3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model
Background & Aims Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use mo...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/108004 https://orcid.org/0000-0002-1015-1270 |
| _version_ | 1826209246656593920 |
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| author | Farrar, Christian T. DePeralta, Danielle K. Day, Helen Rietz, Tyson A. Wei, Lan Lauwers, Gregory Y. Keil, Boris Subramaniam, Arun Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter Sinskey, Anthony J |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Farrar, Christian T. DePeralta, Danielle K. Day, Helen Rietz, Tyson A. Wei, Lan Lauwers, Gregory Y. Keil, Boris Subramaniam, Arun Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter Sinskey, Anthony J |
| author_sort | Farrar, Christian T. |
| collection | MIT |
| description | Background & Aims
Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy.
Methods
Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content.
Results
ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver.
Conclusions
EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis. |
| first_indexed | 2024-09-23T14:19:30Z |
| format | Article |
| id | mit-1721.1/108004 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:19:30Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1080042022-09-29T08:44:32Z 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model Farrar, Christian T. DePeralta, Danielle K. Day, Helen Rietz, Tyson A. Wei, Lan Lauwers, Gregory Y. Keil, Boris Subramaniam, Arun Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter Sinskey, Anthony J Massachusetts Institute of Technology. Department of Biology Sinskey, Anthony J Background & Aims Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. Methods Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. Results ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. Conclusions EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis. National Cancer Institute (U.S.) (CA140861) National Institutes of Health. National Institute for Biomedical Imaging and Bioengineering (EB009062) Sanofi Aventis (Firm) 2017-04-10T15:03:39Z 2017-04-10T15:03:39Z 2015-05 2015-03 Article http://purl.org/eprint/type/JournalArticle 0168-8278 http://hdl.handle.net/1721.1/108004 Farrar, Christian T., DePeralta, Danielle K.; Day, Helen; et al. “3D Molecular MR Imaging of Liver Fibrosis and Response to Rapamycin Therapy in a Bile Duct Ligation Rat Model.” Journal of Hepatology 63, no. 3 (September 2015): 689–696. © 2015 European Association for the Study of the Liver. https://orcid.org/0000-0002-1015-1270 en_US http://dx.doi.org/10.1016/j.jhep.2015.04.029 Journal of Hepatology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Farrar, Christian T. DePeralta, Danielle K. Day, Helen Rietz, Tyson A. Wei, Lan Lauwers, Gregory Y. Keil, Boris Subramaniam, Arun Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter Sinskey, Anthony J 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title | 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title_full | 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title_fullStr | 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title_full_unstemmed | 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title_short | 3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| title_sort | 3d molecular mr imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model |
| url | http://hdl.handle.net/1721.1/108004 https://orcid.org/0000-0002-1015-1270 |
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