Effect of rt-PA on Shear Wave Mechanical Assessment and Quantitative Ultrasound Properties of Blood Clot Kinetics In Vitro.

OBJECTIVE: The consequences associated with blood clots are numerous and are responsible for many deaths worldwide. The assessment of treatment efficacy is necessary for patient follow-up and to detect treatment-resistant patients. The aim of this study was to characterize the effect of treatment on blood clots in vitro using quantitative ultrasound parameters. METHODS: Blood from 10 pigs was collected to form three clots per pig in gelatin phantoms. Clots were subjected to 1) no treatment, 2) rt-PA (recombinant tissue plasminogen activator) treatment after 20 minutes of clotting, and 3) rt-PA treatment after 60 minutes of clotting. Clots were weighted before and after the experiment to assess the treatment effect by the mass loss. The clot kinetics was studied over 100 minutes using elastography (Young's modulus, shear wave dispersion, and shear wave attenuation). Homodyne K-distribution (HKD) parameters derived from speckle statistics were also studied during clot formation and dissolving (diffuse-to-total signal power ratio and intensity parameters). RESULTS: Treated clots loosed significantly more mass than non-treated ones (P < .005). A significant increase in Young's modulus was observed over time (P < .001), and significant reductions were seen for treated clots at 20 or 60 minutes compared with untreated ones (P < .001). The shear wave dispersion differed for treated clots at 60 minutes versus no treatments (P < .001). The shear wave attenuation decreased over time (P < .001), and was different for clots treated at 20 minutes versus no treatments (P < .031). The HKD intensity parameter varied over time (P < .032), and was lower for clots treated at 20 and 60 minutes than those untreated (P < .001 and P < .02). CONCLUSION: The effect of rt-PA treatment could be confirmed by a decrease in Young's modulus and HKD intensity parameter. The shear wave dispersion and shear wave attenuation were sensitive to late and early treatments, respectively. The Young's modulus, shear wave attenuation, and HKD intensity parameter varied over time despite treatment.

Resonance, Velocity, Dispersion, and Attenuation of Ultrasound-Induced Shear Wave Propagation in Blood Clot In Vitro Models.

OBJECTIVE: Improve the characterization of mechanical properties of blood clots. Parameters derived from shear wave (SW) velocity and SW amplitude spectra were determined for gel phantoms and in vitro blood clots. METHODS: Homogeneous phantoms and phantoms with gel or blood clot inclusions of different diameters and mechanical properties were analyzed. SW amplitude spectra were used to observe resonant peaks. Parameters derived from those resonant peaks were related to mimicked blood clot properties. Three regions of interest were tested to analyze where resonances occurred the most. For blood experiments, 20 samples from different pigs were analyzed over time during a 110-minute coagulation period using the Young modulus, SW frequency dispersion, and SW attenuation. RESULTS: The mechanical resonance was manifested by an increase in the number of SW spectral peaks as the inclusion diameter was reduced (P < .001). In blood clot inclusions, the Young modulus increased over time during coagulation (P < .001). Descriptive spectral parameters (frequency peak, bandwidth, and distance between resonant peaks) were linearly correlated with clot elasticity values (P < .001) with R2 = .77 for the frequency peak, .60 for the bandwidth, and .48 for the distance between peaks. The SW dispersion and SW attenuation reflecting the viscous behavior of blood clots decreased over time (P < .001), mainly in the early stage of coagulation (first minutes). CONCLUSION: The confined soft inclusion configuration favored SW mechanical resonances potentially challenging the computation of spectral-based parameters, such as the SW attenuation. The impact of resonances can be reduced by properly selecting the region of interest for data analysis.

Review of Envelope Statistics Models for Quantitative Ultrasound Imaging and Tissue Characterization.

The homodyned K-distribution and the K-distribution, viewed as a special case, as well as the Rayleigh and the Rice distributions, viewed as limit cases, are discussed in the context of quantitative ultrasound (QUS) imaging. The Nakagami distribution is presented as an approximation of the homodyned K-distribution. The main assumptions made are (1) the absence of log-compression or application of nonlinear filtering on the echo envelope of the radiofrequency signal and (2) the randomness and independence of the diffuse scatterers. We explain why other available models are less amenable to a physical interpretation of their parameters. We also present the main methods for the estimation of the statistical parameters of these distributions. We explain why we advocate the methods based on the X-statistics for the Rice and the Nakagami distributions and the K-distribution. The limitations of the proposed models are presented. Several new results are included in the discussion sections, with proofs in the appendix.

