Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

Transplantation Within 6 Months of Registration does not Enhance Survival for Patients with Perihilar Cholangiocarcinoma.

OBJECTIVES: Determine if timing of transplantation affects patient mortality. BACKGROUND: Neoadjuvant therapy and liver transplantation has emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known. METHODS: We reviewed all patients registered for a standardized pCCA protocol between 1996 - 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256). RESULTS: The median (interquartile range) time from registration to transplant or drop out was 5.74 (3.25-7.06) months. Compared to a short wait time (0-3 months), longer waiting times did not affect all-cause mortality: (3-6 months) hazard ratio (HR) 0.98; 95% CI 0.52-1.84; (6-9 months) HR 0.80; 95% CI 0.39-1.65; (9-12 months) HR 0.56; 95% CI 0.26-1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR 0.97; 95% CI 0.67-1.42; AB or B blood group HR 0.93; 95% CI 0.62-1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR 0.92; 95% CI 0.87-0.97). This benefit began after a 6 month waiting time minimum (HR 0.53; 95% CI 0.26-1.10) and increased further after 9 months (HR; 0.43 95% CI 0.20-0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI 0.98-1.00). CONCLUSIONS: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival.

Acquired ductopenia: an insight into imaging findings.

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management.

Imaging of Biliary Tree Abnormalities.

Pathologic conditions of the biliary system, although common, can be difficult to diagnose clinically. Challenges in biliary imaging include anatomic variants and the dynamic nature of the biliary tract, which can change with age and intervention, blurring the boundaries of normal and abnormal. Choledochal cysts can have numerous appearances and are important to diagnose given the risk of cholangiocarcinoma potentially requiring surgical resection. Choledocholithiasis, the most common cause of biliary dilatation, can be difficult to detect at US and CT, with MRI having the highest sensitivity. However, knowledge of the imaging pitfalls of MRI and MR cholangiopancreatography is crucial to avoid misinterpretation. Newer concepts in biliary tract malignancy include intraductal papillary biliary neoplasms that may develop into cholangiocarcinoma. New paradigms in the classification of cholangiocarcinoma correspond to the wide range of imaging appearances of the disease and have implications for prognosis. Accurately staging cholangiocarcinoma is imperative, given expanding curative options including transplant and more aggressive surgical options. Infections of the biliary tree include acute cholangitis or recurrent pyogenic cholangitis, characterized by obstruction, strictures, and central biliary dilatation. Inflammatory conditions include primary sclerosing cholangitis, which features strictures and fibrosis but can be difficult to differentiate from secondary causes of sclerosing cholangitis, including more recently described entities such as immunoglobulin G4-related sclerosing cholangitis and COVID-19 secondary sclerosing cholangitis. The authors describe a wide variety of benign and malignant biliary tract abnormalities, highlight differentiating features of the cholangitides, provide an approach to interpretation based on the pattern of imaging findings, and discuss pearls and pitfalls of imaging to facilitate accurate diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

Liver stiffness measurement by magnetic resonance elastography predicts cirrhosis and decompensation in alcohol-related liver disease.

PURPOSE: To evaluate magnetic resonance elastography (MRE)-based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD. METHODS: Patients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation. RESULTS: A total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0-2.2, p = 0.002-0.003) and hepatic decompensation (HR = 1.2-1.3, p = 0.0001-0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables. CONCLUSIONS: MRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.

Disease severity prognostication in primary sclerosing cholangitis: a validation of the Anali scores and comparison with the potential functional stricture.

OBJECTIVES: Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALIGd and ANALINoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS). MATERIALS AND METHODS: This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALIGd and ANALINoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis). RESULTS: Inter-reader agreement was almost perfect (Ï° = 0.81) for PFS, but only moderate-(Ï° = 0.55) for binary ANALINoGd. For binary ANALIGd, the agreement was slightly better on HBP (Ï° = 0.64) than on arterial-phase (AP) (Ï° = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively). CONCLUSION: ANALINoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients. CLINICAL RELEVANCE STATEMENT: The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients. KEY POINTS: Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.

Acquisition Efficiency and Technical Repeatability of Dual-Frequency 3D Vector MR Elastography of the Liver.

BACKGROUND: MR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers. PURPOSE: To establish a practical simultaneous dual-frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz. STUDY TYPE: Retrospective. SUBJECTS: One hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual-frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE. FIELD STRENGTH/SEQUENCE: 3-T, single- or dual-frequency MRE at 30 Hz and 60 Hz. ASSESSMENT: Liver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4-point scale (0-3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores. STATISTICAL TESTS: Measurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland-Altman plots, and repeatability coefficient (RC). Mann-Whitney U tests were used to evaluate the differences in image quality between different methods. A P-value <0.05 was considered statistically significant. RESULTS: Success rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = -4.523). DATA CONCLUSION: Compared with conventional and second harmonic methods, simultaneous dual-frequency had better image quality, high success rate and the advantage of intrinsic co-registration, while the second harmonic method can be an alternative if custom waveform is not available. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Imaging cholangiocarcinoma: CT and MRI techniques.

