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.

Optical single-sideband (OSSB) Raman laser system based on an atomic filter for atom gravimeters.

Phase-modulator-generated laser for Raman transition is widely used in atom gravimeters to simplify a system and improve robustness. However, the induced additional sidebands (ASBs) lead to systematic errors in gravity measurement. This work presents a novel, to our knowledge, method to generate an optical single-sideband (OSSB) laser for Raman transition through phase modulation based on a Faraday anomalous dispersion atomic filter (FADOF). The experimental result indicates that it can reduce the additional sidebands with a signal-to-noise ratio (SNR, the intensity ratio of carrier and unwanted sidebands) of better than 50 dB, and the phase shift caused by ASBs is demonstrated to be effectively suppressed from 358.8 to 2.2 mrad. Furthermore, this system has already been applied on an atom gravimeter to achieve a primary gravity measurement. It shows that the FADOF-based Raman laser system is a new scheme for a compact atom absolute gravimeter.

MR elastography as a biomarker for prediction of early and late recurrence in HBV-related hepatocellular carcinoma patients before hepatectomy.

PURPOSE: To investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy. METHOD: In total, 180 patients (median age, 52 years; interquartile range, 41-50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR. RESULTS: Seventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860. CONCLUSIONS: Quantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.

Active stabilization of terrestrial magnetic field with potassium atomic magnetometer.

This paper introduces a magnetically quiet environment where the magnetic-field noise is actively suppressed using an optically pumped potassium magnetometer. In a large dynamic range of Earth's magnetic fields, the magnetic-resonance signals of potassium are completely separated in frequency, and we experimentally demonstrate that one of them could be used to measure and compensate magnetic-field noise. The magnetic-field noise floor after stabilization is ∼100 fT/Hz under a bias field ranging from 20 to 100 µT. This method could be useful for fundamental-physics experiments and biomedical sciences where a large dynamic range of quiet magnetic fields is needed.

Imaging features of gadoxetic acid-enhanced MR imaging for evaluation of tumor-infiltrating CD8 cells and PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: Tumor-infiltrating CD8 cells and expression of programmed cell death ligand 1 (PD-L1) are immune checkpoint markers in patients with hepatocellular carcinoma (HCC). We aimed to determine the ability of preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings to predict CD8 cell density and PD-L1 expression in HCC. METHODS: A total of 120 patients with HCC who underwent 3.0-T gadoxetic acid-enhanced MRI before curative resection from January 2016 to June 2020 were enrolled and divided into a training set (n = 84) and a testing set (n = 36). Thirty-four patients with advanced stage HCC who received anti-PD-1 inhibitor between January 2017 and April 2020 and underwent pretreated gadoxetic acid-enhanced MRI scans were enrolled in an independent validation set. PD-L1 expression and CD8 cell infiltration were assessed with immunohistochemical staining, respectively. Two radiologists blinded to pathology results evaluated the pretreated MR features in consensus. Logistic regression and the receiver operating characteristic curve (ROC) analyses were used to determine the value of image features to predict high CD8 cell density, PD-L1 positivity and the combination of high CD8 cell density and PD-L1 positivity in HCC in the training set and validated the findings in the testing set. The associations of MRI predictors with the objective response to immunotherapy were assessed in the independent validation. RESULTS: In the training set, the independent MRI predictors were irregular tumor margin (ITM, P = 0.008) and peritumoral low signal intensity (PLSI) on hepatobiliary phase (HBP) images (P < 0.001) for PD-L1 positivity, absence of an enhancing capsule (AEC, P = 0.001) and PLSI on HBP images (P = 0.025) for high CD8 cell density, and PLSI on HBP images (P = 0.001) and ITM (P = 0.023) for the both. The area under the curves (AUCs) of the predictive models for evaluating PD-L1 positivity, high CD8 cell density and the combination of high CD8 cell density and PD-L1 positivity were 0.810 and 0.809, 0.740 and 0.728, and 0.809 and 0.874 in the training and testing set, respectively. The objective response was demonstrated to be associated with the combination of PLSI on HBP images and ITM (PHI, P = 0.004), and the combination of PLSI on HBP images and AEC (PHA, P = 0.012) in the independent validation set. CONCLUSIONS: Pretreated MRI features have the potential to identify patients with HCC in an immune-activated state and predict outcomes of immunotherapy. Trial registration The study was retrospectively registered on March 5, 2020 with registration no. [2020] 02-012-01.

Liver stiffness measurement by magnetic resonance elastography is not affected by hepatic steatosis.

