Ultrasensitive US Microvessel Imaging of Hepatic Microcirculation in the Cirrhotic Rat Liver.

Background Liver microcirculation dysfunction plays a vital role in the occurrence and development of liver diseases, and thus, there is a clinical need for in vivo, noninvasive, and quantitative evaluation of liver microcirculation. Purpose To evaluate the feasibility of ultrasensitive US microvessel imaging (UMI) in the visualization and quantification of hepatic microvessels in healthy and cirrhotic rats. Materials and Methods In vivo studies were performed to image hepatic microvasculature by means of laparotomy in Sprague-Dawley rats (five cirrhotic and five control rats). In vivo conventional power Doppler US and ex vivo micro-CT were performed for comparison. UMI-based quantifications of perfusion, tortuosity, and integrity of microvessels were compared between the control and cirrhotic groups by using the Wilcoxon test. Spearman correlations between quantification parameters and pathologic fibrosis, perfusion function, and hepatic hypoxia were evaluated. Results UMI helped detect minute vessels below the liver capsule, as compared with conventional power Doppler US and micro-CT. With use of UMI, lower perfusion indicated by vessel density (median, 22% [IQR, 20%-28%] vs 41% [IQR, 37%-46%]; P = .008) and fractional moving blood volume (FMBV) (median, 6.4% [IQR, 4.8%-8.6%] vs 13% [IQR, 12%-14%]; P = .008) and higher tortuosity indicated by the sum of angles metric (SOAM) (median, 3.0 [IQR, 2.9-3.0] vs 2.7 [IQR, 2.6-2.9]; P = .008) were demonstrated in the cirrhotic rat group compared with the control group. Vessel density (r = 0.85, P = .003), FMBV (r = 0.86, P = .002), and median SOAM (r = -0.83, P = .003) showed strong correlations with pathologically derived vessel density labeled with dextran. Vessel density (r = -0.81, P = .005) and median SOAM (r = 0.87, P = .001) also showed strong correlations with hepatic tissue hypoxia. Conclusion Contrast-free ultrasensitive US microvessel imaging provided noninvasive in vivo imaging and quantification of hepatic microvessels in cirrhotic rat liver. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Fetzer in this issue.

Quantitative Shear Wave Speed Assessment for Muscles With the Diagnosis of Taut Bands and/or Myofascial Trigger Points Using Probe Oscillation Shear Wave Elastography: A Pilot Study.

OBJECTIVE: To use probe oscillation shear wave elastography (PROSE) with two vibration sources to generate two shear waves in the imaging plane to quantitatively assess the shear wave speeds (SWSs) of muscles with and without the diagnosis of taut bands (TB) and/or myofascial trigger points (MTrPs). METHODS: Thirty-three patients were scanned with the PROSE technique. Shear waves were generated through continuous vibration of the ultrasound probe, while the shear wave motions were detected using the same probe. SWSs for the sides with and without TBs and/or MTrPs were computed and compared. The pressure pain thresholds (PPTs) were measured as an indicator of maximum pain tolerance of patients. The statistical differences between the SWSs with and without TBs and/or MTrPs with different PPT values were analyzed using the nonparametric Wilcoxon rank-sum test. RESULTS: The mean SWSs for the sides with TBs and/or MTrPs are faster than that of the contralateral side without TBs and/or MTrPs. A significant difference was observed between mean SWSs with and without TBs and/or MTrPs without any information of PPT, with rank-sum test P < .005. Additionally, with the information of PPT, a significant difference was observed between mean SWSs for the sides with and without TBs and/or MTrPs, for PPT values between 0 and 50 N/cm2 (P < .005), but for PPT values between 50 and 90 N/cm2 , it was difficult to differentiate mean SWSs with and without TBs and/or MTrPs. CONCLUSION: Our preliminary results show that SWSs measured from patients had a significant difference between the mean SWSs with and without TBs and/or MTrPs.

Three-Dimensional Ultrasound Localization Microscopy with Bipartite Graph-Based Microbubble Pairing and Kalman-Filtering-Based Tracking on a 256-Channel Verasonics Ultrasound System with a 32 × 32 Matrix Array.

