OBJECTIVE: Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE.
METHODS: A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization.
RESULTS: In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80.
CONCLUSIONS: In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.

Ultrasound has been a popular clinical imaging modality for decades. It is a well-established means of displaying the macroscopic anatomy of soft-tissue structures. While conventional ultrasound methods, i.e., B-mode and Doppler methods, are well proven and continue to advance technically in many ways, e.g., by extending into higher frequencies and taking advantage of harmonic phenomena in tissues, fundamentally new so-called quantitative ultrasound (QUS) technologies also are emerging and offer exciting promise for making significant improvements in clinical imaging and characterization of disease. These emerging quantitative methods include spectrum analysis, image statistics, elasticity imaging, contrast-agent methods, and flow-detection and -measurement techniques. Each provides independent information. When used alone, each can provide clinically valuable imaging capabilities; when combined with each other, their capabilities may be more powerful in many applications. Furthermore, all can be used fused with other imaging modalities, such as computed tomography (CT), magnetic-resonance (MR), positron-emission-tomography (PET), or single-photon emission computerized tomography (SPECT) imaging, to offer possibly even greater improvements in detecting, diagnosing, imaging, evaluating, and monitoring disease. This chapter focuses on QUS methods that are based on spectrum analysis and image statistics.

Modelling ultrasound speckle to characterise tissue properties has generated considerable interest. As speckle is dependent on the underlying tissue architecture, modelling it may aid in tasks such as segmentation or disease detection. For the transplanted kidney, where ultrasound is used to investigate dysfunction, it is unknown which statistical distribution best characterises such speckle. This applies to the regions of the transplanted kidney: the cortex, the medulla and the central echogenic complex. Furthermore, it is unclear how these distributions vary by patient variables such as age, sex, body mass index, primary disease or donor type. These traits may influence speckle modelling given their influence on kidney anatomy. We investigate these two aims.
B-mode images from n = 821 kidney transplant recipients (one image per recipient) were automatically segmented into the cortex, medulla and central echogenic complex using a neural network. Seven distinct probability distributions were fitted to each region\'s histogram, and statistical analysis was performed.
The Rayleigh and Nakagami distributions had model parameters that differed significantly between the three regions (p ≤ 0.05). Although both had excellent goodness of fit, the Nakagami had higher Kullbeck-Leibler divergence. Recipient age correlated weakly with scale in the cortex (Ω: ρ = 0.11, p = 0.004), while body mass index correlated weakly with shape in the medulla (m: ρ = 0.08, p = 0.04). Neither sex, primary disease nor donor type exhibited any correlation.
We propose the Nakagami distribution be used to characterize transplanted kidneys regionally independent of disease etiology and most patient characteristics.

Quantitative ultrasound (QUS) methods characterizing the backscattered echo signal have been of use in assessing tissue microstructure. High-frequency (30 MHz) QUS methods have been successful in detecting metastases in surgically excised lymph nodes (LNs), but limited evidence exists regarding the efficacy of QUS for evaluating LNs in vivo at clinical frequencies (2-10 MHz). In this study, a clinical scanner and 10-MHz linear probe were used to collect radiofrequency (RF) echo data of LNs in vivo from 19 cancer patients. QUS methods were applied to estimate parameters derived from the backscatter coefficient (BSC) and statistics of the envelope-detected RF signal. QUS parameters were used to train classifiers based on linear discriminant analysis (LDA) and support vector machines (SVMs). Two BSC-based parameters, scatterer diameter and acoustic concentration, were the most effective for accurately detecting metastatic LNs, with both LDA and SVMs achieving areas under the receiver operating characteristic (AUROC) curve ≥0.94. A strategy of classifying LNs based on the echo frame with the highest cancer probability improved performance to 88% specificity at 100% sensitivity (AUROC = 0.99). These results provide encouraging evidence that QUS applied at clinical frequencies may be effective at accurately identifying metastatic LNs in vivo, helping in diagnosis while reducing unnecessary biopsies and surgical treatments.

In this study, we compared multiple quantitative ultrasound metrics for the purpose of differentiating muscle in 20 healthy, 10 dystrophic and 10 obese mice. High-frequency ultrasound scans were acquired on dystrophic (D2-mdx), obese (db/db) and control mouse hindlimbs. A total of 248 image features were extracted from each scan, using brightness-mode statistics, Canny edge detection metrics, Haralick features, envelope statistics and radiofrequency statistics. Naïve Bayes and other classifiers were trained on single and pairs of features. The a parameter from the Homodyned K distribution at 40 MHz achieved the best univariate classification (accuracy = 85.3%). Maximum classification accuracy of 97.7% was achieved using a logistic regression classifier on the feature pair of a2 (K distribution) at 30 MHz and brightness-mode variance at 40MHz. Dystrophic and obese mice have muscle with distinct acoustic properties and can be classified to a high level of accuracy using a combination of multiple features.

