目的：單光子發射電腦斷層攝影不管是在臨床的核子醫學或者是在分子影像的領域都扮演了重要的角色。然而，定量準確度卻會受到光子在行進的過程中與原子作用所產生的衰減以及散射效應所影響。在本篇研究，我們使用自行發展的基於電腦斷層之均值衰減修正法（CTMAC）以及目前較常見的修正方法，透過一些物理假體以及大老鼠之單光子發射電腦斷層攝影/電腦斷層掃描（SPECT/CT）的資料，同時進行衰減以及散射修正之後，來比較其修正結果之優劣。材料與方法：使用放射性同位素99mTc或其標誌物99mTc-sestamibi對物理假體以及大老鼠進行填充或注射之後，藉由一臺搭配孔徑大小為1.2 mm平行孔準直儀的小動物單光子發射電腦斷層攝影對物體進行旋轉造影，而三個加馬攝影機在造影的過程當中總共取96個投影，每個投影則是取樣120秒，並且使用三個能窗(130-137、137-144以及144-151 keV)對物體在不同角度的活度分佈情況進行造影。單光子發射電腦斷層攝影造影結束之後，是使用管電壓為80 kVp的電腦斷層掃描對物體進行造影，之後是使用修改過的三維錐狀射束FDK演算法對掃描得到的資料進行影像重建。單光子發射電腦斷層攝影的資料除了基於電腦斷層在疊代的影像重建過程當中同時進行衰減補償的方法(CTIACR)是使用序列子集期望值最大化（OSEM）演算法進行衰減補償以及影像重建之外，其餘的方法皆是使用濾波反投影（FBP）法來進行影像重建。在衰減修正的部分，我是使用張氏法、基於電腦斷層的衰減修正法、基於電腦斷層在疊代的影像重建過程當中同時進行衰減補償的方法以及基於電腦斷層之均值衰減修正法對造影的資料進行衰減修正。在散射修正的部分，我是使用三能窗法對投影資料進行修正，評估得到的散射成分是在影像重建之前從主能窗的投影資料當中扣除，之後是使用校正因數（calibration factor）將重建得到的光子計數分佈轉換成為活度濃度的分佈情況。結果：在物理假體實驗的部分，我們使用平均百分誤差（MPE）來評估只有對投影資料進行衰變修正（decay correction）的原始影像，以及只有進行散射修正的影像，還有散射修正結合張氏法、基於電腦斷層的衰減修正法、基於電腦斷層在疊代的影像重建過程當中同時進行衰減補償的方法以及基於電腦斷層之均值衰減修正法所得到的修正結果。在大鼠體積均勻假體的實驗，前面提到五種搭配所得到的修正誤差分別為：-10.61、-36.90、-3.02、0.71、1.31與3.81%，在四等份假體活度濃度較高的部分為：-12.59、-35.85、-4.16、-4.35、-1.23與-1.12%，在四等份假體活度濃度較低的部分為：-6.86、-31.32、2.77、2.46、0.44與7.22%，在同心圓假體內層的部分則是：-4.22、-28.12、13.41、-3.39、-1.72與-0.77%，在同心圓假體外層的部分則是：-36.32、-53.24、-34.58、-39.85、-27.74與-36.09%。在大老鼠實驗的部分，散射修正結合四種衰減修正方法所得到的結果可以說是相當接近。結論：對一個大鼠體積的物體來說，光子的衰減效應對於定量所造成的影響值得去重視。我們所開發的CTMAC可在最短的時間內得到不錯的衰減修正結果，而一些目前較常見被使用的衰減修正方法也能夠得到很好的修正結果，但所花的時間較長。對小動物單光子發射電腦斷層攝影的造影資料進行衰減以及散射修正之後，就能夠達到準確定量的活度濃度分佈情況。

Objective： SPECT is an important molecular imaging modality in both clinical and preclinical applications. However, its quantitative accuracy is limited by photon attenuation and scatter effect when photons interact with atoms. In this study, we developed a new attenuation correction (AC) method, CT-based mean attenuation correction (CTMAC) method, and compared with various state-of-the-art methods to assess the AC phenomenon as described above. AC and scatter correction (SC) were realized by using the SPECT/CT data that were acquired from various physical phantoms and a rat. Materials and Methods： The physical phantoms and a SD rat, which were injected 99mTc, were scanned by a parallel-hole small animal SPECT scanner for evaluating AC. The parameters were set as follows: 1.2 mm parallel-hole aperture diameter, 96 projections acquired by three γ-cameras, 120 seconds per projection which were recorded within three energy windows (130-137, 137-144, and 144-151 keVs). After finishing the above experiments, they were imaged by the 80 kVp micro-CT scanner and were reconstructed with a modified 3D cone-beam Feldkamp algorithm. Moreover, the SPECT data were reconstructed with FBP except CT-based iterative attenuation compensation during reconstruction (CTIACR) method which was based on OSEM algorithm. Chang’s, CT-based attenuation correction (CTAC), CTIACR and CTMAC methods were performed for AC, and scatter was estimated and corrected by taking advantage of the triple-energy-window method (TEW). After filtering, the data were subtracted from the primary window projections before reconstruction. Absolute quantification was derived from a known activity point source scan. Results： In the physical-phantom studies, we compared the images with original, SC only, and the scatter-corrected images with AC performed by using the Chang’s, CTAC, CTIACR, as well as the CTMAC methods. The mean percentage error (MPE) for evaluating the above five configurations are -10.61, -36.90, -3.02, 0.71, 1.31 and 3.81% in the rat-sized phantom, -12.59, -35.85, -4.16, -4.35, -1.23 and -1.12% in the part of the quartering phantom which contained the higher activity concentration, -6.86, -31.32, 2.77, 2.46, 0.44 and 7.22% in the phantom’s part of the lower activity concentration, -4.22, -28.12, 13.41, -3.39, -1.72 and -0.77% in the inner layer of the concentric circle phantom, -36.32, -53.24, -34.58, -39.85, -27.74 and -36.09% in the outer layer of the concentric circle phantom. For the SD rat examination, we found out that SC in combination with four AC methods can obtain quite similar results. Conclusion： The effect of photon attenuation in rat-sized objects is significant. The CTMAC method needs the shortest correction time and can obtain a very good AC result. Attenuation correction obtained from CT data in combination with scatter correction allows accurate quantification in small animal SPECT imaging but it takes more time.

