Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients.

OBJECTIVE: Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis. METHODS: Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS. RESULTS: Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0-4 vs. 5-6 points) (OR, 9.20; 95% CI: 4.68-18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13-7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0-4 vs. 5-6 points) (HR, 1.73; 95% CI: 1.19-2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0-4 points group had shorter OS than those in the FLIS 5-6 points group [20 months (95% CI, 14.7-25.3) vs. 43 months (95% CI, 27.7-58.3); P=0.001]. CONCLUSION: Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.

Inflammatory Pseudotumor of the Liver or Intrahepatic Cholangiocarcinoma, That's the Question: A Review of the Literature.

An inflammatory pseudotumor of the liver is a rare tumor-like lesion composed of polymorphous inflammatory cell infiltrates and variable amounts of fibrosis that can often mimic a malignant liver neoplasm. The etiology of inflammatory pseudotumors of the liver is unknown; symptoms are faint and imaging non-specific. Thus, it is often hard to make a diagnosis preoperatively and it is not so rare to over-treat patients with this disease or vice versa. Thus, more profound knowledge is necessary to plan appropriate disease management. We reported our two cases and systematically searched the literature regarding IPTL. We selected articles published in English from four databases, PubMed, Scopus, Web of Science and Google Scholar, and we included only articles with consistent data. Twenty nine papers fulfilling criteria for the review were selected. The analysis of 69 cases published from 1953 confirmed that the risk factors are unclear, the imaging data is not specific, and biopsy is crucial but not so widely used in clinical practice due to the procedure's related risks, and relatively low effectiveness and improvement in imaging analysis. Regarding treatment, surgeons have moved towards a more conservative attitude over the years due to better imaging quality and patient surveillance. However, surgery remains the modality of choice for most cases with an indeterminate diagnosis. Even if an inflammatory pseudotumor of the liver is a benign tumor with a good prognosis, not requiring any treatment in most cases, sometimes it remains challenging to differentiate it from ICC; therefore, there is a solid recommendation to manage this condition with a multidisciplinary team.

CEUS LI-RADS in Combination With the Serum Biomarker-Based ASAP Model Improves the Diagnostic Performance of HCC in High-Risk Patients.

OBJECTIVE: To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients. METHODS: This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV. RESULTS: The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05). CONCLUSION: CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV.

Evaluation of combined hepatocellular-cholangiocarcinoma using CEUS LI-RADS: correlation with pathological characteristics.

OBJECTIVE: To explore the factors that influence the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-ICC). METHODS: Between September 2014 to July 2020, the CEUS features of 58 patients with pathologically confirmed cHCC-ICC were retrospectively evaluated and assigned according to the CEUS LI-RADS (version 2017). The pathological characteristics of nodules categorizing as different CEUS LI-RADS categories were compared. Multivariate logistic regression analysis was conducted to explore potential factors that may influence the CEUS LI-RADS classification of cHCC-ICC. RESULTS: According to CEUS LI-RADS, 32.8% (19/58), 63.8% (37/58), and 3.4% (2/58) were categorized as LR-5, LR-M, and LR-TIV, respectively. There was significant difference between the LR-M and LR-5 groups with regard to the pathological grade, nodule size, and HCC/ICC-component ratio of cHCC-ICC. Multivariate logistic regression analysis identified tumor size and the relative proportions of hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (ICC) components as the independent influencing factors. CONCLUSION: Tumor size and the relative proportion of HCC and ICC components within the nodule had a significant impact on the CEUS LI-RADS classification of cHCC-ICC.

Discontinuous peripheral enhancement of focal liver lesions on CT and MRI: outside the box of typical cavernous hemangioma.

The discontinuous peripheral enhancement is a pattern of enhancement usually attributed to typical cavernous hemangioma, that is the most common benign solid lesion of the liver. The discontinuous peripheral enhancement, however, may be encountered in many other benign and malignant focal liver lesions as an atypical presentation or evolution, and hemangiomas with discontinuous peripheral hyperenhancement on hepatic arterial phase may not always have the typical post-contrast pattern on portal venous and delayed phases. Therefore, abdominal radiologists may be challenged in their practice by lesions with discontinuous peripheral enhancement. This pictorial essay aims to review the spectrum of benign and malignant focal liver lesions that may show discontinuous peripheral enhancement. A particular point of interest is the diagnostic tree pathway that may guide the radiologists in the differential diagnosis.