Three-dimensional (3D) ultrasound localization microscopy (ULM) using a 2-D matrix probe and microbubbles (MBs) has been recently proposed to visualize microvasculature beyond the ultrasound diffraction limit in three spatial dimensions. However, 3D ULM suffers from several limitations: (1) high system complexity due to numerous channel counts, (2) complex MB flow dynamics in 3D, and (3) extremely long acquisition time. To reduce the system complexity while maintaining high image quality, we used a sub-aperture process to reduce received channel counts. To address the second issue, a 3D bipartite graph-based method with Kalman filtering-based tracking was used in this study for MB tracking. An MB separation approach was incorporated to separate high concentration MB data into multiple, sparser MB datasets, allowing better MB localization and tracking for a limited acquisition time. The proposed method was first validated in a flow channel phantom, showing improved spatial resolutions compared with the contrasted enhanced power Doppler image. Then the proposed method was evaluated with an in vivo chicken embryo brain dataset. Results showed that the reconstructed 3D super-resolution image achieved a spatial resolution of around 52 µm (smaller than the wavelength of around 200 µm). Microvessels that cannot be resolved clearly using localization only, can be well identified with the tailored 3D pairing and tracking algorithms. To sum up, the feasibility of the 3D ULM is shown, indicating the great possibility in clinical applications.

Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis.

OBJECTIVE: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. DESIGN: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. RESULTS: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). CONCLUSION: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses.

BACKGROUND AND AIMS: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs. METHODS: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed. RESULTS: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs. CONCLUSIONS: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.

How does liver steatosis affect diagnostic performance of 2D-SWE.SSI: assessment from aspects of steatosis degree and pathological types.

OBJECTIVE: Two-dimensional shear wave elastography performed by SurperSonics (2D-SWE.SSI) performs well in evaluating liver fibrosis. Steatosis is one of confounding factors which might decrease accuracy, and its effect on 2D-SWE.SSI is still controversial. Our purpose is to evaluate the diagnostic performance of 2D-SWE.SSI affected by different steatosis stages and pathological types in chronic hepatitis B (CHB) patients. METHODS: 2D-SWE.SSI was performed on 1306 CHB patients. All patients were divided into mild steatosis, moderate to severe steatosis, and non-steatosis groups. Subgroup analysis was performed according to pathological type. Liver biopsy was reference standard. Propensity score matching was performed to adjust for differences in patient characteristics. The median values of different steatosis group were compared by non-parametric tests before and after propensity score matching. The area under the receiver operating characteristic curve (AUC) was analyzed to assess the diagnostic performance in different steatosis groups. RESULTS: The median values were not significantly different in different steatosis degrees expected in F0-1 patients. The AUC of 2D-SWE.SSI was not affected by different stages of liver steatosis for cirrhosis (= F4) (0.896, 0.853, 0.929, p = 0.34). The high AUCs (0.847, 0.856) were achieved in the non-steatosis and mild steatosis groups, and all were significantly higher than those of the moderate to severe steatosis group for ≥ F2. Moreover, the panacinar type had the best AUC (0.980 for F4 and 0.930 for ≥ F2). CONCLUSION: In conclusion, moderate to severe steatosis affects 2D-SWE.SSI in CHB patients. These patients had high LSM values in patients with F0-1 and lower accuracy in ≥ F2. Patients with panacinar steatosis have the highest overall diagnostic performance. KEY POINTS: • 2D-SWE.SSI was widely used in evaluating liver fibrosis and it has many confounding factors. Steatosis is one of the confounding factors and its effect on 2D-SWE.SSI was controversial. • Our study based on 1306 CHB patients with liver biopsy found that 2D-SWE.SSI might be affected by moderate to severe liver steatosis in diagnostically significant fibrosis (≥ F2) of CHB patients. • Patients with steatosis of the panacinar type have the highest overall diagnostic performance.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Changes in spinal cord hemodynamics reflect modulation of spinal network with different parameters of epidural stimulation.

