Urban, Matthew W.

AbstractEmbolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold‐standard procedure, but it is time‐consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert–Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.

Characterization of mechanical properties of tissue has become an important area of study over the last two decades. Shear wave elastography (SWE) is being used in many clinical applications to characterize, and multiple mechanical properties are being reported. To more comprehensively characterize soft tissues, we have focused on frequency-domain methods for evaluating viscoelasticity. We measure the shear wave velocity and attenuation and the variation with frequency. We will present results with the Kelvin-Voigt fractional derivative model and general power laws to characterize data from SWE experiments in tissue-mimicking phantoms and exvivo and in vivo tissue. Tissue mimicking phantoms from CIRS, inc., that have varying amounts of viscoelasticity will be investigated. Measurements from ex vivo and in vivo liver and kidney will also be used for this study. We will examine the range of the power-law exponents associated with these samples and the different models to provide understanding of the range of these parameters and how well tissue mimicking phantoms realize the parameters measured in soft tissues.

Osteochondritis Dissecans (OCD) is a joint defect in which a crack in thesubchondral bone causes a separation of both subchondral bone and overlying cartilage from the bulk of the bone. Because there is an increased prevalence of OCD among youth athletes, an efficient, accurate, and non-ionizing screening method for this condition is being pursued. The aim of this project is to develop a clinical ultrasound image reconstruction algorithm that increases the detectability of bone surface defects, such as OCD. The proposed algorithm is a modified delay-multiply-and-sum (DMAS) algorithm that uses data acquired through synthetic aperture methods. The modifications made to the DMAS algorithm relevant to this work include transmit apodization and incoherent data summation. The modified DMAS algorithm was tested on data generated from k-Wave simulations and validated with experiments using bone mimicking material. Using both k-Wave and the bone mimicking material, we modeled fractures in the capitellum of the humerus with separations of 1, 2, and 3 mm. For experiments, we used synthetic aperture acquisitions using a Verasonics V1 system with a linear array (L7-4). The modified DMAS algorithm was found to enhance the clarity of bone surface defects when compared against DAS and DMAS algorithms.

Shear wave elastography (SWE) is an established ultrasonic imaging technique, that provides quantitative measurements of tissue mechanical properties. This technique relies on the combination of acoustic radiation force push beams to generate propagating shear waves and ultrafast imaging, which allows high two-dimensional imaging frame rates to capture the induced motion. Utilizing coherent plane wave compounding (PWC) can improve signal-to-noise ratio (SNR) of acquired data. While the image quality improves, the pulse repetition frequency (PRF) is reduced, reaching limiting bandwidths to perform SWE. To address these challenges, a method for making SWE measurements with high PRF and SNR is presented. The idea follows the Time Aligned Sequential Tracking method, proposed to allow SWE with enhanced SNR in conventional clinical ultrasound scanners. The time alignment process is applied here to the full field-of-view, acquired by using plane waves transmitted at different angles. In this way, the full PRF and SNR gains are obtained. Results are shown from experiments in tissue-mimicking phantoms, where motion and extracted shear wave velocity are compared for the traditional and proposed data processing schemes. Preliminary results on arterial phantoms are also discussed, to emphasize the beneficial effects of the method in dispersive geometries.

Shear Wave Elastography (SWE) has been used to estimate arterial stiffness, an important biomarker for early cardiovascular diseases. In arterial SWE, the carotid artery is excited with acoustic radiation force and the observed wave propagation characteristics are used to estimate the arterial stiffness. We present an efficient guided wave inversion procedure, where the elastic modulus of the arterial wall is estimated by matching wave dispersion from experiments and simulation. Central to the proposed approach is an efficient forward model that computes the dispersion relation for the incompressible, immersed cylindrical tube; the model achieves high efficiency by combining semi-analytical finite element methods, selective reduced integration, and perfectly matched discrete layers. We utilize this forward model in an optimization framework to develop a streamlined methodology to estimate the modulus of the arterial wall. In this talk, we present the formulation of the method as well as validation using phantom experiments on 10 rubber tubes (VytaFlex-10), followed by preliminary work on inverting for the viscoelastic modulus.

Shear wave elasticity imaging applies an acoustic radiation force to generate shear waves, where the shear wave speed is often estimated with time-of-flight calculations. To characterize the errors in time-of-flight estimates of the shear wave speed, three-dimensional simulated shear wave particle velocities and shear wave particle displacements are computed with time-domain Green's functions for a Kelvin-Voigt model. Estimated shear wave speeds are obtained from cross correlations and time-to-peak calculations, and the results demonstrate the effects of time-domain dispersion and noise on estimates of the shear wave speed. Time-domain dispersion of the propagating shear wave produces large errors in estimates performed with shear wave particle velocities and/or cross-correlations close to the push beam, and in the absence of noise, the errors in the shear wave speed estimated at the focal depth diminish with distance from the push beam. However, shear wave attenuation also increases sensitivity to noise as the distance from the push beam increases. Time-to-peak and cross-correlation methods consistently achieve much smaller errors with shear wave particle displacements than with shear wave particle velocities. Furthermore, cross-correlations are much more robust with respect to noise, and larger values of the shear viscosity increase the sensitivity of each method to noise.

