Engineering an ultrathin and flexible CARS endoscope

描述(申请人提供)：疾病的诊断和病变组织的手术切除依赖于光学成像，训练有素的人类观察者可以清楚地区分健康组织和正常组织。目前使用的染色和生物标记物有助于区分细胞和组织结构的化学和形态。然而，在体内使用这些标记物、生物标记物和纳米颗粒对于常规临床实践和疾病诊断只在体外进行，具有安全性和监管方面的问题。尽管如此，医学上还是需要在活体内获得这种分子特异性的高分辨率成像。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亚细胞图像分辨率的无标记化学对比度。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，而看起来不会损害活组织。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技术带入临床。另一种与相干拉曼散射兼容的内窥镜技术，如相干反斯托克斯拉曼散射(CARS)，使用扫描光纤以视频速率扫描激光以形成图像。这项技术从超薄而灵活的内窥镜中产生高质量的基于激光的图像。在这个项目中，正在进行具体的设计改进，以生产第一个超薄和灵活的内窥镜，用于以临床上可接受的内窥镜组织诊断和手术的图像采集速率进行相干拉曼散射。特殊照明光纤和微光学透镜组件将定制设计、制造并在组织上进行测试。这种新型内窥镜的性能将与一系列量化里程碑进行比较，并直接与组织学进行比较。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成像活组织的能力。这种技术的未来用途将是直接和快速地评估肿瘤边缘和其他病变组织，而不必在手术和内窥镜检查期间进行重复的活组织检查。 与公共健康相关：将设计和开发一种新型的微型内窥镜，它可以生成特定分子突出显示的视频图像，而不会在生命系统中添加任何药物、化学物质或颗粒。这项技术使用扫描的激光，这种激光不被细胞吸收，但可以帮助确定组织的疾病状态，而不需要取出任何组织进行病理检查。

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.