醫師發現在患者回診時，儘管已從超音波影像中發現患者的肌肉功能性正在 下降，也就是緩慢走向纖維化的過程，然患者本身並無疼痛等異常不適感，往往 造成無法及早配合適當的療程而造成後遺症加重，甚至肌肉完全失去其功能的遺 憾。本研究藉由使用術後拍攝之超音波影像進行軟體部分的影像後處理後，將可 用的資訊整理出來並量化，提供醫師作為診斷參考之用，並給予病人復健效果的 初步標準。因此本研究的主要貢獻在於提供醫師客觀的量化正常組織受放射線傷 害的指標，並能在早期發現患者的肌肉惡化情形，進而選擇適當的時間點切入做 復健療程。
本篇由於時間關係，僅使用蛋白仿體作為初步量化的實驗驗證，然在生物體 上真正的驗證仍有可進步的空間，如接下來將以老鼠的雙腿，其中一腿進行放射 線照射，另一腿則作為控制組，在術後分別間隔一段時間如一週後利用本所附設 隻小動物超音波儀進行超音波影像的拍攝，並輸入本系統作量化的評估，同時在 各間隔的時間點對兩腿分別做步態分析，記錄每次拍攝時腿部肌肉的變化情形，
再將兩者的結果對照，可完整的驗證本系統在實際生物體上的使用情形。
另外一部分則由於本系統的影像來源受限於需要開啟儀器內建的消除雜訊系 統，若不開啟將會造成超音波反射的回聲訊號(Speckle noise)被誤判為肌肉纖維部 分，造成高估的情形。將來若能開發出去除雜訊的影像後處理系統，根本性的解 決誤判的情形，餘下的22 組數據就有辦法用來分析，如此一來對於患者分析數據 的完整性將大大的提升。
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參考文獻
1. Archambeau, J O, Pezner, R., and Wasserman, T. (1995). Pathophysiology of irradiated skin and breast. Int J Radiat Oncol Biol Phys, 31(5), 1171-1185. doi:
10.1016/0360-3016(94)00423-i
2. Baum, B J, Zheng, C, Cotrim, A P, Goldsmith, C M, Atkinson, J C, Brahim, J S, . . . Illei, G G (2006). Transfer of the AQP1 cDNA for the correction of
radiation-induced salivary hypofunction. Biochim Biophys Acta, 1758(8), 1071-1077. doi: 10.1016/j.bbamem.2005.11.006
3. Bezdek, J C (1981). Pattern Recognition with Fuzzy Objective Function
Algorithms. New York: Plenum Press.
4. Citrin, D., Cotrim, A P, Hyodo, F, Baum, B J, Krishna, M C, & Mitchell, J B (2010). Radioprotectors and mitigators of radiation-induced normal tissue injury.
Oncologist, 15(4), 360-371. doi: 10.1634/theoncologist.2009-S104
5. Cooper, J S, Fu, K, Marks, J, and Silverman, S (1995). Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys, 31(5), 1141-1164. doi: 10.1016/0360-3016(94)00421-g
6. Cotrim, A P, Hyodo, F, Matsumoto, K, Sowers, A L, Cook, J A, Baum, B J, . . . Mitchell, J B (2007). Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res, 13(16), 4928-4933. doi:
10.1158/1078-0432.ccr-07-0662
7. Dorr, W, and Hendry, J H (2001). Consequential late effects in normal tissues.
76
Radiother Oncol, 61(3), 223-231.
8. Dunn, J C (1974). A fuzzy relative of the isodata process and its use in detecting compact well separated clusters. Journal of Cybernetics, 3(3), 32-57.
9. Dvorak, H F (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med, 315(26), 1650-1659. doi:
10.1056/nejm198612253152606
10. Fajardo, L F (1982). Pathology of radiation injury. New York: Masson.
11. Fowler, J F (1984). The first James Kirk memorial lecture. What next in fractionated radiotherapy? Br J Cancer Suppl, 6, 285-300.
12. Greis, C (2011). Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc, 49(1-4), 137-149. doi: 10.3233/ch-2011-1464
13. Hadi, A M, Mouchaers, K T, Schalij, I, Grunberg, K, Meijer, G A,
Vonk-Noordegraaf, A, . . . Belien, J A (2011). Rapid quantification of myocardial fibrosis: a new macro-based automated analysis. Cell Oncol (Dordr), 34(4), 343-354. doi: 10.1007/s13402-011-0035-7
14. Laug, W E, DeClerck, Y A, and Jones, P A (1983). Degradation of the subendothelial matrix by tumor cells. Cancer Res, 43(4), 1827-1834.
15. Siegal, T, and Pfeffer, M R (1995). Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability. Int J
Radiat Oncol Biol Phys, 31(1), 57-64. doi: 10.1016/0360-3016(94)e0305-4
16. Stamenkovic, I (2000). Matrix metalloproteinases in tumor invasion and metastasis.
77
Semin Cancer Biol, 10(6), 415-433. doi: 10.1006/scbi.2000.0379
17. Szabo, T L (2004). Diagnostic Ultrasound Imaging: Inside Out. CH8-10.
18. Thames, H D, Jr, Withers, H R, Peters, L J, and Fletcher, G H (1982). Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int J Radiat Oncol Biol Phys, 8(2), 219-226.
