Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced - Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI)

Purpose: Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can measure vascular perfusion. We investigated how a combined OE-DCE PAI protocol can measure vascular oxygenation and perfusion to a cutaneous healing model.

Procedures: We developed a cutaneous "punch" wound model and photographed the wounds to track healing for 9 days. We performed OE-DCE PAI on Day 0, 3, 6, and 9. OE PAI was performed with 21% O₂ and 100% O₂ breathing gases to measure oxyhemoglobin (HbO₂), deoxyhemoglobin (Hb), total hemoglobin (HbT), and oxygen saturation (%sO₂), along with changes in these parameters caused by a change in breathing gas (ΔHb, ΔHbO₂, ΔHbT, ΔsO₂). To perform DCE PAI, indocyanine green (ICG) was administered intravenously while monitoring the PAI signal for 10 min as the agent washed through the wound area, which was used to evaluate the wash-out rate.

Results: The average wound size was significantly smaller only by Day 6. For comparison, OE PAI measured a significant increase in HbO₂, Hb, HbT, and %sO₂ immediately after creating the wound, which significantly decreased by Day 3 and continued to decrease towards values for normal tissue by Day 9. The vascular wash-out rate significantly increased by Day 3, and continued to increase during the healing process. Notably, the wash-out rate can be assessed at a single PAI absorbance wavelength and by simply comparing signal amplitudes without advanced analysis, which may facilitate clinical translation.

Conclusions: OE-DCE PAI can monitor significant changes in vascular perfusion and oxygenation prior to significant changes in cutaneous wound size. These results establish OE-DCE PAI as a tool for future pre-clinical wound healing studies and eventual clinical translation.