层状生物媒质中的聚焦声场研究
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摘要
近年来,用于无创伤治疗肿瘤的高强度聚焦超声(HIFU)技术,已经成为人们关注的热点。大量的实验研究表明,HIFU的治疗机理,主要是利用焦域的声能转化为热能,使病灶组织升温而发生热坏死或灭活。在临床治疗中,生物体大多是由多层组织构成的,HIFU声焦域的位置和形状会受到生物组织结构和发射声强的影响。因此,为了对声焦域准确定位并有效杀灭病灶,研究层状生物媒质中的HIFU声场是非常必要的。
本文采用KZK方程描述层状媒质中的聚焦超声波传播,分析了声波传播中媒质衰减、衍射、非线性以及媒质边界的作用。采用时域有限差分数值算法求解KZK方程,并利用该算法计算了凹球面换能器在不同条件下的声场。理论分析了层状生物媒质中的HIFU声场特性变化,同时分析了接近实际HIFU治疗的水-脂肪-肝三层生物组织模型中,HIFU声焦域的变化规律。为了实验验证模拟分析结果,分别测量了水-琼脂-水、水-琼脂-蓖麻油媒质结构中,线性及非线性情况下,声轴平面上的声压分布。实验测量结果和数值模拟结果规律符合较好,验证了理论分析的有效性。
理论分析和实验结果均表明,传播媒质结构和发射声压对凹球面换能器HIFU声场分布都有影响,其声焦域特性的变化规律较好地解释了相关文献中关于生物组织中不同辐照强度和辐照深度的损伤实验现象,为分析HIFU治疗时生物组织的声焦域与损伤区域关系提供了依据。
In recent years, the high intensity focused ultrasound (HIFU) which is used for non-contacting treating tumor gets hold of more and more attention. The mechanism of HIFU sonication is that temperature rising, caused by sound energy transformation to thermal energy in focused region, results in focus tissue necrotizing or disrupting. During clinical therapy, both tissue conformation and sound intensity have influences on the site and shape of HIFU sound field in the multi-layer biological tissue. In order to locate sound field exactlyand treat focus effectively, the HIFU sound field in layer biological media has been studied.
The "KZK" equation, which takes into account the sound absorption, diffraction, nonlinearity and media boundary, was adopted to describe focused ultrasonic wave in layer media in this paper. A time domain numerical solution to the "KZK" equation was used to calculate HIFU sound field of a concave spherical ultrasound transducer in different initial conditions. The variation laws of HIFU sound field and sound focal region in the water-fat-liver layer media, which was used to simulate sound propagation of HIFU sonication were analyzed. Then, some experiments were carried out to validate the numerical simulating results. The pressure distributions of sound axial plane were measured in the layered water-agar pattern-water media and water-agar pattern-castor oil media in different sound pressure conditions. Good agreements with simulation show the availability of theoretical analysis.
Both theoretical analyses and experimental results show that absorption of layered media and nonlinearity of high intensity sound pressure have influences on the HIFU sound focal regions. Our research results can explain the damage phenomena in related literatures perfectly. It provides a reference basis for analyzing the relation between sound focal region and lesion of tissue in HIFU sonication.
本文采用KZK方程描述层状媒质中的聚焦超声波传播,分析了声波传播中媒质衰减、衍射、非线性以及媒质边界的作用。采用时域有限差分数值算法求解KZK方程,并利用该算法计算了凹球面换能器在不同条件下的声场。理论分析了层状生物媒质中的HIFU声场特性变化,同时分析了接近实际HIFU治疗的水-脂肪-肝三层生物组织模型中,HIFU声焦域的变化规律。为了实验验证模拟分析结果,分别测量了水-琼脂-水、水-琼脂-蓖麻油媒质结构中,线性及非线性情况下,声轴平面上的声压分布。实验测量结果和数值模拟结果规律符合较好,验证了理论分析的有效性。
理论分析和实验结果均表明,传播媒质结构和发射声压对凹球面换能器HIFU声场分布都有影响,其声焦域特性的变化规律较好地解释了相关文献中关于生物组织中不同辐照强度和辐照深度的损伤实验现象,为分析HIFU治疗时生物组织的声焦域与损伤区域关系提供了依据。
In recent years, the high intensity focused ultrasound (HIFU) which is used for non-contacting treating tumor gets hold of more and more attention. The mechanism of HIFU sonication is that temperature rising, caused by sound energy transformation to thermal energy in focused region, results in focus tissue necrotizing or disrupting. During clinical therapy, both tissue conformation and sound intensity have influences on the site and shape of HIFU sound field in the multi-layer biological tissue. In order to locate sound field exactlyand treat focus effectively, the HIFU sound field in layer biological media has been studied.
