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Immune checkpoint inhibitors (ICI) have been used to treat hepatocellular carcinoma (HCC) since 2017. The safety of ICIs in the setting of solid organ transplantation remains controversial. When used in the post-transplant setting, ICIs have been associated with high allograft rejection rates, but there are few published reports on the use of ICIs prior to transplant. We present the first reported case of rescue liver re-transplantation after loss of the first allograft due to severe acute rejection with extensive hepatic necrosis in the setting of pre-transplant ICI therapy with the PD-1 inhibitor nivolumab. It is likely that the durable immune response triggered by nivolumab contributes to graft rejection, therefore extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting.

The Liver Imaging Reporting and Data System (LI-RADS) provides standardized lexicon, technique, interpretation, and reporting of liver imaging in patients at risk for hepatocellular carcinoma (HCC). When applied to at-risk populations, LI-RADS achieves higher than 95% positive predictive value for the noninvasive diagnosis of HCC on computed tomography (CT), MRI and contrast-enhanced ultrasound (CEUS). This article focuses on similarities and differences between the CT/MRI diagnostic algorithm (CT/MRI LI-RADS) and the CEUS diagnostic algorithm (CEUS LI-RADS) to inform health care professionals for efficient and appropriate clinical decisions through the management of patients at risk.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

This update expands on a previously published liver assessment algorithm to include the evaluation of nodules in patients at risk for hepatocellular carcinoma by incorporating the contrast agent–en...

Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from non-hepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.

ObjectivesThis study assesses the risk of progression of Liver Imaging Reporting and Data System (LI-RADS) categories, and the effects of inter-exam changes in modality or radiologist on LI-RADS categorization.MethodsClinical LI-RADS v2014 CT and MRI exams at our institution between January 2014 and September 2017 were retrospectively identified. Untreated LR-1, LR-2, LR-3, and LR-4 observations with at least one follow-up exam were included. Three hundred and seventy-two observations in 214 patients (149 male, 65 female, mean age 61 ± 10years) were included during the study period (715 exams total). Cumulative incidence curves for progression to malignant LI-RADS categories (LR-5 or LR-M) and to LR-4 or higher were generated for each index category and compared using log-rank tests with a resampling extension. Relationships between inter-exam changes in LI-RADS category and modality or radiologist, adjusted for inter-exam time intervals, were modeled using mixed effect logistic regressions.ResultsMedian inter-exam follow-up interval and total follow-up duration were 123 and 227 days, respectively. Index LR-1, LR-2, LR-3, and LR-4 differed significantly in their cumulative incidences of progression to malignant categories (p&nbsp

The Liver Imaging Reporting and Data System (LI-RADS) is composed of four individual algorithms intended to standardize the lexicon, as well as reporting and care, in patients with or at risk for hepatocellular carcinoma in the context of surveillance with US; diagnosis with CT, MRI, or contrast material–enhanced US; and assessment of treatment response with CT or MRI. This report provides a broad overview of LI-RADS, including its historic development, relationship to other imaging guidelines, composition, aims, and future directions. In addition, readers will understand the motivation for and key components of the 2018 update. © RSNA, 2018

BACKGROUND: Non-invasive assessment of the hemodynamic changes of cirrhosis could help guide therapeutic development and clinical management of these patients. PURPOSE: To determine whether free-breathing 4D flow MRI with self-navigation can assess the hemodynamic changes in cirrhosis. STUDY TYPE: Retrospective. FIELD STRENGTH / SEQUENCE: 3T / free-breathing time-resolved three-directional velocity encoding MRI with soft gating and golden-angle view ordering. ASSESSMENT: Measurements of the supra-celiac abdominal aorta (SCA), supra-renal abdominal aorta (SRA), celiac trunk (CeT), superior mesenteric artery (SMA), splenic artery (SpA), common hepatic artery (CHA), portal vein (PV), and supra-renal inferior vena cava (IVC) were acquired by two readers. Novel measures of hepatic vascular resistance (hepatic arterial relative resistance, HARR; portal resistive index, PRI) were developed to quantify cirrhosis-related alterations blood flow. STATISTICAL ANALYSIS: Bland-Altman, linear regression, Tukey’s multiple comparison test. RESULTS: 44 of 47 studies yielded measurable data (94%). There was high inter-reader concordance across all measured arterial structures (range; r = 0.948 – 0.987) and the IVC (r = 0.972), with moderate concordance in the PV (r = 0.866). Conservation of mass analysis showed moderate to high concordance between large vessels (SRA vs. IVC; r = 0.806), small vessels (Celiac vs. CHA+SpA; r = 0.939), and across capillary beds (CeT+SMA vs. PV; r = 0.862). There was increased splanchnic flow in patients with portosystemic shunting (PSS) relative to control patients and patients with cirrhosis but without PSS (p < 0.0001 across CeT, SpA, and CHA). HARR was elevated and PRI was decreased in patients with PSS compared to both other groups. DATA CONCLUSION: 4D flow MRI with self-navigation is technically reliable, showing promise for quantitative assessment of the hemodynamic changes in cirrhosis. Novel quantitative metrics of hepatic vascular resistance correlate with PSS. SUMMARY STATEMENT: Free-breathing, self-navigated 4D flow MRI enables quantification of the hemodynamic changes in cirrhosis, allowing development of quantitative metrics which correlate with altered hepatic and portal blood flow.

