Contrast-enhanced ultrasound liver imaging reporting and data system: clinical validation in a prospective multinational study in North America and Europe.

BACKGROUND AND AIMS: The objective of this study is to determine the diagnostic accuracy of the American College of Radiology Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System LR-5 characterization for HCC diagnosis in North American or European patients. APPROACH AND RESULTS: A prospective multinational cohort study was performed from January 2018 through November 2022 at 11 academic and nonacademic centers in North America and Europe. Patients at risk for HCC with at least 1 liver observation not previously treated, identified on ultrasound (US), or multiphase CT or MRI performed as a part of standard clinical care were eligible for the study. All participants were examined with CEUS of the liver within 4 weeks of CT/MRI or tissue diagnosis to characterize up to 2 liver nodules per participant using ACR CEUS Liver Imaging Reporting and Data System. Definite HCC diagnosis on the initial CT/MRI, imaging follow-up, or histology for CT/MRI-indeterminate nodules were used as reference standards. A total of 545 nodules had confirmed reference standards in 480 patients, 73.8% were HCC, 5.5% were other malignancies, and 20.7% were nonmalignant. The specificity of CEUS LR-5 for HCC was 95.1% (95% CI 90.1%-97.7%), sensitivity 62.9% (95% CI 57.9%-67.7%), positive predictive value 97.3% (95% CI 94.5%-98.7%), and negative predictive value 47.7% (95% CI 41.7%-53.8%). In addition, benign CEUS characterization (LR-1 or LR-2) had 100% specificity and 100% positive predictive value for nonmalignant liver nodules. CONCLUSIONS: CEUS Liver Imaging Reporting and Data System provides an accurate categorization of liver nodules in participants at risk for HCC.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.

LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

Synoptic Reporting of Focal Liver Masses in at Risk Patients: Algorithmic Diagnosis and CEUS LI-RADS.

OBJECTIVES: Reporting contrast-enhanced ultrasound (CEUS) for focal liver masses in at risk patients is a challenging task. Traditionally used prose reporting (PR) is inconsistent and lacks standardization. We propose synoptic reporting (SR), encompassing algorithmic interpretation and liver imaging and reporting data system (LI-RADS) categorization. METHODS: A software worksheet from Kailo Medical (Melbourne, AU), incorporates the CEUS algorithm for liver interpretation and CEUS LI-RADS categorization. Part 1. Feasibility of SR: twenty participants of varying experience were presented a brief lecture on SR, algorithmic approach to liver mass interpretation, and CEUS LI-RADS categorization. Ten representative liver masses were shown as unknown cases. Participants inputted data into SR worksheets. Results and LI-RADS category were generated solely by SR. Data were categorized as "correct" or "incorrect." Part 2. Prospective Analysis: Ninety-one patients for SR and 56 for PR, all were tested for completeness, efficiency, and user satisfaction. RESULTS: Part 1: Junior participants, pass rate 81.6%, and senior participants, pass rate 83.3% showed no difference in performance. Part 2: Completeness: SR 98.4% and PR 87.0%. Efficiency: Average total time to completion: SR 11 minutes and PR 20 minutes. User satisfaction: Ultrasound technologists, all referring physicians, and six out of seven radiologists preferred SR over PR. Major benefits cited were total time saved, consistency and accuracy in documentation, and report completeness. CONCLUSIONS: SR is a reliable and useful tool in clinical practice to report liver masses on ultrasound and assign an appropriate LI-RADS categorization and management pathway. This ultimately improves communication with referring clinicians and leads to better patient outcomes.

A Novel Technology for Resolution of CEUS Imaging Problems in Patients With High BMI and Fatty Liver.

