Molecular MRI of collagen to diagnose and stage liver fibrosis.
Molecular MRI of collagen to diagnose and stage liver fibrosis.
复制标题
DOI：
10.1016/j.jhep.2013.06.026
复制
发表时间：
2013-11
影响因子：
25.7
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Fuchs, Bryan C.;Wang, Huifang;Yang, Yan;Wei, Lan;Polasek, Miloslav;Schuehle, Daniel T.;Lauwers, Gregory Y.;Parkar, Ashfaq;Sinskey, Anthony J.;Tanabe, Kenneth K.;Caravan, Peter
评估肝纤维化的金标准是活检，尽管存在侵入性和采样误差以及并发症（包括发病率和死亡率）等限制。因此，非侵入性地量化纤维化以促进慢性肝病的早期诊断并提供监测疾病进展的手段是一个主要的未满足的医疗需求。本研究的目的是评估几种磁共振成像（MRI）技术对肝纤维化分期的能力。一个钆（Gd）为基础的MRI探头针对I型胶原蛋白（称为EP-3533）被用来非侵入性阶段的四氯化碳（CCl 4）小鼠模型中的肝纤维化和结果进行了比较，其他MRI技术，包括弛豫时间，扩散和磁化转移测量。最敏感的MR生物标志物是EP-3533注射后肝脏：肌肉对比噪声比（ΔCNR）的变化。我们观察到ΔCNR与肝羟脯氨酸（即胶原蛋白）水平（r=0.89）以及ΔCNR与常规Ishak纤维化评分之间存在强正线性相关性。此外，区分早期（Ishak ≤3）和晚期（Ishak ≥ 4）纤维化的受试者工作曲线下面积（AUR 0 C）为0.942±0.052（p<0.001）。相比之下，其他MRI技术对该模型中的纤维化变化不敏感。我们开发了一种使用胶原特异性探针的MRI技术，用于诊断和分期肝纤维化，并在CCl 4小鼠模型中进行了验证。这种方法应该提供更好的手段来监测患者的疾病进展。
The gold standard in assessing liver fibrosis is biopsy despite limitations like invasiveness and sampling error and complications including morbidity and mortality. Therefore, there is a major unmet medical need to quantify fibrosis noninvasively to facilitate early diagnosis of chronic liver disease and provide a means to monitor disease progression. The goal of this study was to evaluate the ability of several magnetic resonance imaging (MRI) techniques to stage liver fibrosis. A gadolinium (Gd)-based MRI probe targeted to type I collagen (termed EP-3533) was utilized to noninvasively stage liver fibrosis in a carbon tetrachloride (CCl4) mouse model and the results were compared to other MRI techniques including relaxation times, diffusion and magnetization transfer measurements. The most sensitive MR biomarker was the change in liver:muscle contrast to noise ratio (ΔCNR) after EP-3533 injection. We observed a strong positive linear correlation between ΔCNR and liver hydroxyproline (i.e. collagen) levels (r=0.89) as well as ΔCNR and conventional Ishak fibrosis scoring. In addition, the area under the receiver operating curve (AUR0C) for distinguishing early (Ishak ≤3) from late (Ishak ≥ 4) fibrosis was 0.942±0.052 (p<0.001). By comparison, other MRI techniques were not as sensitive to changes in fibrosis in this model. We have developed a MRI technique using a collagen-specific probe for diagnosing and staging liver fibrosis, and validated it in the CCl4 mouse model. This approach should provide a better means to monitor disease progression in patients.
登录
查看更多内容
影响因子：
13.5
作者：
Bedossa, P;Dargère, D;Paradis, V
通讯作者：
Paradis, V
影响因子：
12.6
作者：
Yin, Meng;Talwalkar, Jayant A.;Ehman, Richard L.
通讯作者：
Ehman, Richard L.
影响因子：
168.9
作者：
Imbert-Bismut, F;Ratziu, V;Poynard, T
通讯作者：
Poynard, T
影响因子：
4.4
作者：
Chow, April M.;Gao, Darwin S.;Wu, Ed X.
通讯作者：
Wu, Ed X.
影响因子：
29.4
作者：
Popov Y;Sverdlov DY;Sharma AK;Bhaskar KR;Li S;Freitag TL;Lee J;Dieterich W;Melino G;Schuppan D
通讯作者：
Schuppan D