Noninvasive Staging of Hepatic Steatosis Using Calibrated 2D US with Liver Biopsy as the Reference Standard.

Background Accumulation of lipid in the liver (ie, hepatic steatosis) is the basis of nonalcoholic fatty liver disease (NAFLD). Asymptomatic steatosis can lead to nonalcoholic steatohepatitis and downstream complications. Purpose To assess the diagnostic performance of calibrated US (CAUS) as a method for detection and staging of hepatic steatosis in comparison with liver biopsy. Materials and Methods Two-dimensional US images in 223 consecutive patients who underwent US-guided liver biopsy from May 2012 to February 2016 were retrospectively analyzed by two observers using CAUS. CAUS semiautomatically estimates echo-level and texture parameters, with particular interest in the residual attenuation coefficient (RAC), which is the remaining steatosis-driven attenuation obtained after correction of the beam profile. Data were correlated with patient characteristics and histologically determined steatosis grades and fibrosis stages. The data were equally divided into training and test sets to independently train and test logistic regression models for detection (>5% fat) and staging (>33% and >66% fat) of hepatic steatosis by using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 195 patients (mean age, 50 years ± 13 [SD]; 110 men) were included and divided into a training set (n = 97 [50%]) and a test set (n = 98 [50%]). The average CAUS interobserver correlation coefficient was 0.95 (R range, 0.87-0.99). The best correlation with steatosis was found for the RAC parameter (R = 0.78, P < .01), while no correlation was found for fibrosis (R = 0.14, P = .054). Steatosis detection using RAC showed an AUC of 0.97 (95% CI: 0.94, 1.00), and the multivariable AUC was found to be 0.97 (95% CI: 0.95, 1.00). The predictive performance for moderate and severe hepatic steatosis using RAC was 0.93 (95% CI: 0.88, 0.98) and 0.93 (95% CI: 0.87, 0.98), respectively. Conclusion The calibrated US parameter residual attenuation coefficient detects and stages steatosis accurately with limited interobserver variability, and performance is not hampered by the presence of fibrosis. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Grant in this issue.

Transcutaneous vs. intraoperative quantitative ultrasound for staging bovine hepatic steatosis.

The aim of this study was to test the hypothesis that quantitative analysis of transcutaneous (Transc) ultrasound (US) images can predict the liver fat content with similar accuracy and precision as using intraoperative (Intraop) US. The second goal was to investigate if a tissue mimicking phantom (TMP) might be used as reference for automatic gain compensation (AGC) vs. depth instead of using the data of a set of cows without hepatic alterations. A study was performed in post partum dairy cows (N = 151), as an animal model of human nonalcoholic fatty liver disease (NAFLD), to test these hypotheses. Five Transc and five Intraop US liver images were acquired in each animal and a liver biopsy was taken. In liver tissue samples, triacylglycerol (TAG) content was measured by biochemical analysis and hepatic alterations, other than hepatic steatosis, were excluded by clinical examination. Several preprocessing steps were performed before the ultrasound tissue characteristics (UTC) parameters of B-mode images were derived. Stepwise multiple linear regression analysis was performed on a training set (N = 76) and the results were used on the test group (N = 75) to predict the TAG content in the liver. In all cases, the residual attenuation coefficient (ResAtt) was the only selected parameter. Receiver operating characteristics (ROC) analysis was applied to assess the performance and area under the curve (AUC) of predicting TAG and to compare the sensitivity and specificity of the methods used. High ROC values for AUC (95%), sensitivity (87%) and specificity (83%) for both Intraop and Transc applications with control group as well as with phantom-based AGC were obtained. Consequently, it can be concluded that Transc results are equivalent to Intraop results. Furthermore, equivalent ROC values, when using TMP AGC, indicates the potential use of TMP-based corrections instead of normal group-based corrections. The high predictive values indicate that noninvasive quantitative US has a great potential for staging and screening on hepatic steatosis in cows.

Ultrasound image analysis offers the opportunity to predict plasma progesterone concentrations in the estrous cycle in cows: a feasibility study.