In this study functional ultrasound (fUS) imaging has been implemented to explore the local hemodynamics response induced by electrical epidural stimulation and to study real-time in vivo functional changes of the spinal cord, taking advantage of the superior spatiotemporal resolution provided by fUS. By quantifying the hemodynamics and electromyographic response features, we tested the hypothesis that the temporal hemodynamics response of the spinal cord to electrical epidural stimulation could reflect modulation of the spinal circuitry and accordingly respond to the changes in parameters of electrical stimulation. The results of this study for the first time demonstrate that the hemodynamics response to electrical stimulation could reflect a neural-vascular coupling of the spinal cord. Response in the dorsal areas to epidural stimulation was significantly higher and faster compared to the response in ventral spinal cord. Positive relation between the hemodynamics and the EMG responses was observed at the lower frequencies of epidural stimulation (20 and 40 Hz), which according to our previous findings can facilitate spinal circuitry after spinal cord injury, compared to higher frequencies (200 and 500 Hz). These findings suggest that different mechanisms could be involved in spinal cord hemodynamics changes during different parameters of electrical stimulation and for the first time provide the evidence that neural-vascular coupling of the spinal cord circuitry could be related to specific organization of spinal cord vasculature and hemodynamics.

Liver Stiffness Measured with Two-dimensional Shear-Wave Elastography Is Predictive of Liver-related Events in Patients with Chronic Liver Disease Due to Hepatis B Viral Infection.

Background Liver stiffness measurement has been proposed as a noninvasive marker for predicting liver-related complications of cirrhosis. Purpose To evaluate the predictive value of liver stiffness measurement by using two-dimensional (2D) shear-wave elastography (SWE) for liver-related events among patients with chronic hepatitis B. Materials and Methods This retrospective study recruited consecutive patients with chronic hepatitis B who were referred for liver biopsy between May 2011 and May 2015. All patients underwent 2D SWE before biopsy, and a subset of patients underwent transient elastography. Patients were followed up for 4 years through the electronic medical records or telephone interviews. Univariable and multivariable logistic regression analyses were used to determine prognostic factors. Accuracy of prognostic parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results Among 430 patients (mean age, 38 years; range, 18-67 years) including 328 men and 102 women, 29 patients developed liver-related events. Multivariable analysis demonstrated that liver stiffness measured with 2D SWE, spleen longitudinal diameter at US, age, and albumin level were predictive factors of liver-related events. The AUC of the multivariable model was higher (0.89; 95% confidence interval [CI]: 0.86, 0.92) but not significantly different from that of 2D SWE (0.86; 95% CI: 0.82, 0.89; P = .23) and was significantly higher than that of the fibrosis stage (0.72; 95% CI: 0.68, 0.76; P < .001), the aspartate aminotransferase-to-platelet ratio index (0.80; 95% CI: 0.76, 0.84; P < .001), and the fibrosis-4 index (0.84; 95% CI: 0.80, 0.87; P = .02). In a subset of patients with available transient elastography (n = 188), the multivariable model, 2D SWE, and transient elastography showed comparable performance (AUC: 0.91 vs 0.86 vs 0.88, respectively). When inflammatory activity was considered, the multivariable model was highly accurate in patients with low-grade inflammation and normal levels of alanine aminotransferase (AUC: 0.97 and 0.94, respectively). Conclusion The multivariable model and two-dimensional shear-wave elastography are more accurate in predicting liver-related events than are the fibrosis stage and serum markers of liver fibrosis tests. © RSNA, 2020 Online supplemental material is available for this article.

Three-dimensional US for Quantification of Volumetric Blood Flow: Multisite Multisystem Results from within the Quantitative Imaging Biomarkers Alliance.