OBJECTIVES: In high-BMI patients with and without fatty liver, we evaluate performance of a commercially available specially designed ultrasound probe (SDP) for scanning at depth. Greyscale and contrast-enhanced ultrasound (CEUS) capability of SDP for parenchymal assessment and liver mass characterization, emphasizing HCC, is compared with standard curvilinear probes. METHODS: This retrospective study included 60 patients. Fifty-five with measured BMI included 46/55 (84%) overweight or obese, and 9/55(16%) in the normal range with severe fatty liver. Fifty-six patients with focal liver abnormality included 37 with a mass and 19 with post-ablative treatment site. Masses included 23 confirmed malignancies, 15 HCC, 4 ICC, and 4 metastases. SDP followed suboptimal ultrasound using a standard probe. Images with varying fat content were compared for depth of penetration on greyscale and ability of CEUS to diagnose tumors. RESULTS: SDP showed statistically significant improvement P = <.05 in CEUS penetration for all degrees of fatty liver (mild, moderate, and severe). In malignant tumors, SDP improved detection of lesion washout in the portal venous/late phase (PVP/LP) at depth >10 cm, and in all malignant masses (P < .05). Fifteen confirmed deep HCC showed arterial phase hyperenhancement on standard probe in 10/15 (67%) and 15/15 (100%) on SDP. PVP/LP washout on standard probe was shown in 4/15 (26%) and on SDP, 14/15, (93%). Therefore, 93% of LR-5 tumors were diagnosed with SDP. Removing necessity for biopsy. CONCLUSIONS: Metabolic syndrome and obesity challenge ultrasound, especially CEUS. SDP overcame limitations of standard probes for CEUS penetration especially in fatty liver. SDP was optimal for the liver mass characterization by detecting washout.

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

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

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Hepatocellular Carcinoma in Evolution: Correlation with CEUS LI-RADS.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a high incidence worldwide and a high associated mortality. Well-recognized risk factors that cause a predisposition to the development of HCC include chronic infection with the hepatitis B or C virus, alcohol-related and non-alcohol-related fatty liver disease, and cirrhosis. In these chronically diseased livers, benign regenerative nodules can increase in size and develop cellular atypia that progress into dysplastic nodules and ultimately HCC. This sequence of hepatocarcinogenesis is coupled with changes in nodule vascularity, including progressive decreased density of portal triads and induced neoangiogenesis, resulting in increased hepatic arterial recruitment. Changes in vascularity result in an array of patterns of nodule enhancement and washout, which can be sensitively depicted with dynamic real-time contrast-enhanced US. Regenerative nodules are isoenhancing relative to the liver with all phases, while HCC classically shows avid arterial phase hyperenhancement with late mild washout. In between, there is great variation as nodules evolve through progressive grades of dysplasia toward HCC. Observed patterns of enhancement and washout can be used to diagnose or stratify the risk of malignancy in liver nodules by using the diagnostic algorithm described by the American College of Radiology Liver Imaging Reporting and Data System (LI-RADS). This facilitates the detection and close monitoring of potential early-stage disease. LI-RADS categorizes nodules according to a probabilistic likelihood for HCC with criteria for LR-5 nodules that are highly specific for the diagnosis of HCC, allowing treatment without exposing the patient to invasive biopsy. An invited commentary by Fetzer is available online. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Characterization of Focal Liver Masses: A Multicenter Comparison of Contrast-Enhanced Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

OBJECTIVES: To demonstrate the usefulness of contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver masses via a direct comparison to standard ultrasound and computed tomography/magnetic resonance imaging (CT/MRI). METHODS: A cohort of 214 patients with previously undiagnosed focal liver masses were included from 5 different centers. Each patient was imaged using CEUS and CT and/or MRI. Anonymized and randomized images were interpreted by 4 separate blind readers from 3 of the participating centers (2 readers for CEUS and 2 readers for CT/MRI). Readers were blinded to patient demographics and past medical history. Readers were asked to decide if the lesion was benign or malignant, provide a final diagnosis for the lesion, and provide a confidence interval. Results were compared to truth standard from pathology or expert consensus. RESULTS: In determination of malignancy, CEUS had a sensitivity of 95%, specificity of 82%, PPV of 82%, NPV of 95%, statistically better than standard ultrasound (sensitivity 82%, specificity 56%, PPV 60%, NPV 78%) with P < .01 and not statistically different from CT (sensitivity 90%, specificity 73% PPV 81%, NPV 86%) or MRI (sensitivity 85%, specificity 79%, PPV 68%, NPV 91%) with P ≥ .01. In assigning a final diagnosis, CEUS had an accuracy of 78% statistically better than standard ultrasound (46%) with P < .01 and not statistically different from CT (68%) or MRI (71%) with P > .01. CONCLUSIONS: In the evaluation of focal liver lesions, both for determination of malignancy and in accuracy of final diagnosis, CEUS performs better than standard ultrasound and at least equivalent to both CT and MRI.

