Roberto J. Lavarello

Ex vivo Study of Quantitative Ultrasound Parameters in Fatty Rabbit Livers

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and can often lead to fibrosis, cirrhosis, cancer and complete liver failure. Liver biopsy is the current standard of care to quantify hepatic steatosis but it comes with increased patient risk and only samples a small portion of the liver. Imaging approaches to assess NAFLD include proton density fat fraction (PDFF) estimated via MRI and shear wave elastography. However, MRI is expensive and shear wave elastography is not sensitive to fat content of the liver. On the other hand, ultrasonic attenuation and the backscatter coefficient (BSC) have been observed to be sensitive to levels of fat in the liver. Ultrasound evaluation offers low risk to the patient and the ability to examine the majority of the liver, as compared to liver biopsy. Therefore, a need exists to further develop ultrasonic-based techniques to quantify hepatic steatosis. In this study we explored the use of attenuation and a principal component analysis (PCA) of the BSC to detect and quantify hepatic steatosis in vivo in a rabbit model of fatty liver.

Ultrasonic Attenuation and Backscatter Coefficient Estimates of Rodent-Tumor-Mimicking Structures: Comparison of Results among Clinical Scanners

In vivo estimations of the frequency-dependent acoustic attenuation (α) and backscatter (η) coefficients using radiofrequency (rf) echoes acquired with clinical ultrasound systems must be independent of the data acquisition setup and the estimation procedures. In a recent in vivo assessment of these parameters in rodent mammary tumors, overall agreement was observed among α and η estimates using data from four clinical imaging systems. In some cases, particularly in highly-attenuating heterogeneous tumors, multisystem variability was observed. This paper compares α and η estimates of a well-characterized rodent-tumor-mimicking homogeneous phantom scanned using seven transducers with the same four clinical imaging systems: a Siemens Acuson S2000, an Ultrasonix RP, a Zonare Z.one and a VisualSonics Vevo2100. α and η estimates of lesion-mimicking spheres in the phantom were independently assessed by three research groups, who analyzed their systems rf echo signals. Imaging-system-based estimates of α and η of both lesion-mimicking spheres were comparable to through-transmission laboratory estimates and to predictions using Farans theory, respectively. A few notable variations in results among the clinical systems were observed but the average and maximum percent difference between α estimates and laboratory-assessed values was 11% and 29%, respectively. Excluding a single outlier dataset, the average and maximum average difference between η estimates for the clinical systems and values predicted from scattering theory was 16% and 33%, respectively. These results were an improvement over previous interlaboratory comparisons of attenuation and backscatter estimates. Although the standardization of our estimation methodologies can be further improved, this study validates our results from previous rodent breast-tumor model studies.

Density imaging using inverse scattering.

Inverse scattering is considered one of the most robust and accurate ultrasonic tomography methods. Most inverse scattering formulations neglect density changes in order to reconstruct sound speed and acoustic attenuation. Some studies available in literature suggest that density distributions can also be recovered using inverse scattering formulations. Two classes of algorithms have been identified. (1) The separation of sound speed and density contributions from reconstructions using constant density inverse scattering algorithms at multiple frequencies. (2) The inversion of the full wave equation including density changes. In this work, the performance of a representative algorithm for each class has been studied for the reconstruction of circular cylinders: the dual frequency distorted Born iterative method (DF-DBIM) and the T-matrix formulation. Root mean square error values lower than 30% were obtained with both algorithms when reconstructing cylinders up to eight wavelengths in diameter with moderate density changes. However, in order to provide accurate reconstructions the DF-DBIM and T-matrix method required very high signal-to-noise ratios and significantly large bandwidths, respectively. These limitations are discussed in the context of practical experimental implementations.

