Quantitative imaging of collagen morphology in human scars

摘要 拟议研究的总体目标是开发和验证高分辨率双折射成像。的 胶原蛋白的固有双折射提供了一种有吸引力的对比机制来研究胶原蛋白 人类皮肤和疤痕的形态学。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，以减少疤痕， 治疗反应的定量测量。此外，这种工具还将提供监测能力， 根据客观指标计划和优化治疗干预措施，并将有助于对抗严重的 瘢痕形成可能对受影响患者的生活质量造成的后果。然而，电流双折射 成像方法缺乏分辨单个胶原束所需的空间分辨率。 具体目的1提高了偏振敏感光学频域成像（PS-1）的空间分辨率。 OFDI）体系。一种新的光源，将两个相邻的光谱区域合成为一个更宽的光谱区域。 光谱将提高轴向分辨率的两倍。短焦距物镜透镜将提供高横向 分辨率为了管理由此产生的景深减小，可以使用具有不同焦点位置的多个图像 将被采集并合并到单个高分辨率横截面视图中。 具体目标2开发和制造双折射模型，以验证私营部门对外直接投资的绩效。 组织模拟体模，由乳胶橡胶制成，包含可控的小区域， 诱导的双折射，将提供一个有用的目标，研究限制在空间分辨率和双折射 私营部门对外直接投资水平。这些见解对于优化组织双折射的重建至关重要， 用于告知生物组织中双折射特征的正确解释。 Specific Aim 3将对人体皮肤和疤痕样本进行离体成像。用PS成像的胶原结构- 将对外直接投资与相应的组织学切片进行比较，以建立一个中国的双折射特征目录。 正常的皮肤和疤痕。随着空间分辨率的提高，PS-OFDI将能够分辨单个胶原蛋白， 束，并提供疤痕组织的全面表征。量化胶原蛋白的图像指标 结构，并可在未来用于评估疤痕的严重程度将被开发。 结合起来，成功完成拟议的研究将产生，表征和验证一个 这是一种强大的成像方法，可用于人体皮肤瘢痕的非侵入性评估。

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.