US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

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.

Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images.

BACKGROUND: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. METHODS: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). RESULTS: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. CONCLUSIONS: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

3D fusion is superior to 2D point-to-point contrast-enhanced US to evaluate the ablative margin after RFA for hepatocellular carcinoma.

PURPOSE: To compare the efficiency of three-dimensional (3D) and two-dimensional (2D) contrast-enhanced ultrasound (CEUS)-derived techniques in evaluating the ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: In total, 98 patients with 98 HCCs were enrolled. The 2D CEUS point-to-point imaging (2D CEUS-PI) was conducted by comparing the pre- and post-RFA 2D CEUS images manually, and the 3D CEUS fusion imaging (3D CEUS-FI) was conducted by fusing the pre- and post-RFA 3D CEUS images automatically. These two techniques were compared in distinguishing an adequate AM ≥ 5 mm. Risk factors for local tumor progression (LTP) after RFA were analyzed by the Kaplan-Meier method with log-rank test. RESULTS: The mean registration time of 3D CEUS-FI and 2D CEUS-PI was 5.0 and 9.3 min, respectively (p < 0.0001). The kappa coefficient was 0.680 for agreement between 2D CEUS-PI and 3D CEUS-FI in the evaluation of AM (p < 0.0001). Tumors with AM < 5 mm by 2D CEUS-PI were all identified as AM < 5 mm by 3D CEUS-FI. Nonetheless, 16 (26%) tumors identified as AM ≥ 5 mm by 2D CEUS-PI were re-classified as AM < 5 mm by 3D CEUS-FI. During a median follow-up time of 31.2 months (range, 3.2-66.0 months), LTP was identified in 8 tumors. The estimated 1-/2-/3-year cumulative incidence of LTP was 4.4%, 8.1%, and 10.3%, respectively. Higher estimated cumulative incidence of LTP was identified in tumors with AM < 5 mm by 2D CEUS-PI (at 3-year, 27.2% vs 0%; p < 0.001), and by 3D CEUS-FI (at 3-year, 20.7% vs 0%; p = 0.004). CONCLUSION: 3D CEUS-FI excelled in the evaluation of AM when compared with 2D CEUS-PI. With equivalent efficacy in the prediction of LTP, 3D CEUS-FI was superior to 2D CEUS-PI for its automatic and time-saving procedure. CLINICAL RELEVANCE STATEMENT: 3D CEUS fusion imaging may serve as an effective tool in evaluating ablative margin and predicting local tumor progression after RFA in HCC. KEY POINTS: • Both 2D and 3D CEUS-derived techniques could evaluate ablative margin (AM) after RFA for hepatocellular carcinoma. • 3D CEUS fusion imaging was more precise in the evaluation of AM compared to 2D CEUS point-to-point imaging, with advantages of its automatic and time-saving procedure. • An inadequate AM < 5 mm evaluated by CEUS-derived techniques was the only risk factor of LTP after RFA for hepatocellular carcinoma (p < 0.001 for 2D CEUS point-to-point imaging, and p = 0.004 for 3D CEUS fusion imaging).

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience.

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.

Preferential Hematopoietic Differentiation in Induced Pluripotent Stem Cells Derived From Human Umbilical Cord Arterial Endothelial Cells.

BACKGROUND: The major obstacle for applications of human induced pluripotent stem cells (hiPSCs) is efficient and controlled lineage-specific differentiation. Hence, a deeper understanding of the initial populations of hiPSCs is required to instruct proficient lineage commitment. METHODS: hiPSCs were generated from somatic cells by transduction of 4 human transcription factors (OCT4, SOX2, KLF4, and C-MYC) using Sendai virus vectors. Genome-wide DNA methylation analysis and transcriptional analysis were performed to evaluate the pluripotent capacity and somatic memory state of hiPSCs. Flow cytometric analysis and colony assays were performed to assess the hematopoietic differentiation capacity of hiPSCs. RESULTS: Here, we reveal human umbilical arterial endothelial cell-derived induced pluripotent stem cells (HuA-iPSCs) exhibit indistinguishable pluripotency in comparison with human embryonic stem cells and hiPSCs derived from other tissues of origin (umbilical vein endothelial cells, cord blood, foreskin fibroblasts, and fetal skin fibroblasts). However, HuA-iPSCs retain a transcriptional memory typical of the parental human umbilical cord arterial endothelial cells, together with a strikingly similar DNA methylation signature to umbilical cord blood-derived induced pluripotent stem cells that distinguishes them from other human pluripotent stem cells. Ultimately, HuA-iPSCs are most efficient in targeted differentiation toward hematopoietic lineage among all human pluripotent stem cells based on the functional and quantitative evaluation of both flow cytometric analysis and colony assays. Application of the Rho-kinase activator significantly reduces the effects of preferential hematopoietic differentiation in HuA-iPSCs, reflected in CD34+ cell percentage of day 7, hematopoietic/endothelial-associated gene expression, and even colony-forming unit numbers. CONCLUSIONS: Collectively, our data suggest that somatic cell memory may predispose HuA-iPSCs to differentiate more amenably into hematopoietic fate, bringing us closer to generating hematopoietic cell types in vitro from nonhematopoietic tissue for therapeutic applications.

Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study.

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.