A study on the reconstruction of moderate contrast targets using the distorted born iterative method

Previous tomographic methods using ultrasound for reconstructing sound speed and attenuation images suffered from convergence issues for targets with moderate speed of sound contrast. Convergence problems can be overcome by the use of the multiple frequency, distorted Born iterative method (DBIM). The implementation of DBIM for measurement configurations in which receiver positions are fixed was studied, and a novel regularization scheme was developed. The regularization parameter needed to stabilize the inversion process initially was found through the Rayleigh quotient iteration, then relaxed according to the relative residual error between the measured and estimated scattered fields. The DBIM was successfully stabilized for both full and partial receiver angular coverage without a significant loss in spatial resolution. The effects of variable density in the reconstructions were briefly explored through simulations. The ability to reconstruct targets with moderate contrast was validated through experimental measurements. Speed of sound profiles for balloons filled with saline in a background of water were reconstructed using multiple frequency DBIM techniques. The mean squared error for speed of sound reconstructions of the balloon phantoms with 16.4% sound speed contrast was 1.1%.

A regularized inverse approach to ultrasonic pulse-echo imaging

An inverse-theoretic approach to ultrasonic pulse-echo imaging based on nonquadratic regularization is presented, and its effectiveness is investigated computationally by: 1) evaluating the quality of the reconstruction of speckle-based images as a function of the transmit-receive bandwidth and focal number of the transducer; 2) comparing the reconstructed images with those obtained by using conventional B-mode imaging. The L-curve and the generalized cross-validation methods were evaluated as automatic regularization parameter selection techniques. The inversion using regularization produced better results than conventional B-mode imaging for high signal-to-noise ratios (SNRs). A lower bound of 30 dB for the SNR was found for this study, below which several of the image features were lost during the reconstruction process in order to control the distortion due to the noise

On the estimation of backscatter coefficients using single-element focused transducers

The ultimate goal of quantitative ultrasound (QUS) imaging methods based on backscatter coefficient (BSC) estimates is to obtain system-independent structural information about samples. In the current study, three BSC estimation methods were compared and evaluated using the same backscattered pressure datasets in order to assess their consistency. BSC estimates were obtained from two phantoms with embedded glass spheres and compared to theoretical BSCs calculated using size distributions estimated using optical microscopy. Effective scatterer diameter and concentration estimates of the glass spheres were also obtained from the estimated BSCs. One estimation method needed to be compensated by more than an order of magnitude in amplitude in order to produce BSCs comparable to the other two methods. All calibration methods introduced different frequency-dependent effects, which could have noticeable effects on the bias of QUS estimates derived from experimental BSCs. Although in most cases the experimental QUS estimates obtained with all three methods were observed to differ by less than 10%, larger differences are expected depending on both the pressure focusing gain of the transducer (proportional to the ratio of the square of the aperture radius to the product of the wavelength and focal length) and ka range used in the estimation.

Comparison of Ultrasound Attenuation and Backscatter Estimates in Layered Tissue-Mimicking Phantoms among Three Clinical Scanners

Backscatter and attenuation coefficient estimates are needed in many quantitative ultrasound strategies. In clinical applications, these parameters may not be easily obtained because of variations in scattering by tissues overlying a region of interest (ROI). The goal of this study is to assess the accuracy of backscatter and attenuation estimates for regions distal to nonuniform layers of tissue-mimicking materials. In addition, this work compares results of these estimates for “layered” phantoms scanned using different clinical ultrasound machines. Two tissue-mimicking phantoms were constructed, each exhibiting depth-dependent variations in attenuation or backscatter. The phantoms were scanned with three ultrasound imaging systems, acquiring radio frequency echo data for offline analysis. The attenuation coefficient and the backscatter coefficient (BSC) for sections of the phantoms were estimated using the reference phantom method. Properties of each layer were also measured with laboratory techniques on test samples manufactured during the construction of the phantom. Estimates of the attenuation coefficient versus frequency slope, α0, using backscatter data from the different systems agreed to within 0.24 dB/cm-MHz. Bias in the α0 estimates varied with the location of the ROI. BSC estimates for phantom sections whose locations ranged from 0 to 7 cm from the transducer agreed among the different systems and with theoretical predictions, with a mean bias error of 1.01 dB over the used bandwidths. This study demonstrates that attenuation and BSCs can be accurately estimated in layered inhomogeneous media using pulse-echo data from clinical imaging systems.

