Mapping relative acoustic radiation force and attenuation using shear waves and mechanical reciprocity, methods and systems thereof

Abstract

A method employing the principle of mechanical reciprocity to image the relative acoustic attenuation called shear wave reciprocity imaging (SRI). SRI does not require the pre-stored sample signal for acoustic attenuation evaluation. In SRI, sequential marching pushes similar to acoustic radiation force impulse (ARFI) imaging are excited from an array transducer, and the reciprocal displacements are collected similarly to the plane wave single-track location method (p-STL).

Description

TITLEMAPPING RELATIVE ACOUSTIC RADIATION FORCE AND ATTENUATION USING SHEAR WAVES AND MECHANICAL RECIPROCITY, METHODS AND SYSTEMS THEREOF

[0001] This invention was made with government support under EB034769 awarded by the National Institute of Health. The government has certain rights in the invention.

[0002] This application claims priority from U.S. Provisional Application No. 63 / 696,248, filed September 18, 2024, which is incorporated herein by reference.FIELD

[0003] This application relates to the field of ultrasonic tissue characterization, imaging, and ultrasound Shearwave Elastography (USWE).BACKGROUND

[0004] Ultrasound Shearwave Elastography (USWE) provides contrast based on tissue stiffness complementary to conventional US imaging. Although most commercially available USWE systems assume that tissue is elastic, elasticity alone is not a reliable discriminant for many pathologies.SUMMARY

[0005] An aspect of the present application is directed to a method of mapping acoustic radiation force using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations; pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push location and the second track location: measuring frequency-dependent shear wave speed; measuring attenuation of the shear waves; measuring differences in displacement due to differences inlocal acoustic radiation force that is attributed to attenuation coefficient difference; constructing multifrequency parametric two-dimensional maps capturing local tissue viscoelasticity.

[0006] Another aspect of the present application is directed to a method of mapping ultrasound attenuation using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations; pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push location and the second track location: measuring differences in displacement due to differences in local ultrasound attenuation; constructing two-dimensional maps of local tissue ultrasound attenuation from reciprocity relations and measured differences in displacements.

[0007] These and other aspects, objects, features, and advantages of the example embodiments will become apparent to those having ordinary skill in the art upon consideration of the following detailed description of example embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] An understanding of the features and advantages of the present application will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the application may be utilized, and the accompanying drawings. The figures herein are for illustrative purposes only and are not necessarily drawn to scale.

[0009] FIG.1 shows original and reciprocal displacements due to F1. δ11is the displacement due to F1at position 1, and δ21is the displacement due to F1at position 2.

[0010] FIG.2 shows sequential design and IQ data collection of SRI, marching push sequences are deployed on a linear array transducer. PB represents the Bthpush ensemble, and TA,Brepresents the track channel at Ath position in Bthensemble. For each ensemble, rawRF data in the ROI due to shear wave propagation are collected by plane wave compounding with many frames that depend on the track PRF.

[0011] FIG.3 shows the steps of generating a reciprocity map. Blue arrows represent the displacement data recorded due to a specific push force, and green arrows represent the reciprocal displacement data recorded from the channel having the same axial position as the specific push due to the reciprocal push forces.

[0012] FIG.4 shows quantified reciprocal displacements and ratio in a phantom with the same attenuation. δ12is measured at the red point due to F1and δ21is measured at the blue point due to F2. The error bar plot illustrates the average and standard deviation of the reciprocal ratio between δ12and δ21with varying auto-correlation kernel size.

[0013] FIGS.5A and 5B show validation of shear reciprocity in the ROI with the (FIG.5A) same attenuation and (FIG.5B) different attenuation. The region inside the yellow dashed circle has a higher attenuation coefficient than that outside. δ21is measured at the red point due to F1and δ12is measured at the blue point due to F2. Error bar plots illustrate the average and standard deviation of the reciprocal ratio with varying aperture size. Assume that the background and inclusion have the same attenuation power law exponents.

[0014] FIGS.6A-6C show reciprocal displacement ratio on the axial direction. FIG. 6A depicts applications of F1and F2to the background (∼0.5 dB / MHz / cm). The plot is the reciprocal displacement ratio δ12 / δ21due to F1and F2, respectively. FIG.6B depicts application of F1to the background (∼0.5 dB / MHz / cm) and F3to the inclusion (∼1.0 dB / MHz / cm). The plot is the reciprocal displacement ratio δ13 / δ31due to F1and F3, respectively. The high attenuation region is circled and marked in B-mode and plot, respectively. The red dashed line (equals 1) represents that both radiation forces have the same reciprocal displacements. FIG.6C depicts the positions of F1, F2, and F3plus an enhanced reciprocity map.

[0015] FIG.7 shows maps reconstructed from CIRS attenuation phantom contains background (α = 0.5 dB / MHz / cm), Type I (α = 1.00 dB / MHz / cm), Type II (α= 0.22 dB / MHz / cm), Type III (α = 1.00 dB / MHz / cm) and Type IV (α = 0.25 dB / MHz / cm) inclusions. The results illustrate the images of (I) B-mode with marked inclusion, (II) SWEI in (m / s), (III) radiation force map (Equation (Eqn) (8)), (IV) reciprocity map based on axial displacement ratio (Eqn (9)), and (V) enhanced reciprocity map (Eqn (12)). Force and reciprocity maps do not have units.