ChatGPT yields low accuracy in determining LI-RADS scores based on free-text and structured radiology reports in German language.

Background: To investigate the feasibility of the large language model (LLM) ChatGPT for classifying liver lesions according to the Liver Imaging Reporting and Data System (LI-RADS) based on MRI reports, and to compare classification performance on structured vs. unstructured reports. Methods: LI-RADS classifiable liver lesions were included from German written structured and unstructured MRI reports with report of size, location, and arterial phase contrast enhancement as minimum inclusion requirements. The findings sections of the reports were propagated to ChatGPT (GPT-3.5), which was instructed to determine LI-RADS scores for each classifiable liver lesion. Ground truth was established by two radiologists in consensus. Agreement between ground truth and ChatGPT was assessed with Cohen's kappa. Test-retest reliability was assessed by passing a subset of n = 50 lesions five times to ChatGPT, using the intraclass correlation coefficient (ICC). Results: 205 MRIs from 150 patients were included. The accuracy of ChatGPT at determining LI-RADS categories was poor (53% and 44% on unstructured and structured reports). The agreement to the ground truth was higher (k = 0.51 and k = 0.44), the mean absolute error in LI-RADS scores was lower (0.5 ± 0.5 vs. 0.6 ± 0.7, p < 0.05), and the test-retest reliability was higher (ICC = 0.81 vs. 0.50), in free-text compared to structured reports, respectively, although structured reports comprised the minimum required imaging features significantly more frequently (Chi-square test, p < 0.05). Conclusions: ChatGPT attained only low accuracy when asked to determine LI-RADS scores from liver imaging reports. The superior accuracy and consistency throughout free-text reports might relate to ChatGPT's training process. Clinical relevance statement: Our study indicates both the necessity of optimization of LLMs for structured clinical data input and the potential of LLMs for creating machine-readable labels based on large free-text radiological databases.

The American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System and its modified version in diagnosing hepatocellular carcinoma via Sonazoid: a meta-analysis.

Background: The American College of Radiology (ACR) developed the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) for pure blood contrast agents, but Sonazoid was not included. Modifications to LI-RADS have been proposed for Sonazoid. The purpose of this meta-analysis was to identify and compare the diagnostic efficacy of the two LI-RADS algorithms of Sonazoid. Methods: We searched the PubMed, MEDLINE, Web of Science, Embase, and Cochrane Library databases from databases inception to August 31, 2023, to find original studies on the ACR LI-RADS and/or modified LI-RADS algorithm with Sonazoid used as the contrast agent in patients with high-risk hepatocellular carcinoma (HCC). A bivariate random-effects model was used. Data pooling, meta-regression, and sensitivity analysis were performed for meta-analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the methodological quality, and the Deeks funnel plot asymmetry test was used to evaluate the publication bias. Results: A meta-analysis of 10 studies with 1,611 observations was conducted. The pooled data for ACR LI-RADS category 5 (LR-5) and modified LR-5 were respectively as follows: pooled sensitivity, 0.70 [95% confidence interval (CI): 0.64-0.75] and 0.81 (95% CI: 0.76-0.86) (P<0.05); pooled specificity, 0.90 (95% CI: 0.82-0.94) and 0.87 (95% CI: 0.81-0.91) (P>0.05); and pooled area under the summary receiver operating characteristic curve, 0.84 and 0.91. The diagnostic performance of LI-RADS category M (LR-M) of the two algorithms was comparable. Study heterogeneity was observed. Conclusions: The results indicated that modified LR-5 algorithm demonstrated improved diagnostic sensitivity compared with the ACR LR-5 algorithm of Sonazoid, with differences observed between the different versions. Further research is needed to validate and explore the optimal diagnostic criteria for HCC using Sonazoid. Before the database search was conducted, this study was registered on PROSPERO (International Prospective Register of Systematic Reviews; CRD42023455220).

