Molecular MRI of collagen to diagnose and stage liver fibrosis
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Sinskey_Molecular MRI.pdf
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1.26 MB
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Author(s)
Fuchs, Bryan C.
Wang, Huifang
Yang, Yan
Wei, Lan
Polasek, Miloslav
Schühle, Daniel T.
Lauwers, Gregory Y.
Parkar, Ashfaq
Tanabe, Kenneth K.
Caravan, Peter
Date Issued
November 2013
Journal
Journal of Hepatology
Publisher
Elsevier
Citation
Fuchs, Bryan C., Huifang Wang, Yan Yang, Lan Wei, Miloslav Polasek, Daniel T. Schühle, Gregory Y. Lauwers, Ashfaq Parkar, Anthony J. Sinskey, Kenneth K. Tanabe, and Peter Caravan. "Molecular MRI of collagen to diagnose and stage liver fibrosis." Journal of Hepatology 59:5 (November 2013), pp. 992-998.
Version
Author's final manuscript
Abstract
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 (CCl[subscript 4]) 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 (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.
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.
Description
Available in PMC 2014 November 01.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.jhep.2013.06.026
