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In this study the dynamic behavior of a layered viscoelastic medium in response to the harmonic and impulsive acoustic radiation force applied to its surface was investigated both theoretically and experimentally. An analytical solution for a layered viscoelastic compressible medium in frequency and time domains was obtained using the Hankel transform. A special incompressible case was considered to model soft biological tissues. To verify our theoretical model, experiments were performed using tissue-like gel-based phantoms with varying mechanical properties. A 3.5 MHz single-element focused ultrasound transducer was used to apply the radiation force at the surface of the phantoms. A phase-sensitive optical coherence tomography (OCT) system was used to track the displacements of the phantom surface. Theoretically predicted displacements were compared with experimental measurements. The role of the depth dependence of the elastic properties of a medium in its response to an acoustic pulse at the surface was studied. It was shown that the low-frequency vibrations at the surface are more sensitive to the deep layers than high-frequency ones. Therefore, the proposed model in combination with spectral analysis can be used to evaluate depth-dependent distribution of the mechanical properties based on the measurements of the surface deformation.

Using a microbubble-based acoustic radiation force approach, spatial variations of Young's modulus and shear viscosity of the porcine vitreous humors in two groups-young pigs (6 months old) and mature pigs (2 to 3 years old)-were measured in situ. The measurements in these groups (4 specimens in each group) were performed in several positions along an anterior-to-posterior direction. At each position, microbubbles were generated by focusing a nanosecond pulsed laser beam and the displacement of each microbubble in response to an impulsive acoustic radiation force was measured every 10 μs using a custom-made high-pulse-repetition-frequency ultrasound system. Based on measured dynamics of the microbubble, Young's modulus and shear viscosity at various locations of the vitreous were reconstructed. Young's moduli of the young and mature porcine vitreous at anterior region were the highest, whereas the central region had the lowest values, indicating the clear spatial variations in the vitreous humor elasticity in both groups.

A high pulse repetition frequency ultrasound system for an ex vivo measurement of mechanical properties of an animal crystalline lens was developed and validated. We measured the bulk displacement of laser-induced microbubbles created at different positions within the lens using nanosecond laser pulses. An impulsive acoustic radiation force was applied to the microbubble, and spatio-temporal measurements of the microbubble displacement were assessed using a custom-made high pulse repetition frequency ultrasound system consisting of two 25 MHz focused ultrasound transducers. One of these transducers was used to emit a train of ultrasound pulses and another transducer was used to receive the ultrasound echoes reflected from the microbubble. The developed system was operating at 1 MHz pulse repetition frequency. Based on the measured motion of the microbubble, Young's moduli of surrounding tissue were reconstructed and the values were compared with those measured using the indentation test. Measured values of Young's moduli of four bovine lenses ranged from 2.6 ± 0.1 to 26 ± 1.4 kPa, and there was good agreement between the two methods. Therefore, our studies, utilizing the high pulse repetition frequency ultrasound system, suggest that the developed approach can be used to assess the mechanical properties of ex vivo crystalline lenses. Furthermore, the potential of the presented approach for in vivo measurements is discussed.

An approach to assess the mechanical properties of a viscoelastic medium using laser-induced microbubbles is presented. To measure mechanical properties of the medium, dynamics of a laser-induced cavitation microbubble in viscoelastic medium under acoustic radiation force was investigated. An objective lens with a 1.13 numerical aperture and an 8.0 mm working distance was designed to focus a 532 nm wavelength nanosecond pulsed laser beam and to create a microbubble at the desired location. A 3.5 MHz ultrasound transducer was used to generate acoustic radiation force to excite a laser-induced microbubble. Motion of the microbubble was tracked using a 25 MHz imaging transducer. Agreement between a theoretical model of bubble motion in a viscoelastic medium and experimental measurements was demonstrated. Young’s modulii reconstructed using the laser-induced microbubble approach were compared with those measured using a direct uniaxial method over the range from 0.8 to 13 kPa. The results indicate good agreement between methods. Thus, the proposed approach can be used to assess the mechanical properties of a viscoelastic medium.

Noninvasively probing the biomechanical properties of crystalline lens has been challenging due to its unique features such as location inside the eye and being optically and ultrasonically transparent. Here we introduce a method of relying on the spectral analysis of the lens surface response to a mechanical stimulation for the depthdependent assessment of lens biomechanical properties. In this method, acoustic radiation force (ARF) is used to remotely induce the deformation on the surface of the crystalline lens, and a phase-sensitive optical coherence tomography (PhS-OCT) system, co-focused with ARF, utilized to monitor the localized temporal response of ARFinduced deformations on the lens surface. The dominant frequency from the amplitude spectra of the surface response is obtained as the indicator of the depthwise elasticity distribution. Pilot experiments were performed on tissue-mimicking layered phantoms and ex vivo porcine crystalline lens. Results indicate that the frequency response of the sample surface is contributed by the mechanical properties of layers located at different depths and the depthdependent elastic properties can be revealed from the amplitude spectrum. Further study will be focused on combining the experimental measurements with theoretical model and inverse numerical method for depth-resolved elastography of the crystalline lens.