Pediatric contrast-enhanced ultrasound: shedding light on the pursuit of approval in the United States.

For two decades, pediatric contrast US has been well accepted throughout Europe and other parts of the world outside the United States because of its high diagnostic efficacy and extremely favorable safety profile. This includes intravenous (IV) administration, contrast-enhanced US (CEUS) and the intravesical application, contrast-enhanced voiding urosonography (ceVUS). However, the breakthrough for pediatric contrast US in the United States did not come until 2016, when the U.S. Food and Drug Administration (FDA) approved the first pediatric indication for a US contrast agent. This initial approval covered the use of Lumason (Bracco Diagnostics, Monroe Township, NJ) for the evaluation of focal liver lesions via IV administration in children. A second pediatric indication followed shortly thereafter, when the FDA extended the use of Lumason for assessing known or suspected vesicoureteral reflux via intravesical application in children. Both initial pediatric approvals were granted without prospective pediatric clinical trials, based instead on published literature describing favorable safety and efficacy in children. Three years later, in 2019, the FDA approved Lumason for pediatric echocardiography following a clinical trial involving a total of 12 subjects at 2 sites. The story of how we achieved these FDA approvals spans more than a decade and involves the extraordinary dedication of two professional societies, namely the International Contrast Ultrasound Society (ICUS) and the Society for Pediatric Radiology (SPR). Credit also must be given to the FDA staff for their commitment to the welfare of children and their openness to compelling evidence that contrast US is a safe, reliable, radiation-free imaging option for our pediatric patients. Understanding the history of this approval process will impact the practical application of US contrast agents, particularly when expanding off-label indications in the pediatric population. This article describes the background of the FDA's approval of pediatric contrast US applications to better illuminate the potential pathways to approvals of future indications.

Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement.

This multidisciplinary update of the Society of Radiologists in Ultrasound consensus statement on liver elastography incorporates the large volume of new information available in the literature since the initial publication. The recommended procedure for acquiring stiffness measurements is reviewed. There has been substantial improvement in the acoustic radiation force impulse (ARFI) technology-most notably the addition of a quality assessment of the shear wave propagation. Due to the efforts of the Quantitative Imaging Biomarkers Alliance, or QIBA, the variability of liver stiffness measurements between systems had decreased. There are now effective treatments for hepatitis B and hepatitis C, and follow-up after effective treatment should be based on the use of the delta change of the value obtained at viral eradication or suppression. Because the detection of compensated advanced chronic liver disease (cACLD) is very important, the new guidelines are made based on the probability of cACLD for given stiffness values. The panel recommends a vendor-neutral rule of four for interpretation for ARFI techniques. This new method simplifies interpretation of liver stiffness results and is more clinically relevant.

RadioGraphics Update: Contrast-enhanced US Approach to the Diagnosis of Focal Liver Masses.

Editor's Note.-Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.

Contrast-enhanced US in Local Ablative Therapy and Secondary Surveillance for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high incidence of recurrence following therapy. Therefore, secondary surveillance (scheduled follow-up imaging after treatment) is an important part of disease management. The recent approval in the United States for use of a microbubble-based contrast agent for US liver imaging promotes the increased use of contrast-enhanced US (CEUS) in patients with HCC. Although the criteria for the diagnosis of HCC at CEUS are well described, there is a paucity of published literature describing the role of CEUS in ablative therapy and secondary surveillance. In the setting of ablative therapy, CEUS can have vital roles, including patient selection, intraprocedural guidance, and immediate postprocedural assessment. Although CEUS is not widely used, the authors found that it can be used to accurately detect residual or recurrent tumor, characterize the geographic pattern of recurrence (intrazonal, extrazonal, segmental, or remote), and assess for tumor in vein. In addition, similar to primary surveillance, secondary surveillance includes assessment of the entire liver for evaluation of new nodules. Arterial phase hyperenhancement is the reference standard characteristic of disease recurrence at secondary surveillance with CEUS. ©RSNA, 2019 See discussion on this article by Rodgers.

