Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo
Aims: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tiss...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Oxford University Press
2016
|
| Online Access: | http://hdl.handle.net/1721.1/103946 https://orcid.org/0000-0002-7832-7156 |
| _version_ | 1811074289168809984 |
|---|---|
| author | Hara, Tetsuya Ughi, Giovanni J. McCarthy, Jason R. Erdem, S. Sibel Mauskapf, Adam Lyon, Samantha C. Fard, Ali M. Edelman, Elazer R. Tearney, Guillermo J. Jaffer, Farouc A. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Hara, Tetsuya Ughi, Giovanni J. McCarthy, Jason R. Erdem, S. Sibel Mauskapf, Adam Lyon, Samantha C. Fard, Ali M. Edelman, Elazer R. Tearney, Guillermo J. Jaffer, Farouc A. |
| author_sort | Hara, Tetsuya |
| collection | MIT |
| description | Aims: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage.
Methods and results: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001).
Conclusion: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing. |
| first_indexed | 2024-09-23T09:46:42Z |
| format | Article |
| id | mit-1721.1/103946 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:46:42Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/1039462022-09-30T16:47:56Z Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo Hara, Tetsuya Ughi, Giovanni J. McCarthy, Jason R. Erdem, S. Sibel Mauskapf, Adam Lyon, Samantha C. Fard, Ali M. Edelman, Elazer R. Tearney, Guillermo J. Jaffer, Farouc A. Harvard University--MIT Division of Health Sciences and Technology Edelman, Elazer R. Edelman, Elazer R. Aims: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. Methods and results: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). Conclusion: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing. National Institutes of Health (U.S.) (NIH grant R01HL108229) National Institutes of Health (U.S.) (NIH grant R01HL122388) American Heart Association (#13POST14640021) American Heart Association (#13GRNT17060040) Massachusetts General Hospital (MGH ECOR Support Fund) National Institutes of Health (U.S.) (NIH R01GM49039) National Institutes of Health (U.S.) (NIH R01HL093717) Kanae Foundation for Research Abroad 2016-08-17T15:39:14Z 2016-08-17T15:39:14Z 2015-12 Article http://purl.org/eprint/type/JournalArticle 0195-668X 1522-9645 http://hdl.handle.net/1721.1/103946 Hara, Tetsuya, Giovanni J. Ughi, Jason R. McCarthy, S. Sibel Erdem, Adam Mauskapf, Samantha C. Lyon, Ali M. Fard, Elazer R. Edelman, Guillermo J. Tearney, and Farouc A. Jaffer. “ Intravascular Fibrin Molecular Imaging Improves the Detection of Unhealed Stents Assessed by Optical Coherence Tomography in Vivo .” European Heart Journal (December 18, 2015): ehv677. https://orcid.org/0000-0002-7832-7156 en_US http://dx.doi.org/10.1093/eurheartj/ehv677 European Heart Journal Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Oxford University Press Edelman via Crummett |
| spellingShingle | Hara, Tetsuya Ughi, Giovanni J. McCarthy, Jason R. Erdem, S. Sibel Mauskapf, Adam Lyon, Samantha C. Fard, Ali M. Edelman, Elazer R. Tearney, Guillermo J. Jaffer, Farouc A. Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title | Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title_full | Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title_fullStr | Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title_full_unstemmed | Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title_short | Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| title_sort | intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo |
| url | http://hdl.handle.net/1721.1/103946 https://orcid.org/0000-0002-7832-7156 |
| work_keys_str_mv | AT haratetsuya intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT ughigiovannij intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT mccarthyjasonr intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT erdemssibel intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT mauskapfadam intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT lyonsamanthac intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT fardalim intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT edelmanelazerr intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT tearneyguillermoj intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo AT jafferfarouca intravascularfibrinmolecularimagingimprovesthedetectionofunhealedstentsassessedbyopticalcoherencetomographyinvivo |