Tomographic Reconstruction of Three-Dimensional Volumes Using the Distorted Born Iterative Method

Although real imaging problems involve objects that have variations in three dimensions, a majority of work examining inverse scattering methods for ultrasonic tomography considers 2-D imaging problems. Therefore, the study of 3-D inverse scattering methods is necessary for future applications of ultrasonic tomography. In this work, 3-D reconstructions using different arrays of rectangular elements focused on elevation were studied when reconstructing spherical imaging targets by producing a series of 2-D image slices using the 2-D distorted Born iterative method (DBIM). The effects of focal number f/#, speed of sound contrast Deltac, and scatterer size were considered. For comparison, the 3-D wave equation was also inverted using point-like transducers to produce fully 3-D DBIM image reconstructions. In 2-D slicing, blurring in the vertical direction was highly correlated with the transmit/receive elevation point-spread function of the transducers for low Deltac. The eventual appearance of overshoot artifacts in the vertical direction were observed with increasing Deltac. These diffraction-related artifacts were less severe for smaller focal number values and larger spherical target sizes. When using 3-D DBIM, the overshoot artifacts were not observed and spatial resolution was improved. However, results indicate that array configuration in 3-D reconstructions is important for good image reconstruction. Practical arrays were designed and assessed for image reconstruction using 3-D DBIM.

Cross-imaging system comparison of backscatter coefficient estimates from a tissue-mimicking material

A key step toward implementing quantitative ultrasound techniques in a clinical setting is demonstrating that parameters such as the ultrasonic backscatter coefficient (BSC) can be accurately estimated independent of the clinical imaging system used. In previous studies, agreement in BSC estimates for well characterized phantoms was demonstrated across different laboratory systems. The goal of this study was to compare the BSC estimates of a tissue mimicking sample measured using four clinical scanners, each providing RF echo data in the 1-15 MHz frequency range. The sample was previously described and characterized with single-element transducer systems. Using a reference phantom for analysis, excellent quantitative agreement was observed across the four array-based imaging systems for BSC estimates. Additionally, the estimates from data acquired with the clinical systems agreed with theoretical predictions and with estimates from laboratory measurements using single-element transducers.

Characterization of Thyroid Cancer in Mouse Models Using High-Frequency Quantitative Ultrasound Techniques

Currently, the evaluation of thyroid cancer relies on the use of fine-needle aspiration biopsy, as non-invasive imaging methods do not provide sufficient levels of accuracy for the diagnosis of this disease. In this study, the potential of quantitative ultrasound methods for characterization of thyroid tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic scanning system (40 MHz) was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice were acquired having different predispositions to developing three thyroid anomalies: C-cell adenoma, papillary thyroid carcinoma (PTC) and follicular variant papillary thyroid carcinoma (FV-PTC). A fourth set of mice that did not develop thyroid anomalies (normal mice) were used as controls. The backscatter coefficient was estimated from excised thyroid lobes the different mice. From the backscatter coefficient versus frequency (25-45 MHz), the effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated. From the envelope of the backscattered signal, the homodyned K distribution was used to estimate the k parameter (ratio of coherent to incoherent signal energy) and the μ parameter (number of scatterers per resolution cell). Statistically significant differences were observed between cancerous thyroids and normal thyroids based on the ESD, EAC and μ parameters. The mean ESD values were 18.0 ± 0.92, 15.9 ± 0.81 and 21.5 ± 1.80 μm for the PTC, FV-PTC and normal thyroids, respectively. The mean EAC values were 59.4 ± 1.74, 62.7 ± 1.61 and 52.9 ± 3.42 dB (mm(-3)) for the PTC, FV-PTC and normal thyroids, respectively. The mean μ values were 2.55 ± 0.37, 2.59 ± 0.43 and 1.56 ± 0.99 for the PTC, FV-PTC and normal thyroids, respectively. Statistically significant differences were observed between cancerous thyroids and C-cell adenomas based on the ESD and EAC parameters, with an estimated ESD value of 21.3 ± 1.50 μm and EAC value of 54.7 ± 2.24 dB mm(-3) for C-cell adenomas. These results suggest that high-frequency quantitative ultrasound may enhance the ability to detect and classify diseased thyroid tissues.