Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China. Multivariable logistic regression was performed to assess risk factors associated with MASH. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate diagnostic performance in predicting MASH in training and validation groups (6:4 ratio of participants), and for a post hoc subgroup analysis of hepatitis B virus infection and diabetes. Results A total of 424 participants (median age, 47 years; IQR, 34-59 years; 244 male) were evaluated, including 332 participants (78%) with MASH and 92 (22%) without. Attenuation coefficient (AC) (odds ratio [OR], 3.32 [95% CI: 1.94, 5.71]; P < .001), alanine aminotransferase (ALT) level (OR, 4.42 [95% CI: 1.78, 10.94]; P = .001), and international normalized ratio (INR) (OR, 0.59 [95% CI: 0.37, 0.95]; P = .03) were independently associated with MASH. A combined model (AC, ALT, and INR) had AUCs of 0.85 (95% CI: 0.79, 0.91) and 0.77 (95% CI: 0.69, 0.85) for predicting MASH in the training and validation groups, respectively. AUC values for the subgroups with and without diabetes were 0.83 (95% CI: 0.72, 0.94) and 0.81 (95% CI: 0.75, 0.87) and for the subgroups with and without hepatitis B were 0.82 (95% CI: 0.74, 0.90) and 0.79 (95% CI: 0.71, 0.87), respectively. Conclusion A model combining AC, ALT level, and INR showed good discrimination ability for predicting MASH in participants with MAFLD. Clinical trial registration no. NCT04551716 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Reuter in this issue.

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.

Outcomes Following Different Thermal Ablation Strategies in Patients with Unresectable Colorectal Liver Metastases.

Background For patients with unresectable colorectal liver metastases (CRLM), clinical guidelines recommend imaging-guided thermal ablation combined with systemic therapy. However, the optimal thermal ablation strategy remains unclear. Purpose To compare long-term outcomes between patients who underwent upfront ablation or delayed ablation for unresectable CRLM. Materials and Methods This retrospective study included patients with unresectable CRLM (three or fewer lesions; diameter, <3 cm) admitted to one of seven hospitals between October 2009 and December 2020. Upfront ablation was performed 2-4 weeks before the start of systemic therapy, and delayed ablation was performed 2-3 months after the start of systemic therapy. Propensity score matching was applied to adjust for differences in baseline variables between groups. Disease-free survival (DFS) was the primary outcome. Overall survival (OS), complications, and adverse events were secondary outcomes. Outcomes were compared between groups by using the log-rank test. Results In total, 255 patients who underwent delayed ablation (mean age, 57 years ± 11 [SD]; 184 men [72%]) and 103 patients who underwent upfront ablation (mean age, 56 years ± 12; 72 men [70%]) were included. After propensity score matching (n = 100 in both groups), the 5-year DFS for patients who underwent upfront ablation was better compared with patients who underwent delayed ablation (36% vs 21%; P = .02). For 5-year OS, no evidence of a difference was observed between ablation strategies (delayed ablation, 59% vs upfront ablation, 64%; P = .49). Additionally, no differences were observed between ablation strategies with respect to the rates of ablative complications (delayed ablation, 6% vs upfront ablation, 5%; P = .76) or drug-related adverse events (delayed and upfront ablation both 9%; P = .99). Conclusion In patients with relatively few (three or fewer) and small (<3 cm) unresectable CRLM, upfront thermal ablation combined with adjuvant systemic therapy led to better DFS compared with delayed ablation. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Deep learning based on carotid transverse B-mode scan videos for the diagnosis of carotid plaque: a prospective multicenter study.

