Measuring Oxygen and Hemoglobin Saturation Distributions in Skin Grafts

描述(由申请人提供)：这项提案概述了一种新产品的开发，以及一种同时测量皮肤皮下PO2和血红蛋白氧饱和度的新方法。这种名为“氧气球”的产品将在皮肤移植、皮肤溃疡和截肢的治疗疗法的开发中得到广泛应用。能够测量皮肤和底层组织之间的PO2，并使用单一产品测量皮肤中的血红蛋白饱和度，这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供应的影响。用最优化方法和多中心模型对不同氧浓度下的“氧球”发光光谱进行了曲线拟合。通常，亚表面发光的多波长强度研究由于吸收成分(氧合和脱氧血红蛋白和黑色素)和组织光散射而导致的光的波长相关衰减而变得复杂。使用“氧气球”的方法学方法将利用这些组分的已知光谱行为来拟合“氧气球”的发光发射光谱，并根据拟合的参数确定PO2和血红蛋白氧饱和度。这一创新的方法代表了在测量创面氧气利用率方面的重大进步，也在使用荧光探针测量体内组织生化和生理方面取得了关键进展。新方法将允许对荧光发射进行多波长分析，以量化覆盖组织中分析物的浓度，同时补偿发射强度随波长变化的衰减。该方法的开发将遵循使用日益复杂的样本矩阵的逐步发展，从缓冲液到血红蛋白溶液，再到皮肤移植。第一阶段研究为发展的三个阶段中的每一个阶段都有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转化为商业产品，用于临床实践。 与公共健康相关：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。除了测量循环中的氧气外，还可以测量组织中特定位置的氧气，这一能力为医生开发方法以促进糖尿病、压疮、皮肤移植和截肢患者的皮肤愈合提供了一个强大的新工具。应用于这些问题的方法论方法有望广泛应用于许多细胞生物化学和生理学的荧光探针，并成为分析生命系统中组织行为的一种普遍应用的方法。

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.