Quantitative ultrasound envelope statistics imaging as a screening approach for pediatric hepatic steatosis and liver fibrosis: using biomarker and transient elastography as reference standards.

Quantitative ultrasound (QUS) envelope statistics imaging is an emerging technique for the assessment of hepatic steatosis in adults. Blood tests are currently recommended as the screening tool for pediatric hepatic steatosis, a condition that can lead to liver fibrosis in children. This study examined the utility of QUS envelope statistics imaging in grading biomarker-diagnosed hepatic steatosis and detecting liver fibrosis in a pediatric population. A total of 173 subjects was enrolled (Group A) for QUS envelope statistics imaging using two statistical distributions, Nakagami and homodyned K (HK) models, and information entropy. QUS parameter values were compared with the hepatic steatosis index (HSI) and steatosis grade (G0: HSI <30; G1: 30 ≤ HSI <36; G2: 36 ≤ HSI <41.6; G3: ≥41.6). An additional cohort of 63 subjects (Group B) was recruited to undergo both QUS envelope statistics imaging and liver stiffness measurements (LSM) obtained from the transient elastography (Fibroscan), with a cutoff value set at 5 kPa to indicate liver fibrosis. The diagnostic performances were evaluated using the area under the receiver operating characteristic curve (AUROC). QUS envelope statistics imaging generated the AUROC values for steatosis grading at levels ≥ G1, ≥ G2, and ≥ G3 ranged from 0.94 to 0.97, 0.91 to 0.93, and 0.83 to 0.87, respectively, and produced an AUROC range of between 0.82 and 0.84 for identifying liver fibrosis. QUS envelope statistics imaging integrates the benefits of both biomarkers and elastography, enabling the screening of hepatic steatosis and detection of liver fibrosis in a pediatric population.

Ultrasound single-phase CBE imaging for monitoring radiofrequency ablation of the liver tumor: A preliminary clinical validation.

Radiofrequency ablation (RFA) is an alternative treatment for early-stage hepatocellular carcinoma (HCC). The production of gas bubbles by RFA indicates threshold temperature of tissue necrosis and results in changes in backscattered energy (CBE) when ultrasound monitors RFA. In this study, ultrasound single-phase CBE imaging was used as a means of monitoring RFA of the liver tumor by analyzing the backscattering of ultrasound from gas bubbles in the liver. A total of 19 HCC patients were enrolled in the study. An ultrasound system was used during RFA to monitor the ablation process and acquire raw image data consisting of backscattered signals for single-phase CBE imaging. On the basis of single-phase CBE imaging, the area corresponding to the range of gas bubbles was compared with the tumor sizes and ablation zones estimated from computed tomography. During RFA, ultrasound single-phase CBE imaging enabled improved visualization of gas bubbles. Measured gas bubble areas by CBE were related to tumor size (the Spearman correlation coefficient r s = 0.86; p < 0.05); less dependent on the ablation zone. Approximately 95% of the data fell within the limits of agreement in Bland-Altman plots, and 58% of the data fell within the 95% CI. This study suggests that single-phase CBE imaging provides information about liver tumor size because of the abundant vessels in liver tumors that promote the generation of gas bubbles, which serve as natural contrast agents in RFAs to enhance ultrasound backscattering. Ultrasound single-phase CBE imaging may allow clinicians to determine if the required minimum RFA efficacy level is reached by assessing gas bubbles in the liver tumors.

Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy.

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.

Quantitative imaging of ultrasound backscattered signals with information entropy for bone microstructure characterization.

Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient rs, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (rs = - 0.83; p < 0.05). Small-window entropy imaging also performed well in discriminating young and old participants (p < 0.05) and postmenopausal women with low versus moderate-to-high osteoporosis risk (the area under the ROC curve = 0.80; cut-off value = 2.65; accuracy = 86.00%; sensitivity = 71.43%; specificity = 88.37%). Ultrasound small-window entropy imaging has great potential in bone tissue characterization and osteoporosis assessment.

