Molecular MR imaging of liver fibrosis: a feasibility study using rat and mouse models.
Molecular MR imaging of liver fibrosis: a feasibility study using rat and mouse models.
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DOI：
10.1016/j.jhep.2012.04.035
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发表时间：
2012-09
影响因子：
25.7
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Polasek, Miloslav;Fuchs, Bryan C.;Uppal, Ritika;Schuehle, Daniel T.;Alford, Jamu K.;Loving, Galen S.;Yamada, Suguru;Wei, Lan;Lauwers, Gregory Y.;Guimaraes, Alexander R.;Tanabe, Kenneth K.;Caravan, Peter
肝活检是目前评估肝纤维化的临床黄金标准，它是有创的，有抽样误差，不是筛查、监测或临床决策的最佳选择。纤维化的特征是细胞外基质蛋白过度堆积，包括I型胶原。我们假设，以I型胶原为靶点的分子磁共振成像(MRI)可以为纤维化的评估提供一种直接和非侵入性的方法。用二乙基亚硝胺造成大鼠肝纤维化，用四氯化碳造成小鼠肝纤维化。在静脉注射之前和之后立即对动物进行成像。给予胶原靶向探针EP-3533或非靶向对照Gd-DTPA。从T1图和T1加权图像评估磁共振(MR)信号洗出特性。对肝组织进行肝纤维化病理评分，并分析肝组织中Gd和羟脯氨酸的含量。EP-3533增强MR在延迟成像上显示较高的信号强度(正常信号增强小鼠：对照组=0.39±0.04，纤维化小鼠=0.55±0.03，p<；0.01)，而肝纤维化肝脏的信号消失较慢(肝T1/2=51.3±3.6vs42.0±2.5min，p<；0.05和54.5±1.9对44.1±2.9min，p<；0.01)。Gd-DTPA增强MR不能区分肝纤维化和正常对照动物。肝组织中EP-3533 Gd浓度与羟脯氨酸水平(r=0.74(大鼠)，r=0.77(小鼠))和Ishak评分(r=0.84(大鼠)，r=0.79(小鼠))呈显著正相关。肝纤维化的分子核磁共振成像用胶原蛋白特异性探针识别两种啮齿动物疾病模型中的纤维化组织。
Liver biopsy, the current clinical gold standard for assessment of fibrosis, is invasive and has sampling errors, and is not optimal for screening, monitoring, or clinical decision-making. Fibrosis is characterized by excessive accumulation of extracellular matrix proteins including type I collagen. We hypothesize that molecular magnetic resonance imaging (MRI) with a probe targeted to type I collagen could provide a direct and non-invasive method for assessment of fibrosis. Liver fibrosis was generated in rats with diethylnitrosamine and in mice with carbon tetrachloride. Animals were imaged prior to and immediately following i.v. administration of either collagen-targeted probe EP-3533 or non-targeted control Gd-DTPA. Magnetic resonance (MR) signal wash-out characteristics were evaluated from T1 maps and T1-weighted images. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. EP-3533 enhanced MR showed greater signal intensity on delayed imaging (normalized signal enhancement mice: control = 0.39±0.04, fibrotic = 0.55±0.03, p <0.01) and slower signal washout in fibrotic liver compared to controls (liver t1/2 = 51.3±3.6 vs 42.0±2.5 min, p <0.05 and 54.5±1.9 vs 44.1±2.9 min, p <0.01 for fibrotic vs controls in rat and mouse models, respectively). Gd-DTPA enhanced MR could not distinguish fibrotic from control animals. EP-3533 gadolinium concentration in liver showed strong positive correlations with hydroxyproline levels (r = 0.74 (rats), r = 0.77 (mice)) and with Ishak scoring (r = 0.84 (rats), r = 0.79 (mice)). Molecular MRI of liver fibrosis with a collagen-specific probe identifies fibrotic tissue in two rodent models of disease.
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