Acoustic Radiation Force (ARF) stimulation is actively used in ultrasound elastography to estimate mechanical properties of tissue. Compared with ultrasound imaging, OCT provides advantage in both spatial resolution and signal-to-noise ratio. Therefore, a combination of ARF and OCT technologies can provide a unique opportunity to measure viscoelastic properties of tissue, especially when the use of high intensity radiation pressure is limited for safety reasons. In this presentation we discuss a newly developed theoretical model of the deformation of a layered viscoelastic medium in response to an acoustic radiation force of short duration. An acoustic impulse was considered as an axisymmetric force generated on the upper surface of the medium. An analytical solution of this problem was obtained using the Hankel transform in frequency domain. It was demonstrated that layers at different depths introduce different frequency responses. To verify the developed model, experiments were performed using tissue-simulating, inhomogeneous phantoms of varying mechanical properties. The Young’s modulus of the phantoms was varied from 5 to 50 kPa. A single-element focused ultrasound transducer (3.5 MHz) was used to apply the radiation force with various durations on the surface of phantoms. Displacements on the phantom surface were measured using a phase-sensitive OCT at 25 kHz repetition frequency. The experimental results were in good agreement with the modeling results. Therefore, the proposed theoretical model can be used to reconstruct the mechanical properties of tissue based on ARF/OCT measurements.

In this study the dynamic behavior of a layered viscoelastic medium in response to the impulsive acoustic radiation force applied to its surface was investigated. To verify our theoretical model, experiments were performed using tissue-like gel-based phantoms of varying mechanical properties. A 3.5 MHz single-element focused transducer was used to apply the radiation force at the surface of the phantoms and a phase-sensitive OCT system was used to track the displacements on the phantom surface. The results of this study demonstrate good agreement between theoretical predictions and experimental measurements. It was demonstrated that layers at different depths introduce responses at different frequencies. Therefore, the proposed model in combination with spectral analysis can be used to evaluate depth dependant distribution of the mechanical properties based the measurements on the tissue surface.

The mechanical properties of ex vivo animal lenses from three groups were evaluated: old bovine (25–30 mo old, n = 4), young bovine (6 mo old, n = 4) and young porcine (6 mo old, n = 4) eye globes. We measured the dynamics of laser-induced microbubbles created at different locations within the crystalline lenses. An impulsive acoustic radiation force was applied to the microbubble, and the microbubble displacements were measured using a custom-built high pulse repetition frequency ultrasound system. Based on the measured dynamics of the microbubbles, Young's moduli of bovine and porcine lens tissue in the vicinity of the microbubbles were reconstructed. Age-related changes and location-dependent variations in the Young's modulus of the lenses were observed. Near the center, the old bovine lenses had a Young's modulus approximately fivefold higher than that of young bovine and porcine lenses. The gradient of Young's modulus with respect to radial distance was observed in the lenses from three groups.

An approach to assess the mechanical properties of a viscoelastic medium using laser-induced microbubbles is presented. A 532 nm wavelength nanosecond pulsed laser beam was focused into a phantom to create a microbubble at the desired location. A 3.5 MHz ultrasound transducer was used to generate acoustic radiation force to excite the laser-induced microbubble. Motion of the microbubble was tracked using a 25 MHz imaging transducer. An agreement between a theoretical model of bubble motion in viscoelastic medium and experimental measurements was demonstrated. Young's moduli reconstructed using the laser-induced microbubble approach were compared with those of direct measurements. Thus, the proposed approach can be used to assess the mechanical properties of viscoelastic medium such as soft tissue.

An ultrasound-based method to locally assess the shear modulus of a medium is reported. The proposed approach is based on the application of an impulse acoustic radiation force to an inhomogeneity in the medium and subsequent monitoring of the spatio-temporal response. In our experimental studies, a short pulse produced by a 1.5-MHz highly focused ultrasound transducer was used to initiate the motion of a rigid sphere embedded into an elastic medium. Another 25 MHz focused ultrasound transducer operating in pulse-echo mode was used to track the displacement of the sphere. The experiments were performed in gel phantoms with varying shear modulus to demonstrate the relationship between the displacement of the sphere and shear modulus of the surrounding medium. Because the magnitude of acoustic force applied to sphere depends on the acoustic material properties and, therefore, cannot be used to assess the absolute value of shear modulus, the temporal behavior of the displacement of the sphere was analyzed. The results of this study indicate that there is a strong correlation between the shear modulus of a medium and spatio-temporal characteristics of the motion of the rigid sphere embedded in this medium.

The motion of a rigid sphere in a viscoelastic medium in response to an acoustic radiation force of short duration was investigated. Theoretical and numerical studies were carried out first. To verify the developed model, experiments were performed using rigid spheres of various diameters and densities embedded into tissue-like, gel-based phantoms of varying mechanical properties. A 1.5 MHz, single-element, focused transducer was used to apply the desired radiation force. Another single-element, focused transducer operating at 25 MHz was used to track the displacements of the sphere. The results of this study demonstrate good agreement between theoretical predictions and experimental measurements. The developed theoretical model accurately describes the displacement of the solid spheres in a viscoelastic medium in response to the acoustic radiation force.

