Contrast-Enhanced Ultrasound With Perfluorobutane for Hepatocellular Carcinoma Diagnosis: Comparison of Imaging Phases and Diagnostic Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Low dose of contrast agent and low radiation liver computed tomography with deep-learning-based contrast boosting model in participants at high-risk for hepatocellular carcinoma: prospective, randomized, double-blind study.

OBJECTIVE: To investigate the image quality and lesion conspicuity of a deep-learning-based contrast-boosting (DL-CB) algorithm on double-low-dose (DLD) CT of simultaneous reduction of radiation and contrast doses in participants at high-risk for hepatocellular carcinoma (HCC). METHODS: Participants were recruited and underwent four-phase dynamic CT (NCT04722120). They were randomly assigned to either standard-dose (SD) or DLD protocol. All CT images were initially reconstructed using iterative reconstruction, and the images of the DLD protocol were further processed using the DL-CB algorithm (DLD-DL). The primary endpoint was the contrast-to-noise ratio (CNR), the secondary endpoint was qualitative image quality (noise, hepatic lesion, and vessel conspicuity), and the tertiary endpoint was lesion detection rate. The t-test or repeated measures analysis of variance was used for analysis. RESULTS: Sixty-eight participants with 57 focal liver lesions were enrolled (20 with HCC and 37 with benign findings). The DLD protocol had a 19.8% lower radiation dose (DLP, 855.1 ± 254.8 mGy·cm vs. 713.3 ± 94.6 mGy·cm, p = .003) and 27% lower contrast dose (106.9 ± 15.0 mL vs. 77.9 ± 9.4 mL, p < .001) than the SD protocol. The comparative analysis demonstrated that CNR (p < .001) and portal vein conspicuity (p = .002) were significantly higher in the DLD-DL than in the SD protocol. There was no significant difference in lesion detection rate for all lesions (82.7% vs. 73.3%, p = .140) and HCCs (75.7% vs. 70.4%, p = .644) between the SD protocol and DLD-DL. CONCLUSIONS: DL-CB on double-low-dose CT provided improved CNR of the aorta and portal vein without significant impairment of the detection rate of HCC compared to the standard-dose acquisition, even in participants at high risk for HCC. KEY POINTS: • Deep-learning-based contrast-boosting algorithm on double-low-dose CT provided an improved contrast-to-noise ratio compared to standard-dose CT. • The detection rate of focal liver lesions was not significantly differed between standard-dose CT and a deep-learning-based contrast-boosting algorithm on double-low-dose CT. • Double-low-dose CT without a deep-learning algorithm presented lower CNR and worse image quality.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Differentiation between small (< 4.5 cm) true subepithelial tumors and ectopic pancreas in the small bowel on computed tomography enterography.

OBJECTIVES: To identify imaging features that can differentiate ectopic pancreas from true subepithelial tumors (SETs) in the small bowel using CT enterography and to assess whether radiologists' performance for the differentiation can be improved with the knowledge of significant CT findings. METHODS: CT images of ectopic pancreas (n = 29) and pathologically proven SETs (n = 61) were retrospectively reviewed by two radiologists in consensus. CT items analyzed included lesion location, contour (round, ovoid, flat/conformed), growth pattern, margin, homogeneity, necrosis, feeding vessel, surface ulceration, and enhancement pattern. For quantitative analysis, Hounsfield unit, longer diameter (LD), and shorter diameter (SD) of the lesion were measured. Univariate and multivariate analyses were performed. Diagnostic performance for differentiating ectopic pancreas from SETs was independently evaluated by two other radiologists using a receiver operating characteristic analysis. RESULTS: Age < 63 years, female sex, flat/conformed appearance, homogeneous enhancement, the absence of feeding vessels and necrosis, and an LD/SD ratio > 1.5 were significant variables for differentiating ectopic pancreas from small bowel SETs (p < 0.05). In the multivariate analysis, flat/conformed appearance, the absence of feeding vessels, and female sex remained suggestive features for ectopic pancreas. Area under the curve values for differentiating between two disease entities increased by both independent reviewers with knowledge of these significant CT features. CONCLUSIONS: Ectopic pancreas in the small bowel can be effectively differentiated from small (< 4.5 cm) true SETs by a flat/conformed appearance and the absence of feeding vessels on CT enterography. In addition, radiologists' performance for differentiating ectopic pancreas from small bowel SETs was improved with the knowledge of these significant CT findings. KEY POINTS: • Ectopic pancreas in the small bowel can be differentiated from small (< 4.5 cm) subepithelial tumors on CT. • Differential CT findings of the ectopic pancreas are a flat or conformed appearance and the absence of a feeding vessel. • Radiologists' performance for differentiating ectopic pancreas from small bowel SETs can be improved with the knowledge of differential CT findings.

Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma.

OBJECTIVES: To evaluate the diagnostic accuracy of perfluorobutane contrast-enhanced ultrasonography (CEUS) for hepatocellular carcinoma (HCC) and to explore how accuracy can be improved compared to conventional diagnostic criteria in at-risk patients. METHODS: A total of 123 hepatic nodules (≥ 1 cm) from 123 at-risk patients who underwent perfluorobutane CEUS between 2013 and 2020 at three institutions were retrospectively analyzed. Ninety-three percent of subjects had pathological results, except benign lesions stable in follow-up images. We evaluated presence of arterial phase hyperenhancement (APHE), washout time and degree, and Kupffer phase (KP) defects. KP defects are defined as hypoenhancing lesions relative to the liver in KP. HCC was diagnosed in two ways: (1) Liver Imaging Reporting and Data System (LI-RADS) criteria defined as APHE and late (≥ 60 s)/mild washout, and (2) APHE and Kupffer (AK) criteria defined as APHE and KP defect. We explored grayscale features that cause misdiagnosis of HCC and reflected in the adjustment. Diagnostic performance was compared using McNemar's test. RESULTS: There were 77 HCCs, 15 non-HCC malignancies, and 31 benign lesions. An ill-defined margin without hypoechoic halo on grayscale applied as a finding that did not suggest HCC. Regarding diagnosis of HCC, sensitivity of AK criteria (83.1%; 95% confidence interval [CI]: 72.9-90.7%) was higher than that of LI-RADS criteria (75.3%; 95% CI: 64.2-84.4%; p = 0.041). Specificity was 91.3% (95% CI: 79.2-97.6%) in both groups. CONCLUSION: On perfluorobutane CEUS, diagnostic criteria for HCC using KP defect with adjustment by grayscale findings had higher diagnostic performance than conventional criteria without losing specificity. KEY POINTS: • Applying Kupffer phase defect instead of late/mild washout and adjusting with grayscale findings can improve the diagnostic performance of perfluorobutane-enhanced US for HCC. • Adjustment with ill-defined margins without a hypoechoic halo for features unlikely to be HCC decreases false positives for HCC diagnosis using the perfluorobutane-enhanced US. • After adjustment with grayscale findings, the sensitivity and accuracy of the APHE and Kupffer criteria were higher than those of the LI-RADS criteria; specificity was 91.3% for both.

Prediction of residual tumor and overall survival after first-line surgery in patients with pancreatic ductal adenocarcinoma using preoperative magnetic resonance imaging findings.

BACKGROUND: Complete resection is the only potentially curative treatment in patients with pancreatic ductal adenocarcinoma (PDA) and is associated with a longer overall survival (OS) than incomplete resection of tumor. Hence, prediction of the resection status after surgery would help predict the prognosis of patients with PDA. PURPOSE: To predict residual tumor (R) classification and OS in patients who underwent first-line surgery for PDA using preoperative magnetic resonance imaging (MRI). MATERIAL AND METHODS: In this study, 210 patients with PDA who underwent MRI and first-line surgery were randomly categorized into a test group (n=150) and a validation group (n=60). The R classification was divided into R0 (no residual tumor) and R1/R2 (microscopic/macroscopic residual tumor). Preoperative MRI findings associated with R classification and OS were assessed by using logistic regression and Cox proportional hazard models. In addition, the prediction models for the R classification and OS were validated using calibration plots and C statistics. RESULTS: On preoperative MRI, portal vein encasement (odds ratio 4.755) was an independent predictor for R1/R2 resection (P=0.040). Tumor size measured on MRI (hazard ratio [HR] per centimeter 1.539) was a predictor of OS, along with pathologic N1 and N2 stage (HR 1.944 and 3.243, respectively), R1/R2 resection (HR 3.273), and adjuvant chemoradiation therapy (HR 0.250) (P<0.050). Calibration plots demonstrated satisfactory predictive performance. CONCLUSION: Preoperative MRI was valuable for predicting R1/R2 resection using portal vein encasement. Tumor size measured on MRI was useful for the prediction of OS after first-line surgery for PDA.

Current Status of Experimental Animal Skin Flap Models: Ischemic Preconditioning and Molecular Factors.