[0016] FIG.8 shows maps reconstructed from fabricated attenuation phantoms. Recipes are based on Table II. The results illustrate the images of (I) B-mode with marked inclusion, (II) SWEI in (m / s), (III) radiation force map (Eqn (8)), (IV) reciprocity map based on axial displacement ratio (Eqn (9)), and (V) enhanced reciprocity map.

[0017] FIG.9 shows maps reconstructed from porcine kidney phantoms. The results illustrate the images of (I) B-mode with marked inclusion, (II) SWEI in (m / s), (III) radiation force map (Eqn (8)), (IV) reciprocity map based on axial displacement ratio (Eqn (9)), and (V) enhanced reciprocity map.

[0018] FIG.10 is an illustration of mechanical reciprocity.

[0019] FIG.11 exemplifies acoustic radiation force (ARF).

[0020] FIG.12 exemplifies attenuation measurement.

[0021] FIG.13 shows an illustration of verasonics experimental implementations in tissue-mimicking phantom.

[0022] FIG.14 shows an illustration of verasonics experimental implementations in tissue-mimicking phantom.

[0023] FIG.15 shows K-wave simulations in tissue-mimicking phantom.

[0024] FIG.16 shows K-wave simulations in tissue-mimicking phantom.

[0025] FIG.17 shows an exemplary attenuation map.

[0026] FIG. 18 shows attenuation estimator vs. elasticity estimator.

[0027] FIGS. 19A-19B exemplify image formation.

[0028] FIG. 20 shows spatial sensitivity maximalized in focal zone.

[0029] FIG. 21 shows elasticity in SRI.

[0030] FIG. 22 demonstrates proof of ARF-induced reciprocity.

[0031] FIG. 23 shows the results of an experiment with SRI maps.

[0032] FIG 24 shows porcine kidney phantoms.DETAILED DESCRIPTION

[0033] Reference will be made in detail to certain aspects and exemplary embodiments of the application, illustrating examples in the accompanying structures and figures. The aspects of the application will be described in conjunction with the exemplary embodiments, including methods, materials and examples, such description is non-limiting and the scope of the application is intended to encompass all equivalents, alternatives, and modifications, either generally known, or incorporated here. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. One of skill in the art will recognize many techniques and materials similar or equivalent to those described here, which could be used in the practice of the aspects and embodiments of the present application. The described aspects and embodiments of the application are not limited to the methods and materials described.

[0034] As used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the content clearly dictates otherwise.

[0035] Ranges may be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will beunderstood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "10" is disclosed, the "less than or equal to 10" and “greater or equal to 10” is also disclosed. When two or more value are disclosed, all possible ranges between any two values are disclosed.

[0036] A new ultrasound image formation method, termed here as “shear-wave reciprocity imaging” (SRI), to produce images based on the sound speed and attenuation of tissue. These acoustic properties carry important diagnostic information but are not revealed in conventional B-mode images except as artifacts. For example, in breast imaging the “posterior features” (shadowing / enhancement) BiRADS descriptor depends on these properties. In contrast to conventional B-mode imaging that produces speckle images of variations in tissue acoustic impedance, SRI is presented here as a method for speckle-free imaging of an attenuation / sound speed parameter. SRI images are complementary to both B- mode and elastography images yet are produced using the same backscatter imaging geometry as conventional ultrasound. SRI relies on the principle of mechanical reciprocity to measure local variations in acoustic radiation force, which relate to attenuation and sound speed. While using acoustic radiation force impulses similar to ARFI imaging, SRI is designed to be insensitive to elastic properties and to specifically image the attenuation / sound speed parameter. The aims of this disclosure are to implement SRI on a linear-array imaging system, characterize its sensitivity and resolution through in vivo measurements prior tobiopsy, and validate SRI in ex vivo breast tissue from mastectomy. The additional information provided by SRI ultimately improves lesion categorization and reduces the number of biopsies required by replacing qualitative estimates of lesion attenuation from B- mode shadowing with parametric acoustic images.

[0037] Acoustic radiation force is the quantity that the reciprocity relationship yields, then the relationship between attenuation coefficient and acoustic radiation force is used to infer the relative attenuation. In certain embodiments, this application discloses a system that measures radiation forces, and then a system that then does the conversion to attenuation coefficient.Static Reciprocity

[0038] Reciprocity implies a mutual relationship between two entities. In elastic body mechanics, reciprocity describes the relationship between two loading conditions (forces) and the displacements that result. If a force F1is applied at position 1 first and then F2at position 2, as shown in FIG. 1, the stored energy equals:

[0039] When F2is applied first, the stored energy equals:

[0040] where δ11is the displacement at position 1 in the direction of F1due to the application of F1, and δ21is the displacement at position 2 in the direction of F2due to the application of F1. Similar definitions can be used to express 622 and 612. Since the total energy stored in both cases is equal, hence the static reciprocity can be:F1δ12= F2δ21Shear Wave Reciprocity

