Strategies for High-Resolution Imaging of Epithelial Ovarian Cancer by Laparoscopic Nonlinear Microscopy
Strategies for High-Resolution Imaging of Epithelial Ovarian Cancer by Laparoscopic Nonlinear Microscopy
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DOI：
10.1593/tlo.09310
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发表时间：
2010-06-01
影响因子：
5
通讯作者：
Zipfel, Warren R.
中科院分区：
文献类型：
--
作者：
Williams, Rebecca M.;Flesken-Nikitin, Andrea;Zipfel, Warren R.
卵巢癌由于发现较晚，仍然是妇科癌症中最常见的致死性疾病。在这里，通过使用人类标本和三种小鼠卵巢癌模型，我们测试了非线性成像方法的可行性，多光子显微镜（MPM）和二次谐波发生（SHG）作为卵巢癌诊断的补充工具。我们证明，MPM/SHG的内在组织发射允许可视化的未固定的，未切片的，和未染色的组织在一个分辨率相当于常规处理的组织切片。除了允许正常和肿瘤组织之间的歧视，根据病理标准，该方法有利于标本的形态学评估和检测卵巢表面上皮细胞的非常早期的细胞变化。细胞内源性荧光和胶原结构改变的红移已被确定为常规病理技术无法辨别的额外癌症相关变化。重要的是，在体内腹腔镜MPM/SHG的可行性证明了使用“棒”的目标透镜。通过低放大率识别组织蛋白酶活性指标，然后进行MPM腹腔镜成像，进一步促进了肿瘤病变的活体检测。综上所述，这些结果表明，MPM可能是可翻译的临床设置作为内窥镜的方法，适合高分辨率的光学活检，以及病理学工具，快速初步评估卵巢癌样本。
Ovarian cancer remains the most frequently lethal of the gynecologic cancers owing to the late detection of this disease. Here, by using human specimens and three mouse models of ovarian cancer, we tested the feasibility of nonlinear imaging approaches, the multiphoton microscopy (MPM) and second harmonic generation (SHG) to serve as complementary tools for ovarian cancer diagnosis. We demonstrate that MPM/SHG of intrinsic tissue emissions allows visualization of unfixed, unsectioned, and unstained tissues at a resolution comparable to that of routinely processed histologic sections. In addition to permitting discrimination between normal and neoplastic tissues according to pathological criteria, the method facilitates morphometric assessment of specimens and detection of very early cellular changes in the ovarian surface epithelium. A red shift in cellular intrinsic fluorescence and collagen structural alterations have been identified as additional cancer-associated changes that are indiscernible by conventional pathologic techniques. Importantly, the feasibility of in vivo laparoscopic MPM/SHG is demonstrated by using a "stick" objective lens. Intravital detection of neoplastic lesions has been further facilitated by low-magnification identification of an indicator for cathepsin activity followed by MPM laparoscopic imaging. Taken together, these results demonstrate that MPM may be translatable to clinical settings as an endoscopic approach suitable for high-resolution optical biopsies as well as a pathology tool for rapid initial assessment of ovarian cancer samples.