Utility of quantitative ultrasound in community screening for hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Quantitative ultrasound facilitates clinical grading of hepatic steatosis (the early stage of NAFLD). However, the utility of quantitative ultrasound as a first-line method for community screening of hepatic steatosis remains unclear. Therefore, this study aimed to investigate the utility of quantitative ultrasound to screen for hepatic steatosis and for metabolic evaluation at the community level. In total, 278 participants enrolled from a community satisfied the study criteria. Each subject underwent anthropometric and biochemical examinations, and abdominal ultrasound imaging was performed to measure the controlled attenuation (CAP), integrated backscatter (IB), and information Shannon entropy (ISE). The assessment outcomes were compared with the fatty liver index (FLI), hepatic steatosis index (HSI), metabolic syndrome (MetS), and insulin resistance to evaluate the screening performance through the area under the receiver operating characteristic curve (AUROC) and Delong's test. Ultrasound ISE, CAP, and IB were effective in screening hepatic steatosis, MetS, and insulin resistance. In screening for hepatic steatosis, the AUROCs of ISE, CAP, and IB were 0.85, 0.83, and 0.80 (the cutoff FLI = 60), respectively, and 0.84, 0.75, 0.77 (the cutoff HSI = 36), respectively, and those for the evaluation of MetS and insulin resistance were 0.79, 0.75, 0.79, respectively, and 0.83, 0.76, 0.78, respectively. Delong's test revealed that ISE outperformed CAP and IB for the detection of hepatic steatosis and insulin resistance (P < .05). Based on the present results, ultrasound ISE is a potential imaging biomarker during first-line community screening of hepatic steatosis and insulin resistance.

Considerations of Ultrasound Scanning Approaches in Non-alcoholic Fatty Liver Disease Assessment through Acoustic Structure Quantification.

Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatic fibrosis and cirrhosis. Acoustic structure quantification (ASQ), based on statistical analysis of ultrasound echoes, is an emerging technique for hepatic steatosis diagnosis. A standardized measurement protocol for ASQ analysis was suggested previously; however, an optimal ultrasound scanning approach has not been concluded thus far. In this study, the suitability of scanning approaches for the ASQ-based evaluation of hepatic steatosis was investigated. Hepatic fat fractions (HFFs; liver segments VIII, III and VI) of 70 living liver donors were assessed with magnetic resonance spectroscopy. A clinical ultrasound machine equipped with a 3-MHz convex transducer was used to scan each participant using the intercostal, epigastric and subcostal planes to acquire raw data for estimating two ASQ parameters (Cm2 and focal disturbance [FD] ratio) of segments VIII, III and VI, respectively. The parameters were plotted as functions of the HFF for calculating the values of the correlation coefficient (r) and probability value (p). The diagnostic performance of the parameters in discriminating between the normal and steatotic (≥5 and ≥10%) groups was also compared using receiver operating characteristic (ROC) curves. The Cm2 and FD ratio values measured using the epigastric and subcostal planes did not correlate with the severity of hepatic steatosis. However, intercostal imaging exhibited a higher correlation between the ASQ parameters and HFF (r = -0.64, p < 0.001). The diagnostic performance of Cm2 and FD ratio in detecting hepatic steatosis using intercostal imaging was also satisfactory (areas under ROC curves >0.8). Intercostal imaging is an appropriate scanning approach for ASQ analysis of the liver.

Ultrasound single-phase CBE imaging for monitoring radiofrequency ablation.

Radiofrequency (RF) ablation (RFA) is the most commonly used minimally invasive procedure for thermal ablation of liver tumors. Ultrasound not only provides real-time feedback of the electrode location for RFA guidance but also enables visualization of the tissue temperature. Changes in backscattered energy (CBE) have been widely applied to ultrasound temperature imaging for assessing thermal ablation. Pilot studies have revealed that significant shadowing features appear in CBE imaging and are caused by the electrode and RFA-induced gas bubbles. To resolve this problem, the current study proposed ultrasound single-phase CBE imaging based on positive CBE values. An in vitro model with tissue samples derived from the porcine tenderloin was used to validate the proposed method. During RFA with various electrode lengths, ultrasound scans of tissue samples were obtained using a clinical ultrasound scanner equipped with a convex array transducer of 3 MHz. Raw image data comprising 256 scan lines of backscattered RF signals were acquired for B-mode, conventional CBE, and single-phase CBE imaging by using the proposed algorithmic scheme. The ablation sizes estimated using CBE imaging and gross examinations were compared to calculate the correlation coefficient. The experimental results indicated that single-phase CBE imaging largely suppressed artificial CBE information in the shadowed region. Moreover, compared with conventional CBE imaging, single-phase CBE imaging provided a more accurate estimation of ablation sizes (the correlation coefficient was higher than 0.8).

Monitoring Radiofrequency Ablation Using Ultrasound Envelope Statistics and Shear Wave Elastography in the Periablation Period: An In Vitro Feasibility Study.

Radiofrequency ablation (RFA) is a minimally invasive method for treating tumors. Shear wave elastography (SWE) has been widely applied in evaluating tissue stiffness and final ablation size after RFA. However, the usefulness of periablation SWE imaging in assessing RFA remains unclear. Therefore, this study investigated the correlation between periablation SWE imaging and final ablation size. An in vitro porcine liver model was used for experimental validation (n = 36). During RFA with a power of 50 W, SWE images were collected using a clinical ultrasound system. To evaluate the effects of tissue temperature and gas bubbles during RFA, changes in the ablation temperature were recorded, and image echo patterns were measured using B-mode and ultrasound statistical parametric images. After RFA, the gross pathology of each tissue sample was compared with the region of change in the corresponding periablation SWE image. The experimental results showed that the tissue temperature at the ablation site varied between 70°C and 100°C. Hyperechoic regions and changes were observed in the echo amplitude distribution induced by gas bubbles. Under this condition, the confounding effects (including the temperature increase, tissue stiffness increase, and presence of gas bubbles) resulted in artifacts in the periablation SWE images, and the corresponding region correlated with the estimated final ablation size obtained from the gross pathology (r = 0.8). The findings confirm the feasibility of using periablation SWE imaging in assessing RFA.

Acoustic structure quantification by using ultrasound Nakagami imaging for assessing liver fibrosis.

Acoustic structure quantification (ASQ) is a recently developed technique widely used for detecting liver fibrosis. Ultrasound Nakagami parametric imaging based on the Nakagami distribution has been widely used to model echo amplitude distribution for tissue characterization. We explored the feasibility of using ultrasound Nakagami imaging as a model-based ASQ technique for assessing liver fibrosis. Standard ultrasound examinations were performed on 19 healthy volunteers and 91 patients with chronic hepatitis B and C (n = 110). Liver biopsy and ultrasound Nakagami imaging analysis were conducted to compare the METAVIR score and Nakagami parameter. The diagnostic value of ultrasound Nakagami imaging was evaluated using receiver operating characteristic (ROC) curves. The Nakagami parameter obtained through ultrasound Nakagami imaging decreased with an increase in the METAVIR score (p < 0.0001), representing an increase in the extent of pre-Rayleigh statistics for echo amplitude distribution. The area under the ROC curve (AUROC) was 0.88 for the diagnosis of any degree of fibrosis (≥F1), whereas it was 0.84, 0.69, and 0.67 for ≥F2, ≥F3, and ≥F4, respectively. Ultrasound Nakagami imaging is a model-based ASQ technique that can be beneficial for the clinical diagnosis of early liver fibrosis.

Ultrasound window-modulated compounding Nakagami imaging: Resolution improvement and computational acceleration for liver characterization.

