Optical probe for microscopic cancer identification in minute structures

描述(申请人提供)：光学相干断层扫描(OCT)是内窥镜检查的一个新兴分支，可以在体内获得体腔和组织内的横断面图像。前瞻性的OCT探头观察探头前面的组织，以便可以看到和避免狭窄和敏感区域。对于许多临床应用，例如胰腺癌的鉴定，探头应该尽可能窄。我们建议制造和测试保持高光学分辨率但直径仅约一毫米的前瞻探头。唯一具有类似直径的其他前瞻性探测器是反向旋转的棱镜装置，该装置使用高速机械运动，这可能会限制其用途。除了光学(MF)和微电子机械系统(MEMS)方面的专家外，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)方面久负盛名的专家，以及一位经验丰富的内窥镜OCT研究员(JB)。此外，我们的团队有两名杰出的医生(MR和PF)，他们在OCT成像方面拥有丰富的临床和医学研究经验。这些医生认识到临床上对小直径前瞻性OCT探头的迫切需求，以成像胰胆管、乳腺导管、胃和血管组织中的癌症，并期待着该探头的临床应用，包括胰腺病变的诊断成像。这项提议是使用内窥镜探头中常见的梯度折射率(GRIN)透镜来构建紧凑的光学系统。我们提出了一种新的光学结构，在这种结构中，光通过透镜来回传播。这简化了结构，同时保持了图像的高光学质量。最重要的是，它使探头的直径最小化。微型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铸造厂制造。我们中的一位(卫生署)对类似的芯片有相当的经验。组装探测器并不是一件容易的事，因为组件太小了。然而，该集团在类似问题上拥有丰富的经验，并已制定了使用微型定位器来固定和对准部件的计划。经过彻底的台架测试，这些探头将用于亚利桑那大学现有的OCT系统，以成像大鼠模型的胃壁。通过将OCT图像与胃壁的光学显微镜图像进行比较，将验证用于活体、微创胃成像的探头的性能。在R21的概念验证工作之后，未来的工作将集中在开发胰腺癌成像的临床工具上。与公共卫生相关：小直径探头通过对受限区域的组织成像来诊断癌症的需求尚未得到满足，例如狭窄的胰管。用相干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。这项研究将保持前瞻性内窥镜探头的优点，同时将直径从约2.4 mm减少到1 mm。这项新技术将加强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.