Enhanced heat deposition using ultrasound contrast agent - modeling and experimental observations

Ultrasound contrast agents (UCA), created originally for visualization and diagnostic purposes, recently have been suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by the contrast agents, considered as problematic in diagnostic imaging, might have beneficial impact in therapeutic applications such as targeted hyperthermia-based or ablation treatments. Introduction of gas microbubbles into the tissue to be treated can improve the effectiveness of current treatments by limiting the temperature rise to the treated site and minimising the damage to the surrounding healthy tissues. To this end, proper assessment of the governing parameters of energy absorption by ultrasonically induced stabilized bubbles is important for both diagnostic and therapeutic ultrasound applications. The current study was designed to predict theoretically and measure experimentally the dissipation and heating effects of encapsulated UCA in a well-controlled and calibrated environment. The ultrasonic effects of the microbubble concentration, transmitted intensity, and frequency on power dissipation and stability of the UCA have been studied. The maximal temperature elevation obtained during 300 s experiments was 21/spl deg/C, in a 10 ml volume target containing UCA, insonified by unfocused 3.2 MHz continuous wave (CW) at spatial average intensity of 1.1 W/cm/sup 2/ (182 kPa). The results also suggest that higher frequencies are more efficiently absorbed by commonly used UCA. In particular, for spatial average intensity of 1.1 W/cm/sup 2/ and concentration of 5/spl middot/10/sup 6/ microspheres/cm/sup 3/, no significant reduction of UCA absorption was noticed during the first 150 s for insonation at 3.2 MHz and the first 100 s for insonation at 1 MHz. In addition, when lower average intensity of 0.5 W/cm/sup 2/ (160 kPa) at 3.2 MHz was used, the UCA absorptivity sustained for almost 200 s. Thus, when properly activated, UCA may be suitable for localized hyperthermic therapies.

[1]  Dhiman Chatterjee,et al.  A Newtonian rheological model for the interface of microbubble contrast agents. , 2003, Ultrasound in medicine & biology.

[2]  P. Einziger,et al.  Effectiveness of acoustic power dissipation in lossy layers , 2004 .

[3]  A. Brayman,et al.  A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents. , 2003, The Journal of the Acoustical Society of America.

[4]  Sheila Podell,et al.  Physical and biochemical stability of Optison®, an injectable ultrasound contrast agent , 1999, Biotechnology and applied biochemistry.

[5]  Herbert Lawrence Anderson,et al.  A physicist's desk reference , 1989 .

[6]  Charles C. Church,et al.  The effects of an elastic solid surface layer on the radial pulsations of gas bubbles , 1995 .

[7]  T. Leighton The Acoustic Bubble , 1994 .

[8]  Thomas Dreyer,et al.  Full-wave modeling of therapeutic ultrasound: nonlinear ultrasound propagation in ideal fluids. , 2002, The Journal of the Acoustical Society of America.

[9]  K. Nightingale,et al.  A preliminary evaluation of the effects of primary and secondary radiation forces on acoustic contrast agents , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[10]  D. Lohse,et al.  Sound scattering and localized heat deposition of pulse-driven microbubbles , 2000, The Journal of the Acoustical Society of America.

[11]  Katherine W Ferrara,et al.  Dynamics of therapeutic ultrasound contrast agents. , 2002, Ultrasound in medicine & biology.

[12]  William R Wagner,et al.  Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. , 2005, Cancer research.

[13]  Irene A. Stegun,et al.  Handbook of Mathematical Functions. , 1966 .

[14]  J. C. Jaeger,et al.  Conduction of Heat in Solids , 1952 .

[15]  D. R. Bacon,et al.  Absorption of finite amplitude focused ultrasound. , 1991, The Journal of the Acoustical Society of America.

[16]  J. Zagzebski,et al.  Pressure-dependent attenuation in ultrasound contrast agents. , 2002, Ultrasound in medicine & biology.

[17]  Faqi Li,et al.  Study of a "biological focal region" of high-intensity focused ultrasound. , 2003, Ultrasound in medicine & biology.

[18]  K. Tachibana,et al.  Gene transfer with echo-enhanced contrast agents: comparison between Albunex, Optison, and Levovist in mice--initial results. , 2003, Radiology.

[19]  E Stride,et al.  The potential for thermal damage posed by microbubble ultrasound contrast agents. , 2004, Ultrasonics.

[20]  D. Watmough,et al.  The effect of gas bubbles on the production of ultrasound hyperthermia at 0.75 MHz: a phantom study. , 1993, Ultrasound in medicine & biology.

[21]  N de Jong,et al.  Absorption and scatter of encapsulated gas filled microspheres: theoretical considerations and some measurements. , 1992, Ultrasonics.

[22]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[23]  R. Eckersley,et al.  Acoustic characterization of contrast agents for medical ultrasound imaging , 2003 .

[24]  K Hynynen,et al.  MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh. , 2003, Physics in medicine and biology.

[25]  P. Dayton,et al.  Mechanisms of contrast agent destruction , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[26]  J. Wu,et al.  Temperature rise generated by ultrasound in the presence of contrast agent. , 1998, Ultrasound in medicine & biology.

[27]  R. Y. Chiao,et al.  Subharmonic Imaging with Microbubble Contrast Agents: Initial Results , 1999, Ultrasonic imaging.

[28]  K. Hynynen The threshold for thermally significant cavitation in dog's thigh muscle in vivo. , 1991, Ultrasound in medicine & biology.

[29]  G. ter Haar,et al.  Temperature rise recorded during lesion formation by high-intensity focused ultrasound. , 1997, Ultrasound in medicine & biology.

[30]  Sverre Holm,et al.  Modelling of the ultrasound return from Albunex microspheres , 1994 .

[31]  Y. Nishimura,et al.  Increased heating efficiency of hyperthermia using an ultrasound contrast agent: a phantom study. , 1998, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[32]  Ultrasonic scattering cross sections of shell-encapsulated gas bubbles immersed in a viscoelastic liquid: first and second harmonics. , 2003, Ultrasonics.

[33]  S. Ginter Numerical simulation of ultrasound-thermotherapy combining nonlinear wave propagation with broadband soft-tissue absorption. , 2000, Ultrasonics.

[34]  D. Lohse,et al.  The acoustics of diagnostic microbubbles: dissipative effects and heat deposition. , 2000, Ultrasonics.

[35]  C. Cain,et al.  Microbubble-enhanced cavitation for noninvasive ultrasound surgery , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[36]  Ronald A. Roy,et al.  Measurements of bubble-enhanced heating from focused, MHz-frequency ultrasound in a tissue-mimicking material. , 2001, Ultrasound in medicine & biology.

[37]  L. Hoff,et al.  Oscillations of polymeric microbubbles: effect of the encapsulating shell , 2000, The Journal of the Acoustical Society of America.