OBJECTIVES: To evaluate the relationship between biopsy-assessed hepatic steatosis, magnetic resonance imaging (MRI)-assessed proton density fat fraction (PDFF), and magnetic resonance elastography (MRE)-assessed liver stiffness measurement (LSM), in patients with or at risk for nonalcoholic fatty liver disease (NAFLD). METHODS: A retrospective study was performed, encompassing 256 patients who had a liver biopsy and MRI/MRE examination performed within 1 year. Clinical and laboratory data were retrieved from the electronic medical record. Hepatic steatosis and fibrosis were assessed by histopathological grading/staging. First, we analyzed the diagnostic performance of PDFF for distinguishing hepatic steatosis with the receiver operating characteristic analyses. Second, variables influencing LSM were screened with univariant analyses, then identified with multivariable linear regression. Finally, the potential relationship between PDFF and LSM was assessed with linear regression after adjustment for other influencing factors, in patients with diagnosed steatosis (PDFF ≥ 5%). RESULTS: The diagnostic accuracy of PDFF in distinguishing steatosis grades (S0-3) was above 0.82. No significant difference in LSM was found between patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. No statistically significant relationship was found between the LSM and PDFF (estimate = - 0.02, p = 0.065) after adjustment for fibrosis stage and age in patients with diagnosed steatosis (PDFF ≥ 5%). CONCLUSIONS: In patients with NAFLD, the severity of hepatic steatosis has no significant influence on the liver stiffness measurement with magnetic resonance elastography. KEY POINTS: • The MRI-based proton density fat fraction provides a quantitative assessment of hepatic steatosis with high accuracy. • No significant effect of hepatic steatosis on MRE-based liver stiffness measurement was found in patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. • After adjusting for fibrosis stage and age, there was no statistically significant relationship between liver stiffness and proton density fat fraction in patients with hepatic steatosis (p = 0.065).

Can modified LI-RADS increase the sensitivity of LI-RADS v2018 for the diagnosis of 10-19 mm hepatocellular carcinoma on gadoxetic acid-enhanced MRI?

PURPOSE: To evaluate whether the Liver Imaging Reporting and Data System (LI-RADS) v2018 LR-5 criteria can be modified to increase sensitivity without reducing specificity for diagnosing 10-19 mm hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: A total of 133 high-risk consecutive patients with 174 small observations (10-19 mm) detected on gadoxetic acid-enhanced MRI were retrospectively studied. LI-RADS MRI major features (MFs) and ancillary features (AFs) were reviewed by two independent radiologists in consensus. Observations were categorized using LI-RADS v2018 MFs. Independently significant AFs were identified through logistic regression analysis. Upgraded LR-5 criteria were developed by combining independently significant AFs with MFs of LR-3 or LR-4 v2018. The sensitivity and specificity of the new diagnostic criteria were compared with those of LR-5 v2018 using McNemar's test. RESULTS: Three of the AFs favoring malignancy [mild-moderate T2 hyperintensity, transitional phase (TP) hypointensity and fat in mass] were independently significant features for diagnosing 10-19 mm HCC. The upgraded LR-5 criteria (mLI-RADS VII: LR-4 + mild-moderate T2 hyperintensity/TP hypointensity or LR-3 + fat in mass) yielded a significantly greater sensitivity than that of the LR-5 v2018 criteria (70.4% vs 55.1%; p < 0.001), whereas the specificity was not significantly different (94.7% vs 98.7%, p = 0.250). CONCLUSIONS: Independently significant AFs may be used to upgrade an observation from LR-3/LR-4 to LR-5, which can improve the sensitivity without impairing the specificity for diagnosing 10-19 mm HCC on gadoxetic acid-enhanced MRI.

Thermal and temporal characteristics of Faraday anomalous dispersion optical filters based on a hollow cathode lamp.

As a new, to the best of our knowledge, alternative to the saturated vapor-cell-based Faraday anomalous dispersion optical filter (FADOF), the FADOF based on a hollow cathode lamp (HCL-FADOF) not only enables the FADOF to work normally at room temperature without heating, but also has some new features due to the inherent characteristics of the HCL. In this Letter, we implement an HCL-FADOF operating on the rubidium D2 line and experimentally investigate the effect of ambient temperature on its performance and cold-start characteristics. Results show that the HCL-FADOF can provide excellent stability within a large temperature range, even at temperatures below 0°C. A comparison of the start performance between the HCL-FADOF and FADOF using saturated vapor cells is also provided. This work shows unique features of the HCL-FADOF in a low-temperature environment and its quick-start advantage, which provides a solid foundation for extensive applications.

Multiparametric magnetic resonance imaging/magnetic resonance elastography assesses progression and regression of steatosis, inflammation, and fibrosis in alcohol-associated liver disease.

BACKGROUND: Magnetic resonance imaging (MRI) and MRI-based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol-associated liver disease (ALD). METHODS: We utilized four different preclinical mouse models in our study: Model 1-mice were fed a fast-food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2-mice were fed chronic-binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin-22 at different time points to induce disease regression; Model 3-mice were administered CCl4 for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4-mice were administered EtOH plus CCl4 for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions. RESULTS: Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three-parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression (r = 0.84, p < 0.0001) and regression (r = 0.79, p < 0.0001) as measured by collagen content in livers. CONCLUSION: This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.

Improving laser power stability with a photosensitive lens.

