Hypointensity In Hepatobiliary Phase Research Articles

Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging.

The liver imaging reporting and data system (LI-RADS) diagnostic table has 15 cells and is too complex. The diagnostic performance of LI-RADS for hepatocellular carcinoma (HCC) is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). To evaluate the ability of the simplified LI-RADS (sLI-RADS) to diagnose HCC on EOB-MRI. A total of 331 patients with 356 hepatic observations were retrospectively analysed. The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLI-RADS. The algorithms of sLI-RADS A-D are as follows: The single threshold for sLI-RADS A and B was 10 mm, that is, classified observations ≥ 10mm using an algorithm of 10-19 mm observations (sLI-RADS A) and ≥ 20 mm observations (sLI-RADS B) in the diagnosis table of LI-RADS v2018, respectively, while the classification algorithm remained unchanged for observations < 10 mm; the single threshold for sLI-RADS C and D was 20 mm, that is, for < 20 mm observations, the algorithms for < 10 mm observations (sLI-RADS C)and 10-19 mm observations (sLI-RADS D) were used, respectively, while the algorithm remained unchanged for observations ≥ 20 mm. With hepatobiliary phase (HBP) hypointensity as a major feature (MF), the final sLI-RADS (F-sLI-RADS) was formed according to the optimal sLI-RADS, and its diagnostic performance was evaluated. The times needed to classify the observations according to F-sLI-RADS and LI-RADS v2018 were compared. The optimal sLI-RADS was sLI-RADS D (with a single threshold of 20 mm), because its sensitivity was greater than that of LI-RADS v2018 (89.8% vs 87.0%, P = 0.031), and its specificity was not lower (89.4% vs 90.1%, P > 0.999). With HBP hypointensity as an MF, the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018 (93.0% vs 87.0%, P < 0.001) and sLI-RADS D (93.0% vs 89.8%, P = 0.016), without a lower specificity (86.5% vs 90.1%, P = 0.062; 86.5% vs 89.4%, P = 0.125). Compared with that of LI-RADS v2018, the time to classify lesions according to F-sLI-RADS was shorter (51 ± 21 s vs 73 ± 24 s, P < 0.001). The use of sLI-RADS with HBP hypointensity as an MF may improve the sensitivity of HCC diagnosis and reduce lesion classification time.

Does threshold growth benefit imaging criteria when used as a major diagnostic imaging feature for hepatocellular carcinoma?

PurposeTo evaluate the added value of threshold growth (TG) for imaging criteria for diagnosing hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI. MethodsPatients who underwent preoperative gadoxetic acid-enhanced MRI because of absence of ‘definite HCC’ (Liver Imaging Reporting and Data System category 5) on prior CT or MRI between January 2016 and December 2020 were retrospectively analyzed. The sensitivity and specificity for ‘definite HCC’ according to the criteria of the European Association for the Study of the Liver [EASL], Asian Pacific Association for the Study of the Liver [APASL], and Korean Liver Cancer Association-National Cancer Center [KLCA-NCC] were separately calculated with and without TG as a major imaging feature. The results were compared using generalized estimating equations. ResultsOf 202 nodules in 154 patients, 19 % showed TG. When TG was used as a major imaging feature, the sensitivity of EASL were significantly higher than when it was not used (59.2 % vs. 51.4 %, p = 0.001), whereas the sensitivities of APASL and KLCA-NCC did not significantly differ. No significant difference was found in the specificities of the three imaging criteria when TG was used or not (p ≥ 0.16). Of 11 HCCs additionally detected when TG was added to EASL criteria, 9 showed transitional-phase or hepatobiliary-phase hypointensity without portal venous-phase washout. ConclusionTG had added value for improving the sensitivity of EASL criteria for gadoxetic acid-enhanced MRI without extending washout to transitional-phase or hepatobiliary-phase images.

