Simulations and measurements of optical images of insonified ultrasound contrast microbubbles

Ultrasound contrast agents (UCAs) are used in a clinical setting to enhance the backscattered signal from the blood pool to estimate perfusion and blood flow. The UCAs consist of encapsulated microbubbles, measuring 1-10 /spl mu/m in diameter. Acoustic characterization of UCAs is generally carried out from an ensemble of bubbles. The measured signal is a complicated summation of all signals from the individual microbubbles. Hence, characterization of a single bubble from acoustic measurements is complex. In this study, 583 optical observations of freely flowing, oscillating, individual microbubbles from an experimental UCA were analyzed. The excursions during ultrasound exposure were observed through a microscope. Images were recorded with a high frame rate camera operating at 3 MHz. Microbubbles on these images were measured offline, and maximal excursions were determined. A technique is described to determine the diameters of the bubbles observed. We compared the maximal excursions of microbubbles of the same initial size in an ultrasound field with a 500 kHz center frequency at acoustic amplitudes ranging from 0.06 MPa to 0.85 MPa. It was concluded that maximal excursions of identical bubbles can differ by 150% at low acoustic pressures (mechanical index or MI<0.2). At a high acoustic pressure (MI=1.2) an image sequence was recorded on which a bubble collapsed, but an apparently identical bubble survived.

[1]  I. T. Young,et al.  Quantitative Microscopy , 1984, Definitions.

[2]  P. Dayton,et al.  Simultaneous optical and acoustical observations of contrast agents , 1997, 1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118).

[3]  Hsien-Che Lee.  Review of image-blur models in a photographic system using the principles of optics , 1990 .

[4]  P. Dayton,et al.  Optical and acoustical observations of the effects of ultrasound on contrast agents , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[5]  Y. Takeuchi.  Pulsed stroboscopic visualizer to synchronously monitor the microballoon under insonification , 1998, 1998 IEEE Ultrasonics Symposium. Proceedings (Cat. No. 98CH36102).

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

[7]  L. Rayleigh.  Investigations in optics, with special reference to the spectroscope , 1880 .

[8]  Carmel M. Moran,et al.  Handbook of contrast echocardiography LV function and myocardial perfusion , 2001 .

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

[10]  I T Young,et al.  A comparison of different focus functions for use in autofocus algorithms. , 1985, Cytometry.

[11]  G. F. C. SEARLE,et al.  Practical Physics , 1894, Nature.

[12]  Paul A. Dayton,et al.  Experimental and theoretical analysis of individual contrast agent behavior , 1999, 1999 IEEE Ultrasonics Symposium. Proceedings. International Symposium (Cat. No.99CH37027).

[13]  L. Hoff.  Acoustic properties of ultrasonic contrast agents , 1996 .

[14]  Anil K. Jain.  Fundamentals of Digital Image Processing , 2018, Control of Color Imaging Systems.

[15]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[16]  B. Goldberg,et al.  Ultrasound Contrast Imaging of Prostate Tumors , 2002 .

[17]  Charles T. Lancée,et al.  Higher harmonics of vibrating gas-filled microspheres. Part one: simulations , 1994 .

[18]  J. Gorce,et al.  Influence of Bubble Size Distribution on the Echogenicity of Ultrasound Contrast Agents: A Study of SonoVue™ , 2000, Investigative radiology.

[19]  S. Gibson,et al.  Experimental test of an analytical model of aberration in an oil-immersion objective lens used in three-dimensional light microscopy. , 1992, Journal of the Optical Society of America. A, Optics and image science.

[20]  K W Ferrara,et al.  Direct video-microscopic observation of the dynamic effects of medical ultrasound on ultrasound contrast microspheres. , 1998, Investigative radiology.

[21]  N. Kudo,et al.  A high-magnification and high-speed system for the observation of microbubbles under ultrasound exposure , 1999, 1999 IEEE Ultrasonics Symposium. Proceedings. International Symposium (Cat. No.99CH37027).

[22]  P. Stokseth.  Properties of a Defocused Optical System , 1969 .

[23]  T. Shiina,et al.  [Ultrasound scattering properties of Albunex microspheres]. , 1998, Nihon rinsho. Japanese journal of clinical medicine.

[24]  Nico de Jong,et al.  New ultrasound contrast agents and technological innovations. , 1996 .

[25]  L. J. Thomas,et al.  Regularized linear method for reconstruction of three-dimensional microscopic objects from optical sections. , 1992, Journal of the Optical Society of America. A, Optics and image science.

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

[27]  Feng Yan,et al.  BR1: A New Ultrasonographic Contrast Agent Based on Sulfur Hexafluoride-Filled Microbubbles , 1995, Investigative radiology.

[28]  N de Jong,et al.  Acoustic modeling of shell-encapsulated gas bubbles. , 1998, Ultrasound in medicine & biology.

[29]  T. Milster,et al.  Theory of high-NA imaging in homogeneous thin films , 1996 .

[30]  H. Netten,et al.  Autofocusing in microscopy based on the OTF and sampling , 1994 .

[31]  Lord Rayleigh F.R.S..  LVI. Investigations in optics, with special reference to the spectroscope , 1879 .

[32]  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.

[33]  Barry B. Goldberg,et al.  Intravenous Contrast Agent For Ultrasound Doppler: In Vivo Measurement Of Small Tumor Vessel Dose-response , 1990, [1990] Proceedings of the Twelfth Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[34]  N de Jong,et al.  Detection procedures of ultrasound contrast agents. , 2000, Ultrasonics.

[35]  M. Postema,et al.  Real-time optical imaging of individual microbubbles in an ultrasonic field , 2001, 2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263).

[36]  Bertil Matérn,et al.  Precision of area estimation: a numerical study , 1989 .

[37]  D. Agard,et al.  Computational adaptive optics for live three-dimensional biological imaging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[38]  D. Agard.  Optical sectioning microscopy: cellular architecture in three dimensions. , 1984, Annual review of biophysics and bioengineering.

[39]  M. Postema,et al.  Optically observed microbubble coalescence and collapse , 2002, 2002 IEEE Ultrasonics Symposium, 2002. Proceedings..

[40]  N de Jong,et al.  Optical imaging of contrast agent microbubbles in an ultrasound field with a 100-MHz camera. , 2000, Ultrasound in medicine & biology.