Background Quantitative blood flow (QBF) measurements that use pulsed-wave US rely on difficult-to-meet conditions. Imaging biomarkers need to be quantitative and user and machine independent. Surrogate markers (eg, resistive index) fail to quantify actual volumetric flow. Standardization is possible, but relies on collaboration between users, manufacturers, and the U.S. Food and Drug Administration. Purpose To evaluate a Quantitative Imaging Biomarkers Alliance-supported, user- and machine-independent US method for quantitatively measuring QBF. Materials and Methods In this prospective study (March 2017 to March 2019), three different clinical US scanners were used to benchmark QBF in a calibrated flow phantom at three different laboratories each. Testing conditions involved changes in flow rate (1-12 mL/sec), imaging depth (2.5-7 cm), color flow gain (0%-100%), and flow past a stenosis. Each condition was performed under constant and pulsatile flow at 60 beats per minute, thus yielding eight distinct testing conditions. QBF was computed from three-dimensional color flow velocity, power, and scan geometry by using Gauss theorem. Statistical analysis was performed between systems and between laboratories. Systems and laboratories were anonymized when reporting results. Results For systems 1, 2, and 3, flow rate for constant and pulsatile flow was measured, respectively, with biases of 3.5% and 24.9%, 3.0% and 2.1%, and -22.1% and -10.9%. Coefficients of variation were 6.9% and 7.7%, 3.3% and 8.2%, and 9.6% and 17.3%, respectively. For changes in imaging depth, biases were 3.7% and 27.2%, -2.0% and -0.9%, and -22.8% and -5.9%, respectively. Respective coefficients of variation were 10.0% and 9.2%, 4.6% and 6.9%, and 10.1% and 11.6%. For changes in color flow gain, biases after filling the lumen with color pixels were 6.3% and 18.5%, 8.5% and 9.0%, and 16.6% and 6.2%, respectively. Respective coefficients of variation were 10.8% and 4.3%, 7.3% and 6.7%, and 6.7% and 5.3%. Poststenotic flow biases were 1.8% and 31.2%, 5.7% and -3.1%, and -18.3% and -18.2%, respectively. Conclusion Interlaboratory bias and variation of US-derived quantitative blood flow indicated its potential to become a clinical biomarker for the blood supply to end organs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Forsberg in this issue.

How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy.

OBJECTIVES: To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). METHODS: Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. RESULTS: Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46 kPa for ≥ F2, 10.94 kPa for ≥ F3, and 15.88 kPa for F4, than those with normal TB (7.62 kPa, 8.26 kPa, and 11.01 kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. CONCLUSION: Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. KEY POINTS: • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.

Quantitative Inflammation Assessment for Crohn Disease Using Ultrasensitive Ultrasound Microvessel Imaging: A Pilot Study.

OBJECTIVES: Crohn disease (CD) is a chronic inflammation in the digestive tract that affects millions of Americans. Bowel vascularity has important diagnostic information because inflammation is associated with blood flow changes. We recently developed an ultrasensitive ultrasound microvessel imaging (UMI) technique with high vessel sensitivity. This study aimed to evaluate the feasibility of UMI to assist CD detection and staging. METHODS: Ultrasound microvessel imaging was performed on 76 bowel wall segments from 48 symptomatic patients with CD. Clinically indicated computed tomographic/magnetic resonance enterography was used as the reference standard. The vessel-length ratio (VLR, the number of vessel pixels in the bowel wall segment normalized to the segment length) was derived in both conventional color flow imaging (CFI) and UMI to quantitatively stage disease activity. Receiver operating characteristic curves were then analyzed between different disease groups. RESULTS: The VLR-CFI and VLR-UMI detected similar correlations between vascularization and disease activity: severe inflammation had a higher VLR than normal/mildly inflamed bowels (P < .05). No significant difference was found between quiescent and mild CD due to the small sample size. The VLR-CFI had more difficulties in distinguishing quiescent versus mild CD compared to the VLR-UMI. After combining the VLR-UMI with thickness, in the receiver operating characteristic curve analysis, the areas under the curves (AUCs) improved to AUC1 = 0.996 for active versus quiescent CD, AUC2 = 0.978 for quiescent versus mild CD, and AUC3 = 0.931 for mild versus severe CD, respectively, compared to those using thickness alone (AUC1 = 0.968; P = .04; AUC2 = 0.919; P = .16; AUC3 = 0.857; P = .01). CONCLUSIONS: Ultrasound microvessel imaging offers a safe and cost-effective tool for CD diagnosis and staging, which may potentially assist disease activity classification and therapy efficacy evaluation.

2D shear wave elastography combined with MELD improved prognostic accuracy in patients with acute-on-chronic hepatitis B liver failure.

