Methods, systems and computer program products for constructive shear wave ultrasound imaging

Methods, systems and computer program products for determining a mechanical parameter for a sample having a target region using constructive shear wave displacement is provided. The method includes generating a first shear wave in the target region at a first excitation position and a second shear wave in the target region at a second excitation position; transmitting tracking pulses in the target region at a tracking position that is between the first and second excitation positions; receiving corresponding echo signals for the tracking pulses at the tracking position in the target region; and determining at least one mechanical parameter of the target region based on at least one parameter of a constructive shear wave displacement from the first and second shear waves simultaneously displacing tissue at the tracking position.

RELATED APPLICATIONS

This application is a 35 U.S.C. § 371 national stage application of PCT International Application No. PCT/US2016/028622, filed Apr. 21, 2016 the disclosure of which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to ultrasound imaging and analysis, and in particular, to determining mechanical parameters of a sample from constructive arrival times in shear wave ultrasound imaging.

BACKGROUND

Acoustic Radiation Force (ARF) shear wave elasticity imaging methods typically use a transverse propagation velocity of mechanical shear waves in materials to estimate mechanical properties of a sample, such as material elasticity constants. These techniques may be adapted into imaging systems to compute the local shear wave propagation velocity as a function of both axial and lateral position. The velocity may be calculated by estimating the differences in arrival times of the shear waves, either at different recording locations or from different excitation locations.

For example, acoustic radiation force (ARF) arises from a transfer of momentum from a sound wave to the medium through which it is traveling due to both absorption and scattering of the wave and is described by K. R. Nightingale, M. Palmeri, R. Nightingale, and G. Trahey, “On the feasibility of remote palpation using acoustic radiation force,” J Acoust Soc Am, vol. 110, pp. 625-634, 2001 and G. R. Torr, “The Acoustic Radiation Force,” Am. J. Phys., vol. 52, pp. 402-408, 1984.

F→=2⁢α⁢⁢I→c(1)
where α is the acoustic attenuation, I is the acoustic intensity, c is the speed of sound, and F is the force applied to the medium. Ultrasonic Shear Wave Elasticity Imaging (SWEI) utilizes this acoustic radiation force by applying ultrasonic pushing pulses that displace the tissue on the order of microns and tracking the propagation of the transverse wave that propagates away from the region of excitation.

SWEI is currently used to characterize the stiffness of tissues, including liver fibrosis. Initial implementations of SWEI involved using sparse displacement fields in inverted wave equation solutions, or time-of-flight algorithms, in which shear wave arrival times are estimated at multiple spatial locations with an assumed direction of propagation. See M. L. Palmeri, M. H. Wang, J. J. Dahl, K. D. Frinkley, K. R. Nightingale, and L. Zhai “Quantifying Hepatic Shear Modulus In Vivo Using Acoustic Radiation Force. Accept. UMB, 34(4):546-558 (April 2008). Additional improvements to SWEI include using multiple shear wave sources that can create a unique shear wave morphology that can be tracked at a single location using correlation-based methods, with the benefit of reduced shear wave speed estimation variance. See U.S. Pat. No. 8,225,666 and U.S. Patent Publication No. 2011/0184,287, the disclosures of which are hereby incorporated by reference in their entireties.

Currently used SWEI techniques that utilize acoustic radiation force to generate shear waves typically require diagnostic ultrasound arrays to generate and track shear waves, with significant signal processing overhead to calculate shear wave arrival times and to estimate shear wave speeds.

SUMMARY OF EMBODIMENTS OF THE INVENTION

In some embodiments, a method for determining a mechanical parameter for a sample having a target region using constructive shear wave displacement is provided. The method includes generating a first shear wave in the target region at a first excitation position and a second shear wave in the target region at a second excitation position; transmitting tracking pulses in the target region at a tracking position that is between the first and second excitation positions; receiving corresponding echo signals for the tracking pulses at the tracking position in the target region; and determining at least one mechanical parameter of the target region based on at least one parameter of a constructive shear wave displacement from the first and second shear waves simultaneously displacing tissue at the tracking position.

