Fulawka Lukasz, Blaszczyk Jakub, Tabakov Martin, Halon Agnieszka
Molecular Pathology Centre Cellgen, ul. Piwna 13, 50-353, Wroclaw, Poland.
Department of Computational Intelligence, Wroclaw University of Science and Technology, wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
Sci Rep. 2022 Feb 24;12(1):3166. doi: 10.1038/s41598-022-06555-3.
The proliferation index (PI) is crucial in histopathologic diagnostics, in particular tumors. It is calculated based on Ki-67 protein expression by immunohistochemistry. PI is routinely evaluated by a visual assessment of the sample by a pathologist. However, this approach is far from ideal due to its poor intra- and interobserver variability and time-consuming. These factors force the community to seek out more precise solutions. Virtual pathology as being increasingly popular in diagnostics, armed with artificial intelligence, may potentially address this issue. The proposed solution calculates the Ki-67 proliferation index by utilizing a deep learning model and fuzzy-set interpretations for hot-spots detection. The obtained region-of-interest is then used to segment relevant cells via classical methods of image processing. The index value is approximated by relating the total surface area occupied by immunopositive cells to the total surface area of relevant cells. The achieved results are compared to the manual calculation of the Ki-67 index made by a domain expert. To increase results reliability, we trained several models in a threefold manner and compared the impact of different hyper-parameters. Our best-proposed method estimates PI with 0.024 mean absolute error, which gives a significant advantage over the current state-of-the-art solution.
增殖指数(PI)在组织病理学诊断中至关重要,尤其是在肿瘤诊断方面。它是通过免疫组织化学法基于Ki-67蛋白表达来计算的。PI通常由病理学家对样本进行视觉评估来确定。然而,由于观察者内和观察者间的差异较大且耗时,这种方法远非理想。这些因素促使业界寻求更精确的解决方案。在诊断领域日益流行的虚拟病理学,借助人工智能,可能有潜力解决这个问题。所提出的解决方案通过利用深度学习模型和模糊集解释来检测热点,从而计算Ki-67增殖指数。然后,通过经典的图像处理方法,利用获得的感兴趣区域对相关细胞进行分割。通过将免疫阳性细胞占据的总表面积与相关细胞的总表面积相关联来估算指数值。将所取得的结果与领域专家手动计算的Ki-67指数进行比较。为了提高结果的可靠性,我们以三倍的方式训练了多个模型,并比较了不同超参数的影响。我们提出的最佳方法估计PI的平均绝对误差为0.024,这比当前的最先进解决方案具有显著优势。