Regularized Ultrasound Phantom-Free Local Attenuation Coefficient Slope (ACS) Imaging in Homogeneous and Heterogeneous Tissues.

Attenuation maps or measurements based on the local attenuation coefficient slope (ACS) in quantitative ultrasound (QUS) have shown potential for the diagnosis of liver steatosis. In liver cancers, tissue abnormalities and tumors detected using ACS are also of interest to provide new image contrast to clinicians. Current phantom-based approaches have the limitation of assuming a comparable speed of sound between the reference phantom and insonified tissues. Moreover, these methods present the inconvenience for operators to acquire data on phantoms and patients. The main goal was to alleviate these drawbacks by proposing a methodology for constructing phantom-free regularized (PF-R) local ACS maps and investigate the performance in both homogeneous and heterogeneous media. The proposed method was tested on two tissue-mimicking media with different ACS constructed as homogeneous phantoms, side-by-side and top-to-bottom phantoms, and inclusion phantoms with different attenuations. Moreover, an in vivo proof-of-concept was performed on healthy, steatotic, and cancerous human liver datasets. Modifications brought to previous works include: 1) a linear interpolation of the power spectrum in the log scale; 2) the relaxation of the underlying hypothesis on the diffraction factor; 3) a generalization to nonhomogeneous local ACS; and 4) an adaptive restriction of frequencies to a more reliable range than the usable frequency range. Regularization was formulated as a generalized least absolute shrinkage and selection operator (LASSO), and a variant of the Bayesian information criterion (BIC) was applied to estimate the Lagrangian multiplier on the LASSO constraint. In addition, we evaluated the proposed algorithm when applying median filtering before and after regularization. Tests conducted showed that the PF-R yielded robust results in all tested conditions, suggesting potential for additional validation as a diagnosis method.

Ultrafast Myocardial Principal Strain Ultrasound Elastography During Stress Tests: In Vitro Validation and In Vivo Feasibility.

Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.

Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease.

OBJECTIVE: To develop a quantitative ultrasound (QUS)- and elastography-based model to improve classification of steatosis grade, inflammation grade, and fibrosis stage in patients with chronic liver disease in comparison with shear wave elastography alone, using histopathology as the reference standard. METHODS: This ancillary study to a prospective institutional review-board approved study included 82 patients with non-alcoholic fatty liver disease, chronic hepatitis B or C virus, or autoimmune hepatitis. Elastography measurements, homodyned K-distribution parametric maps, and total attenuation coefficient slope were recorded. Random forests classification and bootstrapping were used to identify combinations of parameters that provided the highest diagnostic accuracy. Receiver operating characteristic (ROC) curves were computed. RESULTS: For classification of steatosis grade S0 vs. S1-3, S0-1 vs. S2-3, S0-2 vs. S3, area under the receiver operating characteristic curve (AUC) were respectively 0.60, 0.63, and 0.62 with elasticity alone, and 0.90, 0.81, and 0.78 with the best tested model combining QUS and elastography features. For classification of inflammation grade A0 vs. A1-3, A0-1 vs. A2-3, A0-2 vs. A3, AUCs were respectively 0.56, 0.62, and 0.64 with elasticity alone, and 0.75, 0.68, and 0.69 with the best model. For classification of liver fibrosis stage F0 vs. F1-4, F0-1 vs. F2-4, F0-2 vs. F3-4, F0-3 vs. F4, AUCs were respectively 0.66, 0.77, 0.72, and 0.74 with elasticity alone, and 0.72, 0.77, 0.77, and 0.75 with the best model. CONCLUSION: Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.

Deformability of ascending thoracic aorta aneurysms assessed using ultrafast ultrasound and a principal strain estimator: In vitro evaluation and in vivo feasibility.

BACKGROUND: Noninvasive vascular strain imaging under conventional line-by-line scanning has a low frame rate and lateral resolution and depends on the coordinate system. It is thus affected by high deformations due to image decorrelation between frames. PURPOSE: To develop an ultrafast time-ensemble regularized tissue-Doppler optical-flow principal strain estimator for aorta deformability assessment in a long-axis view. METHODS: This approach alleviated the impact of lateral resolution using image compounding and that of the coordinate system dependency using principal strain. Accuracy and feasibility were evaluated in two aorta-mimicking phantoms first, and then in four age-matched individuals with either a normal aorta or a pathological ascending thoracic aorta aneurysm (TAA). RESULTS: Instantaneous aortic maximum and minimum principal strain maps and regional accumulated strains during each cardiac cycle were estimated at systolic and diastolic phases to characterize the normal aorta and TAA. In vitro, principal strain results matched sonomicrometry measurements. In vivo, a significant decrease in maximum and minimum principal strains was observed in TAA cases, whose range was respectively 7.9 ± 6.4% and 8.2 ± 2.6% smaller than in normal aortas. CONCLUSIONS: The proposed principal strain estimator showed an ability to potentially assess TAA deformability, which may provide an individualized and reliable evaluation method for TAA rupture risk assessment.

Shear Wave Elastography and Quantitative Ultrasound as Biomarkers to Characterize Deep Vein Thrombosis In Vivo.

OBJECTIVE: Investigate shear wave elastography (SWE) and quantitative ultrasound (QUS) parameters in patients hospitalized for lower limb deep vein thrombosis (DVT). METHOD: Sixteen patients with DVT were recruited and underwent SWE and radiofrequency data acquisitions for QUS on day 0, day 7, and day 30 after the beginning of symptoms, in both proximal and distal zones of the clot identified on B-mode scan. SWE and QUS features were computed to differentiate between thrombi at day 0, day 7, and day 30 following treatment with heparin or oral anticoagulant. The Young's modulus from SWE was computed, as well as QUS homodyned K-distribution (HKD) parameters reflecting blood clot structure. Median and interquartile range of SWE and QUS parameters within clot were taken as features. RESULTS: In the proximal zone of the clot, the HKD ratio of coherent-to-diffuse backscatter median showed a significant decrease from day 7 to day 30 (P = .036), while the HKD ratio of diffuse-to-total backscatter median presented a significant increase from day 7 to day 30 (P = .0491). In the distal zone of the clot, the HKD normalized intensity of the echo envelope median showed a significant increase from day 0 to day 30 (P = .0062). No SWE features showed statistically significant differences over time. Nonetheless, a trend of lower median of Young's modulus within clot for patients who developed a pulmonary embolism was observed. CONCLUSION: QUS features may be relevant to characterize clot's evolution over time. Further analysis of their clinical interpretation and validation on a larger dataset would deserve to be studied.

Statistical modeling of ultrasound signals related to the packing factor of wave scattering phenomena for structural characterization.

The two-dimensional homodyned K-distribution has been widely used to model the echo envelope of ultrasound radio frequency (RF) signals in the field of medical ultrasonics. The main contribution of this work is to present a theoretical framework for supporting this model of the echo envelope and statistical models of the RF signals and their Hilbert transform in the case in which the scatterers' positions may be dependent. In doing so, the law of large numbers, Lyapounov's central limit theorem, and the Berry-Esseen theorem are being used. In particular, the proposed theoretical framework supports a previous conjecture relating the scatterer clustering parameter of the homodyned K-distribution to the packing factor W, which is related to the spatial organization of the scatterers, appearing in statistical physics or backscatter coefficient modeling. Simulations showed that the proposed modeling is valid for a number of scatterers and packing factors varying by steps of 2 from 1 to 21 and 1 to 11, respectively. The proposed framework allows, in principle, the detection of the structural information taking place at a scale smaller than the wavelength based solely on the statistical analysis of the RF signals or their echo envelope, although this goal was previously achieved based on the spectral analysis of ultrasound signals.

Quantitative ultrasound imaging of soft biological tissues: a primer for radiologists and medical physicists.

Quantitative ultrasound (QUS) aims at quantifying interactions between ultrasound and biological tissues. QUS techniques extract fundamental physical properties of tissues based on interactions between ultrasound waves and tissue microstructure. These techniques provide quantitative information on sub-resolution properties that are not visible on grayscale (B-mode) imaging. Quantitative data may be represented either as a global measurement or as parametric maps overlaid on B-mode images. Recently, major ultrasound manufacturers have released speed of sound, attenuation, and backscatter packages for tissue characterization and imaging. Established and emerging clinical applications are currently limited and include liver fibrosis staging, liver steatosis grading, and breast cancer characterization. On the other hand, most biological tissues have been studied using experimental QUS methods, and quantitative datasets are available in the literature. This educational review addresses the general topic of biological soft tissue characterization using QUS, with a focus on disseminating technical concepts for clinicians and specialized QUS materials for medical physicists. Advanced but simplified technical descriptions are also provided in separate subsections identified as such. To understand QUS methods, this article reviews types of ultrasound waves, basic concepts of ultrasound wave propagation, ultrasound image formation, point spread function, constructive and destructive wave interferences, radiofrequency data processing, and a summary of different imaging modes. For each major QUS technique, topics include: concept, illustrations, clinical examples, pitfalls, and future directions.

