title: Localization and quantification of platelet-rich thrombi in large blood vessels with near-infrared fluorescence imaging.
abstract: BACKGROUND
  Imaging of thrombus formation in vivo has been limited by the inability to directly visualize and measure thrombi in large blood vessels in real time. Near-infrared light, with its superior tissue penetration and reduced scatter, could potentially solve this problem.
  
  
  RESULTS
  Platelets were labeled with the near-infrared fluorophore IR-786. Optimal total fluorescence yield occurred at 6 attomoles of IR-786 per platelet. IR-786-labeled platelets were tested for their ability to detect thrombus formation in large animal model systems relevant to common human vascular procedures. Invisible near-infrared light did not distort the surgical field in any way, and even after optimization of per-platelet fluorescent yield, platelets remained fully functional. Intravenous infusion of just 3.6x10(10) labeled platelets into a 35-kg Yorkshire pig permitted thrombus visualization, with a signal-to-background ratio > or = 2, for at least 2 hours in coronary, carotid, and femoral vessels. Platelet-rich, actively growing clots were monitored in real time and quantified with respect to size and kinetics after injury to vessels, cutaneous incisions, intravascular stent insertion, or introduction of embolic coils. Similarly, formed clots were monitored in real time during thrombolysis with streptokinase and heparin. Vessel patency was assessed independently with a second near-infrared fluorescent blood pool agent.
  
  
  CONCLUSIONS
  IR-786-labeled platelets provide sensitive, specific, and real-time visualization of thrombi in thick-walled blood vessels. In addition to immediate application in cardiac, transplant, and vascular surgery, the mechanisms that underlie thrombus formation in large blood vessels can now be investigated.
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA. rflaumen@bidmc.harvard.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Flaumenhaft
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tanaka
authors.forename: Gwenda J
authors.initials: GJ
authors.lastname: Graham
authors.forename: Alec M
authors.initials: AM
authors.lastname: De Grand
authors.forename: Rita G
authors.initials: RG
authors.lastname: Laurence
authors.forename: Kozo
authors.initials: K
authors.lastname: Hoshino
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000737:chemistry* / Q000502:physiology; D001808:Blood Vessels / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013552:Swine; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology