Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease.

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness. Materials and Methods This prospective, observational, cross-sectional study (March 2021 to November 2021) enrolled adults with NAFLD, stratified according to the Fibrosis-4 (FIB-4) index (≤1.3, >1.3 and <2.67, ≥2.67), at two sites to assess SWE with five US systems and VCTE with one system. Each participant underwent 12 elastography examinations over two separate days within 1 week, with each day's examinations conducted by a different operator. VCTE and SWE measurements were reported in units of meters per second. The primary end point was the different-day, different-operator reproducibility coefficient (RDCDDDO) pooled across systems for SWE and individually for VCTE. Secondary end points included system-specific RDCDDDO, same-day, same-operator repeatability coefficient (RCSDSO), and between-system same-day, same-operator reproducibility coefficient. The planned sample provided 80% power to detect a pooled RDCDDDO of less than 35%, the prespecified performance threshold. Results A total of 40 participants (mean age, 60 years ± 10 [SD]; 24 women) with low (n = 17), intermediate (n = 15), and high (n = 8) FIB-4 scores were enrolled. RDCDDDO was 30.7% (95% upper bound, 34.4%) for SWE and 35.6% (95% upper bound, 43.9%) for VCTE. SWE system-specific RDCDDDO varied from 24.2% to 34.3%. The RCSDSO was 21.0% for SWE (range, 13.9%-35.0%) and 19.6% for VCTE. The SWE between-system same-day, same-operator reproducibility coefficient was 52.7%. Conclusion SWE met the prespecified threshold, RDCDDDO less than 35%, with VCTE having a higher RDCDDDO. SWE variability was higher between different systems. These estimates advance liver US-based noninvasive test qualification by (a) defining expected variability, (b) establishing that serial examination variability is lower when performed with the same system, and (c) informing clinical trial design. ClinicalTrials.gov Identifier NCT04828551 © RSNA, 2024 Supplemental material is available for this article.

Voxel-based tumor dose correlates to complete pathologic necrosis after transarterial radioembolization for hepatocellular carcinoma.

PURPOSE: The transarterial radioembolization (TARE) dose is traditionally calculated using the single-compartment Medical Internal Radiation Dose (MIRD) formula. This study utilized voxel-based dosimetry to correlate tumor dose with explant pathology in order to identify dose thresholds that predicted response. METHODS: All patients with HCC treated with TARE using yttrium-90 [90Y] glass microspheres at a single institution between January 2015 - June 2023 who underwent liver transplantation were eligible. The [90Y] distribution and dose-volume histograms were determined using Simplicity90 (Mirada Medical, Oxford UK) with a Bremsstrahlung SPECT/CT. A complete response was assigned if explant pathology showed complete necrosis and the patient had not undergone additional treatments to the same tumor after TARE. Logistic regression and receiver operator characteristic (ROC) curves were constructed to evaluate dose thresholds correlated with response. RESULTS: Forty-one patients were included. Twenty-six (63%) met criteria for complete response. Dose to 95% (D95), 70% (D70), and 50% (D50) of the tumor volume were associated with likelihood of complete response by logistic regression (all p < 0.05). For lesions with complete response versus without, the median D95 was 813 versus 232 Gy, D70 was 1052 versus 315 Gy, and D50 was 1181 versus 369 Gy (all p < 0.01). A D95 > 719 Gy had the highest accuracy at 68% (58% sensitivity, 87% specificity) for predicting complete response. Median percent of tumor volume receiving at least 100 Gy (V100), 200 Gy (V200), 300 Gy (V300), and 400 Gy (V400) also differed by pathologic response: the median V100, V200, V300, and V400 was 100% versus 99%, 100% versus 97%, 100% versus 74%, and 100% versus 43% in the complete response versus non-complete response groups, respectively (all p < 0.05). CONCLUSION: Voxel-based dosimetry was well-correlated with explant pathology. The D95 threshold had the highest accuracy, suggesting the D95 may be a relevant target for multi-compartment dosimetry.