Hepatic steatosis causes nonalcoholic fatty liver disease. Whole-body vibration (WBV) has been recommended to allow patients who have difficulty engaging in exercise to improve the grade of hepatic steatosis. This study proposed using ultrasound parametric imaging of the homodyned K (HK) distribution to evaluate the effectiveness of WBV treatments in alleviating hepatic steatosis. Sixty mice were assigned to control (n = 6), sedentary (n = 18), WBV (n = 18), and exercise (swimming) (n = 18) groups. Mice were fed a high-fat diet to induce hepatic steatosis and underwent the intervention for 4, 8, and 16 weeks. Ultrasound scanning was performed in vivo on each mouse after the interventions for ultrasound HK imaging using the parameter μ (the scatterer clustering parameter). Histopathological examinations and the intraperitoneal glucose tolerance test were carried out for comparisons with ultrasound findings. At the 16th week, WBV and exercise groups demonstrated lower body weights, glucose concentrations, histopathological scores (steatosis and steatohepatitis), and μ parameters than the control group (p < 0.05). The steatosis grade was significantly lower in the WBV group (mild) than in the exercise group (moderate) (p < 0.05), corresponding to a reduction in the μ parameter. A further analysis revealed that the correlation between the steatosis grade and the μ parameter was 0.84 (p < 0.05). From this animal study we conclude that WBV may be more effective than exercise in reducing the progression of hepatic steatosis, and ultrasound HK parametric imaging is an appropriate method for evaluating WBV’s effect on hepatic steatosis.

This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the International Society of Lymphology (ISL) stage. Ultrasonic measurements were made around the middle thigh (n = 150). Radiofrequency data were acquired using a clinical scanner and 8-MHz linear probe. Envelope statistical analysis was performed using constant false alarm rate processing and homodyned K (HK) distribution. The attenuation coefficient was calculated using the spectral log-difference technique. The backscatter coefficient (BSC) was obtained by the reference phantom method with attenuation compensation according to the attenuation coefficients in the dermis and hypodermis, and then effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated with a Gaussian model. Receiver operating characteristic curves of QUS parameters were obtained using a linear regression model. A single QUS parameter with high area under the curve (AUC) differed between the dermis (ESD and EAC) and hypodermis (HK) parameters. The combinations with ESD and EAC in the dermis, HK parameters in the hypodermis and typical features (dermal thickness and echogenic regions in the hypodermis) improved classification performance between ISL stages 0 and ≥I (AUC = 0.90 with sensitivity of 75% and specificity of 91%) in comparison with ESD and EAC in the dermis (AUC = 0.82) and HK parameters in the hypodermis (AUC = 0.82). In vivo QUS assessment by BSC and envelope statistical analyses can be valuable for non-invasively classifying an extremely early stage of lymphedema, such as ISL stage I, and following its progression.

BACKGROUND: Considerable progress of ultrasound simulation on blood has enhanced the characterizing of red blood cell (RBC) aggregation.
OBJECTIVE: A novel simulation method aims at modeling the blood with different RBC aggregations and concentrations is proposed.
METHODS: The modeling process is as follows: (i) A three-dimensional scatterer model is first built by a mapping with a Hilbert space-filling curve from the one-dimensional scatterer distribution. (ii) To illustrate the relationship between the model parameters and the RBC aggregation level, a variety of blood samples are prepared and scanned to acquire their radiofrequency signals in-vitro. (iii) The model parameters are determined by matching the Nakagami-distribution characteristics of envelope signals simulated from the model with those measured from the blood samples.
RESULTS: Nakagami metrics m estimated from 15 kinds of blood samples (hematocrits of 20%, 40%, 60% and plasma concentrations of 15%, 30%, 45%, 60%, 75%) are compared with metrics estimated by their corresponding models (each with different eligible parameters). Results show that for the three hematocrit levels, the mean and standard deviation of the root-mean-squared deviations of m are 0.27 ± 0.0026, 0.16 ± 0.0021, 0.12 ± 0.0018 respectively.
CONCLUSIONS: The proposed simulation model provides a viable data source to evaluate the performance of the ultrasound-based methods for quantifying RBC aggregation.