Microvascular invasion-negative hepatocellular carcinoma: Prognostic value of qualitative and quantitative Gd-EOB-DTPA MRI analysis

ObjectivesThe purpose of this study was to establish a model for predicting the prognosis of patients with microvascular invasion (MVI)-negative hepatocellular carcinoma (HCC) based on qualitative and quantitative analyses of Gd-EOB-DTPA magnetic resonance imaging (MRI). Materials and methodsConsecutive patients with MVI-negative HCC who underwent preoperative Gd-EOB-DTPA MRI between January 2015 and December 2019 were retrospectively enrolled.In total, 122 patients were randomly assigned to the training and validation groups at a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed to identify significant clinical parameters and MRI features, including quantitative and qualitative parameters associated with prognosis, which were incorporated into a predictive nomogram. The end-point of this study was recurrence-free survival. Outcomes were compared between groups using the Kaplan–Meier method with the log-rank test. ResultsDuring a median follow-up period of 58.86 months, 38 patients (31.15 %) experienced recurrence. Multivariate analysis revealed that lower relative enhancement ratio (RER), hepatobiliary phase hypointensity without arterial phase hyperenhancement, Liver Imaging Reporting and Data System category, mild-moderate T2 hyperintensity, and higher aspartate aminotransferase levels were risk factors associated with prognosis and then incorporated into the prognostic model. C-indices for training and validation groups were 0.732 and 0.692, respectively. The most appropriate cut-off value for RER was 1.197. Patients with RER ≤ 1.197 had significantly higher postoperative recurrence rates than those with RER > 1.197 (p = 0.004). ConclusionThe model integrating qualitative and quantitative imaging parameters and clinical parameters satisfactorily predicted the prognosis of patients with MVI-negative HCC.

Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis

PurposeWe aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis. MethodsThirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child–Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups. ResultsALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008). ConclusionThe sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.

LI-RADS category 3, 4, and M observations: a multiple parameters diagnostic model for hepatocellular carcinoma.

Hepatic lesions categorized as LR-3, LR-4, and LR-M are challenging to accurately assess and diagnose. To combine potential clinical and/or magnetic resonance imaging (MRI) features for a more comprehensive hepatocellular carcinoma (HCC) versus non-HCC diagnosis for patients with LR-3, LR-4, and LR-M graded lesions. Data were consecutively retrieved from 82 at-risk patients with LR-3 (n = 43), LR-4 (n = 20), and LR-M (n = 23) lesions. Significant findings for the differentiation of HCC and non-HCC, including MRI features and clinical factors, were identified with univariable and multivariable analyses. The variables for a prediction model were selected through stepwise use of Akaike's Information Criterion (AIC) to build multivariable logistic regression model. Serum alpha-fetoprotein (AFP) >16.2 ng/mL (odds ratio [OR] = 22.4; P = 0.006), septum (OR = 52.1; P = 0.011), and hepatobiliary phase (HBP) hypointensity (OR = 40.2; P = 0.001) were confirmed as independent predictors of HCC. When combining the three predictors and mild-moderate T2 hyperintensity, the model (AIC = 50.91) showed good accuracy with a C-index of 0.948. In at-risk patients with LR-3, LR-4, or LR-M lesions, integrating AFP, septum, HBP hypointensity, and mild-moderate T2 hyperintensity achieved high diagnostic performance for the diagnosis of HCC.

Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. We enrolled patients with chronic hepatitisC who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. The final study cohort comprised 482 patients (median age 70.5years; 242 men). The median follow-up period was 36.8months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p<0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

MRI Features for Predicting Microvascular Invasion and Postoperative Recurrence in Hepatocellular Carcinoma Without Peritumoral Hypointensity.