OBJECTIVES: Accurate detection of carotid plaque using ultrasound (US) is essential for preventing stroke. However, the diagnostic performance of junior radiologists (with approximately 1 year of experience in carotid US evaluation) is relatively poor. We thus aim to develop a deep learning (DL) model based on US videos to improve junior radiologists' performance in plaque detection. METHODS: This multicenter prospective study was conducted at five hospitals. CaroNet-Dynamic automatically detected carotid plaque from carotid transverse US videos allowing clinical detection. Model performance was evaluated using expert annotations (with more than 10 years of experience in carotid US evaluation) as the ground truth. Model robustness was investigated on different plaque characteristics and US scanning systems. Furthermore, its clinical applicability was evaluated by comparing the junior radiologists' diagnoses with and without DL-model assistance. RESULTS: A total of 1647 videos from 825 patients were evaluated. The DL model yielded high performance with sensitivities of 87.03% and 94.17%, specificities of 82.07% and 74.04%, and areas under the receiver operating characteristic curve of 0.845 and 0.841 on the internal and multicenter external test sets, respectively. Moreover, no significant difference in performance was noted among different plaque characteristics and scanning systems. Using the DL model, the performance of the junior radiologists improved significantly, especially in terms of sensitivity (largest increase from 46.3 to 94.44%). CONCLUSIONS: The DL model based on US videos corresponding to real examinations showed robust performance for plaque detection and significantly improved the diagnostic performance of junior radiologists. KEY POINTS: • The deep learning model based on US videos conforming to real examinations showed robust performance for plaque detection. • Computer-aided diagnosis can significantly improve the diagnostic performance of junior radiologists in clinical practice.

Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers.

OBJECTIVES: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). METHODS: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. RESULTS: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. CONCLUSION: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. KEY POINT: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare.

Up-Front Versus Delayed Thermal Ablation for Colorectal Liver Oligometastases: A Multicenter Retrospective Study Using Propensity Score Matching.

BACKGROUND. Thermal ablation combined with systemic therapy is an accepted treatment of colorectal liver oligometastases (CLOM). Consensus is lacking regarding the optimal timing of thermal ablation relative to systemic therapy. OBJECTIVE. The purpose of our study was to compare delayed and up-front thermal ablation in terms of efficacy and safety in the treatment of patients with CLOM. METHODS. This retrospective multicenter study included 440 patients (316 men, 124 women; mean age, 57.1 ± 11.1 [SD] years) with CLOM from nine hospitals between October 2009 and December 2020. Patients underwent delayed (n = 322) or up-front (n = 118) thermal ablation in combination with systemic therapy. Analyses included all patients using crude data, all patients using inverse probability treatment weighting (IPTW), and a subset of patients using propensity score matching (PSM) at a 1:1 ratio to balance baseline variables (108 matched patients for each group [i.e., delayed ablation and up-front ablation]). Patients were classified as having a low or high tumor burden score (TBS) on the basis of the number and size of the liver metastases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), complications from ablation, and adverse events (AEs) from systemic therapy. Survival analysis used the Kaplan-Meier method. RESULTS. The median follow-up was 2.9 years. The 5-year PFS was 17.1% for delayed ablation versus 33.6% for up-front ablation in all patients and 17.9% versus 34.7% after PSM. Delayed ablation was associated with worse PFS in the crude analysis (HR = 0.62), IPTW analysis (HR = 0.66), and PSM analysis (HR = 0.62) (all p < .05). No analysis showed a significant difference in OS between delayed and up-front ablation. Crude, IPTW, and PSM analyses showed better PFS for up-front compared with delayed ablation in patients with a low TBS (HR = 0.62-0.67; all p < .05); none of these analyses showed significant difference in PFS in patients with a high TBS. Delayed ablation and up-front ablation groups showed no difference in frequency of grade III or IV ablation complications (4.7% vs 6.8%, p = .38) or grade III or IV systemic therapy AEs (12.4% vs 10.2%, p = .53). CONCLUSION. In patients with CLOM, up-front ablation achieved better PFS compared with delayed ablation, although only among patients with a low TBS. CLINICAL IMPACT. These findings could help optimize clinical implementation of thermal ablation in patients who are not candidates for surgical resection.

Long-term efficacy and safety of microwave ablation for hepatocellular carcinoma adjacent to the gallbladder with a diameter ≤ 5 cm: a multicenter, propensity score matching study.