Multiparametric in vivo ultrasound shear wave viscoelastography on farm-raised fatty duck livers: human radiology imaging applied to food sciences.

Nine mulard ducks that were being raised for foie gras (steatosis) production went through in vivo shear wave (SW) elastography imaging of their liver during the force-feeding period to investigate changes in liver tissue characteristics. A total of 4 imaging sessions at an interval of 3 to 4 d were conducted at the farm on each animal. Three ducks were sacrificed at the second, third, and fourth imaging sessions for histopathology analysis of all animals at these time points. Six SW elastography parameters were evaluated: SW speed, SW attenuation, SW dispersion, Young's modulus, viscosity, and shear modulus. Shear waves of different frequencies propagate with different phase velocities. Thus, SW speed and other dependent parameters such as Young's modulus, viscosity, and shear modulus were computed at 2 frequencies: 75 and 202 Hz. Each parameter depicted a statistically significant trend along the force-feeding process (P-values between 0.001 and 0.0001). The fat fraction of the liver increased over the 12-day period of feeding. All parameters increased monotonically over time at 75 Hz, whereas modal relations were seen at 202 Hz. Shear wave dispersion measured between 75 and 202 Hz depicted a plateau from day 5. Based on this validation, proposed imaging methods are aimed to be used in the future on naturally fed ducks and geese.

In vivo Ultrafast Quantitative Ultrasound and Shear Wave Elastography Imaging on Farm-Raised Duck Livers during Force Feeding.

Shear wave elastography (speed and dispersion), local attenuation coefficient slope and homodyned-K parametric imaging were used for liver steatosis grading. These ultrasound biomarkers rely on physical interactions between shear and compression waves with tissues at both macroscopic and microscopic scales. These techniques were applied in a context not yet studied with ultrasound imaging, that is, monitoring steatosis of force-fed duck livers from pre-force-fed to foie gras stages. Each estimated feature presented a statistically significant trend along the feeding process (p values <10-3). However, whereas a monotonic increase in the shear wave speed was observed along the process, most quantitative ultrasound features exhibited an absolute maximum value halfway through the process. As the liver fat fraction in foie gras is much higher than that seen clinically, we hypothesized that a change in the ultrasound scattering regime is encountered for high-fat fractions, and consequently, care has to be taken when applying ultrasound biomarkers to grading of severe states of steatosis.

Pilot clinical study of quantitative ultrasound spectroscopy measurements of erythrocyte aggregation within superficial veins.

BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S10). RESULTS: W and Din vivo measurements were positively correlated with the ex vivoS10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

Added Value of Quantitative Ultrasound and Machine Learning in BI-RADS 4-5 Assessment of Solid Breast Lesions.

The purpose of this study was to evaluate various combinations of 13 features based on shear wave elasticity (SWE), statistical and spectral backscatter properties of tissues, along with the Breast Imaging Reporting and Data System (BI-RADS), for classification of solid breast lesions at ultrasonography by means of random forests. One hundred and three women with 103 suspicious solid breast lesions (BI-RADS categories 4-5) were enrolled. Before biopsy, additional SWE images and a cine sequence of ultrasound images were obtained. The contours of lesions were delineated, and parametric maps of the homodyned-K distribution were computed on three regions: intra-tumoral, supra-tumoral and infra-tumoral zones. Maximum elasticity and total attenuation coefficient were also extracted. Random forests yielded receiver operating characteristic (ROC) curves for various combinations of features. Adding BI-RADS category improved the classification performance of other features. The best result was an area under the ROC curve of 0.97, with 75.9% specificity at 98% sensitivity.

Reconstruction of Viscosity Maps in Ultrasound Shear Wave Elastography.

