Influence of dispersion slope on the diagnosis of liver fibrosis by the shear wave in metabolic dysfunction-associated steatotic liver disease.

AIM: Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut-off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings. METHODS: Patients (n = 159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut-off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut-off values between the two groups were calculated. RESULTS: Fibrosis stage cut-off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut-off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut-off value for both groups was 13.2 m/s/kHz. CONCLUSIONS: Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS > 13.2 m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.

Clinical significance of dispersion imaging by shear wave elastography in the treatment and diagnosis of pancreatic cancer.

BACKGROUND AND AIM: Recently, dispersion imaging by shear wave elastography has been developed to visualize a tissue viscosity-related factor by measuring the dispersion slope. However, clinical significance of dispersion imaging in the field of pancreatic cancer is unknown. This study aimed to investigate the clinical significance of dispersion imaging in the treatment and diagnosis of pancreatic cancer. METHODS: We measured shear wave dispersion slope (SWD) (m/s/kHz) and shear wave elasticity (SWE) (kPa) in patients with pancreatic ductal adenocarcinoma (PDA). The primary endpoint was the relationship between the changes in SWD and SWE values before and after chemotherapy and the response to chemotherapy. Secondary endpoints included SWD and SWE values in relation to differences between PDA and non-PDA sites and histopathological scores of stroma, inflammation, fibrosis, and necrosis in endoscopic ultrasound-guided fine-needle aspiration specimens. RESULTS: Fifty-six patients were included, 30 of whom underwent chemotherapy. There was no relationship between the changes of SWD and SWE values and chemotherapy responses. In 56 patients, the median SWD value was 12.20 m/s/kHz (interquartile range [IQR]: 10.88-13.61) at PDA sites and 13.57 m/s/kHz (IQR: 12.28-16.20) at non-PDA sites (P = 0.005). The median SWE value was 8.18 kPa (IQR: 7.00-9.74) at PDA sites and 6.14 kPa (IQR: 5.40-6.77) at non-PDA sites (P < 0.001). Histopathological evaluation revealed that inflammation scores were correlated with SWD values (rs  = 0.42, P < 0.001). CONCLUSIONS: Dispersion imaging in pancreatic cancer would be useful for diagnosis and assessing inflammation.

Associations Between Multiparametric US-Based Indicators and Pathological Status in Patients with Metabolic Associated Fatty Liver Disease.

OBJECTIVE: Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) using ultrasonography holds significant clinical value. The associations between ultrasound (US)-based parameters and the pathological spectra remain unclear and controversial. This study aims to investigate the associations thoroughly. METHODS: The participants with MAFLD undergoing liver biopsy and multiparametric ultrasonography were prospectively recruited from December 2020 to September 2022. Three US-based parameters, namely attenuation coefficient (AC), liver stiffness (LS) and dispersion slope (DS) were obtained. The relationship between these parameters and steatosis grades, inflammation grades and fibrosis stages was examined. RESULTS: In this study with 116 participants, AC values significantly differed across distinct steatosis grades (p < 0.001), while DS and LS values varied among inflammation grades (p < 0.001) and fibrosis stages (p < 0.001). The area under the receiver operating characteristic curves (AUCs) of AC ranged from 0.82 to 0.84 for differentiating steatosis grades, while AUCs of LS ranged from 0.62 to 0.76 for distinguishing inflammation grades and 0.83-0.95 for discerning fibrosis stages. AUCs for DS ranged from 0.79 to 0.81 in discriminating inflammation grades and 0.80-0.88 for differentiating fibrosis stages. Subgroup analysis revealed that LS demonstrated different trends in inflammation grade but consistent trends in fibrosis stage across subgroups, whereas DS showed consistent trends for both inflammation grade and fibrosis stage across all subgroups. CONCLUSION: AC values indicate the degree of hepatic steatosis but not inflammation or fibrosis. LS values are determined only by fibrosis stage and are not associated with inflammation grades. DS values are associated with both fibrosis and inflammation grades.

Influence of Measurement Depth and Acquisition Parameters on Shear Wave Speed and Shear Wave Dispersion in Certified Phantoms Using a Canon Aplio Clinical Ultrasound Scanner.

