Engineering an ultrathin and flexible CARS endoscope

描述（由申请人提供）：疾病的诊断和患病组织的手术切除依赖于光学成像，受过训练的人类观察者可以清楚地区分健康组织和正常组织。目前使用的染色剂和生物标志物有助于区分细胞和组织结构的化学和形态。然而，这些染色剂、生物标志物和纳米颗粒的体内使用对于常规临床实践具有安全性和监管问题，并且疾病诊断仅在体外进行。尽管如此，医学上仍需要在活体内获得这种分子特异性高分辨率成像。相干拉曼散射是一种很有前途的技术，它可以在视频速率下提供无标记的化学对比度和亚细胞图像分辨率。这种拉曼信号是由近红外激光产生的，它探测细胞内的化学键，同时不会损害活组织。然而，传统的内窥镜不是基于激光扫描的，因此不适合将这种先进的成像带入临床。与相干拉曼散射（例如相干反斯托克斯拉曼散射（汽车））兼容的替代内窥镜技术使用扫描激光以视频速率形成图像的扫描光纤。该技术可通过可弯曲和柔性内窥镜产生高质量的激光图像。在该项目中，正在进行特定的设计修改，以生产第一个可弯曲和柔性内窥镜，用于以内窥镜组织诊断和手术临床上可接受的图像采集速率进行相干拉曼散射。特殊照明光纤和微型光学透镜组件将进行定制设计、制造和组织测试。该新型内窥镜的性能将与一组定量里程碑进行比较，并与组织学进行直接比较。到这个为期两年的项目结束时，将建立在没有生物标志物的情况下以亚细胞空间和化学分辨率对活组织进行成像的能力。这种技术的未来用途将是直接和快速评估肿瘤边缘和其他病变组织，而无需在手术和内窥镜检查期间进行重复活检。 公共卫生相关性：一种新型的微型内窥镜将被设计和开发，它可以生成视频图像，其中突出显示特定的分子，而无需向生命系统中添加任何药物，化学品或颗粒。该技术使用扫描激光，不被细胞吸收，但可以帮助确定组织的疾病状态，而无需取出任何组织进行病理学检查。

DESCRIPTION (provided by applicant): The diagnosis of disease and surgical removal of diseased tissue relies on optical imaging that the trained human observer can clearly distinguish between healthy and normal tissue. Currently stains and biomarkers are used that help differentiate both the chemistry and morphology of cellular and tissue structures. However, in vivo use of these stains, biomarkers, and nanoparticles have safety and regulatory concerns for routine clinical practice and disease diagnosis is performed only outside the body. Nonetheless, there is medical need to obtain this molecularly- specific high-resolution imaging inside the living human body. Coherent Raman scattering is a promising technology that offers label-free chemical contrast with sub-cellular image resolution at video rates. This Raman signal is generated by near-infrared laser light that probes the chemical bonds within cells while not appearing to damage living tissue. However, traditional endoscopes are not based on laser scanning and thus not suitable for taking this advanced imaging into the clinic. An alternative endoscope technology, compatible with coherent Raman scattering, such as coherent anti-Stokes Raman scattering (CARS), uses a scanning optical fiber that scans laser light to form images at video rates. This technology produces high-quality laser-based images from an ultrathin and flexible endoscope. In this project, specific design modifications are being made to produce the first ultrathin and flexible endoscope for coherent Raman scattering at image acquisition rates that are clinically acceptable for endoscopic tissue diagnosis and surgery. Specialty illumination optical fiber and micro-optical lens assemblies will be custom designed, fabricated, and tested on tissue. The performance of this new endoscope will be compared against a set of quantitative milestones, and for direct comparison to histology. By the end of this two year project, the ability to image living tissue with sub-cellular spatial and chemical resolution without biomarkers will be established. Future uses of such technology will be the direct and rapid assessment of tumor margins and other diseased tissue without having to take repeated biopsies during surgery and endoscopic examination. PUBLIC HEALTH RELEVANCE: A new type of mini-endoscope will be designed and developed that generated video images with specific molecules highlighted without adding any drug, chemical, or particle into the living system. The technique uses scanned laser light that is not absorbed by the cells, but can help determine the disease state of tissue without taking out any tissue for pathology.