Skin flaps are necessary in plastic and reconstructive surgery for the removal of skin cancer, wounds, and ulcers. A skin flap is a portion of skin with its own blood supply that is partially separated from its original position and moved from one place to another. The use of skin flaps is often accompanied by cell necrosis or apoptosis due to ischemia-reperfusion (I/R) injury. Proinflammatory cytokines, such as nuclear factor kappa B (NF-κB), inhibitor of kappa B (IκB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and oxygen free radicals are known causative agents of cell necrosis and apoptosis. To prevent I/R injury, many investigators have suggested the inhibition of proinflammatory cytokines, stem-cell therapies, and drug-based therapies. Ischemic preconditioning (IPC) is a strategy used to prevent I/R injury. IPC is an experimental technique that uses short-term repetition of occlusion and reperfusion to adapt the area to the loss of blood supply. IPC can prevent I/R injury by inhibiting proinflammatory cytokine activity. Various stem cell applications have been studied to facilitate flap survival and promote angiogenesis and vascularization in animal models. The possibility of constructing tissue engineered flaps has also been investigated. Although numerous animal studies have been published, clinical data with regard to IPC in flap reconstruction have never been reported. In this study, we present various experimental skin flap methods, IPC methods, and methods utilizing molecular factors associated with IPC.

Reduction of olecranon fractures with no or minimal dorsal cortex comminution based on the contour of the posterior ulnar cortex: does it restore the greater sigmoid notch?

INTRODUCTION: When treating olecranon fractures surgically, surgeons rely on the contour of the posterior cortex of the proximal ulna. However, it is unclear whether the greater sigmoid notch (GSN) is restored anatomically by this method. We analyzed whether reduction of fractures based on the posterior ulnar cortex contour is reliable for restoration of the GSN contour in displaced olecranon fractures with no or minimal dorsal cortex comminution. MATERIALS AND METHODS: We performed a retrospective review of 23 patients with Mayo type 2 olecranon fractures with no or minimal dorsal cortex comminution who were treated surgically. We analyzed pre- and postoperative elbow CT images and measured the interfragmentary distance (IFD), articular step-off, articular gap, contour defect and GSN angle to evaluate the restoration of the GSN contour. RESULTS: The mean preoperative IFD and contour defect were 16.5 mm (range 4.3-35.6 mm) and 4.3 mm (range 0.7-13.3 mm), respectively. Postoperatively, there was no residual IFD, and the mean contour defect decreased significantly to 1.4 mm (range 0-3.7 mm). The residual articular step-off and gap were 0.2 mm (range 0-3.8 mm) and 1.0 mm (range 0-5.9 mm), respectively. Acceptable GSN restoration was achieved in 14 of 23 patients (60.9%). Sixteen patients had > 2 mm of preoperative contour defect, and 7 (43.8%) achieved acceptable GSN restoration; the remaining 7 patients (100%) who had < 2 mm of the contour defect achieved acceptable GSN restoration. Patients whose preoperative contour defect was > 2 mm had a higher risk of unacceptable GSN restoration, with an odds ratio of 2.29 (p = 0.019). CONCLUSIONS: In displaced olecranon fractures without significant dorsal cortex comminution, reduction based on the posterior ulnar cortex could be reliable for fractures with under 2 mm of preoperative contour defect, but not for those with > 2 mm of contour defect. LEVEL OF EVIDENCE: IV.

Nurses' perspectives of the patient care experience assessment items using importance-performance analysis.

AIM: This study aimed to evaluate the importance and performance of hospital nurses for patient experience evaluation items from the perspective of care providers and to identify the items that need improvement. BACKGROUND: Patient experience includes customized treatment and services that focus on patient satisfaction and needs, with healthcare providers participating as partners. METHODS: The study was conducted using a cross-sectional survey design, and data were collected on the importance and performance of 15 out of 24 patient experience evaluation items. The sample population consisted of 193 direct care nurses from two hospitals in South Korea. RESULTS: The results showed the items with significant differences in importance and performance ('concentrate here' areas) such as 'description of a drug' (t = 2.26, p = .025), 'listening to patients' (t = 6.64, p < .001), 'description of adverse drug reactions' (t = 10.19, p < .001), 'clean hospital environment' (t = 2.95, p = .004) and 'easy notification of complaints' (t = 8.37, p < .001). CONCLUSION: The findings highlight the importance of awareness and performance in patient experience evaluation items from the nurses' perspective. While some items were recognized as important but not performing well, others were identified as important and performing well. IMPLICATIONS FOR NURSING MANAGEMENT: As identified in this study, nursing managers should strive to develop nursing practice standards and educational programs for nurses to improve patient experiences. It is crucial that these changes are reflected in policies.

