title: High-resolution optical mapping of inflammatory macrophages following endovascular arterial injury.
abstract: OBJECTIVE
  Inflammation following arterial injury mediates vascular restenosis, a leading cause of cardiovascular morbidity. Here we utilize intravital microscopy (IVM) and a dextran-coated nanosensor to spatially map inflammatory macrophages in vivo following endovascular injury of murine carotid arteries.
  
  
  METHODS
  C57Bl/6 mice (n = 23) underwent endovascular guidewire carotid arterial injury. At day 14 or day 28 post-injury, mice underwent fluorescence IVM, 24 h after injection with the near-infrared fluorescent macrophage nanosensor CLIO-VT680. Adventitial collagen was concomitantly imaged using second harmonic generation (SHG) IVM. Correlative fluorescence microscopy and immunohistochemistry were performed.
  
  
  RESULTS
  Two-plane IVM reconstructions detected macrophage inflammation in the arterial wall that was elevated at day 14 compared to day 28 animals (P < 0.05). SHG-based collagen imaging of the outer arterial wall facilitated analysis of the macrophage-rich, inflamed neointima. Histological analyses and fluorescence microscopy data demonstrated increased macrophage infiltration in day 14 compared to day 28 neointima.
  
  
  CONCLUSIONS
  We demonstrate that the macrophage response to arterial injury can be imaged in vivo using IVM-based molecular imaging, and shows a higher macrophage influx at day 14 compared to day 28 post-injury.
authors.affiliation: Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Room 3206, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.forename: Chase W
authors.initials: CW
authors.lastname: Kessinger
authors.forename: Brian
authors.initials: B
authors.lastname: Thompson
authors.forename: Jason R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000175:diagnosis*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D058426:Neointima / Q000473:pathology; D061848:Optical Imaging / Q000379:methods*; D057772:Vascular System Injuries / Q000175:diagnosis* / Q000473:pathology