Inflammation modulates murine venous thrombosis resolution in vivo: Assessment by multimodal fluorescence molecular imaging

Crystal M Ripplinger, Chase W. Kessinger, Chunqiang Li, Jin Won Kim, Jason R. McCarthy, Ralph Weissleder, Peter K. Henke, Charles P. Lin, Farouc A. Jaffer

Research output: Contribution to journalArticle

20 Scopus citations

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. Methods and Results-Murine DVT were created with topical 5% FeCl3 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). Conclusion-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.

Original languageEnglish (US)
Pages (from-to)2616-2624
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number11
DOIs
StatePublished - Nov 2012

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Keywords

  • Deep vein thrombosis
  • Inflammation
  • Macrophage
  • Molecular imaging
  • Post-thrombotic syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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