Veronica Rotemberg

IMPROVING THE ROBUSTNESS OF TIME-OF-FLIGHT BASED SHEAR WAVE SPEED RECONSTRUCTION METHODS USING RANSAC IN HUMAN LIVER IN VIVO

The stiffness of tissue can be quantified by measuring the shear wave speed (SWS) within the medium. Ultrasound is a real-time imaging modality capable of tracking the propagation of shear waves in soft tissue. Time-of-flight (TOF) methods have previously been shown to be effective for quantifying SWS from ultrasonically tracked displacements. However, the application of these methods to in vivo data is challenging due to the presence of additional sources of error, such as physiologic motion or spatial inhomogeneities in tissue. This article introduces the use of random sample consensus (RANSAC), a model fitting paradigm robust to the presence of gross outlier data, for estimating the SWS from ultrasonically tracked tissue displacements in vivo. SWS reconstruction is posed as a parameter estimation problem and the RANSAC solution to this problem is described. Simulations using synthetic TOF data show that RANSAC is capable of good stiffness reconstruction accuracy (mean error 0.5 kPa) and precision (standard deviation 0.6 kPa) over a range of shear stiffness (0.6-10 kPa) and proportion of inlier data (50%-95%). As with all TOF SWS estimation methods, the accuracy and precision of the RANSAC reconstructed shear modulus decreases with increasing tissue stiffness. The RANSAC SWS estimator was applied to radiation force induced shear wave data from 123 human patient livers acquired with a modified SONOLINE Antares ultrasound system (Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA) in a clinical setting before liver biopsy was performed. Stiffness measurements were not possible in 19 patients due to the absence of shear wave propagation inside the liver. The mean liver stiffness for the remaining 104 patients ranged from 1.3 to 24.2 kPa and the proportion of inliers for the successful reconstructions ranged between 42% to 99%. Using RANSAC for SWS estimation improved the diagnostic accuracy of liver stiffness for delineating fibrosis stage compared with ordinary least squares (OLS) without outlier removal (AUROC = 0.94 for F >or= 3 and AUROC = 0.98 for F = 4). These results show that RANSAC is a suitable method for estimating the SWS from noisy in vivo shear wave displacements tracked by ultrasound.

Changes in shear wave speed pre- and post-induction of labor: a feasibility study.

To explore the feasibility of using shear wave speed (SWS) estimates to detect differences in cervical softening pre‐ and post‐ripening in women undergoing induction of labor.

The impact of hepatic pressurization on liver shear wave speed estimates in constrained versus unconstrained conditions.

Increased hepatic venous pressure can be observed in patients with advanced liver disease and congestive heart failure. This elevated portal pressure also leads to variation in acoustic radiation-force-derived shear wave-based liver stiffness estimates. These changes in stiffness metrics with hepatic interstitial pressure may confound stiffness-based predictions of liver fibrosis stage. The underlying mechanism for this observed stiffening behavior with pressurization is not well understood and is not explained with commonly used linear elastic mechanical models. An experiment was designed to determine whether the stiffness increase exhibited with hepatic pressurization results from a strain-dependent hyperelastic behavior. Six excised canine livers were subjected to variations in interstitial pressure through cannulation of the portal vein and closure of the hepatic artery and hepatic vein under constrained conditions (in which the liver was not free to expand) and unconstrained conditions. Radiation-force-derived shear wave speed estimates were obtained and correlated with pressure. Estimates of hepatic shear stiffness increased with changes in interstitial pressure over a physiologically relevant range of pressures (0-35 mmHg) from 1.5 to 3.5 m s(-1). These increases were observed only under conditions in which the liver was free to expand while pressurized. This behavior is consistent with hyperelastic nonlinear material models that could be used in the future to explore methods for estimating hepatic interstitial pressure noninvasively.

Combined ultrasonic thermal ablation with interleaved ARFI image monitoring using a single diagnostic curvilinear array: A feasibility study

The goal of this work is to demonstrate the feasibility of using a diagnostic ultrasound system (Siemens Antares™ and CH6–2 curvilinear array) to ablate ex vivo liver with a custom M-mode sequence and monitor the resulting tissue stiffening with 2-D Acoustic Radiation Force Impulse (ARFI) imaging. Images were taken before and after ablation, as well as in 5- s intervals during the ablation sequence in order to monitor the ablation lesion formation temporally. Ablation lesions were generated at depths up to 1.5 cm from the surface of the liver and were not visible in B-mode. ARFI images showed liver stiffening with heating that corresponded to discolored regions in gross pathology. As expected, the contrast of ablation lesions in ARFI images is observed to increase with ablation lesion size. This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage and monitor the formation of the ablation lesion with ARFI imaging.

Ultrasonic characterization of the nonlinear properties of canine livers by measuring shear wave speed and axial strain with increasing portal venous pressure

Elevated hepatic venous pressure is the primary source of complications in advancing liver disease. Ultrasound imaging is ideal for potential noninvasive hepatic pressure measurements as it is widely used for liver imaging. Specifically, ultrasound based stiffness measures may be useful for clinically monitoring pressure, but the mechanism by which liver stiffness increases with hepatic pressure has not been well characterized. This study is designed to elucidate the nonlinear properties of the liver during pressurization by measuring both hepatic shear wave speed (SWS) and strain with increasing pressure. Tissue deformation during hepatic pressurization was tracked in 8 canine livers using successively acquired 3-D B-mode volumes and compared with concurrently measured SWS. When portal venous pressure was increased from clinically normal (0-5mmHg) to pressures representing highly diseased states at 20mmHg, the liver was observed to expand with axial strain measures up to 10%. At the same time, SWS estimates were observed to increase from 1.5-2m/s at 0-5mmHg (baseline) to 3.25-3.5m/s at 20mmHg.