The "KZK" equation, which takes into account the sound absorption, diffraction, nonlinearity and media boundary, was adopted to describe focused ultrasonic wave in layer media in this paper. A time domain numerical solution to the "KZK" equation was used to calculate HIFU sound field of a concave spherical ultrasound transducer in different initial conditions. The variation laws of HIFU sound field and sound focal region in the water-fat-liver layer media, which was used to simulate sound propagation of HIFU sonication were analyzed. Then, some experiments were carried out to validate the numerical simulating results. The pressure distributions of sound axial plane were measured in the layered water-agar pattern-water media and water-agar pattern-castor oil media in different sound pressure conditions. Good agreements with simulation show the availability of theoretical analysis.
Both theoretical analyses and experimental results show that absorption of layered media and nonlinearity of high intensity sound pressure have influences on the HIFU sound focal regions. Our research results can explain the damage phenomena in related literatures perfectly. It provides a reference basis for analyzing the relation between sound focal region and lesion of tissue in HIFU sonication.
引文
[1] J. G. Lynn, R. L. Zwemer, A. J. Chick. A new method for the generation and use of focused ultrasound in experimental biology. J. Gen. Physiol., 1942,26(1):179~193
[2] J. G. Lynn, T. J. Putnam. Histological and cerebral lesions produced by focused ultrasound. Am. J. Pathol., 1944, 20(3):637~649
[3] W. J. Fry, W. H. Mosberg. J. W. Barnard. Production of focal destructive lesionsin the central nervous system with ultrasound. J. Neurosurg., 1954,11(2):471~478
[4] A. K. Burov, G. D. Andreevskaya. Action of high intensity ultrasonic vibrations on malignant tumors in animals and man. Doklady Akad.Nauk S.S.S.R., 1956,106:239~241,ibid,445~448
[5] A. Sibille, F. Prat, J. Y. Chapelon. Characterization of extra- corporeal ablation of normal and tumor-bearing liver tissue by high intensity focused ultrasound. Ultrasound Med. & Bio., 1993, 19(9):803~813
[6] L. A. Frizzell, C. A. Linke, E. L. Carstensen, et al. Thresholds for focal ultrasonic lesions in rabbit kidney,liver and testicle. IEEE Trans.Biomed.Eng., 1977, 24(2): 393~396
[7] L. A. Frizzell. Threshold for damage to mammalian live by high intensity focused ultrasound. IEEE Trans. U. F. F. C., 1988, 35(5):578~581
[8] C. R. Hill, I. Rivens, M. G. Vaughan, et al. Lesion development in focused ultrasound surgery: A general model. Ultrasound. in Med. & Bio. 1994,20(3):259~269
[9] T. C. Robinson, P. P. Lele. An analysis of lesion development in brain and in plastics by high intensity focused ultrasound at low megahertz frequencies. J. Acoust. Soc. Am., 1997, 51(4):1333~1351
[10] R.L. Clarke, G. R. Ter Haar. Mechanisms of lesion formation by high intensity focused ultrasound. Ultrasound Med. & Bio., 1995, 21(4):432~440
[11] N. A. Watkin, G. R. Ter Haar, I. Rivers. The intensity dependence of the site of maximal energy deposition in focused ultrasound surgery. Ultrasound in Med.&Bio.,1996,22(4):483~491
[12] P. M. Meaney, M. D. Cahill, G. R. Ter Haar. The intensity dependence of lesion position shift during focused ultrasound surgery. Ultrasound in Med. & Bio., 2000,26(3):441~450
