Marked Washout Research Articles

Perfluorobutane-Enhanced CEUS in Intrahepatic Cholangiocarcinoma: Correlating Imaging Features With Liver Backgrounds and Tumor Sizes

ObjectiveTo investigate Sonazoid contrast-enhanced ultrasound (CEUS) features of intrahepatic cholangiocarcinoma (ICC) based on liver backgrounds and tumor sizes. MethodsA retrospective analysis was conducted on patients with histopathologically diagnosed ICC at two centers. Patients underwent Sonazoid CEUS examination at a dose of 0.0165 mL/kg before surgery or biopsy. Continuous imaging was recorded for the first 70 s, followed by intermittent scanning every 15–20 s for 5 min, with a Kupffer phase captured after an 8-min delay. Patients were categorized by liver backgrounds and tumor sizes. Two ultrasound experts evaluated the enhancement patterns of ICCAs during the arterial, portal, delayed, and Kupffer phases according to current guidelines. ResultsFrom February 2019 to July 2022, a total of 85 ICC lesions were included. ICCs were categorized into normal liver (n = 24), chronic liver disease with fibrosis (n = 40), and cirrhosis (n = 21) groups based on different liver backgrounds, and into groups measuring ≤30 mm (n = 22), 31–50 mm (n = 32), and >50 mm (n = 31) based on tumor sizes. Most ICCs in liver fibrosis or liver cirrhosis tended to show non-rim enhancement in arterial phase (p = 0.022) and relatively later washout (39.9 ± 8.5 s vs. 39.7 ± 13.0 s) compared with those on a normal liver background (28.1 ± 5.6 s) (p < 0.001). Based on CEUS Liver Imaging Reporting and Data System, the diagnostic performance of LR-M criteria showed an accuracy of 100% in our high-risk populations. ICCs of ≤30 mm more commonly showed non-rim enhancement in arterial phase (p = 0.003) and relatively later washout (41.3 ± 12.5 s) compared with larger ICCs (p = 0.046). In the Kupffer phase, all ICCs showed marked washout with sharp margin delineation on Sonazoid CEUS, regardless of liver backgrounds and tumor sizes. ConclusionSonazoid CEUS features of ICCs differ according to different liver backgrounds and tumor sizes. Arterial phase non-rim enhancement and relatively later washout were more commonly observed in ICCs on liver fibrosis or cirrhosis background or smaller ICCs (≤30 mm).

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma

ObjectiveWe aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. MethodsHCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. ResultsOf the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. ConclusionDCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

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.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Unique portal venous phase imaging discordance between CEUS and MRI: a valuable predictor of intrahepatic cholangiocarcinoma?

We have long noted unique portal venous phase (PVP) imaging discordance of focal liver masses between CEUS, showing rapid marked washout, and MRI, showing progressive or sustained enhancement. We postulate association of this unique discordance with intrahepatic cholangiocarcinoma (ICC) and causal relationship to different contrast agent behavior. We investigate this unique discordance, propose its clinical significance for ICC diagnosis, and confirm further histologic associations. Cases were collected within our CEUS department and from pathology records over a ten-year interval. This retrospective review includes 99 patients, 73 with confirmed ICC and 26 other diagnoses,showing unique PVP discordance. The CEUS and MRI enhancement characteristics were compared for all patients. Unique discordance is identified in 67/73 (92%) ICC and difference between the PVP appearance on MRI and CEUS is statistically significant (p< 0.0001). Arterial phase enhancement did not show statistically significant difference between CEUS and MRI, p> 0.05. Other diagnoses showing unique discordance include especially lymphoma (n=7), sclerosed hemangioma (n=6), HCC (n=4), metastases (n=2), and other rare entities. ICC shows this discrepant intermodality enhancement pattern in a statistically significant number of cases and should be considered along with other LR-M features in at-risk patients. Discordance is also rarely seen in a number of other liver lesions.

Performance of current versus modified CEUS LI-RADS in the diagnosis of non-hepatocellular carcinoma malignancies.

