Dual frequency method for simultaneous translation and real-time imaging of ultrasound contrast agents within large blood vessels.

A dual frequency excitation method for simultaneous translation and selective real-time imaging of microbubbles is presented. The method can distinguish signals originating from free flowing and static microbubbles. This method is implemented on a programmable scanner with a broadband linear array. The programmable interface allows for dynamic variations in the acoustic parameters and aperture attributes, enabling application of this method to large blood vessels located at varying depths. The performance of the method was evaluated in vitro (vessel diameter 2mm) by quantifying the sensitivity of the method to various acoustic, microbubble, and fluid flow parameters. It was observed that the static microbubble response maximized at the approximate resonance frequency of the microbubble population (estimated from a coulter counter measurement), thus, signifying the need for dual frequency excitation. The static microbubble signal declined from 25 to 12 dB with increasing centerline flow velocities (2.65-15.9cm/s); indicating the applicable range of flow velocities. The maximum intensity of the static microbubbles signal scaled with variations in the microbubble concentration. The rate of increment of static microbubble signal was independent of microbubble concentration. It was deduced that the rate of increment of the static microbubble signal is primarily a function of the pulse frequency, whereas the maximum static microbubble signal intensity is dependent on three parameters: (a) the pulse frequency, (b) the flow velocity and (c) the microbubble concentration. The proposed dual frequency sequence may enable the application of radiation force for optimizing the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities.

[1]  M. O’Donnell,et al.  Blood Flow Estimation Error with Intravascular Ultrasound Due to In-Plane Component of Flow , 2003, Ultrasonic imaging.

[2]  K. Furie,et al.  Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2008, Circulation.

[3]  Simon C Watkins,et al.  Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. , 1998, Circulation.

[4]  R. Domeniconi,et al.  Carotid arteries in the dog: structure and histophysiology , 2006 .

[5]  J. Hossack,et al.  Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[6]  K W Ferrara,et al.  Selective imaging of adherent targeted ultrasound contrast agents , 2007, Physics in medicine and biology.

[7]  M. Versluis,et al.  9B-3 Orthogonal Observations of Vibrating Microbubbles , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[8]  J. Lindner,et al.  Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1 , 2007, Circulation.

[9]  Ross Williams,et al.  Radial modulation imaging of microbubble contrast agents at high frequency. , 2008, Ultrasound in medicine & biology.

[10]  T. Krouskop,et al.  Phantom materials for elastography , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

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

[12]  K. Ley,et al.  Ultrasound Assessment of Inflammation and Renal Tissue Injury With Microbubbles Targeted to P-Selectin , 2001, Circulation.

[13]  J. Pober,et al.  Cellular and molecular biology of cardiac transplant rejection , 2000, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[14]  T. Kiviniemi Assessment of coronary blood flow and the reactivity of the microcirculation non‐invasively with transthoracic echocardiography , 2008, Clinical physiology and functional imaging.

[15]  D. Ramage,et al.  Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model. , 1996, Circulation.

[16]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[17]  A. Bouakaz,et al.  Radial Modulation of Microbubbles for Ultrasound Contrast Imaging , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[18]  A. Klibanov Ultrasound molecular imaging with targeted microbubble contrast agents , 2007, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[19]  D. May,et al.  Nondestructive subharmonic imaging , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[20]  P. Dayton,et al.  Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size , 2000, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[21]  P. Dayton,et al.  Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles. , 1999, Ultrasound in medicine & biology.

[22]  Paul A Dayton,et al.  The magnitude of radiation force on ultrasound contrast agents. , 2002, The Journal of the Acoustical Society of America.

[23]  Susannah H Bloch,et al.  Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging , 2004, Molecular imaging.

[24]  Lawrence A. Crum,et al.  Bjerknes forces on bubbles in a stationary sound field , 1975 .

[25]  Paul A Dayton,et al.  Tailoring the Size Distribution of Ultrasound Contrast Agents: Possible Method for Improving Sensitivity in Molecular Imaging , 2007, Molecular imaging.

[26]  Paul A Dayton,et al.  Asymmetric oscillation of adherent targeted ultrasound contrast agents. , 2005, Applied physics letters.

[27]  P. Phillips,et al.  Contrast pulse sequences (CPS): imaging nonlinear microbubbles , 2001, 2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263).

[28]  S. Kaul,et al.  In vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells. , 1994, Circulation research.

[29]  John A Hossack,et al.  Enhanced targeting of ultrasound contrast agents using acoustic radiation force. , 2007, Ultrasound in medicine & biology.

[30]  Ronald A. Roy,et al.  On the role of shear viscosity in mediating inertial cavitation from short-pulse, megahertz-frequency ultrasound , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.