Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2001-01-19
2002-10-08
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06461303
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to a method for detecting an ultrasound contrast agent in a soft tissue and quantitating blood perfusion through regions of tissue by detecting the contrast agent in the tissue.
2. Description of the Related Art
An ultrasound contrast agent is a solution of small gas bubbles (diameter ~5 &mgr;m) that is injected into the blood stream. Such bubbles show strong and non-linear scattering of ultrasound at the frequencies used for medical ultrasound imaging. Medical applications of the contrast agents include, but are not limited to, enhancing imaging of blood vessels, improving the detection of the endocardium as a border of the ventricular cavities, and improving the detection of blood jets through leaking cardiac valves or septal defects.
There has also been great hopes that ultrasound contrast agent should be able to detect and quantify blood perfusion through the tissue, especially the myocardial tissue where coronary disease strongly influences the myocardial perfusion. The widespread occurrence of coronary artery disease as a major cause of death in the western world has made this application of the contrast agents and methods for detection of the contrast agents in the tissue a target for development of various types of ultrasound contrast agents.
Second harmonic ultrasound imaging, is today the commonly used method for detecting and imaging ultrasound contrast agent in the tissue. The non-linear elastic properties of the contrast agent bubbles produce higher harmonic components and sub harmonic components of the transmitted pulse frequency band in the scattered signal directly in the scattering process. However, with the present wideband transducer technology it is only possible to utilize the second harmonic component of the signal by transmitting an ultrasound pulse with frequency spectrum in the lower part of the active frequency band of a wideband transducer. The second harmonic component of the scattered signal is then received in the upper part of the transducer frequency band.
Forward propagation of the ultrasound pulse through the tissue produces a distortion of the pulse due to pressure dependent propagation velocity. The distortion is limited by acoustic power absorption in the tissue, so that in practice we get high enough amplitude of the 2nd harmonic band in the pulse to use this harmonic band for imaging of soft tissue itself. With venous injection of contrast agent, the 2nd harmonic frequency band of the scattered signal from the myocardial tissue has, however, comparable amplitude to the 2nd harmonic frequency band of the signal from contrast agent in the myocardium. The back scattered tissue signal then represents a background noise for the detection of the contrast agent, and hence limits the detectability of low concentrations of the agent based on the 2nd harmonic component of the back scattered signal.
The non-linear elasticity of the contrast agent is much stronger than that of the tissue. Accordingly, considerable distortion of the scattered pulse directly in the scattering process results with high amplitudes in the 3rd and 4th harmonic component of the incident pulse frequency band. More importantly, the scattered amplitudes from the contrast agent in these frequency bands are much stronger than the scattered amplitudes in the 3rd and 4th harmonic frequency bands from the tissue. Therefore, the use of harmonic frequency bands higher than the 2nd component of the transmitted pulse frequency band for detection and imaging of the contrast agent provides improved separation between the signal amplitudes from the contrast agent and the signal amplitudes from the tissue.
There are however several practical problems in utilizing the 3rd and 4th harmonic component of the transmitted frequency band for detection and imaging of ultrasound contrast agent, as well as using such imaging to grade the degree of blood perfusion through tissue:
The first problem is that the present medical ultrasound transducers have so narrow a bandwidth that it is not possible to transmit a pulse with frequency band around f
0
, and receive back-scattered frequency components in the frequency bands around 3f
0
and 4f
0
with adequate sensitivity. Adequate wideband transducers have been made by highly damping the transducers, but this reduces the sensitivity to the signal scattered from the contrast agent in the myocardium below tolerable limits. According to the present invention, a transducer is used with capabilities of transmitting frequencies in a band around f
0
, with high sensitivity in the receive band around the 3rd or 4th harmonic component of the transmit band. In the particular implementation of the invention, the high receive sensitivity is obtained by using resonant operation of the transducer in the receive band with minimal dampening.
For the invention to fully work, the transmitted pulse must have sufficiently limited amplitude in the receive frequency bands. A solution to this problem is presented according to the invention by either bandpass filtering the transmitted pulse both in the transducer and/or electrically before driving the transducer, or by using band limited pulse generator with linear drive amplifiers of the array transducer elements.
A second problem associated with utilizing the 3rd and 4th harmonic component of the transmitted frequency band for detection and imaging of ultrasound contrast agent is that the pulse distortion in the scattering from the contrast agent bubbles, highly depends on the amplitude of the pulse incident on the bubble. Absorption of the transmitted pulse attenuates the incident amplitude with depth, depending on the transmitted frequency f
0
. In addition, the beam divergence past the transmit focus will produce an amplitude attenuation with depth. In the normal imaging situation, the amplitude of the transmitted pulse hence attenuates with depth, giving a subsequent reduction in the distortion of the scattered pulse from the contrast agent with depth. This produces a depth variable detection of the contrast agent, and presents severe problems for imaging and quantitation of regions of reduced blood perfusion in the myocardium.
The power absorption in the tissue considerably reduces with the frequency, being approximately 0.5 dB/cmMHz. Hence, by using a low transmitted center frequency at for example f
0
=0.875 MHz, the total absorption attenuation from 2-10 cm is ~3.5 dB. Geometric focussing of the beam to the far end of the image range may be used to compensate for this absorption attenuation. Due to diffraction at such low frequencies, the maximal amplitude in the focussed beam is found closer to the transducer than the geometric focus. By locating the geometric transmit focus beyond the image range, at for example 12 cm, the transmit beam focussing will give a gain of ~3.4 dB from 2-10 cm with a 18 mm circular aperture. Hence, by using sufficiently low transmit frequency, one can obtain approximately constant incident amplitude over a limited image range by proper selection of transmit aperture and focus.
A transmit center frequency of 0.875 MHz, gives 3rd and 4th harmonic center frequencies at 2.625 MHz and 3.5 MHz, which are typical frequencies used for cardiac imaging. These frequencies produce tolerable absorption attenuation of the backscattered signal so that it can be compensated for by a depth variable receiver gain. A receive frequency in the range of 2.5-4 MHz also gives a lateral resolution of the receive beam comparable to that with regular echocardiography.
To obtain a narrower transmit beam at all ranges and to further improve the equalization of the incident pulse amplitude with depth according to the invention, the depth along the receive beam is divided into sub-ranges. Each sub-range is observed at different time intervals with different transmit pulses, where the focus of each transmit pulse is located within the corresponding receive range, and both the transmit focus, the transmit amplitude, and the tra
Cohen & Pontani, Lieberman & Pavane
Imam Ali M.
Lateef Marvin M.
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