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Label-free evaluation of angiogenic sprouting in microengineered devices using ultrahigh-resolution optical coherence microscopy

Abstract. Understanding the mechanism of angiogenesis could help to decipher wound healing and embryonic development and to develop better treatment for diseases such as cancer. Microengineered devices were developed to reveal the mechanisms of angiogenesis, but monitoring the angiogenic process nondestructively in these devices is a challenge. In this study, we utilized a label-free imaging technique, ultrahigh-resolution optical coherence microscopy (OCM), to evaluate angiogenic sprouting in a microengineered device. The OCM system was capable of providing ∼1.5-μm axial resolution and ∼2.3-μm transverse resolution. Three-dimensional (3-D) distribution of the sprouting vessels in the microengineered device was imaged over 0.6×0.6×0.5  mm3, and details such as vessel lumens and branching points were clearly visualized. An algorithm based on stretching open active contours was developed for tracking and segmenting the sprouting vessels in 3-D-OCM images. The lengths for the first-, second-, and third-order vessels were measured as 127.8±48.8  μm (n=8), 67.3±25.9  μm (n=9), and 62.5±34.7  μm (n=10), respectively. The outer diameters for the first-, second-, and third-order vessels were 13.2±1.0, 8.0±2.1, and 4.4±0.8  μm, respectively. These results demonstrate OCM as a promising tool for nondestructive and label-free evaluation of angiogenic sprouting in microengineered devices.