The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize liver imaging in patients at high risk for hepatocellular carcinoma (HCC), and it uses a diagnostic algorithm to assign categories that reflect the relative probability of HCC, non-HCC malignancies, or benign focal liver lesions. In addition to major imaging features, ancillary features (AFs) are used by radiologists to refine the categorization of liver nodules. In the present document, we discuss and explain the application of AFs currently defined within the LI-RADS guidelines. We also explore possible additional AFs visible on contrast-enhanced ultrasonography (CEUS). Finally, we summarize the management of CEUS LI-RADS features, including the role of current and potential future AFs.

Background The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC). Methods Chemotherapy-naïve patients with advanced NSCLC were eligible. In the phase I dose-escalation cohort (3 + 3 design), patients received nab-paclitaxel (80 or 100 mg/m2 given intravenously on days 1, 8 and 15) plus cisplatin (60 or 75 mg/m2 given intravenously on day 1) every 4 weeks. The maximum tolerated dose was not reached. Nab-paclitaxel (100 mg/m2 given intravenously on days 1, 8 and 15) plus cisplatin (75 mg/m2 given intravenously on day 1) every 4 weeks was selected for the phase II cohort. The primary endpoint was the objective response rate (ORR). Results Twenty-three patients (phase I, n = 6; phase II, n = 17) were enrolled, and 22 patients were eligible. The median age was 67.5 years (range 37–75), 90.9% were males, 45.5% had adenocarcinoma and 81.8% had stage IV disease. The ORR was 59.1% (90% confidence interval (CI); 41.8–74.4), and the disease control rate was 86.4% (95% CI; 66.7–95.3). The median progression-free survival was 5.1 months (95% CI; 4.0–6.7), and the median overall survival was 24.2 months (95% CI; 8.4 months to not estimable). The common grade ≥ 3 adverse events were neutropenia (31.8%), leukopenia (27.3%), lung infection (18.2%) and hyponatremia (18.2%). There was one instance of grade 2 interstitial pneumonia and no treatment-related death. Conclusions Nab-paclitaxel plus cisplatin was well tolerated and associated with encouraging response outcomes in chemotherapy-naïve patients with advanced NSCLC. Further investigation is warranted. Trial registration UMIN Clinical Trials Registry: UMIN000011776; Date of registration: 17 September 2013; Date of enrolment of the first participant to the trial: 23 January 2014.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications. The 2012 guideline requires updating as, previously, the differences in the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients.

We herein report a case of immune-related colitis induced by the long-term use of nivolumab. A 62-year-old Japanese man was treated with nivolumab at 3 mg/kg every 2 weeks for advanced lung adenocarcinoma. The patient was admitted to our hospital due to non-bloody watery diarrhea after the 70th dose of nivolumab. A biopsy specimen of the colon mucosa revealed evidence of colitis with cryptitis and crypt microabscesses. He was diagnosed with immune-related colitis and started on predonisolone 60 mg/day. Subsequently, his symptoms remarkably resolved. Consideration of immune-related adverse events up to several years after the initiation of nivolumab is important.

Author(s): Kielar, Ania Z; Chernyak, Victoria; Bashir, Mustafa R; Do, Richard K; Fowler, Kathryn J; Mitchell, Donald G; Cerny, Milena; Elsayes, Khaled M; Santillan, Cynthia; Kamaya, Aya; Kono, Yuko; Sirlin, Claude B; Tang, An | Abstract: The computed tomography / magnetic resonance imaging (CT/MRI) Liver Imaging Reporting a Data System (LI-RADS) is a standardized system for diagnostic imaging terminology, technique, interpretation, and reporting in patients with or at risk for developing hepatocellular carcinoma (HCC). Using diagnostic algorithms and tables, the system assigns to liver observations category codes reflecting the relative probability of HCC or other malignancies. This review article provides an overview of the 2017 version of CT/MRI LI-RADS with a focus on MRI. The main LI-RADS categories and their application will be described. Changes and updates introduced in this version of LI-RADS will be highlighted, including modifications to the diagnostic algorithm and to the optional application of ancillary features. Comparisons to other major diagnostic systems for HCC will be made, emphasizing key similarities, differences, strengths, and limitations. In addition, this review presents the new Treatment Response algorithm, while introducing the concepts of MRI nonviability and viability. Finally, planned future directions for LI-RADS will be outlined.Level of evidence5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:1459-1474.