Acoustic Radiation Force Impulse (ARFI) Imaging-Based Needle Visualization

Ultrasound-guided needle placement is widely used in the clinical setting, particularly for central venous catheter placement, tissue biopsy and regional anesthesia. Difficulties with ultrasound guidance in these areas often result from steep needle insertion angles and spatial offsets between the imaging plane and the needle. Acoustic Radiation Force Impulse (ARFI) imaging leads to improved needle visualization because it uses a standard diagnostic scanner to perform radiation force based elasticity imaging, creating a displacement map that displays tissue stiffness variations. The needle visualization in ARFI images is independent of needle-insertion angle and also extends needle visibility out of plane. Although ARFI images portray needles well, they often do not contain the usual B-mode landmarks. Therefore, a three-step segmentation algorithm has been developed to identify a needle in an ARFI image and overlay the needle prediction on a coregistered B-mode image. The steps are: (1) contrast enhancement by median filtration and Laplacian operator filtration, (2) noise suppression through displacement estimate correlation coefficient thresholding and (3) smoothing by removal of outliers and best-fit line prediction. The algorithm was applied to data sets from horizontal 18, 21 and 25 gauge needles between 0–4 mm offset in elevation from the transducer imaging plane and to 18G needles on the transducer axis (in plane) between 10° and 35° from the horizontal. Needle tips were visualized within 2 mm of their actual position for both horizontal needle orientations up to 1.5 mm offset in elevation from the transducer imaging plane and on-axis angled needles between 10°–35° above the horizontal orientation. We conclude that segmented ARFI images overlaid on matched B-mode images hold promise for improved needle visibility in many clinical applications.

Concurrent ARFI imaging and HIFU ablation using a diagnostic transducer array and ultrasound system with custom beam sequences

Background, Motivation and Objective: High-intensity focused ultrasound (HIFU) has primarily been performed using a specialized ultrasound transducer for therapy and either a separate transducer for imaging or a different imaging modality. Accurate localization and monitoring of HIFU treatment is important to improving the efficacy of the treatment as well as minimizing complications. The goal of this work was to demonstrate the feasibility of using a diagnostic ultrasound system to perform spot ablations in liver with concurrent Acoustic Radiation Force Impulse (ARFI) stiffness imaging in order to monitor lesion formation. Statement of Contribution/Methods: A diagnostic ultrasound system (Siemens Antares™ and CH6-2 curvilinear array) was used to both: 1) ablate ex vivo liver samples with a custom M-mode sequence and 2) to monitor the resulting tissue stiffening with 2-D ARFI imaging. Ablation patterns were generated using a grid of varying numbers of heating locations. Results: ARFI images showed irreversible liver stiffening with heating that corresponded to discolored regions in gross pathology. Images were taken before and after ablation, as well as in 5-second intervals during ablation to monitor the increase in stiffness contrast and extent with time. No gaseous body formation was observed during the ablations in B-mode, thus lesions were not visualized in matched B-mode images. In order to mimic the presence of a stiffer tumor, bovine muscle tissue was inserted into a liver sample, and subtraction images (pre-post ARFI) clearly distinguished the ablated (stiffened) liver tissue from the stiffer bovine tissue. Discussion and Conclusions: This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage, and monitor the formation of the ablation lesion. Future work will involve testing this treatment system in vivo.

Characterizing expansion and stiffening of the canine liver with increasing hepatic pressure

Hepatic venous pressure is increased in advancing liver disease and is considered the primary source of of complications (such as variceal bleeding and ascites). Measurement of clinically significant increases in portal pressure is important for managing liver disease and is performed using the invasive method, hepatic venous pressure gradient (HVPG). We have previously reported that ARFI based shear wave speed (SWS) estimate increases with increasing hepatic venous pressure require an underlying tissue deformation. However, the mechanical behavior of the liver during pressurization is not well understood. In this work, tissue deformation during hepatic pressurization was tracked using successively acquired 3-D B-mode volumes and compared with concurrently accrued SWS datasets.

Comparison between Acoustic Radiation Force Impulse (ARFI)-based hepatic stiffness quantification in deformed and undeformed pressurized canine livers

Increased hepatic interstitial pressure can be observed in patients with advanced liver disease and is associated with worsened clinical outcomes. Elevated hepatic stiffness has been reported clinically with increases in hepatic venous pressure gradient (HVPG). An experiment was designed to determine whether stiffness increase exhibited with hepatic pressurization results from a strain-dependent hyperelastic behavior. Six excised canine livers were subjected to variations in interstitial pressure through cannulation of the portal vein and closure of the hepatic artery and hepatic vein under constrained conditions (in which the liver was not free to expand) and unconstrained conditions. Radiation force derived shear wave speed estimates were obtained and correlated with pressure. Estimates of hepatic shear stiffness increased with changes in interstitial pressure over a physiologically relevant range of pressures (0-35mmHg) from 1.5 to 3.5 m/s. These increases were observed only under conditions in which the liver was free to expand while pressurized.

2D and 3D Bayesian displacement estimation

Bayesian displacement estimation has been previously demonstrated in 1D and shown to reduce estimation and jitter and often bias. Here it is shown that the 1D implementation is directly extendable to 2D and 3D. 2D simulations are used to determine the validity of the perturbed likelihood function and empirically determine values for the scaling term α. 3D translation stage and in vivo cardiac experiments are used to examine the algorithms performance for estimating displacements. The 2D simulations determined that a cap should be placed on the full scaling term (SNR/α). The 3D translation stage experiments show better performance in all three dimensions, and the 3D in vivo results show significant qualitative improvements as well as improvements in estimated levels of estimation variance.