Change in viscoelastic properties of biological tissues may often be symptomatic of a dysfunction that can be correlated to tissue pathology. Shear wave elastography is an imaging method mainly used to assess stiffness but with the potential to measure viscoelasticity of biological tissues. This can enable tissue characterization; and thus, can be used as a marker to improve diagnosis of pathological lesions. In this study, a frequency-shift method based framework is presented for the reconstruction of viscosity by analyzing the spectral properties of acoustic radiation force-induced shear waves. The aim of the study was to investigate the feasibility of viscosity reconstruction maps in homogeneous as well as heterogeneous samples. Experiments were performed in four in vitro phantoms, two ex vivo porcine liver samples, two ex vivo fatty duck liver samples, and one in vivo fatty goose liver. Successful viscosity maps were reconstructed in homogeneous and heterogeneous phantoms with embedded mechanical inclusions having different geometries. Quantitative values of viscosity obtained for two porcine liver tissues, two fatty duck liver samples, and one goose fatty liver were (mean ± SD) 0.61 ± 0.21, 0.52 ± 0.35; 1.28 ± 0.54, 1.36 ± 0.73, and 1.67 ± 0.70 Pa.s, respectively.

Diagnostic Accuracy of Echo Envelope Statistical Modeling Compared to B-Mode and Power Doppler Ultrasound Imaging in Patients With Clinically Diagnosed Lateral Epicondylosis of the Elbow.

OBJECTIVES: To compare the accuracy of homodyned K quantitative ultrasound (QUS) with that of B-mode and Doppler ultrasound imaging for discriminating between lateral epicondylosis (LE) and asymptomatic elbows. METHODS: This prospective study received Institutional Review Board approval, and participants provided written informed consent. Between February 2015 and March 2017, 30 LE elbows in 27 patients and 24 asymptomatic elbows in 13 volunteers underwent B-mode, Doppler, and radiofrequency ultrasound imaging of the common extensor tendon (CET) and radial collateral ligament (RCL). Two readers classified the elbows independently on the basis of a review of B-mode and Doppler images. The global and local estimates of QUS parameters (µ n , 1/α, and k) were computed in the CET and CET-RCL regions, respectively, and the area of each region was calculated. A random-forest classifier identified the most discriminating 3-parameter combination: CET global estimate of 1/α, CET-RCL area, and local estimate of k. RESULTS: The patients with LE had a mean age of 50 years (range, 31-66 years), and the volunteers had a mean age of 50 years (range, 37-57 years). The area under the receiver operating characteristic curve, sensitivity, and specificity of reader 1, reader 2, and the QUS-based model were 0.80 (95% confidence interval [CI], 0.66-0.95), 0.72 (95% CI, 0.56-0.89), and 0.88 (95% CI, 0.72-1.04); 0.79 (95% CI, 0.66-0.93), 0.65 (95% CI, 0.47-0.82), and 0.84 (95% CI, 0.67-1.01); and 0.82 (95% CI, 0.80-0.85), 0.73, and 0.79, respectively. CONCLUSIONS: An automated, computer-based QUS technique diagnosed LE with accuracy of 0.82. This technique could provide quantitative biomarkers for the characterization of LE disease.

Assessment of Carotid Artery Plaque Components With Machine Learning Classification Using Homodyned-K Parametric Maps and Elastograms.

Quantitative ultrasound (QUS) imaging methods, including elastography, echogenicity analysis, and speckle statistical modeling, are available from a single ultrasound (US) radio-frequency data acquisition. Since these US imaging methods provide complementary quantitative tissue information, characterization of carotid artery plaques may gain from their combination. Sixty-six patients with symptomatic ( n = 26 ) and asymptomatic ( n = 40 ) carotid atherosclerotic plaques were included in the study. Of these, 31 underwent magnetic resonance imaging (MRI) to characterize plaque vulnerability and quantify plaque components. US radio-frequency data sequence acquisitions were performed on all patients and were used to compute noninvasive vascular US elastography and other QUS features. Additional QUS features were computed from three types of images: homodyned-K (HK) parametric maps, Nakagami parametric maps, and log-compressed B-mode images. The following six classification tasks were performed: detection of 1) a small area of lipid; 2) a large area of lipid; 3) a large area of calcification; 4) the presence of a ruptured fibrous cap; 5) differentiation of MRI-based classification of nonvulnerable carotid plaques from neovascularized or vulnerable ones; and 6) confirmation of symptomatic versus asymptomatic patients. Feature selection was first applied to reduce the number of QUS parameters to a maximum of three per classification task. A random forest machine learning algorithm was then used to perform classifications. Areas under receiver-operating curves (AUCs) were computed with a bootstrap method. For all tasks, statistically significant higher AUCs were achieved with features based on elastography, HK parametric maps, and B-mode gray levels, when compared to elastography alone or other QUS alone ( ). For detection of a large area of lipid, the combination yielding the highest AUC (0.90, 95% CI 0.80-0.92, ) was based on elastography, HK, and B-mode gray-level features. To detect a large area of calcification, the highest AUC (0.95, 95% CI 0.94-0.96, ) was based on HK and B-mode gray level features. For other tasks, AUCs varied between 0.79 and 0.97. None of the best combinations contained Nakagami features. This study shows the added value of combining different features computed from a single US acquisition with machine learning to characterize carotid artery plaques.