The high proportion of HCC in CEUS LR-M decreases the sensitivity of LR-5 for the diagnosis of HCC. However, when modifying LR-M criteria to further improve the sensitivity of LR-5, it is also important not to compromise the diagnostic performance (especially sensitivity) of LR-M for non-hepatocellular carcinoma malignancies (non-HCCMs). The purpose of this study was to evaluate the diagnostic performance of CEUS LI-RADS (2017 version) for non-HCCMs and to explore the impact of modified CEUS LI-RADS on the diagnostic performance of LR-M. In this retrospective study, patients with pathologically confirmed non-HCCMs were evaluated. Two radiologists independently interpreted the major CEUS features and categorized the liver lesions. New LR-M criteria were applied: early washout (< 45 s) or marked washout (< 5 min). The sensitivity values of the current and modified CEUS LR-M were assessed and then compared using a paired χ2 test. Cohen's κ was used to compare the inter-reader agreement of the LI-RADS categories. A total of 131 non-HCCMs were ultimately selected, including 71 intrahepatic cholangiocarcinomas, 26 combined hepatocellular cholangiocarcinomas, 29 metastases, and 5 other non-HCCMs. The numbers of LR-M, LR-5, LR-4, and LR-3 in liver lesions were 111, 18, 1, and 1, respectively. The inter-reader agreement of the LI-RADS categories for non-HCCMs was 0.59. The sensitivity of the current CEUS LR-M in diagnosing non-HCCMs was 84.7%. By adjusting the early washout time to < 45 s, the sensitivity of LR-M was 80.9%. By adjusting the marked washout time within 5 min, the sensitivity of LR-M was 72.5%. CEUS LR-M has high sensitivity in diagnosing non-HCCMs. For LR-M nodules with nonrim arterial phase hyperenhancement and early washout, advancing the time of early washout to < 45 s has a minimal impact on the sensitivity of LR-M in diagnosing non-HCCMs compared to the condition of increasing the marked washout within 5 min.

Diagnosis of hepatocellular carcinoma using Sonazoid: a comprehensive review.

Sonazoid contrast-enhanced ultrasonography (CEUS) is a promising technique for the detection and diagnosis of focal liver lesions, particularly hepatocellular carcinoma (HCC). Recently, a collaborative effort between the Korean Society of Radiology and Korean Society of Abdominal Radiology resulted in the publication of guidelines for diagnosing HCC using Sonazoid CEUS. These guidelines propose specific criteria for identifying HCC based on the imaging characteristics observed during Sonazoid CEUS. The suggested diagnostic criteria include nonrim arterial phase hyperenhancement, and the presence of late and mild washout, or Kupffer phase washout under the premise that the early or marked washout should not occur during the portal venous phase. These criteria aim to improve the accuracy of HCC diagnosis using Sonazoid CEUS. This review offers a comprehensive overview of Sonazoid CEUS in the context of HCC diagnosis. It covers the fundamental principles of Sonazoid CEUS and its clinical applications, and introduces the recently published guidelines. By providing a summary of this emerging technique, this review contributes to a better understanding of the potential role of Sonazoid CEUS for diagnosing HCC.

Contrast enhancement early after renal malignancy cryoablation: imaging findings associated with benignity.

Contrast enhancement by MRI done early after cryoablation for renal malignancies may suggest residual tumor (RT). However, we have observed MRI enhancement within 48 h of cryoablation in patients who had no contrast enhancement 6weeks later. Our purpose was to identify features of 48-h contrast enhancement in patients without RT. This single-center retrospective study included consecutive patients who underwent percutaneous cryoablation of renal malignancies in 2013-2020, exhibited cryoablation-zone MRI contrast enhancement 48h later, and had available 6-week MRI scans. Persistent or growing CE at 6weeks vs. 48 h was classified as RT. A washout index was calculated for each 48-h MRI, and its performance for predicting RT was assessed by receiver operating characteristic curve analysis. We included 60 patients with 72 cryoablation procedures and 83 cryoablation zones exhibiting 48-h contrast enhancement; mean age was 66 ± 17years. Clear-cell renal cell carcinoma accounted for 95% of tumors. Of the 83 48-h enhancement zones, RT was observed in eight while 75 were benign. The 48-h enhancement was consistently visible at the arterial phase. Washout was significantly associated with RT (p < 0.001) and gradually increasing contrast enhancement with benignity (p < 0.009). A washout index below - 1.1 predicted RT with 88% sensitivity and 84% specificity. MRI contrast enhancement 48 h after cryoablation of renal malignancies was usually benign. Washout was associated with residual tumor, with a washout index value below - 1.1 exhibiting good performance in predicting residual tumor. These findings may help to guide decisions about repeat cryoablation. Magnetic resonance imaging contrast enhancement 48h after cryoablation of renal malignancies rarely indicates residual tumor, which is characterized by washout with a washout index lower than - 1.1. • Contrast enhancement at the arterial phase of magnetic resonance imaging done 48h after cryoablation of a renal malignancy is usually benign. • Residual tumor manifesting as contrast enhancement at the arterial phase is characterized by subsequent marked washout. • A washout index below - 1.1 has 88% sensitivity and 84% specificity for residual tumor.

