Assessment of microcirculation dynamics during cutaneous wound healing phasesin vivousing optical microangiography

Abstract

Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

Accessing to arteriovenous blood flow dynamics response using combined laser speckle contrast imaging and skin optical clearing

“…However, LDF cannot simultaneously provide microvascular structural and functional information because of lacking adequate spatiotemporal resolution; TiVi is insensitive to the velocity of red blood cells [6]. Furthermore, some other highresolution optical imaging modalities, such as intravital microscopy (IVM) [7,8], optical coherence tomography (OCT) [9] and photoacoustic microscopy (PAM) [10], have also been applied to image the cutaneous microcirculation. Unfortunately, IVM usually depends on the dorsal skinfold chamber, which may accompany with bleeding and changes in the physiological environment [11,12]; Due to lack of sufficient temporal resolution, it is difficult for OCT and PAM to monitor a large field of view of the cutaneous blood flow dynamical response [13][14][15].…”

Optical coherence tomography angiography monitors human cutaneous wound healing over time

“…Therefore, identifying and accurately assessing the characteristic vascular changes that occur throughout each phase and correlating them with structural changes could provide a basis for wound healing assessment. For example, monitoring the vascular features associated with re-epithelialization, reformation of the dermalepidermal junction, the subsequent thickening of the newly formed epidermis, and dermal remodeling could be used to as indicators for normal wound healing (5). Additionally, any deviations from normal could be addressed with treatment adjustments to ensure optimal recovery.…”

Segmentation and quantification of blood vessels for OCT-based micro-angiograms using hybrid shape/intensity compounding

“…We have previously shown how OMAG can be utilized to monitor wound healing process and its various phases from a qualitative point of view [Yousefi et al, 2014]. In the following sections, we utilize the proposed segmentation method to quantify the healing process and angiogenesis.…”

“…The proposed method is then used to monitor changes in the vasculature and the vessel diameter [Jung et al, 2013; Yousefi et al, 2014]. Non-invasive in vivo OMAG images were acquired from the pinna of a healthy ~6 weeks old male hairless mouse (Crl:SKH1-Hrhr) weighting approximately 25g.…”

“…To generate the OMAG images of microcirculatory tissue beds in vivo, we utilized a high speed spectral domain OCT (SD-OCT) system, which was reported in [Yousefi et al, 2014]. Briefly, the system used a light source with the center wavelength of 1310 nm and bandwidth of 65 nm, providing an axial resolution of ~12 μm in air.…”