[13] 刘宝琴,熊树华,王智彪,等.体外不同频率高强度聚焦超声的生物学焦域.中国超声医学杂志,2002,18(6):417~420
[14] 刘宝琴,熊树华,李发琪,等.辐照深度对高强度聚焦超声的生物学焦域的影响.中国超声医学杂志,2002,18(8):565~568
[15] P. M. Meaney, R. L. Clarker, G. R. Ter Haar, et al. A 3-D finite element model for computation of temperature profiles and regions of thermal damage during focused ultrasound surgery exposures. Ultrasound in Med. & Bio., 1998, 24(9):1489~1499
[16] Zhibiao Wang, Jin Bai, Faqi Li, et al. Study of a “biological focal region”of high-intensity focused ultrasound. Ultrasound in Med. & Bio., 2003, 29(5):749~754
[17] Qiang Zhang, Faqi Li, Ruo Feng, et al. Numerical simulation of the transient temperature field from an annular focused ultrasonic transducer. Ultrasound in Med. & Bio., 2003, 29(4):585~589
[18] 侯秀珍,徐祯祥,金长善,等.高强度聚焦超声热疗中无损测温的实验研究.中国超声医学杂志.2002,18(9):653~657
[19] 沙卫红,李瑜元,聂玉强,等.高强度聚焦超声定位损伤离体牛肝的量效学研究.临床超声医学杂志,2004,6(1):1~3
[20] 李发琪,王智彪,杜永洪,等.高强度聚焦超声“切除”组织的剂量学研究.中国超声医学杂志,2006,23(4):839~843
[21] H. T. O'neil. Theory of focusing radiator. J. Acoust. Soc. Am. 1949, 21:516~526
[22] B. G. Lucsa,Acoust. Soc. Am., 1983,73(6): 1966~1971
[23] B. G. Lucsa, T. G. Muir. The field of a focusing source. J. Acoust. Soc. Am., 1983, 72(4):1289~1296
[24] 喻明,张德俊.不同激励聚焦声源的焦斑特性比较.南京大学学报,2000,36(3):357~362
[25] 张樯,许坚毅,冯若,等.环状 HIFU 换能器焦域形态的数值模拟研究.中国超声医学杂志,2001,17(5):321~324
[26] B. G. Lucsa, T. G. Muir. Field of a finite-amplitude focusing source. J. Acoust. Soc. Am., 1983, 74(5):1522~1528
[27] W. Swindell. A theoretical study of nonlinear effects with focused ultrasound in tissues: an “acoustic bragg peak” Ultrasound in Med. & Bio., 1984, 11(1):121~130
[28] T. S. Hart, M. F. Hamilton. Nonlinear effects in sound beams. J. Acoust. Soc. Am., 1988,84(5): 1488~1496
[29] M. F. Hamilton, D. T. Blackstock. Nonlinear acoustics. editors Academic Press, 1998. 137~138,426~427
[30] J. Berntsen. Numerical calculations of finite amplitude sound beams. in frontiers of nonlinear acoustics: 12th ISNA. M. F. Hamilon and D. T. Blackstock, Eds. London:Elsevier, 1990. 191~196
[31] P. T. Christopher,K. J. Parker. New approaches to nonlinear diffractive field propagation. J. Acoust. Soc. Am., 1991, 90(1):488~499
[32] V. A. Khokhlove, R. Souchon, J. Ravakkoli, et al. Numerical modeling of finite-amplitude sound beams: shock formation in the near field of a cw plane piston source. J. Acoust. Soc. Am., 2001,110(1):95~108
[33] Y. S. Lee, M. F. Hamilton. Time-domain modeling of pulsed finite amplitude sound beams. J. Acoust. Soc. Am., 1995,97(2):906~931
[34] R. O. Cleveland, M. F. Hamilton, D. T. Blackstock. Time-domain modeling of finite-amplitude sound in relaxing fluids. J. Acoust. Soc. Am., 1996, 99(6):3312~3318
[35] M. A. Averkiou, M. F. Hamilton. Nonlinear distortion of short pulse and focused circular pistons. J. Acoust. Soc. Am., 1997, 102(5):2539~2548
[36] 夏荣民,寿文德,孙俊霞,等.自聚焦换能器的声场研究.应用声学,2000,20(5):16~20
[37] 毛彦欣,程建政,张德俊.凹球面 HIFU 换能器声焦域的位置和形状.中国超声医学杂志.2004,20(7):558~560
[38] Yadong Li, Quan Chen, J. Zagzebski. Harmonic ultrasound fields through layered liquid media. IEEE Trans. U. F. F. C., 2004, 51(2):146~152
[39] 薛洪惠,刘晓宙,龚秀芬,等.聚焦超声波在层状生物媒质中的二次谐波声场的理论与实验研究.物理学报,2005,54(11):5233~5238
[40] 杜功焕,朱哲民,龚秀芬著.声学基础.第二版.南京:南京大学出版社,2001.
