High-resolution optical mapping of inflammatory macrophages following endovascular arterial injury

Mol Imaging Biol. 2013 Jun;15(3):282-9. doi: 10.1007/s11307-012-0599-2.


Purpose: 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.

Procedures: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Arteries / pathology*
  • Carotid Artery Injuries / diagnosis*
  • Cell Proliferation
  • Endothelial Cells / pathology
  • Endothelium, Vascular / pathology
  • Image Processing, Computer-Assisted
  • Inflammation / pathology*
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Neointima / pathology
  • Optical Imaging / methods*
  • Vascular System Injuries / diagnosis*
  • Vascular System Injuries / pathology