In vivo laser speckle imaging reveals microvascular remodeling and hemodynamic changes during wound healing angiogenesis |
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Authors: | Abhishek Rege Nitish V Thakor Kevin Rhie Arvind P Pathak |
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Institution: | (1) Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;(2) Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, 720 Rutland Ave, 217 Traylor Bldg, Baltimore, MD 21205, USA; |
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Abstract: | Laser speckle contrast imaging (LSCI) is a high-resolution and high contrast optical imaging technique often used to characterize
hemodynamic changes in short-term physiological experiments. In this study, we demonstrate the utility of LSCI for characterizing
microvascular remodeling and hemodynamic changes during wound healing angiogenesis in vivo. A 2 mm diameter hole was made
in the mouse ear and the periphery of the wound imaged in vivo using LSCI over 12 days. We were able to visualize and quantify
the vascular and perfusion changes that accompanied wound healing in the microenvironment proximal to the wound, and validated
these changes with histology. We found that consistent with the stages of wound healing, microvessel density increased during
the initial inflammatory phase (i.e., day 0–3), stayed elevated through the tissue formation phase (i.e., until day 7) and
returned to baseline during the tissue remodeling phase (i.e., by day 12). Concomitant “wide area mapping” of blood flow revealed
that tissue perfusion in the wound periphery initially decreased, gradually increased from day 3–7, and subsided as healing
completed. Interestingly, some regions exhibited a reestablishment of tissue perfusion approximately 6 days earlier than the
~18 days usually reported for the long term remodeling phase. The results from this study demonstrate that LSCI is an ideal
platform for elucidating in vivo changes in microvascular hemodynamics and angiogenesis, and has the potential to offer invaluable
insights in a range of disease models involving abnormal hemodynamics, such as diabetes and tumors. |
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