Multivariable Quantitative US Parameters for Assessing Hepatic Steatosis.

Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.

Liver stiffness does not affect ultrasound-guided attenuation coefficient measurement in the evaluation of hepatic steatosis.

AIM: Recently, a new method has been developed to diagnose hepatic steatosis with attenuation coefficients based on the ultrasound-guided attenuation parameter (UGAP). We investigated whether fibrosis identified by hepatic stiffness measurements based on magnetic resonance elastography (MRE) affects attenuation coefficient measurement using UGAP for the evaluation of hepatic steatosis. METHODS: A total of 608 patients with chronic liver disease were analyzed. Correlations between magnetic resonance imaging-determined proton density fat fraction (PDFF) or MRE value and attenuation coefficients were evaluated. In addition, the interaction between hepatic fibrosis and the attenuation coefficient was analyzed. RESULTS: The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.724, indicating a strong relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.187, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were < 0.001, 0.277, and 0.903, respectively. In patients with non-alcoholic fatty liver disease (n = 169), the r between PDFF values and attenuation coefficient values was 0.695, indicating a moderate relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.068, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were <0.001, 0.948, and 0.706, respectively. CONCLUSION: UGAP-determined attenuation coefficient was weakly affected by liver stiffness, an indicator of hepatic fibrosis.

Utility of Attenuation Coefficient Measurement Using an Ultrasound-Guided Attenuation Parameter for Evaluation of Hepatic Steatosis: Comparison With MRI-Determined Proton Density Fat Fraction.

OBJECTIVE: Recently, a new method was developed to diagnose hepatic steatosis by measuring attenuation coefficients that are based on the ultrasound-guided attenuation parameter (UGAP). We investigated the diagnostic ability of these coefficients to detect steatosis that was identified using the proton density fat fraction (PDFF) on MRI in patients with chronic liver disease. MATERIALS AND METHODS: A total of 126 patients with chronic liver disease (non-hepatitis B, non-hepatitis C) were analyzed. The diagnostic ability of UGAP-determined attenuation coefficients was evaluated using ROC curve analysis, and the correlation between MRI-determined PDFF values and attenuation coefficient values was determined. RESULTS: The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.746 (95% CI, 0.657-0.815) (p < 0.001), corresponding to a strong relationship. The diagnostic ability of attenuation coefficients for steatosis grades ≥ 1, ≥ 2, and 3 as determined by PDFF were 0.922 (95% CI, 0.870-0.973), 0.874 (95% CI, 0.814-0.934), and 0.892 (95% CI, 0.835-0.949), respectively. The r between PDFF values and attenuation coefficient values was 0.559 (95% CI, 0.391-0.705) (p < 0.001) in patients with mild or no steatosis (grade ≤ 1). In addition, the r between PDFF values and attenuation coefficient values was 0.773 (95% CI, 0.657-0.853) (p < 0.001) in obese patients (body mass index [weight in kilograms divided by the square of height in meters] ≥ 25). The diagnostic ability of attenuation coefficients for patients with steatosis grades ≥ 1, ≥ 2, and 3 as determined by PDFF were 0.884 (95% CI, 0.792-0.976), 0.863 (95% CI, 0.778-0.947), and 0.889 (95% CI, 0.813-0.965), respectively. CONCLUSION: UGAP-determined attenuation coefficient values had a good diagnostic ability to detect hepatic steatosis.

Conformational Change Observed in the Active Site of Class C ß-Lactamase MOX-1 upon Binding to Aztreonam.

We solved the crystal structure of the class C ß-lactamase MOX-1 complexed with the inhibitor aztreonam at 1.9Å resolution. The main-chain oxygen of Ser315 interacts with the amide nitrogen of aztreonam. Surprisingly, compared to that in the structure of free MOX-1, this main-chain carboxyl changes its position significantly upon binding to aztreonam. This result indicates that the interaction between MOX-1 and ß-lactams can be accompanied by conformational changes in the B3 ß-strand main chain.

Crystal structure of Mox-1, a unique plasmid-mediated class C ß-lactamase with hydrolytic activity towards moxalactam.

Mox-1 is a unique plasmid-mediated class C ß-lactamase that hydrolyzes penicillins, cephalothin, and the expanded-spectrum cephalosporins cefepime and moxalactam. In order to understand the unique substrate profile of this enzyme, we determined the X-ray crystallographic structure of Mox-1 ß-lactamase at a 1.5-Å resolution. The overall structure of Mox-1 ß-lactamase resembles that of other AmpC enzymes, with some notable exceptions. First, comparison with other enzymes whose structures have been solved reveals significant differences in the composition of amino acids that make up the hydrogen-bonding network and the position of structural elements in the substrate-binding cavity. Second, the main-chain electron density is not observed in two regions, one containing amino acid residues 214 to 216 positioned in the Ω loop and the other in the N terminus of the B3 ß-strand corresponding to amino acid residues 303 to 306. The last two observations suggest that there is significant structural flexibility of these regions, a property which may impact the recognition and binding of substrates in Mox-1. These important differences allow us to propose that the binding of moxalactam in Mox-1 is facilitated by the avoidance of steric clashes, indicating that a substrate-induced conformational change underlies the basis of the hydrolytic profile of Mox-1 ß-lactamase.

Attenuation Coefficient Measurement Using a High-Frequency (2-9 MHz) Convex Transducer for Children Including Fatty Liver.