The goal of this study was to investigate the dynamic behavior of a rigid sphere in viscoelastic medium in response to the impulsive acoustic radiation force. Theoretical and numerical studies were carried out first. Then, to verify our theoretical and numerical models, the experiments were performed using rigid spheres of various diameters and densities embedded into tissue-like gel-based phantoms of varying mechanical properties. A 1.5 MHz single-element focused transducer was used to apply the desired radiation force. Another single-element focused transducer operating at 25 MHz was used to track the displacements of the sphere. The results of this study demonstrate good agreement between theoretical predictions and experimental measurements. The developed theoretical model accurately describes the displacement of the solid spheres in viscoelastic medium in response to the acoustic radiation force and thus can be used to evaluate mechanical properties of tissue

Acoustic radiation force on a scatterer in tissue depends on the compressibility and shear modulus of both the tissue and the scatterer. This force is related to the monopole and dipole scattering coefficients. The finite shear modulus of the tissue decreases the radiation force in comparison with the force exerted on the same scatterer surrounded by liquid. Shear moduli for soft tissue range from several kilopascals (breast, liver) to tens of kilopascals and higher for cornea, cartilage, and cancerous tissue. As reported previously, the radiation force on a bubble in tissue having 100 kPa shear modulus is 50% less than if the bubble is in water. This difference decreases for scatterers with finite shear moduli, examples of which are reported here. Additionally, displacement of a scatterer due to radiation force is inversely proportional to the shear modulus of the tissue, which permits measurement of the latter. Experiments demonstrating this technique are reviewed. In these experiments, the radiation force is applied to a gas microbubble produced by laser-induced optical breakdown, while displacement of the microbubble is measured by high-frequency ultrasound as a function of time. Results are reported for tissue-mimicking phantoms and animal crystalline lenses in vitro.

According to the most widely accepted theory of presbyopia, the age-related loss of accommodation is attributed to Young's modulus changes in the lens. Previously, we have developed an approach to measure the mechanical properties of viscoelastic medium using microbubbles and acoustic radiation force. In this study, we tested this technique to assess the mechanical properties of bovine lenses ex-vivo. An impulsive acoustic radiation force was applied to laser-induced microbubbles created with nanosecond laser pulses at different locations in the lens. An acoustic radiation force with typical duration less than 150 μs was generated by a 3.5 MHz transducer. For accurate spatio-temporal measurements of the microbubble's displacement, a custom-made ultrasound system consisting of two 25 MHz transducers was built. The first transducer emitted a train of pulses and the other transducer received the train of echoes reflected from the microbubble. The developed system was operating at 400 kHz pulse repetition fre...

Measurements of mechanical properties of tissue can be used in many applications ranging from disease diagnosis to treatment planning and monitoring. In this paper, we present a technique to measure mechanical properties of the tissue undergoing laser surgery during which the cavitation bubble is introduced. Utilizing the laser‐induced microbubble, the mechanical properties of the tissue were assessed by measuring displacement and oscillations of the bubble under applied acoustic radiation force. The bubbles were produced using a nanosecond pulsed laser operating at 532 nm. Using the lens (0.92 numerical aperture, 11.5‐mm focal length), the laser beam was focused inside the gelatin to create microbubbles ranging from 80‐ to 250‐cm diameter. The bubbles were then interrogated using acoustic pulses of different durations and amplitudes. First, the size of each laser‐induced microbubble was estimated by measuring the laser‐produced shock wave and pulse‐echo ultrasound signals. Then, a 1.5‐MHz transducer gene...

An accurate assessment of mechanical properties of tissue is desired in many applications ranging from biomedical research to medical diagnostics and surgery. Currently, several methods to assess shear elasticity of tissue are available while the techniques to measure tissue viscosity are not yet fully developed. However, shear viscosity is an indicative functional parameter of soft tissue. In addition, the local changes of shear viscosity can affect the accuracy of shear elasticity assessment. Therefore, in this study, an acoustic radiation force approach to assess both shear elasticity and viscosity of tissue is developed. Such approach is based on monitoring of the spatio‐temporal displacement of an ultrasound inhomogeneity in response to applied impulsive radiation force. In experiments, a 2‐mm‐diameter solid sphere was embedded into the gel phantoms with varying shear elasticity and viscosity. The sphere was then perturbed using acoustic radiation force produced by a single‐element focused ultrasound...

Lasers are used in many biomedical and clinical applications, ranging from diagnosis to therapy. In eye microsurgery, for example, a pulsed laser beam produces a localized surgical effect through the formation of a cavitation microbubble as a result of tissue photodisruption occurring in the focal zone. However, to insure successful presurgical planning, surgical procedure, and postoperative stages of pathology treatment, the mechanical properties of the tissue must be analyzed before selective laser intervention. Since microbubbles are already produced during laser surgery, we have developed an integrated approach utilizing these laser‐induced microbubbles as reporters of tissue viscoelasticity. Specifically, we have derived a general model of gas bubble dynamics in viscoelastic media to describe both translation and oscillations of the microbubble exposed to the acoustic radiation force. Furthermore, an ultrasound method based on temporal measurement of passive acoustic emission from cavity during laser...