Polarized Light Laparascopy of Occult Cancer Metastases

总结： 对于癌症患者，预后和治疗选择从根本上依赖于对肿瘤的分期评估。 潜在的癌症，即，确定是否存在远处转移。尽管有所改善 在可用的分期工具中，包括横截面放射成像和腹腔镜检查， 胃肠道和妇科恶性肿瘤的分期差异很大， 作为一个共同的问题。高达30%的患者与这些恶性肿瘤有远处复发的癌症 仅在美国，这相当于约15，000例 患者每年这些复发性腹膜炎常发生在腹膜表面， 这是因为常规方法在初始分期期间不能检测到小转移（通常<3 mm）。 我们的目标是通过增加腹腔镜检查的能力， 发现这种微小的隐匿性转移为了实现这一目标，我们将设计和构建一个光学附件 用于标准腹腔镜，这将允许偏振光成像（目标1）。偏振门控是一个很好的- 这是已知的技术，以突出显示表面特征，并因此预期增加检测灵敏度， 浅表腹膜转移将通过比较标准与 用于检测组织内尺寸明确的高度散射物体的偏振门控腹腔镜检查 沉积在离体动物腹膜组织表面上的肿瘤和癌细胞簇（Aim 2）。 最后，极化门控腹腔镜的可行性和安全性将在一个小型的首次在人类 研究（目标3）。我们的配件的光学设计将依赖于一个可拆卸的套筒与外部光学过滤器， 腹腔镜的远端，以线性地照射用于照亮腹膜的白色光。在 在近端，半波液晶延迟器将允许图像的自动、接近视频速率的收集 相对于入射在所述偏振层上的偏振光以平行或垂直的几何形状偏振。 腹膜这些正交偏振图像的总和可用于重建标准腹腔镜检查 图像，而它们的差异预计将显示出增强的对比度，用于观察表面特征。到 为了表征这种方法的敏感性，我们将首先使用组织模型进行研究， 我们确定散射对比度，大小和深度特征的特点，可以检测和 使用偏振的相应水平的检测增强。体外研究将在 正常大鼠暴露的腹膜，其上沉积有小的癌细胞簇（亚mm-3 mm大小 来证实我们的体外实验结果最后，我们将进行一项有限的研究（10例患者），以评估可行性， 差异偏振光腹腔镜检测成人腹膜转移瘤的安全性 胃肠道或妇科恶性肿瘤。基于非常初步的体外人体组织测量， 与标准腹腔镜检查相比，我们期望使用我们的装置的对比度增强接近两倍。

Summary: For cancer patients, prognosis and treatment selection fundamentally rely on the staging assessment of the underlying cancer, i.e., determining the absence or presence of distant metastases. Despite improvements in the available staging tools, including cross-sectional radiographic imaging and laparoscopy, the accuracy of staging for gastrointestinal and gynecologic malignancies varies tremendously, with “under-staging” considered as a common problem. Up to 30% of patients with these malignancies have distant recurrence of cancer shortly after major resections with curative intent; in the United States alone, this corresponds to about 15,000 patients per year. These recurrences, which often occur on the surface of the peritoneum, are thought to arise from the inability of conventional methods to detect small metastases (typically < 3mm) during initial staging. Our goal is to significantly improve the staging accuracy of peritoneal laparoscopy by increasing its capacity to detect such small, occult metastases. To achieve this goal, we will design and construct an optical accessory for standard laparoscopes, which will allow for polarized light imaging (Aim 1). Polarization-gating is a well- known technique to highlight surface features, and is thus expected to increase the detection sensitivity for superficial peritoneal metastases. This hypothesis will be tested by comparing the efficiency of standard versus polarization-gated laparoscopy for detecting highly scattering objects of well-defined size within tissue phantoms and cancerous cell clusters deposited on the surface of ex vivo animal peritoneal tissues (Aim 2). Finally, the feasibility and safety of polarization-gated laparoscopy will be evaluated in a small first-in-human study (Aim 3). The optical design of our accessory will rely on a removable sleeve with external optical filters at the distal end of the laparoscope, to linearly polarize the white light used to illuminate the peritoneum. At the proximal end, a half-wave liquid crystal retarder will allow for automated, near video-rate collection of images polarized in either parallel or perpendicular geometries relative to the polarized light incident on the peritoneum. The sum of these orthogonally-polarized images can be used to reconstruct standard laparoscopy images, while their difference is expected to show enhanced contrast for observing surface features. To characterize the sensitivity of this approach, we will first perform studies using tissue phantoms that will enable us to identify the scattering contrast, size and depth characteristics of features that can be detected and the corresponding levels of detection enhancement using polarization. Ex vivo studies will be performed on exposed peritoneum of normal rats on which small cancerous cell clusters (sub mm-3mm size) are deposited to confirm our in vitro findings. Finally, we will conduct a limited study (10 patients) to assess feasibility and safety of differentially-polarized light laparoscopy for detection of peritoneal metastases in adult patients with gastrointestinal or gynecologic malignancies. Based on very preliminary ex vivo human tissue measurements, we expect a nearly two-fold contrast enhancement using our device compared to standard laparoscopy.