19. van Leeuwen-Segarceanu, E M, Dorresteijn, L D, Pillen, S, Biesma, D H, Vogels, O J, and van Alfen, N (2012). Progressive muscle atrophy and weakness after treatment by mantle field radiotherapy in Hodgkin lymphoma survivors. Int J
Radiat Oncol Biol Phys, 82(2), 612-618. doi: 10.1016/j.ijrobp.2010.11.064
20. Woolley, D E (1984). Collagenolytic mechanisms in tumor cell invasion. Cancer
Metastasis Rev, 3(4), 361-372.
21. Yang, Y, and Huang, S Y (2007). Image segmentation by fuzzy c-means clustering algorithm with a novel penalty term. Computing and Informatics, 26(1), 17-31.
22. Yang, Y, Zheng, C, and Lin, P (2005). Fuzzy c-means clustering algorithm with a novel penalty term for image segmentation. Opto-Electronics Review, 13(4), 309-315.
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附錄二
圖 A- 1 患者 9 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
0 32 62 158 251 417
Area(pixels)
Patient No.9 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
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0 32 62 158 251 417
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Time after therapy(days)
88
圖 A- 2 患者 12 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
6 32 62 144 235
Area(pixels)
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Time after therapy(days)
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89
圖 A- 3 患者 18 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
7 33 61 140 240
Area(pixels)
Patient No.18 (Tumor side)
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7 33 61 140 240
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90
圖 A- 4 患者 19 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
6 32 76 158 242
Area(pixels)
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6 32 76 158 242
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Patient No.19 (Fiber ratio)
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Time after therapy(days)
91
圖 A- 5 患者 20 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
13 41 72 160 251
Area(pixels)
Patient No.20 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
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13 41 72 160 251
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Patient No.20 (Fiber ratio)
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Time after therapy(days)
92
圖 A- 6 患者 23 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
2 37 66 142 239
Area(pixels)
Patient No.23 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0.00%
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2 37 66 142 239
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Time after therapy(days)
93
圖 A- 7 患者 28 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
0 27 59 137
Area(pixels)
Patient No.28 (Tumor side)
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0 10000 20000 30000 40000 50000 60000 70000
0 27 59 137
Area(pixels)
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Time after therapy(days)
94
圖 A- 8 患者 28 號肌肉纖維比例統計曲線
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0 27 59 137
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Patient No.28 (Fiber ratio)
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Time after therapy(days)
95
圖 A- 9 患者 30 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
5 40 68
Area(pixels)
Patient No.30 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0 10000 20000 30000 40000 50000 60000 70000
5 40 68
Area(pixels)
Patient No.30 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
96
圖 A- 10 患者 30 號肌肉纖維比例統計曲線
0.00%
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5 40 68
Fiber ratio(%)
Patient No.30 (Fiber ratio)
Tumor side Non tumor side
Time after therapy(days)
97
圖 A- 11 患者 31 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
5 35 70
Area(pixels)
Patient No.31 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0 10000 20000 30000 40000 50000 60000 70000
5 35 70
Area(pixels)
Patient No.31 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
98
圖 A- 12 患者 31 號肌肉纖維比例統計曲線
0.00%
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5 35 70
Fiber ratio(%)
Patient No.31 (Fiber ratio)
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Time after therapy(days)
99
圖 A- 13 患者 32 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
7 34 63
Area(pixels)
Patient No.32 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0 10000 20000 30000 40000 50000 60000 70000
7 34 63
Area(pixels)
Patient No.32 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
100
圖 A- 14 患者 32 號肌肉纖維比例統計曲線
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7 34 63
Fiber ratio(%)
Patient No.32 (Fiber ratio)
Tumor side Non tumor side
Time after therapy(days)
101
圖 A- 15 患者 34 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
2 30 64
Area(pixels)
Patient No.34 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0 10000 20000 30000 40000 50000 60000 70000
2 30 64
Area(pixels)
Patient No.34 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
102
圖 A- 16 患者 34 號肌肉纖維比例統計曲線
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2 30 64
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Patient No.34 (Fiber ratio)
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Time after therapy(days)
103
圖 A- 17 患者 35 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
4 34
Area(pixels)
Patient No.35 (Tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
0 10000 20000 30000 40000 50000 60000 70000
4 34
Area(pixels)
Patient No.35 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
104
圖 A- 18 患者 35 號肌肉纖維比例統計曲線
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4 34
Fiber ratio(%)
Patient No.35 (Fiber ratio)
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Time after therapy(days)
105
圖 A- 19 患者 36 號肌肉組成統計曲線
0 10000 20000 30000 40000 50000 60000 70000
0 27
Area(pixels)
Patient No.36 (Tumor side)
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Time after therapy(days)
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0 27
Area(pixels)
Patient No.36 (Non tumor side)
Whole Muscle Fiber cell Muscle cell
Time after therapy(days)
106
圖 A- 20 患者 36 號肌肉纖維比例統計曲線
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0 27
Fiber ratio(%)
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Time after therapy(days)