Fiber Scanning Stimulated Raman Scattering (SRS) Endoscope

描述（由申请人提供）：在肿瘤手术中，实现最大程度的肿瘤切除而对健康组织的附带损害最小是一个挑战，因为没有可靠的视觉线索来指示切除的完整性。相反，在显微镜下，肿瘤和非浸润组织之间的差异是明显的。然而，传统的组织病理学技术要求将组织从手术视野中移除，进行处理和染色。因此，组织病理学既不能原位进行，也不能实时进行。手术效果不佳在脑癌手术中极为常见（美国每年有64,000例）。通过术后MRI， 76%的病例在手术腔中发现了可以安全切除的肿瘤。在大多数病例中，肿瘤复发发生在切除腔附近。在手术时实时成像切除边缘的活体技术将是非常可取的。受激拉曼散射（SRS）显微镜结合了传统组织学的形态学和化学成像的优点，但不需要去除组织或染色。因此，它可以在现场和实时使用。的映射

DESCRIPTION (provided by applicant): Achieving maximal tumor removal with minimal collateral damage to healthy tissue is a challenge in tumor surgery, because there are no reliable visual cues to indicate completeness of resection. In contrast, on a microscopic level, the differences between tumor and non-infiltrated tissues are clear. However, traditional histopathologic techniques require that the tissue be removed from the operative field, processed, and stained. Therefore, histopathology can neither be performed in situ nor in real-time. Suboptimal surgical results are extremely common in brain cancer surgery (64,000 US cases/year). Tumor that could have been safely removed has been identified in the operative cavity in 76% of cases, by post-operative MRI. In most cases, tumor recurrence occurs near the resection cavity. An in vivo technique for real-time imaging of the resection margins at the time of surgery would be highly desirable. Stimulated Raman Scattering (SRS) microscopy combines the advantages of morphological and chemical imaging of traditional histology but without requiring tissue removal or dye staining. It can thus be used in situ and in real- time. Mapping of a 2x2cm2 area can be achieved in approximately 2.5min and has the potential to provide quantitative clinical endpoints for brain tumor surgery. The accuracy of tumor detection in an animal model of glioblastoma with a state-of-the-art research-type SRS microscope has been shown to be comparable to traditional H&E microscopy, without requiring tissue removal or staining. However, there is no system that meets all the requirements for clinical SRS imaging. The present proposal is to develop a handheld SRS endoscope that is suited for use in a surgical cavity and achieves diagnostically relevant image quality and imaging speed. The goal of Phase 1 is to obtain proof-of-concept by leveraging established technologies, to the largest degree possible. None of the components have been designed for the purpose of SRS endoscopy but should be able to be modified to work for that purpose, with predictable limitations. If Phase 1 proof-of-concept is achieved, custom components would be designed in Phase 2 to improve image quality and speed. The PI has assembled a multidisciplinary team of academic, industrial and clinical thought leaders for laser engineering, miniaturized scanner development, optical design, and clinical validation. The specific aims are to (1) develop an all-fiber scanning fiber SRS endoscope and (2) rigorously demonstrate that the SRS endoscope produces diagnostically relevant image quality.