综述
磁共振弹性成像在肝纤维化定量诊断与分期中的研究进展
磁共振成像, 2021,12(12) : 112-114,117. DOI: 10.12015/issn.1674-8034.2021.12.027
摘要

肝纤维化(liver fibrosis,LF)是指肝脏细胞外基质尤其是胶原纤维的异常积累,LF不加干预或干预不足可进展为肝硬化甚至肝癌。早期LF组织学上是可逆的。磁共振弹性成像(magnetic resonance elastography,MRE)是一种评估组织机械特性的稳健技术,也是目前评估LF最准确的无创影像学手段。肝脏MRE的目的是在形态学可见之前尽早观察到组织学变化,为临床尽早采取干预措施防止纤维化进一步发展提供依据。随着磁共振技术的不断进步,LF无创定量诊断及分期取得了较大进展。现就MRE在LF定量诊断与分期中的研究进展予以综述。

引用本文: 赵俊苹, 李红, 刘昊沅, 等.  磁共振弹性成像在肝纤维化定量诊断与分期中的研究进展 [J] . 磁共振成像, 2021, 12(12) : 112-114,117. DOI: 10.12015/issn.1674-8034.2021.12.027.
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肝纤维化(liver fibrosis,LF)是指肝脏细胞外基质尤其是胶原纤维的异常积累,LF不加干预可发展为肝硬化甚至肝癌。早期LF是可逆的,专家共识[1]认为Sun等[2]提出P-I-R分类可用于评估LF动态变化,在组织学上进一步明确了LF逆转的定义。磁共振弹性成像(magnetic resonance elastography,MRE)可无创评估组织机械特性,对早期LF做出有效诊断[3, 4],为临床尽早采取干预措施提供依据,减少肝硬化及肝癌的发生。现已有多个研究表明其诊断效能高于超声、CT、扩散加权成像及血清学等临床评分系统[5, 6, 7, 8, 9, 10, 11]

1 MRE在评价肝纤维化严重程度及其分期中的应用
1.1 LF分期

肝脏损伤常以纤维化的程度和肝硬化的形成来分期,用于评估疾病进展情况,影响治疗及预后。现国内外对LF进行分期的标准有很多,较常用的是Scheuer法即根据穿刺活检后的结果分为F0期(无纤维化)、F1期(汇管区扩大)、F2期(纤维间隔形成)、F3期(纤维间隔伴小叶)、F4期(可能或肯定肝硬化)。Scheuer法虽然认识到炎症对肝纤维化的严重性,但对分期的定义尚不明确。而Sun等[2]根据纤维间隔的所占比例不同,将LF分为进展型(progressive,P)、逆转型(regressive,R)和不确定型(indeterminate,I)三类,即P-I-R分类,此分类不仅在病理学上明确了LF分期,且指出了LF逆转的定义。

1.2 MRE弹性值与LF相关性的研究

LF所致的组织机械特性(应变、刚度和粘弹性等)改变可通过测量弹性图的肝脏硬度值(liver stiffness measurement,LSM)来显示人体组织硬度的差异,从而作为诊断LF程度的依据[12,13]

袁鸿鹏[14]、Jayakumar等[15]分别通过自己的研究表明MRE的肝脏硬化与纤维化显著相关。Ajmera[16]团队的一项前瞻性队列研究对102例经活检证实的肝硬化患者先后进行MRE和肝活检,然后重复配对肝活检和MRE评估。结果显示在未经调整的分析中,MRE肝硬度增加15%与组织学纤维化进展的概率增加呈正相关(OR 3.56;95% CI:1.17~10.76;P=0.0248)。即使在对年龄,性别和身体质量指数进行多变量调整后,这些发现仍具有临床和统计学意义(校正后OR 3.36;95%CI:1.10~10.31;P=0.0339)。此研究表明MRE肝硬度增加15%可反映肝纤维化组织学进程,且MRE肝硬度增加15%是进展为晚期纤维化的最强预测因子(OR 4.90;95% CI:1.35~17.84;P=0.0159)。然而,此研究虽然对肝组织学的纵向变化与MRE之间的关系进行了严格的评估,但通过对快速进展期的患者进行长期随访显示,其中60%可能被肝活检错误分类,导致不能反映真正的组织学进展。另一方面,由于进展超过一个纤维化阶段的患者数量有限,使得“剂量反应”不能得到充分说明。因此,更多跨纤维化分期的进展性病例研究是值得期待的。

1.3 MRE在LF分期中的应用

张显怡等[4]通过MRE对20名健康志愿者及57例肝活检证实为LF患者的肝脏弹性值进行分析,研究结果表明MRE对早期LF具有较高的诊断效能,其诊断LF F1~F4期的ROC曲线下面积(area under the curve,AUC)分别为0.92、0.94、0.95、0.99。Xiao等[17]的一项荟萃分析表明MRE和实时剪切波弹性成像对LF分期的诊断准确率最高,一项对100多名患者进行的前瞻性横断面研究[18]也显示MRE在识别LF (第1期或更多期)方面比瞬时弹性成像更准确。与Lefebvre等[19]的研究结果一致。

