Measuring Oxygen and Hemoglobin Saturation Distributions in Skin Grafts

描述（由申请人提供）：本提案概述了新产品的开发，以及同时测量皮肤中皮下PO2和血红蛋白氧饱和度的新方法。该产品，“氧球”，将发现广泛用于皮肤移植，皮肤溃疡和截肢愈合疗法的发展。在皮肤和底层组织之间的界面测量PO2和测量血红蛋白饱和度的能力，将有助于研究人员和临床医生评估氧气对愈合的影响以及治疗对改变局部氧气可用性的影响。“Oxyspheres”在不同氧浓度下的发光发射光谱将使用优化方法和多位点模型进行曲线拟合。通常情况下，多波长强度的亚表面发光的研究是复杂的吸收成分（氧和脱氧血红蛋白和黑色素）和组织光散射的光的波长依赖性衰减。使用“Oxyspheres”的方法学途径将利用这些组分的已知光谱行为来拟合“Oxyspheres”发光发射光谱，并根据拟合参数确定PO2和血红蛋白氧饱和度。这种创新的方法代表了测量伤口中氧气可用性的重大进步，并且它还在使用荧光探针测量体内组织生物化学和生理学方面取得了重大进展。新方法将允许荧光发射的多波长分析，以量化上覆组织中分析物的浓度，同时补偿发射强度的波长依赖性衰减。该方法的开发将遵循逐步开发，使用从缓冲液到血红蛋白溶液再到皮肤移植物的日益复杂的样品基质。第一阶段的研究为三个发展阶段中的每一个阶段都制定了明确的里程碑和可行性标准。第二阶段将把产品和分析方法发展成商业产品，用于临床实践。 公共卫生相关性：这项研究将开发一种创新的新产品，可以同时测量组织氧张力和血红蛋白氧饱和度。除了测量可从循环中获得的氧气之外，测量组织中特定位置处可获得的氧气的能力为医生提供了一种强大的新工具，该医生开发了增强患有糖尿病、压力性溃疡、皮肤移植和截肢的患者的皮肤愈合的方法。应用于这些问题的方法学途径有望普遍应用于细胞生物化学和生理学的许多荧光探针，并成为分析生命系统中组织行为的普遍应用方法。

DESCRIPTION (provided by applicant): This proposal outlines the development of a new product, and a new methodological approach to the simultaneous measurement of subdermal PO2 and hemoglobin oxygen saturation in skin. The product, "Oxyspheres", will find wide use in the development of healing therapies for skin grafts, skin ulcers, and amputations. The capability to measure PO2 at the interface between skin and underlying tissues and to measure hemoglobin saturation in the skin with a single product will assist researchers and clinicians in evaluating the effects of oxygen on healing and the effects of therapies on altering local oxygen availability. The luminescence emission spectra of "Oxyspheres" at different oxygen concentrations will be curve fit using optimization methods and a multisite model. Typically, multiwavelength intensity studies of subsurface luminescence are complicated by wavelength-dependent attenuation of light by absorbing components (oxy- and deoxy-hemoglobin and melanin) and by tissue light scattering. The methodological approach for using "Oxyspheres" will take advantage of the known spectral behaviors of these components to fit "Oxyspheres" luminescence emission spectra and to determine PO2 and hemoglobin oxygen saturation from the fitting parameters. This innovative approach represents a significant advancement in measuring oxygen availability in wounds, and it also makes a critical advancement in using fluorescent probes to measure tissue biochemistry and physiology in vivo. The new methods will allow multiwavelength analysis of fluorescence emission to quantify concentrations of analytes in overlying tissues while compensating for wavelength dependent attenuation of emission intensities. Development of the method will follow a stepwise development using samples matrixes of increasing complexity, from buffer to hemoglobin solutions, to skin grafts. Phase I research has well defined milestones and feasibility criteria for each of the three stages of development. Phase II will advance the products and analytical methods into commercial products to be used in clinical practice. PUBLIC HEALTH RELEVANCE: This research will develop an innovative new product that can measure tissue oxygen tensions and hemoglobin oxygen saturations simultaneously. The ability to measure oxygen available at specific locations in tissue in addition to measuring oxygen available from the circulation provides a powerful new tool to physicians developing methods to enhance skin healing in patients suffering from diabetes, pressure ulcers, skin grafts, and amputations. The methodological approach applied to these problems promises to have general application to many fluorescent probes of cellular biochemistry and physiology and to become a generally applied method for analyzing tissue behavior in living systems.