Three-dimensional ultrasound fusion imaging in precise needle placement for thermal ablation of hepatocellular carcinoma.

PURPOSE: To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. METHODS: A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. RESULTS: According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. CONCLUSIONS: Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

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.

Predicting Infectious Complications after Percutaneous Thermal Ablation of Liver Malignancies: A 12-year Single-Center Experience.

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.

Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.

OBJECTIVES: The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS: Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS: Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT: Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS: • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

Nomogram based on high-frequency shear wave elastography (SWE) to evaluate chronic changes after kidney transplantation.

OBJECTIVES: To construct a nomogram with high-frequency shear wave elastography (SWE) as a noninvasive method to accurately assess chronic changes in renal allografts. METHODS: A total of 191 renal transplantation patients (127 cases in the training group and 64 cases in the verification group) were included in this study. All patients received conventional ultrasound and high-frequency SWE examination, followed directly by biopsy the next day. The chronic changes were divided into mild, moderate, and severe. Multivariate logistic analyses were used to select significant variables, which were used to develop the nomogram. Nomogram models were assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). RESULTS: The cutoff value of SWE in mild, moderate, and severe chronic changes was 18.9, 22.5, and 27.6 kPa, respectively. The areas under the curve (AUCs) of SWE in the differential diagnosis of mild and moderate to severe chronic changes and mild to moderate and severe chronic changes were 0.817 and 0.870, respectively. Multivariate analysis showed that time since transplantation, proteinuria, glomerular filtration rate, echogenicity, and SWE were independent diagnostic factors for moderate to severe chronic changes (all p < 0.05); thus, a nomogram was successfully developed. The AUCs of the nomogram in the training and validation groups were 0.905 and 0.938, respectively. The high agreement between the model predictions and the actual observations was confirmed by calibration plot and DCA. CONCLUSIONS: Based on SWE, the nomogram provided an insightful and applicable tool to evaluate chronic changes in renal allografts. KEY POINTS: • In kidney transplantation, compared with acute changes, chronic changes are significantly correlated with cortical stiffness. • SWE shows good performance in identifying mild to moderate and severe chronic changes, with an AUC of 0.870. • Time since transplantation, proteinuria, glomerular filtration rate, echogenicity, and SWE are independent diagnostic factors for moderate to severe chronic changes in renal allografts.

Predicting symptomatic post-hepatectomy liver failure in patients with hepatocellular carcinoma: development and validation of a preoperative nomogram.

OBJECTIVE: To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. RESULTS: A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5 kPa, Child-Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer-Lemeshow goodness-of-fit test, p = 0.641, p = 0.06, and p = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. CONCLUSION: An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. CLINICAL RELEVANCE STATEMENT: A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in 'how much remnant is enough in liver resection'. KEY POINTS: • An elevated liver stiffness with the best cutoff value of 9.5 kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child-Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

Analysis of Sonazoid contrast-enhanced ultrasound for predicting the risk of microvascular invasion in hepatocellular carcinoma: a prospective multicenter study.

OBJECTIVES: The aim of this study was to evaluate the potential of Sonazoid contrast-enhanced ultrasound (SNZ-CEUS) as an imaging biomarker for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: From August 2020 to March 2021, we conducted a prospective multicenter study on the clinical application of Sonazoid in liver tumor; a MVI prediction model was developed and validated by integrating clinical and imaging variables. Multivariate logistic regression analysis was used to establish the MVI prediction model; three models were developed: a clinical model, a SNZ-CEUS model, and a combined model and conduct external validation. We conducted subgroup analysis to investigate the performance of the SNZ-CEUS model in non-invasive prediction of MVI. RESULTS: Overall, 211 patients were evaluated. All patients were split into derivation (n = 170) and external validation (n = 41) cohorts. Patients who had MVI accounted for 89 of 211 (42.2%) patients. Multivariate analysis revealed that tumor size (> 49.2 mm), pathology differentiation, arterial phase heterogeneous enhancement pattern, non-single nodular gross morphology, washout time (< 90 s), and gray value ratio (≤ 0.50) were significantly associated with MVI. Combining these factors, the area under the receiver operating characteristic (AUROC) of the combined model in the derivation and external validation cohorts was 0.859 (95% confidence interval (CI): 0.803-0.914) and 0.812 (95% CI: 0.691-0.915), respectively. In subgroup analysis, the AUROC of the SNZ-CEUS model in diameter ≤ 30 mm and ˃ 30 mm cohorts were 0.819 (95% CI: 0.698-0.941) and 0.747 (95% CI: 0.670-0.824). CONCLUSIONS: Our model predicted the risk of MVI in HCC patients with high accuracy preoperatively. CLINICAL RELEVANCE STATEMENT: Sonazoid, a novel second-generation ultrasound contrast agent, can accumulate in the endothelial network and form a unique Kupffer phase in liver imaging. The preoperative non-invasive prediction model based on Sonazoid for MVI is helpful for clinicians to make individualized treatment decisions. KEY POINTS: • This is the first prospective multicenter study to analyze the possibility of SNZ-CEUS preoperatively predicting MVI. • The model established by combining SNZ-CEUS image features and clinical features has high predictive performance in both derivation cohort and external validation cohort. • The findings can help clinicians predict MVI in HCC patients before surgery and provide a basis for optimizing surgical management and monitoring strategies for HCC patients.

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.

Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.