In recent years, several attempts have been made to evaluate the activity of a corpus luteum by determining its sonographic echo texture. In all of these studies the values of the echo texture parameters depended on the type and settings of the ultrasound machine. Therefore, the aim of the study was to investigate if a quantitative analysis of ultrasound (US) images of the corpus luteum (CL) after calibration of the ultrasound machine enables the assessment of the peripheral plasma progesterone (P4) level. Ten Holstein Friesian cows were examined daily at Days 4 to 8, 10 to 16, and -5 to -1 (Day 1=ovulation) of the estrous cycle. B-mode sonography of the corpora lutea was performed and blood samples were taken for plasma P4 analysis. US images were calibrated and analyzed using a software package (CAUS) developed by the authors. In addition to the area of the CL (Total Area, TotA; Tissue Area interactive, TisAi; Tissue Area Automatic, TisAa), the following US parameters were calculated from the gray level histogram and from the size of the speckles: Mean, Standard Deviation (SD) and Signal-to-Noise Ratio (SNR=Mean/SD) of echo levels, Residual Attenuation (ResAtt), Axial and Lateral speckle size (Ax and Lat, respectively). The inter-individual variability of the P4 level was expressed by the coefficient of variability (CV), averaged over all days. It appeared that the CV of the absolute P4 was high (0.65) and the P4 relative to that at Day 4 and at Day 16 was of comparable magnitude. Correlations of US parameters with P4 were highest for the P4 relative to Day 16 (P4_rel_D16). This relative P4 measure was then used for further analysis. The correlations of P4_rel_D16 with TotA, TisAa (CL area after automatic segmentation of tissue) and ResAtt were found the highest (R=0.68, 0.74, and -0.42, respectively). Multiple linear regression analysis, incorporating all US parameters revealed the formula: P4_rel_D16(pred)=-0.315+0.225TisAa-0.023ResAtt, and a goodness of fit: R(2)=0.59 (p<0.001). This formula was then used to "predict" for each image the P4_rel_D16 from the estimated US parameters. A high correlation of the predicted with the measured P4_rel_D16 was found: R=0.77. Classification of images using the predicted P4_rel_D16 to be in the range >0.80 (corresponding to 0.95 times the average_P4_rel_D16 measured during the "static" phase of the luteal cycle) by ROC analysis was correctly made in 88% of cases. In conclusion the quantitative analysis of calibrated ultrasound images may yield a good prediction of cyclic changes of P4 levels and has potential for predicting the phase in the estrous cycle of a cow.

Correlation based 3-D segmentation of the left ventricle in pediatric echocardiographic images using radio-frequency data.

Clinical diagnosis of heart disease might be substantially supported by automated segmentation of the endocardial surface in three-dimensional (3-D) echographic images. Because of the poor echogenicity contrast between blood and myocardial tissue in some regions and the inherent speckle noise, automated analysis of these images is challenging. A priori knowledge on the shape of the heart cannot always be relied on, e.g., in children with congenital heart disease, segmentation should be based on the echo features solely. The objective of this study was to investigate the merit of using temporal cross-correlation of radio-frequency (RF) data for automated segmentation of 3-D echocardiographic images. Maximum temporal cross-correlation (MCC) values were determined locally from the RF-data using an iterative 3-D technique. MCC values as well as a combination of MCC values and adaptive filtered, demodulated RF-data were used as an additional, external force in a deformable model approach to segment the endocardial surface and were tested against manually segmented surfaces. Results on 3-D full volume images (Philips, iE33) of 10 healthy children demonstrate that MCC values derived from the RF signal yield a useful parameter to distinguish between blood and myocardium in regions with low echogenicity contrast and incorporation of MCC improves the segmentation results significantly. Further investigation of the MCC over the whole cardiac cycle is required to exploit the full benefit of it for automated segmentation.

Interactive vs. automatic ultrasound image segmentation methods for staging hepatic lipidosis.

The aim of this study was to test the hypothesis that automatic segmentation of vessels in ultrasound (US) images can produce similar or better results in grading fatty livers than interactive segmentation. A study was performed in postpartum dairy cows (N=151), as an animal model of human fatty liver disease, to test this hypothesis. Five transcutaneous and five intraoperative US liver images were acquired in each animal and a liverbiopsy was taken. In liver tissue samples, triacylglycerol (TAG) was measured by biochemical analysis and hepatic diseases other than hepatic lipidosis were excluded by histopathologic examination. Ultrasonic tissue characterization (UTC) parameters--Mean echo level, standard deviation (SD) of echo level, signal-to-noise ratio (SNR), residual attenuation coefficient (ResAtt) and axial and lateral speckle size--were derived using a computer-aided US (CAUS) protocol and software package. First, the liver tissue was interactively segmented by two observers. With increasing fat content, fewer hepatic vessels were visible in the ultrasound images and, therefore, a smaller proportion of the liver needed to be excluded from these images. Automatic-segmentation algorithms were implemented and it was investigated whether better results could be achieved than with the subjective and time-consuming interactive-segmentation procedure. The automatic-segmentation algorithms were based on both fixed and adaptive thresholding techniques in combination with a 'speckle'-shaped moving-window exclusion technique. All data were analyzed with and without postprocessing as contained in CAUS and with different automated-segmentation techniques. This enabled us to study the effect of the applied postprocessing steps on single and multiple linear regressions ofthe various UTC parameters with TAG. Improved correlations for all US parameters were found by using automatic-segmentation techniques. Stepwise multiple linear-regression formulas where derived and used to predict TAG level in the liver. Receiver-operating-characteristics (ROC) analysis was applied to assess the performance and area under the curve (AUC) of predicting TAG and to compare the sensitivity and specificity of the methods. Best speckle-size estimates and overall performance (R2 = 0.71, AUC = 0.94) were achieved by using an SNR-based adaptive automatic-segmentation method (used TAG threshold: 50 mg/g liver wet weight). Automatic segmentation is thus feasible and profitable.