[2] J. G. Lynn, T. J. Putnam. Histological and cerebral lesions produced by focused ultrasound. Am. J. Pathol., 1944, 20(3):637~649
[3] W. J. Fry, W. H. Mosberg. J. W. Barnard. Production of focal destructive lesionsin the central nervous system with ultrasound. J. Neurosurg., 1954,11(2):471~478
[4] A. K. Burov, G. D. Andreevskaya. Action of high intensity ultrasonic vibrations on malignant tumors in animals and man. Doklady Akad.Nauk S.S.S.R., 1956,106:239~241,ibid,445~448
[5] A. Sibille, F. Prat, J. Y. Chapelon. Characterization of extra- corporeal ablation of normal and tumor-bearing liver tissue by high intensity focused ultrasound. Ultrasound Med. & Bio., 1993, 19(9):803~813
[6] L. A. Frizzell, C. A. Linke, E. L. Carstensen, et al. Thresholds for focal ultrasonic lesions in rabbit kidney,liver and testicle. IEEE Trans.Biomed.Eng., 1977, 24(2): 393~396
[7] L. A. Frizzell. Threshold for damage to mammalian live by high intensity focused ultrasound. IEEE Trans. U. F. F. C., 1988, 35(5):578~581
[8] C. R. Hill, I. Rivens, M. G. Vaughan, et al. Lesion development in focused ultrasound surgery: A general model. Ultrasound. in Med. & Bio. 1994,20(3):259~269
[9] T. C. Robinson, P. P. Lele. An analysis of lesion development in brain and in plastics by high intensity focused ultrasound at low megahertz frequencies. J. Acoust. Soc. Am., 1997, 51(4):1333~1351
[10] R.L. Clarke, G. R. Ter Haar. Mechanisms of lesion formation by high intensity focused ultrasound. Ultrasound Med. & Bio., 1995, 21(4):432~440
[11] N. A. Watkin, G. R. Ter Haar, I. Rivers. The intensity dependence of the site of maximal energy deposition in focused ultrasound surgery. Ultrasound in Med.&Bio.,1996,22(4):483~491
[12] P. M. Meaney, M. D. Cahill, G. R. Ter Haar. The intensity dependence of lesion position shift during focused ultrasound surgery. Ultrasound in Med. & Bio., 2000,26(3):441~450
[13] 刘宝琴,熊树华,王智彪,等.体外不同频率高强度聚焦超声的生物学焦域.中国超声医学杂志,2002,18(6):417~420
[14] 刘宝琴,熊树华,李发琪,等.辐照深度对高强度聚焦超声的生物学焦域的影响.中国超声医学杂志,2002,18(8):565~568
[15] P. M. Meaney, R. L. Clarker, G. R. Ter Haar, et al. A 3-D finite element model for computation of temperature profiles and regions of thermal damage during focused ultrasound surgery exposures. Ultrasound in Med. & Bio., 1998, 24(9):1489~1499
[16] Zhibiao Wang, Jin Bai, Faqi Li, et al. Study of a “biological focal region”of high-intensity focused ultrasound. Ultrasound in Med. & Bio., 2003, 29(5):749~754
