臺灣博碩士論文加值系統

近年來，超音波對比劑已被廣泛應用於各種成像模式下超音波訊號的增強，而以超音波對比劑為媒介，應用稀釋理論來計算血液動力學中各項參數的研究則尚在起步的階段。其主要原因是由於稀釋理論過於簡化實際的狀況，欲套用於真實的系統中必須克服許多實際的問題，才能得到正確的血流參數。
在本論文的研究中，我們設計了完整的實驗架構，針對稀釋理論應用於實際系統的適用情形做詳細地討論。我們分別以空心球體及微灌流仿體為待測系統，比較其時間─強度曲線中的各項參數，以及輸出∕輸入端曲線deconvolution結果和理論值的差異。結果顯示在特定的理想狀況下，血流參數分析的結果才能和稀釋理論的推導相近，當待測系統的特性和理想狀況不符時，所得的結果仍可成功地作定性分析，但定量的血流參數計算則需要更進一步的分析研究。

In recent years, ultrasonic contrast agents have been widely used to enhance ultrasonic backscattered signals in various imaging modes. However, research on estimating hemodynamic parameters based on traditional indicator-dilution theory with ultrasonic contrast agents is still at an early stage, due to complications encountered in clinical situations.
In this thesis, we experimentally investigate the validity of applying the dilution theory under various flow conditions. Both a spherical ball system and a perfusion phantom system are explored. Parameters derived from experimental data and deconvolution of input and output curves are compared to theory. Results show that experimental parameters are close to theoretical values only in some specific situations. Nonetheless, when the experimental system deviate from an ideal system, qualitative analysis is still possible but flow quantification requires further investigation.

第一章 緒論1
1.1 超音波對比劑簡介1
1.1.1 超音波對比劑簡史1
1.1.2 超音波對比劑的種類[4]2
1.1.3 目前超音波對比劑的相關研究領域3
1.2 Indicator-Dilution方法源起[12]7
1.3 研究動機9
1.4 論文架構10
第二章 理論基礎11
2.1 稀釋理論（Dilution Theory）[17]11
2.1.1 瞬間注射(bolus injection)12
2.1.2 定流量(constant flow)注射12
2.2 Time-Intensity曲線的參數分析15
2.2.1 Time-Intensity曲線擷取方式15
2.2.2 各項參數分析16
2.3 以輸入/輸出端TI曲線求取transfer function的技巧20
第三章 實驗架構22
3.1 實驗用對比劑22
3.1.1 以人體白蛋白調配22
3.1.2 使用Levovist23
3.2 實驗系統架設24
3.2.1 訊號發射及接收24
3.2.2 空心球體實驗25
3.2.3 空心球體mixing chamber的形式26
3.2.4 血液透析管實驗27
3.3 實驗資料處理28
第四章 實驗結果及分析29
4.1 稀釋理論在不同實驗條件下的適用情形29
4.1.1 不同空心球型式的mixing chamber29
4.1.2 有效體積(effective volume)的影響33
4.1.3 使用不同的超音波對比劑34
4.2 以血液透析管為mixing chamber36
4.2.1 輸出端TI曲線分析37
4.2.2 利用curve-fitting降低雜訊38
4.2.3 參數分析自動化41
4.3 利用deconvolution降低輸入端波形的影響44
4.3.1 單一mixing chamber44
4.3.2 兩個mixing chamber46
4.4 其他參數分析48
4.4.1 相對流量及體積48
4.4.2 curve-fitting後的各項參數50
第五章 結論與討論52
5.1 τ及MTT的分析52
液體流動的型態52
濃度和強度間的關係54
雜訊56
微氣泡濃度 vs. baseline57
分析技巧58
5.2 Deconvolution的適用性60
5.3 結論62
5.4 未來工作63
參考資料64
附錄A 傳統Doppler模式的方法及限制67
附錄B Wiener filter公式推導70