OBJECTIVE: The aim of the work described here was to investigate the relative contribution of confounding factors on liver shear wave speed (SWS) and shear wave dispersion slope (SWDS) measurements in three certified phantoms using a Canon Aplio clinical ultrasound scanner. METHODS: A Canon Aplio i800 i-series ultrasound system (Canon Medical Systems Corporation, Otawara, Tochigi, Japan) with i8CX1 convex array (center frequency = 4 MHz) was used to examine dependencies caused by the depth, width and height of the acquisition box (AQB), the depth and size of the region of interest (ROI), the AQB angle and the pressure of the ultrasound probe on the surface of the phantom. RESULTS: Results revealed that depth is the most significant confounder in both SWS and SWDS measurements. AQB angle, height and width and ROI size exhibited minimal confounding effects on measurements. For SWS, the most consistent measurement depth is when the top of the AQB is placed between 2 and 4 cm, and the ROI is located between 3 and 7 cm deep. For SWDS, results indicate that measurement values significantly decrease with depth from the surface of the phantom until approximately 7 cm deep, and consequently no stable area of AQB placement or ROI depth exists. CONCLUSION: In contrast to SWS, the same ideal acquisition depth range cannot necessarily be applied to SWDS measurements because of a significant depth dependency.

Shear Wave Dispersion Slope Measured with Shear Wave Dispersion Imaging Is Associated with Variceal Hemorrhage in Cirrhotic Patients.

Background and Objectives: Portal hypertension (PH), as the main consequence of cirrhosis, leads to the development of gastroesophageal varices (GEVs). Variceal hemorrhage (VH) caused by the rupture of GEVs is a life-threatening emergency. Thus, the prediction of VH risk is considerably important. Our pilot study aimed to identify the risk factors of variceal hemorrhage (VH) in cirrhosis. Materials and Methods: Cirrhotic patients were prospectively included and divided into two groups according to the presence or absence of VH. Conventional ultrasound and shear wave dispersion (SWD) imaging were conducted to detect the portal vein diameter, spleen diameter, ascites, liver stiffness (LS) and shear wave dispersion slope (SWDS). The laboratory tests were recorded, including platelets (PLT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin (ALB). The risk factors of VH were screened using univariate analyses and identified using multivariate logistic regression. The ROC curves were used to assess diagnostic accuracy. Comparisons between AUCs were performed using the Delong method. Results: Sixty-five patients with 22 VHs were finally included. The SWDS, spleen diameter and ascites were identified as independent risk factors for VH. The SWDS showed good performance for diagnosing VH (AUC = 0.768, 95% CI: 0.647−0.864), and sensitively identified 95.5% (95% CI: 77.2%−99.9%) of patients with VH. Including the three risk factors in multivariate logistic regression, we obtained a formula for diagnosing VH: −20.749 + 0.804 × SWDS + 0.449 × spleen diameter + 1.803 × ascites (no ascites = 0, ascites = 1). Comparison of AUCs revealed that the formula (AUC = 0.900, 95% CI: 0.800−0.961) performed better than LS, SWDS, and spleen diameter in diagnosing VH (p < 0.001; p < 0.05; p < 0.05). Conclusions: SWDS is a sensitive parameter for assessing the risk of VH. Combining the SWDS, spleen diameter and ascites resulted in good diagnostic accuracy.

Viscoelasticity assessment for in vivo quantification of muscle contusion injury in rats using shear wave elastography.

The aim of the study described here was to investigate the role of viscoelasticity in assessing muscle fibrosis and inflammation in a rat model of contusion using quantitative shear wave elastography (SWE). Unilateral gastrocnemius muscle contusion was induced in 32 male rats using an impactor apparatus. The contralateral muscles served as the control group. SWE was applied to the control group and rats 1, 3, 14 and 21 d after successful modeling (each time point group, n = 8). Histologic features were used as reference standards. The degree of fibrosis was moderately correlated with shear wave speed (r = 0.53), whereas the degree of inflammation was well correlated with shear wave dispersion (SWD) slope (r = 0.74). The area under the receiver operating characteristic curve (AUC) for the dispersion slope for muscle inflammation and fibrosis assessment was 0.87 (95% confidence interval: 0.705-0.963), which exceeded that of the shear wave speed (0.68, 95% confidence interval: 0.494-0.834). The larger decline in dispersion slope in the fibrotic stage than in the inflammation stage (1-d group vs. 14-d group or 21-d group, p < 0.05) indicated better predictive performance than the shear wave speed.

