Yang Euitaek, Khaled Alia, Liang Xiaofei, de la Cerda Jorge, Schuler F William, Goel Shreya, Pagel Mark D
Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Physics, University of Wisconsin, 1111 Highland Avenue #1005, Madison, WI, 53705, USA.
Mol Imaging Biol. 2024 Dec;26(6):995-1004. doi: 10.1007/s11307-024-01966-2. Epub 2024 Nov 12.
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.
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% O and 100% O breathing gases to measure oxyhemoglobin (HbO), deoxyhemoglobin (Hb), total hemoglobin (HbT), and oxygen saturation (%sO), along with changes in these parameters caused by a change in breathing gas (ΔHb, ΔHbO, ΔHbT, ΔsO). 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.
The average wound size was significantly smaller only by Day 6. For comparison, OE PAI measured a significant increase in HbO, Hb, HbT, and %sO 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.
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.
皮肤伤口愈合的临床前模型有助于改善临床伤口护理。氧增强光声成像（OE PAI）可测量氧合情况，动态对比增强（DCE）PAI可测量血管灌注。我们研究了联合使用OE-DCE PAI方案如何测量皮肤愈合模型中的血管氧合和灌注情况。
我们建立了一个皮肤“打孔”伤口模型，并对伤口进行拍照以追踪9天的愈合情况。我们在第0、3、6和9天进行了OE-DCE PAI。OE PAI使用21% O和100% O呼吸气体进行，以测量氧合血红蛋白（HbO）、脱氧血红蛋白（Hb）、总血红蛋白（HbT）和氧饱和度（%sO），以及呼吸气体变化引起的这些参数的变化（ΔHb、ΔHbO、ΔHbT、ΔsO）。为了进行DCE PAI，静脉注射吲哚菁绿（ICG），同时在10分钟内监测PAI信号，观察该试剂在伤口区域的洗脱过程，以此评估洗脱率。
仅在第6天，平均伤口大小显著减小。相比之下，OE PAI测量发现，伤口形成后立即出现HbO、Hb、HbT和%sO显著增加，到第3天显著下降，并在第9天继续下降至接近正常组织的值。血管洗脱率在第3天显著增加，并在愈合过程中持续增加。值得注意的是，洗脱率可在单个PAI吸收波长下通过简单比较信号幅度进行评估，无需复杂分析，这可能有助于临床转化。
OE-DCE PAI可在皮肤伤口大小发生显著变化之前监测血管灌注和氧合的显著变化。这些结果确立了OE-DCE PAI作为未来临床前伤口愈合研究及最终临床转化工具的地位。