Can Modifications of LR-M Criteria Improve the Diagnostic Performance of Contrast-Enhanced Ultrasound LI-RADS for Small Hepatic Lesions up to 3 cm?

To assess the diagnostic performance of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) version 2017 for small hepatic lesions of ≤3 cm before and after changing the LR-M criteria. We retrospectively analyzed the CEUS examination of 179 patients who were at high risk of hepatocellular carcinoma (HCC) with focal hepatic lesions ≤3 cm (194 lesions in total) and evaluated the diagnostic capability of the American College of Radiology and modified CEUS LI-RADS algorithms. Revision of the early washout time to 45 seconds increased the sensitivity of LR-5 in predicting HCC (P = .004), with no significant decrease in specificity (P = .118). It also made better the specificity of LR-M in predicting non-HCC malignancies (P = .001), with no significant decrease in sensitivity (P = .094). However, using within 3 minutes as the criterion for marked washout time improved the LR-5 sensitivity (P < .001) but decreased its specificity (P = .009) in predicting HCC, whereas the specificity of LR-M in predicting non-HCC malignancies increased (P < .001), but the sensitivity decreased (P = .027). CEUS LI-RADS (v2017) is a valid method for predicting HCC risk in high-risk patients. The diagnostic performance of LR-5 and LR-M could boost when the early washout time is revised to 45 seconds.

Nodules Identified on Surveillance Ultrasound for HCC: CEUS or MRI as the Initial Test?

Following positive surveillance ultrasound (US), magnetic resonance imaging (MRI) is recommended for further characterization. We propose contrast-enhanced ultrasound (CEUS) shows equivalent efficacy. This prospective institutional review board approved study recruited 195 consecutive at-risk patients with a positive surveillance US. All had CEUS and MRI. Biopsy (n=44) and follow-up are gold standard. MRI and CEUS results are classified according to liver imaging reporting and data system (LI-RADS)and patient outcome. As an US-based modality, CEUS is superior in confirming findings from surveillance US, correlation in 189/195 (97%) on CEUS compared to 153/195 (79%) on MRI. Within these negative MRI examinations, there are 2 hepatocellular carcinoma (HCC) and 1 cholangiocarcinoma (iCCA) diagnosed on CEUS and proven by biopsy. From 195 patients, there are 71 malignant diagnoses from all sources, including 58 LR-5 (45 on MRI and 54 on CEUS) and 13 others, including HCC outside of LR-5 category, and LR-M with biopsy proven iCCA (3 on MRI and 6 on CEUS). CEUS and MRI show concordant results in the majority of patients (146/195,75%), including 57/146 malignant and 89/146 benign diagnoses. There are 41/57 concordant LR-5 and 6/57 concordant LR-M. When CEUS and MRI are discordant, CEUS upgraded 20 (10 biopsy-proven) from MRI LR-3/4 to CEUS LR-5 or LR-M by showing washout (WO) that MRI failed to show. Additionally, CEUS characterized time and intensity of WO and diagnosed 13/20 LR-5 by showing late and weak WO and 7 LR-M by showing fast and marked WO. CEUS is 81% sensitive and 92% specific in diagnosing malignancy. MRI is 64% sensitive and 93% specific. CEUS performance is at least equivalent if not superior to MRI for initial evaluation of lesions from surveillance US.

Prediction of Microvascular Invasion in Combined Hepatocellular-Cholangiocarcinoma Based on Pre-operative Clinical Data and Contrast-Enhanced Ultrasound Characteristics.