Efficacy of shear wave dispersion imaging for viscoelastic assessment of the liver in acute graft-versus-host disease rats.

Background: To investigate the feasibility of using shear wave dispersion (SWD) imaging to evaluate hepatic acute graft-versus-host disease (aGVHD) in a rat model. Methods: To establish an aGVHD model, 30 Wistar rats were subjected to bone marrow transplantation, 10 Fischer 344 rats were used as donors, and 6 Wistar rats were used as the control group. Each week, 6 rats were randomly chosen and divided into groups of 1 week (1 w) to 5 weeks (5 w). For each subgroup, the rats received a clinical index assessment and shear wave dispersion (SWD) examination with 2 quantitative values, shear wave (SW) speed and SWD slope. The histological characteristics were then used as the reference standard to divide the rats into the aGVHD group and the no aGVHD (nGVHD) group. Results: In the 2 weeks (2 w) group, only SWD slope [median: 7.26, interquartile range (IQR): 7.04 to 7.31] showed a significant increase in the measured value (P<0.05). The value of the 3 weeks (3 w) group (median: 7.88, IQR: 7.84 to 8.49) significantly increased compared with the 2 w value (P<0.05). Although the value increased gradually from week 3 to week 5, it had no statistical significance (P>0.05). The SW speed [mean ± standard deviation (SD): 1.54±0.11, 95% confidence interval (CI): 1.48 to 1.59] and SWD slope (mean ± SD: 8.29±0.56, 95% CI: 7.99 to 8.59) of the aGVHD group were higher than those of the control group and the nGVHD group (P<0.001). The correlation of SWD slope with pathological grade was the highest (r=0.798, P<0.01), followed by SW speed (r=0.785, P<0.01), and the correlation of clinical index with pathological grade was the lowest (r=0.751, P<0.01). In addition, the area under the receiver operating characteristic (ROC) curve (AUC) value of aGVHD using the SWD slope was 0.844 (95% CI: 0.67 to 0.95, sensitivity: 93.75%, specificity: 78.57%), which was higher than the AUC of both SW speed and clinical index, and the difference was statistically significant compared to the AUC of the clinical index. Conclusions: The SWD slope could show significant abnormalities earlier than SW speed and clinical index and is also more consistent with the change in aGVHD severity level. The SWD slope may help in detecting hepatic aGVHD during ultrasound SWD examination.

Stratifying Non-alcoholic Steatohepatitis With the Non-invasive Ultrasound Markers Shear Wave Dispersion Slope and Shear Wave Velocity: An Animal Study.

We evaluated the significance of the ultrasound (US) markers shear wave dispersion slope (SWDS) and shear wave velocity (SWV) for identification of non-alcoholic steatohepatitis (NASH) and high-risk NASH; the latter was defined as the presence of steatohepatitis, a non-alcoholic fatty liver disease activity score (NAS) ≥4 or a fibrosis stage ≥2. Thirty-six male Sprague-Dawley (SD) rats were assigned to two groups: the study (n = 30) and control (n = 6) groups. To initiate non-alcoholic steatohepatitis, study group rats were fed a diet deficient in methionine and choline. All rats were examined using ultrasonography to obtain the SWDS and SWV parameters of the liver at the same time points. Fatty liver pathological grades were determined after euthanasia; the livers were categorized in the normal (n = 6), NAFL (non-alcoholic fatty liver) (n = 10) and NASH (n = 20) subgroups based on the NAS scoring system. They were also categorized into subgroups F0 (n = 22), F1 (n = 3), F2 (n = 7) and F3 (n = 4) on the basis of the METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) scoring system. Measurement differences between various grades were evaluated by analysis of variance (ANOVA) or the Mann-Whitney U-test. We used logistic regression to calculate a combination of the two parameters for combined assessment of parameters. The diagnostic value of SWDS, SWV and the two-variable model was determined by receiver operating characteristic (ROC) curve analysis. This analysis revealed stepwise increases in SWDS and SWV with increasing NAFLD severity. The accuracy of SWDS in diagnosing NASH was good (area under the ROC curve [AUC]: 0.88) and was superior to that of SWV (AUC: 0.76). The combination of SWV and SWDS exhibited higher performance (AUC: 0.90). SWV was higher than SWDS in participants with a fibrosis grade ≥2 (high-risk NASH). For identification of high-risk NASH, SWV exhibited the best diagnostic performance (AUC: 0.89), which was equivalent to that of the two-variable model (AUC: 0.88) and slightly higher than that of SWDS (AUC: 0.85). This study indicates that of the US-based markers, SWDS outperforms SWV in identifying NASH in rats and that combining the two markers may increase their clinical utility in guiding NAFLD and NASH treatment.