Bowel Ultrasound State of the Art: Grayscale and Doppler Ultrasound, Contrast Enhancement, and Elastography in Crohn Disease.

Bowel ultrasound (US) is accurate for assessing bowel inflammation and complications in Crohn disease. Additionally, contrast-enhanced US provides a quantitative, objective measurement of inflammatory activity in inflammatory bowel disease, and shear wave elastography predicts the stiffness of bowel, an increase of which suggests less response to medical therapy, often necessitating surgery. Overall, bowel US is an excellent, safe, and repeatable choice for routine surveillance and for urgent imaging. We describe an approach to evaluating inflammatory bowel disease and review its features on standard grayscale US with Doppler imaging and show how contrast-enhanced US and shear wave elastography can distinguish between inflammatory and fibrostenotic bowel.

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules.

BACKGROUND & AIMS: The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. METHODS: A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500). RESULTS: The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 [47%]) and the LR-4 202 (HCC 173 [87%]). CONCLUSIONS: The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis. LAY SUMMARY: This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis.

Integration of Contrast-enhanced US into a Multimodality Approach to Imaging of Nodules in a Cirrhotic Liver: How I Do It.

Accurate characterization of cirrhotic nodules and early diagnosis of hepatocellular carcinoma (HCC) are of vital importance. Currently, computed tomography (CT) and magnetic resonance (MR) imaging are standard modalities for the investigation of new nodules found at surveillance ultrasonography (US). This article describes the successful integration of contrast material-enhanced US into a multimodality approach for diagnosis of HCC and its benefits in this population. The application of contrast-enhanced US immediately following surveillance US allows for prompt dynamic contrast-enhanced evaluation, removing the need for further imaging of benign lesions. Contrast-enhanced US also provides dynamic real-time assessment of tumor vascularity so that contrast enhancement can be identified regardless of its timing or duration, allowing for detection of arterial hypervascularity and portal venous washout. The purely intravascular nature of US contrast agents is valuable as the rapid washout of nonhepatocyte malignancies is highly contributory to their differentiation from HCC. The authors believe contrast-enhanced US provides complementary information to CT and MR imaging in the characterization of nodules in high-risk patients. © RSNA, 2017 Online supplemental material is available for this article.

Contrast-enhanced US Approach to the Diagnosis of Focal Liver Masses.

Focal liver lesions are commonly encountered and often demonstrate nonspecific findings at initial imaging. Although most incidentally discovered liver lesions are benign, their noninvasive diagnosis is necessary, especially if they are large or atypical. Imaging characterization of focal liver lesions and exclusion of malignancy are of prime importance, particularly in high-risk populations. Contrast agent-enhanced ultrasonography of liver lesions is both accurate and reproducible for evaluation of benign and malignant liver tumors. Use of an imaging algorithm and a controlled sonographic technique, including dedicated arterial phase cine imaging and imaging every 30 seconds in the portal venous phase and the delayed (or late) phase, is essential for accurate characterization. This algorithmic analysis of focal liver lesions focuses first on the determination of malignancy by imaging the portal venous phase and the late phase; washout in these phases correlates with a malignant tumor, and sustained enhancement in these phases is suggestive that a lesion is benign. In addition, the timing and the intensity of washout differentiate hepatocellular malignancies from nonhepatocellular malignancies. Nonhepatocellular tumors demonstrate early and strong washout, whereas hepatocellular malignancies show delayed and weak washout. Subsequent analysis of dynamic real-time enhancement patterns in the arterial phase demonstrates specific enhancement patterns of common benign and malignant focal liver lesions. Hemangiomas show classic peripheral nodular enhancement, and spoke-wheel centrifugal enhancement is suggestive of focal nodular hyperplasia. Hepatic adenomas may show centripetal filling. However, arterial phase enhancement in malignancy has less specificity. Online supplemental material is available for this article. ©RSNA, 2017 •.

Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

OBJECTIVE: The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. MATERIALS AND METHODS: One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. RESULTS: Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%. CONCLUSION: Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.