The goal of the study described here was to define the predictive value of pre-operative clinical information and contrast-enhanced ultrasound (CEUS) imaging characteristics in combined hepatocellular-cholangiocarcinoma (CHC) patients with microvascular invasion (MVI). Seventy-six patients with pathologically confirmed CHC were enrolled in this study, comprising 18 patients with MVI-positive status and 58 with MVI-negative CHC nodules. The pre-operative clinical data and CEUS imaging features were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the potential predictors of MVI in CHC. Recurrence-free survival (RFS) after hepatectomy was compared between patients with different MVI status using the log-rank test and Kaplan-Meier survival curves. Univariate analysis indicated that the following parameters of patients with CHC significantly differed between the MVI-positive and MVI-negative groups (p<0.05): tumor size, α-fetoprotein ≥400 ng/mL, enhancement patterns in arterial phase and marked washout during the portal venous phase on CEUS. On multivariate logistic regression analysis, only the CEUS characteristics of heterogeneous enhancement (odds ratio=6.807; 95% confidence interval [CI]: 1.099, 42.147; p=0.039) and marked washout (odds ratio=4.380; 95% CI: 1.050,18.270; p=0.043) were identified as independent predictors of MVI in CHC. The combination of the two risk factors in predicting MVI achieved a better diagnostic performance than each parameter alone, with an area under the receiver operating characteristic curve of 0.736 (0.622, 0.830). After hepatectomy, CHC patients with MVI exhibited earlier recurrence compared with those without MVI (hazard ratio=1.859; 95% CI: 0.8699-3.9722, p=0.046). The CEUS imaging features of heterogeneous enhancement in the arterial phase and marked washout during the portal venous phase were the potential predictors of MVI in CHC. Aside from that, CHC patients with MVI had an earlier recurrence rate than those without MVI after surgery.

CEUS and CT/MRI LI-RADS in Association With Serum Biomarkers for Differentiation of Combined Hepatocellular-Cholangiocarcinoma From Hepatocellular Carcinoma.

BackgroundCombined Hepatocellular-cholangiocarcinoma (cHCC-CCAs) are with both unambiguously differentiated hepatocellular and biliary components. cHCC-CCAs show various imaging features similar to hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (ICCs), which makes the differential diagnosis between them challenging. The accurate diagnosis of cHCC-CCAs is of great importance in selecting treatment methods and performing patient management.PurposeTo investigate the diagnostic efficacy of CEUS and CT/MRI LI-RADS in association with tumor biomarkers for differentiation of cHCC-CCAs from HCCs.MethodsA total of 54 cHCC-CCAs and 55 HCCs in two centers were retrospectively collected. The diagnostic criteria for cHCC-CCAs if one or more of the following conditions were satisfied: (1) arterial phase hyperenhancement (APHE) on CEUS and LR-M on CT/MRI; (2) LR-5 on both CEUS and CT/MRI with elevated carbohydrate antigen 19-9 (CA19-9); (3) LR-M on both CEUS and CT/MRI with elevated alphafetoprotein (AFP). The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated.ResultsThe rates of APHE and Rim-APHE on CEUS in cHCC-CCAs were 81.5% and 9.3%, respectively. The rate of early and marked washout on CEUS in cHCC-CCAs were 59.3% and 27.8%, respectively. 64.8% and 25.9% of cHCC-CCAs showed APHE and Rim-APHE on CT/MRI, respectively. 46.3% and 35.2% of cHCC-CCAs showed washout and delay enhancement on CT/MRI, respectively. The kappa value of LI-RADS categories of cHCC-CCAs on CEUS and CT/MRI was 0.319 (P=0.008). The sensitivity, specificity, accuracy and AUC of the aforementioned diagnostic criteria for cHCC-CCAs were 64.8%, 84.4%, 76.1% and 0.746, respectively.ConclusionThe combination of the CEUS and CT/MRI LI-RADS with serum tumor markers shows promising diagnostic performance of cHCC-CCAs.

Diagnostic performance and interreader agreement of CEUS LI-RADS in ≤ 30mm liver nodules with different experienced radiologists.