[1] B. B. Goldberg, "The Beginnings of Ultrasound Contrast", Ultrasound Contrast Agents, P1-8, 1997
[2] Gramiak R. Shah PM. Kramer DH, "Ultrasound Cardiography Contrast Studies in Anatomy and Function", Radiology 92, 939-948, 1969
[3] J. Ophir, K. J. Parker, "Contrast Agents in Diagnostic Ultrasound", Ultrasound in Med. & Biol., Vol.15, No. 4, pp. 319-333, 1989
[4] 周定遠, “超音波對比劑簡介”, 中華民國超音波學會http://www.sumroc.org.tw/sumroc/book/echo5-6.html
[5] F. Forsberg, "Physics of Ultrasound Contrast Agents", Ultrasound Contrast Agents, P9-20, 1997
[6] F. Forsberg, B. B. Goldberg, "New Imaging techniques with Ultrasound Contrast Agents", Ultrasound Contrast Agents, P178-192, 1997
[7] de Jong N, "Improvements in Ultrasound Contrast Agents", IEEE Engineering in Medicine and Biology, P72-82,Nov./Dec. 1996
[8] P. Toertoli, D. Bagnai, and D. Righi, "Quantitative Analysis of Doppler Spectrum Modifications Yielded by Contrast Agents Insonified at High Pressure", IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, Vol. 46 ,No 1, January 1999
[9] P. Tortoli, M. Pratesi, V. Michelassi, "Doppler Spectra from Contrast Agents Crossing an Ultrasound Field", IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, VOL. 47, NO. 3, MAY 2000
[10] L. M. Wang, K. K. Shung, "Contrast Medium Assisted Fluid Flow Measurement", IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol. 42, NO. 2, March 1995
[11] K. K. Shung and R. R. Flenniken, “Time-Domain Ultrasonic Contrast Blood Flowmetry”, Ultrasound in Med. & Biol., Vol. 21, No. 1, pp. 71-78, 1995
[12] F. S. Grodins, “Basic Concepts in the Determination of Vascular Volumes by Indicator-Dilution Methods”, Circulation Research, Vol. X, March 1962
[13] A. N. Demaria, W. Bommer, O. L. Kwan, K. Riggs, M. Smith, J. Waters, “In Vivo Correlation of Thermodilution Cardiac Output and Videodensitometric Indicator-Dilution Curves Obtained From Contrast Two-Dimensional Echocardiograms”, American College of Cardiology, Vol. 3. No. 4, April 1984:999-1004
[14] S. Kaul, P. Kelly, J. D. Oliner, W. P. Glasheen, M. W. Leller, D. D.Watson, “Assessment of Regional Myocardial Blood Flow With Myocardial Contrast Two-Dimensional Echocardiography”, JACC Vol. 13 No. 2, February 1989:468-82
[15] D Rovai., S. Nissen, J. Elion, M Smith., A. L’abbate, O. L. Kwan, A. N. Demaria, “Contrast Echo Washout Curves From the Left Ventricle: Application of Basic Principles of Indicator-Dilution Theory and Calculation of Ejection Fraction”, JACC Vol. 10 No. 1, July 1987:125-34
[16] T. R. Porter, A. D’sa, C. Turner, L. A. Jones, A. J Minisi, P. K. Mohanty, G. W. Vetrovec, J. V. Nixon, “Myocardial Contrast Echocardiography for the Assessment of Coronary Blood Flow Reverse: Validation in Humans”, JACC Vol. 21 No. 2, February 1993:349-55
[17] X. Chen, K. Q. Schwarz, D. Phillips, S. D. Steinmetz, and R. Schief, ”A Mathematical Model for the Assessment of Hemodynamic Parameters Using Quantitative Contrast Echocardiography”, IEEE Transactions on Biomedical Engineering, VOL. 45, NO. 6, June 1998
[18] D. O. Cooney, "Biomedical Engineering Principles", Marcel Dekker, INC. New York and Basel, 1976
[19] A. D’ Sa, “Acoustic Densitometry” ,white paper of Hewlett-Packard Company
[20] J.H.T. Bates, "Deconvolution of Tracer and Dilution Data Using the Wiener Filter", IEEE Transaction on Biomedical Engineering, Vol. 38. No. 12, December 1991
[21] W. K. Mark, G. William, T. Kuldeep, G. Adrian, K. Sanjiv, "Myocardial Contrast Echocardiography Without Significant Hemodynamic Effects or Reactive Hyperemia: A Major Advantage in the Imaging of Regional Myocardial Perfusion", JACC Vol. 12, No. 4, October 1988:1039-47
[22] B. Schrope, V. L. Newhouse, and V. Uhlendorf, “Simulated Capillary Blood Flow Measurement Using A Nonlinear Ultrasonic Contrast Agent”, Ultrasonic Imaging 14, 134-158, 1992
[23] J. Hindle, A. C. Perkins, "A Perfusion Phantom for the Evaluation of Ultrasound Contrast Agents", Ultrasound in Med. & Biol., Vol. 20 No. 3, pp. 309-314, 1994
[24] S. L. Bridal, O. Lucidarme, J-M. Correas, P. N. Burns, J-F. Moreau, G. Berger, “Quantification of Ultrasound Contrast Agent in an In Vitro Perfusion Phantom”, IEEE Ultrasonics Symposium, 1999
[25] L. Axel, "Cerebral Blood Flow Determination by Rapid-Sequence Computed Tomography", Radiology 137:679-686, Dec. 1980
[26] H. Medwin, "Counting bubbles acoustically: A review", Ultrasonics, vol. 15, pp. 7-13, 1977
[27] A. T. Kerr and J. W. Hunt, “A Method for Computer Simulation of Ultrasound Doppler Color Flow Images - I. Theory and Numerical Method”, Ultrasound in Medicine & Biology, vol(18), No. 10, 1992.
[28] J. A. Jensen, “Estimation of Blood Velocity Using Ultrasound”, Combridge University Press, 1996.
[29] Rsmussen K, ”Review: Methodological problems related to measurement of quantitative blood flow with the ultrasound doppler technique”, Scand J Clin & Lab Invest. 47(4): 303-9,1987.
[30] P. N. Burns, C. C. Jaffe, “Quantitative flow measurements with Doppler ultrasound: techniques, accuracy, and limitations”, Radiologic Clinics of North America, 23(4):641-57, 1985 Dec.
[31] M. Casty, D. P. Giddens, “25 + 1 channel pulsed ultrasound Doppler velocity meter for quantitative flow measurements and turbulence analysis”, Ultrasound in Medicine & Biology, 10(2):161-72, 1984.
[32] 李百祺, “醫用超音波原理”, Chapter 8 , 73-76, 1999