Gadoxetate-enhanced MRI Features of Proliferative Hepatocellular Carcinoma Are Prognostic after Surgery.

Background Hepatocellular carcinomas (HCCs) are heterogeneous neoplasms, and the prognosis varies based on the subtype. Two broad molecular classes of HCC have been proposed: a proliferative and a nonproliferative class. Purpose To evaluate the gadoxetate-enhanced MRI findings of the proliferative class HCC and its prognostic significance after surgery. Materials and Methods This retrospective cohort study evaluated patients with surgically resected treatment-naive single HCC (≤5 cm) who underwent hepatic resection from January 2010 through February 2013 and preoperative gadoxetate-enhanced MRI. A Cox proportional hazards model was used to determine the predictive factors for overall survival (OS), intrahepatic distant recurrence, and extrahepatic metastasis (EM). The mean follow-up period was 75.5 months ± 30.2 (standard deviation). Multivariable logistic regression was performed to determine factors associated with proliferative class HCC. Results A total of 158 patients (mean age, 57 years ± 11; 128 men and 30 women) were evaluated. Forty-two of the 158 HCCs (26.6%) were proliferative class HCCs (17 macrotrabecular-massive HCCs, 14 keratin 19-positive HCCs, 10 scirrhous HCCs, and one sarcomatoid HCC). The proliferative class was associated with worse OS (hazard ratio [HR], 3.1; 95% CI: 1.5, 6.0; P = .01) and higher rates of intrahepatic distant recurrence (HR, 1.83; 95% CI: 1.1, 2.9; P = .01) and EM (HR, 9.97; 95% CI: 3.2, 31.4; P < .001). Rim arterial phase hyperenhancement (APHE) at gadoxetate-enhanced MRI (odds ratio [OR], 6.35; 95% CI: 1.9, 21.7; P = .01) and high serum α-fetoprotein (>100 ng/mL) (OR, 4.18; 95% CI: 1.64, 10.7; P = .01) were independent predictors for proliferative HCC. The presence of rim APHE was associated with poor OS (HR, 2.4; 95% CI: 1.2, 4.9; P = .02) and higher rates of EM (HR, 7.4; 95% CI: 2.5, 21.7; P < .01). Conclusion The proliferative class of hepatocellular carcinoma (HCC) is an independent factor for poor overall survival with increased rates of intrahepatic and extrahepatic metastasis. Rim arterial phase hyperenhancement at gadoxetate-enhanced MRI may help to identify proliferative class HCC and predict poor overall survival and an increased incidence of extrahepatic metastasis. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Krinsky and Shanbhogue in this issue.

Evaluation of LI-RADS Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma in Liver Transplant Candidates: Intraindividual Comparison between CT and Hepatobiliary Agent-enhanced MRI.

Background The Liver Imaging Reporting and Data System (LI-RADS), version 2018, treatment response algorithm (TRA) is used to assess hepatocellular carcinoma (HCC) after local-regional therapy (LRT). However, its diagnostic performance has not yet been fully compared between CT and hepatobiliary agent (HBA)-enhanced MRI in patients who have undergone liver transplant (LT). Purpose To compare the diagnostic performance of LI-RADS TRA when using CT versus using HBA-enhanced MRI in an intraindividual manner according to pathologic results. Materials and Methods Between January 2011 and September 2019, 165 patients with 237 clinically suspected HCCs underwent LRT followed by LT and were retrospectively included. All patients underwent both CT and HBA-enhanced MRI after LRT and before LT. Three radiologists independently assessed tumor viability with both modalities by using LI-RADS TRA and reached a consensus. Pathologic tumor viability categorized as either completely (100%) or incompletely (<100%) necrotic obtained from the explanted liver served as the reference standard. Sensitivity and specificity of the LI-RADS TRA in the consensus reading were then compared between CT and HBA-enhanced MRI by using the ratio estimator approach. Interobserver agreements were calculated by using Fleiss κ statistics. Results There were 165 patients (mean age, 62 years ± 9 [standard deviation]; 135 men) with a total of 237 lesions, of which 107 were viable tumors (45.1%) at pathologic evaluation. With the LI-RADS TRA, sensitivity and specificity of the viable category for detection of viable HCCs at pathologic evaluation were 42.1% (45 of 107 lesions) and 95.4% (124 of 130 lesions) with CT and 52.3% (56 of 107 lesions) and 93.9% (122 of 130 lesions) with HBA-enhanced MRI, with a significant difference in sensitivity but not specificity (P = .009 and P = .42, respectively). Interobserver agreements for the LI-RADS TRA were substantial for both CT and HBA-enhanced MRI (κ, 0.69 for both). Conclusion In patients who underwent local-regional therapy for hepatocellular carcinoma before liver transplant, hepatobiliary agent-enhanced MRI was more sensitive than CT in evaluating tumor viability with the Liver Imaging Reporting and Data System, version 2018, treatment response algorithm. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Bashir and Mendiratta-Lala in this issue.