MASLD: What We Have Learned and Where We Need to Go-A Call to Action.

Since its introduction in 1980, fatty liver disease (now termed metabolic dysfunction-associated steatotic liver disease [MASLD]) has grown in prevalence significantly, paralleling the rise of obesity worldwide. While MASLD has been the subject of extensive research leading to significant progress in the understanding of its pathophysiology and progression factors, several gaps in knowledge remain. In this pictorial review, the authors present the latest insights into MASLD, covering its recent nomenclature change, spectrum of disease, epidemiology, morbidity, and mortality. The authors also discuss current qualitative and quantitative imaging methods for assessing and monitoring MASLD. Last, they propose six unsolved challenges in MASLD assessment, which they term the proliferation, reproducibility, reporting, needle-in-the-haystack, availability, and knowledge problems. These challenges offer opportunities for the radiology community to proactively contribute to their resolution. The authors conclude with a call to action for the entire radiology community to claim a seat at the table, collaborate with other societies, and commit to advancing the development, validation, dissemination, and accessibility of the imaging technologies required to combat the looming health care crisis of MASLD.

Distinguishing characteristics of xanthogranulomatous cholecystitis and gallbladder adenocarcinoma: a persistent diagnostic dilemma.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis which can resemble gallbladder adenocarcinoma (GAC) on preoperative imaging and present technical challenges in the performance of cholecystectomy. We examined our experience with each pathology to identify distinguishing characteristics that may guide patient counseling and surgical management. METHODS: A retrospective review of all pathologically confirmed cases of XGC and GAC following cholecystectomy between 2015 and 2021 at a single institution was performed. Clinical, biochemical, radiographic, and intraoperative features were compared. RESULTS: There were 37 cases of XGC and 20 cases of GAC. Patients with GAC were older (mean 70.3 years vs 58.0, p = 0.01) and exclusively female (100% vs 45.9%, p < 0.0001). There were no significant differences in accompanying symptoms between groups (nausea/vomiting, fevers, or jaundice). The mean maximum white blood cell count was elevated for XGC compared to GAC (16.4 vs 8.6 respectively, p = 0.044); however, there were no differences in the remainder of the biochemical profile, including bilirubin, liver transaminases, CEA, and CA 19-9. The presence of an intraluminal mass (61.1% vs 9.1%, p = 0.0001) and lymphadenopathy (18.8%. vs 0.0%, p = 0.045) were associated with malignancy, whereas gallbladder wall thickening as reported on imaging (87.9% vs 38.9%, p = 0.0008) and gallstones (76.5% vs. 50.0%, p = 0.053) were more often present with XGC. Cases of XGC more often had significant adhesions/inflammation (83.8% vs 55.0%, p = 0.03). CONCLUSION: Clinical features that may favor benign chronic cholecystitis over gallbladder adenocarcinoma include younger age, male gender, current or prior leukocytosis, and the absence of an intraluminal mass or lymphadenopathy. Laparoscopic cholecystectomy is a safe surgical option for equivocal presentations. Intraoperative frozen section or intentional staging of more extensive procedures based upon final histopathology are valuable surgical strategies.

Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement. METHODS: Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI. RESULTS: Treatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively). CONCLUSIONS: In adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF. CLINICAL TRIAL NUMBER: NCT01265498. IMPACT AND IMPLICATIONS: Although central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

Imaging to Predict Prognosis in Hepatocellular Carcinoma: Current and Future Perspectives.