[0041] In ultrasound, acoustic radiation force (ARF) is defined as:

[0042] where α, Isptaand c denote the material’s acoustic absorption coefficient, absorbed temporal average intensity and sound speed, respectively. In a weakly scattering medium such as tissue, the acoustic absorption coefficient is nearly equivalent to the acoustic attenuation coefficient. Assume that two acoustic pushes and their reciprocal displacements during shear wave propagation satisfy the theorem from Eqn (3). One of ordinary skill will understand that the push pulses can be in any order, such as in order 1,2,3,...,N, or in a random sequence, or odd then even, or whatever may be the choice. Therefore, the shear reciprocity can be expressed as:

[0043] The reciprocal displacements can be used as temporal total or peak-to-peak displacements within the tracked time. If the intensities and sound speeds are similar between the two positions, then only the attenuation coefficients are considered. Thus, the ratio of the radiation forces is approximately equal to the ratio of the attenuation coefficients. This can be expressed as:Sequential Design and Axial Motion Track

[0044] The ARFI push and the p-STL track methods are applied to generate and record shear wave signals. A focused push beam, marked as B representing the Bth push, uses a few hundred microseconds of excitation to induce the shear wave. Once the push excitation is completed, all channels on the transducer are active to record backscattered data and track scattered axial motion from the shear wave. A three-angle spatial compounding plane wave tracks shear-induced axial displacements for each push ensemble. One of ordinary skill will understand that the use of three-angle compounding is not limiting, andgreater numbers of angles, fewer numbers of angles, or no angles may all be used alternatively according to choice. Use TA,Bto denote the positions of the tracked data, where A is the position of the track channels and B is the order of the pushes as illustrated in FIG.2. In this process, there are A ensemble frames of 3-D radio frequency (RF) data (each ensemble contains axial, lateral, and track frames data) collected, corresponding to the number of pushes. These RF data are demodulated to obtain the phase based in-phase and quadrature (IQ) data for calculating the axial displacements. If M and N are in axial and shear wave track frame directions, the average axial displacement within the selected region can be calculated using the Kasai or Loupas auto-correlation methods. One of ordinary skill will understand that the motion is tracked ultrasonically and not the specific motion estimator used. One of ordinary skill will understand that any well-known method for tracking tissue motion with ultrasound can be used. SRI Algorithms

[0045] Use auto-correlation methods to obtain 4D displacement data including axial, lateral, track frame, and ensemble directions. Time-varying displacement signals of each spatial pixel can be captured for further calculations from each ensemble along the track frame direction. To characterize the degree of attenuation, radiation force, and reciprocity maps are reconstructed to localize benign and malignant lesions. Choosing the matched data from the push force and reciprocal positions is the critical step to constructing a radiation force map. Matrix Aforceincluding push force and reciprocal positions are built in this step. The selected displacement data at push force and reciprocal positions can form another matrix bdisp. Based on Eqn (6), the radiation force [F1, F2, F3, ..., FB]T for each row of the image can be obtained by solving the Aforcex= bdispequation:

[0046] where A denotes the spatial channel position of force or displacement on the array transducer corresponding with FIG.2. Based on Eqn (6), the reciprocity map is the cumulation of all the reciprocal computations over the region of interest. The procedure of generating a reciprocity map is suggested by FIG.3 and can be expressed as:

[0047] Here is an example to find a specific displacement from the data: δ(10,3,5) represents the 5th row of the displacement tracked at the position T(10,3) as shown in FIG.2 due to the 3rd push. The raw displacements are recorded from Eqn (7). In Eqns (7)-(8), the temporal cumulative or peak-to-peak displacements should be used for each pixel, which equals:or

[0048] where A and B represent the track channels and order of pushes corresponding with Fig.2, and T denotes the total time flight of the tracked displacement data in frame direction for each ensemble. The contrast stretched force and reciprocity maps are filtered by:

[0049] to obtain the processed maps with appropriate contrast and digital range. SLand SH represent the scaling parameters, which are determined based on the bin values from the histogram. These parameters are used to control the dynamic range of the input image. In this study, SLand SHrepresent the edge values corresponding to bin counts exceeding the lowest 5% of bins. Let Rforcedenote the force map from Eqn (8) after contrast stretching and Rdisp denote the reciprocity map from Eqn (9) after contrast stretching. The enhanced map based on shear wave reciprocity is then defined as:ReRforce× Rdisp

[0050] The enhanced map provides higher contrast which may help clinicians easier to differentiate the benign and malignant lesions. All the maps should be taken into consideration together when diagnosing the malignant tissues.Analysis