Joint segmentation and classification of hepatic lesions in ultrasound images using deep learning.

OBJECTIVES: To develop a convolutional neural network system to jointly segment and classify a hepatic lesion selected by user clicks in ultrasound images. METHODS: In total, 4309 anonymized ultrasound images of 3873 patients with hepatic cyst (n = 1214), hemangioma (n = 1220), metastasis (n = 1001), or hepatocellular carcinoma (HCC) (n = 874) were collected and annotated. The images were divided into 3909 training and 400 test images. Our network is composed of one shared encoder and two inference branches used for segmentation and classification and takes the concatenation of an input image and two Euclidean distance maps of foreground and background clicks provided by a user as input. The performance of hepatic lesion segmentation was evaluated based on the Jaccard index (JI), and the performance of classification was based on accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC). RESULTS: We achieved performance improvements by jointly conducting segmentation and classification. In the segmentation only system, the mean JI was 68.5%. In the classification only system, the accuracy of classifying four types of hepatic lesions was 79.8%. The mean JI and classification accuracy were 68.5% and 82.2%, respectively, for the proposed joint system. The optimal sensitivity and specificity and the AUROC of classifying benign and malignant hepatic lesions of the joint system were 95.0%, 86.0%, and 0.970, respectively. The respective sensitivity, specificity, and the AUROC for classifying four hepatic lesions of the joint system were 86.7%, 89.7%, and 0.947. CONCLUSIONS: The proposed joint system exhibited fair performance compared to segmentation only and classification only systems. KEY POINTS: • The joint segmentation and classification system using deep learning accurately segmented and classified hepatic lesions selected by user clicks in US examination. • The joint segmentation and classification system for hepatic lesions in US images exhibited higher performance than segmentation only and classification only systems. • The joint segmentation and classification system could assist radiologists with minimal experience in US imaging by characterizing hepatic lesions.

Radio-pathologic correlation of biphenotypic primary liver cancer (combined hepatocellular cholangiocarcinoma): changes in the 2019 WHO classification and impact on LI-RADS classification at liver MRI.

OBJECTIVES: To explain the new changes in pathologic diagnoses of biphenotypic primary liver cancer (PLC) according to the updated 2019 World Health Organization (WHO) classification and how it impacts Liver Imaging Reporting and Data System (LI-RADS) classification using gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS: We retrospectively included 209 patients with pathologically proven biphenotypic PLCs according to the 2010 WHO classification who had undergone preoperative Gd-EOB-MRI between January 2009 and December 2018. Imaging analysis including LI-RADS classification and pathologic review including the proportion of tumor components were performed. Frequencies of each diagnosis and subtype according to the 2010 and 2019 WHO classifications were compared, and changes in LI-RADS classification were evaluated. Univariable and multivariable analysis were performed to determine significant tumor component for LI-RADS classification. RESULTS: Of the 209 biphenotypic PLCs of the 2010 WHO classification, 177 (84.7%) were diagnosed as bipheonotypic PLCs, 25 (12.0%) as hepatocellular carcinomas (HCCs), and 7 (3.3%) as cholangiocarcinomas (CCAs) using the 2019 WHO classification. Of the 177 biphenotypic PLCs, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. There were no significant differences in the proportion of LR-5 and LR-M categories between the WHO 2010 and 2019 classifications (p = 0.941). Proportion of HCC component was the only independent factor for LI-RADS classification (adjusted odds ratio, 1.02; p < 0.001). CONCLUSION: According to the 2019 WHO classification, 15% of biphenotypic PLCs from the 2010 WHO classification were re-diagnosed as HCCs or CCAs, and a substantial proportion of biphenotypic PLCs of the 2019 WHO classification could be categorized as LR-4 or LR-5 on Gd-EOB-MRI. KEY POINTS: • Among 209 diagnosed biphenotypic PLCs according to the 2010 WHO classification, 177 (84.7%) lesions were reclassified as bipheonotypic PLCs, 25 (12.0%) as HCCs, and 7 (3.3%) as CCAs using the 2019 WHO classification. • Of the 177 biphenotypic PLCs at the 2019 WHO classification, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. • LI-RADS classification relied on the proportion of HCC component (adjusted odds ratio,1.02; p < 0.001).

