臺灣博碩士論文加值系統

肝臟方面的疾病深深地影響著國人的健康與壽命，一般認為肝病演變進程為「肝炎→肝纖維化→肝硬化→肝癌」。其中肝硬化是由肝纖維化(liver fibrosis)漸進地演變而來，在這過程中會出現許多併發症，例如：門靜脈高壓、食道靜脈曲張、脾腫大、腹水等等。已有許多文獻資料顯示，脾臟硬度(spleen stiffness)會隨著肝臟硬化程度、門靜脈高壓的程度或是食道靜脈曲張嚴重程度上升而隨之上升，且脾臟的體積與肝纖維化的程度呈現正相關。目前用於評估肝纖維化的黃金標準為經皮肝臟穿刺組織檢查，為一侵入性的檢查，所以存在著一定的風險與限制。因此期望找到非侵入性的方式來進行肝纖維化的評估，而磁振彈性造影(MR elastography)為一種非侵入性的磁振造影檢查方式，可藉由此技術來定量地量測體內軟組織的硬度。
本回朔性研究收錄了109位受檢者，這些受檢者皆有進行常規腹部磁振造影檢查(含磁振彈性造影)，且在造影檢查前或後90天內有進行肝臟病理組織切片檢查。脾臟硬度值、肝臟硬度值由磁振彈性影像中量測得知；脾臟體積值經由磁振影像量測得知。分析脾臟體積值及硬度值與肝纖維化分期的關係、探討被動式驅動器放置位置對脾臟硬度值的影響與比較脾臟體積值、脾臟硬度值與肝臟硬度值對重度肝纖維化(F3~F4)的鑑別力。
結果顯示脾臟的體積值及硬度值對肝纖維化分期都有正向線性相關存在。脾臟的體積值及硬度值皆可以當作肝纖維化分期的工具，但是脾臟硬度值效果較好。被動式驅動器放置於左側與右側胸壁量測結果具有顯著性差異，且放置於左側胸壁得到之脾臟硬度值對於肝纖維化分期的效果較好。
總結本研究結果，脾臟硬度值比脾臟體積值更能用來預測肝纖維化的程度，且若要量測脾臟硬度值應將被動式驅動器放置於左側胸壁，而對於鑑別重度肝纖維化，脾臟硬度值的效果優於脾臟體積值，甚至與肝臟硬度值效果相似，若將肝臟硬度值與脾臟硬度值合併在一起評估，會得到最佳的鑑別效果。

The liver diseases deeply affect people’s health and lifespan. Generally considered that the evolutionary processes of liver diseases are as below: liver hepatitis, liver fibrosis, liver cirrhosis and finally is hepatic carcinoma. Liver cirrhosis is progressively evolved from liver fibrosis. In this process, there will be many complications, such as portal hypertension, esophageal varices, splenomegaly and ascites. Massive reports showed that spleen stiffness will increase with the portal hypertension degree and the severity of esophageal varices, and that spleen volume has positive correlation with liver fibrosis. For assessing liver fibrosis stages, liver biopsy is the gold standard. However, it is invasive, and it contains unavoidable risks and limits. As a result, we expect to find a noninvasive method to assess liver fibrosis stages. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that can quantitatively measure the soft tissue’s stiffness value.
This study retrospectively enrolled 109 subjects, who underwent routine abdominal MRI and MRE. All of them underwent pathological examinations 90 days before or after MRI study. We measured the spleen stiffness and the liver stiffness from MRE images, and the spleen volume from MRI images. The relationships between the spleen volume, the spleen stiffness and the liver fibrosis stages were analyzed. We also investigated the impact on the position of passive driver to the spleen stiffness values. Compared the diagnostic accuracy for advanced fibrosis (F3~F4) between the spleen stiffness, the spleen volume and the liver stiffness.
In our study, the spleen volume and the spleen stiffness are both positive linear correlated with liver fibrosis stage. The spleen volume and the spleen stiffness both can be used for staging liver fibrosis, but the spleen stiffness has better performance.
In conclusion, the spleen stiffness measured by MRE is a better predictor for staging liver fibrosis. If we want to measure the spleen stiffness, it is more suitable to put the passive driver on patient’s left chest wall. For discriminating advanced liver fibrosis, the accuracy of the spleen stiffness is better than the spleen volume, even as good as the liver stiffness. If we combine the liver stiffness and the spleen stiffness to discriminate the advanced liver fibrosis, the performance is the best.

