Laboratory for Optical and Computational Instrumentation, Department of Biomedical Engineering, University of Wisconsin - Madison, 1550 Engineering Drive, Madison, WI, 53706, USA.
Medical Physics Department, University of Wisconsin - Madison, 1111 Highland Avenue, Madison, WI, 53706, USA.
BMC Cancer. 2017 Feb 6;17(1):102. doi: 10.1186/s12885-017-3090-2.
Ovarian cancer remains the most deadly gynecological cancer with a poor aggregate survival rate; however, the specific rates are highly dependent on the stage of the disease upon diagnosis. Current screening and imaging tools are insufficient to detect early lesions and are not capable of differentiating the subtypes of ovarian cancer that may benefit from specific treatments.
As an alternative to current screening and imaging tools, we utilized wavelength dependent collagen-specific Second Harmonic Generation (SHG) imaging microscopy and optical scattering measurements to probe the structural differences in the extracellular matrix (ECM) of normal stroma, benign tumors, endometrioid tumors, and low and high-grade serous tumors.
The SHG signatures of the emission directionality and conversion efficiency as well as the optical scattering are related to the organization of collagen on the sub-micron size scale and encode structural information. The wavelength dependence of these readouts adds additional characterization of the size and distribution of collagen fibrils/fibers relative to the interrogating wavelengths. We found a strong wavelength dependence of these metrics that are related to significant structural differences in the collagen organization and are consistent with the dualistic classification of type I and II serous tumors. Moreover, type I endometrioid tumors have strongly differing ECM architecture than the serous malignancies. The SHG metrics and optical scattering measurements were used to form a linear discriminant model to classify the tissues, and we obtained high accuracy (>90%) between high-grade serous tumors from the other tissue types. High-grade serous tumors account for ~70% of ovarian cancers, and this delineation has potential clinical applications in terms of supplementing histological analysis, understanding the etiology, as well as development of an in vivo screening tool.
SHG and optical scattering measurements provide sub-resolution information and when combined provide superior diagnostic power over clinical imaging modalities. Additionally the measurements are able to delineate the different subtypes of ovarian cancer and may potentially assist in treatment protocols. Understanding the altered collagen assembly can supplement histological analysis and provide new insight into the etiology. These methods could become an in vivo screening tool for earlier detection which is important since ovarian malignancies can metastasize while undetectable by current clinical imaging resolution.
卵巢癌仍然是最致命的妇科癌症，总体存活率较差；然而，具体的存活率高度依赖于诊断时疾病的阶段。目前的筛查和成像工具不足以检测早期病变，也不能区分可能受益于特定治疗的卵巢癌亚型。
作为当前筛查和成像工具的替代方法，我们利用波长依赖的胶原特异性二次谐波产生 (SHG) 成像显微镜和光散射测量来探测正常基质、良性肿瘤、子宫内膜样肿瘤以及低级别和高级别浆液性肿瘤的细胞外基质 (ECM) 的结构差异。
发射方向和转换效率的 SHG 特征以及光散射与亚微米大小的胶原组织有关，并编码结构信息。这些读出的波长依赖性增加了相对于询问波长的胶原原纤维/纤维的大小和分布的额外特征。我们发现这些指标具有很强的波长依赖性，与胶原组织的显著结构差异有关，并且与 I 型和 II 型浆液性肿瘤的双重分类一致。此外，I 型子宫内膜样肿瘤的 ECM 结构与浆液性恶性肿瘤有很大的不同。SHG 指标和光散射测量用于形成线性判别模型来对组织进行分类，我们在高级别浆液性肿瘤与其他组织类型之间获得了>90%的高精度分类。高级别浆液性肿瘤占卵巢癌的~70%，这种区分在补充组织学分析、了解病因以及开发体内筛查工具方面具有潜在的临床应用。
SHG 和光散射测量提供了亚分辨率信息，当组合使用时，提供了比临床成像模式更高的诊断能力。此外，这些测量能够描绘不同的卵巢癌亚型，并可能有助于治疗方案的制定。了解胶原组装的改变可以补充组织学分析，并为病因提供新的见解。这些方法可能成为早期检测的体内筛查工具，因为卵巢恶性肿瘤在当前临床成像分辨率下无法检测到的情况下就可能转移。