Intra-individual comparison of dual portal venous phases for non-invasive diagnosis of hepatocellular carcinoma at gadoxetic acid-enhanced liver MRI.

OBJECTIVES: To compare the diagnostic performances of first and second portal venous phases (PVP1 and PVP2) in revealing washout and capsule appearance for non-invasive HCC diagnoses in gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS: This retrospective study included 123 at-risk patients with 160 hepatic observations (HCCs, n = 116; non-HCC malignancies, n = 18; benign, n = 26) showing arterial phase hyper-enhancement (APHE) ≥ 1 cm at Gd-EOB-MRI. The mean time intervals from gadoxetic acid injection to PVP1 and PVP2 acquisitions were 53 ± 2 s and 73 ± 3 s, respectively. After evaluating image findings independently, imaging findings and diagnoses were finalized by a consensus of two radiologists using either PVP1 or PVP2 image sets according to the LI-RADS v2018 or EASL criteria. Sensitivity, specificity, and accuracy were compared. RESULTS: Among HCCs, more washout and enhancing capsule were observed in PVP2 (83.6% and 27.6%) than in PVP1 (50.9% and 19.8%) (p < 0.001, both). The PVP2 set presented significantly higher sensitivity (83.6% vs. 53.5%, LI-RADS; 82.8% vs. 50.0%, EASL; p < 0.001, both) and accuracy (0.88 vs. 0.73, LI-RADS; 0.88 vs. 0.72, EASL; p < 0.001, both) than the PVP1 set without significant specificity loss (93.2% vs. 93.2%, by LI-RADS or EASL; p = 0.32, both). None of the non-HCC malignancy was non-invasively diagnosed as HCC in both PVP image sets. CONCLUSION: Late acquisition of PVP detected washout and enhancing capsule of HCC more sensitively than early acquisition, enabling accurate diagnoses of HCC, according to LI-RADS or EASL criteria. KEY POINTS: • Among HCCs, more washout and enhancing capsules were observed in PVP2 than PVP1, quantitatively and qualitatively. • The portal venous phase acquired at around 70 s after contrast media administration (PVP2) provided significantly higher sensitivity and AUC value than PVP1 by using LI-RADS v2018 or EASL criteria. • More HCCs were categorized as LR-5 in PVP2 than in PVP1 images, and the specificity of PVP2 (93.5%) was comparable with PVP1 (93.5%).

Comparisons between image quality and diagnostic performance of 2D- and breath-hold 3D magnetic resonance cholangiopancreatography at 3T.

OBJECTIVES: To compare the image quality and diagnostic performance of 2D MRCP to those of breath-hold 3D MRCP using compressed sensing (CS-MRCP) and gradient and spin-echo (GRASE-MRCP) at 3T. METHODS: From January to November 2018, patients who underwent pancreatobiliary MRI including 2D MRCP and two breath-hold 3D MRCP using CS and GRASE at 3T were included. Three radiologists independently evaluated image quality, motion artifact, and pancreatic cyst conspicuity. Diagnostic performance was assessed for bile duct anatomic variation, bile duct, and pancreatic diseases using a composite algorithm as reference standards. Pancreatic lesion detectability and conspicuity were evaluated using JAFROC and generalized estimating equation analysis. RESULTS: One hundred patients (male = 50) were included. Bile duct anatomic variation, bile duct and pancreatic diseases were present in respectively 31, 15, and 79 patients. Breath-hold 3D MRCP provided better image quality than 2D MRCP (3.5 ± 0.6 in 2D MRCP; 4.0 ± 0.7 in GRASE-MRCP and 3.9 ± 0.8 in CS-MRCP, p < 0.001 for both). There was no difference in motion artifact between 2D and breath-hold 3D MRCP (p = 0.1). Breath-hold 3D CS-MRCP provided better pancreatic cyst conspicuity than 2D MRCP (2.7 [95% CI: 2.5-3.0] vs. 2.3 [95% CI: 2.1-2.5], p = 0.001). There were no significant differences between the diagnostic performance of the three sequences in the detection of bile duct anatomic variation or pancreatic lesions (p > 0.05). CONCLUSION: Breath-hold 3D MRCP with GRASE or CS can provide better image quality than 2D MRCP in a comparable scan time. KEY POINTS: • Breath-hold 3D MRCP using compressed sensing (CS) or gradient and spin-echo (GRASE) provided a better image quality with less image blurring than 2D MRCP. • There were no significant differences between 2D MRCP and breath-hold 3D MRCP in either motion artifact or the number of non-diagnostic exams. • There were no significant differences between 2D MRCP and either type of breath-hold 3D MRCP in the diagnosis of bile duct anatomic variation or detection of pancreatic lesions.