This work deals with the development of a methodology to evaluate the concentration in cell or particle suspensions from ultrasound images. The novelty of the method is based on two goals: first, it should be valid when the energy reaching the scatterers is unknown and cannot be measured or calibrated. In addition, it should be robust against echo overlap which may occur due to high scatterer concentration. Both characteristics are especially valuable in quantitative ultrasound analysis in the clinical context. In this regard, the present work considers the ability of envelope statistics models to characterize ultrasound images. Envelope statistical analysis are based on the examination of the physical properties of a medium through the study of the statistical distribution of the backscattered signal envelop. A review of the statistical distributions typically used to characterize scattering mediums was conducted. The main parameters of the distribution were estimated from simulations of signals backscattered by particle suspensions. Then, the ability of these parameters to characterize the suspension concentration was analyzed and the µ parameter from the Homodyned-K distribution resulted as the most suitable parameter for the task. Simulations were also used to study the impact of noise, signal amplitude variability and dispersion of particle sizes on the estimation method. The efficiency of the algorithm on experimental measurements was also evaluated. To this end, two sets of ultrasound images were obtained from suspensions of 7 µm and 12 µm polystyrene particles in water, using a 20 MHz focused transducer. The methodology proved to be efficient to quantify the concentration of particle suspensions in the range between 5 and 3000 particles/µl, achieving similar results for both particle sizes and for different signal-to-noise ratios.

BACKGROUND: The homodyned-K (HK) distribution is an important statistical model for describing ultrasound backscatter envelope statistics. HK parametric imaging has shown potential for characterizing hepatic steatosis. However, the feasibility of HK parametric imaging in assessing human hepatic steatosis in vivo remains unclear.
METHODS: In this paper, ultrasound HK μ parametric imaging was proposed for assessing human hepatic steatosis in vivo. Two recent estimators for the HK model, RSK (the level-curve method that uses the signal-to-noise ratio (SNR), skewness, and kurtosis based on the fractional moments of the envelope) and XU (the estimation method based on the first moment of the intensity and two log-moments, namely X- and U-statistics), were investigated. Liver donors (n=72) and patients (n=204) were recruited to evaluate hepatic fat fractions (HFFs) using magnetic resonance spectroscopy and to evaluate the stages of fatty liver disease (normal, mild, moderate, and severe) using liver biopsy with histopathology. Livers were scanned using a 3-MHz ultrasound to construct μ RSK and μ XU images to correlate with HFF analyses and fatty liver stages. The μ RSK and μ XU parametric images were constructed using the sliding window technique with the window side length (WSL) =1-9 pulse lengths (PLs). The diagnostic values of the μ RSK and μ XU parametric imaging methods were evaluated using receiver operating characteristic (ROC) curves.
RESULTS: For the 72 participants in Group A, the μ RSK parametric imaging with WSL =2-9 PLs exhibited similar correlation with log10(HFF), and the μ RSK parametric imaging with WSL = 3 PLs had the highest correlation with log10(HFF) (r=0.592); the μ XU parametric imaging with WSL =1-9 PLs exhibited similar correlation with log10(HFF), and the μ XU parametric imaging with WSL =1 PL had the highest correlation with log10(HFF) (r=0.628). For the 204 patients in Group B, the areas under the ROC (AUROCs) obtained using μ RSK for fatty stages ≥ mild (AUROC1), ≥ moderate (AUROC2), and ≥ severe (AUROC3) were (AUROC1, AUROC2, AUROC3) = (0.56, 0.57, 0.53), (0.68, 0.72, 0.75), (0.73, 0.78, 0.80), (0.74, 0.77, 0.79), (0.74, 0.78, 0.79), (0.75, 0.80, 0.82), (0.74, 0.77, 0.83), (0.74, 0.78, 0.84) and (0.73, 0.76, 0.83) for WSL =1, 2, 3, 4, 5, 6, 7, 8 and 9 PLs, respectively. The AUROCs obtained using μ XU for fatty stages ≥ mild, ≥ moderate, and ≥ severe were (AUROC1, AUROC2, AUROC3) = (0.75, 0.83, 0.81), (0.74, 0.80, 0.80), (0.76, 0.82, 0.82), (0.74, 0.80, 0.84), (0.76, 0.80, 0.83), (0.75, 0.80, 0.84), (0.75, 0.79, 0.85), (0.75, 0.80, 0.85) and (0.73, 0.77, 0.83) for WSL = 1, 2, 3, 4, 5, 6, 7, 8 and 9 PLs, respectively.
CONCLUSIONS: Both the μ RSK and μ XU parametric images are feasible for evaluating human hepatic steatosis. The WSL exhibits little impact on the diagnosing performance of the μ RSK and μ XU parametric imaging. The μ XU parametric imaging provided improved performance compared to the μ RSK parametric imaging in characterizing human hepatic steatosis in vivo.