Clinical impact of MRI on indeterminate findings on contrast-enhanced CT suspicious of HCC.

OBJECTIVES: In patients evaluated for hepatocellular carcinoma (HCC), magnetic resonance imaging (MRI) is often used secondarily when multiphase contrast-enhanced computed tomography (ceCT) is inconclusive. We investigated the clinical impact of adding MRI. MATERIALS AND METHODS: This single-institution retrospective study included 48 MRI scans (44 patients) conducted from May 2016 to July 2023 due to suspicion of HCC on a multiphase ceCT scan. Data included medical history, preceding and subsequent imaging, histology when available, and decisions made at multidisciplinary team meetings. RESULTS: In case of possible HCC recurrence, 63% of the MRI scans were diagnostic of HCC. For 80% of the negative MRI scans, the patients were diagnosed with HCC within a median of 165 days in the suspicious area of the liver. In case of possible de-novo HCC in patients with cirrhosis, 22% of the scans were diagnostic of HCC and 33% of the negative MRI scans were of patients diagnosed with HCC within a median of 109 days. None of the non-cirrhotic patients with possible de-novo HCC and negative MRI scans (64%) were later diagnosed with HCC, but 3/5 of the indeterminate scans were of patients diagnosed with HCC in a biopsy. CONCLUSIONS: Secondary MRI to a multiphase ceCT scan suspicious of HCC is highly valuable in ruling out HCC in non-cirrhotic patients and in diagnosing HCC non-invasively in cirrhotic patients and patients with prior HCC. Patients with cirrhosis or prior HCC are still at high risk of having HCC if MRI results are inconclusive or negative.

Tumor-like conditions that mimic liver tumors.

Non-neoplastic tumor-like conditions of the liver can appear similar to hepatic neoplasms. In many cases, a biopsy is required to confirm the pathology. However, several tumor-like conditions can be correctly diagnosed or suggested prospectively, thus saving patients from unnecessary anxiety and expense. In this image-focused review, we present the ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scan features of eight such entities. Clues that indicate the correct pathology are discussed, and the usual clinical setting is described. Many of these lesions are treated differently from true neoplasms, and the current treatment plan is discussed in many of the cases presented. After reviewing this article, the reader will have a better understanding of these lesions and the situations in which they should be included in the differential diagnosis.

A Modified Targetoid Feature Emphasizing Thin-Rim APHE to Improve the Diagnostic Performance of LI-RADS for Malignant Hepatic Tumors.

Objective: To identify imaging features that help distinguish between HCCs and non-HCC malignancies assigned to LI-RADS M (LR-M) and evaluate the diagnostic performance of a LI-RADS with targetoid criteria using thin-rim arterial phase hyperenhancement (APHE). Materials and Methods: This retrospective study included 381 patients (387 observations) at high-risk for HCC who underwent enhanced-MRI before surgery. Three radiologists reviewed images for LI-RADS categorization of hepatic observations. Univariate and multivariate analysis was conducted to determine reliable features to differentiate between HCC and non-HCC malignancies among the LR-M lesions. The thin-rim (<30%) APHE was defined based on the thickest thickness of rim APHE compared with the tumor radius, and a modified LI-RADS emphasizing thin-rim APHE as a specific feature of LR-M was established. We compared the diagnostic performance of modified LR-M and LI-RADS 5 (LR-5) with the conventional one. Results: Thin-rim APHE and targetoid diffusion-weighted imaging (DWI) were found as independent predictive factors of non-HCC malignancies, while enhancing capsule, thick-rim APHE and peripheral washout were noted as independent variables significantly associated with HCC of LR-M (P<0.05). The noticeable diagnostic performance of thin-rim APHE in distinguishing non-HCC malignancies from HCCs using the ROC curve. Emphasizing thin-rim APHE on targetoid features, the modified LR-M revealed significantly superior specificity and accuracy (89.4% vs 81.1%, P=0.004; and 87.9% vs 82.2%, P=0.027, respectively) while maintaining high sensitivity (82.2% vs 86.0%; P=0.529) compared with the LR-M. Meanwhile, the modified LR-5 achieved greater sensitivity and accuracy (88.6% vs 79.7%, P=0.004; and 85.8% vs 80.1%, P=0.036, respectively) for diagnosing HCC, without compromising specificity (78.3% vs.81.1%; P=0.608) compared with the LR-5. Conclusion: Thin-rim APHE may be the specific imaging feature for differentiating non-HCC malignancies from HCCs within LR-M. The modified targetoid criteria emphasizing thin-rim APHE can improve the diagnostic performance of LI-RADS for hepatic malignancies.