In some embodiments, the at least one parameter of the constructive shear wave displacement comprises at least one of a time of a peak displacement of tissue, an inflection in a displacement slope of tissue displacement at the tracking position and a relative or absolute displacement amplitude of the constructive shear wave displacement from the first and second shear waves.

In some embodiments, the tracking position is substantially equidistant from the first and second displacement positions such that the first and second shear waves arrive at the tracking position to create the constructive shear wave displacement at substantially a same arrival time that increases a tissue displacement at the tracking position at the arrival time as compared to a displacement of the first shear wave in an absence of the second shear wave or a displacement of the second shear wave in an absence of the first shear wave.

In some embodiments, generating a first shear wave at a first displacement position and a second shear wave in the target region at a second displacement position comprises generating three or more shear waves at three or more displacement positions, wherein the three or more displacement positions are substantially equidistant from the tracking position.

In some embodiments, determining at least one mechanical parameter of the target region is based on analyzing echo signals at the tracking position to determine a time-of-flight difference and/or velocity estimate of the shear wave.

In some embodiments, the first and second displacement positions correspond to positions of ultrasound array elements that transmit a displacement pulse sufficient to generate a shear wave in the region of interest.

In some embodiments, the tracking position corresponds to a position of an ultrasound array element that transmits the tracking pulses and receives the echo signals.

In some embodiments, the at least one mechanical parameter includes at least one of shear elasticity modulus, Young's modulus, storage modulus dynamic shear viscosity, shear wave velocity and mechanical impedance of the target region.

In some embodiments, the target region comprises an in vivo human tissue sample.

In some embodiments, the target region comprises in vitro biomaterials.

In some embodiments, the echo signals of the sample are detected with an internally inserted ultrasound probe array.

In some embodiments, the echo signals of the sample are detected with an externally applied ultrasound array.

In some embodiments, the first and second shear waves are generated with an applied shear wave source comprising an ultrasound transducer and/or mechanical vibrator.

In some embodiments, the first and second shear waves comprise a displacement that is orthogonal to a direction of the first and second shear waves.

According to some embodiments, A computer program product for determining a mechanical parameter for a sample having a target region using constructive shear wave displacement is provided. The computer program product includes a non-transient computer readable medium having computer readable program code embodied therein. The computer readable program code includes: computer readable program code configured to generate a first shear wave in the target region at a first excitation position and a second shear wave in the target region at a second excitation position; computer readable program code configured to transmit tracking pulses in the target region at a tracking position that is between the first and second excitation positions; computer readable program code configured to receive corresponding echo signals for the tracking pulses at the tracking position in the target region; and computer readable program code configured to determine at least one mechanical parameter of the target region based on at least one parameter of a constructive shear wave displacement from the first and second shear waves simultaneously displacing tissue at the tracking position.

According to some embodiments, an ultrasound system for determining a mechanical parameter for a sample having a target region using constructive shear wave displacement is provided. The ultrasound system includes an ultrasound transducer array and a controller configured to control the ultrasound transducer array. The controller includes: a shear wave generator configured to generate a first shear wave in the target region at a first excitation position and a second shear wave in the target region at a second excitation position; and a signal analyzer configured to transmit tracking pulses in the target region at a tracking position that is between the first and second excitation positions and to receive corresponding echo signals for the tracking pulses at the tracking position in the target region, and to determine at least one mechanical parameter of the target region based on at least one parameter of a constructive shear wave displacement from the first and second shear waves simultaneously displacing tissue at the tracking position.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Like numbers refer to like elements throughout. In the figures, the thickness of certain lines, layers, components, elements or features may be exaggerated for clarity.

The present invention is described below with reference to block diagrams and/or flowchart illustrations of methods, apparatus (systems) and/or computer program products according to embodiments of the invention. It is understood that each block of the block diagrams and/or flowchart illustrations, and combinations of blocks in the block diagrams and/or flowchart illustrations, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, and/or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer and/or other programmable data processing apparatus, create means for implementing the functions/acts specified in the block diagrams and/or flowchart block or blocks.