[0051] The effect of auto-correlation kernel size on the reciprocal displacement ratio is investigated in FIG. 4. In a phantom with the same attenuation, the performance of the kernel size between 0.25λ and 0.75λ is poor due to the standard deviation being higher than 0.10. Kernels between 1.00k and 2.00k have a closer average and lower standard deviation. Kernel size over 2.00k is also not suggested, because SRI is aimed at measuring ARF or attenuation within a small axial range. The results for the case of shear wave reciprocity validation with a significantly higher reciprocal displacement ratio, when radiation force was applied to higher attenuation ROI, are shown in FIGS. 5A-5B. Compared to the 0.5 dB / MHz / cm region in FIG. 5 A with F / 2.5, the logarithmic of the 1.0 dB / MHz / cm region inFIG.5B with F / 2.5 is about 45 times larger, even though the ratios in FIG.5B are less than 2. Thus, the ratio is large enough to differentiate tissues with 50% attenuation difference. Moreover, the investigation of the on-axial shear wave reciprocity in FIGS.6A-6C show that high attenuation inclusion has a higher ratio than the background, demonstrating the feasibility and reliability of the SRI in advance. Note that the high ratio parts in the shallow depth field (∼7-8 mm) should be neglected because of the layers formed by the phantom surface and ultrasound gel. The validation cases prove that shear wave reciprocity is a feasible biomarker to measure ARF or acoustic attenuation.

[0052] Comparisons between elastograms and SRI maps in tissuemimic phantom are shown in FIG.7 and FIG.8. The solution of ARF provides the map constructions in (IV). In addition, the reciprocity map based on the force ratio is derived from the radiation force map. An enhanced reciprocity map is obtained based on the two maps in (V) and (VI). Compared to the elastograms, SRI contributes to a higher contrast map and clearer inclusion margin if the tissue shows less effect on elasticity than acoustic attenuation. Enhanced contrast reciprocity maps show the advantage of being diagnostically convenient. The experiment in porcine kidney phantoms initially demonstrates that SRI can characterize high attenuation tissues in the phantom, and the future aim is the application of SRI in ex vivo investigations. In addition, a curved linear array transducer will be employed to investigate deeper tissue SRI for the next step.

[0053] Investigations in CIRS, fabricated, and porcine kidney phantoms demonstrate that SRI is a feasible method for 2D map reconstruction and differentiating high attenuation between background and inclusions. However, the limitation of current SRI is that the effects of sound speed and absorbed temporal average intensity are neglected. The absorbed temporal average intensity could present a critical subject for future research. In a study of a phantom, inclusions have the same attenuation and elasticity but different echogenicity, weobserved higher reciprocal displacement when focused on a lower echogenicity inclusion. Variations in echogenicity may lead to differences in absorbed intensities.

[0054] SRI is a novel technique proposed for estimating the acoustic attenuation of tissues. It utilizes a linear array transducer to measure the radiation force and reciprocal ratio, providing 2D maps for evaluating attenuation. The feasibility and functionality of SRI have been demonstrated in phantom experiments. As an attenuation biomarker, SRI exhibits high performance and sensitivity in phantoms with varying attenuation distributions.

[0055] An aspect of the present application is directed to a method of mapping acoustic radiation force using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations; pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push location and the second track location: measuring frequency-dependent shear wave speed; measuring attenuation of the shear waves; measuring differences in displacement due to differences in local acoustic radiation force that is attributed to attenuation coefficient difference; constructing multifrequency parametric two-dimensional maps capturing local tissue viscoelasticity.

[0056] In some embodiments, the method further comprises the step of sequential marching pushes, in any order, are excited from an array transducer, and the reciprocal displacements are collected.

[0057] In some embodiments, the method further comprises the step of inducing a shear wave by excitation of tissue using a focused push beam. In some further embodiments, once the push excitation is completed, the method comprises the step of recording on a plurality of channels on a transducer backscattered data and track scattered axial motion fromthe shear wave. In some still further embodiments, the method comprises the step of tracking shear-induced axial displacements for each push ensemble.

[0058] In some embodiments, the method comprises the step of collecting A ensemble frames of 3-D radio frequency (RF) data, wherein each ensemble includes axial, lateral, and track frames data, corresponding to the number of pushes. In some further embodiments the method further comprises the step of demodulating RF data to obtain the phase based in- phase and quadrature (IQ) data for calculating the axial displacements. In some still further embodiments, the method comprises the step of using auto-correlation methods to obtain 4D displacement data including axial, lateral, track frame, and ensemble directions.

[0059] In some embodiments, the method comprises the step of capturing time- varying displacement signals of each spatial pixel for calculations from each ensemble along the track frame direction.

[0060] In some embodiments, the method comprises the step of choosing matched data from the push force and reciprocal positions to construct a radiation force map.

[0061] In some embodiments, the method comprises the step of deriving the relative attenuation of the tissue using the proportional relationship between acoustic radiation force and attenuation coefficient. In some further embodiments the method further comprises the step of bootstrapping the reciprocity-derived attenuation measurements with low spatial resolution attenuation measurements using reference phantom, frequency downshift, or related methods.

[0062] Another aspect of the present application is directed to a method of mapping ultrasound attenuation using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations; pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push locationand the second track location: measuring differences in displacement due to differences in local ultrasound attenuation; constructing two-dimensional maps of local tissue ultrasound attenuation from reciprocity relations and measured differences in displacements.