To explore the diagnostic performance and interreader agreement of CEUS LI-RADS in diagnosing ≤ 30mm liver nodules with different experienced radiologists. Between January 2018 and October 2020, 244 patients at high-risk for HCC who underwent CEUS were enrolled. Two novice radiologists and two expert radiologists independently evaluated LI-RADS categories and main features. Kappa (κ) and Kendall'stests wereemployed to evaluate the interreader agreement of CEUS LI-RADS. The diagnostic performance was determined based on sensitivity, specificity, accuracy, PPV and NPV. The interreader agreement for arterial phase hyperenhancement, late and mild washout, early washout, and rim hyperenhancement was moderate to almost perfect (κ, 0.44-0.93) among the different levels of radiologists. The interreader agreement for the LI-RADS categories was substantial to almost perfect (κ, 0.78-0.88). However, the interreader agreement for marked washout was fair to moderate (κ, 0.28-0.50). When CEUS LR-5 was used as a diagnostic criterion for HCC, there were no statistical differences in sensitivity, specificity, accuracy, PPV and NPV among the radiologists (p > 0.05), except for the differences between Reader 4 and the remaining three radiologists in terms of accuracy and sensitivity (p < 0.05). CEUS LI-RADS has good diagnostic agreement for ≤ 30mm liver nodules among experienced radiologists.

Using new criteria to improve the differentiation between HCC and non-HCC malignancies: clinical practice and discussion in CEUS LI-RADS 2017.

Using contrast-enhanced ultrasound (CEUS) to evaluate the diagnostic performance of liver imaging reporting and data system (LI-RADS) version 2017 and to explore potential ways to improve the efficacy. A total of 315 nodules were classified as LR-1 to LR-5, LR-M, and LR-TIV. New criteria were applied by adjusting the early washout onset (< 45s) and the time of marked washout (within 3min). Two subgroups of the LR-M nodules were recategorized as LR-5, respectively. The diagnostic performance was evaluated by calculating the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). By adjusting early washout onset to < 45s, the LR-5 as a standard for diagnosing HCC had an improved sensitivity (74.1% vs. 56.1%, P < 0.001) without significant change in PPV (93.3% vs. 96.1%, P = 0.267), but the specificity was decreased (48.3% vs. 78.5%, P = 0.018). The LR-M as a standard for the diagnosis of non-HCC malignancies had an increase in specificity (89.2% vs. 66.2%, P < 0.001) but a decrease in sensitivity (31.5% vs. 68.4%, P = 0.023). After reclassification according to the time of marked washout, the sensitivity of the LR-5 increased (80% vs. 56.1%, P < 0.001) without a change in PPV (94.9% vs. 96.1%, P = 0.626) and specificity (80% vs. 78.5%, P = 0.879). For reclassified LR-M nodules, the specificity increased (87.5% versus 66.2%, P < 0.001) with a non-significant decrease in sensitivity (47.3% vs. 68.4%, P = 0.189). The CEUS LI-RADS showed good confidence in diagnosing HCC while tended to misdiagnose HCC as non-HCC malignancies. Adjusting the marked washout time within 3min would reduce the possibility of this misdiagnosis.

Dual-Time-Point 18F-Fluorocholine PET/CT Improves Characterization of Thyroid Nodules in Patients Referred for Primary Hyperparathyroidism: A Proof of Concept Study.

Thyroid nodules frequently coexist with primary hyperparathyroidism (pHPT). Because of the increasing use of 18F-fluorocholine (18F-FCH) PET/CT in patients with pHPT, evaluation of its clinical utility for thyroid nodules characterization in this population is of paramount importance. Herein, we investigate the value of dual-point 18F-FCH PET/CT in the diagnosis of thyroid cancer in patients referred for pHPT imaging who have thyroid nodules. All pHPT patients who underwent a dual-time point 18F-FCH PET/CT (at 5 and 60 minutes postinjection) between July 2019 and December 2020 were analyzed. Only those with a thyroid nodule greater than 10-mm and pathological analysis (criterion standard) were included. Nodule-to-thyroid SUVmax ratio was calculated at the 2 study points, as well as the 18F-FCH washout index (WO%). Twenty-seven patients (32 nodules) were included in this study. The final diagnoses were as follows: 27 benign nodules including 2 NIFTPs (noninvasive follicular thyroid neoplasm with papillary-like nuclear features) and 5 cancers of follicular origin. Early uptake ratio was significantly higher in malignant lesions than in benign nodules (P = 0.0008). Thyroid cancers were also characterized by a marked 18F-FCH washout index (WO% benign vs cancer: 2.9% ± 4.1% vs 45.5% ± 13.4%, P = 0.0001). Using a WO% threshold of 22.1%, 25/27 benign nodules and 5/5 malignant lesions were accurately classified (sensitivity of 100%, specificity of 92.6%, positive predictive value of 71.4%, and negative predictive value of 100%). The false-positive findings were related to the 2 NIFTPs that share similarities with thyroid cancer. Our preliminary results suggest to perform a dual-time-point PET/CT acquisition protocol in pHPT patients with uncharacterized centimeter thyroid nodules. However, the real impact of these promising results should be assessed by prospective studies on a larger cohort of patients.