This article reports unique aspects of the management of hepatocellular carcinoma. The study aimed to determine if next‐generation sequencing of blood‐derived circulating tumor DNA from patients with hepatocellular carcinoma could identify actionable somatic molecular alterations. Illustrative examples of treated patients and of in silico molecular dynamic simulation to reveal genomic variant function are included., Background. Because imaging has a high sensitivity to diagnose hepatocellular carcinoma (HCC) and tissue biopsies carry risks such as bleeding, the latter are often not performed in HCC. Blood‐derived circulating tumor DNA (ctDNA) analysis can identify somatic alterations, but its utility has not been characterized in HCC. Materials and Methods. We evaluated 14 patients with advanced HCC (digital ctDNA sequencing [68 genes]). Mutant relative to wild‐type allele fraction was calculated. Results. All patients (100%) had somatic alterations (median = 3 alterations/patient [range, 1–8]); median mutant allele fraction, 0.29% (range, 0.1%–37.77%). Mutations were identified in several genes: TP53 (57% of patients), CTNNB1 (29%), PTEN (7%), CDKN2A (7%), ARID1A (7%), and MET (7%); amplifications, in CDK6 (14%), EGFR (14%), MYC (14%), BRAF (7%), RAF1 (7%), FGFR1 (7%), CCNE1 (7%), PIK3CA (7%), and ERBB2/HER2 (7%). Eleven patients (79%) had ≥1 theoretically actionable alteration. No two patients had identical genomic portfolios, suggesting the need for customized treatment. A patient with a CDKN2A‐inactivating and a CTNNB1‐activating mutation received matched treatment: palbociclib (CDK4/6 inhibitor) and celecoxib (COX‐2/Wnt inhibitor); des‐gamma‐carboxy prothrombin level decreased by 84% at 2 months (1,410 to 242 ng/mL [normal: ≤7.4 ng/mL]; alpha fetoprotein [AFP] low at baseline). A patient with a PTEN‐inactivating and a MET‐activating mutation (an effect suggested by in silico molecular dynamic simulations) received sirolimus (mechanistic target of rapamycin inhibitor) and cabozantinib (MET inhibitor); AFP declined by 63% (8,320 to 3,045 ng/mL [normal: 0–15 ng/mL]). Conclusion. ctDNA derived from noninvasive blood tests can provide exploitable genomic profiles in patients with HCC. Implications for Practice. This study reports that blood‐derived circulating tumor DNA can provide therapeutically exploitable genomic profiles in hepatocellular cancer, a malignancy that is known to be difficult to biopsy.

Given the high prevalence, increasing incidence, and significant morbidity and mortality related to hepatocellular carcinoma (HCC), a robust and cost-effective screening and surveillance program is needed. Most societies recommend ultrasound for HCC screening, despite lack of standardization in imaging acquisition, reporting content and language, and follow-up recommendations. The American College of Radiology Ultrasound Liver Imaging Reporting and Data System (US LI-RADS) fills this unmet need by providing standardization in the use of US in at-risk patients. It is anticipated that US LI-RADS will improve the performance of ultrasound for HCC screening and surveillance and unify management recommendations.

The Liver Imaging Reporting and Data System (LI-RADS) was designed to standardize the interpretation and reporting of observations seen on studies performed in patients at risk for development of hepatocellular carcinoma (HCC). The LI-RADS algorithm guides radiologists through the process of categorizing observations on a spectrum from definitely benign to definitely HCC. Major features are the imaging features used to categorize observations as LI-RADS 3 (intermediate probability of malignancy), LIRADS 4 (probably HCC), and LI-RADS 5 (definite HCC). Major features include arterial phase hyperenhancement, washout appearance, enhancing capsule appearance, size, and threshold growth. Observations that have few major criteria are assigned lower categories than those that have several, with the goal of preserving high specificity for the LR-5 category of Definite HCC. The goal of this paper is to discuss LI-RADS major features, including definitions, rationale for selection as major features, and imaging examples.

Contrast-enhanced ultrasound (CEUS) is a specialized form of ultrasound (US) performed with an intravenous injection of microbubble contrast agents. It has been successfully used for a variety of applications including characterization of liver tumors. In April 2014, the American College of Radiology (ACR) convened a working group of international experts to develop ACR CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS). An initial version of CEUS LI-RADS was published in August 2016. Although the CEUS LI-RADS concept and principles for liver lesion characterization, using dynamic contrast enhancement features, are similar to those for CT or MRI, there are significant differences between CT/MRI and CEUS LI-RADS. Therefore, CEUS LI-RADS has different diagnostic features and a unique characterization algorithm. The size of a lesion, the type and degree of arterial phase enhancement, the presence of washout, and the timing and degree of washout are the major features used for categorization. This paper describes key differences between CT/MRI and CEUS, and provides a diagnostic algorithm of CEUS LI-RADS with detailed, step-by-step instructions and imaging examples of CEUS LI-RADS categories.

The Liver Imaging Reporting and Data System (LI-RADS) uses an algorithm to assign categories that reflect the probability of hepatocellular carcinoma (HCC), non-HCC malignancy, or benignity. Unlike other imaging algorithms, LI-RADS utilizes ancillary features (AFs) to refine the final category. AFs in LI-RADS v2017 are divided into those favoring malignancy in general, those favoring HCC specifically, and those favoring benignity. Additionally, LI-RADS v2017 provides new rules regarding application of AFs. The purpose of this review is to discuss ancillary features included in LI-RADS v2017, the rationale for their use, potential pitfalls encountered in their interpretation, and tips on their application.