[0063] The present application is further illustrated by the following examples that should not be construed as limiting. The contents of all references, patents, and published patent applications cited throughout this application, as well as the Figures and Tables, are incorporated herein by reference.EXAMPLESExample 1: Materials and Methods

[0064] This section introduces the SRI implementation through the experiments.First, an experimental investigation was conducted to demonstrate the feasibility of shear reciprocity in phantoms. Second, further investigations were completed in CIRS and fabricated phantoms to prove that the SRI algorithms work with different attenuation coefficients and exhibit contrast between background and inclusion. Third, investigations of fabricated kidney phantoms proved that the SRI method is feasible in animal tissues. All experiments were implemented on a Verasonics Vantage 64 LE system, and an ATL L7-4 transducer was applied to collect the data.Validation of the Shear Reciprocity

[0065] The feasibility of the shear reciprocity and the performance of the compounding plane wave track were validated through an attenuation CIRS phantom. Radiation forces and reciprocal displacements were recorded through a two-pushes design with a compounding plane wave track. In this experiment, 400-micron pushes with 4MHz center frequency were applied to induce shear waves. 5MHz short-term (1 cycle) track beams were used to record the axial displacements.

[0066] The first validation was implemented on the homogeneous (same attenuation) background with a focus at 25 mm. One push center was set up on the 20thtransducer channel, and the other was on the 109thtransducer channel. Before starting the second validation, the center of a higher attenuation inclusion (∼1.0 dB / MHz / cm) was aligned at the center of the B-mode image. One push was still on the 20thtransducer channel, and the other was on the central channel. Data from the two validations were collected with the aperture sizes between F / 2 and F / 4. SRI in Phantoms

[0067] The investigation aims to validate the feasibility of the new proposed methods in imaging. Radiation force and reciprocity maps were generated based on Eqns (8)-(9) through CIRS attenuation and fabricated phantoms. The number of pushes depends on the lateral size of the ROI. The parameters for generating maps are provided in Table I. Sequential scan follows FIG.2. Signal and image processing follow Eqns (7)- (13).

[0068] The CIRS phantom has a background with an attenuation coefficient of 0.5 dB / MHz / cm. Four inclusions have attenuation coefficients equal to 1.0 dB / MHz / cm (Type I and III inclusions) and 0.22-0.25 dB / MHz / cm (Type II and IV inclusions). The average sound speed of the inclusions is between 1531 and 1542 m / s which has a small difference with the background (1531 m / s). The contrast of the inclusions is between +2 to +4 dB higher than the background, making them difficult to identify in the B-mode images. The Young’s modulus of the inclusions, approximately within 10 kPa, is similar to that of the background. Therefore, the CIRS phantom is appropriate for investigating the attenuation effects on SRI.

[0069] Previous studies have demonstrated that an evaporated milk added gel phantom has higher acoustic attenuation than a pure gel phantom. Additional silicon dioxide (SiO2) can also increase acoustic attenuation. The recipe for fabricating an attenuation phantom is shown in Table II. Gelation 200 bloom, cornstarch (provides scatterers), evaporated milk, SiO2, deionized water, a 6mm-diameter steel rod, and a cubic mold were used to make a phantom. The background was made from gelatin, cornstarch, and deionized water on day 1: (i)Fix the steel rod in the middle of the cubic mold with a test tube holder. (ii)Add the mixture of gelatin and cornstarch to 600 ml of deionized water. (iii)Heat the solution to 70ºC and stir well until 30ºC. (iv)Pour the solution into the cubic mold and wait for the jellification overnight. Inclusion contained extra evaporated milk and SiO2was made on day 2: (i)Remove the steel rod from the mold to leave an empty cylinder for the inclusion. (ii)Add the mixture of gelatin and cornstarch to 100 ml of deionized water and evaporatedmilk. (iii)Heat the solution to 90ºC and stir well until 30ºC. (iv)Add the solution slowly to the empty cylinder and wait over 3 hours. SRI in Fabricated Kidney Phantoms

[0070] The human kidney has a higher attenuation than other organs, such as the brain, liver, and spleen. A porcine kidney sample was used as a substitute for a human kidney. The process of making the background of kidney phantoms is the same as the description in subsection B. Add 300 ml solution of the mixture of gelatin and cornstarch to the bottom of the mold. Put a fresh piece of porcine kidney, about the size of a dice, onto the jellified bottom layer. Immerse the porcine kidney in another 300 ml gelatin and cornstarch solution to form a kidney-embedded phantom. Transducer and beam parameters remain the same as in Table I. The Recipe of the background remains the same as the phantom A in Table II.Example 2: Validation of the Shear Reciprocity

[0071] First and foremost, validating the feasibility of reciprocity in shear-induced displacements is the prerequisite for producing a 2D reciprocity map. Data were collected from the background of the CIRS phantom that the ROI has the same distributions of attenuation, sound speed, contrast, and elasticity.

