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研究生: 張開永
Sai Aung Kyaw Oo
論文名稱: 弱監督式多實例學習深度學習方法應用於預測H&E染色子宮內膜切片微衛星不穩定性
Weakly-supervised Multiple Instance Learning Approaches for Predicting Microsatellite Instability using H&E Endometrium Tissue Microarray
指導教授: 王靖維
Ching-Wei Wang
口試委員: 許昕
Hsin Hsiu
許維君
Wei-Chun Hsu
鄭智嘉
Chih-Chia Cheng
趙載光
Tai-Kuang Chao
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 醫學工程研究所
Graduate Institute of Biomedical Engineering
論文出版年: 2023
畢業學年度: 111
語文別: 中文
論文頁數: 69
中文關鍵詞: 子宮內膜癌精準腫瘤學深度學習組織病理學組織微陣列全景域影像多實例學習弱監督學習
外文關鍵詞: Endometrial carcinoma, Precision oncology, Deep learning, Histopathology, Tissue microarray, Whole-slide image, Multiple instance learning, Weakly supervised learning
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  • 本研究改進了2019 年Campanella. 等人發表於Nature Medicine 的MIL_RNN
    [1] 方法,並提出了兩種預測子宮內膜染色全玻片影像微衛星狀態(Microsatellite
    status) 的模型:Proposed method 1 與Proposed method 2。為確保提出模型的適應性
    與可訓練性,我們使用了三個不同的數據集進行訓練與驗證。數據集一包含H&E
    染色的子宮內膜微陣列(Tissue microarray, TMA)全玻片影像(WSIs),數據集二
    包含H&E 染色的子宮內膜癌G1G2 級別的WSIs,數據集三則包含H&E 染色的子
    宮內膜癌G3 級別的WSIs。
    • 在數據集一中,Proposed method 1 與Proposed method 2 在準確率(Accuracy)、
    精確率(Precision)、召回率(Recall) 和F1-分數(F1-score) 等指標上均優於原
    始的MIL_RNN 方法。也將數據集一分別測試在七種不同模型,結果顯示
    Proposed method 1 在準確率、召回率和F1-分數上表現最好。。
    • 在數據集二和數據集三中,我們將在數據集一中表現前兩名的弱監督學
    習方法Proposed method 1 和CLAM [2] 與原始的MIL_RNN 模型進行比較。
    在數據集二中Proposed method 1 與CLAM 的F1 分數最高,在數據集三中
    Proposed method 1 的F1-分數為最高。
    • 最後,根據這三組數據集的結果,我們推論多實例學習模型的F1-分數與訓
    練集數據量成正比,而Proposed method 1 的特異度(Specificity) 與訓練集中
    的類別數量差異成反比。
    綜上所述,本論文提出了兩種預測子宮內膜染色全玻片影像微衛星狀態的模
    型,這些模型在性能上優於原始的MIL_RNN 方法。它們在不同的數據集上表現
    出色,並為模型性能與訓練集特徵之間的關係提供了洞見。


    This study improves upon the MIL_RNN method proposed by Campanella et al.
    in Nature Medicine in 2019 [1] and proposes two models, Proposed method 1 and Proposed
    method 2, for predicting the microsatellite status of endometrial cancer from wholeslide
    images stained with hematoxylin and eosin (H&E). To ensure the adaptability and
    trainability of the models, three different datasets were used for training and validation.
    Dataset 1 consisted of H&E-stained tissue microarray (TMA) whole-slide images (WSIs)
    of endometrial samples, Dataset 2 included H&E-stained WSIs of endometrial carcinoma
    G1G2, and Dataset 3 comprised H&E-stained WSIs of endometrial carcinoma G3.
    • In Dataset 1, both Proposed method 1 and Proposed method 2 exhibited superior
    performance in terms of accuracy, precision, recall, and F1-score compared to the
    original MIL_RNN method. Also, Dataset 1 was tested on seven different models
    individually, and the results showed that Proposed Method 1 performed the best in
    terms of accuracy, recall, and F1 score.
    • In Dataset 2 and Dataset 3, Proposed method 1 and the weakly supervised learning
    method CLAM [2], both ranking in the top two in Dataset 1, were compared with
    the original MIL_RNN model. Proposed method 1 and CLAM achieved the highest
    F1-scores in Dataset 2, while Proposed method 1 attained the highest F1-score in
    Dataset 3.
    • Lastly, based on the results from these three datasets, we inferred that the F1-score
    of the multiple instance learning model is directly proportional to the amount of
    training data, and the specificity of Proposed method 1 is inversely proportional to
    the difference in class quantities in the training set.
    In conclusion, this study proposes two models, Proposed method 1 and Proposed method
    2, for predicting the microsatellite status of endometrial cancer from H&E-stained wholeslide
    images, which outperform the original MIL_RNN method in terms of performance.
    These models demonstrate excellent performance across different datasets and provide insights
    into the relationship between model performance and training set characteristics.

    摘要. . . . . . . . . . . . . . . . . . . . . . . . . . . . II Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . III 致謝. . . . . . . . . . . . . . . . . . . . . . . . . . . V 目錄. . . . . . . . . . . . . . . . . . . . . . . . . . . . VI 圖目錄. . . . . .. . . . . . . . . . . . . . . . . . . . . . VIII 表目錄. . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI 第一章緒論. . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 研究動機. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 研究目標. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 論文貢獻. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.4 論文架構. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 第二章研究背景. . . . . . . .. . . . . . . . . . . . . . . . . 5 2.1 樣本製備及染色方法. . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.2 弱監督式深度學習方法之文獻. . . . . . . . . . . . . . . . . . . . . . 6 2.3 深度學習應用於組織病理學之文獻. . . . . . . . . . . . . . . . . . . 7 第三章研究方法. . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.1 TMA core detection model . . . . . . . . . . . . . . . . . . . . . . . . . 16 3.2 Multi-instance learning model . . . . . . . . . . . . . . . . . . . . . . . 19 3.2.1 Proposed method 1 的backbone network . . . . . . . . . . . . . 21 3.2.2 Proposed method 2 的backbone network . . . . . . . . . . . . . 24 3.3 Recurrent neural network model . . . . . . . . . . . . . . . . . . . . . . 28 第四章實驗設計與結果. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1 研究中所使用的資料集. . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.2 實驗設備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 4.3 實驗結果. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 4.3.1 H&E 染色Endometrial tissue mircoarray . . . . . . . . . . . . . 38 4.3.2 H&E 染色Endometrial carcinoma G1G2 whole slide image . . . 39 4.3.3 H&E 染色Endometrial carcinoma G3 whole slide image . . . . . 40 4.3.4 資料量與模型綜合表現(F1-score) 關係. . . . . . . . . . . . . 41 4.3.5 資料類別平均與模型特異度(Specificity) 關係. . . . . . . . . 42 4.3.6 消融實驗. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 第五章結論與未來展望. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5.1 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5.2 未來發展. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 參考文獻. . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . 46

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