We report a case of simultaneous macroamylasemia and macrolipasemia complicated with mucosa-associated lymphoid tissue (MALT) lymphoma. A 78-year-old man presented with hyperamylasemia and hyperlipasemia for 2 years and was misdiagnosed with chronic pancreatitis at another hospital. However, his other pancreatic enzymes were normal, his amylase-creatinine clearance ratio was low, and no definite findings of pancreatic disease were evident. Immunological analyses revealed that both amylase and lipase were bound to immunoglobulin (Ig) A-κ, and that serum IgA was high (827.1 mg/dL). He was diagnosed with simultaneous macroamylasemia and macrolipasemia. Since these diseases are associated with malignancy, an additional investigation was performed which revealed the complication of MALT lymphoma, and polymerase chain reaction analysis showed monoclonal immunoglobulin light chain gene rearrangement (κ >> λ). In this case, macroamylasemia and macrolipasemia may have developed due to the formation of macroenzymes resulting from excess IgA-κ secreted by the MALT lymphoma. Simultaneous macroamylasemia and macrolipasemia are very rare and difficult to diagnose and can lead to diagnostic and therapeutic errors. When encountering atypical clinical features associated with hyperamylasemia and hyperlipasemia, the possibility of macroenzymes and underlying diseases such as lymphoproliferative disorders should be considered.

The epidemic of increasing fatty liver disease and liver cancer worldwide, and especially in Western society, has given new importance to non-invasive liver imaging. Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents provides unique advantages over computed tomography (CT) and magnetic resonance imaging (MRI), the currently established methods. CEUS provides determination of malignancy and allows excellent differential diagnosis of a focal liver mass, based on arterial phase enhancement patterns and assessment of the timing and intensity of washout. Today, increased use of CEUS has provided safe and rapid diagnosis of incidentally detected liver masses, improved multidisciplinary management of nodules in a cirrhotic liver, facilitated ablative therapy for liver tumors and allowed diagnosis of hepatocellular carcinoma without biopsy. Benefits of CEUS include the dynamic real-time depiction of tumor perfusion and the fact that it is a purely intravascular agent, accurately reflecting tumoral and inflammatory blood flow. CEUS has many similarities to contrast-enhanced CT and MRI but also unique differences, which are described. The integration of CEUS into a multimodality imaging setting optimizes patient care.

Background Carboplatin plus nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the available first-line treatments for non-small cell lung cancer (NSCLC) patients. However, the efficacy of carboplatin plus nab-PTX as second-line, remains unknown. We examined the efficacy of carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients. Methods We retrospectively reviewed advanced non-squamous NSCLC patients who received carboplatin plus nab-PTX as a second-line chemotherapy regimen after cisplatin plus pemetrexed in our hospital between March 2013 and December 2017. We assessed clinical characteristics, efficacy, and toxicities. Results Forty-four patients were recruited. The overall response rate (ORR) was 29% and the disease control rate (DCR), 69%. The median progression-free survival (mPFS) was 3.7 months (95% CI: 2.4–5.5 months) and the median overall survival, 16.6 months (95% CI:8.8–19.5 months). We assessed the ORR and mPFS using the best overall response in the prior regimen. The ORR and mPFS were better in the PD group (ORR; 44% and mPFS: 5.6 months). Conclusions Carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients is a treatment option. There were several cases where cisplatin plus pemetrexed was not effective, but Carboplatin plus nab-PTX was.

PURPOSE: To describe a single-center preliminary experience with gadoxetate disodium–enhanced abbreviated MRI for hepatocellular carcinoma (HCC) screening and surveillance in patients with cirrhosis or chronic hepatitis B virus (cHBV). MATERIALS AND METHODS: This was a retrospective study of consecutive patients aged 18 years and older with cirrhosis or cHBV who underwent at least one gadoxetate-enhanced abbreviated MRI examination for HCC surveillance from 2014 through 2016. Examinations were interpreted prospectively by one of six abdominal radiologists for clinical care. Clinical, imaging, and other data were extracted from electronic medical records. Diagnostic adequacy was assessed in all patients. Diagnostic accuracy was assessed in the subset of patients who could be classified as having HCC or not having HCC on the basis of a composite reference standard. RESULTS: In this study, 330 patients (93% with cirrhosis; 45% women; mean age, 59 years) underwent gadoxetate-enhanced abbreviated MRI. In the 330 patients, 311 (94.2%) baseline gadoxetate-enhanced abbreviated MRI examinations were diagnostically adequate. Of 141 (43%) of the 330 patients, 91.4% (129 of 141) could be classified as not having HCC and 8.6% (12 of 141) could be classified as having HCC. Baseline gadoxetate-enhanced abbreviated MRI had 0.92 sensitivity (95% confidence interval [CI]: 0.62, 1.00) and 0.91 specificity (95% CI: 0.84, 0.95) for detection of HCC. Of the 330 patients who underwent baseline gadoxetate-enhanced abbreviated MRI, 187 (57%) were lost to follow-up. CONCLUSION: Gadoxetate-enhanced abbreviated MRI is feasible clinically, has a high diagnostic adequacy rate, and, on the basis of our preliminary experience, accurately depicts HCC in high-risk patients. Strategies to enhance follow-up compliance are needed. © RSNA, 2019 Keywords: Abdomen/GI, Cirrhosis, Liver, MR-Imaging, Oncology, Screening Supplemental material is available for this article.