OBJECTIVE: To compare the long-term efficacy and safety of microwave ablation (MWA) as first-line therapy for hepatocellular carcinoma (HCC) adjacent versus nonadjacent to the gallbladder. MATERIALS AND METHODS: From 2006 to 2018, 657 patients with ≤5 cm HCC who underwent percutaneous ultrasound-guided MWA as first-line therapy from 5 hospitals were enrolled in this retrospective study. Patients were grouped into the adjacent group (n = 49) and the nonadjacent group (n = 608) according to whether the tumor was adjacent to the gallbladder. Propensity score matching (PSM) was used to balance baseline variables between the two groups. RESULTS: Forty-eight patient pairs were matched after PSM. For the PSM cohort, during a median follow-up time of 60 months, there were no differences in PFS (hazard ratio [HR], 1.011; 95% confidence interval [CI], 0.647-1.578; p = 0.963) or OS (HR 0.925; 95% CI 0.522-1.639; p = 0.789) between the adjacent and nonadjacent groups. Univariate and multivariate analyses revealed that the tumor adjacent to the gallbladder was not an independent risk factor for PFS or OS (all p > 0.05). Subgroup analysis showed comparable PFS and OS between the two groups in the <3 cm subgroup and the 3-5 cm subgroups (all p > 0.05). In addition to more use of assistive technology (p < 0.05), the adjacent group shared comparable local tumor progression, complications, technical success rate, and hospital stay (all p > 0.05) to the nonadjacent group. CONCLUSION: There were comparable long-term efficacy and complications between patients with HCC adjacent and nonadjacent to the gallbladder treated with MWA.

The application of MWA to HCC adjacent and nonadjacent to the gallbladder resulted in comparable PFS and OS and complications.For both cohorts, MWA shared comparable complications (immediate and delayed), LTP, hospitalization, and operative time.MWA might be a first-line alternative for ≤5 cm HCC adjacent to the gallbladder with the use of assistive technologies and advances in technology.

Efficacy of Multiple Modified Methods of Criteria for LR-M Liver Nodules of Different Sizes: Clinical Practice and Discussion in CEUS LI-RADS Version 2017.

OBJECTIVES: To assess the diagnostic performance of the modified LR-M method of CEUS LI-RADS version 2017 with nodules of different sizes. METHODS: This retrospective study included consecutive patients with high risk for HCC who underwent CEUS between 2019 and 2021, demonstrating an LR-M observed using CEUS LI-RADS version 2017. Four modified LR-M methods were used to evaluate nodules of different sizes. The diagnostic performances of the four modified LR-M methods were assessed in LR-M nodules of different sizes by the area under the receiver operating characteristic curve (AUC). RESULTS: The 261 patients with LR-M observations included 166 HCCs and 95 non-HCCs. A total of 133 nodules were <30 mm and defined as group A, 78 nodules were 30-50 mm in size and defined as group B, and 50 nodules were >50 mm and defined as group C. The AUCs between criterion I, II, III, and IV were not significantly different in all LR-M nodules. The AUCs of the ROC curves between criterion I, II, III, and IV were not significantly different in group A. However, the AUC of criterion IV was significantly higher than that of criterion I and III in group B, and the AUCs of criterion I and criterion III were both not significant in group B; the AUC of criterion IV was not significant in group C. CONCLUSIONS: The modified LR-M method could moderate the detection effectiveness in differentiating HCC from other lesions. According to tumor size, the selection of appropriate modified LR-M diagnostic criteria could effectively improve the diagnostic performance of LR-M.

On-Site Diagnostic Ability of CEUS/CT/MRI for Hepatocellular Carcinoma (2019-2022): A Multicenter Study.

OBJECTIVES: To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS: Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS: Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS: Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.

Fully automatic tumor segmentation of breast ultrasound images with deep learning.

