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超声造影剂微泡非线性动力学响应的机理及相关应用

于洁 郭霞生 屠娟 章东

超声造影剂微泡非线性动力学响应的机理及相关应用

于洁, 郭霞生, 屠娟, 章东
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  • 随着生命科学及现代医学的发展, 一体化无创精准诊疗已经日益成为人们关注的焦点问题, 而关于超声造影剂微泡的非线性效应的相关机理、动力学建模及其在超声医学领域中的应用研究也得到了极大的推动. 本文对下列课题进行了总结和讨论, 包括: 1)基于Mie散射技术和流式细胞仪对造影剂微泡参数进行定征的一体化解决方案; 2)通过对微泡包膜的黏弹特性进行非线性修正, 构建新的包膜微泡动力学模型; 3)探索造影剂惯性空化阈值与其包膜参数之间的相关性; 以及4)研究超声联合造影剂微泡促进基因/药物转染效率并有效降低其生物毒性的相关机理.
    • 基金项目: 国家重点基础研究发展计划(批准号: 2011CB707900)、国家自然科学基金(批准号: 61072027, 81127901, 81227004, 11374155, 11174141, 11274170, 11474001和11474161)和国家高技术研究发展计划(批准号: 2012AA022702)资助的课题.
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    Hernot S, Klibanov A L 2008 Adv. Drug Deliver. Rev. 60 1153

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    Lindner J R 2009 Nat Rev Cardiol 6 475

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    Stride E P, Coussios C C 2010 P. I. Mech. Eng. H 224 171

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    Mitragotri S 2005 Nat. Rev. Drug Discov. 4 255

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    Escoffre J M, Mannaris C, Geers B, Novell A, Lentacker I, Averkiou M, Bouakaz A 2013 IEEE T. Ultrason. Ferr. 60 78

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    Faez T, Emmer M, Kooiman K, Versluis M, Van der Steen A, De Jong N 2013 IEEE T. Ultrason. Ferr. 60 7

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    Dejong N, Cornet R, Lancee C T 1994 Ultrasonics 32 447

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    Rayleigh 1917 Philos Mag 34 94

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    Plesset M S 1949 J. Appl. Mech.-T. Asme 16 277

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    Roy R A, Madanshetty S I, Apfel R E 1990 J. Acoust. Soc. Am. 87 2451

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    Hoff L, Sontum P C, Hovem J M 2000 J. Acoust. Soc. Am. 107 2272

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    Tu J, Swalwell J E, Giraud D, Cui W C, Chen W Z, Matula T J 2011 IEEE Trans. Ultrason. Ferr. 58 955

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    Morgan K E, Allen J S, Dayton P A, Chomas J E, Klibanov A L, Ferrara K W 2000 IEEE Trans. Ultrason. Ferr. 47 1494

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    Chatterjee D, Sarkar K 2003 Ultrasound Med. Biol. 29 1749

    [24]

    Sarkar K, Shi W T, Chatterjee D, Forsberg F 2005 J. Acoust. Soc. Am. 118 539

    [25]

    Doinikov A A, Dayton P A 2007 J. Acoust. Soc. Am. 121 3331

    [26]

    Sijl J, Dollet B, Ouvervelde M, Garbin V, Rozendal T, De Jong N, Lohse D, Versluis M 2010 J. Acoust. Soc. Am. 128 3239

    [27]

    Emmer M, Van Wamel A, Goertz D E, De Jong N 2007 Ultrasound Med. Biol. 33 941

    [28]

    Viti J, Mori R, Guidi F, Versluis M, De Jong N, Tortoil P 2012 IEEE Trans. Ultrason. Ferr. 59 2818

    [29]

    Van der Meer S M, Marmottant P G, Hilgenfeldt S, Versluis M, Lohse D, Chin C T, Bouakaz A, Mastik F, Emmer M 2005 2005 IEEE Ultrasonics Symposium 1-4 974

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    De Jong N, Emmer M, Chin C T, Bouakaz A, Mastik F, Lohse D, Versluis M 2007 Ultrasound Med. Biol. 33 653

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    Sijl J, Overvelde M, Dollet B, Garbin V, De Jong N, Lohse D, Versluis M 2011 J. Acoust. Soc. Am. 129 1729

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    Emmer M, Van Wamel A, Goertz D E, Versluis M, De Jong N 2006 2006 IEEE Ultrasonics Symposium 1-5 1545

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    Overvelde M, Garbin V, Sijl J, Dollet B, De Jong N, Lohse D, Versluis M 2010 Ultrasound Med. Biol. 36 2080

