Polarized Light Laparascopy of Occult Cancer Metastases

摘要： 对于癌症患者来说，预后和治疗选择从根本上取决于对 潜在的癌症，即决定是否存在远处转移。尽管有了改进 在现有的分期工具中，包括横断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，认为“分期不足”。 作为一个常见的问题。高达30%的这些恶性肿瘤患者有远处复发的癌症 在有治疗意图的大手术后不久；仅在美国，这相当于大约15,000 每年的病人数量。这些通常发生在腹膜表面的复发被认为是发生的。 由于常规方法无法在初始分期期间发现微小的转移瘤(通常为3毫米)。 我们的目标是通过增加腹膜腹腔镜术的能力来显著提高其分期准确性 发现如此微小、隐蔽的转移瘤。为了实现这一目标，我们将设计和制造一种光学配件 用于标准的腹腔镜，这将允许偏振光成像(目标1)。偏振选通是一种良好的 已知的突出表面特征的技术，因此有望提高对 腹膜浅表转移。这一假设将通过比较标准和 用于检测组织内大小明确的高度散射物体的偏振门控腹腔镜检查 体外动物腹膜组织表面沉积的幻影和癌细胞群(目标2)。 最后，偏振门控腹腔镜手术的可行性和安全性将在一项小型首例人类试验中进行评估。 研究(目标3)。我们配件的光学设计将依赖于带有外部滤光片的可拆卸套筒 腹腔镜的远端，用来线性偏振用于照亮腹膜的白光。在 近端，半波液晶延迟器将允许自动、接近视频率的图像采集 以平行或垂直几何形状相对于入射到 腹膜。这些正交偏振图像的和可以用于重建标准的腹腔镜术 虽然它们的不同之处预计会显示出增强的对比度，以观察表面特征。至 为了表征这种方法的敏感性，我们将首先使用组织模体进行研究，这将使 US以识别可检测到的地物的散射对比度、大小和深度特征以及 使用偏振进行相应级别的检测增强。体外研究将在 裸露的正常大鼠腹膜，其上有小的癌细胞群(亚毫米-3毫米大小) 以证实我们的体外研究结果。最后，我们将进行一项有限的研究(10名患者)，以评估可行性和 差偏振光腹腔镜检查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， 我们预计，与标准的腹腔镜相比，使用我们的设备可以获得近两倍的对比度增强。

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.