Quantitative imaging of collagen morphology in human scars

点击翻译按钮获取中文摘要

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.