Accordingly, the present invention may be embodied in hardware and/or in software (including firmware, resident software, micro-code, etc.). Furthermore, embodiments of the present invention may take the form of a computer program product on a computer-usable or computer-readable non-transient storage medium having computer-usable or computer-readable program code embodied in the medium for use by or in connection with an instruction execution system.

Embodiments according to the present invention are described herein with reference to the term “tissue.” It will be understood that the term tissue can include biological materials, such as, blood, organs, vessels, and other biological objects found in a body. It will be further understood that embodiments according to the present invention may be applicable to humans as well as other species. Embodiments according to the present invention may also be utilized to image objects other than tissue.

It will be understood that the scope of the present invention includes, for example, two dimensional (2D) ultrasound imaging and 3D (or volumetric) ultrasound imaging. In addition, the components of the ultrasound imaging described herein may be packaged as a single unit or packaged separately and interconnected to provide the functions described herein.

Embodiments according to the present invention are also described by reference to Acoustic Radiation Force Imaging (ARFI) which is described in greater detail, for example, in U.S. Pat. No. 6,371,912, the entire disclosure of which is incorporated herein by reference. An acoustic radiation force may be used to apply a force to tissue thereby causing the tissue to move in the direction of the force and/or to generate a shear wave.

As used herein, a “shear wave” is a form of sample displacement in which a shear wave source, such as ultrasound energy, is transmitted into the sample in one direction and generates an extended shear wave the propagates in another direction that is substantially orthogonal to the direction of the shear wave source. The displacement caused by a shear wave source may be in a range between about 0.1 μm and about 300 μm. Other displacements can be provided.

The term “time of arrival” refers herein to the measured elapsed time between the transmission of a transmitting signal and the return of a corresponding reflected signal. The time of arrival is measured by conventional measurement techniques.

As illustrated inFIG. 1, an ultrasound system10includes a controller20, a signal analyzer30and an ultrasound transducer array40. The ultrasound transducer array40may include a plurality of array elements42at positions P1through PN. The array elements42are configured to transmit and receive ultrasound signals50, and may be contacted to a target medium such as a tissue medium60. As illustrated, the tissue medium60includes a target region62. The ultrasound array40may include ultrasound array elements42that define transmit/receive locations for transmitting and receiving ultrasound signals along a direction D1. In some embodiments, the array40may be configured to transmit sufficient ultrasound energy, for example, by applying an impulse excitation acoustic radiation force to the medium60, to generate a shear wave that propagates in a direction D2that is orthogonal to D1. The array40may also be configured to interrogate the tissue medium60, for example, using ARFI or B-mode imaging techniques to monitor the tissue through time before and/or after the shear wave excitation force has been applied. ARFI imaging is discussed in U.S. Pat. Nos. 6,371,912; 6,951,544 and 6,764,448, the disclosures of which are hereby incorporated by reference in their entireties. Shear waves are discussed in U.S. Pat. Nos. 8,118,744 and 6,764,448, the disclosures of which are hereby incorporated by reference in their entireties. The ultrasound transducer array40may be a one-dimensional array configured to generate two-dimensional images or the ultrasound transducer array40may be a two-dimensional array configured to generate three-dimensional images.

The controller20may include a shear wave generator22and the signal analyzer30may include a constructive shear wave analyzer32. The shear wave generator22and the constructive shear wave analyzer32may be configured to control the array40and/or to analyze echo signals received by the array40as described herein. The shear wave generator22and the constructive shear wave analyzer32may include hardware, such as control and/or analyzing circuits, and/or software stored on a non-transient computer readable medium for carrying out operations described herein.