Current clinically used ultrasound elastography is obtained when tissue undergoes small deformation (<2% strain). However, small deformation may not be large enough to characterize tissues that exhibit similar elasticity properties to normal tissue at small deformation but behave differently from normal tissue at large deformation (>10% strain). Therefore, tissue elasticity properties measured at large deformation may provide better diagnostic differentiation. Combining the quasi-static and shear wave ultrasound elastography methods, we propose a noninvasive method to estimate the nonlinear elasticity property of tissue. To test this method, cubic tissue-mimicking phantoms were constructed. We progressively compressed the phantom to produce a series of stepwise stress states. At every stress state, we conducted shear wave measurements in which two acoustic radiation force pushes generated shear waves, which were measured using ultrafast imaging in order to estimate the local shear modulus. For every compression step, we tracked incremental tissue displacements between two successive frames and then accumulated these displacements for all steps to obtain the cumulative displacements and strains. Using the shear modulus and cumulative strain images we calculated the stress map under an incompressibility assumption. Finally, we obtained the local stress-strain curve that reflected the nonlinear elasticity of the tested material.

Shear wave elasticity imaging (SWEI) uses an acoustic radiation force to generate shear waves, and then soft tissue mechanical properties are obtained by analyzing the shear wave data. In SWEI, the shear wave speed is often estimated with time-of-flight (TOF) calculations. To characterize the errors produced by TOF calculations, three-dimensional (3D) simulated shear waves are described by time-domain Green's functions for a Kelvin-Voigt model evaluated for multiple combinations of the shear elasticity and the shear viscosity. Estimated shear wave speeds are obtained from cross correlations and time-to-peak (TTP) calculations applied to shear wave particle velocities and shear wave particle displacements. The results obtained from these 3D shear wave simulations indicate that TTP calculations applied to shear wave particle displacements yield effective estimates of the shear wave speed if noise is absent, but cross correlations applied to shear wave particle displacements are more robust when the effects of noise and shear viscosity are included. The results also show that shear wave speeds estimated with TTP methods and cross correlations using shear wave particle velocities are more sensitive to increases in shear viscosity and noise, which suggests that superior estimates of the shear wave speed are obtained from noiseless or noisy shear wave particle displacements.

The surface tension of biological fluids is an important parameter because the mechanical properties of fluids are closely linked with hematological diseases and other pathophysiologies. Capillary waves are associated with fluid mechanical properties. Here, we propose a method that utilizes the acoustic radiation force (ARF) to generate propagating waves and optical coherence tomography (OCT) to measure the wave motion. This ARF-OCT method is capable of evaluating the surface tension of fluids, water and porcine whole blood in this study, based on the dispersion relation of capillary waves. Two-dimensional Fourier transforms were used to decompose frequency components of wave motion images to obtain a k-space representation and estimate the wave phase velocity. The phase velocity of capillary waves was obtained from the experimental results and compared to theoretical calculations. The surface tensions of water and porcine whole blood were determined from the experimental results. We first report that capillary waves measured with OCT can be a new promising modality for measuring the surface tension of fluids. The proposed method could be used to differentiate actual pathologic fluids or blood from those taken from healthy subjects and as a biomarker in future biomedical applications.

AbstractEvaluating mechanical properties of biological soft tissues and viscous mucus is challenging because of complicated dynamic behaviors. Soft condensed matter models have been successfully used to explain a number of dynamical behaviors. Here, we reported that optical coherence elastography (OCE) is capable of quantifying mechanical properties of soft condensed matters, micellar fluids. A 7.5 MHz focused transducer was utilized to generate acoustic radiation force exerted on the surface of soft condensed matters in order to produce Rayleigh waves. The waves were recorded by optical coherence tomography (OCT). The Kelvin‐Voigt model was adopted to evaluate shear modulus and loss modulus of soft condensed matters. The results reported that various concentrations of micellar fluids can provide reasonable ranges of elasticity from 65.71 to 428.78 Pa and viscosity from 0.035 to 0.283 Pa·s, which are close to ranges for actual biological samples, like mucus. OCE might be a promising tool to differentiate pathologic mucus samples from healthy cases as advanced applications in the future.