张凯等[20]选取40例LF病例,先行MRE检查,后经肝脏穿刺病理活检确诊。其中MRE漏诊2例,2例均经活检证实为F1期,误诊1例F2期为F1期,漏诊率5.00%、误诊率2.50%,F3、F4期检查结果与活检结果一致。在Loomba等[21]的研究中也有12名患者被错误分类,其中9名活检显示为F0~F2期纤维化的患者被归类为晚期纤维化,3名F3~F4期纤维化的患者被归类为F0~F2期纤维化,MRE将晚期纤维化与F0~F2期纤维化区分开来的AUC为0.924 (P<0.0001)。虽然张凯等[20]与Loomba等[21]的研究均表明MRE对晚期纤维化的预测更加准确,但其二者的研究结果也显示出了MRE对早期LF良好的诊断效能。人体组织弹性模量在部分区域内可能存在重复情况,当正常组织和病理组织重复时会影响MRE的诊断,这也造成了张凯等[20]研究中的两例漏诊。但是总的来说,MRE对各期LF的检出都是有效的,指导临床早期干预,逆转早期LF,防止晚期LF进一步发展,这对降低肝硬化乃至肝癌的发生发展都具有重大意义。

2 MRE技术进展
2.1 设备

在目前的肝脏MRE扫描中应用较多的是刚性塑料驱动器,这给患者的检查过程带来了不适,丁丽等[22]开发的一种柔性气动驱动器,极大地改善了患者的体验感,相比于刚性驱动器,柔性驱动器更加贴合胸壁,能够使得波的传播更加均匀,且二者获得的肝脏硬度值差异无统计学意义[23]

2.2 序列

目前常见的MRE序列是梯度回波序列(gradient echo,GRE)、自旋回波序列(spin echo,SE)、自旋回波-平面回波序列(spin echo-echo planar imaging,SE-EPI)及平衡稳态自由进动序列。其中GRE-MRE序列是最常用的序列[24],但其容易受肝脏铁质沉积的影响[25, 26, 27],导致肝脏硬度的测量不稳定。而铁超载在慢性肝病患者中并不少见,对此,SE-EPI序列成为了更佳的选择。已有研究表明,SE-EPI对磁场的均匀性不太敏感[28,29],且该序列基于视图共享的重建策略可以避免呼吸运动伪影,这使得其在铁超载、屏气困难的患者中仍然能够准确地进行图像采集[30]

2.3 后处理技术

目前常用的后处理方式分为二维(2D)和三维(3D),2D即选择肝脏最大层面处扫描4层图像并从两个方向上的波传播数据进行分析,此种后处理方式可能由于波的传播不完整导致肝脏硬度的测量误差[31]。而3D后处理方式可以对全肝进行扫描,实现对波的传播数据进行全面分析,并且能够消除产生干扰的纵向传播波,使得到的肝脏硬度值更加稳定、准确[32]。Loomba[30]的一项前瞻性研究也表明3D-MRE的成像模式较2D-MRE更为准确。此外,更有研究表明,将3D后处理技术与SE-EPI序列结合,不仅能增加扫描范围、提高图像信噪比及准确率,还能在肝纤维化分期诊断中显现出良好性能[32, 33, 34]。但是由于3D-MRE扫描时间长,技术要求更高,故普及率不高,但其应用前景是值得期待的[35]

2.4 ROI的勾画

常规ROI的勾画往往是手动的,避开肝脏边缘、胆管及大血管等,取平均值作为肝脏硬度值,或者直接选取肝脏最大截面的平均值。此种手动勾画方法易受勾画者的主观影响,且对于不均匀性肝纤维化患者、LF进程不一致者等不能准确评估其纤维化分期[36]。而Rezvani[37]等提出的一种基于全肝容积的容积分割测量法可以通过分析软件对肝脏进行分段,进而提供LF硬度值的分布情况,使得LF评估更加准确、具体。此外,还有学者提出自动肝弹性计算[38,39]算法来通过自动在图像中定位肝脏,检测肝脏边缘、绘制ROI。

3 展望

现已有多个研究表明MRE对早期LF的诊断及评估具有显著优势,这将有利于临床早期干预,降低肝硬化及肝癌的发生率。同时,MRE还可检出由肝脏病变引起的尚未见临床症状的食管静脉曲张[40,41]和门脉高压症[42]。当联合脾脏硬度一起测量的时候,肝脏硬度值似乎更加准确、稳定[43]

此外,MRE还可用于肝脏肿瘤、炎症的特征描述。Thompson等[44]的一项初步研究显示原发性肝癌的组织病理学分级和肿瘤硬度之间可能存在关系,低分化肝细胞癌往往比高分化和中等分化肝细胞癌具有更高的硬度,且原发性肝癌早期就已有外周硬度的升高,这可能有助于早期原发性肝癌的检出。急性炎症可由于炎症细胞的募集以及炎症造成的肝脏水肿和充血导致肝包膜的实质扩张和拉伸,从而使得肝脏硬度普遍增加,而慢性炎症或亚急性炎症仅导致肝脏硬度的轻度增加(低于3 kPa)[45]。虽然目前的MRE技术很难对肝脏硬度进行量化和与纤维化分开,但这一目标有望随着MRE技术的进展在未来实现。

总之,肝脏MRE是一个很有前景的研究领域,其技术的发展更是进一步提高了肝脏疾病诊断的准确性及特异性。

利益冲突
作者利益冲突声明:

全体作者均声明无利益冲突。

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