The shear wave generator22and the constructive shear wave analyzer32may determine a mechanical parameter for the target region62of the sample tissue60by generating and analyzing constructive shear waves. As shown inFIGS. 1 and 2, the shear wave generator22may generate a first shear wave in the target region62at a first excitation source position S1(Block100;FIG. 2) and a second shear wave in the target region62at a second excitation source position S2(Block102;FIG. 2). The controller20can control the array40to emit tracking pulses in the target region62at a tracking position T that is between the first and second source excitation positions S1, S2(Block104;FIG. 2). Corresponding echo signals for the tracking pulses at the tracking position T in the target region62are received by the array40(Block106;FIG. 2). The constructive shear wave analyzer32determines at least one mechanical parameter of the target region62based on the echo signal at position T (Block108;FIG. 2). For example, the mechanical parameter may be based on a time of a peak displacement of tissue, an inflection in a displacement slope of tissue displacement at the tracking position T and/or a relative or absolute displacement amplitude of a constructive shear wave displacement from the first and second shear waves. In this configuration, the constructive shear wave from the first and second shear waves may increase a signal to noise ratio and provide an improved ultrasound signal as compared to a single shear wave.

The shear waves may be generated simultaneously at Blocks100and102, and the position T may be substantially equidistant from the positions S1, S2so that the shear waves arrive at position T at approximately the same time in a tissue region with substantially homogeneous tissue stiffness. However, any suitable configuration of two or more constructive shear waves that have an arrival time at a common position may be used. For example, time-of-flight information may be used to select a timing of constructive shear wave arrival times at the position T and/or to select a spacing of the source excitation positions S1, S2so that the equidistant spacing of the tracking position T from the source excitation positions S1, S2and simultaneous excitation is not required to achieve a constructive or additive shear wave at the tracking position T.

FIG. 3illustrates an ultrasound array200including a linear array of transducers210, including ultrasound transducers corresponding to the first and second excitation positions S1, S2and the tracking position T. The tracking position T may be substantially the same distance X from the first and second excitation positions S1, S2such that the first and second shear waves arrive at the tracking position T at substantially a same arrival time so as to increase a tissue displacement at the tracking position T at the arrival time as compared to a displacement of the first shear wave (in an absence of the second shear wave) or the second shear wave (in an absence of the first shear wave). The first and second shear waves will generally have the same arrival time at the tracking position T if the tracking position T is substantially the same distance X from the first and second excitation positions S1, S2if the tissue in the target region62ofFIG. 1has substantially uniform stiffness with a substantially constant shear wave speed cT between the source excitation positions S1, S2and the tracking position T and/or the distance X is sufficiently small. For example, in some embodiments, the distance X is less than two shear wavelengths. The source of the shear waves at positions S1, S2generates the first and second shear waves at a common time t0and each shear wave arrives at the tracking position T at an arrival time t1. It should be understood that the configuration ofFIG. 3may be achieved using three ultrasound elements on an ultrasound array, such as the array40ofFIG. 1, or by using discrete pistons at each source excitation position S1, S2and tracking position T.

The excitation sources may be provided by any suitable configuration of multiple sources that are spaced-apart and/or timed such that the resulting shear waves constructively come together at the tracking location to augment the individual amplitudes of the shear waves taken individually. The tracking pulses may be used to determine at least one mechanical parameter of the target region62, including a shear elasticity modulus, Young's modulus, storage modulus dynamic shear viscosity, shear wave velocity and mechanical impedance of the target region62using any suitable technique, including SWEI analysis techniques known to those of skill in the art.

In addition, it should be understood that more than two excitation sources may be used, such as in a matrix (two-dimensional) array as illustrated inFIGS. 4 and 5. Moreover, the excitation sources may be provided by one- or two-dimensional ultrasound transducer arrays, a ring or two-dimensional matrix array that provides a “ring” of sources, and/or piston transducers that are physically separated from one another. Accordingly, it should be understood that the shear waves at the source excitation position S1, S2may be generated with an ultrasound transducer and/or a mechanical vibrator. The excitation sources may transmit a displacement pulse sufficient to generate a shear wave in the region of interest.