OBJECTIVES: To evaluate accuracy of two-dimensional shear wave elastography (2D SWE) and develop and validate a new prognostic score in predicting prognosis of acute-on-chronic liver failure (ACLF) patients. METHODS: From 1 October 2013 to 30 September 2015, we consecutively enrolled 290 patients, sequentially collected data (including 2D SWE, ultrasound parameters, laboratory data and prognostic scores) and recorded patients' outcome (recovering/steady or worsening) during a 90-day follow-up period. We evaluated ability of 2D SWE to predict outcomes of acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients. We developed a new score (MELD-SWE, combining MELD and SWE values) for predicting mortality risk of ACLF-HBV in 179 patients in a derivation group, and validated in 111 patients. RESULTS: 2D SWE values were higher in worsening patients than recovering/steady ones (p < 0.001). Accuracy of 2D SWE in predicting outcomes of ACLF-HBV was comparable to that of the MELD score (p = 0.441). MELD-SWE showed a significantly higher prognostic value than MELD in both derivation (AUROC, 0.80 vs. 0.76, p = 0.040) and validation (AUROC, 0.87 vs. 0.82, p = 0.018) group. CONCLUSIONS: The MELD-SWE score, combining MELD and SWE values, was superior to MELD alone for outcoming prediction in patients with ACLF-HBV. KEY POINTS: • 2D SWE is a simple prognostic evaluation tool in patients with ACLF-HBV. • MELD-SWE was created in this study: 1.3×MELD + 0.3×2D SWE (kPa). • MELD-SWE score was superior to MELD alone for outcoming prediction in ACLF-HBV. • In this study, 46.8 was the optimal cut-off value of MELD-SWE score.

Three-Dimensional Shear Wave Elastography for Differentiating Benign From Malignant Thyroid Nodules.

OBJECTIVES: To prospectively evaluate the diagnostic performance of 3-dimensional (3D) shear wave elastography (SWE) for assessing thyroid nodules. METHODS: A total of 176 surgically or cytologically confirmed thyroid nodules (63 malignant and 113 benign) in 176 patients who had undergone conventional ultrasound (US), 2-dimensional (2D) SWE, and 3D SWE examinations were included in this study. Quantitative elasticity values (mean elasticity, maximum elasticity, and standard deviation of elasticity of a large region of interest and mean elasticity of a 2-mm region of interest) were measured on 2D and 3D SWE. Diagnostic performances of conventional US, 2D SWE, and 3D SWE were assessed. The role of 2D and 3D SWE in reducing unnecessary fine-needle aspiration (FNA) for nodules with low suspicion was also evaluated. RESULTS: The diagnostic performances in terms of the area under the receiver operating characteristic curve were 0.612 for conventional US, 0.836 for 2D SWE (P < .001 in comparison with conventional US), and 0.839 for 3D SWE (P < .001 in comparison with conventional US). The mean elasticity achieved the highest diagnostic performance in 2D SWE, whereas the standard deviation of elasticity achieved the highest performance in 3D SWE, although no significant difference was found between them (P > .05). Three-dimensional SWE increased the specificity in comparison with 2D SWE (88.5% versus 82.3%; P = .039). For the 37 nodules with low suspicion on conventional US imaging, 2D SWE was able to avoid unnecessary FNA in 77.1% (27 of 35) of benign nodules, and 3D SWE further increased the number to 88.6% (31 of 35). CONCLUSIONS: Three-dimensional SWE is a useful tool for predicting thyroid nodule malignancy and reducing unnecessary FNA procedures in thyroid nodules with low suspicion of malignancy.

Clinical acceptance testing and scanner comparison of ultrasound shear wave elastography.

Because of the rapidly growing use of ultrasound shear wave elastography (SWE) in clinical practices, there is a significant need for development of clinical physics performance assessment methods for this technology. This study aims to report two clinical medical physicists' tasks: (a) acceptance testing (AT) of SWE function on ten commercial ultrasound systems for clinical liver application and (b) comparison of SWE measurements of targets across vendors for clinical musculoskeletal application. For AT, ten GE LOGIQ E9 XDclear 2.0 scanners with ten C1-6-D and ten 9L-D transducers were studied using two commercial homogenous phantoms. Five measurements were acquired at two depths for each scanner/transducer pair by two operators. Additional tests were performed to access effects of different coupling media, phantom locations and operators. System deviations were less than 5% of group mean or three times standard deviation; therefore, all systems passed AT. A test protocol was provided based on results that no statistically significant difference was observed between using ultrasound gel and salt water for coupling, among different phantom locations, and that interoperator and intraoperator coefficient of variation was less than 3%. For SWE target measurements, two systems were compared - a Supersonic Aixplorer scanner with a SL10-2 and a SL15-4 transducer, and an abovementioned GE scanner with 9L-D transducer. Two stepped cylinders with diameters of 4.05-10.40 mm were measured both longitudinally and transaxially. Target shear wave speed quantification was performed using an in-house MATLAB program. Using the target shear wave speed deduced from phantom specs as a reference, SL15-4 performed the best at the measured depth. However, it was challenging to reliably measure a 4.05 mm target for either system. The reported test methods and results could provide important information when dealing with SWE-related tasks in the clinical environment.