Based on Gadolinium Ethoxybenzyl DTPA-Enhanced MRI: Diagnostic Performance of the Category-Modified LR-5 Criteria in Patients At Risk for Hepatocellular Carcinoma.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients.

Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma.

Purpose: This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed Imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, Version 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19-14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05-8.93; p=0.04), and the absence of arterial phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18-18.47; p<0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors. Conclusion: In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

The comparison of contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI LI-RADS for nodules ≤2 cm in patients at high risk for HCC: a prospective study.

Objectives: To investigate the consistency of LI-RADS of CEUS and EOB-MRI in the categorization of liver nodules ≤2cm in patients at high risk for HCC. Methods: Patients at high risk for HCC with nodules ≤2cm who underwent CEUS and EOB-MRI in our hospital were prospectively enrolled. The CEUS images and EOB-MRI imaging of each liver nodule were observed to evaluate inter-observer consistency and category according to CEUS LI-RADS V2017 and CT/MRI LI-RADS V2017 criteria double blinded. Pathology and/or follow-up were used as reference standard. Results: A total of 127 nodules in 119 patients met the inclusion criteria. The inter-observer agreement was good on CEUS and EOB-MRI LI-RADS (kappa = 0.76, 0.76 p < 0.001). The inter-modality agreement was fair (kappa=0.21, p < 0.001). There was no statistical difference in PPV and specificity between CEUS and EOB-MRI LR-5 for HCC, while the difference in AUC was statistically significant. We used new criteria (CEUS LR-5 and EOB-MRI LR-4/5 or CEUS LR-4/5 and EOB-MRI LR-5) to diagnose HCC. The sensitivity, specificity, and AUC of this criteria was 63.4%, 95.6%, and 0.80. Conclusions: CEUS and EOB-MRI showed fair inter-modality agreement in LI-RADS categorization of nodules ≤2 cm. The inter-observer agreement of CEUS and EOB-MRI LI-RADS were substantial. CEUS and EOB-MRI LR-5 have equally good positive predictive value and specificity for HCC ≤ 2cm, and combining these two modalities may better diagnose HCC ≤ 2 cm. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04212286.

Intravital imaging: dynamic insights into liver immunity in health and disease.

Inflammation is a critical component of most acute and chronic liver diseases. The liver is a unique immunological organ with a dense vascular network, leading to intense crosstalk between tissue-resident immune cells, passenger leucocytes and parenchymal cells. During acute and chronic liver diseases, the multifaceted immune response is involved in disease promoting and repair mechanisms, while upholding core liver immune functions. In recent years, single-cell technologies have unravelled a previously unknown heterogeneity of immune cells, reshaping the complexity of the hepatic immune response. However, inflammation is a dynamic biological process, encompassing various immune cells, orchestrated in temporal and spatial dimensions, and driven by multiorgan signals. Intravital microscopy (IVM) has emerged as a powerful tool to investigate immunity by visualising the dynamic interplay between different immune cells and their surroundings within a near-natural environment. In this review, we summarise the experimental considerations to perform IVM and highlight recent technological developments. Furthermore, we outline the unique contributions of IVM to our understanding of liver immunity. Through the lens of liver disease, we discuss novel immune-mediated disease mechanisms uncovered by imaging-based studies.

[68Ga]Ga-NODAGA-TriGalactan, a low molecular weight tracer for the non-invasive imaging of the functional liver reserve.