[0072] Before the validation, determining the matched autocorrelation kernel sizes is helpful for the accuracy of reciprocal ratio computation.65-volts push forces F1and F2were applied to the left and right, respectively. Their reciprocal displacements, δ12and δ21, near focus were recorded at the red and blue points, respectively using compounding plane wave track as shown in FIG.4. FIG.4 exhibits an example of the measured reciprocal displacements based on Eqns (10) and (11). Since the sound speed, contrast, and attenuation coefficients are closed between the two points, the ideal reciprocal ratio should be 1 as shown in a red dashed line in FIG.4 when the same voltage radiation forces are applied. From FIG. 4, the average reciprocal ratio of the kernel sizes from 0.25λ to 2.0λ equals 1.01±0.30, 1.16±0.20, 1.06±0.14, 1.01±0.07, 0.99±0.04, 0.98±0.03, 1.03±0.04, and 1.04±0.06 if peak-to- peak displacement method applied. Therefore, kernel size between 1.0λ and 2.0λ should be selected to calculate axial displacement due to their average (approach to 1) and smaller standard deviations.

[0073] The feasibility of shear reciprocity was validated in another experiment as shown in FIGS.5A-5B. Effects of varying aperture, the same focus but different F / #, were also investigated in this study. A 1.5λ kernel size was selected to calculate axial displacement. Approximately reciprocal displacements were observed in the ROI with the same attenuation (∼0.5 dB / MHz / cm) shown in FIG.5A. Furthermore, the reciprocal displacement ratio based on Eqn (6) approached the expected attenuation ratio α2 / α1 = 1, shown as a red dashed line in FIG.5A. In another ROI with different attenuationdistributions, F1was applied to a lower attenuation (∼0.5 dB / MHz / cm) region and F2to a higher attenuation (∼1.0 dB / MHz / cm) region. Therefore, the expected attenuation ratio α2 / α1=2. Assuming that the attenuation power law exponent is a constant everywhere in the phantom, FIG.5B shows that the reciprocal displacement ratio between δ12and δ21approaches 2.0, particularly the peak-to-peak displacements. Compared with FIG.5A, the reciprocal displacement ratio of FIG.5B is significantly higher than 1. Details of the displacement and reciprocal ratio are shown in Table III.

[0074] A further investigation of the on-axial reciprocal displacement ratio is shown in FIGS.6A-6C. Push beams with 65 volts and F / 2.5 were used to induce shear waves. Three angles compounding plane wave tracks were applied to track the displacements.1.5λ kernel was selected for the post-processing of the IQ data. Data were collected from the CIRS phantom, and the selected ROI contains the background and type III inclusion. In FIG.6A, F1and F2were applied to the background with the same attenuation. The reciprocal displacement ratio (δ12 / δ21) due to F1and F2is around 1 marked as a red dashed line. In FIG. 6B, F1was applied to the background, and F3was applied to a high attenuation inclusion. The reciprocal displacement ratio (δ13 / δ31) is around 1 in the background, but it significantly increases in the range of the inclusion. FIG.6C illustrates the positions of F1, F2, and F1in the same B-mode. Furthermore, an enhanced reciprocal map corresponds with the results in FIGS.6A and 6B. SRI in Phantoms

[0075] Validations of 2D SRI maps are shown in this subsection. The results of the CIRS attenuation phantom are illustrated in FIG.7. The attenuation of the background (∼0.5 dB / MHz / cm) is lower than the Type I and III inclusions ((∼1.0 dB / MHz / cm) ) and higher than the Type II (∼0.22 dB / MHz / cm) and IV (∼0.25 dB / MHz / cm) inclusions. Localizing the inclusions in B-mode grayscale images and elastograms is difficult because the echogenicitycontrast and elasticity between the background and inclusions are small enough. From the results, type I and III inclusions exhibit significantly higher values than the background, demonstrating that the inclusions have higher force or attenuation than the background. In contrast with type I and II inclusions, type II and IV inclusions show lower force or attenuation.

[0076] Validations of 2D SRI maps in the fabricated attenuation phantoms can provide more reliable evidence. The phantoms were carefully fabricated to maintain the difference in echogenicity contrast and elasticity between the background and inclusions, which were as small as possible. In FIG. 8, particularly Phantom B, the inclusion is not easily found in Bmodeimages. Both elastograms cannot find the inclusions due to the same elasticity in the ROI. However, higher attenuation inclusions can be easily observed in force and reciprocity maps.SRI in Fabricated Kidney Phantoms

[0077] FIG. 9 shows the potential of SRI maps to detect animal tissues from three phantoms. Although the kidney samples show higher elasticity than the background in kidney A, it is difficult to determine the sample size. It becomes easier to capture a small sample at a shallow depth when using radiation force or attenuation as the marker. Furthermore, SRI maps can still localize the larger kidney samples at a depth of about 30mm Example 3: Feasibility of ARF-Induced Mechanical Reciprocity

[0078] FIG. 10 is an illustration of mechanical reciprocity, showing the forces and displacements involved in the mechanical reciprocity relationship. δ21is the displacement at position 2 due to F1, and δ12is the displacement at position 1 due to F2.