Transabdominal Ultrasound for Follow-Up of Incidentally Detected Low-Risk Pancreatic Cysts: A Prospective Multicenter Study.

OBJECTIVE. The purpose of this study is to investigate the detection rate of transabdominal ultrasound (TAUS) for pancreatic cysts incidentally detected on CT or MRI as well as the factors that influence detection rates. SUBJECTS AND METHODS. Fifty-seven patients with low-risk pancreatic cysts (n = 77; cyst size, 5 mm to 3 cm) that were incidentally detected on CT or MRI were prospectively enrolled at five institutions. At each institution, TAUS was independently performed by two radiologists who assessed detection of cysts, cyst location and size, and the diameter of the main pancreatic duct (MPD). Cyst detection rates based on cyst size, location, and multiplicity and the body mass index of the patient were compared using the Mann-Whitney test. Kappa statistics and the interclass correlation coefficient were used to evaluate interobserver agreement regarding cyst detection and consistency of cyst size and the diameter of the MPD on TAUS versus prior CT or MRI. RESULTS. The detection rate for known low-risk pancreatic cysts was 81.8% (63/77) and 83.1% (64/77) for TAUS conducted by each of the two radiologists. The detection rate for larger (≥ 10 mm) cysts was significantly higher than that for smaller cysts (89.0% vs 63.6% for TAUS performed and interpreted by radiologist 1 [TAUS 1] and 89.0% vs 68.2% for TAUS conducted and interpreted by radiologist 2 [TAUS 2]; p < .05). A higher detection rate was noted for cysts located outside the tail of the pancreas compared with those located in the tail (89.5% vs 65.0% for TAUS 2; p = .01), and the detection rate was also significantly higher for single cysts than for multiple cysts (90.9% vs 69.7% for TAUS 1; p = .02). However, no significant difference was observed for body mass index. Interobserver agreement was excellent regarding the size of the detected cysts (inter-class correlation coefficient: 0.964 [95% CI, 0.940-0.979] for CT, TAUS 1, and TAUS 2 and 0.965 [95% CI. 0.924-986] for MRI, TAUS 1, and TAUS 2) and the diameter of the MPD (interclass correlation coefficient, 0.934; 95% CI, 0.898-0.959). CONCLUSION. TAUS could be a useful alternative imaging tool for surveillance of known low-risk pancreatic cysts, especially single pancreatic cysts and those that are of larger size (≥ 1 cm) or are located outside the tail.

Determining the Intellectual Structure and Academic Trends of Smart Home Health Care Research: Coword and Topic Analyses.

