Intraoperative Polarization-Sensitive OCT for Assessing Breast Tumor Margins

总结 乳腺癌是一个全球性的医疗保健负担，不仅对诊断患有这种疾病的患者，而且对他们的 家人和朋友乳腺癌的手术治疗虽然成功，但有很大的局限性， 增加患者焦虑，增加成本，并可能增加局部复发和终身术后的风险 并发症主要的局限性源于缺乏术中显微镜评估的手术 肿瘤边缘我们的学术，临床和工业代表的凝聚力和生产力的团队， 成功开发并首次展示了术中光学相干的使用 在乳腺癌手术期间使用新的用于肿瘤边缘的体内人体成像的断层扫描（OCT）， 手持式手术成像探头。此外，干涉合成孔径的发展和使用 用于体内成像的ISAM显微镜（ISAM）已经显示出分辨率和景深的重要改进。 尽管取得了这些进展，但在识别组织微观结构方面仍然存在挑战，特别是在正常组织之间。 纤维间质和致密的肿瘤组织，它们都是高度散射的结构。为了应付这些挑战， 我们提出了偏振敏感OCT（PS-OCT）和PS-ISAM的新颖和创新应用， 在人乳腺癌手术中的术中体内成像，并假设这些将改善 与标准OCT/ISAM相比，阳性乳腺肿瘤边缘的检测灵敏度和特异性。意识到 癌症的存在和进展显著改变了基于胶原的组织微环境， PS-OCT灵敏地检测和量化组织胶原蛋白的双折射，为早期检测提供了可能 癌症和改变的微环境。通过利用ISAM和其他计算光学图像 分割算法，我们可以更充分地表征组织/肿瘤微环境。通过四 具体目标，我们将实施硬件和创新的软件贡献，以构建一个术中 能够实时OCT/ISAM和PS-OCT/PS-ISAM的多模式系统，然后使用该系统进行研究 这些成像模式在临床人体研究中的性能，以确定 离体和体内PS-OCT/PS-ISAM优于标准OCT/ISAM，并与标准治疗评估进行比较 包括术后组织病理学和术中视觉/触觉提示。圆满完成 该项目预计将建立这些新的光学成像技术的临床术中使用， 目标是降低目前乳腺癌外科治疗中不可接受的高再手术率。

SUMMARY Breast cancer is a global healthcare burden, not only for the patients diagnosed with this disease, but also their families and friends. The surgical treatment of breast cancer, while successful, has significant limitations that increase patient anxiety, increase costs, and can increase the risk for local recurrence and lifelong post-operative complications. A primary limitation stems from the lack of an intraoperative microscopic assessment of surgical tumor margins. Our cohesive and productive team with academic, clinical, and industrial representation has successfully developed and demonstrated for the first time the use of intraoperative optical coherence tomography (OCT) for in vivo human imaging of tumor margins during breast cancer surgery using a novel handheld surgical imaging probe. Additionally, the development and use of interferometric synthetic aperture microscopy (ISAM) for in vivo imaging has shown an important improvement in resolution and depth-of-field. Despite these advances, challenges remain for identifying tissue microstructure, particularly between normal fibrous stroma and dense tumor tissue, which are both highly scattering structures. To address these challenges, we propose the novel and innovative application of polarization-sensitive OCT (PS-OCT) and PS-ISAM for intraoperative in vivo imaging in human breast cancer surgery, and hypothesize that these will improve the detection sensitivity and specificity of positive breast tumor margins over standard OCT/ISAM. Realizing that the presence and progression of cancer significantly alters the collagen-based tissue microenvironment, the use of PS-OCT to sensitively detect and quantify birefringence of tissue collagen offers the potential for earlier detection of cancer and the altered microenvironment. By leveraging ISAM and other computational optical image segmentation algorithms, we can more fully characterize the tissue/tumor microenvironment. Through four specific aims, we will implement hardware and innovative software contributions to construct an intraoperative multi-mode system capable of real-time OCT/ISAM and PS-OCT/PS-ISAM, then use this system to investigate the performance of these imaging modes in clinical human studies to determine the sensitivity and specificity of ex vivo and in vivo PS-OCT/PS-ISAM over standard OCT/ISAM, and against the standard-of-care assessments which include post-operative histopathology and intraoperative visual/tactile cues. The successful completion of this project is expected to establish the clinical intraoperative use of these new optical imaging techniques, with the goal of reducing the current unacceptably high reoperation rates in the surgical treatment of breast cancer.