BACKGROUND: Breast ultrasound (BUS) imaging is one of the most prevalent approaches for the detection of breast cancers. Tumor segmentation of BUS images can facilitate doctors in localizing tumors and is a necessary step for computer-aided diagnosis systems. While the majority of clinical BUS scans are normal ones without tumors, segmentation approaches such as U-Net often predict mass regions for these images. Such false-positive problem becomes serious if a fully automatic artificial intelligence system is used for routine screening. METHODS: In this study, we proposed a novel model which is more suitable for routine BUS screening. The model contains a classification branch that determines whether the image is normal or with tumors, and a segmentation branch that outlines tumors. Two branches share the same encoder network. We also built a new dataset that contains 1600 BUS images from 625 patients for training and a testing dataset with 130 images from 120 patients for testing. The dataset is the largest one with pixel-wise masks manually segmented by experienced radiologists. Our code is available at https://github.com/szhangNJU/BUS_segmentation. RESULTS: The area under the receiver operating characteristic curve (AUC) for classifying images into normal/abnormal categories was 0.991. The dice similarity coefficient (DSC) for segmentation of mass regions was 0.898, better than the state-of-the-art models. Testing on an external dataset gave a similar performance, demonstrating a good transferability of our model. Moreover, we simulated the use of the model in actual clinic practice by processing videos recorded during BUS scans; the model gave very low false-positive predictions on normal images without sacrificing sensitivities for images with tumors. CONCLUSIONS: Our model achieved better segmentation performance than the state-of-the-art models and showed a good transferability on an external test set. The proposed deep learning architecture holds potential for use in fully automatic BUS health screening.

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

US Shear-Wave Elastography Dispersion for Characterization of Chronic Liver Disease.

Background Little is known about the benefits of the use of dispersion slope (DS) as a viscosity-related parameter derived from two-dimensional (2D) shear-wave elastography (SWE) in the stratification of hepatic pathologic stages. Purpose To evaluate whether DS as an additional parameter can improve the diagnostic performance in detecting liver necroinflammation, fibrosis, and steatosis. Materials and Methods In this prospective study, consecutive participants with chronic liver disease who underwent liver biopsy and 2D SWE were recruited between July 2019 and September 2020. DS and liver stiffness (LS) measurements were obtained with use of a 2D SWE system immediately before biopsy. The biopsy specimens were assessed to obtain the scores of fibrosis, necroinflammation, and steatosis. Differences in the area under the receiver operating characteristic curve (AUC) were used to compare the diagnostic performance of DS, LS, and a combination of DS and LS. Results There were 159 participants evaluated (among them, 79 participants with chronic hepatitis B and 11 participants with nonalcoholic fatty liver disease). The distributions of DS values among various necroinflammatory activities (P = .02) and fibrosis stages (P < .001) were different. Moreover, DS was only associated with fibrosis after subgroup analysis based on the fibrosis stages and necroinflammatory activities (P < .001). The AUCs of DS in detecting clinically significant fibrosis (fibrosis stage ≥F2), cirrhosis (fibrosis stage of F4), and moderate to severe necroinflammatory activity (necroinflammatory activity ≥A2) were 0.72 (95% CI: 0.64, 0.79), 0.71 (95% CI: 0.63, 0.78), and 0.64 (95% CI: 0.55, 0.71), respectively. The differences of AUCs were not apparent for the DS and LS combination model after excluding DS (fibrosis stage ≥F2: 0.00 [95% CI: 0.00, 0.01], fibrosis stage of F4: -0.01 [95% CI: -0.02, 0.00], and necroinflammatory activity ≥A2: 0.00 [95% CI: 0.00, 0.01]). Conclusion The addition of dispersion slope derived from two-dimensional shear-wave elastography did not improve the diagnostic performance in detecting liver fibrosis, necroinflammation, or steatosis in patients with primarily viral hepatitis. ClinicalTrials.gov registration no.: NCT03777293 © RSNA, 2022 Online supplemental material is available for this article.

