title: Inflammation modulates murine venous thrombosis resolution in vivo: assessment by multimodal fluorescence molecular imaging.
abstract: OBJECTIVE
  Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2 integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo.
  
  
  RESULTS
  Murine DVT were created with topical 5% FeCl(3) application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy. Day 4 analyses showed robust relationships among in vivo thrombus macrophages, matrix metalloproteinase activity, and fluorescein isothiocyanate-dextran deposition (r>0.70; P<0.01). In a serial 2-time point study, mice with DVT underwent intravital microscopy at day 4 and day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (P<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography was used and detected macrophages within jugular DVT (P<0.05 versus sham controls).
  
  
  CONCLUSIONS
  Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo and can inform the magnitude of thrombus resolution.
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Cardiovascular Research Center, 185 Cambridge St, Suite 3206, Boston, MA 02114, USA.
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Ripplinger
authors.forename: Chase W
authors.initials: CW
authors.lastname: Kessinger
authors.forename: Chunqiang
authors.initials: C
authors.lastname: Li
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Jason R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002712:Chlorides; D003911:Dextrans; D004195:Disease Models, Animal; D005268:Femoral Vein / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005290:Ferric Compounds; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007601:Jugular Veins / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D010690:Phlebography; D011379:Prognosis; D015203:Reproducibility of Results; D012501:Saphenous Vein / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D020246:Venous Thrombosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D002712:Chlorides; D003911:Dextrans; D005290:Ferric Compounds; D005456:Fluorescent Dyes; C015219:fluorescein isothiocyanate dextran; D020782:Matrix Metalloproteinases; D016650:Fluorescein-5-isothiocyanate; C024555:ferric chloride