The focus of hepatocellular carcinoma (HCC) research for many years has been on noninvasive diagnosis. Standardized systematic algorithms composed of combinations of precise features now serve as diagnostic imaging markers of HCC and constitute a major innovation for liver imaging. In clinical practice, the diagnosis of HCC is based primarily on imaging and secondarily on pathologic analysis if the imaging features are not specific. Whereas accurate diagnosis is essential, the next phase of innovation for HCC will likely encompass predictive and prognostic markers. HCC is a biologically heterogeneous malignancy because of complex molecular, pathologic, and patient-level factors that impact the outcomes of treatment. In recent years, there have been many advances in systemic therapy to augment and extend the existing large cache of local and regional options. However, the guideposts for treatment decisions are neither sophisticated nor individualized. This review provides an overview of prognosis in HCC from the patient to the imaging feature level with a focus on future directions toward more individualized treatment guidance.

Pancreatic Cyst Surveillance: Who, Why, How?

Pancreatic cystic lesions (PCLs) are widely prevalent and commonly encountered in abdominal radiology. Some PCLs can be definitively identified at imaging as benign subtypes or those with malignant potential, while others remain indeterminate. Notably, the degree of malignant potential and natural history of the most common subtype, branch-duct intraductal papillary mucinous neoplasms, are not clearly established. In the work-up of PCLs, patients may further be identified as high-risk individuals who are at elevated risk of pancreatic ductal adenocarcinoma due to familial and genetic factors. This review describes current PCL surveillance and management guidelines and highlights ongoing controversies and future directions to aid radiologists in their daily practice.

Development of a Model including MRI Features for Predicting Advanced-stage Recurrence of Hepatocellular Carcinoma after Liver Resection.

Background Identifying patients at high risk for advanced-stage hepatocellular carcinoma (HCC) recurrence after liver resection may improve patient survival. Purpose To develop a model including MRI features for predicting postoperative advanced-stage HCC recurrence. Materials and Methods This single-center, retrospective study includes consecutive adult patients who underwent preoperative contrast-enhanced MRI and curative-intent resection for early- to intermediate-stage HCC (from December 2011 to April 2021). Three radiologists evaluated 52 qualitative features on MRI scans. In the training set, Fine-Gray proportional subdistribution hazard analysis was performed to identify clinical, laboratory, imaging, pathologic, and surgical variables to include in the predictive model. In the test set, the concordance index (C-index) was computed to compare the developed model with current staging systems. The Kaplan-Meier survival curves were compared using the log-rank test. Results The study included 532 patients (median age, 54 years; IQR, 46-62 years; 465 male patients), 302 patients from the training set (median age, 54 years; IQR, 46-63 years; 265 male patients), and 128 patients from the test set (median age, 53 years; IQR, 46-63 years; 108 male patients). Advanced-stage recurrence was observed in 38 of 302 (12.6%) and 15 of 128 (11.7%) of patients from the training and test sets, respectively. Serum neutrophil count (109/L), tumor size (in centimeters), and arterial phase hyperenhancement proportion on MRI scans were associated with advanced-stage recurrence (subdistribution hazard ratio range, 1.16-3.83; 95% CI: 1.02, 7.52; P value range, <.001 to .02) and included in the predictive model. The model showed better test set prediction for advanced-stage recurrence than four staging systems (2-year C-indexes, 0.82 [95% CI: 0.74, 0.91] vs 0.63-0.68 [95% CI: 0.52, 0.82]; P value range, .001-.03). Patients at high risk for HCC recurrence (model score, ≥15 points) showed increased advanced-stage recurrence and worse all-stage recurrence-free survival (RFS), advanced-stage RFS, and overall survival than patients at low risk for HCC recurrence (P value range, <.001 to .02). Conclusion A model combining serum neutrophil count, tumor size, and arterial phase hyperenhancement proportion predicted advanced-stage HCC recurrence better than current staging systems and may identify patients at high risk. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Tsai and Mellnick in this issue.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

LI-RADS: Looking Back, Looking Forward.

