Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1999-05-26
2001-02-13
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06186951
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to ultrasonic imaging, and more particularly relates to methods for measuring blood flow rate and perfusion employing ultrasound contrast agents.
BACKGROUND OF THE INVENTION
The accurate measurement of blood flow and blood perfusion is of great clinical importance for evaluating physiologic function and clinical conditions. Noninvasive Doppler sonography has been used to provide information on blood velocity and techniques have been developed to estimate volumetric blood flow rates from Doppler velocity measurements. Measurement of volumetric blood flow using traditional Doppler generally requires the determination of vessel size, beam/vessel angle and some estimate of the spatial variations in velocity. These requirements limit the accuracy of volumetric flow rate assessments because of the many sources of error in the velocity estimation using Doppler methods, such as errors in the estimation of vessel diameter and beam/vessel angle.
Ultrasonic contrast agents, which most commonly take the form of encapsulated gaseous micro-bubbles, which scatter ultrasound effectively, have been demonstrated to enhance ultrasonic images of blood and Doppler signals. With recent improvements in their ability to persist over longer periods of time, ultrasonic contrast agents hold great potential for improved blood flow and perfusion measurements in local tissue regions and organs. As their interactions with ultrasound are radically different from blood or soft tissue, the application of ultrasonic contrast agents opens new ground for developing new and better methods for quantification and characterization of fluid flow.
Ultrasound contrast agents can be used as blood volume contrast agents because they become distributed within the vascular space, travel at the same velocity as the blood flow rate or velocity, and remain relatively stable in the body during clinical observation periods. These characteristics provide the potential for mean flow rate estimation based on the indicator dilution principle using the contrast time-video intensity curve in ultrasonic images following a bolus injection. Such a process is described in the article “Mathematical Modeling of the Dilution Curves for Ultrasonic Contrast Agents,” by C. M. Sehgal et al., J. Ultrasound Med., 16:471-479, 1997. However, current ultrasound methods that use the time-intensity curve in ultrasonic images following a bolus injection of a contrast medium are somewhat limited at present because 1) the interaction of ultrasound with contrast agents is not well understood; 2) the lack of knowledge of the number concentration of contrast agent and the rate of delivery, sometimes referred to as the “input function”; and 3) video intensity in ultrasonic images is a nonlinear conversion of returned echo amplitude from scatterers. Thus, improved methods of flow rate measurement using such contrast agents are required.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide improved methods for determining fluid flow rate and perfusion rate using ultrasonic contrast agents and imaging techniques.
In accordance with the present invention, a first method for determining the perfusion rate (volume of blood/time/tissue volume) of a fluid in a region includes the steps of introducing an ultrasound contrast agent into the fluid at an upstream location to the region and monitoring the region to determine an initial level of the contrast agent. A pulse of ultrasonic energy sufficient to reduce the level of the contrast agent backscatter is applied to create a region of diminished backscatter of known volume in the region. The region is then monitored to determine a time required for the contrast agent level to be restored to the initial level.
A method for determining the flow rate of a fluid in a conduit includes the steps of introducing an ultrasound contrast agent into the conduit at an upstream location, applying a pulse of ultrasonic energy sufficient to reduce the level of the contrast agent at a first downstream location of the conduit, thereby establishing a zone of reduced ultrasonic backscatter in the fluid at the first downstream location, and monitoring a second location, downstream from the first downstream location, and determining a time required for the zone of reduced ultrasonic backscatter to reach the second location.
In an alternate method for determining the flow rate of a fluid in a conduit, an ultrasound contrast agent is introduced into the conduit at an upstream location and ultrasonic energy sufficient to reduce the level of the contrast agent is applied to at least a first downstream location and second downstream location of the conduit, thereby establishing at least two zones of reduced ultrasonic backscatter in the fluid separated by a predetermined distance defined by the first downstream location and second downstream location. A third location, downstream from the first and second downstream locations, is monitored to determine a time period between the first and second zone of reduced ultrasonic backscatter reaching said third location.
Preferably, in each of the methods of the present invention, the pulse of ultrasonic energy used to diminish the contrast agent concentration level is relatively low frequency ultrasound at a frequency near a resonant frequency of the contrast agent whereas the monitoring steps are performed using, low level, high frequency ultrasound, which generally produces finer spatial resolution than low frequency ultrasound.
An ultrasonic apparatus for performing perfusion rate measurements of a fluid carrying a contrast agent into a tissue region in accordance with the present invention includes an ultrasound source capable of providing a first ultrasound signal in the form of a focused pulse of ultrasound energy at a frequency and magnitude sufficient to physically modify the contrast agent particles in a target area in the tissue region as well as a second ultrasound signal provided at a frequency and magnitude which does not substantially physically modify the contrast agent, the second ultrasound signal for monitoring the target area of the ultrasound source. A controller is operatively coupled to the ultrasound source and operates the source such that the second signal is provided to determine an initial measurement of the contrast agent in the target area, the first signal is provided to modify at least a portion of the contrast agent in the target area and the second signal is again provided to monitor the level of contrast agent in the target area. The processor calculates the time required to restore the contrast agent level to the initial level and establishes a perfusion rate therefrom.
The ultrasound source can take the form of a single broadband ultrasonic transducer assembly, such as an array, or can take the form of first and second transducers providing the first and second signals, respectively. Preferably, the first and second signals are projected on a common axis directed to the target area. When first and second transducers are employed, preferably, such transducers are substantially coaxial. However, the first and second transducers can also be arranged in a substantially adjacent arrangement and angularly directed to a common target area
An ultrasonic apparatus for performing flow rate measurements of a fluid carrying a contrast agent in a conduit in accordance with the present invention includes a first ultrasound transducer for providing a focused pulse of ultrasound energy at a frequency and magnitude sufficient to modify the contrast agent in a first target area. The apparatus also includes a second ultrasound transducer, operating at a frequency and magnitude which does not substantially physically modify the contrast agent, for monitoring a second target area which is a predetermined distance downstream from the first transducer. A controller is operatively coupled to and controls the first and second ultrasound transducers, such that the first transducer is operable by the control
Deng Cheri Xiaoyu
Lizzi Frederic Louis
BakerBotts L.L.P.
Imam Ali M.
Lateef Marvin M.
Riverside Research Institute
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