We evaluated the measurement feasibility and diagnostic ability of an ultrasound-guided attenuation parameter (UGAP) using a high-frequency convex transducer in children. This retrospective study included all consecutive children who underwent abdomen ultrasonography from July to December 2020. Attenuation coefficients (ACs) of the liver were measured using both 1- to 6-MHz (AC1-6) and 2- to 9-MHz (AC2-9) probes of the LOGIQ E10 system (GE Healthcare). t-Tests and Pearson's or partial correlation analyses were performed, and AC cutoff values for diagnosing fatty liver were obtained from receiver operating characteristic curve analyses. Finally, 118 patients (M:F = 83:35, mean age: 10.2 ± 4.1 y) were evaluated, and the measurement success rate was 98.3% (116/118) for AC2-9. AC1-6 was available in children with a liver depth greater than 9 cm. The ratio of interquartile range to median of the AC2-9 was lower than that of the AC1-6 (4.3 vs. 8.5, p < 0.001). In the normal group (n = 41), the AC2-9 values were not associated with age, sex or body mass index. For the evaluation of steatosis, the AC2-9 values exhibited a positive correlation with the MR fat fraction (coefficient = 0.498, p < 0.001). The cutoff value of 0.699 dB/cm/MHz had 90.2% sensitivity and 100% specificity for diagnosing fatty liver. In conclusion, measurements of ACs using a high-frequency convex transducer are feasible even in small children, with lower measurement variability. The AC2-9 values also had good diagnostic performance for pediatric fatty liver.

Two-dimensional shear wave elastography and ultrasound-guided attenuation parameter for progressive non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: We investigated the usefulness of combining two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter for assessing the risk of progressive non-alcoholic steatohepatitis, defined as non-alcoholic steatohepatitis with a non-alcoholic fatty liver disease activity score of ≥4 and a fibrosis stage of ≥2. METHODS: This prospective study included 202 patients with non-alcoholic fatty liver disease who underwent two-dimensional shear wave elastography, ultrasound-guided attenuation parameter, vibration-controlled transient elastography, the controlled attenuation parameter, and liver biopsy on the same day. Patients were grouped according to liver stiffness measurement using two-dimensional shear wave elastography and the attenuation coefficient, assessed using the ultrasound-guided attenuation parameter: A, low liver stiffness measurement/low attenuation coefficient; B, low liver stiffness measurement/high attenuation coefficient; C, high liver stiffness measurement/low attenuation coefficient; and D, high liver stiffness measurement/high attenuation coefficient. RESULTS: Two-dimensional shear wave elastography and vibration-controlled transient elastography had equivalent diagnostic performance for fibrosis. The areas under the curve of the ultrasound-guided attenuation parameter for identifying steatosis grades ≥S1, ≥S2, and S3 were 0.89, 0.91, and 0.92, respectively, which were significantly better than those of the controlled attenuation parameter (P<0.05). The percentages of progressive non-alcoholic steatohepatitis in Groups A, B, C, and D were 0.0%, 7.7%, 35.7%, and 50.0%, respectively (P<0.001). The prediction model was established as logit (p) = 0.5414 × liver stiffness measurement (kPa) + 7.791 × attenuation coefficient (dB/cm/MHz)-8.401, with area under the receiver operating characteristic curve, sensitivity, and specificity values of 0.832, 80.9%, and 74.6%, respectively; there was no significant difference from the FibroScan-aspartate aminotransferase score. CONCLUSION: Combined assessment by two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter is useful for risk stratification of progressive non-alcoholic steatohepatitis and may be convenient for evaluating the necessity of specialist referral and liver biopsy.

A New Method to Quantify Concentration of Microbubbles in Attenuating Media Using Bubble Destruction Curve Analysis of the Contrast-Enhanced Ultrasound.

It is known that the microbubbles of Sonazoid are accumulated in the liver parenchyma due to the phagocytosis of Kupffer cells in the sinusoid. Because this phagocytic function decreases due to the progression of fibrosis in chronic liver disease, the deterioration of the liver function may be quantified by measuring the concentration of the accumulated Sonazoid microbubbles. In this article, a new method to quantify the concentration of microbubbles accumulated in attenuating media is proposed. This method utilizes the contrast-enhanced imaging with high mechanical index, measures the depth of the bubble destruction for each frame and analyze the shape of the destruction curve to estimate the concentration of the bubbles. A phantom experiment was performed with various concentrations of the contrast agent Sonazoid solution as well as various attenuation coefficients of the viscous media. Because of the theoretical model proposed, the estimated attenuation indexes, related to the concentration of Sonazoid microbubbles, were independent of the background attenuation of the propagating medium. The result suggest it has a potential to quantify Sonazoid concentration in the liver parenchyma more precisely against different liver attenuation conditions.

The B-Mode Image-Guided Ultrasound Attenuation Parameter Accurately Detects Hepatic Steatosis in Chronic Liver Disease.

The purpose of our study was to evaluate the diagnostic accuracy of the ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in comparison with the controlled attenuation parameter (CAP), using histopathology as the reference standard. We prospectively analyzed 163 consecutive chronic liver disease patients who underwent UGAP, CAP, computed tomography and a liver biopsy on the same day between April 2016 and July 2017. Radiofrequency signals corresponding to the images were compensated by the reference signal previously measured from the uniform phantom with known attenuation (0.44 dB/cm/MHz). The attenuation coefficient was calculated from the signals' decay slope. The median attenuation coefficient values in patients with S0 (n = 62), S1 (n = 63), S2 (n = 23) and S3 grade (n = 15) were 0.485, 0.560, 0.660 and 0.720, respectively. Significant correlations were found between attenuation coefficient and percentage steatosis, CAP values and liver-to-spleen computed tomography attenuation ratio (p < 0.001). The areas under the receiver operating characteristic curve of UGAP for identifying ≥S1, ≥S2 and ≥S3 were 0.900, 0.953 and 0.959, respectively, which were significantly better than the results obtained with CAP for identifying ≥S2 and ≥S3. In conclusion, UGAP had high diagnostic accuracy for detecting hepatic steatosis in patients with chronic liver disease.