BACKGROUND: Determination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure. RESULTS: For synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA. CONCLUSION: [68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique.

Comparison of the efficacy of the gadoxetic acid MRI-derived relative enhancement index (REI) and functional liver imaging score (FLIS) in predicting liver function: validation with Albumin-Bilirubin (ALBI) grade.

PURPOSE: This study compared the predictive performance of the relative enhancement index (REI) derived from gadoxetic acid (GA)-enhanced MRI with that of the functional liver imaging score (FLIS) in estimating liver function among patients with chronic liver disease (CLD) or liver cirrhosis (LC) by validating them with the albumin-bilirubin (ALBI) grade. MATERIALS AND METHODS: We retrospectively examined 166 patients (79 women, 87 men; 57.4 years) who were diagnosed with LC or CLD and underwent GA-enhanced MRI between August 2020 and September 2023. The enhancement ratio (ER) is calculated using the formula: ER = [hepatobiliary phase liver signal (SI HBP20)-precontrast liver signal (SI pre)]/SI pre. The REI is calculated using the formula: REI = Liver Volume (LV) × ER. FLIS was assigned from the sum of three HBP image features, each scored between 0 and 2: liver parenchymal enhancement, biliary contrast excretion, and portal vein sign. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff values of ER, REI, and FLIS in differentiating between ALBI grades. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated for REI and FLIS to distinguish the ALBI grades. Spearman's rank correlation was used to evaluate the ER, REI, and FLIS correlations between the ALBI grades. To evaluate inter-reader reliability for LV, ER, REI, and FLIS, intraclass correlation coefficient (ICC) was used. RESULTS: ROC curve analysis showed that the optimal cutoff value of REI for predicting ALBI Grade 1 was 899-905 for readers 1 and 2 and 461-477 for ALBI Grade 3, respectively. REI performed best in predicting ALBI Grade 1, achieving an accuracy range of 94%-92.2%, sensitivity of 94.9%-94.1%, and specificity of 91.7%-87.5% for readers 1 and 2, respectively. All parameters showed high accuracy in distinguishing ALBI Grade 3 from other grades. However, REI outperformed the others, showing an accuracy range of 98.8%-97.6%, sensitivity of 94.4%-94.4%, and specificity of 99.3%-98% for readers 1 and 2, respectively. REI showed the best and very strong correlation with ALBI for both readers. CONCLUSION: REI showed a very strong correlation with the ALBI grades for assessing liver function. It outperformed FLIS in predicting the ALBI grades, indicating its potential as a radiologic tool comparable to or better than FLIS in predicting liver function, especially given its dependence on liver volume.

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

OBJECTIVE: We 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. METHODS: HCC 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. RESULTS: Of 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. CONCLUSION: DCE-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.

