Full polarization characterization by OCT

描述（由申请人提供）：拟议研究的长期目标是开发一种新型的非侵入性工具，用于表面病变的显微成像，包括癌症和烧伤。短期目标是将所提出的技术应用于小动物成像。本文提出的穆勒矩阵光学相干断层成像技术（OCT）首次在微观尺度（约10微米）下实时成像完整生物组织的完整偏振特性。光偏振特性是生理状态的敏感指标，如胶原含量和生物组织异常，如坏死，它们可以为成像提供新的对比机制。最初，这项技术可能会对小动物实验研究产生影响，因为它可以减少所需的动物数量和进行研究所需的时间，还可以改善研究的时间相关性。除了即时应用之外，这项技术还具有检测各种浅表人类疾病的潜力，例如口腔癌、皮肤癌、宫颈癌、结肠癌和膀胱癌以及皮肤烧伤，这些疾病可以直接检测，也可以通过内窥镜检测，正如传统oct已经证明的那样，Mueller矩阵可以完全表征任何材料的极化特性。申请人小组率先采用了Mueller-matrix OCT，并证明了这种新的成像方式可以显示传统OCT无法观察到的组织结构。Mueller-matrix OCT已经在烧伤中显示了惊人的极化对比。提出的研究的具体目的如下，其中动物实验将具有双重焦点：皮肤癌成像（动物模型1）和烧伤成像（动物模型2）。目的1。开发自由空间Mueller-matrix OCT系统，对生物组织的Mueller矩阵进行实时深度和横向分辨率成像。目标2。表征所提出的系统的能力，并了解OCT偏振对比的起源，通过成像组织样本离体。将穆勒矩阵图像与常规显微镜和偏振光显微镜的相应组织学结果进行比较，并确定穆勒矩阵图像与组织学结构之间的关系。目标3。利用光纤进一步发展自由空间穆勒矩阵OCT系统，并构建用于体内应用的手持式探针。将光纤系统的实验结果与原自由空间系统的实验结果进行比较。目标4。通过在小鼠模型（动物模型1）中对体内皮肤癌成像来表征所提出的手持式探针的能力。与常规显微镜和偏振光显微镜的组织学结果相比，检测皮肤癌的位置、大小和穆勒基质对比。在动物模型中分析和描述皮肤癌的时间进展。目标5。通过在迷你猪模型（动物模型2）中对体内皮肤烧伤成像来表征所提出的手持式探针的能力。检测皮肤烧伤的横向范围、深度和穆勒基质对比，并与常规显微镜和偏光显微镜的组织学结果进行比较。分析和描述动物模型烧伤的时间愈合过程。

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to develop a novel, non-invasive tool for microscopic imaging of superficial lesions, including cancers and burns. The short-term goal is to apply the proposed technology in small-animal imaging. The proposed technique, Mueller-matrix optical coherence tomograph, (OCT), can image in real time the complete polarization properties of intact biological tissues for the first time at the microscopic scale (about 10 microns) in vivo. Optical polarization properties are sensitive indicators of physiological states such as the collagen content and abnormalities of biological tissues such as necrosis, and they can provide novel contrast mechanisms for imaging. Initially, this technology will likely have an impact on small-animal experimental studies because it can reduce the number of animals needed and the time required to conduct a study and can also improve the temporal correlation of a study. In addition to the immediate applications, this technology has the potential to detect various superficial human diseases--such as oral, skin, cervical, colon, and bladder cancers as well as skin burns--that can be accessed either directly or endoscopically as already demonstrated by conventional OCT. Mueller matrices can completely characterize the polarization properties of any material. The applicants' group pioneered Mueller-matrix OCT and demonstrated that this new imaging modality reveals tissue structures that are not observable with conventional OCT. Striking polarization contrast has already been shown in burns by Mueller-matrix OCT. The specific aims of the proposed research are as follows, in which the animal experiments will have dual foci: the imaging of skin cancers (animal model 1) and the imaging of burns (animal model 2). Aim 1. Develop a free-space Mueller-matrix OCT system to image Mueller matrices of biological tissues with both depth and lateral resolutions in real time. Aim 2. Characterize the capability of the proposed system and understand the origin of OCT polarization contrast by imaging tissue samples ex vivo. Compare the Mueller-matrix images with the corresponding histological results from both conventional and polarization light microscopes and identify the relationships between the Mueller-matrix images and the histological structures. Aim 3. Further develop the free-space Mueller-matrix OCT system using fiber optics and construct a hand-held probe for in vivo applications. Compare the experimental results from the fiber-optic system with those from the original free-space system. Aim 4. Characterize the capability of the proposed hand-held probe by imaging skin cancers in vivo in a mouse model (animal model 1). Detect the location, size, and Mueller-matrix contrast of skin cancers in comparison with the histological results from both conventional and polarization light microscopes. Analyze and characterize the temporal progression of skin cancer in the animal model. Aim 5. Characterize the capability of the proposed hand-held probe by imaging skin burns in vivo in a mini-pig model (animal model 2). Detect the lateral extent, depth, and Mueller-matrix contrast of skin burns in comparison with the histological results from both conventional and polarization light microscopes. Analyze and characterize the temporal healing process of burns in the animal model.