Contrast-Enhanced Ultrasound Patterns for the Non-invasive Diagnosis of Hepatocellular Carcinoma: A Prospective Multicenter Study in Histologically Proven Liver Lesions in a Real-Life Setting Demonstrating the Benefit of Extended Late Phase Observation

The hallmark for the non-invasive diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in cirrhosis is arterial phase hyperenhancement (APHE), followed by late-onset (>60 s), mild washout. Large retrospective studies report this pattern of washout to occur in the vast majority of HCCs. However, a prospective multicenter validation of these findings is still missing. Thus, we initiated a prospective multicenter validation study assessing CEUS enhancement patterns in focal liver lesions of patients at risk for HCC. We analyzed lesions that were eventually histology proven in a real-life setting. CEUS patterns were assessed for subgroups of HCC, intrahepatic cholangiocellular carcinoma (iCCA) and non-HCC, non-iCCA lesions. The diagnosis was HCC in 316 lesions (median size: 40 mm), iCCA in 26 lesions (median size: 47.5 mm) and non-HCC, non-iCCA in 53 lesions (median size: 27 mm). Overall, 85.8% of HCCs exhibited APHE. APHE followed by washout occurred in 72.8% of HCCs and 50% of iCCAs and non-HCC, non-iCCA malignancies (p < 0.05). Early and marked washout was associated more commonly with iCCA; HCCs exhibited mostly late and mild washout (onset >4–6 min in 10% of cases). Our prospective data confirm that the typical pattern of APHE followed by late-onset, mild washout occurs in the majority of HCCs.

Differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced ultrasound: A systematic review and meta-analysis

To explore the diagnostic ability of contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies reporting the diagnostic accuracy of CEUS in differentiating ICC from HCC. The diagnostic ability of CEUS was assessed based on the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) with 95% confidence intervals (CIs). The methodologic quality was assessed by the QUADAS-2 tool. Subgroup analyses, meta-regression and investigation of publication bias were performed to identify the source of heterogeneity. A total of eight studies were included, consisting of 1,116 patients with HCC and 529 with ICC. The general diagnostic performance of CEUS in distinguishing ICC and HCC were as follows: pooled sensitivity, 0.92 (95% CI: 0.84-0.96); pooled specificity, 0.87 (95% CI: 0.79-0.92); pooled PLR, 7.1 (95% CI: 4.1-12.0); pooled NLR, 0.09 (95% CI: 0.05-0.19); pooled DOR, 76 (95% CI: 26-220) and AUC, 0.95 (95% CI: 0.93-0.97). Different liver background may be a potential factor that influenced the diagnostic accuracy of CEUS according to the subgroup analysis, with the pooled DOR of 89.67 in the mixed liver background group and 46.87 in the cirrhosis group, respectively. Six informative CEUS features that may help differentiate HCC from ICC were extracted. The three CEUS features favoring HCC were arterial phase hyperenhancement (APHE), mild washout and late washout (>60s); the three CEUS favoring ICC were arterial rim enhancement, marked washout and early washout (<60s). No potential publication bias was observed. CEUS showed great diagnostic ability in differentiating ICC from HCC, which may be promising for noninvasive evaluation of these diseases.