Performance of two dimensional displacement and strain estimation techniques using a phased array transducer.

The goal of this study was to investigate the applicability of conventional 2-D displacement and strain imaging techniques to phased array radiofrequency (RF) data. Furthermore, the possible advantages of aligning and stretching techniques for the reduction of decorrelation artefacts was examined. Data from both realistic simulations and phantoms were used in this study. Recently, the used processing concepts were successfully applied to linear array data. However, their applicability to sector scan data is not trivial because of the polar grid. Homogeneous and inhomogeneous tissue phantoms were simulated at a range of strains (0 to 5%) using Field II((c)). The inhomogeneous phantom, a commonly used tumor/lesion model, was also constructed using gelatin/agar solutions. A coarse-to-fine displacement algorithm was applied, using aligning and stretching to enhance re-correlation. Vertical and horizontal strains were reconstructed from the axial and lateral displacements. Results revealed that the error on displacement estimates was lower when using 2-D data windows rather than 1-D windows. For regions at large depths and large insonification angles, the allowed lateral window size was limited. Still, 1-D windows resulted in larger errors. The re-correlation techniques resulted in a significant increase in the elastographic signal-to-noise ratio (SNRe) and elastographic contrast-to-noise ratio (CNRe) of the vertical and horizontal strain components. An increase of the SNRe of 5-20 dB was observed over a range of strains (0.5 to 5.0%). In the inhomogeneous phantom, a vertical SNRe of 27.7 dB and a horizontal SNRe of 16.7 dB were measured in the background. The vertical and horizontal CNRe were 35 dB and 23.1 dB, respectively. For the experimental data, lower SNRe (vertical: 19.1 dB; horizontal: 11.4 dB) and CNRe (vertical: 33.3 dB; horizontal: 12.5 dB) were found. In conclusion, 2-D window matching of sector scan data is feasible and outperforms 1-D window matching. Furthermore, the use of re-correlation techniques enhances both precision and contrast of strain images.

Performance evaluation of methods for two-dimensional displacement and strain estimation using ultrasound radio frequency data.

In elastography, several methods for 2-D strain imaging have been introduced, based on both raw frequency (RF) data and speckle-tracking. Although the precision and lesion detectability of axial strain imaging in terms of elastographic signal-to-noise ratio (SNRe) and elastographic contrast-to-noise ratio (CNRe) have been reported extensively, analysis of lateral precision is still lacking. In this paper, the performance of different 2-D correlation RF- and envelope-based strain estimation methods was evaluated using simulation data and phantom experiments. Besides window size and interpolation methods for subsample displacement estimation, the influence of recorrelation techniques was examined. Precision and contrast of the measured displacements and strains were assessed using the difference between modeled and measured displacements, SNRe and CNRe. In general, a 2-D coarse-to-fine displacement estimation method is favored, using envelope data for window sizes exceeding the theoretical upper bound for strain estimation. Using 2-D windows of RF data resulted in better displacement estimates for both the axial and lateral direction than 1-D RF-based or envelope-based techniques. Obtaining subsample lateral displacement estimates by fitting a predefined shape through the cross-correlation function (CCF) yielded results similar to those obtained with up-sampling of RF data in the lateral direction. Using a CCF model was favored because of the decreased computation time. Local aligning and stretching of the windows (recorrelation) resulted in an increase of 2-17 and 6-7 dB in SNRe for axial and lateral strain estimates, respectively, over a range of strains (0.5 to 5.0%). For a simulated inhomogeneous phantom (2.0% applied strain), the measured axial and lateral SNRes were 29.2 and 20.2 dB, whereas the CNRes were 50.2 dB and 31.5 dB, respectively. For the experimental data, lower SNRe (axial: 28.5 dB; lateral: 17.5 dB) and CNRe (axial: 39.3 dB; lateral: 31 dB) were found. In conclusion, a coarse-to-fine approach is favored using RF data on a fine scale. The use of 2D parabolic interpolation is favored to obtain subsample displacement estimates. Recorrelation techniques, such as local aligning and stretching, increase SNRe and CNRe in both directions.