Ultrasound Nakagami imaging is an attractive method for visualizing changes in envelope statistics. Window-modulated compounding (WMC) Nakagami imaging was reported to improve image smoothness. The sliding window technique is typically used for constructing ultrasound parametric and Nakagami images. Using a large window overlap ratio may improve the WMC Nakagami image resolution but reduces computational efficiency. Therefore, the objectives of this study include: (i) exploring the effects of the window overlap ratio on the resolution and smoothness of WMC Nakagami images; (ii) proposing a fast algorithm that is based on the convolution operator (FACO) to accelerate WMC Nakagami imaging. Computer simulations and preliminary clinical tests on liver fibrosis samples (n=48) were performed to validate the FACO-based WMC Nakagami imaging. The results demonstrated that the width of the autocorrelation function and the parameter distribution of the WMC Nakagami image reduce with the increase in the window overlap ratio. One-pixel shifting (i.e., sliding the window on the image data in steps of one pixel for parametric imaging) as the maximum overlap ratio significantly improves the WMC Nakagami image quality. Concurrently, the proposed FACO method combined with a computational platform that optimizes the matrix computation can accelerate WMC Nakagami imaging, allowing the detection of liver fibrosis-induced changes in envelope statistics. FACO-accelerated WMC Nakagami imaging is a new-generation Nakagami imaging technique with an improved image quality and fast computation.

Monitoring radiofrequency ablation using real-time ultrasound Nakagami imaging combined with frequency and temporal compounding techniques.

Gas bubbles induced during the radiofrequency ablation (RFA) of tissues can affect the detection of ablation zones (necrosis zone or thermal lesion) during ultrasound elastography. To resolve this problem, our previous study proposed ultrasound Nakagami imaging for detecting thermal-induced bubble formation to evaluate ablation zones. To prepare for future applications, this study (i) created a novel algorithmic scheme based on the frequency and temporal compounding of Nakagami imaging for enhanced ablation zone visualization, (ii) integrated the proposed algorithm into a clinical scanner to develop a real-time Nakagami imaging system for monitoring RFA, and (iii) investigated the applicability of Nakagami imaging to various types of tissues. The performance of the real-time Nakagami imaging system in visualizing RFA-induced ablation zones was validated by measuring porcine liver (n = 18) and muscle tissues (n = 6). The experimental results showed that the proposed algorithm can operate on a standard clinical ultrasound scanner to monitor RFA in real time. The Nakagami imaging system effectively monitors RFA-induced ablation zones in liver tissues. However, because tissue properties differ, the system cannot visualize ablation zones in muscle fibers. In the future, real-time Nakagami imaging should be focused on the RFA of the liver and is suggested as an alternative monitoring tool when advanced elastography is unavailable or substantial bubbles exist in the ablation zone.

A survey of ultrasound elastography approaches to percutaneous ablation monitoring.

Percutaneous thermal ablation has been widely used as a minimally invasive treatment for tumors. Treatment monitoring is essential for preventing complications while ensuring treatment efficacy. Mechanical testing measurements on tissue reveal that tissue stiffness increases with temperature and ablation duration. Different types of imaging methods can be used to monitor ablation procedures, including temperature or thermal strain imaging, strain imaging, modulus imaging, and shear modulus imaging. Ultrasound elastography demonstrates the potential to become the primary imaging modality for monitoring percutaneous ablation. This review briefly presented the state-of-the-art ultrasound elastography approaches for monitoring radiofrequency ablation and microwave ablation. These techniques were divided into four groups: quasi-static elastography, acoustic radiation force elastography, sonoelastography, and applicator motion elastography. Their advantages and limitations were compared and discussed. Future developments were proposed with respect to heat-induced bubbles, tissue inhomogeneities, respiratory motion, three-dimensional monitoring, multi-parametric monitoring, real-time monitoring, experimental data center for percutaneous ablation, and microwave ablation monitoring.

Optical coherence tomography: a new strategy to image planarian regeneration.