口試委員審定書 ＃
誌謝 i
中文摘要 ii
ABSTRACT iv
目錄 vi
圖目錄 x
表目錄 xv
第一章 緒論 1
1.1 研究緣起 1
1.2 研究主旨與目的 2
1.3 研究方向 4
1.4 研究貢獻 5
1.5 論文架構 6
第二章 造影系統與影像重建演算法 7
2.1 單光子發射電腦斷層攝影基本原理 7
2.1.1 平行孔準直儀 7
2.1.2 加馬攝影機. 10
2.1.3 單光子發射電腦斷層攝影. 12
2.2 電腦斷層攝影基本原理 13
2.2.1 電腦斷層攝影. 13
2.2.2 CT值. 15
2.3 單光子發射電腦斷層攝影之影像重建演算法 15
2.3.1 解析式重建演算法. 15
2.3.2 疊代式重建演算法. 20
第三章 輻射衰減 28
3.1 光子與物質的作用 28
3.2 衰減修正 33
第四章 材料與方法 45
4.1 儀器設備 45
4.1.1 小動物單光子發射電腦斷層攝影儀 46
4.1.2 小動物電腦斷層掃描儀 48
4.1.3 影像對位與融合 49
4.2 實驗材料 51
4.2.1 物理假體實驗 51
4.2.2 動物實驗 55
4.3 雙線性模型 56
4.4 三能窗散射修正法 62
4.5 衰減修正法 68
4.5.1 張氏法 68
4.5.2 基於電腦斷層的衰減修正法 74
4.5.3 基於電腦斷層在疊代的影像重建過程當中同時進行衰減補償的方法 81
4.5.4 基於電腦斷層之均值衰減修正法 86
4.6 校正因數 95
4.7 物理假體修正結果評估之參數 96
第五章 結果與討論 99
5.1 散射修正之結果 99
5.2 衰減修正結合散射修正之結果 104
5.2.1 物理假體實驗衰減修正結合散射修正之結果 104
5.2.2 動物實驗衰減修正結合散射修正之結果 117
5.3 衰減修正結合散射修正所需之時間 120
5.4 討論 123
第六章 結論與未來發展方向 134
6.1 結論 134
6.2 未來發展方向 136
參考文獻 138