Background: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk. Methods: Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily ( n = 25) versus placebo ( n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint. Results: Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders. Conclusions: Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713.

The Liver Imaging Reporting And Data System (LI-RADS) was created with the support of the American College of Radiology (ACR) to standardize the acquisition, interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). A comprehensive and rigorous system developed by radiologists, hepatologists, pathologists, and surgeons, LI-RADS addresses a wide range of imaging contexts. Currently, 4 algorithms are available publicly on the ACR website: ultrasound for HCC surveillance, computed tomography and magnetic resonance imaging for HCC diagnosis and tumor staging, contrast-enhanced ultrasound for HCC diagnosis, and computed tomography/magnetic resonance imaging for treatment response assessment. Each algorithm is supported by a decision tree, categorization table, lexicon, atlas, technical requirements, and reporting and management guidance. Category codes reflecting the relative probability of HCC and malignancy are assigned to imaging-detected liver observations, with emerging evidence suggesting that LI-RADS accurately stratifies HCC and malignancy probabilities. LI-RADS is an evolving system and has been updated and refined iteratively since 2011 based on scientific evidence, expert opinion, and user feedback, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Concurrent with its most recent update, LI-RADS was integrated into the American Association for the Study of Liver Diseases HCC guidance released in 2018. We anticipate continued refinement of LI-RADS and progressive adoption by radiologists worldwide, with the eventual goal of culminating in a single unified system for international use.

To study correlates of presenteeism among Japanese IT employees, a cross-sectional study in 440 employees of four IT companies were studied with a net-based questionnaire survey. A structural regression analysis revealed that presenteeism was directly associated with common mental symptoms and job strain, common mental symptoms mediated the effects of job strain and poor workplace social support as well as high Harm Avoidance and low Self-directedness and Cooperativeness upon presenteeism. IT company workers presenteeism may be a result of complicated effects of common mental symptoms, job strain and poor workplace social support, and personality traits.

Contrast-enhanced ultrasound (CEUS) is a specific form of ultrasound imaging performed with intravenous administration of microbubble contrast agents. It has been extensively used for liver tumor characterization and was recently added to the American College of Radiology Liver Imaging Reporting and Data System (CEUS LI-RADS). This paper describes technical recommendations for successful liver CEUS lesion characterization, and provides imaging protocol and Lexicon of imaging findings.

The Liver Imaging Reporting and Data System (LI-RADS) is a reporting system created for the standardized interpretation of liver imaging findings in patients who are at risk for hepatocellular carcinoma (HCC). This system was developed with the cooperative and ongoing efforts of an American College of Radiology-supported committee of diagnostic radiologists with expertise in liver imaging and valuable input from hepatobiliary surgeons, hepatologists, hepatopathologists, and interventional radiologists. In this article, the 2017 version of LI-RADS for computed tomography and magnetic resonance imaging is reviewed. Specific topics include the appropriate population for application of LI-RADS; technical recommendations for image optimization, including definitions of dynamic enhancement phases; diagnostic and treatment response categories; definitions of major and ancillary imaging features; criteria for distinguishing definite HCC from a malignancy that might be non-HCC; management options following LI-RADS categorization; and reporting. ©RSNA, 2017.

PURPOSE: To assess the performance of computer-aided diagnosis (CAD) systems and to determine the dominant ultrasonographic (US) features when classifying benign versus malignant focal liver lesions (FLLs) by using contrast material–enhanced US cine clips. MATERIALS AND METHODS: One hundred six US data sets in all subjects enrolled by three centers from a multicenter trial that included 54 malignant, 51 benign, and one indeterminate FLL were retrospectively analyzed. The 105 benign or malignant lesions were confirmed at histologic examination, contrast-enhanced computed tomography (CT), dynamic contrast-enhanced magnetic resonance (MR) imaging, and/or 6 or more months of clinical follow-up. Data sets included 3-minute cine clips that were automatically corrected for in-plane motion and automatically filtered out frames acquired off plane. B-mode and contrast-specific features were automatically extracted on a pixel-by-pixel basis and analyzed by using an artificial neural network (ANN) and a support vector machine (SVM). Areas under the receiver operating characteristic curve (AUCs) for CAD were compared with those for one experienced and one inexperienced blinded reader. A third observer graded cine quality to assess its effects on CAD performance. RESULTS: CAD, the inexperienced observer, and the experienced observer were able to analyze 95, 100, and 102 cine clips, respectively. The AUCs for the SVM, ANN, and experienced and inexperienced observers were 0.883 (95% confidence interval [CI]: 0.793, 0.940), 0.829 (95% CI: 0.724, 0.901), 0.843 (95% CI: 0.756, 0.903), and 0.702 (95% CI: 0.586, 0.782), respectively; only the difference between SVM and the inexperienced observer was statistically significant. Accuracy improved from 71.3% (67 of 94; 95% CI: 60.6%, 79.8%) to 87.7% (57 of 65; 95% CI: 78.5%, 93.8%) and from 80.9% (76 of 94; 95% CI: 72.3%, 88.3%) to 90.3% (65 of 72; 95% CI: 80.6%, 95.8%) when CAD was in agreement with the inexperienced reader and when it was in agreement with the experienced reader, respectively. B-mode heterogeneity and contrast material washout were the most discriminating features selected by CAD for all iterations. CAD selected time-based time-intensity curve (TIC) features 99.0% (207 of 209) of the time to classify FLLs, versus 1.0% (two of 209) of the time for intensity-based features. None of the 15 video-quality criteria had a statistically significant effect on CAD accuracy—all P values were greater than the Holm-Sidak α-level correction for multiple comparisons. CONCLUSION: CAD systems classified benign and malignant FLLs with an accuracy similar to that of an expert reader. CAD improved the accuracy of both readers. Time-based features of TIC were more discriminating than intensity-based features. (©) RSNA, 2017 Online supplemental material is available for this article.