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    Hay T A, Ilinskii Y A, Zabolotskaya E A, Hamilton M F 2013 J. Acoust. Soc. Am. 134 1454

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    Shams M M, Dong M Z, Mahinpey N 2014 Aiche J. 60 2660

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    Shen Y Y, Longo M L, Powell R L 2008 J. Colloid Interf. Sci. 327 204

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    Faez T, Emmer M, Docter M, Sijl J, Versluis M, De Jong N 2011 Ultrasound Med. Biol. 37 958

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    Van der Meer S M, Dollet B, Voormolen M M, Chin C T, Bouakaz A, De Jong N, Versluis M, Lohse D 2007 J. Acoust. Soc. Am. 121 648

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    Marmottant P, Van der Meer S, Emmer M, Versluis M, De Jong N, Hilgenfeldt S, Lohse D 2005 J. Acoust. Soc. Am. 118 3499

    [40]

    Doinikov A A, Haac J F, Dayton P A 2009 Ultrasonics 49 269

    [41]

    De Jong N, Emmer M, Van Wamel A, Versluis M 2009 Med. Biol. Eng. Comput. 47 861

    [42]

    Guo X S, Li Q, Zhang Z, Zhang D, Tu J 2013 J. Acoust. Soc. Am. 134 1622

    [43]

    Dayton P A, Morgan K E, Klibanov A L, Brandenburger G H, Ferrara K W 1999 IEEE Trans. Ultrason. Ferr. 46 220

    [44]

    Matula T J, Swalwell J, Tu J, Cui W C, Chen W Z 2011 IEEE International Ultrasonics Symposium (IUS) Orlando, FL, USA, October 18-21, 2011 p156

    [45]

    Tu J, Guan J F, Qiu Y Y, Matula T J 2009 J. Acoust. Soc. Am. 126 2954

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    Wu J, Nyborg W L 2008 Adv. Drug Deliver. Rev. 60 1103

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    Maruvada S, Hynynen K 2004 Ultrasound Med. Biol. 30 67

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    Feril L B, Kondo T, Zhao Q L, Ogawa R, Tachibana K, Kudo N, Fujimoto S, Nakamura S 2003 Ultrasound Med. Biol. 29 331

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    Yu H, Xu L 2014 J. Control. Release 174 151

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    Miller D L, Thomas R M 1995 Ultrasound Med. Biol. 21 1059

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    Flynn H G, Church C C 1988 J. Acoust. Soc. 84 985

    [53]

    Newman C, Bettinger T 2007 Gene Ther. 14 465

    [54]

    Chen S Y, Shohet R V, Bekeredjian R, FrenkelP, Grayburn P A 2003 J. Am. Coll. Cardiol. 42 301

    [55]

    Sheyn D, Kimelman-Bleich N, Pelled G, Zilberman Y, Gazit D, Gazit Z 2008 Gene Ther. 15 257

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    Duvshani-Eshet M, Benny O, Morgenstern A, Machluf M 2007 Mol. Cancer Ther. 6 2371

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    Duvshani-Eshet M, Machluf M 2007 Cancer Gene Ther. 14 306

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    Collins C G, Tangney M, Larkin J O, Casey G, Whelan M C, Cashman J, Murphy J, Soden D, Vejda S, Mckenna S, Kiely B, Collins J K, Barrett J, Aarons S, O’Sullivan G C 2006 Cancer Gene Ther. 13 1061

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    Paul S, Katiyar A, Sarkar K, Chatterjee D, Shi W T, Forsberg F 2010 J. Acoust. Soc. Am. 127 3846

    [63]

    Tsiglifis K, Pelekasis N A 2008 J. Acoust. Soc. Am. 123 4059

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    Li Q, Matula T J, Tu J, Guo X S, Zhang D 2013 Phys. Med. Biol. 58 985

    [65]

    Chang P P, Chen W S, Mourad P D, Poliachik S L, Crum L A 2001 IEEE Trans. Ultrason. Ferr. 48 161

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    Chen W S, Matula T J, Brayman A A, Crum L A 2003 J. Acoust. Soc. Am. 113 643

    [67]

    Tu J, Matula T J, Brayman A A, Crum L A 2006 Ultrasound Med. Biol. 32 281

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    Apfel R E, Holland C K 1991 Ultrasound Med. Biol. 17 179

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    Deng C X, Xu Q H, Apfel R E, Holland C K 1996 Ultrasound Med. Biol. 22 939

    [70]