[0079] Exemplifying ARF, FIG. 11 illustrates long-duration ultrasound pulses (200- 400 gs) generate a transient force and measurable tissue deformation. Acoustic radiation force F is proportional to the attenuation coefficient a. As shown in FIG. 12, based on theARF and reciprocity formulas, the ARF-induced reciprocity can be expressed asHowever, compared to c, a is the dominant factor in controlling the ARF. I1and I2are similar in a weakly scattering medium such as tissue, therefore

[0080] Verasonics experimental implementations in tissue-mimicking phantom are illustrated in FIG. 13. F1, F2, S1,S2represent push force 1, push force 2, record site 1, and record site 2, respectively. Therefore, δ21indicates the displacement recorded at site 2 due to push force 1, and the same definition applies to δ12. Elasticity was ~20kPa in the region of interest (ROI), and a 3.0mm-radius inclusion was centered at a depth of 29mm. The attenuation coefficients of the background and inclusion were 0.5 and 1.0 dB / cm / MHz. Ftand F2bypassed the inclusion. The results indicated that the similar δ21and δ12were recorded.

[0081] Another illustration of verasonics experimental implementations in tissuemimicking phantom is shown in FIG. 14. F1, F2, S1,S2represent push force 1, push force 2, record site 1, and record site 2, respectively. Therefore, δ21indicates the displacement recorded at site 2 due to push force 1, and the same definition applies to δ12. Elasticity was ~20kPa in the region of interest (RO I), and a 3.0mm-radius inclusion was centered at a depth of 29mm. The attenuation coefficients of the background and inclusion were 0.5 and 1.0 dB / cm / MHz. F1bypassed the inclusion, while F2passed through the inclusion. The results indicated that

[0082] K-wave simulations in tissue-mimicking phantom are shown in FIG. 15.Elasticity was ~20kPa in the region of interest (ROI), and a 3.0mm-radius inclusion was centered at a depth of 29mm. The attenuation coefficients of the background and inclusionwere 0.5 and 1.0 dB / cm / MHz. F1and F2bypassed the inclusion. The results indicated that the similar δ21and δ12were recorded.

[0083] Additional K-wave simulations in tissue-mimicking phantom are shown in FIG. 16. Elasticity was ~20kPa in the region of interest (ROI), and a 3.0mm-radius inclusion was centered at a depth of 29mm. The attenuation coefficients of the background and inclusion were 0.5 and 1.0 dB / cm / MHz. F1bypassed the inclusion, while F2passed through the inclusion. The results indicated that

[0084] FIG. 17 shows an attenuation map, where a high-attenuation inclusion was centered at a depth of 29mm, and ARF sequences were scanned across the ROI. Simulation and experiment results illustrated that the inclusion can be clearly distinguished from the low- attenuation background. In FIG. 18, shear wave elasticity imaging (SWEI) and shear wave reciprocity imaging (SRI) maps within the ROI that have uniform elasticity but varying attenuation. The inclusion has a similar elasticity to that of the background, while it has an attenuation coefficient approximately 0.2 dB / cm / MHz higher than the background.

[0085] FIGS. 19A-19B exemplify image formation. For FIG. 19A, sequential design and signal tracking of SRI: Marching push sequences are deployed on a linear array transducer. PNrepresents the Nthpush ensemble, and (N, N — 1) represents the tracking at the Nthposition due to (A — 1)thpush. Red and green represent push and track lines, respectively. For each ensemble, raw RF data within the ROI due to shear wave propagation are collected using planewave compounding (PWC) with multiple frames. As shown in FIG. 19B, reciprocity yields a system of equations and forms an attenuation map.

[0086] For FIG. 20, K-wave simulations of the acoustic field of a focused beam steered to the left and right of a 1.4mm inclusion at the beam focus. Note the 8mm diameter inclusion centered at (-5,10) mm. The background has an attenuation coefficient of 0.5dB / cm / MHz, while both inclusions are 0.7dB / cm / MHz. The pressure amplitude at thefocus as a function of lateral position changes little as the beam sweeps laterally, despite the presence of the near-field inclusion. The acoustic radiation force tracks the variation in the attenuation coefficient associated with the small inclusion at the focal depth. This suggests that changes in radiation force in the focal zone are maximally sensitive to variations in attenuation coefficient in the focal zone, while the effect of near-field variations in attenuation coefficient is blurred.

[0087] FIG.21 shows elasticity in SRI. K-wave simulated displacement results for analyzing the influence of elasticity. In this model, the focus (F / 2.25 at 30mm) of F1 was directed toward the background, while F2 was concentrated on the inclusion. Shear wave displacement is plotted over an area of 1.5 mm by 1.5 mm centered at the focus. (a)0.5 dB / cm / MHz, 20 kPa background with 0.5 dB / cm / MHz, 20 kPa inclusion; (b)0.5 dB / cm / MHz, 20 kPa background with 1.0 dB / cm / MHz, 20 kPa inclusion; (c)0.5 dB / cm / MHz, 20 kPa background with 1.0 dB / cm / MHz, 40 kPa inclusion; (d)-(i)0.5 dB / cm / MHz, 20 kPa background with 0.5 dB / cm / MHz, 25-50 kPa (5 kPa increasing step) inclusion. The peak-to- peak ratios from (a) to (i) are 1.00, 1.72, 1.90, 0.96, 0.95, 1.15, 1.09, 1.21, and 1.26, respectively. (j)ratio of the inclusions with varying elasticity. The dashed line represents a ratio of one. (k)ratio of the inclusions with varying elasticity and attenuation.

