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FOXP3-stained image analysis for follicular lymphoma: Optimal adaptive thresholding with maximal nucleus coverage

机译:滤泡性淋巴瘤的FOXP3染色图像分析:具有最大细胞核覆盖率的最佳自适应阈值

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Immunohistochemical detection of FOXP3 antigen is a usable marker for detection of regulatory T lymphocytes (TR) in formalin fixed and paraffin embedded sections of different types of tumor tissue. TR plays a major role in homeostasis of normal immune systems where they prevent auto reactivity of the immune system towards the host. This beneficial effect of TR is frequently "hijacked" by malignant cells where tumor-infiltrating regulatory T cells are recruited by the malignant nuclei to inhibit the beneficial immune response of the host against the tumor cells. In the majority of human solid tumors, an increased number of tumor-infiltrating FOXP3 positive TR is associated with worse outcome. However, in follicular lymphoma (FL) the impact of the number and distribution of TR on the outcome still remains controversial. In this study, we present a novel method to detect and enumerate nuclei from FOXP3 stained images of FL biopsies. The proposed method defines a new adaptive thresholding procedure, namely the optimal adaptive thresholding (OAT) method, which aims to minimize under-segmented and over-segmented nuclei for coarse segmentation. Next, we integrate a parameter free elliptical arc and line segment detector (ELSD) as additional information to refine segmentation results and to split most of the merged nuclei. Finally, we utilize a state-of-the-art super-pixel method, Simple Linear Iterative Clustering (SLIC) to split the rest of the merged nuclei. Our dataset consists of 13 region-of-interest images containing 769 negative and 88 positive nuclei. Three expert pathologists evaluated the method and reported sensitivity values in detecting negative and positive nuclei ranging from 83-100% and 90-95%, and precision values of 98-100% and 99-100%, respectively. The proposed solution can be used to investigate the impact of FOXP3 positive nuclei on the outcome and prognosis in FL.
机译:FOXP3抗原的免疫组织化学检测是检测不同类型肿瘤组织的福尔马林固定和石蜡包埋切片中调节性T淋巴细胞(TR)的有用标记。 TR在正常免疫系统的体内平衡中起主要作用,在正常体内,它们可阻止免疫系统对宿主的自发反应。 TR的这种有益作用经常被恶性细胞“劫持”,其中恶性细胞核吸收肿瘤浸润的调节性T细胞以抑制宿主对肿瘤细胞的有益免疫应答。在大多数人类实体瘤中,肿瘤浸润性FOXP3阳性TR的增加与预后差有关。但是,在滤泡性淋巴瘤(FL)中,TR的数量和分布对结局的影响仍然存在争议。在这项研究中,我们提出了一种新的方法来检测和枚举从FL活检的FOXP3染色图像中的核。所提出的方法定义了一种新的自适应阈值处理程序,即最佳自适应阈值处理(OAT)方法,该方法旨在最小化用于粗分割的分割不足和分割过度的核。接下来,我们集成无参数的椭圆弧和线段检测器(ELSD)作为附加信息,以细化分割结果并拆分大部分合并的核。最后,我们利用最先进的超像素方法,简单线性迭代聚类(SLIC)来分割其余的合并核。我们的数据集包含13个感兴趣的区域图像,其中包含769个负核和88个正核。三名专家病理学家评估了该方法,并报告了检测负核和正核的灵敏度值,分别为83-100%和90-95%,精确度值分别为98-100%和99-100%。所提出的解决方案可用于调查FOXP3阳性核对FL的结局和预后的影响。

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