Near field effect on elasticity measurement for cartilage-bone structure using Lamb wave method.

BACKGROUND: Cartilage elasticity changes with cartilage degeneration. Hence, cartilage elasticity detection might be an alternative to traditional imaging methods for the early diagnosis of osteoarthritis. Based on the wave propagation measurement, Shear wave elastography (SWE) become an emerging non-invasive elasticity detection method. The wave propagation model, which is affected by tissue shapes, is crucial for elasticity estimating in SWE. However, wave propagation model for cartilage was unclear. METHODS: This study aimed to establish a wave propagation model for the cartilage-bone structure. We fabricated a cartilage-bone structure, and studied the elasticity measurement and wave propagation by experimental and numerical Lamb wave method (LWM). RESULTS: Results indicated the wave propagation model satisfied the lamb wave theory for two-layered structure. Moreover, a near field region, which affects wave speed measurements and whose occurrence can be prevented if the wave frequency is larger than one critical frequency, was observed. CONCLUSION: Our findings would provide a theoretical foundation for further application of LWM in elasticity measurement of cartilage in vivo. It can help the application of LWM to the diagnosis of osteoarthritis.

Virtual Touch Quantification of the Salivary Glands for Diagnosis of Primary Sjögren Syndrome.

OBJECTIVES: To investigate the value of salivary gland stiffness measured by Virtual Touch quantification (VTQ; Siemens Medical Solutions, Erlangen, Germany) for assessment of primary Sjögren syndrome. METHODS: Fifty-four patients with primary Sjögren syndrome, 35 patients without primary Sjögren syndrome (patients with dry mouth and dry eye symptoms), and 52 healthy control volunteers were included in this study. Patients with primary Sjögren syndrome were classified as early or advanced stage by labial gland biopsies. All participants underwent B-mode sonography, on which the salivary glands (parotid and submandibular) were identified and VTQ measurements of shear wave velocity (SWV) were obtained. The diagnostic performance of SWV was evaluated by sensitivity and specificity at the optimum cutoff point and the area under the receiver operating characteristic curve. RESULTS: For submandibular glands, the mean SWV ± SD values were 2.25 ± 0.34 m/s in patients with early-stage primary Sjögren, 1.84 ± 0.20 m/s in patients without primary Sjögren syndrome, and 1.82 ± 0.27 m/s in healthy controls (P< .001). With cutoff values of 2.15 and 2.10 m/s to separate patients with early-stage primary Sjögren syndrome from those without Sjögren syndrome and healthy controls, the sensitivity and specificity were 77.1% and 85.4% and 79.2% and 83.9%, respectively. For parotid glands, the SWV values were 2.78 ± 0.82 m/s in patients with early-stage primary Sjögren syndrome, 1.93 ± 0.33 m/s, in patients without primary Sjögren syndrome, and 1.85 ± 0.31 m/s in healthy controls (P < .001). With cutoff values of 2.18 and 2.10 m/s to separate patients with early-stage primary Sjögren syndrome from those without Sjögren syndrome and healthy controls, the sensitivity and specificity were 89.3 % and 75.3% and 91.4% and 80.0%. CONCLUSIONS: The VTQ technique might be a useful noninvasive strategy for assessment of salivary glands in the early stage of primary Sjögren syndrome.

Quantitative Assessment of Left Ventricular Diastolic Stiffness Using Cardiac Shear Wave Elastography: A Pilot Study.