The planarian is widely used as a model for studying tissue regeneration. In this study, we used optical coherence tomography (OCT) for the real-time, high-resolution imaging of planarian tissue regeneration. Five planaria were sliced transversely to produce 5 head and 5 tail fragments. During a 2-week regeneration period, OCT images of the planaria were acquired to analyze the signal attenuation rates, intensity ratios, and image texture features (including contrast, correlation, homogeneity, energy, and entropy) to compare the primitive and regenerated tissues. In the head and tail fragments, the signal attenuation rates of the regenerated fragments decreased from -0.2 dB/µm to -0.05 dB/µm, between Day 1 and Day 6, and then increased to -0.2 dB/µm on Day 14. The intensity ratios decreased to approximately 0.8 on Day 6, and increased to between 0.8 and 0.9 on Day 14. The texture parameters of contrast, correlation, and homogeneity exhibited trends similar to the signal attenuation rates and intensity ratios during the planarian regeneration. The proposed OCT parameters might provide biological information regarding cell apoptosis and the formation of a mass of new cells during planarian regeneration. Therefore, OCT imaging is a potentially effective method for planarian studies.

Considering angle selection when using ultrasound electrode displacement elastography to evaluate radiofrequency ablation of tissues.

Percutaneous radiofrequency ablation (RFA) is a minimally invasive treatment to thermally destroy tumors. Ultrasound-based electrode-displacement elastography is an emerging technique for evaluating the region of RFA-induced lesions. The angle between the imaging probe and the RFA electrode can influence electrode-displacement elastography when visualizing the ablation zone. We explored the angle effect on electrode-displacement elastography to measure the ablation zone. Phantoms embedded with meatballs were fabricated and then ablated using an RFA system to simulate RFA-induced lesions. For each phantom, a commercial ultrasound scanner with a 7.5 MHz linear probe was used to acquire raw image data at different angles, ranging from 30° to 90° at increments of 10°, to construct electrode-displacement images and facilitate comparisons with tissue section images. The results revealed that the ablation regions detected using electrode-displacement elastography were highly correlated with those from tissue section images when the angle was between 30° and 60°. However, the boundaries of lesions were difficult to distinguish, when the angle was larger than 60°. The experimental findings suggest that angle selection should be considered to achieve reliable electrode-displacement elastography to describe ablation zones.

Monitoring radiofrequency ablation with ultrasound Nakagami imaging.

PURPOSE: Radiofrequency ablation (RFA) is a widely used alternative modality in the treatment of liver tumors. Ultrasound B-mode imaging is an important tool to guide the insertion of the RFA electrode into the tissue. However, it is difficult to visualize the ablation zone because RFA induces the shadow effect in a B-scan. Based on the randomness of ultrasonic backscattering, this study proposes ultrasound Nakagami imaging, which is a well-established method for backscattered statistics analysis, as an approach to complement the conventional B-scan for evaluating the ablation region. METHODS: Porcine liver samples (n = 6) were ablated using a RFA system and monitored by employing an ultrasound scanner equipped with a 7.5 MHz linear array transducer. During the stages of ablation (0-12 min) and postablation (12-24 min), the raw backscattered data were acquired at a sampling rate of 30 MHz for B-mode, Nakagami imaging, and polynomial approximation of Nakagami imaging. The contrast-to-noise ratio (CNR) was also calculated to compare the image contrasts of the B-mode and Nakagami images. RESULTS: The results demonstrated that the Nakagami image has the ability to visualize changes in the backscattered statistics in the ablation zone, including the shadow region during RFA. The average Nakagami parameter increased from 0.2 to 0.6 in the ablation stage, and then decreased to approximately 0.3 at the end of the postablation stage. Moreover, the CNR of the Nakagami image was threefold that of the B-mode image, showing that the Nakagami image has a better image contrast for monitoring RFA. Specifically, the use of the polynomial approximation equips the Nakagami image with an enhanced ability to estimate the range of the ablation region. CONCLUSIONS: This study demonstrated that ultrasound Nakagami imaging based on the analysis of backscattered statistics has the ability to visualize the RFA-induced ablation zone, even if the shadow effect exists in the B-scan.