臺灣博碩士論文加值系統

甲狀腺癌是最常見的惡性腫瘤。在近幾十年來，發生率有上升的趨勢。所以，如何提升偵測甲狀腺腫瘤的靈敏度，以及提升診斷的正確率，也就變得越來越重要。在此論文中，我們提出了一個創新的電腦輔助方法，來量化甲狀腺癌的超音波影像特徵。我們主要是針對超音波影像呈現微細鈣化以及不均質迴音兩項特徵進行影像處理以及分析。以驗證我們提出來的創新指標，是否可以提升甲狀腺癌的診斷準確率。

在第一部分針對傳統超音波鈣化的量化，在256個甲狀腺腫瘤（173個良性，83個惡性）的驗證之後，良惡性的腫瘤間有顯著的差異(p<0.001, AUC=0.746)。再針對手術切除後有病理報告證實的腫瘤（102個良性，79個惡性）進行驗證，也得到良惡性的腫瘤間有顯著的差異的結果(p<0.001, AUC=0.763)。研究中也比較電腦量化的超音波指標與傳統超音波鈣化在評估腫瘤上的差異，顯示在惡性腫瘤中，傳統超音波鈣化的比例為48.19(40 of 83)。在良性腫瘤中，傳統超音波鈣化的比例為10.98(19 of 173)。這個研究證實了，電腦量化的超音波鈣化指標，相較於傳統的評估方式，是一個較靈敏較客觀的方式，對甲狀腺癌的診斷，可以提升更靈敏的評估。

在第二部分針對傳統超音波不均質迴音的評估，在400個甲狀腺腫瘤（271個良性，129個惡性）的驗證之後，良惡性的腫瘤間有顯著的差異(p<0.001, AUC=0.714)。在本研究中也證實傳統超音波不均質&;#24315;音的評估並無法有效的區分出良惡性腫瘤。而傳統超音波較明顯的不均質&;#24315;音，也有較高的電腦量化不均質迴音指標。證實新的指標，相較於傳統超音波不均質&;#24315;音，可以更有效分辨良惡性腫瘤。在濾泡腫瘤上，對於濾泡腫瘤的良惡性在術前也可以提供有效的評估。

在我們的研究中，可以觀察到，電腦輔助量化超音波指標，的確可以有效地提升甲狀腺腫瘤的診斷率。未來在臨床上的應用，量化超音波及傳統超音波多指標的統合診斷方式將是可行的發展方向。

Thyroid cancer is the most common endocrine malignancy. The incidence is increasing in the past decades. How to improve the detection rate and diagnostic accuracy has become an urgent issue. We proposed the novel computerized methods in this thesis to quantify the ultrasonic features of thyroid cancer. We included two ultrasonic features which were microcalcifications and heterogeneity in this thesis to test whether computerized method could be helpful in diagnosis of thyroid cancer.
The first part was to improve the ultrasonographic detection rates of thyroid cancers with microcalcifications, we proposed to enhance the sensitivity of sonographic calcifications detection and to avoid inter-observer variation by a computerized quantification method in a prospective setting. A total of 256 nodules were included (173 benign, 83 malignant). Among them, the diagnosis of 181 nodules (102 benign, 79 malignant) were verified by surgical pathology. Quantification of cystic components and calcifications was automatically performed by a proprietary program (AmCAD-UT) implemented with methods proposed in this paper. The calcification index (CI) between benign and malignant nodules diagnosed by combined FNA biopsy and surgical pathology results (total number, 256) showed a significant difference (p<0.001, AUC=0.746). Furthermore, we excluded patients without surgical pathology results for further validation, and the CI between benign and malignant nodules confirmed by pathology results (total number, 181) showed a significant difference (p<0.001, AUC=0.763). To learn whether our computer program increased our diagnostic capabilities, we analyzed human investigators and their abilities to detect and evaluate. In this study, calcifications were noted in 48.19% (40 of 83) of malignant thyroid nodules and in 10.98% (19 of 173) of benign nodules. This new computer-aided diagnosis method to evaluate the sonographic calcifications of thyroid nodules is a more sensitive and more objective method. It can provide better sensitivity than conventional methods in the diagnosis of thyroid malignancies containing microcalcifications.
The second part is to test whether the computerized quantification of ultrasonic heterogeneity can aid the diagnosis of thyroid malignancy, we evaluated ultrasonic heterogeneity by an objective and quantitative computerized method in a prospective setting. A total of 400 nodules including 271 benign thyroid nodules and 129 malignant thyroid nodules were evaluated. Quantification of ultrasonic heterogeneity (heterogeneity index, HI) was performed by a proprietary program implemented with methods proposed in this paper. The HI values between benign and malignant nodules, diagnosed by a combination of fine-needle aspiration (FNA) and surgical pathology results, are significantly different (p<0.001, AUC=0.714). Ultrasonic heterogeneity (US-H) of these samples assessed by an experienced clinician could not significantly differentiate between benign and malignant thyroid nodules. However, the nodules with marked heterogeneity of US-H showed higher HI values than that of nodules with homogeneous US-H assessment. These results indicate that using the new computer-aided diagnosis method to evaluate the ultrasonic heterogeneity of thyroid nodules is an objective and quantitative method that is correlated to the conventional US-H assessment but can aid in the diagnosis of thyroid malignancy better.

口試委員會審定書 4
誌謝 5
中文摘要 6
英文摘要 8
第一章 緒論 11
1.1. 研究背景 11
1.1.1. 甲狀腺癌的發生率 11
1.1.2. 甲狀腺癌的超音波診斷 12
1.2. 研究假說及目的 19
第二章 研究方法與材料 20
2.1. 量化超音波鈣化指標 20
2.1.1. 受試腫瘤 20
2.1.2. 超音波器材 20
2.1.3. 超音波檢查步驟 20
2.1.4. 超音波囊性組成與超音波的鈣化點之量化分析 (Cystic component and calcifications) 21
2.3鈣化指標與不均質指標的比較 27
第三章 結果 28
3.1. 鈣化指標驗證 28
3.1.1. 鈣化指標評估良惡性腫瘤 28
3.1.2. 鈣化指標評估不同大小的腫瘤 28
3.1.3. 鈣化指標評估不同囊性組成比例的腫瘤 28
3.1.4. 鈣化指標與人工的超音波鈣化評估 29
3.2. 不均質指標驗證 30
3.2.1. 不均質指標評估良惡性腫瘤 30
3.2.2. 不均質指標評估不同大小的腫瘤 30
3.2.3. 不均質指標評估不同囊性組成比例的腫瘤 30
3.2.4. 不均質指標與人工的超音波不均質度評估比較 31
3.2.5. 不均質指標在濾泡腫瘤的分析 31
3.3. 鈣化指標與不均質指標的比較 31
第四章 討論 32
第五章 展望 39
第六章 英文部分 41
6.1. Computerized Detection and Quantification of Microcalcifications in Thyroid Nodules 41
6.1.1. Introduction 41
6.1.2. Materials and Methods 43
6.1.3. Results 48
6.1.4. Discussion and Summary 50
6.2. Computerized Quantification of Ultrasonic Heterogeneity in Thyroid Nodules 55
6.2.1. Introduction 55
6.2.2. Materials and Methods 56
6.2.3. Results 62
6.2.4. Discussion 65
6.2.5. Conclusions 70
第七章 圖表 71
7.1. 表 (表1至表7) 71
7.2. 圖 (圖1至圖23) 78
第八章 附錄：博士班修業期間所發表之相關論文 102
第九章 參考文獻 103

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