Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2001-11-20
2003-03-18
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06533728
ABSTRACT:
TECHNICAL FIELD
The present invention relates to improved methods and apparatus for use of a contrast agent in ultrasonic imaging and, in particular, to improved methods and apparatus for the detection and measurement of contrast agents in regions of interest.
BACKGROUND ART
Ultrasonic transducers and imaging systems are used in many medical applications and, in particular, for the non-invasive acquisition of images of organs and conditions within a patient, typical examples being the ultrasound imaging of fetuses and the heart. Such systems commonly use a linear or phased array transducer having multiple transmitting and receiving elements to transmit and receive narrowly focused and “steerable” beams, or “lines”, of ultrasonic energy into and from the body. The received beams, or lines, are reflected from the body's internal structures and contain amplitude or phase information, or both, that is used to generate images of the body's internal structures.
A primary problem in ultrasonic imaging has been that many of the body's internal structures have similar characteristics as regards the reflection of ultrasonic energy, so that it is difficult to obtain as clear and detailed images of many of the structures as is desired. In particular, many of the structures of interest, such as the muscles of the heart, are perfused with blood, so that it is difficult to distinguish between blood vessels and the chambers of the heart and the heart muscles.
This problem led to the development of alternative methods for imaging certain of the body's structures, such as the blood vessels of the heart. One of the most common imaging techniques, for example, is referred to as an angiogram and requires the injection of a radiofluorescent dye into the vessels to image the blood vessels of the heart with x-rays. Such techniques, however, are invasive or are otherwise unsatisfactory. For example, the use of x-ray imaging carries the risk of potential injury from radiation and involves complex, expensive and hazardous equipment. Also, radiofluorescent dyes are potentially toxic to at least some patients and are not broken down in the body but are flushed from the body by natural waste processes, often requiring hours to disappear from the body.
A more recent development has been ultrasonic imaging using contrast agents injected into the blood stream. Ultrasonic contrast agents are now commercially available and are essentially small bubbles of gas, such as air, formed by agitating a liquid or bubbling gas through a liquid, such as a saline solution or a solution containing a bubble forming compound, such as albumin. When insonicated, the bubbles resonate at their resonant frequency and emit energy at both the fundamental and second harmonic of their resonant frequency, thereby returning an enhanced signal at or around these frequencies and thereby providing an enhanced image of the liquid or tissue containing the contrast agent. It is also well known that the bubbles “disappear” when insonicated and the current theory is that the insonication ruptures the bubble's shell, thereby allowing the gas to dissipate into the surrounding liquid or tissue.
The use of ultrasonic contrast agents is thereby advantageous in allowing enhanced imaging using ultrasonics rather than x-rays, thereby eliminating the radiation hazard and allowing the use of equipment that is significantly less expensive and hazardous to use. Also, the agents are non-toxic and dissolve relatively quickly into waste products, such as air and albumin, that are normally found in the body and that are themselves non-toxic. Further, the insonication of the agent in itself destroys the agent, so that the agent can effectively be “erased” during the imaging process to a degree.
There are, however, a number of persistent problems in ultrasonic imaging using contrast agents. Conventional harmonic ultrasound methods for perfusion analysis require an initial set of data to be acquired before a contrast agent is injected, and a second set of data to be acquired after the contrast agent is injected. Therefore, a number of scans are required, and a significant amount of clinical time is needed to collect data. Furthermore, after the data is obtained, it can be difficult to correlate a region of interest in successive sets of data.
An alternative method for perfusion analysis in ultrasonic contrast agent imaging is harmonic imaging. Harmonic imaging is based on the strong harmonics produced when the “bubbles” of a contrast agent respond to transmitted ultrasound in a non-linear fashion. The reflected signals are processed using filters which provide a first spectrum around a fundamental frequency and a second spectrum around a harmonic frequency. Characteristics of the harmonic and fundamental spectra are compared to determine the comparative amount of signal due to tissue and the amount of signal due to contrast agent. The filters are generally bandpass filters centered around a first frequency, at the fundamental frequency, and a second frequency centered at the expected location of the second harmonic frequency. While useful in some applications, however, there are also problems associated with this type of harmonic imaging. Most importantly, the filtering method used to process the signals expects the second harmonic being located in a predetermined location. In most clinical situations, however, the center frequency of harmonic spectra is displaced by attenuation. Therefore, the results of the harmonic imaging can be inconsistent, or even inaccurate, particularly when the signal is attenuated. Furthermore, the bandpass filter does not filter noise or spurious signals which vary the amplitude of the signal. Since the amplitude at the center of the fundamental frequency and the second harmonic are frequently in calculations for locating the contrast agent and characterizing the tissue, the results are prone to inaccuracies.
The present invention provides a solution to these and other problems of the prior art by providing improved methods for the use of contrast agents in conjunction with ultrasound imagery, and in particular for identifying a contrast agent and characterizing the associated tissue.
SUMMARY OF THE INVENTION
The present invention is a method and apparatus for contrast perfusion data recovery using ultrasound signals. A contrast agent comprising microbubbles is injected into a subject. An ultrasound pulse signal exhibiting a characteristic frequency is directed at a region of interest in the subject, and a corresponding reflected signal is received by the transceiver. Using mathematical synthesizing or reconstruction techniques, a first spectrum is reconstructed from the broadband spectrum around the characteristic or fundamental transmission frequency, and a second, harmonic spectrum is reconstructed from the broadband spectrum around a harmonic frequency. Thereafter, a relationship is determined between the energy characteristics at the fundamental frequency and at the harmonic frequency. The determined relationship indicates a proportion of the return signal that is returned from contrast agent versus a proportion which is returned from tissue, and can therefore be used to characterize the tissue, and more particularly, to identify myocardial perfusion.
In a preferred embodiment of the invention least square error fitting procedures are employed to synthesize the Fourier broadband spectrum. To reconstruct the fundamental spectrum, a constrained Gaussian curve and least squares error fitting procedure are employed. Initially, a broadband harmonic spectrum is produced from the received signal. Next, a Gaussian curve is selected to have a center frequency substantially equivalent to the expected center frequency of the fundamental spectrum. The reconstructed fundamental spectrum is then subtracted from the received broadband spectrum to produce a spectrum mainly comprising the harmonic component. The harmonic spectrum is then reconstructed, again using a least square technique to reconstruct a Gaussian signal
Bae Richard Y.
Belohlavek Marek
Imam Ali M.
Lateef Marvin M.
Mayo Foundation for Medical Education and Research
Quarles & Brady LLP
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