    Deshpande M C, Prausnitz M R 2007 J. Control. Release 118 126

    [71]

    Mitragotri S 2005 Nat. Rev. Drug Discov. 4 255

    [72]

    Tsivgoulis G, Alexandrov A V 2007 Neurotherapeutics 4 420

    [73]

    Miller D L, Pislaru S V, Greenleaf J E 2002 Somat Cell Mol Genet 27 115

    [74]

    Qiu Y, Luo Y, Zhang Y, Cui W, Zhang D, Wu J, Zhang J, Tu J 2010 J. Control. Release 145 40

    [75]

    Zhang C B, Cao H L, Li Q, Tu J, Guo X S, Liu Z, Zhang D 2013 Ultrasound Med. Biol. 39 161

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    Park J, Fan Z Z, Deng C X 2011 J. Biomech. 44 164

    [77]

    Ohl C D, Wolfrm B 2003 Bba-Gen. Subjects 1624 131

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    Qiu Y Y, Zhang C B, Tu J, Zhang D 2012 J.Biomech 45 1339

    [79]

    Tran T A, Roger S, Le Guennec J Y, Tranquart F, Bouakaz A 2007 Ultrasound Med. Biol. 33 158

  • [1]

    Pace N G, Cowley A, Campbell A M 1997 J. Acoust. Soc. Am. 102 1474

    [2]

    Goldberg B B, Raichlen J S, Forsberg F 2001 Ultrasound contrast agents: basic principles and clinical applications (2nd Ed.) (London: Martin Dunitz)

    [3]

    Hernot S, Klibanov A L 2008 Adv. Drug Deliver. Rev. 60 1153

    [4]

    Lindner J R 2009 Nat Rev Cardiol 6 475

    [5]

    Stride E P, Coussios C C 2010 P. I. Mech. Eng. H 224 171

    [6]

    Mitragotri S 2005 Nat. Rev. Drug Discov. 4 255

    [7]

    Ferrara K, Pollard R, Borden M 2007 Annu.Rev. Biomed. Eng. 9 415

    [8]

    Kennedy J E 2005 Nat. Rev. Cancer 5 321

    [9]

    Everbach E C, Francis C W 2000 Ultrasound Med. Biol. 26 1153

    [10]

    Escoffre J M, Mannaris C, Geers B, Novell A, Lentacker I, Averkiou M, Bouakaz A 2013 IEEE T. Ultrason. Ferr. 60 78

    [11]

    Faez T, Emmer M, Kooiman K, Versluis M, Van der Steen A, De Jong N 2013 IEEE T. Ultrason. Ferr. 60 7

    [12]

    Dejong N, Hoff L 1993 Ultrasonics 31 175

    [13]

    Dejong N, Cornet R, Lancee C T 1994 Ultrasonics 32 455

    [14]

    Dejong N, Cornet R, Lancee C T 1994 Ultrasonics 32 447

    [15]

    Church C C 1995 J. Acoust. Soc. Am. 97 1510

    [16]

    Rayleigh 1917 Philos Mag 34 94

    [17]

    Plesset M S 1949 J. Appl. Mech.-T. Asme 16 277

    [18]

    Roy R A, Madanshetty S I, Apfel R E 1990 J. Acoust. Soc. Am. 87 2451

    [19]

    Hoff L, Sontum P C, Hovem J M 2000 J. Acoust. Soc. Am. 107 2272

    [20]

    Chomas J E, Dayton P, Allen J, Morgan K, Ferrara K W 2001 IEEE Trans. Ultrason. Ferr. 48 232

    [21]

    Tu J, Swalwell J E, Giraud D, Cui W C, Chen W Z, Matula T J 2011 IEEE Trans. Ultrason. Ferr. 58 955

    [22]

    Morgan K E, Allen J S, Dayton P A, Chomas J E, Klibanov A L, Ferrara K W 2000 IEEE Trans. Ultrason. Ferr. 47 1494

    [23]

    Chatterjee D, Sarkar K 2003 Ultrasound Med. Biol. 29 1749

    [24]

    Sarkar K, Shi W T, Chatterjee D, Forsberg F 2005 J. Acoust. Soc. Am. 118 539

    [25]

    Doinikov A A, Dayton P A 2007 J. Acoust. Soc. Am. 121 3331

    [26]

    Sijl J, Dollet B, Ouvervelde M, Garbin V, Rozendal T, De Jong N, Lohse D, Versluis M 2010 J. Acoust. Soc. Am. 128 3239

    [27]

