Molecular MRI of collagen to diagnose and stage liver fibrosis

Available in PMC 2014 November 01.

Bibliographic Details
Main Authors: Fuchs, Bryan C., Wang, Huifang, Yang, Yan, Wei, Lan, Polasek, Miloslav, Schühle, Daniel T., Lauwers, Gregory Y., Parkar, Ashfaq, Tanabe, Kenneth K., Caravan, Peter, Sinskey, Anthony J
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Elsevier 2016
Online Access:http://hdl.handle.net/1721.1/103914
https://orcid.org/0000-0002-1015-1270
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author Fuchs, Bryan C.
Wang, Huifang
Yang, Yan
Wei, Lan
Polasek, Miloslav
Schühle, Daniel T.
Lauwers, Gregory Y.
Parkar, Ashfaq
Tanabe, Kenneth K.
Caravan, Peter
Sinskey, Anthony J
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Fuchs, Bryan C.
Wang, Huifang
Yang, Yan
Wei, Lan
Polasek, Miloslav
Schühle, Daniel T.
Lauwers, Gregory Y.
Parkar, Ashfaq
Tanabe, Kenneth K.
Caravan, Peter
Sinskey, Anthony J
author_sort Fuchs, Bryan C.
collection MIT
description Available in PMC 2014 November 01.
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spelling mit-1721.1/1039142022-10-02T02:50:10Z Molecular MRI of collagen to diagnose and stage liver fibrosis Fuchs, Bryan C. Wang, Huifang Yang, Yan Wei, Lan Polasek, Miloslav Schühle, Daniel T. Lauwers, Gregory Y. Parkar, Ashfaq Tanabe, Kenneth K. Caravan, Peter Sinskey, Anthony J Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Sinskey, Anthony J. Available in PMC 2014 November 01. 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. National Cancer Institute (U.S.) (CA140861) Whitehead Institute for Biomedical Research (Grant EB009062) Sanofi Aventis (Firm) (Innovation Award) 2016-08-15T17:52:45Z 2016-08-15T17:52:45Z 2013-11 2013-05 Article http://purl.org/eprint/type/JournalArticle 01688278 http://hdl.handle.net/1721.1/103914 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. https://orcid.org/0000-0002-1015-1270 en_US http://dx.doi.org/10.1016/j.jhep.2013.06.026 Journal of Hepatology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC
spellingShingle Fuchs, Bryan C.
Wang, Huifang
Yang, Yan
Wei, Lan
Polasek, Miloslav
Schühle, Daniel T.
Lauwers, Gregory Y.
Parkar, Ashfaq
Tanabe, Kenneth K.
Caravan, Peter
Sinskey, Anthony J
Molecular MRI of collagen to diagnose and stage liver fibrosis
title Molecular MRI of collagen to diagnose and stage liver fibrosis
title_full Molecular MRI of collagen to diagnose and stage liver fibrosis
title_fullStr Molecular MRI of collagen to diagnose and stage liver fibrosis
title_full_unstemmed Molecular MRI of collagen to diagnose and stage liver fibrosis
title_short Molecular MRI of collagen to diagnose and stage liver fibrosis
title_sort molecular mri of collagen to diagnose and stage liver fibrosis
url http://hdl.handle.net/1721.1/103914
https://orcid.org/0000-0002-1015-1270
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