Optical probe for microscopic cancer identification in minute structures

描述（由申请人提供）：光学相干断层扫描（OCT）是内窥镜的一个新兴分支，可以获得体腔和组织内的体内横截面图像。前瞻性OCT探头观察探针前方的组织，以便狭窄和敏感区域可以可视化和避免。对于许多临床应用，如胰腺癌的鉴定，探针应尽可能窄。我们建议制造和测试前视探头，保持高光学分辨率，但直径只有1毫米左右。另一种具有类似直径的前视探头是一种反向旋转的棱镜装置，这种装置使用高速机械运动，可能会限制其效用。除了光学（MF）和微机电系统（MEMS）专家外，我们的团队还包括一位在设计和实施人类疾病动物模型（ML）方面具有丰富经验的委员会认证兽医，一位在癌症研究（SL）方面有良好声誉的专家，以及一位经验丰富的内窥镜OCT研究员（JB）。此外，我们的团队有两位杰出的医生（MR和PF），在OCT成像方面具有丰富的临床和医学研究经验。这些医生认识到临床迫切需要一种小直径前瞻性OCT探头来成像胰腺胆道、乳腺导管、胃和血管组织的癌症，并期待该探头的临床应用，包括胰腺病变的诊断成像。这一建议是构建一个紧凑的光学系统使用梯度折射率（GRIN）透镜经常发现在内窥镜探头。我们提出了一种新的光学结构，其中光通过透镜来回传播。这简化了构造，同时保持了图像的高光学质量。最重要的是，它最小化了探针的直径。微扫描仪芯片将在路易斯安那州立大学开发，并由一家商业MEMS代工厂制造。我们中的一位（DH）对类似的芯片有相当多的经验。组装探针并非易事，因为元件非常小。然而，该小组在类似问题上有丰富的经验，并且计划使用微型定位器来固定和对齐组件。经过彻底的台架测试，探针将在亚利桑那大学现有的OCT系统中用于大鼠模型的胃壁成像。通过比较OCT图像和胃壁光镜图像，验证探针在体内微创胃成像中的性能。在R21的概念验证之后，未来的工作将集中在胰腺癌成像的临床工具的开发上。公共卫生相关性：目前对小直径探针的需求尚未得到满足，该探针通过对受限区域（如狭窄的胰管）的组织进行成像来诊断癌症。近红外光成像的内窥镜探头已经成为一种强大的临床工具。这项研究将保持前视内窥镜探头的优势，同时将直径从约2.4 mm减小到1 mm。这项新技术将提高对大量患者的诊断和治疗。

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) is an emerging branch of endoscopy that obtains in vivo cross-sectional images within body cavities and tissues. Forward looking OCT probes observe tissue ahead of the probe so that strictures and sensitive areas can be visualized and avoided. For many clinical applications, e.g., pancreatic cancer identification, the probe should be as narrow as possible. We propose to fabricate and test forward looking probes that maintain high optical resolution but are only about one mm in diameter. The only other forward-looking probe with a comparable diameter is a counter-rotating prism device that uses high speed mechanical motions that may limit its utility. In addition to experts in optics (MF) and Micro Electrical Mechanical Systems, or MEMS (DH), our team includes a board certified veterinarian surgeon with extensive experience in the design and implementation of animal models for human diseases (ML), a well established expert in cancer research (SL), and an experienced endoscopic OCT researcher (JB). In addition our team has two distinguished medical doctors (MR and PF) with extensive clinical and medical research experience with OCT imaging. These doctors recognize an urgent unmet clinical need for a small diameter forward looking OCT probe to image cancers in pancreatico-biliary, breast ductal, gastric, and vascular tissues, and are looking forward to clinical applications of the probe, including diagnostic imaging of pancreatic lesions. This proposal is to construct a compact optical system using the graded index (GRIN) lenses often found in endoscopic probes. We propose a novel optical configuration in which the light travels back and forth through the lens. This simplifies construction while preserving the high optical quality of the image. Most importantly, it minimizes the diameter of the probe. The micro-scanner chip will be developed at LSU and fabricated by a commercial MEMS foundry. One of us (DH) has had considerable experience with similar chips. Assembling the probe is not trivial because the components are so small. However, the group has extensive experience with similar problems and a plan using micro-positioners to hold and align the components is in place. After thorough bench testing, the probes will be used in an existing OCT system at the University of Arizona to image the gastric wall in a rat model. The performance of the probes for in vivo, minimally invasive gastric imaging will be validated by comparing OCT images to light microscopic images of the gastric wall. After the proof-of-concept efforts in this R21, future work will focus on development of a clinical tool for pancreatic cancer imaging. PUBLIC HEALTH RELEVANCE: There is an unmet need for small diameter probes to diagnose cancer by imaging tissue in restricted areas, such as in narrow pancreatic ducts. Endoscopic probes that image with coherent near-infrared light have emerged as a powerful clinical tool. This investigation will maintain the advantages of a forward looking endoscopic probe while reducing the diameter from about 2.4 mm to 1 mm. This new technology will enhance the diagnosis and treatment of a significant patient population.