OBJECTIVES: The purpose of this study was to systematically investigate the feasible echocardiographic views for human transthoracic cardiac shear wave elastography (SWE) and the impact of myocardial anisotropy on myocardial stiffness measurements. METHODS: A novel cardiac SWE technique using pulse inversion harmonic imaging and time-aligned sequential tracking was developed for this study. The technique can measure the quantitative local myocardial stiffness noninvasively. Ten healthy volunteers were recruited and scanned by the proposed technique 3 times on 3 different days. RESULTS: Seven combinations of echocardiographic views and left ventricular (LV) segments were found to be feasible for LV diastolic stiffness measurements: basal interventricular septum under parasternal short- and long-axis views; mid interventricular septum under parasternal short- and long-axis views; anterior LV free wall under parasternal short- and long-axis views; and posterior LV free wall under a parasternal short-axis view. Statistical analyses showed good repeatability of LV diastolic stiffness measurements among 3 different days from 70% of the participants for the basal interventricular septum and posterior LV free wall short-axis views. On the same LV segment, the mean diastolic shear wave speed measurements from the short-axis view were statistically different from the long-axis measurements: 1.82 versus 1.29 m/s for the basal interventricular septum; 1.81 versus 1.45 m/s for mid interventricular septum; and 1.96 versus 1.77 m/s for the anterior LV free wall, indicating that myocardial anisotropy plays a substantial role in LV diastolic stiffness measurements. CONCLUSIONS: These results establish the preliminary normal range of LV diastolic stiffness under different scan views and provide important guidance for future clinical studies using cardiac SWE.

Performance of 2-Dimensional Ultrasound Shear Wave Elastography in Liver Fibrosis Detection Using Magnetic Resonance Elastography as the Reference Standard: A Pilot Study.

OBJECTIVES: To investigate the correlation between 2-dimensional (2D) ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard. METHODS: Two-dimensional SWE was performed on 47 patients. One patient was excluded from the study. Each of the remaining 46 patients underwent same-day MRE for clinical purposes. The study was compliant with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board. Informed consent was obtained from each patient. Two-dimensional SWE measurements were acquired from the ninth, eighth, and seventh intercostal spaces. The correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2D SWE in diagnosing liver fibrosis was evaluated by receiver operating characteristic curve analysis using MRE as the standard. RESULTS: The 47 patients who initially underwent 2D SWE included 22 female and 25 male patients (age range, 19-77 years). The highest correlation between 2D SWE and MRE was from the eighth and seventh intercostal spaces (r = 0.68-0.76). The ranges of the areas under the receiver operating characteristic curves for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 to 0.92 when using the eighth and seventh intercostal spaces individually and 0.89 to 0.90 when combined. CONCLUSIONS: The results suggest that 2D SWE and MRE are well correlated when SWE is performed at the eighth and seventh intercostal spaces. The ninth intercostal space is less reliable for diagnosing fibrosis with 2D SWE. Combining measurements from multiple intercostal spaces does not significantly improve the performance of 2D SWE for detection of fibrosis.

Feasibility and reliability of quantifying passive muscle stiffness in young children by using shear wave ultrasound elastography.

OBJECTIVES: The purpose of this study was to investigate the feasibility and reliability of passive muscle stiffness measurements in children by shear wave ultrasound elastography. METHODS: We conducted a prospective cross-sectional study quantifying the passive stiffness of bilateral lateral gastrocnemius muscles during passive stretching in 20 typically developing children (age range, 2.0-12.6 years). Data collected included passive stiffness of the lateral gastrocnemius muscle (shear modulus in kilopascals) at 4 positions of progressive passive foot dorsiflexion, demographic characteristics of the participants, and comparison of demographic characteristics with the shear modulus. RESULTS: Passive stiffness increased with increasing stretching (mean [SD] range of stiffness, 7.1 [2.0] to 36.2 [22.0] kPa). For all 4 foot positions, no significant difference was found between right and left legs (range, P = .42 to P = .98) or between the sexes (range, P = .28 to P > .99). No correlation of passive muscle stiffness with age, body mass index, or ankle range of motion was found. The reliability of measurements was good to excellent (mean [95% confidence interval] range of reliability, 0.67 [0.44-0.83] to 0.80 [0.63-0.90]). CONCLUSIONS: Measurements of passive stiffness of the lateral gastrocnemius muscle are feasible and reliable in children as young as 2 years. Because this study found no significant difference between sex and the side tested in this age group, future studies involving children of this age range may not need to be stratified on the basis of these parameters. Defining normal passive muscle stiffness in children is critical for identifying and understanding the implications of abnormal passive muscle stiffness in children with neuromuscular disorders.