Background The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. Methods We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Results Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Conclusions Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease.

Author(s): Kono, Yuko; Lyshchik, Andrej; Cosgrove, David; Dietrich, Christoph F; Jang, Hyun-Jung; Kim, Tae Kyoung; Piscaglia, Fabio; Willmann, Juergen K; Wilson, Stephanie R; Santillan, Cynthia; Kambadakone, Avinash; Mitchell, Donald; Vezeridis, Alexander; Sirlin, Claude B

Author(s): Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit; Familial NAFLD Cirrhosis Research Consortium | Abstract: BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Medical imaging plays an important role in the diagnosis and management of hepatocellular carcinoma (HCC). The Liver Imaging Reporting and Data System (LI-RADS) was initially created to standardize the reporting and data collection of CT and MR imaging for patients at risk for HCC. As contrast-enhanced ultrasound (CEUS) has been widely used in clinical practice, it has recently been added to the LI-RADS. While CEUS LI-RADS shares fundamental concepts with CT/MRI LI-RADS, there are key differences between the modalities reflecting dissimilarities in the underlying methods of image acquisition and types of contrast material. This review introduces a recent update of CEUS LI-RADS and explains the key differences from CT/MRI LI-RADS.

Author(s): Smorodinsky, Emmanuil; Ansdell, David S; Foster, Zeke W; Mazhar, Sameer M; Cruite, Irene; Wolfson, Tanya; Sugay, Sebastian B; Iussich, Gabriella; Shiehmorteza, Masoud; Kono, Yuko; Kuo, Alexander; Sirlin, Claude B | Abstract: PurposeTo determine the risk of nephrogenic systemic fibrosis (NSF) in a cohort of patients with chronic liver disease.Materials and methodsThis retrospective, Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study was performed at a single tertiary liver center. The study cohort comprised 1167 patients with chronic liver disease followed in a liver clinic and exposed to gadolinium-based contrast agents (GBCAs) between February 2004 and October 2007. A retrospective review of medical records was performed. For each patient, data were collected on demographics, history of GBCA exposure, presence of purported risk factors for NSF, and histopathological evidence of NSF.ResultsOf the 1167 patients with chronic liver disease, 58% (n = 678) had cirrhosis. The patients had a total of 2421 separate GBCA exposures. Fifty-five percent (n = 646) had a single exposure, 19% (n = 218) had two exposures, and 26% (n = 303) had three or more exposures. Seventy-two percent (n = 843) of patients had renal insufficiency, 25 patients (2.1%) had hepatorenal syndrome, 80 patients (6.8%) were in the perioperative liver transplant period, and 49 patients (4.2%) had one or more additional risk factors for NSF. None of the 1167 patients developed NSF.ConclusionChronic liver disease does not appear to be a significant risk factor for NSF.

Purpose To determine the proportion of untreated Liver Imaging Reporting and Data System (LI-RADS) version 2014 category 2, 3, and 4 observations that progress, remain stable, or decrease in category and to compare the cumulative incidence of progression in category. Materials and Methods In this retrospective, longitudinal, single-center, HIPAA-compliant, institutional review board-approved study, 157 patients (86 men and 71 women; mean age ± standard deviation, 59.0 years ± 9.7) underwent two or more multiphasic computed tomographic (CT) or magnetic resonance (MR) imaging examinations for hepatocellular carcinoma surveillance, with the first examination in 2011 or 2012. One radiologist reviewed baseline and follow-up CT and MR images (mean follow-up, 614 days). LI-RADS categories issued in the clinical reports by using version 1.0 or version 2013 were converted to version 2014 retrospectively; category modifications were verified with another radiologist. For index category LR-2, LR-3, and LR-4 observations, the proportions that progressed, remained stable, or decreased in category were calculated. Cumulative incidence curves for progression were compared according to baseline LI-RADS category (by using log-rank tests). Results All 63 index LR-2 observations remained stable or decreased in category. Among 166 index LR-3 observations, seven (4%) progressed to LR-5, and eight (5%) progressed to LR-4. Among 52 index LR-4 observations, 20 (38%) progressed to a malignant category. The cumulative incidence of progression to a malignant category was higher for index LR-4 observations than for index LR-3 or LR-2 observations (each P < .001) but was not different between LR-3 and LR-2 observations (P = .155). The cumulative incidence of progression to at least category LR-4 was trend-level higher for index LR-3 observations than for LR-2 observations (P = .0502). Conclusion Observations classified according to LI-RADS version 2014 categories are associated with different imaging outcomes. (©) RSNA, 2016 Online supplemental material is available for this article.