圖目錄

圖2.1 平行孔準直儀的幾何參數 8
圖2.2 各代電腦斷層掃描儀之示意圖 14
圖2.3 物體所在的座標軸位置與投影角之間的關係 17
圖2.4 目前濾器反投影法會使用的一部分濾器以及它們的形狀 20
圖2.5 疊代式重建演算法的步驟 26
圖3.1 光電效應示意圖 30
圖3.2 康普吞效應示意圖 31
圖3.3 成對發生示意圖. 33
圖3.4 光子衰減示意圖 35
圖3.5 閃爍攝影機的傳統SPECT造影技術示意圖 37
圖3.6 模擬直徑為6公分的均勻圓柱水假體光子的穿透機率示意圖 38
圖3.7點射源位在厚度為D的衰減物質內之示意圖 42
圖3.8 斷層攝影原理示意圖 44
圖4.1 本研究造影所使用之FLEX TriumphTM pre-clinical imaging system. 46
圖4.2 造影的過程當中所搭配的低能量高解析度平行孔準直儀 47
圖4.3 將小動物電腦斷層攝影的影像平滑化的低通濾器 49
圖4.4 將小動物電腦斷層掃描儀的影像平滑化的高斯濾器 51
圖4.5 五根毛細管的SPECT/CT對位影像 52
圖4.6 大鼠尺寸均勻假體 53
圖4.7 同心圓假體 54
圖4.8 動物實驗所使用之SD大鼠 55
圖4.9 管電壓為80 kVp以及140 kVp之Straton管所發射的能譜 59
圖4.10 本實驗所使用之雙線性校正曲線 60
圖4.11 大鼠體積假體的非均勻直線衰減係數分佈圖 61
圖4.12 四等份假體的非均勻直線衰減係數分佈圖 61
圖4.13 同心圓假體的非均勻直線衰減係數分佈圖 62
圖4.14 大鼠的非均勻直線衰減係數分佈圖 62
圖4.15 CZT半導體加馬攝影機在造影的過程當中所測量得到99mTc的能譜以及三能窗法主能窗和兩個次能窗所開的能量位置與寬度 64
圖4.16 大鼠體積假體使用三能窗法進行散射修正之示意圖 65
圖4.17 四等份假體以及同心圓假體所圈選感興趣區域的位置與大小 67
圖4.18 四等份假體以及同心圓假體所圈選背景的位置與大小 67
圖4.19 大鼠體積假體的均勻直線衰減係數分佈圖 69
圖4.20 四等份假體的均勻直線衰減係數分佈圖 69
圖4.21 同心圓假體的均勻直線衰減係數分佈圖 70
圖4.22 大鼠的均勻直線衰減係數分佈圖 70
圖4.23 使用均勻的μ-map計算得到大鼠體積均勻假體的衰減修正因子矩陣 71
圖4.24 使用均勻的μ-map計算得到四等份假體的衰減修正因子矩陣 72
圖4.25 使用均勻的μ-map計算得到同心圓假體的衰減修正因子矩陣 72
圖4.26 使用均勻的μ-map計算得到大鼠的衰減修正因子矩陣 73
圖4.27 張氏法的修正流程圖 74
圖4.28 光子穿透機率投影角的計算數目 76
圖4.29 直線衰減係數取樣點的間隔距離 76
圖4.30 任一個取樣點在座標軸的位置關係示意圖 77
圖4.31 使用非均勻的μ-map計算得到大鼠體積均勻假體的衰減修正因子矩陣 78
圖4.32 使用非均勻的μ-map計算得到四等份假體的衰減修正因子矩陣 79
圖4.33 使用非均勻的μ-map計算得到同心圓假體的衰減修正因子矩陣 79
圖4.34 使用非均勻的μ-map計算得到大鼠的衰減修正因子矩陣 80
圖4.35 基於電腦斷層的衰減修正法修正的流程圖 81
圖4.36 任一個像素位置所發射的光子朝不同投影角方向發射的示意圖 82
圖4.37 基於電腦斷層在疊代的影像重建過程當中同時進行衰減補償的修正流程圖 85
圖4.38 單光子發射電腦斷層攝影任一個探測單元在不同投影角的時候所接收到的光子計數 86
圖4.39 大鼠體積均勻假體實驗第四十一張切面投影資料相對應之衰減修正因子矩陣 92
圖4.40 四等份假體實驗第四十一張切面投影資料相對應之衰減修正因子矩陣 93
圖4.41 同心圓假體實驗第四十一張切面投影資料相對應之衰減修正因子矩陣 93
圖4.42 大鼠實驗第四十一張切面投影資料相對應之衰減修正因子矩陣 94
圖4.43 基於電腦斷層之均值衰減修正法的修正流程圖 95
圖4.44 不同的物理假體其SPECT切面影像所圈選感興趣區域的位置 98
圖5.1 大鼠體積均勻假體散射修正之前與之後的切面影像 100
圖5.2 四等份假體散射修正之前與之後的切面影像 101
圖5.3 同心圓假體散射修正之前與之後的切面影像 102
圖5.4 大鼠心肌灌注造影散射修正之前與之後的切面影像 103
圖5.5 大鼠體積均勻假體經過散射修正並且結合四種不同的衰減修正方法修正之後所得到的切面影像 104
圖5.6 修正之後所得到大鼠體積均勻假體的切面影像 107
圖5.7 四等份假體經過散射修正並且結合四種不同的衰減修正方法修正之後所得到的切面影像 109
圖5.8 修正之後所得到四等份假體的切面影像 111
圖5.9 同心圓假體經過散射修正並且結合四種不同的衰減修正方法修正之後所得到的切面影像 113
圖5.10 修正之後所得到同心圓假體的切面影像 115
圖5.11 大鼠心肌灌注造影經過散射修正並且結合四種不同的衰減修正方法修正之後所得到的切面影像 117
圖5.12 修正之後所得到大鼠心肌灌注造影的切面影像 120
圖5.13 使用基於電腦斷層之均值衰減修正法修正之後所得到不同造影物體四十張切面的立體影像 123
表目錄

表5.1 使用三能窗法散射修正前後四等份假體影像的對比 104
表5.2 使用三能窗法散射修正前後同心圓假體影像的對比 104
表5.3 使用六個不同的參數來評估大鼠體積均勻假體修正之後所得到的結果. 108
表5.4 使用六個不同的參數來評估四等份假體修正之後所得到的結果 112
表5.5 使用六個不同的參數來評估同心圓假體修正之後所得到的結果 116
表5.6 散射修正結合不同的衰減修正法對一張切面進行修正所需之時間 121

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