Quantitative ultrasound and machine learning for assessment of steatohepatitis in a rat model.

OBJECTIVES: To develop a machine learning model based on quantitative ultrasound (QUS) parameters to improve classification of steatohepatitis with shear wave elastography in rats by using histopathology scoring as the reference standard. METHODS: This study received approval from the institutional animal care committee. Sixty male Sprague-Dawley rats were either fed a standard chow or a methionine- and choline-deficient diet. Ultrasound-based radiofrequency images were recorded in vivo to generate QUS and elastography maps. Random forests classification models and a bootstrap method were used to identify the QUS parameters that improved the classification accuracy of elastography. Receiver-operating characteristic analyses were performed. RESULTS: For classification of not steatohepatitis vs borderline or steatohepatitis, the area under the receiver-operating characteristic curve (AUC) increased from 0.63 for elastography alone to 0.72 for a model that combined elastography and QUS techniques (p < 0.001). For detection of liver steatosis grades 0 vs ≥ 1, ≤ 1 vs ≥ 2, ≤ 2 vs 3, respectively, the AUCs increased from 0.70, 0.65, and 0.69 to 0.78, 0.78, and 0.75 (p < 0.001). For detection of liver inflammation grades 0 vs ≥ 1, ≤ 1 vs ≥ 2, ≤ 2 vs 3, respectively, the AUCs increased from 0.58, 0.77, and 0.78 to 0.66, 0.84, and 0.87 (p < 0.001). For staging of liver fibrosis grades 0 vs ≥ 1, ≤ 1 vs ≥ 2, and ≤ 2 vs ≥ 3, respectively, the AUCs increased from 0.79, 0.92, and 0.91 to 0.85, 0.98, and 0.97 (p < 0.001). CONCLUSION: QUS parameters improved the classification accuracy of steatohepatitis, liver steatosis, inflammation, and fibrosis compared to shear wave elastography alone. KEY POINTS: • Quantitative ultrasound and shear wave elastography improved classification accuracy of liver steatohepatitis and its histological features (liver steatosis, inflammation, and fibrosis) compared to elastography alone. • A machine learning approach based on random forest models and incorporating local attenuation and homodyned-K tissue modeling shows promise for classification of nonalcoholic steatohepatitis. • Further research should be performed to demonstrate the applicability of this multi-parametric QUS approach in a human cohort and to validate the combinations of parameters providing the highest classification accuracy.

Estimation of polydispersity in aggregating red blood cells by quantitative ultrasound backscatter analysis.

Quantitative ultrasound techniques based on the backscatter coefficient (BSC) have been commonly used to characterize red blood cell (RBC) aggregation. Specifically, a scattering model is fitted to measured BSC and estimated parameters can provide a meaningful description of the RBC aggregates' structure (i.e., aggregate size and compactness). In most cases, scattering models assumed monodisperse RBC aggregates. This study proposes the Effective Medium Theory combined with the polydisperse Structure Factor Model (EMTSFM) to incorporate the polydispersity of aggregate size. From the measured BSC, this model allows estimating three structural parameters: the mean radius of the aggregate size distribution, the width of the distribution, and the compactness of the aggregates. Two successive experiments were conducted: a first experiment on blood sheared in a Couette flow device coupled with an ultrasonic probe, and a second experiment, on the same blood sample, sheared in a plane-plane rheometer coupled to a light microscope. Results demonstrated that the polydisperse EMTSFM provided the best fit to the BSC data when compared to the classical monodisperse models for the higher levels of aggregation at hematocrits between 10% and 40%. Fitting the polydisperse model yielded aggregate size distributions that were consistent with direct light microscope observations at low hematocrits.