SummaryBackground Abdominal ultrasound fails to detect over one-fourth of hepatocellular carcinoma (HCC) at an early stage in patients with cirrhosis. Identifying patients in whom ultrasound is of inadequate quality can inform interventions to improve surveillance effectiveness. Aim To evaluate and identify predictors of ultrasound quality in patients with cirrhosis. Methods We performed a retrospective cohort study among patients who underwent ultrasound examination for a cirrhosis-related indication between April 2015 and October 2015. Three fellowship-trained abdominal radiologists collectively reviewed all ultrasound exams and categorised exam quality as definitely adequate, likely adequate, likely inadequate and definitely inadequate to exclude liver lesions. We performed multivariable logistic regression to determine characteristics associated with inadequate ultrasound quality. Results Among 941 patients, 191 (20.3%) ultrasounds were inadequate for excluding HCC- 134 definitely inadequate and 57 likely inadequate. In multivariable analysis, inadequate quality was associated with male gender (OR 1.68, 95% CI 1.14–2.48), body mass index category (OR 1.67, 95% CI 1.45–1.93), Child–Pugh B or C cirrhosis (OR 1.93, 95% CI 1.32–2.81), alcohol-related cirrhosis (OR 2.11, 95% CI 1.33–3.37), NASH cirrhosis (OR 2.87, 95% CI 1.71–4.80), and in-patient status (OR 1.55, 95% CI 1.01–2.37). Ultrasounds were inadequate in over one-third of patients with Child–Pugh C cirrhosis, BMI >35, or NASH cirrhosis. Conclusions One in five ultrasounds in patients with cirrhosis are inadequate for exclusion of HCC, which can contribute to surveillance failure. Alternative surveillance modalities are needed in subgroups prone to inadequate ultrasounds including obese patients, those with Child Pugh B or C cirrhosis, and those with alcohol- or NASH-related cirrhosis.

Splenic lymphangioma is a rare, benign lesion of the spleen that is characterized microscopically by a proliferation of thin-walled vascular channels filled by proteinacious material. Based on microscopic features, three types of lymphangiomas are described as simple capillary, cavernous, and cystic; however, the distinction between these types is not uniformly accepted. The cystic type is the most common type and has well described imaging characteristics. However, little is known about the less common cavernous and capillary forms of lymphangioma. Herein, we present a case of a patient with two synchronous colon cancers that presented with a concomitant splenic mass that was initially suspected to be metastatic disease. Despite the use of multiple imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI), nuclear imaging, and contrast-enhanced ultrasound, the final diagnosis of cavernous lymphangioma was made following core needle biopsy of the lesion. A thorough review of literature and this case now demonstrate the difficulty in differentiating atypical forms of splenic lymphangiomas from other benign lesions such as hemangioma.

This study was performed to evaluate the cross section of the thymus in 46 clinically healthy Holstein calves and heifers from birth to 100 weeks of age and 8 age-matched affected animals with chronic bronchopneumonia by ultrasonography. The cross sectional area of the thymus increased in healthy calves and heifers from birth to 31 weeks of age, peaked around 35 weeks of age, and then decreased until 100 weeks after birth. A positive correlation (r = 0.74, P < 0.05) was found between the area in cross section and the weight of the whole thymus in calves and heifers with chronic bronchopneumonia. The cross- sectional areas of the thymus were significantly (P < 0.05) lowered in animals with chronic bronchopneumonia. The cross sections of thymus in clinically healthy calves at 2 weeks of age and heifers at 34 weeks and 87 weeks of age were hypoechoic, moderately hyperechoic and hyperechoic, respectively. The observation of thymus by ultrasonography seems to be an effective tool for estimating the size of the thymus objectively in Holstein calves and heifers from birth to 100 weeks of age. The results of this study prove the approach to be useful and applicable to monitor the growth of thymus in Holstein calves and heifers and their association with chronic pneumonia.

Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.

Large cell carcinoma of the lung with a rhabdoid phenotype is a rare type of lung cancer, and does not commonly metastasize to the small intestine. Herein we describe a 63-yr-old Japanese male with ileus resulting from small intestinal metastasis from lung cancer. Tumour enlargement was rapid and could not be treated with chemotherapy.

Capsular retraction is an infrequent but characteristic feature of malignant liver lesions such as hepatic metastases and intrahepatic cholangiocarcinoma. Rarely, this finding may be observed in association with benign lesions, such as atypical haemangiomas. Capsular retraction has not previously been reported in association with hepatic inflammatory pseudotumour (IPT). Hepatic IPT is an uncommon benign hepatic lesion with a good clinical prognosis. In this report, we discuss the case of a 48-year-old woman with capsular retraction secondary to multifocal hepatic inflammatory IPTs.