To identify MRI features of hepatocellular carcinoma (HCC) that predict microvascular invasion (MVI) and postoperative intrahepatic recurrence in patients without peritumoral hepatobiliary phase (HBP) hypointensity. One hundred and thirty patients with HCC who underwent preoperative gadoxetate-enhanced MRI and curative hepatic resection were retrospectively reviewed. Two radiologists reviewed all preoperative MR images and assessed the radiological features of HCCs. The ability of peritumoral HBP hypointensity to identify MVI and intrahepatic recurrence was analyzed. We then assessed the MRI features of HCC that predicted the MVI and intrahepatic recurrence-free survival (RFS) in the subgroup without peritumoral HBP hypointensity. Finally, a two-step flowchart was constructed to assist in clinical decision-making. Peritumoral HBP hypointensity (odds ratio, 3.019; 95% confidence interval: 1.071-8.512; P=0.037) was an independent predictor of MVI. The sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of peritumoral HBP hypointensity in predicting MVI were 23.80%, 91.04%, 71.23%, 55.96%, and 0.574, respectively. Intrahepatic RFS was significantly shorter in patients with peritumoral HBP hypointensity (P<0.001). In patients without peritumoral HBP hypointensity, the only significant difference between MVI-positive and MVI-negative HCCs was the presence of a radiological capsule (P=0.038). Satellite nodule was an independent risk factor for intrahepatic RFS (hazard ratio,3.324; 95% CI: 1.733-6.378; P<0.001). The high-risk HCC detection rate was significantly higher when using the two-step flowchart that incorporated peritumoral HBP hypointensity and satellite nodule than when using peritumoral HBP hypointensity alone (P<0.001). In patients without peritumoral HBP hypointensity, a radiological capsule is useful for identifying MVI and satellite nodule is an independent risk factor for intrahepatic RFS.

Gadoxetic Acid-Enhanced Liver MRI: Everything You Need to Know.

Since its introduction in the worldwide medical market, gadoxetic acid has attracted considerable interest. The year 2023 marks the 15th anniversary of the introduction of gadoxetic acid in Japan. Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) is the predominantly performed contrast MRI examination for the liver. Its most essential characteristic, namely, the hepatobiliary phase, revolutionized the clinical management of liver disease. Gadoxetic acid-enhanced MRI is currently the most efficient method for focal liver lesion detection and analysis. Meta-analyses demonstrated its excellent effectiveness for the diagnosis of hepatocellular carcinoma and liver metastases. Owing to the extensive usage of gadoxetic acid, a hepatobiliary phase hypointense nodule without arterial phase hyperenhancement is well documented. The existence of such nodules may be a sign of hypervascular hepatocellular carcinoma in nodules and other areas in the liver. Apart from its role in tumor identification and characterization, GA-MRI can help assess response to therapy and liver fibrosis. Therefore, it is proposed to use gadoxetic acid as the first option for MRI of the liver in the majority of patients. The efficacy of gadoxetic acid surpasses its disadvantages, rendering this contrast agent the preferred choice for routine MRI of the liver. The clinical use of GA-MRI is discussed in this review article.

Characterization of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI via contrast-enhanced ultrasound using perfluorobutane.

Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) on gadoxetic acid-enhanced MRI (GA-MRI) may be nonmalignant cirrhosis-associated nodules or hepatocellular carcinomas (HCCs). We aimed to characterize HBP hypointense nodules without APHE on GA-MRI by performing contrast-enhanced ultrasound using perfluorobutane (PFB-CEUS). In this prospective, single-center study, participants at high-risk of HCC having HBP hypointense nodules without APHE at GA-MRI were enrolled. All participants underwent PFB-CEUS; if APHE and late, mild washout or washout in the Kupffer phase were present, the diagnosis of HCC was established according to the v2022 Korean guidelines. The reference standard consisted of histopathology or imaging. The sensitivity, specificity, and positive/negative predictive values of PFB-CEUS for detecting HCC were calculated. Associations between clinical/imaging features and the diagnosis of HCC were evaluated with logistic regression analyses. In total, 67 participants (age, 67.0years ± 8.4; 56 men) with 67 HBP hypointense nodules without APHE (median size, 1.5cm [range, 1.0-3.0cm]) were included. The prevalence of HCC was 11.9% (8/67). The sensitivity, specificity, and positive and negative predictive values of PFB-CEUS for detecting HCC were 12.5%(1/8), 96.6%(57/59), 33.3%(1/3) and 89.1%(57/64), respectively. Mild-moderate T2 hyperintensity on GA-MRI (odds ratio, 5.756; P = 0.042) and washout in the Kupffer phase on PFB-CEUS (odds ratio, 5.828; P = 0.048) were independently associated with HCC. Among HBP hypointense nodules without APHE, PFB-CEUS was specific for detecting HCC, which had a low prevalence. Mild-moderate T2 hyperintensity on GA-MRI and washout in the Kupffer phase on PFB-CEUS may be useful to detect HCC in those nodules.