Elucidation of spleen elasticity and viscosity in a carbon tetrachloride rat model of liver cirrhosis using a new ultrasound elastography.

PURPOSE: Measurement of spleen stiffness (SS) using ultrasound (US) elastography is useful for predicting portal hypertension. However, the mechanism leading to increased SS remains unclear. We jointly developed a new US elastography system (Aplio i-series, Canon Medical Systems) that can easily measure organ viscosity (dispersion slope: DS). We analyzed the cause of increased SS by calculating the shear wave speed (SWs, which reflects fibrosis) and DS of the spleen in carbon tetrachloride (CCL4) rat liver cirrhosis models. METHODS: A total of 13 Sprague-Dawley rats were randomly divided into four groups (C group: 3 rats as control, 2D group: 3 rats injected with CCL4 twice in 1 week, 4D group: 4 rats injected 4 times in 1 week, 6W group: 3 rats injected twice a week for 6 weeks). The SWs and the DS of each group were calculated, and histopathological analysis was performed. RESULTS: The spleen SWs of the 6W group was significantly higher than that of the C group (p = 0.044). The spleen DS did not change after CCL4. The liver SWs of the 4D and 6W groups was significantly higher than that of the C group (p = 0.012 and 0.007, respectively) with fibrosis change on histopathology, and the DS of the 4D group was significantly higher than that of the C group (p = 0.033). Splenic fibrosis was confirmed in the 6W group, but inflammation and necrosis were not seen. CONCLUSION: SS increased due to fibrosis and can be predicted based on SWs and DS values.

Efficacy of shear wave elastography for assessment of liver function in patients with heart failure.

AIMS: Liver dysfunction is important for prognosis in heart failure (HF). Shear wave elastography (SWE), which is a novel ultrasound technique for charactering tissues, has been used in liver diseases. However, clinical implication of SWE, including dispersion slope, remains unknown in heart diseases. This study aimed to evaluate the efficacy of SWE assessing liver function in the severity of HF. METHODS AND RESULTS: We enrolled 316 consecutive patients with or suspected heart diseases, who were classified according to the American College of Cardiology Foundation/American Heart Association stage of HF, including 37 with Stage A, 139 with Stage B, 114 with Stage C, and 26 with Stage D, and 45 normal subjects. Elasticity and dispersion slope of shear wave were assessed according to the HF stage. Elasticity and dispersion slope were not elevated in normal subjects and patients with Stage A. Elasticity was slightly increased from Stage A to Stage C and was remarkably elevated in Stage D (normal: 5.2 ± 1.1 kPa, Stage A: 5.4 ± 1.2 kPa, Stage B: 6.4 ± 1.8 kPa, Stage C: 7.8 ± 3.5 kPa, and Stage D: 17.7 ± 12.7 kPa), whereas dispersion slope was gradually increased from Stage A to Stage D (normal: 9.7 ± 1.7m/s/kHz, Stage A: 10.4 ± 1.6m/s/kHz, Stage B: 11.7 ± 2.4m/s/kHz, Stage C: 13.2 ± 3.4m/s/kHz, and Stage D: 17.6 ± 5.6 m/s/kHz). In the early HF stage, dispersion slope was elevated. In the advanced HF stage, both elasticity and dispersion slope were elevated. Liver function test abnormalities were observed only from Stage C or Stage D. CONCLUSIONS: Dispersion slope could detect early liver damage, and the combination of elasticity and dispersion slope could clarify the progression of liver dysfunction in HF. SWE may be valuable to manage therapeutic strategies in patients with HF.

Accurate Measurements of the Zero-Dispersion Wavelength in Optical Fibers.

We have developed a frequency-domain phase shift system for measuring the zero-dispersion wavelength and the dispersion slope of single-mode optical fibers. A differential phase shift method and nonlinear four-wave mixing technique were also investigated. The frequency-domain phase shift method is used to produce Standard Reference Materials that have their zero-dispersion wavelengths characterized with an expanded uncertainty (k = 2) of ± 0.060 nm.