Chronic liver disease is a major public health problem worldwide. Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves the accumulation of collagen, proteoglycans, and other macromolecules within the extracellular matrix. Fibrosis tends to progress, leading to hepatic dysfunction, portal hypertension, and ultimately cirrhosis. Liver biopsy, the standard of reference for diagnosing liver fibrosis, is invasive, costly, and subject to complications and sampling variability. These limitations make it unsuitable for diagnosis and longitudinal monitoring in the general population. Thus, development of a noninvasive, accurate, and reproducible test for diagnosis and monitoring of liver fibrosis would be of great value. Conventional cross-sectional imaging techniques have limited capability to demonstrate liver fibrosis. In clinical practice, imaging studies are usually reserved for evaluation of the presence of portal hypertension or hepatocellular carcinoma in cases that have progressed to cirrhosis. In response to the rising prevalence of chronic liver diseases in Western nations, a number of imaging-based methods including ultrasonography-based transient elastography, computed tomography–based texture analysis, and diverse magnetic resonance (MR) imaging–based techniques have been proposed for noninvasive diagnosis and grading of hepatic fibrosis across its entire spectrum of severity. State-of-the-art MR imaging–based techniques in current practice and in development for noninvasive assessment of liver fibrosis include conventional contrast material–enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, and MR perfusion imaging. © RSNA, 2009

To compare PRESS and STEAM MR spectroscopy for assessment of liver fat in human subjects.Single-voxel (20 x 20 x 20 mm) PRESS and STEAM spectra were obtained at 1.5T in 49 human subjects with known or suspected fatty liver disease. PRESS and STEAM sequences were obtained with fixed TR (1500 msec) and different TE (five PRESS spectra between TE 30-70 msec, five STEAM spectra between TE 20-60 msec). Spectra were quantified and T2 and T2-corrected peak area were calculated by different techniques. The values were compared for PRESS and STEAM.Water T2 values from PRESS and STEAM were not significantly different (P = 0.33). Fat peak T2s were 25%-50% shorter on PRESS than on STEAM (P0.02 for all comparisons) and there was no correlation between T2s of individual peaks. PRESS systematically overestimated the relative fat peak areas (by 7%-263%) compared to STEAM (P0.005 for all comparisons). The peak area given by PRESS was more dependent on the T2-correction technique than STEAM.Measured liver fat depends on the MRS sequence used. Compared to STEAM, PRESS underestimates T2 values of fat, overestimates fat fraction, and provides a less consistent fat fraction estimate, probably due to J coupling effects.

© 2014 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. Ezetimibe inhibits intestinal cholesterol absorption and lowers low-density lipoprotein cholesterol. Uncontrolled studies have suggested that it reduces liver fat as estimated by ultrasound in nonalcoholic steatohepatitis (NASH). Therefore, we aimed to examine the efficacy of ezetimibe versus placebo in reducing liver fat by the magnetic resonance imaging-derived proton density-fat fraction (MRI-PDFF) and liver histology in patients with biopsy-proven NASH. In this randomized, double-blind, placebo-controlled trial, 50 patients with biopsy-proven NASH were randomized to either ezetimibe 10 mg orally daily or placebo for 24 weeks. The primary outcome was a change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Novel assessment by two-dimensional and three-dimensional magnetic resonance elastography was also performed. Ezetimibe was not significantly better than placebo at reducing liver fat as measured by MRI-PDFF (mean difference between the ezetimibe and placebo arms -1.3%, P = 0.4). Compared to baseline, however, end-of-treatment MRI-PDFF was significantly lower in the ezetimibe arm (15%-11.6%, P < 0.016) but not in the placebo arm (18.5%-16.4%, P = 0.15). There were no significant differences in histologic response rates, serum alanine aminotransferase and aspartate aminotransferase levels, or longitudinal changes in two-dimensional and three-dimensional magnetic resonance elastography-derived liver stiffness between the ezetimibe and placebo arms. Compared to histologic nonresponders (25/35), histologic responders (10/35) had a significantly greater reduction in MRI-PDFF (-4.35 ± 4.9% versus -0.30 ± 4.1%, P < 0.019). Conclusions: Ezetimibe did not significantly reduce liver fat in NASH. This trial demonstrates the application of colocalization of MRI-PDFF-derived fat maps and magnetic resonance elastography-derived stiffness maps of the liver before and after treatment to noninvasively assess treatment response in NASH.

Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis.Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). UsingL1regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses.Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r=0.698,P<0.001) and quantitative (r=0.757,P<0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold.Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

PURPOSE: To evaluate quantitative functional ultrasonography (US) in a murine gel model by using microbubble destruction kinetics to determine whether parametric indices provided with US could help assess angiogenesis. MATERIALS AND METHODS: Institutional Animal Subjects Committee approved experiments and procedures. In 36 normal mice, two 0.4-mL gel implants were placed subcutaneously on either side of spine. One implant contained 0.5, 1.0, or 1.5 microg human basic fibroblast growth factor (bFGF) per milliliter of gel. Functional US quantitative analysis of angiogenesis with microbubble contrast agent was performed on days 3, 6, 9, and 12; histologic data were collected. Time-intensity curve of implant was fitted to mathematic decay model to calculate fractional blood volume and fraction of blood replaced per unit of time. Microvascular density (MVD) and percentage of microvascular area (MVA) were measured after anti-CD31 staining. Spearman rank order correlation was used in analyses. RESULTS: bFGF-containing implants induced MVD of eight, 35, 42, and 42 vessels per square millimeter on days 3, 6, 9, and 12, respectively; in controls, MVD was four vessels/mm2 (P