基于强度传输方程和微分干涉相差显微镜的定量相位成像及其在乳腺癌诊断中的应用

Quantitative Phase Imaging Based on Transport-of-Intensity Equation and Differential Interference Contrast Microscope and Its Application in Breast Cancer Diagnosis

结合光的强度传输方程和微分干涉相差(DIC)显微镜设计了一套定量相位显微成像系统,用以同时揭示癌变过程组织微结构的三维改变以及由此导致的光散射特性的变化。采集257例乳腺浸润性导管癌未染色石蜡包埋组织切片的DIC图像,由强度传输方程获得其二维分布相位图,并由散射相定理进一步导出空间分辨的光散射特性图。结果表明:乳腺浸润性导管癌的分级与组织的约化散射系数、各向异性因子高度相关;随着癌症分级的提高,乳腺浸润性导管癌组织的约化散射系数显著增大,各向异性因子显著减小。利用所得的光散射特性参数预测乳腺浸润性导管癌的癌症分级,准确率可达88%。DIC显微镜自身具有的无标记、高图像衬度等特点使得该实验方法也可以用于新鲜组织或冰冻组织切片,并可用于实时、快速的病理诊断。

A quantitative phase imaging system capable of revealing three-dimensional changes of microstructure and light scattering properties of cancer tissues is developed based on the transport-of-intensity equation using the differential interference contrast （DIC） microscope. The DIC images of unstained paraffin embedded tissue sections of 257 patients with invasive ductal carcinoma are acquired with the quantitative phase imaging system. The corresponding two-dimensional phase maps are obtained with the calculation of the transport-of-intensity equation. The spatially resolved optical properties of the tissues are computed from the two-dimensional phase maps using the scattering-phase theorem afterwards. The results show that the grade of invasive ductal carcinoma has strong correlation with reduced scattering coefficients and anisotropy of tissues. When the grade of invasive ductal carcinoma increases, the reduced scattering coefficient of invasive ductal carcinoma tissues increases significantly,while the anisotropy decreases significantly. The retrieved optical parameters are shown to distinguish invasive ductal carcinoma with different grades with a high accuracy of 88%. Owing to the label-free and high-contrast characteristics of DIC microscope, the proposed approach is also applicable for fresh or frozen tissues, and may have promising applications in real-time and rapid cancer diagnosis.