University of Illinois at Urbana-Champaign, Beckman Institute of Advanced Science and Technology, Quantitative Light Imaging Laboratory, Urbana, Illinois, United StatesbUniversity of Illinois at Urbana-Champaign, Department of Electrical and Computer Engineering, Urbana, Illinois, United States.
University of Illinois at Urbana-Champaign, Beckman Institute of Advanced Science and Technology, Quantitative Light Imaging Laboratory, Urbana, Illinois, United StatescUniversity of Illinois at Urbana-Champaign, Department of Bioengineering, Urbana, Illinois, United StatesdUniversity of California, Biomedical Engineering Department, Davis, California, United States.
J Biomed Opt. 2017 Jun 1;22(6):66016. doi: 10.1117/1.JBO.22.6.066016.
The current practice of surgical pathology relies on external contrast agents to reveal tissue architecture, which is then qualitatively examined by a trained pathologist. The diagnosis is based on the comparison with standardized empirical, qualitative assessments of limited objectivity. We propose an approach to pathology based on interferometric imaging of “unstained” biopsies, which provides unique capabilities for quantitative diagnosis and automation. We developed a label-free tissue scanner based on “quantitative phase imaging,” which maps out optical path length at each point in the field of view and, thus, yields images that are sensitive to the “nanoscale” tissue architecture. Unlike analysis of stained tissue, which is qualitative in nature and affected by color balance, staining strength and imaging conditions, optical path length measurements are intrinsically quantitative, i.e., images can be compared across different instruments and clinical sites. These critical features allow us to automate the diagnosis process. We paired our interferometric optical system with highly parallelized, dedicated software algorithms for data acquisition, allowing us to image at a throughput comparable to that of commercial tissue scanners while maintaining the nanoscale sensitivity to morphology. Based on the measured phase information, we implemented software tools for autofocusing during imaging, as well as image archiving and data access. To illustrate the potential of our technology for large volume pathology screening, we established an “intrinsic marker” for colorectal disease that detects tissue with dysplasia or colorectal cancer and flags specific areas for further examination, potentially improving the efficiency of existing pathology workflows.
当前的外科病理学实践依赖于外部对比剂来揭示组织结构，然后由经过培训的病理学家进行定性检查。诊断是基于与标准化经验、定性评估的比较，这些评估的客观性有限。我们提出了一种基于“未染色”活检的干涉成像的病理学方法，该方法为定量诊断和自动化提供了独特的能力。我们开发了一种基于“定量相位成像”的无标记组织扫描仪，它可以绘制出视场中每个点的光程，从而生成对“纳米级”组织结构敏感的图像。与定性的染色组织分析不同，染色组织分析受到颜色平衡、染色强度和成像条件的影响，光程测量是内在定量的，即可以在不同的仪器和临床站点之间比较图像。这些关键特性允许我们自动化诊断过程。我们将干涉光学系统与高度并行的专用软件算法配对，用于数据采集，使我们能够以与商业组织扫描仪相当的吞吐量进行成像，同时保持对形态的纳米级敏感性。基于测量的相位信息，我们实现了用于成像期间自动对焦的软件工具，以及图像存档和数据访问。为了说明我们的技术在大容量病理学筛查中的潜力，我们为结直肠疾病建立了一个“内在标志物”，该标志物可以检测出具有发育不良或结直肠癌的组织，并标记出特定区域进行进一步检查，从而可能提高现有病理学工作流程的效率。