Cross-sectional imaging plays a crucial role in the detection, diagnosis, staging, and resectability assessment of intra- and extrahepatic cholangiocarcinoma. Despite this vital function, there is a lack of standardized CT and MRI protocol recommendations for imaging cholangiocarcinoma, with substantial differences in image acquisition across institutions and vendor platforms. In this review, we present standardized strategies for the optimal imaging assessment of cholangiocarcinoma including contrast media considerations, patient preparation recommendations, optimal contrast timing, and representative CT and MRI protocols with individual sequence optimization recommendations. Our recommendations are supported by expert opinion from members of the Society of Abdominal Radiology's Disease-Focused Panel (DFP) on Cholangiocarcinoma, encompassing a broad array of institutions and practice patterns.

Precision and Test-Retest Repeatability of Stiffness Measurement with MR Elastography: A Multicenter Phantom Study.

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Interpretation, Reporting, and Clinical Applications of Liver MR Elastography.

Chronic liver disease is highly prevalent and often leads to fibrosis or cirrhosis and complications such as liver failure and hepatocellular carcinoma. The diagnosis and staging of liver fibrosis is crucial to determine management and mitigate complications. Liver biopsy for histologic assessment has limitations such as sampling bias and high interreader variability that reduce precision, which is particularly challenging in longitudinal monitoring. MR elastography (MRE) is considered the most accurate noninvasive technique for diagnosing and staging liver fibrosis. In MRE, low-frequency vibrations are applied to the abdomen, and the propagation of shear waves through the liver is analyzed to measure liver stiffness, a biomarker for the detection and staging of liver fibrosis. As MRE has become more widely used in clinical care and research, different contexts of use have emerged. This review focuses on the latest developments in the use of MRE for the assessment of liver fibrosis; provides guidance for image acquisition and interpretation; summarizes diagnostic performance, along with thresholds for diagnosis and staging of liver fibrosis; discusses current and emerging clinical applications; and describes the latest technical developments.

Multimodality Imaging in Metabolic Syndrome: State-of-the-Art Review.

Metabolic syndrome comprises a set of risk factors that include abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, low high-density lipoprotein levels, and high blood pressure, at least three of which must be fulfilled for diagnosis. Metabolic syndrome has been linked to an increased risk of cardiovascular disease and type 2 diabetes mellitus. Multimodality imaging plays an important role in metabolic syndrome, including diagnosis, risk stratification, and assessment of complications. CT and MRI are the primary tools for quantification of excess fat, including subcutaneous and visceral adipose tissue, as well as fat around organs, which are associated with increased cardiovascular risk. PET has been shown to detect signs of insulin resistance and may detect ectopic sites of brown fat. Cardiovascular disease is an important complication of metabolic syndrome, resulting in subclinical or symptomatic coronary artery disease, alterations in cardiac structure and function with potential progression to heart failure, and systemic vascular disease. CT angiography provides comprehensive evaluation of the coronary and systemic arteries, while cardiac MRI assesses cardiac structure, function, myocardial ischemia, and infarction. Liver damage results from a spectrum of nonalcoholic fatty liver disease ranging from steatosis to fibrosis and possible cirrhosis. US, CT, and MRI are useful in assessing steatosis and can be performed to detect and grade hepatic fibrosis, particularly using elastography techniques. Metabolic syndrome also has deleterious effects on the pancreas, kidney, gastrointestinal tract, and ovaries, including increased risk for several malignancies. Metabolic syndrome is associated with cerebral infarcts, best evaluated with MRI, and has been linked with cognitive decline. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Pickhardt in this issue.

Imaging of Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) continues to be a global health concern, responsible for a significant number of deaths worldwide. Although most individuals who consume alcohol do not develop ALD, heavy drinkers and binge drinkers are at increased risk. Unfortunately, ALD is often undetected until it reaches advanced stages, frequently associated with portal hypertension and hepatocellular carcinoma (HCC). ALD is now the leading indication for liver transplant. The incidence of alcohol-associated hepatitis (AH) surged during the COVID-19 pandemic. Early diagnosis of ALD is therefore important in patient management and determination of prognosis, as abstinence can halt disease progression. The spectrum of ALD includes steatosis, steatohepatitis, and cirrhosis, with steatosis the most common manifestation. Diagnostic techniques including ultrasound, CT, and MRI provide useful information for identifying ALD and excluding other causes of liver dysfunction. Heterogeneous steatosis and transient perfusion changes on CT and MRI in the clinical setting of alcohol-use disorder are diagnostic of severe AH. Elastography techniques are useful for assessing fibrosis and monitoring treatment response. These various imaging modalities are also useful in HCC surveillance and diagnosis. This review discusses the imaging modalities currently used in the evaluation of ALD, highlighting their strengths, limitations, and clinical applications.

Imaging of Fontan-Associated Liver Disease.

ABSTRACT: The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.

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.