[17] Qiang Zhang, Faqi Li, Ruo Feng, et al. Numerical simulation of the transient temperature field from an annular focused ultrasonic transducer. Ultrasound in Med. & Bio., 2003, 29(4):585~589
[18] 侯秀珍,徐祯祥,金长善,等.高强度聚焦超声热疗中无损测温的实验研究.中国超声医学杂志.2002,18(9):653~657
[19] 沙卫红,李瑜元,聂玉强,等.高强度聚焦超声定位损伤离体牛肝的量效学研究.临床超声医学杂志,2004,6(1):1~3
[20] 李发琪,王智彪,杜永洪,等.高强度聚焦超声“切除”组织的剂量学研究.中国超声医学杂志,2006,23(4):839~843
[21] H. T. O'neil. Theory of focusing radiator. J. Acoust. Soc. Am. 1949, 21:516~526
[22] B. G. Lucsa,Acoust. Soc. Am., 1983,73(6): 1966~1971
[23] B. G. Lucsa, T. G. Muir. The field of a focusing source. J. Acoust. Soc. Am., 1983, 72(4):1289~1296
[24] 喻明,张德俊.不同激励聚焦声源的焦斑特性比较.南京大学学报,2000,36(3):357~362
[25] 张樯,许坚毅,冯若,等.环状 HIFU 换能器焦域形态的数值模拟研究.中国超声医学杂志,2001,17(5):321~324
[26] B. G. Lucsa, T. G. Muir. Field of a finite-amplitude focusing source. J. Acoust. Soc. Am., 1983, 74(5):1522~1528
[27] W. Swindell. A theoretical study of nonlinear effects with focused ultrasound in tissues: an “acoustic bragg peak” Ultrasound in Med. & Bio., 1984, 11(1):121~130
[28] T. S. Hart, M. F. Hamilton. Nonlinear effects in sound beams. J. Acoust. Soc. Am., 1988,84(5): 1488~1496
[29] M. F. Hamilton, D. T. Blackstock. Nonlinear acoustics. editors Academic Press, 1998. 137~138,426~427
[30] J. Berntsen. Numerical calculations of finite amplitude sound beams. in frontiers of nonlinear acoustics: 12th ISNA. M. F. Hamilon and D. T. Blackstock, Eds. London:Elsevier, 1990. 191~196
[31] P. T. Christopher,K. J. Parker. New approaches to nonlinear diffractive field propagation. J. Acoust. Soc. Am., 1991, 90(1):488~499
[32] V. A. Khokhlove, R. Souchon, J. Ravakkoli, et al. Numerical modeling of finite-amplitude sound beams: shock formation in the near field of a cw plane piston source. J. Acoust. Soc. Am., 2001,110(1):95~108
[33] Y. S. Lee, M. F. Hamilton. Time-domain modeling of pulsed finite amplitude sound beams. J. Acoust. Soc. Am., 1995,97(2):906~931
[34] R. O. Cleveland, M. F. Hamilton, D. T. Blackstock. Time-domain modeling of finite-amplitude sound in relaxing fluids. J. Acoust. Soc. Am., 1996, 99(6):3312~3318
[35] M. A. Averkiou, M. F. Hamilton. Nonlinear distortion of short pulse and focused circular pistons. J. Acoust. Soc. Am., 1997, 102(5):2539~2548
[36] 夏荣民,寿文德,孙俊霞,等.自聚焦换能器的声场研究.应用声学,2000,20(5):16~20
[37] 毛彦欣,程建政,张德俊.凹球面 HIFU 换能器声焦域的位置和形状.中国超声医学杂志.2004,20(7):558~560
[38] Yadong Li, Quan Chen, J. Zagzebski. Harmonic ultrasound fields through layered liquid media. IEEE Trans. U. F. F. C., 2004, 51(2):146~152
[39] 薛洪惠,刘晓宙,龚秀芬,等.聚焦超声波在层状生物媒质中的二次谐波声场的理论与实验研究.物理学报,2005,54(11):5233~5238
[40] 杜功焕,朱哲民,龚秀芬著.声学基础.第二版.南京:南京大学出版社,2001.