LI-RADS version 2018 treatment response algorithm on extracellular contrast-enhanced MRI in patients treated with transarterial chemoembolization for hepatocellular carcinoma: diagnostic performance and the added value of ancillary features.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm (TRA) (LI-RADS TRA) is used for assessing response of HCC to locoregional therapy (LRT), however, the value of ancillary features (AFs) for TACE-treated HCCs has not been extensively investigated on extracellular agent MRI (ECA-MRI). PURPOSE: To evaluate the diagnostic performance of LI-RADS v2018 TRA on ECA-MRI for HCC treated with transarterial chemoembolization (TACE) and the value of ancillary features. METHODS: This retrospective study included patients who underwent TACE for HCC and then followed by hepatic surgery between January 2019 and June 2023 with both pre- and post-TACE contrast-enhanced MRI available. Two radiologists independently evaluated the post-treated lesions on MRI using LI-RADS treatment response (TR) (LR-TR) algorithm and modified LR-TR (mLR-TR) algorithm in which ancillary features (restricted diffusion and intermediate T2-weighted hyperintensity) were added, respectively. Lesions were categorized as complete pathologic necrosis (100%, CPN) and non-complete pathologic necrosis (< 100%, non-CPN) on the basis of surgical pathology. The diagnostic performance in predicting viable and non-viable tumors based on LR-TR and mLR-TR algorithms was compared using the McNemar test. Interreader agreement was calculated by using Cohen's weighted and unweighted κ. RESULTS: A total of 61 patients [mean age 59 years ± 10 (standard deviation); 47 men] with 79 lesions (57 pathologically viable) were included. For non-CPN prediction, the sensitivity, specificity of LR-TR viable and mLR-TR viable category were 75% (43 of 57), 82% (18 of 22) and 88% (50 of 57), 77% (17 of 22), respectively, the sensitivity of mLR-TR was significantly higher than that of LR-TR (P = 0.016) without difference in specificity (P = 1.000). Interreader agreement for LR-TR and mLR-TR category was moderate (k = 0.50, 95% confidence interval 0.33, 0.67, k = 0.42, 95% confidence interval 0.20, 0.63). The sensitivity of both LR-TR and mLR-TR algorithms in predicting viable tumors between conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) did not have significant difference (cTACE: 76%, 89% vs. DEB-TACE: 73%, 82%). CONCLUSIONS: On ECA-MRI, applying ancillary features to LI-RADS v2018 TRA can improve the sensitivity in predicting pathologic tumor viability in patients treated with TACE for hepatocellular carcinoma with no significant difference in specificity.

Diagnostic Model for Proliferative HCC Using LI-RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI-ICI Combination.

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.

The efficacy of modified contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) using Sonazoid in diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.

Background: The contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) is an algorithm for the diagnosis of hepatocellular carcinoma (HCC) in high-risk populations. Previous studies have shown the algorithm to have high specificity and moderate sensitivity. Nevertheless, it is designated for utilization solely with blood pool contrast agents. Sonazoid, a contrast agent that combines blood pools and Kupffer cells properties, has recently gained approval for marketing in an increased number of countries. Enhanced sensitivity in diagnosing HCC may be achieved through the distinctive Kupffer phase (KP) exhibited by Sonazoid. Certain academics have suggested the modified CEUS LI-RADS using Sonazoid. The main criteria of mild and late (≥60 seconds) washout in CEUS LI-RADS LR-5 were replaced by KP (>10 minutes) defects as the primary criteria. The purpose of this research was to evaluate the effectiveness of the modified CEUS LI-RADS using Sonazoid in diagnosing HCC. Methods: Original studies on Sonazoid and CEUS LI-RADS were searched in the PubMed, Embase, Cochrane Library, and Web of Science databases until 13 July 2023, with no restrictions on language. We enrolled studies that applied Sonazoid for CEUS in patients at high risk of HCC and modified CEUS LI-RADS for the diagnosis of intrahepatic nodules. Meta-analyses, evaluations, case studies, correspondences, remarks, and summaries of conferences were excluded. Additionally, studies that fell outside the scope of this study and contained data on the same patients were also excluded. We evaluated the quality of research by employing the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A bivariate mixed effects model was utilized to conduct a meta-analysis, summarizing the sensitivity and specificity in the diagnosis of HCC. The investigation of potential factors contributing to study heterogeneity was conducted using meta-regression analysis. Results: Out of the 103 studies screened, 6 studies (835 lesions) were included in the final results. Modified CEUS LR-5 exhibited a sensitivity of 0.77 [95% confidence interval (CI): 0.70-0.82; I2=71.98%; P=0.00] and a specificity of 0.88 (95% CI: 0.83-0.92; I2=0.00; P=0.47) for HCC diagnosis, with heterogeneity in sensitivity. The presence of heterogeneity in the study was found to have a significant association with factors such as the study design, the number of image reviewers, the proportion of cirrhosis, the proportion of other non-HCC malignancies (OM) cases, and the type of reference standard (P≤0.05). Conclusions: The modified CEUS LI-RADS LR-5 categorization demonstrates a reasonable level of sensitivity 0.77, but an insufficient level of specificity 0.88 when diagnosing HCC. KP defects cannot be used as a primary feature in the diagnosis of HCC by CEUS LI-RADS, perhaps as an ancillary feature.