Liver Fibrosis Assessment by Viewing Sinusoidal Capillarization: US Molecular Imaging versus Two-dimensional Shear-Wave Elastography in Rats.

Background US elastography is a first-line assessment of liver fibrosis severity; however, its application is limited by its insufficient sensitivity in early-stage fibrosis detection and its measurements are affected by inflammation. Purpose To assess the sensitivity of US molecular imaging (USMI) in early-stage liver fibrosis detection and to determine whether USMI can specifically distinguish fibrosis regardless of inflammation when compared with two-dimensional (2D) shear-wave elastography (SWE). Materials and methods USMI and 2D SWE were performed prospectively (January to June 2021) in 120 male Sprague-Dawley rats with varying degrees of liver fibrosis and acute hepatitis and control rats. Liver sinusoidal capillarization was viewed at CD34-targeted USMI and quantitatively analyzed by the normalized intensity difference (NID). Data were compared by using a two-sided Student t test or one-way analysis of variance. Linear correlation analyses were used to evaluate the relationships between collagen proportionate area values and NID and liver stiffness measurement (LSM) values. Receiver operating characteristic curves were used to assess the diagnostic performance in detecting liver fibrosis. Results Both NID and LSM values showed good linear correlation with collagen proportionate area values (r = 0.91 and 0.87, respectively). No difference was observed between the areas under the receiver operating characteristic curve in detecting stage F0-F1 between USMI and 2D SWE (0.97 vs 0.91, respectively; P = .20). USMI depicted liver fibrosis at an early stage more accurately than 2D SWE (area under the curve, 0.97 vs 0.82, respectively; P = .01). Rats with hepatitis had higher liver stiffness values than control rats (9.83 kPa ± 0.79 vs 6.55 kPa ± 0.38, respectively; P < .001), with no difference in the NID values between control rats and rats with hepatitis (6.75% ± 1.43 vs 6.74% ± 0.86, respectively; P = .98). Conclusion Sinusoidal capillarization viewed at US molecular imaging helped to detect early-stage liver fibrosis more accurately than two-dimensional shear-wave elastography and helped assess fibrosis regardless of inflammation. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Barr in this issue.

Comparison between spleen and liver stiffness measurements by sound touch elastography for diagnosing cirrhosis at different aminotransferase levels: a prospective multicenter study.

OBJECTIVES: To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. METHODS: This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. RESULTS: Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0-1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2-3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). CONCLUSIONS: SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. KEY POINTS: • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels.

Comparison of anatomical thermal ablation and routine thermal ablation for hepatocellular carcinoma≤50 mm: A propensity score matching.

AIM: The present study was to evaluated the clinical value of anatomical thermal ablation to treat hepatocellular carcinoma compared with routine thermal ablation. METHODS: Hepatocellular carcinoma patients with tumor diameter ≤50 mm treated by thermal ablation at our center were retrospectively enrolled from October 2015 to December 2018. Enrolled patients were grouped into the anatomical ablation group and routine ablation group, respectively. To minimize the effects of potential confounders from selection bias, a propensity score matching was carried out. Technical efficacy, recurrence and survivals rates were compared. RESULTS: Altogether 101 patients (119 lesions) were grouped into the anatomical ablation group and 101 patients (131 lesions) into the routine ablation group. The ablation zone volume of the anatomical ablation group was 36.8 (2.5-176.9) ml, significantly larger than that of the routine ablation group (28.5 [28.5 (2.8-184.3) ml] (p = 0.005)). Adjusted with propensity score matching, The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, and 0.0% for the anatomical ablation group and 6.9%, 10.1%, and 10.1% for the routine ablation group, respectively (p = 0.013). The cumulative 1-, 2-, and 3-year progression-free survival rates were 93.4%, 82.7%, and 79.0% for the anatomical ablation group, 74.2%, 56.9%, and 51.6% for the routine ablation group (p = 0.001). CONCLUSIONS: Anatomical ablation could be a favorable ablation strategy to improve therapeutic effect of thermal ablation for HCC with visible feeding vessels and reserved liver function.