Quantitative assessment of oral orbicular muscle deformation after cleft lip reconstruction: an ultrasound elastography study.

Reconstruction of a cleft lip leads inevitably to scar tissue formation. Scar tissue within the restored oral orbicular muscle might be assessed by quantification of the local contractility of this muscle. Furthermore, information about the contraction capability of the oral orbicular muscle is crucial for planning the revision surgery of an individual patient. We used ultrasound elastography to determine the local deformation (strain) of the upper lip and to differentiate contracting muscle from passive scar tissue. Raw ultrasound data (radio-frequency format; rf-) were acquired, while the lips were brought from normal state into a pout condition and back in normal state, in three patients and three normal individuals. During this movement, the oral orbicular muscle contracts and, consequently, thickens in contrast to scar tissue that will not contract, or even expand. An iterative coarse-to-fine strain estimation method was used to calculate the local tissue strain. Analysis of the raw ultrasound data allows estimation of tissue strain with a high precision. The minimum strain that can be assessed reproducibly is 0.1%. In normal individuals, strain of the orbicular oral muscle was in the order of 20%. Also, a uniform strain distribution in the oral orbicular muscle was found. However, in patients deviating values were found in the region of the reconstruction and the muscle tissue surrounding that. In two patients with a successful reconstruction, strain was reduced by 6% in the reconstructed region with respect to the normal parts of the muscle (from 22% to 16% and from 25% to 19%). In a patient with severe aesthetical and functional disability, strain decreased from 30% in the normal region to 5% in the reconstructed region. With ultrasound elastography, the strain of the oral orbicular muscle can be quantified. In healthy subjects, the strain profiles and maximum strain values in all parts of the muscle were similar. The maximum strain of the muscle during pout was 20% +/- 1%. In surgically repaired cleft lips, decreased deformation was observed.

3D cardiac segmentation using temporal correlation of radio frequency ultrasound data.

Semi-automatic segmentation of the myocardium in 3D echographic images may substantially support clinical diagnosis of heart disease. Particularly in children with congenital heart disease, segmentation should be based on the echo features solely since a priori knowledge on the shape of the heart cannot be used. Segmentation of echocardiographic images is challenging because of the poor echogenicity contrast between blood and the myocardium in some regions and the inherent speckle noise from randomly backscattered echoes. Phase information present in the radio frequency (rf) ultrasound data might yield useful, additional features in these regions. A semi-3D technique was used to determine maximum temporal cross-correlation values locally from the rf data. To segment the endocardial surface, maximum cross-correlation values were used as additional external force in a deformable model approach and were tested against and combined with adaptive filtered, demodulated rf data. The method was tested on full volume images (Philips, iE33) of four healthy children and evaluated by comparison with contours obtained from manual segmentation.

Computer-aided B-mode ultrasound diagnosis of hepatic steatosis: a feasibility study.

