Non-invasive longitudinal monitoring of angiogenesis in a murine full-thickness cutaneous wound healing model using high-resolution three-dimensional ultrasound imaging

Background/Purpose: The aim of this study was to evaluate the longitudinal monitoring of angiogenesis in a murine full- thickness cutaneous wound healing model using high- resolution three- dimensional (3D) ultrasound imaging. Methods: Two C57BL/6 mice were used. Two- dimensional (2D) ultrasound images with the Color Doppler mode were acquired at regular spatial intervals on day 9, 11, and 14 after wounding. 3D ultrasound images were processed by reconstructing the 2D ultrasound image sequences. The wounds were harvested on day 14 and serial sections were immunohistologically stained with an anti- CD31 antibody. Results: 3D ultrasound imaging with the Color Doppler mode showed the distribution of microvascular growth on days 9, 11, and 14 after wounding (44.6%, 51.5%, and 27.3% in wound 1, 55.8%, 38.1%, and 35.1% in wound 2, 60.6%, 62.6%, and 63.1% in wound 3, and 15.8%, 42.0%, and 31.9% in wound 4, respectively). A correlation was observed between % vascularity measured by paired 2D ultrasound imaging with the Color Doppler mode and sections immunohistologically stained for the anti- CD31 an- tibody (r=0.927, 0.871, 0.717, and 0.913 for wounds 1, 2, 3, and 4, respectively. P<.01). Conclusion: These results indicate that high- resolution 3D ultrasound imaging is use- ful for longitudinally evaluating the distribution of microvascular growth over the course of healing. KEYWORDS