Laser endoscopy for guided biopsy in the bile duct

描述（由申请人提供）：本申请涉及广泛的挑战领域（06）启用技术和特定的挑战主题06-DK-103：启用成像技术。在胆管良性和恶性狭窄之间的确定是困难的。虽然非侵入性成像方式可以定位狭窄，但由于不存在生物标志物，因此在没有细胞和组织的光学测量的情况下无法做出明确的诊断。经口胆管镜检查是对胆管进行光学成像的侵入性最小的方法，但要到达狭窄处需要长、柔性和小直径的内窥镜。用于所获取图像中的每个像素的成像传感器或光纤的当前技术不允许内窥镜检查和高分辨率内窥镜检查，使得临床医生在对胆管成像时合法地失明。提出了一种新技术，在导管尖端放置一个小型微型扫描仪，使刚性尖端仅为9 mm，弯曲半径为6 mm的坚固柔性轴。以前，这种带有远端微扫描器的导管镜可以在30 Hz（视频速率）下采集600行彩色图像，并已在生猪中进行胆管成像。在本提案中，将为新的可操控“带眼导丝”开发增加头端弯曲和将光学分辨率加倍至HDTV（1024线）。申报的新型带眼导丝直径为1.2 - 1.6 mm，约为标准导丝直径的两倍。新的套管式刷子和镊子工具将被开发用于图像引导活检，并首先在猪胆管中进行测试，然后在至少20名人类受试者中进行测试，其中包括良性和恶性狭窄原因。由于1 mm导管镜可能能够穿过狭窄，因此将测量任何疑似癌的分期或侧向范围。该扫描导管镜的其他临床优势是，低功率、红色、绿色和蓝色激光本身是窄带的，增强的光谱成像和变焦放大率都是用户控制的实时功能。通过增强图像对比度和特征尺寸，可以改善活检部位的选择，并且在内窥镜逆行胆管造影术过程中，临床医生不再必须在法律上失明。在未来，当胆管监测更加普遍时，可以改变激光照明来测量早期癌症和癌前病变的荧光生物标志物特征，而不会增加探针的尺寸，成本或复杂性。 公共卫生相关性：确定胆管疾病的诊断和程度是极其困难的，并且利用当前的内窥镜技术，这些决定是在临床医生法律上盲目的情况下做出的。因此，提出了一种新的用于胆管疾病的图像引导诊断的激光扫描技术，其提供高质量的视频成像。这项新技术将被开发和测试，以提高诊断胆管疾病的效率和准确性，特别是来自良性并发症的癌症，这些并发症可以模仿这种致命的疾病。该项目的目标是提供更高准确性和诊断率的活检，同时引入侵入性较小的临床仪器。拥有一种更有效、侵入性更小的临床仪器有望降低管理不确定性胆管狭窄患者的总体成本。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-DK-103: Enabling Technologies in Imaging. Determination between benign and malignant strictures in the bile ducts is difficult. Although non-invasive imaging modalities can locate the stricture, a definitive diagnosis cannot be made without an optical measurement of cells and tissue as no biomarker exists. Peroral cholangioscopy is the least invasive method to optically image the bile ducts but to reach a stricture requires a long, flexible, and small-diameter endoscope. The current technology of an imaging sensor or optical fiber for each pixel in the acquired image does not allow both ultrathin and high-resolution endoscopy, making the clinician legally blind when imaging the bile duct. A new technology is proposed that puts a small microscanner at the tip of a catheter, making a rigid tip of only 9-mm and a rugged flexible shaft with a 6-mm bending radius. Previously this catheterscope with distal-tip microscanner can acquire 600-line color images at 30 Hz (video rate) and bile duct imaging has been performed in a live pig. In this proposal, the addition of tip bending and a doubling of the optical resolution to HDTV (1024 lines) will be developed for a new steerable "guidewire with eyes". The proposed new guidewire with eyes will be 1.2 to 1.6 mm in diameter, approximately twice the diameter of a standard guidewire. New cannula-style brush and forceps tools will be developed for image-guided biopsy and tested first in pig bile ducts and then in at least 20 human subjects, split between having benign and malignant causes of the stricture. Since the 1-mm catheterscope may be able to traverse the stricture, staging or lateral extent of any suspected carcinoma will be measured. Additional clinical advantages of this scanning catheterscope are that the low-power, red, green, and blue laser light is inherently narrow band and both enhanced spectral imaging and zoom magnification are user-controlled real-time features. By enhancing image contrast and feature size, biopsy site selection can be improved and no longer does the clinician have to be legally blind during an endoscopic retrograde cholangiography procedure. In the future, when bile duct surveillance is more common, the laser illumination can be changed to measure fluorescence biomarker signatures of early cancer and pre-cancer without adding size, cost, or complexity to the probe. PUBLIC HEALTH RELEVANCE: Determining diagnosis and extent of disease in the bile duct is extremely difficult, and with current endoscope technology these decisions are being made with clinicians legally blind. Therefore, a new laser scanning technology for image-guided diagnosis of disease in the bile duct is proposed that affords high quality video imaging. This new technology will be developed and tested for the purpose of improving the efficiency and accuracy of diagnosing bile duct diseases, especially cancer from benign complications that can mimic this deadly disease. The goal of this project is to provide biopsies with higher accuracy and diagnostic yields, while introducing a less invasive clinical instrument. Having a more effective and less invasive clinical instrument is expected to lower overall cost for managing patients with indeterminate biliary strictures.