Quantitative imaging of collagen morphology in human scars

摘要 这项拟议研究的总体目标是开发和验证高分辨率双折射成像。这个 胶原蛋白的本征双折射为研究胶原蛋白提供了一个吸引人的对比机制 人类皮肤和疤痕的形态。瘢痕组织中胶原组织的非侵入性表征 将促进临床试验，研究新的治疗方法，通过提供 治疗反应的量化措施。此外，这样的工具还将提供监测的能力， 根据客观指标规划和优化治疗干预措施，并将有助于抗击严重 疤痕形成可能对受影响患者的生活质量造成的后果。然而，目前的双折射 成像方法缺乏分解单个胶原束所需的空间分辨率。 具体目标1提高偏振敏感光学频域成像(PS-1)的空间分辨率 对外直接投资)制度。一种将两个相邻的光谱区域合成为一个更宽的区域的新光源 光谱将使轴向分辨率提高两倍。而短焦距的物镜可以提供较高的横向 决议。为了管理由此产生的景深降低，具有不同焦位的多幅图像 将被收购并合并为单一的高分辨率横断面图。 特定目标2开发并制作了双折射模体以验证PS-OFDI的性能。 模拟组织的模体，由乳胶橡胶制成，包含可控制的小区域，应力- 诱导双折射，将为研究空间分辨率和双折射的极限提供一个有用的目标。 PS-OFDI水平。这些见解将对优化组织双折射重建和 为正确解释生物组织中的双折射特征提供信息。 《特定目标3》将在体外对人体皮肤和疤痕样本进行成像。PS成像的胶原构筑 对外直接投资将与匹配的组织切片进行比较，以建立一个双折射特征目录。 正常的皮肤和疤痕。随着空间分辨率的提高，PS-OFDI将能够分解单个胶原蛋白 束，并提供疤痕组织的全面特征。量化胶原蛋白的图像指标 未来将制定评估疤痕严重程度的体系结构。 总而言之，拟议研究的成功完成将产生、表征和验证 强大的成像方法，用于非侵入性评估人类皮肤的疤痕。

Abstract The overall goal of the proposed research is to develop and validate high-resolution birefringence imaging. The intrinsic birefringence of collagen offers an attractive contrast mechanism to investigate the collagen morphology in human skin and scars. Non-invasive characterization of the collagen organization in scar tissue would facilitate clinical trials that investigate novel therapeutic approaches to reduce scarring by providing quantitative measures of treatment response. In addition, such a tool would also provide the ability to monitor, plan, and optimize therapeutic interventions based on objective metrics, and would help to combat the severe consequences that scarring can have on the quality of life of affected patients. However, current birefringence imaging methods lack the spatial resolution required to resolve individual collagen bundles. Specific Aim 1 improves the spatial resolution of a polarization sensitive optical frequency domain imaging (PS- OFDI) system. A new light source that synthetically combines two adjacent spectral regions into one broader spectrum will improve the axial resolution two-fold. And a short focal length objective lens will offer high lateral resolution. To manage the resulting reduction of the depth of field, multiple images with different focal positions will be acquired and merged into a single, high-resolution cross-sectional view. Specific Aim 2 develops and fabricates birefringence phantoms to validate the performance of PS-OFDI. Tissue-mimicking phantoms, fabricated from latex rubber and containing small zones of controllable, stress- induced birefringence, will provide a useful target to investigate the limits in spatial resolution and birefringence level of PS-OFDI. These insights will be essential for optimizing the reconstruction of tissue birefringence and for informing on the correct interpretation of birefringence features in biological tissues. Specific Aim 3 will image human skin and scar samples ex vivo. The collagen architecture imaged with PS- OFDI will be compared with matching histological sections to establish a catalog of birefringence features in normal skin and scars. With improved spatial resolution, PS-OFDI will be able to resolve individual collagen bundles, and provide comprehensive characterization of scar tissue. Image metrics that quantify the collagen architecture and that could serve in the future to assess scar severity will be developed. Combined, the successful completion of the proposed research would generate, characterize, and validate a powerful imaging method for non-invasive assessment of scarring in human skin.