Since its initial release in 2011, the Liver Imaging Reporting and Data System (LI-RADS) has evolved and expanded in scope. It started as a single algorithm for hepatocellular carcinoma (HCC) diagnosis with CT or MRI with extracellular contrast agents and has grown into a multialgorithm network covering all major liver imaging modalities and contexts of use. Furthermore, it has developed its own lexicon, report templates, and supplementary materials. This article highlights the major achievements of LI-RADS in the past 11 years, including adoption in clinical care and research across the globe, and complete unification of HCC diagnostic systems in the United States. Additionally, the authors discuss current gaps in knowledge, which include challenges in surveillance, diagnostic population definition, perceived complexity, limited sensitivity of LR-5 (definite HCC) category, management implications of indeterminate observations, challenges in reporting, and treatment response assessment following radiation-based therapies and systemic treatments. Finally, the authors discuss future directions, which will focus on mitigating the current challenges and incorporating advanced technologies. Tha authors envision that LI-RADS will ultimately transform into a probability-based system for diagnosis and prognostication of liver cancers that will integrate patient characteristics and quantitative imaging features, while accounting for imaging modality and contrast agent.

Repeatability of MRI Biomarkers in Nonalcoholic Fatty Liver Disease: The NIMBLE Consortium.

Background There is a need for reliable noninvasive methods for diagnosing and monitoring nonalcoholic fatty liver disease (NAFLD). Thus, the multidisciplinary Non-invasive Biomarkers of Metabolic Liver disease (NIMBLE) consortium was formed to identify and advance the regulatory qualification of NAFLD imaging biomarkers. Purpose To determine the different-day same-scanner repeatability coefficient of liver MRI biomarkers in patients with NAFLD at risk for steatohepatitis. Materials and Methods NIMBLE 1.2 is a prospective, observational, single-center short-term cross-sectional study (October 2021 to June 2022) in adults with NAFLD across a spectrum of low, intermediate, and high likelihood of advanced fibrosis as determined according to the fibrosis based on four factors (FIB-4) index. Participants underwent up to seven MRI examinations across two visits less than or equal to 7 days apart. Standardized imaging protocols were implemented with six MRI scanners from three vendors at both 1.5 T and 3 T, with central analysis of the data performed by an independent reading center (University of California, San Diego). Trained analysts, who were blinded to clinical data, measured the MRI proton density fat fraction (PDFF), liver stiffness at MR elastography (MRE), and visceral adipose tissue (VAT) for each participant. Point estimates and CIs were calculated using χ2 distribution and statistical modeling for pooled repeatability measures. Results A total of 17 participants (mean age, 58 years ± 8.5 [SD]; 10 female) were included, of which seven (41.2%), six (35.3%), and four (23.5%) participants had a low, intermediate, or high likelihood of advanced fibrosis, respectively. The different-day same-scanner mean measurements were 13%-14% for PDFF, 6.6 L for VAT, and 3.15 kPa for two-dimensional MRE stiffness. The different-day same-scanner repeatability coefficients were 0.22 L (95% CI: 0.17, 0.29) for VAT, 0.75 kPa (95% CI: 0.6, 0.99) for MRE stiffness, 1.19% (95% CI: 0.96, 1.61) for MRI PDFF using magnitude reconstruction, 1.56% (95% CI: 1.26, 2.07) for MRI PDFF using complex reconstruction, and 19.7% (95% CI: 15.8, 26.2) for three-dimensional MRE shear modulus. Conclusion This preliminary study suggests that thresholds of 1.2%-1.6%, 0.22 L, and 0.75 kPa for MRI PDFF, VAT, and MRE, respectively, should be used to discern measurement error from real change in patients with NAFLD. ClinicalTrials.gov registration no. NCT05081427 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kozaka and Matsui in this issue.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

The Organ Procurement and Transplantation Network hepatocellular carcinoma classification: Alignment with Liver Imaging Reporting and Data System, current gaps, and future direction.