Fatty liver (steatosis) occurs in obese patients, among others, and is related to the development of diabetes type-2. Timely diagnosis of steatosis is therefore of great importance. Steatosis is also the most common liver disease of high-yielding dairy cattle during early lactation. This makes it a suitable animal model for studying liver steatosis. Furthermore, reference of derived ultrasound parameters against a "gold standard" is possible in cattle by taking a liver biopsy for the assessment of fat concentration. The authors undertook this pilot study to investigate the hypothesis that quantitative, computer-aided B-mode ultrasound enables the noninvasive detection of hepatic steatosis. Echographic images were obtained postpartum from dairy cows (n = 12) in transcutaneous and direct (intraoperative) applications using a convex array transducer at 4.2 MHz. During surgery, a biopsy was taken from the caudate lobe to assess the liver fat content (fat score). A custom-designed software package for computer-aided ultrasound diagnosis (CAUS) was developed. After linearizing the post-processing look-up-table (LUT), the image gray levels were transferred into echo levels in decibels relative to the mean echo level in a tissue-mimicking phantom. The quantitative comparison of transcutaneous and intraoperative images enabled the correction for the attenuation effect of skin and subcutaneous fat layer on the mean echo level in the liver, as well as for the effects of the beam formation and attenuation of liver tissue on the echo level vs. depth. The residual attenuation coefficient (dB/cm) in fatty liver vs. normal liver was estimated and compensated for. Finally, echo level was estimated relative to the phantom used for calibration, and echo texture was characterized by the mean axial and lateral speckle size within the regions of interest. In the no fat/low fat group (n = 5) skin plus fat layer attenuation was 3.4 dB/cm. A correlation of skin layer thickness vs. fat score of r = 0.48 was found. The mean transcutaneous liver tissue echo level correlated well with fat score: r = 0.80. A residual liver attenuation coefficient of 0.76 dB/cm and 1.19 dB/cm was found in medium and high fat liver, respectively. In transcutaneous images, correlation of residual attenuation coefficient with fat score was r = 0.69. Axial and lateral speckle sizes were on the order of 0.2 and 1.0 cm, respectively, and no correlation was found with liver fat content. Results for transcutaneous and intraoperative images were similar. The authors conclude that this pilot study shows the feasibility of calibrated, computer-aided ultrasound for noninvasively diagnosing, possibly even screening, steatosis of the liver.

Quantitative ultrasound imaging of healthy and reconstructed cleft lip: a feasibility study.

OBJECTIVE: To investigate the feasibility of echographic imaging of healthy and reconstructed cleft lip and to estimate tissue dimensions and normalized echo level. METHODS: Echographic images of the upper lip were made on three healthy subjects and two patients using a linear array transducer (7 to 11 MHz bandwidth) and a noncontact gel coupling. Tissue dimensions were measured using calipers. Echo levels were calibrated and were corrected for beam characteristics, gel path, and tissue attenuation using a tissue-mimicking phantom. RESULTS: At the central position of the philtrum, mean thickness (SD) of lip loose connective tissue layer, orbicularis oris muscle, and dense connective layer was 4.0 (0.1) mm, 2.3 (0.7) mm, and 2.2 (0.7) mm, respectively, in healthy lip at rest; and 4.1 (0.9) mm, 3.8 (1.7) mm, and 2.6 (0.6) mm, respectively, in contracted lip. Mean (SD) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was -19.3 (0.6) dB and -10.7 (4.0) dB, respectively, in relaxed condition and -20.7 (1.5) dB and -7.7 (2.3) dB, respectively, in contracted state. Color mode echo images were calculated, showing lip tissues in separate colors and highlighting details like discontinuity of the orbicularis oris muscle and presence of scar tissue. CONCLUSIONS: Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper echographic equipment calibration. Diagnostic potentials of this method for noninvasive evaluation of cleft lip reconstruction outcome are promising.

Regional cardiac wall motion abnormalities during and shortly after anthracyclines therapy.

BACKGROUND: Tissue Doppler imaging (TDI) is a new non-invasive ultrasound technique that enables quantitative assessment of regional myocardial wall motion. A previous study of survivors of childhood malignancies demonstrated abnormalities of regional diastolic wall motion abnormalities many years after treatment with anthracyclines. The purpose of the present study was to investigate this phenomenon during and shortly after treatment. PROCEDURE: A total of 60 patients, age range 4.4-16.0 years, were included in this study: 43 early survivors, with a mean follow-up duration of 2.1 (range 0.3-5.2) years from end of anthracycline treatment, were evaluated retrospectively. Seventeen other patients were evaluated before, during, and 6 months after the end of anthracycline therapy. All patients received moderate cumulative doses of anthracyclines (range 120-450 mg/m2). Echocardiographic examination was performed using standardized conventional and TDI techniques. RESULTS: Of the early survivors, 26 (60%) demonstrated regional LV free wall motion abnormalities. In the prospective group, serial echocardiographic studies revealed three patients (18%) with regional abnormalities of LV free wall motion before starting chemotherapy, but 14 (82%) at the end of treatment. Six months later, however, the incidence decreased to 61% of the survivors. Subject and treatment characteristics, as well as LV wall diameters and fractional shortening were not significantly different for children with or without free wall motion abnormalities. Regional wall motion abnormalities were also seen in the interventricular septum, although this was less frequent. CONCLUSIONS: Regional diastolic wall motion abnormalities are common during and shortly after anthracyclines therapy but may be transient. The authors recommend simultaneous use of both conventional echocardiography & TDI for the monitoring of anthracycline-induced cardiotoxicity.