Long-term efficacy of microwave ablation in the treatment of subcapsular hepatocellular carcinomas of ≤3 cm in diameter: a multicenter, propensity score-matched study.

OBJECTIVE: To compare the long-term efficacy of microwave ablation (MWA) for subcapsular and non-subcapsular hepatocellular carcinomas (HCCs) using propensity score matching (PSM). MATERIALS AND METHODS: Using a multicenter database, we enrolled 430 patients (347 men, 83 women; age range, 15-71 years) with HCCs who received percutaneous ultrasound-guided MWA, between January 2012 and December 2018. The patients were grouped as follows, based on whether the tumor was adjacent to the capsule: subcapsular group (n = 142) and non-subcapsular group (n = 142). To evaluate the correlation between subcapsular position and efficacy of MWA, a Cox proportional hazards model was used to calculate disease-free survival (DFS) and overall survival (OS) based on PSM data. RESULTS: In total, 142 pairs of patients were matched. In the PSM cohort, the 1-year, 3-year, and 5-year DFS rates of the subcapsular and non-subcapsular groups were 84%, 61%, and 47%, respectively, and 85%, 67%, and 58%, respectively, while the 1-year, 3-year, and 5-year OS rates were 98%, 90%, and 84%, respectively, and 98%, 90%, and 88%, respectively. In the PSM cohort, subcapsular position was not an independent risk factor for DFS (hazard ratio [HR] = 1.291, p = 0.196) or OS (HR = 0.926, p = 0.866). Additionally, there were no significant differences in the incidence of local tumor progression, major complications, technical success rate, number of puncture needles, and postoperative hospital stay between the two groups (p > 0.05). CONCLUSION: There were no significant differences in DFS, OS, incidence of local tumor progression, and major complications between patients with subcapsular and non-subcapsular HCCs treated with MWA.

Reliability and diagnostic accuracy of corrected slack angle derived from 2D-SWE in quantitating muscle spasticity of stroke patients.

BACKGROUND: To explore the feasibility of corrected slack angle acquired from two-dimensional shear wave elastography (2D-SWE) for quantitating the spasticity of medial gastrocnemius (MG) in stroke patients. METHODS: Consecutive stroke patients with spastic MG and matched healthy controls were recruited. Intra- and interobserver reliability of 2D-SWE measurement were evaluated, and the correlation between corrected slack angle and modified Ashworth scale (MAS) score was examined. The corrected slack angle before and after botulinum toxin A (BoNT-A) injection was compared and its diagnostic performance in classifying the severity of spasticity were assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: The intra- (0.791 95% CI 0.432-0.932) and interobserver (0.751 95% CI 0.382-0.916) reliability of slack angle acquired with 2D-SWE were good. Significant correlation was found between corrected slack angle and MAS score (R = - 0.849, p < 0.001). The corrected slack angle increased after BoNT-A injection. The cutoff value of MAS ≥ 3 had the highest sensitivity (100%) and specificity (93.33%). The positive predictive value (PPV) for classification of MAS ≥ 1+ and the negative predictive value (NPV) for classification of MAS ≥ 3 were greater than 90%. CONCLUSION: 2D-SWE was a reliable method to quantitate the post-stroke spasticity. The corrected slack angle had advantage in classifying the severity of spasticity, especially in early identification of mild spasticity and confirmation of severe spasticity.

Usefulness of New Shear Wave Elastography Technique for Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

PURPOSE: To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis. METHODS: This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated. RESULTS: Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05). CONCLUSION: STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.

Intracolic ultrasound molecular imaging: a novel method for assessing colonic tumor necrosis factor-α expression in inflammatory bowel disease.

BACKGROUND: While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa. METHODS: MBTNF-α was synthesized via a biotin-streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. RESULTS: On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients. CONCLUSION: Intracolic ultrasound molecular imaging with MBTNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD.