Molecular MRI of collagen to diagnose and stage liver fibrosis

JOURNAL OF HEPATOLOGY

卷:59

Article

Fuchs, Bryan C.^1,2  Wang, Huifang^3,4  Yang, Yan^3,4  Wei, Lan^1,2  Polasek, Miloslav^3,4  Schuehle, Daniel T.^3,4  Lauwers, Gregory Y.^2,5  Parkar, Ashfaq⁶  Sinskey, Anthony J.⁷  Tanabe, Kenneth K.^1,2  Caravan, Peter^3,4 

[1] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA

[4] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

[5] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[6] Fibrosis & Wound Repair, Sanofi, France

[7] MIT, Dept Biol, Cambridge, MA 02139 USA

关键词: Fibrosis;    MRI;    Molecular imaging;    Type 1 collagen;    Non-invasive;    Gadolinium;    EP-3533;    CCl4;   

DOI  :  10.1016/j.jhep.2013.06.026

来源: Elsevier

【 摘 要 】

Background & Aims: 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 non-invasively 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. Methods: A gadolinium (Gd)-based MRI probe targeted to type I collagen (termed EP-3533) was utilized to non-invasively 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. Results: The most sensitive MR biomarker was the change in liver: muscle contrast to noise ratio (Delta CNR) after EP-3533 injection. We observed a strong positive linear correlation between Delta CNR and liver hydroxyproline (i.e. collagen) levels (r = 0.89) as well as Delta CNR 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. Conclusions: We have developed an 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. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free