The Organ Procurement and Transplantation Network (OPTN) updated its allocation policy for liver transplantation to align with the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis of hepatocellular carcinoma (HCC). LI-RADS computed tomography/magnetic resonance imaging algorithm had achieved congruency with the American Association for the Study of Liver Diseases (AASLD) HCC Practice Guidance in 2018, and therefore, alignment of OPTN, LI-RADS, and AASLD unifies HCC diagnostic approaches. The two changes to the OPTN HCC classification are adoption of LI-RADS terminology or lexicon for HCC major imaging features as well as the modification of OPTN Class-5A through the adoption of LI-RADS-5 criteria. However, despite this significant milestone, the OPTN allocation policy may benefit from further refinements such as adoption of treatment response assessment criteria after locoregional therapy and categorization criteria for lesions with atypical imaging appearances that are not specific for HCC. In this review, we detail the changes to the OPTN HCC classification to achieve alignment with LI-RADS, discuss current limitations of the OPTN classification, and explore future directions.

Comparing Survival Outcomes of Patients With LI-RADS-M Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas.

BACKGROUND: There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions. PURPOSE: To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis. STUDY TYPE: Retrospective. SUBJECTS: Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]). FIELD STRENGTH/SEQUENCE: A 1.5 and 3.0 T/3D T1 -weighted gradient echo, T2 -weighted fast spin-echo. ASSESSMENT: The imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected. STATISTICAL TESTS: OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of <0.05 was considered significant. RESULTS: A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS. DATA CONCLUSION: There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Prognostic MRI features to predict postresection survivals for very early to intermediate stage hepatocellular carcinoma.

OBJECTIVES: Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS). MATERIALS AND METHODS: Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS. RESULTS: This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS. CONCLUSION: Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs. CLINICAL RELEVANCE STATEMENT: The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models. KEY POINTS: • Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival. • Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival. • Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years.

Quality Assessment of Ultrasound and Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance: A Systematic Review and Meta-Analysis.

INTRODUCTION: To achieve early detection and curative treatment options, surveillance imaging for hepatocellular carcinoma (HCC) must remain of quality and without substantial limitations in liver visualization. However, the prevalence of limited liver visualization during HCC surveillance imaging has not been systematically assessed. Utilizing a systematic review and meta-analytic approach, we aimed to determine the prevalence of limited liver visualization during HCC surveillance imaging. METHODS: MEDLINE and Embase electronic databases were searched to identify published data on liver visualization limitations of HCC surveillance imaging. An analysis of proportions was pooled using a generalized linear mixed model with Clopper-Pearson intervals. Risk factors were analysed using a generalized mixed model with a logit link and inverse variance weightage. RESULTS: Of 683 records, 10 studies (7,131 patients) met inclusion criteria. Seven studies provided data on liver visualization limitations on ultrasound (US) surveillance exams: prevalence of limited liver visualization was 48.9% (95% CI: 23.5-74.9%) in the overall analysis and 59.2% (95% CI: 24.2-86.9%) in a sensitivity analysis for cirrhotic patients. Meta-regression determined that non-alcoholic fatty liver disease was associated with limited liver visualization on US. Four studies provided data for liver visualization limitations in abbreviated magnetic resonance imaging (aMRI), with inadequate visualization ranging from 5.8% to 19.0%. One study provided data for complete MRI and none for computed tomography. CONCLUSION: A substantial proportion of US exams performed for HCC surveillance provide limited liver visualization, especially in cirrhosis, which may hinder detection of small observations. Alternative surveillance strategies including aMRI may be appropriate for patients with limited US visualization.

Imaging Findings in Cirrhotic Liver: Pearls and Pitfalls for Diagnosis of Focal Benign and Malignant Lesions.

