR),T2 values and the stage of liver fibrosis,grade of inflammation.Receiver operating characteristic(ROC) curve analyses were conducted to evaluate the utility of the MTR value for the prediction of fibrosis stage≥1,≥2,and≥3.
Results
1.There was mild but significant positive correlation between MTR value and the stage of liver fibrosis,the grade of inflammation(P＜0.05,r＝0.343,0.347). Receiver operating characteristic analysis showed that the MTR value could be used to diagnosis liver fibrosis but had poor accuracy.The AUC were 0.692,0.683,0.667 respectively when MTR value was used to predict S≥1,S≥2 and S≥3.However, MTR value was not a statistical significance parameter in predicting the grade of inflammation(P＞0.05).
2.There was no significant correlation between T2 relaxation value and the stage of liver fibrosis,the grade of inflammation(P＞0.05)
Conclusion
1.There is a positive correlation between MTR value and the stage of hepatic fibrosis and grade of inflammation.MTR values can be used to predict the stage of hepatic fibrosis,but the diagnostic accuracy is not high.
2.T2mapping with respiratory triggering technique can be used to obtain the T2 relaxation value of the entire liver.But There was no significant correlation between T2 relaxation value and the stage of liver fibrosis,the grade of inflammation.
PartⅣComparison of Diagnosis Effects on Liver Fibrosis Between DWI and Enhanced Dynamic MRI
Objective
To compare the effectiveness of DWI and enhanced dynamic MRI in evaluating liver fibrosis.
Materials and Methods
A total of 23 patients(S0 8 cases,S1 1 cases,S2 3 cases,S3 1 cases,S4 2 cases, liver cirrhosis 8 cases) who underwent DWI and enhanced dynamic MRI imaging at the same time.ROC curve was used to compare the effect of TIC parameters and ADC value in diagnosing the stage of liver fibrosis.
Results
Using ROC analysis,we found the TIC parameter was not a significant predictor of stage 1 or greater fibrosis,however,hepatic ADC worked as a good predictor with larger AUC(0.925).TIC parameter and ADC values were both significant predictors of stage 3 or greater fibrosis,however,ADC values were still having largest area under the curve of more than 0.9.The AUC of TIC parameters were 0.765～0.871.
Conclusion
DWI method is simple without using contrast agent and its diagnosis effect is higher than TIC parameters of enhanced dynamic MRI -- especially in the diagnosis of mild liver fibrosis.However,each method has its own privilege,so the application should be based on the clinical work and the actual need of patients.
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