    Emmer M, Van Wamel A, Goertz D E, De Jong N 2007 Ultrasound Med. Biol. 33 941

    [28]

    Viti J, Mori R, Guidi F, Versluis M, De Jong N, Tortoil P 2012 IEEE Trans. Ultrason. Ferr. 59 2818

    [29]

    Van der Meer S M, Marmottant P G, Hilgenfeldt S, Versluis M, Lohse D, Chin C T, Bouakaz A, Mastik F, Emmer M 2005 2005 IEEE Ultrasonics Symposium 1-4 974

    [30]

    De Jong N, Emmer M, Chin C T, Bouakaz A, Mastik F, Lohse D, Versluis M 2007 Ultrasound Med. Biol. 33 653

    [31]

    Sijl J, Overvelde M, Dollet B, Garbin V, De Jong N, Lohse D, Versluis M 2011 J. Acoust. Soc. Am. 129 1729

    [32]

    Emmer M, Van Wamel A, Goertz D E, Versluis M, De Jong N 2006 2006 IEEE Ultrasonics Symposium 1-5 1545

    [33]

    Overvelde M, Garbin V, Sijl J, Dollet B, De Jong N, Lohse D, Versluis M 2010 Ultrasound Med. Biol. 36 2080

    [34]

    Hay T A, Ilinskii Y A, Zabolotskaya E A, Hamilton M F 2013 J. Acoust. Soc. Am. 134 1454

    [35]

    Shams M M, Dong M Z, Mahinpey N 2014 Aiche J. 60 2660

    [36]

    Shen Y Y, Longo M L, Powell R L 2008 J. Colloid Interf. Sci. 327 204

    [37]

    Faez T, Emmer M, Docter M, Sijl J, Versluis M, De Jong N 2011 Ultrasound Med. Biol. 37 958

    [38]

    Van der Meer S M, Dollet B, Voormolen M M, Chin C T, Bouakaz A, De Jong N, Versluis M, Lohse D 2007 J. Acoust. Soc. Am. 121 648

    [39]

    Marmottant P, Van der Meer S, Emmer M, Versluis M, De Jong N, Hilgenfeldt S, Lohse D 2005 J. Acoust. Soc. Am. 118 3499

    [40]

    Doinikov A A, Haac J F, Dayton P A 2009 Ultrasonics 49 269

    [41]

    De Jong N, Emmer M, Van Wamel A, Versluis M 2009 Med. Biol. Eng. Comput. 47 861

    [42]

    Guo X S, Li Q, Zhang Z, Zhang D, Tu J 2013 J. Acoust. Soc. Am. 134 1622

    [43]

    Dayton P A, Morgan K E, Klibanov A L, Brandenburger G H, Ferrara K W 1999 IEEE Trans. Ultrason. Ferr. 46 220

    [44]

    Matula T J, Swalwell J, Tu J, Cui W C, Chen W Z 2011 IEEE International Ultrasonics Symposium (IUS) Orlando, FL, USA, October 18-21, 2011 p156

    [45]

    Tu J, Guan J F, Qiu Y Y, Matula T J 2009 J. Acoust. Soc. Am. 126 2954

    [46]

    Wu J, Nyborg W L 2008 Adv. Drug Deliver. Rev. 60 1103

    [47]

    Kobayashi N, Yasu T, Yamada S, Kudo N, Kuroki M, Kawakami M, Miyatake K, Saito M 2002 Ultrasound Med. Biol. 28 949

    [48]

    Maruvada S, Hynynen K 2004 Ultrasound Med. Biol. 30 67

    [49]

    Feril L B, Kondo T, Zhao Q L, Ogawa R, Tachibana K, Kudo N, Fujimoto S, Nakamura S 2003 Ultrasound Med. Biol. 29 331

    [50]

    Yu H, Xu L 2014 J. Control. Release 174 151

    [51]

    Miller D L, Thomas R M 1995 Ultrasound Med. Biol. 21 1059

    [52]

    Flynn H G, Church C C 1988 J. Acoust. Soc. 84 985

    [53]

    Newman C, Bettinger T 2007 Gene Ther. 14 465

    [54]

    Chen S Y, Shohet R V, Bekeredjian R, FrenkelP, Grayburn P A 2003 J. Am. Coll. Cardiol. 42 301

    [55]

    Sheyn D, Kimelman-Bleich N, Pelled G, Zilberman Y, Gazit D, Gazit Z 2008 Gene Ther. 15 257

    [56]

    Duvshani-Eshet M, Benny O, Morgenstern A, Machluf M 2007 Mol. Cancer Ther. 6 2371