Using LI‐RADS With Contrast‐Enhanced Ultrasound

Using LI‐RADS With Contrast‐Enhanced Ultrasound

Differential diagnosis between hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma with conventional ultrasound and contrast-enhanced ultrasound

BackgroundMisclassifications of hepatic alveolar echinococcosis (HAE) as intrahepatic cholangiocarcinoma (ICC) may lead to inappropriate treatment strategies. The aim of this study was to explore the differential diagnosis with conventional ultrasound and contrast-enhanced ultrasound (CEUS).MethodsSixty HAE lesions with 60 propensity score-matched ICC lesions were retrospectively collected. The 120 lesions were randomly divided into a training set (n = 80) and a testing set (n = 40). In the training set, the most useful independent conventional ultrasound and CEUS features was selected for differentiating between HAE and ICC. Then, a simplified US scoring system for diagnosing HAE was constructed based on selected features with weighted coefficients. The constructed US score for HAE was validated in both the training set and the testing set, and diagnostic performance was evaluated.ResultsCompared with ICC lesions, HAE lesions were mostly located in the right lobe and had mixed echogenicity, a pseudocystic appearance and foci calcifications on conventional ultrasound. On CEUS, HAE lesions showed more regular rim-like enhancement than ICC lesions and had late washout with a long enhancement duration. The simplified US score consisted of echogenicity, pseudocystic/calcification, bile duct dilatation, enhancement pattern, enhancement duration, and marked washout. In the testing set, the sensitivity, specificity, LR+, LR- and the area under the ROC curve for the score to differentiate HAE from ICC were 80.0, 81.3%, 4.27, 0.25 and 0.905, respectively.ConclusionsThe US score based on typical features from both conventional ultrasound and CEUS could accurately differentiate HAE from ICC.

The Perfusion Features of Recurrent Hepatocellular Carcinoma After Radiofrequency Ablation Using Contrast-Enhanced Ultrasound and Pathological Stemness Evaluation: Compared to Initial Tumors.

Objective: To investigate the perfusion features of local recurrence in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) with contrast-enhanced ultrasound (CEUS) and pathological correlation, as well as to compare with those of initial HCC.Methods: From 2010 to 2018, 42 patients with recurrent HCC after RFA were enrolled in this study. The initial HCC patients included 32 males and 10 females with an average age of 58.2 ± 8.1 years. The CEUS images for initial HCC lesions and local recurrence after RFA were compared. The perfusion features were analyzed, including enhancement time, process, boundary, morphology, washout time, washout degree, feeding vessels, and internal necrosis. H&E staining and CD133/EpCAM staining were performed with biopsy samples for the stemness study.Results: According to CEUS, 59.5% of initial HCC lesions had centripetal enhancement, and 61.9% of recurrent HCC lesions had homogeneous enhancement in the arterial phase (p < 0.001). A total of 73.8% of initial HCC lesions had well-defined margins at the peak, and 81.0% of recurrent HCC lesions had poorly defined margins (p < 0.001). A total of 78.6% of initial HCC lesions had regular morphology at the peak, and 83.3% of recurrent HCC lesions were irregular (p < 0.001). Feeding vessels were more frequently found in initial HCC lesion (71.4%) than in recurrent HCCs (38.1%, p = 0.002). In the late phase, 60% of initial HCCs had marked washout while 83.3% of recurrent HCC lesion had marked washout (p = 0.019). A total of 31.3% of the initial HCC lesions had internal necrosis areas while only 7.1% of recurrent HCC lesions had internal necrosis areas (p = 0.035). In tumors 3–5 cm in size, the washout time of recurrent HCCs was shorter than that of initial HCCs (50.3 ± 13.5 s vs. 75.6 ± 45.8 s, p = 0.013). Pathological staining showed that the tumor stem cell markers (CD133 and EpCAM) were both highly expressed in recurrent samples compared with initial tumor samples (CD133+: 19 vs. 5%, p = 0.002; EpCAM+:15 vs. 6%, p = 0.005).Conclusions: Recurrent HCC after RFA had more homogeneous enhancement with a poorly defined border, marked washout, and fewer less feeding vessels and inner necrosis areas compared to initial HCC. The stemness study also found upregulated stemness in recurrent HCC. These specific features might be related to the aggressive biological behavior of recurrent HCC.