LI-RADS v2018: utilizing ancillary features on gadoxetic acid-enhanced MRI to improve the diagnostic performance of small hapatocellular carcinoma (≤ 20mm).

To evaluate the role of ancillary features (AFs) of Liver Imaging Reporting and Data System (LI-RADS) in the diagnostic performance of small HCC (≤ 20mm) on gadoxeticacid-enhanced MRI. A total of 154 patients with 183 hepatic observations were analysed in this retrospective study. Observations were categorized using only major features (MFs) and combined MFs and AFs. Independently significant AFs were identified through logistic regression analysis, and upgraded LR-5 criteria were developed using these as new MFs. The diagnostic performance of the modified LI-RADS (mLI-RADS) was calculated and compared with that of LI-RADS v2018 using McNemar's test. Restricted diffusion, transitional and hepatobiliary phase hypointensity were independently significant AFs. The mLI-RADS a, c, e, g, h and i (upgraded LR-4 lesions that were categorized using only MFs to LR-5 using a certain or any one, two, three of the above AFs as new MFs) yielded a significantly greater sensitivity than that of the LI-RADS v2018 (68.0%, 69.1%, 69.1%, 69.1%, 69.1%, 68.0% vs. 61.9%, all p < 0.05), whereas the specificities were not significantly different (84.9%, 86.0%, 84.9%, 83.7%, 84.9%, 87.2% vs. 88.4% all p > 0.05). When independently significant AFs were used to upgrade the LR-4 nodules categorized by combined MFs and AFs (mLI-RADS b, d and f), the sensitivities were improved, but the specificities were decreased (all p < 0.05). Independently significant AFs may be used to upgrade an observation from LR-4 (categorized only using MFs) to LR-5, which can improve diagnostic performance for small HCC.

VICT2 Trait: Prognostic Alternative to Peritumoral Hepatobiliary Phase Hypointensity in HCC.

Background Peritumoral hepatobiliary phase (HBP) hypointensity is an established prognostic imaging feature in hepatocellular carcinoma (HCC), often associated with microvascular invasion (MVI). Similar prognostic features are needed for non-HBP MRI. Purpose To propose a non-hepatobiliary-specific MRI tool with similar prognostic value to peritumoral HBP hypointensity. Materials and Methods From December 2011 to November 2021, consecutive patients with HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled and followed up until recurrence. All MRI scans were reviewed by two blinded radiologists with 7 and 10 years of experiences with liver MRI. A scoring system based on non-hepatobiliary-specific features that highly correlated with peritumoral HBP hypointensity was identified in a stratified sampling-derived training set of the gadoxetate disodium (EOB) group by means of multivariable logistic regression, and its values to predict MVI and recurrence-free survival (RFS) were assessed. Results There were 660 patients (551 men; median age, 53 years; IQR, 45-61 years) enrolled. Peritumoral portal venous phase hypoenhancement (odds ratio [OR] = 8.8), incomplete "capsule" (OR = 3.3), corona enhancement (OR, 2.6), and peritumoral mild-moderate T2 hyperintensity (OR, 2.2) (all P < .001) were associated with peritumoral HBP hypointensity and constituted the "VICT2 trait" (test set area under the receiver operating characteristic curve = 0.84; 95% CI: 0.78, 0.90). For the EOB group, both peritumoral HBP hypointensity (OR for MVI = 2.5, P = .02; hazard ratio for RFS = 2.5, P < .001) and the VICT2 trait (OR for MVI = 5.1, P < .001; hazard ratio for RFS = 2.3, P < .001) were associated with MVI and RFS, despite a higher specificity of the VICT2 trait for MVI (89% vs 80%, P = .01). These values of the VICT2 trait were confirmed in the extracellular contrast agent group (OR for MVI = 4.0; hazard ratio for RFS = 1.7; both P < .001). Conclusion Based on four non-hepatobiliary-specific MRI features, the VICT2 trait was comparable to peritumoral hepatobiliary phase hypointensity in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Subtyping of hepatocellular adenomas using Gd-EOB-DTPA: a qualitative and quantitative analysis.