[0088] FIG.22 is an example of the displacement ratio in the axial direction. For panels A, the applications of F1and F2within the background (∼0.5 dB / cm / MHz). The plot shows the displacement ratioresulting from F1and F2, respectively. In panels B, application of F1to the background (∼0.5 dB / cm / MHz) and F3to the inclusion (∼1.0 dB / cm / MHz). The plot shows the displacement ratiofrom F1and F3, respectively. The high-attenuation area is circled and marked in both the B-mode image and the plot. The red dashed line (equal to 1) indicates that both ARFs produce the same shear wave displacementsin panels C, horizontal attenuation coefficient across the background and inclusion. Values have been adjusted relative to the background attenuation coefficient of 0.5 dB / cm / MHz. In panels D, positions of F1, F2, F3and horizontal measurements, displayed on an SRI map.

[0089] FIG 23 shows maps reconstructed from CIRS phantom contains background (α=0.52 dB / cm / MHz, E=12 kPa), Type I (α=1.01 dB / cm / MHz, E=11.7 kPa), Type II (α=0.22 dB / cm / MHz, E=10.3 kPa), Type III (α=1.08 dB / cm / MHz, E=22.1 kPa) and Type IV (α=0.26 dB / cm / MHz, E=6.5 kPa) inclusions. The results illustrate the images of (a) B-mode with marked inclusion, (b) SWEI images in (kPa), and (c) attenuation map.

[0090] FIG.24 shows maps reconstructed from porcine kidney phantoms. The results illustrate the images of (a) B-mode with marked porcine kidney samples, (b) SWEI in (kPa), and (c) SRI map.

[0091] While various embodiments have been described above, it should be understood that such disclosures have been presented by way of example only and are not limiting. Thus, the breadth and scope of the subject compositions and methods should not be limited by any of the above-described exemplary embodiments but should be defined only in accordance with the following claims and their equivalents.

[0092] The above description is for the purpose of teaching the person of ordinary skill in the art how to practice the present invention, and it is not intended to detail all those obvious modifications and variations of it which will become apparent to the skilled worker upon reading the description. It is intended, however, that all such obvious modifications and variations be included within the scope of the present invention, which is defined by the following claims. The claims are intended to cover the components and steps in any sequence which is effective to meet the objectives there intended, unless the context specifically indicates the contrary.

Claims

WHAT IS CLAIMED IS:

1. A method of mapping acoustic radiation force using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations; pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push location and the second track location: measuring frequency-dependent shear wave speed; measuring attenuation of the shear waves; measuring differences in displacement due to differences in local acoustic radiation force that is attributed to attenuation coefficient difference; constructing multifrequency parametric two-dimensional maps capturing local tissue viscoelasticity.

2. The method of Claim 1, further comprising the step of: sequential marching pushes, in any order, are excited from an array transducer, and the reciprocal displacements are collected.

3. The method of Claim 1, further comprising the step of: inducing a shear wave by excitation of tissue using a focused push beam.

4. The method of Claim 3, wherein once the push excitation is completed, further comprising the step of: recording on a plurality of channels on a transducer backscattered data and track scattered axial motion from the shear wave.

5. The method of Claim 4, further comprising the step of: tracking shear-induced axial displacements for each push ensemble.

6. The method of Claim 1-5, further comprising the step of: collecting A ensemble frames of 3-D radio frequency (RF) data, wherein each ensemble includes axial, lateral, and track frames data, corresponding to the number of pushes.

7. The method of Claim 6, further comprising the step of: demodulating RF data to obtain the phasebased in-phase and quadrature (IQ) data for calculating the axial displacements.

8. The method of Claim 7, further comprising the step of: using auto-correlation methods to obtain 4D displacement data including axial, lateral, track frame, and ensemble directions.

9. The method of Claim 1-8, further comprising the step of: capturing time-varying displacement signals of each spatial pixel for calculations from each ensemble along the track frame direction.

10. The method of Claim 1-9, further comprising the step of: choosing matched data from the push force and reciprocal positions to construct a radiation force map.

11. The method of Claim 1-10 to derive the relative attenuation of the tissue, using the proportional relationship between acoustic radiation force and attenuation coefficient.

12. The method of claim 11, further including the step of bootstrapping the reciprocity-derived attenuation measurements with low spatial resolution attenuation measurements using reference phantom, frequency downshift, or related methods.

13. A method of mapping ultrasound attenuation using shear wave reciprocity imaging comprising: generating displacements and shear waves in a region of interest in a subject from a plurality of spatially offset locations;pushing on tissue at a first push location using acoustic radiation force; tracking displacement of tissue at a second track location; transposing the first push location and the second track location: measuring differences in displacement due to differences in local ultrasound attenuation; constructing two-dimensional maps of local tissue ultrasound attenuation from reciprocity relations and measured differences in displacements.

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