title: Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Giovanni J
authors.initials: GJ
authors.lastname: Ughi
authors.affiliation: Center for System Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: McCarthy
authors.affiliation: Center for System Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: S Sibel
authors.initials: SS
authors.lastname: Erdem
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Mauskapf
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Lyon
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Fard
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA fjaffer@mgh.harvard.edu gtearney@mgh.harvard.edu.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Tearney
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA fjaffer@mgh.harvard.edu gtearney@mgh.harvard.edu.
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
keywords: Fibrin; Molecular imaging; Optical coherence tomography; Stent thrombosis