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Method of ultrasonic detection and localization of contrast agent microbubbles and method for local drug administration by using microbubble carriers

  • US 7,981,040 B2
  • Filed: 04/14/2006
  • Issued: 07/19/2011
  • Est. Priority Date: 04/14/2005
  • Status: Active Grant
First Claim
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1. A method of ultrasonic detection and localization of contrast agent microbubbles, said method comprising the steps of:

  • (a) scanning the relevant anatomic region by transmitting at least one ultrasonic pulse in said region along a plurality of adjacent scan lines;

    (b) receiving the reflected signal along each of said scan lines;

    (c) analyzing the reflected signal along each scan line to identify one signal component deriving from the presence of one microbubble or a small microbubble population and identifying said component of the reflected signal, said analyzing comprising the steps of;

    projecting the reflected signals in one or more multidimensional spaces to highlight the evolution of the reflected signal spectrum with time and/or the phase relationships between reflected signal components having different frequencies or frequency ranges, particularly the signal components at the fundamental frequency of the transmit pulse/s and at the second harmonic of the transmit pulse/s;

    detecting sample reflected ultrasonic signals by transmitting ultrasonic pulses to known tissue samples containing no single microbubble or small microbubble population and on known tissue samples containing a single bubble or a small bubble population;

    projecting the sample reflected ultrasonic signals in the same multidimensional space/s to highlight the evolution of the reflected signal spectrum with time and/or the phase relationships between the reflected signal components having different frequencies or frequency ranges;

    comparing the projections of the sample reflected ultrasonic pulses for simple tissue and tissue having a single microbubble or a small microbubble population in the multidimensional space/s and defining unique characteristics for said projections for simple tissue and tissue having a single microbubble or a small microbubble population;

    analyzing the projections of reflected signals in the multidimensional space/s to identify said diversifying characteristics defined on the basis of the comparison between the projections of sample reflected ultrasonic signals in the multidimensional space/s;

    defining a projection of the reflected signal in said multidimensional space/s as deriving from a single microbubble or a small microbubble population when it has the characteristics of the projection of the sample reflected ultrasonic signal in said multidimensional space/s relating to the known sample of tissue having a single microbubble or a small microbubble population;

    (d) determining the position of the microbubble or the small microbubble population along the corresponding scan line according to the time localization of said component within the duration of the reflected signal, the position of the microbubble or the small microbubble population in the relevant anatomic region being defined by the position of the scan line and the position of the microbubble or the small microbubble population along said scan line; and

    (e) generating a bispectrum for the signals reflected along each scan line.

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