The goal of medical imaging is not only to identify the entity "hepatocellular adenoma," but to detect typical magnetic resonance (MR) patterns of the subtypes so that lesions with a higher malignant transformation rate could be differentiated from those that should just be controlled. To evaluate the differentiation between subtypes of hepatocellular adenomas using hepatobiliary specific contrast agent (Gd-EOB-DTPA) in MR imaging. A total of 11 patients with 39 lesions with histologically proven hepatocellular adenomas were evaluated. Of the, 34 were inflammatory hepatocellular adenomas (IHCA) and 5 were HNF1α adenomas. No β-catenin-mutated adenoma was found. In all patients, a standard protocol considering the guidelines of the international consensus conference of Gd-EOB-DTPA was performed in a 1.5-T scanner. Besides a qualitative analysis of all sequences, we measured the quantitative signal intensity (SI) ratio in all examinations. Qualitative analysis showed that best sequences for differentiation of HNF1α adenomas from IHCA were T1-weighted (T1W) precontrast (P = 0.03) and portalvenous phase (P < 0.0001) as well as arterial phase (P = 0.002). All adenomas were hypointense in hepatobiliary phase (15 min). The quantitative analyses of the SI ratio and of lesion-to-liver contrast (LLC) ratio show statistically significant differences in T1W precontrast (SI: P = 0.035; LLC: P = 0.049) and portalvenous phase (SI: P = 0.002; LLC: P = 0.002). Subtyping of hepatocellular adenomas using Gd-EOB-DTPA is possible due to qualitative and quantitative analyses regarding T1W precontrast and portalvenous phase. In addition, the SI ratio and liver-to-lesion contrast ratio in the arterial phase gave additional qualitative information for differentiation.

Predicting histologic differentiation of solitary hepatocellular carcinoma up to 5 cm on gadoxetate disodium-enhanced MRI

BackgroundTo establish a preoperative score based on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators for predicting histologic differentiation of solitary HCC up to 5 cm.MethodsFrom July 2015 to January 2022, consecutive patients with surgically proven solitary HCC measuring ≤ 5 cm at preoperative EOB-MRI were retrospectively enrolled. All MR images were independently evaluated by two radiologists who were blinded to all clinical and pathologic information. Univariate and multivariate logistic regression analyses were performed to identify significant clinicoradiological features associated with poorly differentiated (PD) HCC, which were then incorporated into the predictive score. The predictive score was validated in an independent validation set by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 182 patients were included, 42 (23%) with PD HCC. According to the multivariate analysis, marked hepatobiliary phase hypointensity (odds ratio [OR], 9.98), LR-M category (OR, 5.60), and serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 3.58) were incorporated into the predictive model; the predictive score achieved an AUC of 0.802 and 0.830 on the training and validation sets, respectively. The sensitivity, specificity, and accuracy of the predictive score were 66.7%, 85.7%, and 81.3%, respectively, on the training set and 66.7%, 81.0%, and 77.8%, respectively, on the validation set.ConclusionThe proposed score integrating two EOB-MRI features and AFP level can accurately predict PD HCC in the preoperative setting.

An improved diagnostic algorithm for subcentimeter hepatocellular carcinoma on gadoxetic acid-enhanced MRI.

Accurate diagnosis of subcentimeter hepatocellular carcinoma (HCC) is a challenge also with gadoxetic acid-enhanced MRI (EOB-MRI). This study aimed to assess the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for subcentimeter HCC and to determine whether new diagnostic criteria (washout either on portal venous phase (PVP) or transitional phase (TP)) would improve the diagnostic performance. We evaluated 240 subcentimeter observations in 225 consecutive treatment-naïve patients at risk of HCC. Final diagnoses were 132 HCCs (all by pathology) and 108 non-HCC (41 by pathology and 67 by follow-up). Two radiologists assessed MR imaging features and assigned LI-RADS categories. A variety of diagnostic criteria were developed by combining significant MRI features based on washout on PVP or TP. Diagnostic performance was compared. Non-rim arterial phase hyperenhancement (non-rim APHE), washout on PVP or TP, and hepatobiliary-phase hypointensity were significant predictors for subcentimeter HCC diagnosis according to multivariable analysis. One criterion (non-rim APHE and washout on PVP or TP) yielded higher sensitivity (68.2% vs. 56.8%, p = 0.011) with comparable specificity (91.7% vs. 92.6%, p > 0.999) compared to the LR-4 category. This criterion had improved sensitivity (68.2% vs. 49.2%, p < 0.001) and slightly decreased specificity (91.7% vs. 94.4%, p = 0.250) compared to non-rim APHE with washout on PVP. LI-RADS exhibits modest diagnostic performance for subcentimeter HCC. Our new criterion (non-rim APHE and non-peripheral washout on PVP or TP) may increase the diagnostic sensitivity without compromised specificity compared to the LR-4 category. • The LR-4 category shows modest diagnostic performance for the diagnosis of subcentimeter HCC on EOB-MRI with a sensitivity and specificity of 56.8% and 92.6%, respectively. • Non-rim APHE, non-peripheral washout on PVP or TP, and HBP hypointensity were independent predictors for the diagnosis of subcentimeter HCC. • The combination of non-rim APHE and non-peripheral washout on PVP or TP improves the sensitivity from 56.8 to 68.2% (p = 0.011) with comparable specificity (91.7 vs. 92.6%, p > 0.999).