BACKGROUND: With the rapid development of information and communication technologies, smart homes are being investigated as effective solutions for home health care. The increasing academic attention on smart home health care has primarily been on the development and application of smart home technologies. However, comprehensive studies examining the general landscape of diverse research areas for smart home health care are still lacking. OBJECTIVE: This study aims to determine the intellectual structure of smart home health care in a time series by conducting a coword analysis and topic analysis. Specifically, it investigates (1) the intellectual basis of smart home health care through overall academic status, (2) the intellectual foci through influential keywords and their evolutions, and (3) intellectual trends through primary topics and their evolutions. METHODS: Analyses were conducted in 5 steps: (1) data retrieval from article databases (Web of Science, Scopus, and PubMed) and the initial dataset preparation of 6080 abstracts from the year 2000 to the first half of 2019; (2) data preprocessing and refinement extraction of 25,563 words; (3) a descriptive analysis of the overall academic status and period division (ie, 4 stages of 3-year blocks); (4) coword analysis based on word co-occurrence networks for the intellectual foci; and (5) topic analysis for the intellectual trends based on latent Dirichlet allocation (LDA) topic modeling, word-topic networks, and researcher workshops. RESULTS: First, regarding the intellectual basis of smart home health care, recent academic interest and predominant journals and research domains were verified. Second, to determine the intellectual foci, primary keywords were identified and classified according to the degree of their centrality values. Third, 5 themes pertaining to the topic evolution emerged: (1) the diversification of smart home health care research topics; (2) the shift from technology-oriented research to technological convergence research; (3) the expansion of application areas and system functionality of smart home health care; (4) the increased focus on system usability, such as service design and experiences; and (5) the recent adaptation of the latest technologies in health care. Based on these findings, the pattern of technology diffusion in smart home health care research was determined as the adaptation of technologies, the proliferation of application areas, and an extension into system design and service experiences. CONCLUSIONS: The research findings provide academic and practical value in 3 aspects. First, they promote a comprehensive understanding of the smart home health care domain by identifying its multifaceted intellectual structure in a time series. Second, they can help clinicians discern the development and dispersion level of their respective disciplines. Third, the pattern of technology diffusion in smart home health care could help scholars comprehend current and future research trends and identify research opportunities based on upcoming research waves of newly adapted technologies in smart home health care.

Effects of a Catechol-Functionalized Hyaluronic Acid Patch Combined with Human Adipose-Derived Stem Cells in Diabetic Wound Healing.

INTRODUCTION: Chronic inflammation and impaired neovascularization play critical roles in delayed wound healing in diabetic patients. To overcome the limitations of current diabetic wound (DBW) management interventions, we investigated the effects of a catechol-functionalized hyaluronic acid (HA-CA) patch combined with adipose-derived mesenchymal stem cells (ADSCs) in DBW mouse models. METHODS: Diabetes in mice (C57BL/6, male) was induced by streptozotocin (50 mg/kg, >250 mg/dL). Mice were divided into four groups: control (DBW) group, ADSCs group, HA-CA group, and HA-CA + ADSCs group (n = 10 per group). Fluorescently labeled ADSCs (5 × 105 cells/100 µL) were transplanted into healthy tissues at the wound boundary or deposited at the HA-CA patch at the wound site. The wound area was visually examined. Collagen content, granulation tissue thickness and vascularity, cell apoptosis, and re-epithelialization were assessed. Angiogenesis was evaluated by immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. RESULTS: DBW size was significantly smaller in the HA-CA + ADSCs group (8% ± 2%) compared with the control (16% ± 5%, p < 0.01) and ADSCs (24% ± 17%, p < 0.05) groups. In mice treated with HA-CA + ADSCs, the epidermis was regenerated, and skin thickness was restored. CD31 and von Willebrand factor-positive vessels were detected in mice treated with HA-CA + ADSCs. The mRNA and protein levels of VEGF, IGF-1, FGF-2, ANG-1, PIK, and AKT in the HA-CA + ADSCs group were the highest among all groups, although the Spred1 and ERK expression levels remained unchanged. CONCLUSIONS: The combination of HA-CA and ADSCs provided synergistic wound healing effects by maximizing paracrine signaling and angiogenesis via the PI3K/AKT pathway. Therefore, ADSC-loaded HA-CA might represent a novel strategy for the treatment of DBW.

Polyphyllin D Shows Anticancer Effect through a Selective Inhibition of Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP2).

Natural products have continued to offer tremendous opportunities for drug development, as they have long been used in traditional medicinal systems. SHP2 has served as an anticancer target. To identify novel SHP2 inhibitors with potential anticancer activity, we screened a library containing 658 natural products. Polyphyllin D was found to selectively inhibit SHP2 over SHP1, whereas two other identified compounds (echinocystic acid and oleanolic acid) demonstrated dual SHP1 and SHP2 inhibition. In a cell-based assay, polyphyllin D exhibited cytotoxicity in Jurkat cells, an acute lymphoma leukemia cell line, whereas the other two compounds were ineffective. Polyphyllin D also decreased the level of phosphorylated extracellular signal-regulated kinase (p-ERK), a proliferation marker in Jurkat cells. Furthermore, knockdown of protein tyrosine phosphatase (PTP)N6 (SHP1) or PTPN11 (SHP2) decreased p-ERK levels. However, concurrent knockdown of PTPN6 and PTPN11 in Jurkat cells recovered p-ERK levels. These results demonstrated that polyphyllin D has potential anticancer activity, which can be attributed to its selective inhibition of SHP2 over SHP1.