目錄
致謝 I
中文摘要 II
Abstract IV
目錄 VI
圖目錄 X
表目錄 XII
1. 緒論 1
1.1. 研究目的與動機 1
1.2. 研究架構 5
2. 背景與文獻回顧 6
2.1. 肝纖維化 6
2.2. 脾腫大 9
2.3. 磁振造影(50) 11
2.3.1. 成像原理 12
2.3.2. T1、T2與T2* 18
2.3.3. 波序參數與脈衝波序 20
2.3.4. T1、T2與組織對比 23
2.3.5. 磁振訊號相位編碼 24
2.4. 磁振彈性造影 26
2.4.1. 彈性模量與剪波 27
2.4.2. 彈性造影概論 29
2.4.3. 磁振彈性造影原理 31
2.4.4. 硬體設備 33
2.4.5. 應用波序 34
2.4.6. 彈性影像重組演算法 36
3. 材料與方法 39
3.1. 研究對象 39
3.2. 研究方法與流程 40
3.2.1. 納入條件及排除條件 40
3.2.2. 磁振造影方法 42
3.2.3. 硬度值量測方法 44
3.2.4. 體積值量測方法 47
3.2.5. 病理分期 48
3.2.6. 統計分析 49
4. 結果 51
4.1. 收錄資料特性 51
4.2. 肝臟硬度值量測結果 52
4.2.1. 兩側肝臟硬度值量測結果比較 52
4.2.2. 肝臟硬度值與肝纖維化分期之相關性 53
4.3. 脾臟硬度值量測結果 56
4.3.1. 兩側脾臟硬度值量測結果比較 56
4.3.2. 脾臟硬度值與肝纖維化分期之相關性 57
4.4. 脾臟體積值與肝纖維化分期之相關性 62
4.5. 脾臟硬度值與肝臟硬度值對肝纖維化分期比較 64
4.6. 鑑別重度肝臟纖維化 67
5. 討論 71
5.1. 研究結果討論 71
5.1.1. 脾臟體積值與肝纖維化的關係 71
5.1.2. 脾臟硬度值與肝纖維化的關係 73
5.1.3. 被動式驅動器放置位置與量測值的關係 75
5.1.4. 鑑別重度肝纖維化的綜合比較 79
5.2. 研究限制 81
5.3. 結論 82
6. 未來展望 83
參考文獻 85
附錄 93

圖目錄
圖 2 1 肝纖維化分期 (F0~F4期) 示意圖。 8
圖 2 2 有無外加磁場(B0)，淨磁場(Net MF)的反應。 13
圖 2 3質子旋進(precession)現象。 14
圖 2 4 M0部分偏轉示意圖。 16
圖 2 5 自由感應衰減(FID)訊號。 17
圖 2 6 當RF pulse關閉後，淨磁矩的反應。 18
圖 2 7 縱向磁矩(Mz)的回復曲線圖。 19
圖 2 8 橫向磁矩(Mxy)的衰減曲線圖。 20
圖 2 9 自旋回音序列(spin-echo pulse sequence)示意圖。 22
圖 2 10 梯度回音序列(Gradient-echo pulse sequence)示意圖。 22
圖 2 11 水、脂肪、固態組織的T1與T2隨時間變化圖。 23
圖 2 12 兩個頻率相同，存在相位差的正弦波圖。 25
圖 2 13 MRE產生的圖，以腹部檢查為例。 32
圖 2 14 MRE硬體設備實際示意圖。 34
圖 2 15 一般磁振彈性造影波序圖。 35
圖 3 1納入研究範圍的受檢者流程圖。 41
圖 3 2 磁振彈性造影檢查示意圖。(以腹部檢查為例) 43
圖 3 3 脾臟硬度值量測示意圖。 45
圖 3 4 肝臟硬度值量測示意圖。 46
圖 4 1平均肝臟硬度值在不同肝纖維化分期(F0~F4)之盒形圖。 55
圖 4 2平均脾臟硬度值在不同肝纖維化分期(F0~F4)之盒形圖。 59
圖 4 3 各肝纖維化分期(F0~F4)之影像。 60
圖 4 4 脾臟體積值在不同肝纖維化分期(F0~F4)之盒形圖。 63
圖 4 5 平均脾臟硬度值(a.)與平均肝臟硬度值(b.)在不同肝纖維化分期(F0~F4)之盒形圖。 66
圖 4 6脾臟硬度值、肝臟硬度值、脾臟體積值及合併肝臟硬度值與脾臟硬度值對於鑑別是否為重度肝纖維化(F0~F2期vs.F3~F4期)之ROC曲線。 69
圖 4 7 以脾臟體積值(圖a)、平均脾臟硬度值(圖b)及平均肝臟硬度值(圖c)將所有受檢者分成兩組(F0~F2 vs.F3~F4)之盒形圖。 70

表目錄
表 2 1 不同切面之梯度磁場設計 17
表 2 2 各種加權影像造影參數 24
表 3 1磁振造影序列之各項參數 42
表 4 1 於各肝纖維化分期的肝臟硬度值 52
表 4 2於各肝纖維化分期的脾臟硬度值 56
表 4 3 鑑別是否為重度肝纖維化(F0~F2vs.F3~F4) 69

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