Radiomics and nomogram of magnetic resonance imaging for preoperative prediction of microvascular invasion in small hepatocellular carcinoma.

BACKGROUNDMicrovascular invasion (MVI) of small hepatocellular carcinoma (sHCC) (≤ 3.0 cm) is an independent prognostic factor for poor progression-free and overall survival. Radiomics can help extract imaging information associated with tumor pathophysiology.AIMTo develop and validate radiomics scores and a nomogram of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in sHCC.METHODSIn total, 415 patients were diagnosed with sHCC by postoperative pathology. A total of 221 patients were retrospectively included from our hospital. In addition, we recruited 94 and 100 participants as independent external validation sets from two other hospitals. Radiomics models of Gd-EOB-DTPA-enhanced MRI and diffusion-weighted imaging (DWI) were constructed and validated using machine learning. As presented in the radiomics nomogram, a prediction model was developed using multivariable logistic regression analysis, which included radiomics scores, radiologic features, and clinical features, such as the alpha-fetoprotein (AFP) level. The calibration, decision-making curve, and clinical usefulness of the radiomics nomogram were analyzed. The radiomic nomogram was validated using independent external cohort data. The areas under the receiver operating curve (AUC) were used to assess the predictive capability.RESULTSPathological examination confirmed MVI in 64 (28.9%), 22 (23.4%), and 16 (16.0%) of the 221, 94, and 100 patients, respectively. AFP, tumor size, non-smooth tumor margin, incomplete capsule, and peritumoral hypointensity in hepatobiliary phase (HBP) images had poor diagnostic value for MVI of sHCC. Quantitative radiomic features (1409) of MRI scans) were extracted. The classifier of logistic regression (LR) was the best machine learning method, and the radiomics scores of HBP and DWI had great diagnostic efficiency for the prediction of MVI in both the testing set (hospital A) and validation set (hospital B, C). The AUC of HBP was 0.979, 0.970, and 0.803, respectively, and the AUC of DWI was 0.971, 0.816, and 0.801 (P < 0.05), respectively. Good calibration and discrimination of the radiomics and clinical combined nomogram model were exhibited in the testing and two external validation cohorts (C-index of HBP and DWI were 0.971, 0.912, 0.808, and 0.970, 0.843, 0.869, respectively). The clinical usefulness of the nomogram was further confirmed using decision curve analysis.CONCLUSIONAFP and conventional Gd-EOB-DTPA-enhanced MRI features have poor diagnostic accuracies for MVI in patients with sHCC. Machine learning with an LR classifier yielded the best radiomics score for HBP and DWI. The radiomics nomogram developed as a noninvasive preoperative prediction method showed favorable predictive accuracy for evaluating MVI in sHCC.