    [57]

    Duvshani-Eshet M, Machluf M 2007 Cancer Gene Ther. 14 306

    [58]

    Collins C G, Tangney M, Larkin J O, Casey G, Whelan M C, Cashman J, Murphy J, Soden D, Vejda S, Mckenna S, Kiely B, Collins J K, Barrett J, Aarons S, O’Sullivan G C 2006 Cancer Gene Ther. 13 1061

    [59]

    Craig R, Cutrera J, Zhu S, Xia X, Lee Y H, Li S 2008 Mol. Ther. 16 901

    [60]

    Marston P L 1991 Appl. Optics 30 3479

    [61]

    Bohren C F, Huffman D R 1998 Absorption and scattering of light by small particles (Weinheim, Germany: Wiley-VCH Verlag GmbH)

    [62]

    Paul S, Katiyar A, Sarkar K, Chatterjee D, Shi W T, Forsberg F 2010 J. Acoust. Soc. Am. 127 3846

    [63]

    Tsiglifis K, Pelekasis N A 2008 J. Acoust. Soc. Am. 123 4059

    [64]

    Li Q, Matula T J, Tu J, Guo X S, Zhang D 2013 Phys. Med. Biol. 58 985

    [65]

    Chang P P, Chen W S, Mourad P D, Poliachik S L, Crum L A 2001 IEEE Trans. Ultrason. Ferr. 48 161

    [66]

    Chen W S, Matula T J, Brayman A A, Crum L A 2003 J. Acoust. Soc. Am. 113 643

    [67]

    Tu J, Matula T J, Brayman A A, Crum L A 2006 Ultrasound Med. Biol. 32 281

    [68]

    Apfel R E, Holland C K 1991 Ultrasound Med. Biol. 17 179

    [69]

    Deng C X, Xu Q H, Apfel R E, Holland C K 1996 Ultrasound Med. Biol. 22 939

    [70]

    Deshpande M C, Prausnitz M R 2007 J. Control. Release 118 126

    [71]

    Mitragotri S 2005 Nat. Rev. Drug Discov. 4 255

    [72]

    Tsivgoulis G, Alexandrov A V 2007 Neurotherapeutics 4 420

    [73]

    Miller D L, Pislaru S V, Greenleaf J E 2002 Somat Cell Mol Genet 27 115

    [74]

    Qiu Y, Luo Y, Zhang Y, Cui W, Zhang D, Wu J, Zhang J, Tu J 2010 J. Control. Release 145 40

    [75]

    Zhang C B, Cao H L, Li Q, Tu J, Guo X S, Liu Z, Zhang D 2013 Ultrasound Med. Biol. 39 161

    [76]

    Park J, Fan Z Z, Deng C X 2011 J. Biomech. 44 164

    [77]

    Ohl C D, Wolfrm B 2003 Bba-Gen. Subjects 1624 131

    [78]

    Qiu Y Y, Zhang C B, Tu J, Zhang D 2012 J.Biomech 45 1339

    [79]

    Tran T A, Roger S, Le Guennec J Y, Tranquart F, Bouakaz A 2007 Ultrasound Med. Biol. 33 158

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  • 收稿日期:  2015-01-05
  • 修回日期:  2015-02-10
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超声造影剂微泡非线性动力学响应的机理及相关应用

  • 1. 近代声学教育部重点实验室, 南京大学物理学院, 南京 210093;
  • 2. 江苏省中医院, 南京 210029
    基金项目: 

    国家重点基础研究发展计划(批准号: 2011CB707900)、国家自然科学基金(批准号: 61072027, 81127901, 81227004, 11374155, 11174141, 11274170, 11474001和11474161)和国家高技术研究发展计划(批准号: 2012AA022702)资助的课题.

摘要: 随着生命科学及现代医学的发展, 一体化无创精准诊疗已经日益成为人们关注的焦点问题, 而关于超声造影剂微泡的非线性效应的相关机理、动力学建模及其在超声医学领域中的应用研究也得到了极大的推动. 本文对下列课题进行了总结和讨论, 包括: 1)基于Mie散射技术和流式细胞仪对造影剂微泡参数进行定征的一体化解决方案; 2)通过对微泡包膜的黏弹特性进行非线性修正, 构建新的包膜微泡动力学模型; 3)探索造影剂惯性空化阈值与其包膜参数之间的相关性; 以及4)研究超声联合造影剂微泡促进基因/药物转染效率并有效降低其生物毒性的相关机理.

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