For example, as shown inFIG. 4, a two-dimensional ultrasound array300of ultrasound transducer or piston elements310, including transducers corresponding to shear wave excitation sources S1, S2, S3and S4and tracking position T, are shown inFIG. 4. As illustrated, the array300includes seventeen elements210; however, any number of elements in rows/columns may be used. The tracking position T may be substantially the same distance from the positions S1, S2, S3and S4such that the shear waves arrive at the tracking position T at substantially a same arrival time so as to increase a tissue displacement at the tracking position T at the arrival time as compared to a displacement of each of the shear waves taken individually. The shear waves will generally have the same arrival time at the tracking position T if the tracking position T is substantially the same distance X from the excitation positions S1, S2, S3and S4if the tissue has substantially uniform stiffness with a substantially constant shear wave speed and the distance between the excitation positions S1, S2, S3and S4and the tracking position T is sufficiently small. The source of the shear waves at positions S1, S2, S3and S4generates four respective shear waves at a common time t0and each shear wave arrives at the tracking position T at a common arrival time t1.

As shown inFIG. 5, the shear wave excitation may be generated by a continuous ring source ultrasound transducer310A with a centrally located tracking transducer or piston310B. A non-continuous ring could also be used with sources that are all substantially equidistant from the central tracking location of the piston310B. The source of the shear waves at the ultrasound transducer310A shear waves from the positions around the ring at a common time t0and the resulting shear waves arrive at the tracking position T at a common arrival time t1. Accordingly, it should be understood that two or more shear waves may be generated by a substantially continuous ring-shaped transducer310to generate shear waves that originate at continuous locations around the ring-shaped transducer310and converge at the tracking position T.

The tracking signals may be detected and/or the shear waves may be generated repeated as described herein through a region of interest, for example, to generate an image. The tracking signals may be detected and/or the shear waves may be generated as described herein with an internally inserted ultrasound probe array or an externally applied ultrasound array. In some embodiments, the target region may be an in vivo human tissue sample; however, in vitro biomaterials, such as engineered tissues or hydrogels may be used.

The mechanical parameter(s) of the sample, such as shear elasticity modulus, Young's modulus, storage modulus dynamic shear viscosity, shear wave velocity and mechanical impedance, can be correlated to measurement of healthy/diseased tissue states, such as by using actual clinical data and known healthy/diseased tissue states. The clinical data can be based on other factors such as demographic information, e.g., age, gender and race, to correlate the measurement of the mechanical parameter(s) with a measurement of healthy/diseased tissue states in a particular demographic group.

In some embodiments, the mechanical parameter(s) of the sample can be monitored as a function of time by performing the shear wave analyzing techniques described herein on a sample repeatedly over a period of time. A healthy/diseased tissue state determination can be based on a change in the mechanical parameter(s) as a function of time. For example, the mechanical parameter(s) can be monitored over a period of minutes, hours, days, weeks, months or even years to determine the progression of the disease and/or the efficacy of treatment.

In some embodiments, the mechanical parameter(s) may be used to form an ultrasound image, such as a B-mode image or an ARFI image.

In some embodiments, improvements of the signal-to-noise ratios may be achieved. For example, as shown inFIGS. 6A-6B, representative simulated data of how displacement amplitude at the central tracking location (FIG. 6A) and the associated SNR (FIG. 6B) change as a function of number of equidistant sources. In this simulation, the sources were placed 5 mm from a central track location, and each source was approximated using an axisymmetric, Gaussian-distributed geometry that had a full width half maximum (FWHM) of 0.1 mm in the same spatial plane as the sources. The material was modeled as purely elastic, with a Young's modulus of 6 kPa and a Poisson's ratio of 0.495 (nearly incompressible). The acoustic radiation force for each source was applied for 50 us, and displacements were tracked at the central location at a 10 kHz rate for a total of 20 ms. The tracking focal configuration was simulated for that of a focused piston with a focal depth of 1.25 cm. As expected, both the displacement magnitude and the associated SNR increase with more sources. While 10 sources were feasible to simulate, the physical size of each source is expected to impose a constraint on how many sources are used, and how closely spaced they can exist. The number of sources, their spacing, and their focal configurations are all parameters that can be optimized for different clinical applications.