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,. HCC usually has typical imaging characteristics, such as the major features established by the Liver Imaging Reporting and Data System. However, HCC can also have a spectrum of atypical or uncommon appearances, such as cystic HCC, hypovascular HCC, or macroscopic fat-containing HCC. HCCs with certain genetic mutations such as CTNNB-1-mutated HCC can harbor unique imaging features not seen in other types of HCC. In addition, malignancies that are less common than HCC, such as cholangiocarcinoma and metastases, which can be difficult to differentiate, can still occur in cirrhotic livers. Atypical imaging features of benign and malignant lesions can be challenging to accurately diagnose. Therefore, familiarity with these features and an understanding of the prevalence of disease entities in cirrhotic livers are key in the daily practice of radiologists for evaluation of cirrhotic livers. The authors illustrate the typical and atypical features of benign and malignant lesions in cirrhosis and discuss the technical pitfalls and unique advantages associated with various imaging modalities in assessing cirrhotic livers, including noncontrast and contrast-enhanced US, CT, and MRI. Work of the U.S. Government published under an exclusive license with the RSNA. Quiz questions for this article are available in the supplemental material.

Universal Liver Imaging Lexicon: Imaging Atlas for Research and Clinical Practice.

The use of standardized terms in assessing and reporting disease processes has well-established benefits, such as clear communication between radiologists and other health care providers, improved diagnostic accuracy and reproducibility, and the enhancement and facilitation of research. Recently, the Liver Imaging Reporting and Data System (LI-RADS) Steering Committee released a universal liver imaging lexicon. The current version of the lexicon includes 81 vetted and precisely defined terms that are relevant to acquisition of images using all major liver imaging modalities and contrast agents, as well as lesion- and organ-level features. Most terms in the lexicon are applicable to all patients undergoing imaging of the liver, and only a minority of the terms are strictly intended to be used for patients with high risk factors for hepatocellular carcinoma. This pictorial atlas familiarizes readers with the liver imaging lexicon and includes discussion of general concepts, providing sample definitions, schematics, and clinical examples for a subset of the terms in the liver imaging lexicon. The authors discuss general, technical, and imaging feature terms used commonly in liver imaging, with the goal of illustrating their use for clinical and research applications. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material is available for this article.

Direct Comparison of Quantitative US versus Controlled Attenuation Parameter for Liver Fat Assessment Using MRI Proton Density Fat Fraction as the Reference Standard in Patients Suspected of Having NAFLD.

Background MRI-derived proton density fat fraction (PDFF) is an accurate, reliable, and safe biologic marker for use in the noninvasive diagnosis of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). Because of the cost and limited availability of MRI, it is necessary to develop an accurate method to diagnose NAFLD with potential point-of-care access. Purpose To compare the diagnostic accuracy of the quantitative US (QUS) fat fraction (FF) estimator with that of the controlled attenuation parameter (CAP) in the diagnosis of NAFLD using contemporaneous MRI-derived PDFF as the reference standard. Materials and Methods Participants with or suspected of having NAFLD were prospectively recruited at the NAFLD Research Center between July 2015 and July 2019. All participants underwent MRI-derived PDFF measurement, transient elastography with CAP measurement, and QUS. QUS FF was derived using computed QUS parameters from the acquired radiofrequency US data using a calibrated reference phantom. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of QUS FF and CAP in the diagnosis of hepatic steatosis (defined as MRI-derived PDFF ≥ 5%). AUCs were compared using the DeLong test. Results A total of 123 participants were included (mean age, 52 years ± 13 [SD]; 67 [54%] women). Of these participants, 100 (81%) had MRI-derived PDFF of 5% or more. QUS FF had a significantly higher AUC for diagnosis of NAFLD than did CAP (0.92 [95% CI: 0.87, 0.98] vs 0.79 [95% CI: 0.67, 0.90], P = .03). QUS FF had a sensitivity of 98% (98 of 100) and a specificity of 48% (11 of 23). CAP had a sensitivity of 87% (87 of 100) and a specificity of 57% (13 of 23). Conclusion The quantitative US fat fraction estimator is more accurate than the controlled attenuation parameter in the diagnosis of hepatic steatosis in patients with or suspected of having nonalcoholic fatty liver disease. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Ito in this issue.