Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues.
Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues.
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DOI：
10.1088/1361-6560/aa6cf1
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发表时间：
2017-06-21
影响因子：
3.5
通讯作者：
Tichauer KM
中科院分区：
文献类型：
--
作者：
Xu X;Wang Y;Xiang J;Liu JTC;Tichauer KM
传统的通过组织学对组织进行分子评估，如果适用于新鲜的较厚的样本，有可能加强手术切缘中的癌症检测和对3D细胞培养分子环境的监测。然而，在较厚的样品中，尽管反复漂洗，大量的背景染色仍然很常见，这会显著降低图像对比度。最近，“配对试剂”方法--使用对照(非靶向)显像剂的共同给药--已被应用于厚样本染色应用，以解决背景染色问题。到目前为止，这些方法包括(1)简单的比率计量法，它对数据中的噪声相对不敏感，但精度取决于染色方案和样品的特性；(2)复杂的成对试剂动力学模型法，它更准确，但对噪声更敏感，需要精确的连续漂洗方案。在这里，推导并测试了一个新的简化数学模型-漂洗配对剂模型(RPAM)，该模型在以前的模型之间提供了良好的平衡，可以适应任意的漂洗成像协议，并且不需要校准成像系统。RPAM是根据以前的模型进行评估的，并通过与3D细胞培养和肿瘤异种移植模型表面目标生物标记物的估计浓度进行比较来验证。这项工作支持使用RPAM作为一种更好的模型来定量分析局部染色的厚组织中的目标生物标记物浓度，因为它被发现与复杂的配对动力学模型的准确性相匹配，同时保留了比率计量法的低噪声敏感性特征。
Conventional molecular assessment of tissue through histology, if adapted to fresh thicker samples, has the potential to enhance cancer detection in surgical margins and monitoring of 3D cell culture molecular environments. However, in thicker samples, substantial background staining is common despite repeated rinsing, which can significantly reduce image contrast. Recently, “paired-agent” methods—which employ co-administration of a control (untargeted) imaging agent—have been applied to thick-sample staining applications to account for background staining. To date, these methods have included (1) a simple ratiometric method that is relatively insensitive to noise in the data but has accuracy that is dependent on the staining protocol and the characteristics of the sample; and (2) a complex paired-agent kinetic modeling method that is more accurate but is more noise-sensitive and requires a precise serial rinsing protocol. Here, a new simplified mathematical model—the rinsing paired-agent model (RPAM)—is derived and tested that offers a good balance between the previous models, is adaptable to arbitrary rinsing-imaging protocols, and does not require calibration of the imaging system. RPAM is evaluated against previous models and is validated by comparison to estimated concentrations of targeted biomarkers on the surface of 3D cell culture and tumor xenograft models. This work supports the use of RPAM as a preferable model to quantitatively analyze targeted biomarker concentrations in topically stained thick tissues, as it was found to match the accuracy of the complex paired-agent kinetic model while retaining the low noise-sensitivity characteristics of the ratiometric method.
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影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
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