Non-hypervascular hepatobiliary phase hypointense lesions detected in patients with hepatocellular carcinoma: a post hoc analysis of SORAMIC trial to identify risk factors for progression

ObjectivesTo identify clinical and imaging parameters associated with progression of non-hypervascular hepatobiliary phase hypointense lesions during follow-up in patients who received treatment for hepatocellular carcinoma.MethodsA total of 67 patients with 106 lesions were identified after screening 538 patients who underwent gadoxetic acid–enhanced MRI within the SORAMIC trial. All patients were allocated to the trial treatment according to the trial scheme, and 61 of 67 patients received systemic treatment with sorafenib (either alone or combined with locoregional therapies) during the trial period. Follow-up images after treatment according to trial scheme were reviewed for subsequent hypervascularization or > 1 cm size increase. The correlation between progression and several imaging and clinical parameters was assessed using univariable and multivariable analyses.ResultsOn a median 178 (range, 48–1072) days follow-up period, progression was encountered in 18 (16.9%) lesions in 12 (17.9%) patients. In univariable analysis size > 12.6 mm (p = 0.070), ECOG-PS (p = 0.025), hypointensity at T1-weighted imaging (p = 0.028), hyperintensity at T2-weighted imaging (p < 0.001), hyperintensity at DWI images (p = 0.007), and cirrhosis (p = 0.065) were correlated with progression during follow-up. Hyperintensity at T2 images (p = 0.011) was an independent risk factor for progression in multivariable analysis, as well as cirrhosis (p = 0.033) and ECOG-PS (p = 0.030).ConclusionsNon-hypervascular hepatobiliary phase hypointense lesions are associated with subsequent progression after treatment in patients with HCC. T2 hyperintensity, diffusion restriction, cirrhosis, and higher ECOG-PS could identify lesions with increased risk. These factors should be considered for further diagnostic evaluation or treatment of such lesions.Key Points• Non-hypervascular hepatobiliary phase hypointense lesions have considerable risk of progression in patients with hepatocellular carcinoma receiving treatment.• T2 hyperintensity, cirrhosis, ECOG-PS, and hyperintensity at DWI are associated with increased risk of progression.• Non-hypervascular hepatobiliary phase hypointense lesions should be considered in the decision-making process of locoregional therapies, especially in the presence of these risk factors.

Do transition and hepatobiliary phase hypointensity improve LI-RADS categorization as an alternative washout: a systematic review and meta-analysis.

The definition of washout in gadoxetate disodium-enhanced MRI (Gd-EOB-MRI) is controversial. The current Liver Imaging Reporting and Data System (LI-RADS) defines washout only in the portal venous phase on Gd-EOB-MRI, leading to low diagnostic sensitivity for HCC. We performed a meta-analysis to compare the diagnostic performance of Gd-EOB-MRI using conventional (cWO) and modified (mWO) definitions of washout. The PubMed and EMBASE databases were searched to identify studies published between January 1, 2010, and August 1, 2021, that compared the diagnostic performance of cWO and mWO for HCC. The mWOs added transition phase (TP) hypointensity (mWO-1), hepatobiliary phase (HBP) hypointensity (mWO-2), or both (mWO-3). The pooled sensitivity and specificity were calculated using a bivariate random-effects model. Study heterogeneity was explored by subgroup analysis and meta-regression analysis. Ten comparative studies with 2391 patients were included. Compared to cWO, the overall mWO yielded significantly higher sensitivity (71% vs. 81%, p = 0.00) and lower specificity (97% vs. 93%, p = 0.01) for diagnosing HCC. The area under the curve (AUC) was 0.90 and 0.94 for the cWO and mWO, respectively. Regarding the three types of mWOs, mWO-2 showed the highest sensitivity (85%) and specificity (96%) for diagnosing HCC. mWO-2 achieved the highest AUC (0.97), followed by mWO-1 (0.90), and mWO-3 (0.89). Average reviewer experience and scanner field strength were significantly associated with study heterogeneity (p < 0.05). Inclusion of TP and HBP hypointensity in the definition of washout improved the sensitivity with slightly lower specificity for diagnosing HCC in LI-RADS. • Compared to the conventional definition of washout, studies using a modified definition had higher sensitivity (71% vs. 81%) but lower specificity (97% vs. 93%) in LI-RADS for the diagnosis of HCC. • Hepatobiliary phase hypointensity may be a preferred alternative washout for HCC diagnosis with the highest area under the curve. • Studies with experienced reviewer or 3.0T MRI showed higher sensitivity and lower specificity for diagnosing HCC when using modified washout (p < 0.05).

Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI: long-term follow-up in a surveillance cohort.

With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data. This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation. A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively. About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules. • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.

Comparison of Gadobenate-Enhanced MRI and Gadoxetate-Enhanced MRI for Hepatocellular Carcinoma Detection Using LI-RADS Version 2018: A Prospective Intraindividual Randomized Study.

BACKGROUND. Gadobenate and gadoxetate show different degrees of intracellular accumulation within hepatocytes, potentially impacting these agents' relative performance for hepatocellular carcinoma (HCC) diagnosis. OBJECTIVE. The purpose of this article was to perform an intraindividual comparison of gadobenate-enhanced MRI and gadoxetate-enhanced MRI for detection of HCC and to assess the impact of inclusion of hepatobiliary phase images on HCC detection for both agents. METHODS. This prospective study enrolled 126 patients (112 men, 14 women; mean age, 52.3 years) at high risk for HCC who consented to undergo two 3-T liver MRI examinations (one using gadobenate [0.05 mmol/kg], one using gadoxetate [0.025 mmol/kg]) separated by 7-14 days. The order of the two contrast agents was randomized. All examinations included postcontrast dynamic and hepatobiliary phase images (120 minutes for gadobenate, 20 minutes for gadoxetate). Three radiologists independently reviewed the gadobenate and gadoxetate examinations in separate sessions and recorded the location of detected observations. Observations were classified using LI-RADS version 2018 and using a LI-RADS modification whereby hepatobiliary phase hypointensity may upgrade observations from category LR-4 to LR-5. Observations classified as LR-5 were considered positive interpretations for HCC. Diagnostic performance for histologically confirmed HCC (n = 96) was assessed. RESULTS. Across readers, sensitivity for HCC for gadobenate versus gadoxetate was 74.0-80.2% versus 54.2-67.7% using dynamic images alone and 82.1-87.4% versus 66.3-81.1% using dynamic and hepatobiliary phase images. For HCCs measuring 1.0-2.0 cm, sensitivity for gadobenate versus gadoxetate was 61.9% (all readers) versus 38.1-57.1% using dynamic images alone and 76.2-85.7% versus 52.4-61.9% using dynamic and hepatobiliary phase images. PPV for HCC ranged from 88.6% to 97.4% across readers, agents, and image sets. CONCLUSION. Sensitivity for HCC was higher for gadobenate than for gadoxetate, whether using dynamic images alone or dynamic and hepatobiliary phase images; the improved sensitivity using gadobenate was more pronounced for small HCCs. Whereas hepatobiliary phase images improved sensitivity for both agents, sensitivity of gadobenate using dynamic images alone compared favorably with that of gadoxetate using dynamic and hepatobiliary phase images. CLINICAL IMPACT. The findings support gadobenate as a preferred agent over gadoxetate when performing liver MRI in patients at high risk for HCC.

Imaging diagnosis of hepatocellular carcinoma: Future directions with special emphasis on hepatobiliary magnetic resonance imaging and contrast-enhanced ultrasound.

Hepatocellular carcinoma (HCC) is a unique cancer entity that can be noninvasively diagnosed using imaging modalities without pathologic confirmation. In 2018, several major guidelines for HCC were updated to include hepatobiliary contrast agent magnetic resonance imaging (HBA-MRI) and contrast-enhanced ultrasound (CEUS) as major imaging modalities for HCC diagnosis. HBA-MRI enables the achievement of high sensitivity in HCC detection using the hepatobiliary phase (HBP). CEUS is another imaging modality with real-time imaging capability, and it is reported to be useful as a second-line modality to increase sensitivity without losing specificity for HCC diagnosis. However, until now, there is an unsolved discrepancy among guidelines on whether to accept “HBP hypointensity” as a definite diagnostic criterion for HCC or include CEUS in the diagnostic algorithm for HCC diagnosis. Furthermore, there is variability in terminology and inconsistencies in the definition of imaging findings among guidelines; therefore, there is an unmet need for the development of a standardized lexicon. In this article, we review the performance and limitations of HBA-MRI and CEUS after guideline updates in 2018 and briefly introduce some future aspects of imaging-based HCC diagnosis.