We propose a method to improve relative laser power stability using a passive photosensitive sunglass lens, which is a commercially available off-the-shelf product. We present a theoretical analysis and identify factors that affect the optimal working state of the lens. A relative laser power stability of 3.3 × 10-5 at 1 s is experimentally achieved, which is more than three times that of 1.2 × 10-4 at 1 s, acquired without power stabilization. This method does not require any active driving device, thereby significantly reducing the complexity and cost of the system, making it suitable for broad applications.

Tumor stiffness measured by 3D magnetic resonance elastography can help predict the aggressiveness of endometrial carcinoma: preliminary findings.

BACKGROUND: Preoperative evaluation of aggressiveness, including tumor histological subtype, grade of differentiation, Federation International of Gynecology and Obstetrics (FIGO) stage, and depth of myometrial invasion, is significant for treatment planning and prognosis in endometrial carcinoma (EC). The purpose of this study was to evaluate whether three-dimensional (3D) magnetic resonance elastography (MRE) can help predict the aggressiveness of EC. METHODS: From August 2015 to January 2019, 82 consecutive patients with suspected uterine tumors underwent pelvic MRI and MRE scans, and 15 patients with confirmed EC after surgical resection were enrolled. According to pathological results (tumor grade, histological subtype, FIGO stage, and myometrial invasiveness), the patients were divided into two subgroups. The independent-samples t-test or Mann-Whitney U test was used to compare the stiffness between different groups. The diagnostic performance was determined with receiver operating characteristic (ROC) curve analysis. RESULTS: The stiffness of EC with ≥ 50 % (n = 6) myometrial invasion was significantly higher than that with < 50 % (n = 9) myometrial invasion (3.68 ± 0.59 kPa vs. 2.61 ± 0.72 kPa, p = 0.009). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 77.8 % specificity for differentiating ≥ 50 % myometrial invasion from < 50 % myometrial invasion of EC. The stiffness of poorly differentiated EC (n = 8) was significantly higher than that of well/moderately differentiated EC (n = 7) (3.47 ± 0.64 kPa vs. 2.55 ± 0.82 kPa, p = 0.028). Using a stiffness of 3.04 kPa as a cutoff value resulted in 75 % sensitivity and 71.4 % specificity for differentiating poorly differentiated from well/moderately differentiated EC. The stiffness of FIGO stage II/III EC was significantly higher than that of FIGO stage I EC (3.69 ± 0.65 kPa vs. 2.72 ± 0.76 kPa, p = 0.030). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 70 % specificity for differentiating FIGO stage I EC from FIGO stage II/III EC. The tumor stiffness value in type II (n = 3) EC was higher than that in type I (n = 12) EC (3.67 ± 0.59 kPa vs. 2.88 ± 0.85 kPa), but the difference was not significant (p = 0.136). CONCLUSIONS: Tumor stiffness measured by 3D MRE may be potentially useful for predicting tumor grade, FIGO stage and myometrial invasion of EC and can aid in the preoperative risk stratification of EC.

Comparison of the diagnostic performance of 2D and 3D MR elastography in staging liver fibrosis.

OBJECTIVES: To compare the diagnostic performance and image quality of state-of-the-art 2D MR elastography (MRE) and 3D MRE in the basic application of liver fibrosis staging. METHODS: This retrospective study assessed data from 293 patients who underwent 2D and 3D MRE examinations. MRE image quality was assessed with a qualitative 2-point grading system by evaluating artifacts. Two experienced analysts independently measured mean liver stiffness values. The interobserver agreement of liver stiffness measurement was assessed by the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of 2D and 3D MRE and blood-based markers for fibrosis staging using the pathology-proven liver fibrosis stage as the gold standard. RESULTS: The image quality provided by 3D MRE was graded as significantly higher than that obtained with the 2D MRE method (p < 0.01). Interobserver agreement in liver stiffness measurements was higher for 3D MRE (ICC: 3D 0.979 vs 2D 0.955). The AUC values for discriminating ≥ F1, ≥ F2, ≥ F3, and F4 fibrosis for 3D MRE (0.89, 0.92, 0.95, and 0.93) were similar to those for 2D MRE (0.89, 0.91, 0.94, and 0.92). Both the 2D and 3D MRE methods provided superior accuracy to the blood-based biomarkers, including APRI, FIB-4, and Forns index, especially for ≥ F2, ≥ F3, and F4 fibrosis stages (all p < 0.01). CONCLUSIONS: While 3D MRE offers certain advantages and opportunities for new applications of MRE, current widely deployed 2D MRE technology has comparable performance in the basic application of detecting and staging liver fibrosis. KEY POINTS: • 2D MRE and 3D MRE have comparable diagnostic performance in detecting and staging liver fibrosis. • 3D MRE has superior image quality and interobserver agreement compared to 2D MRE.

XIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC.

Alcohol-associated liver disease (ALD) has been recognized as the most common cause of advanced liver disease worldwide, though mechanisms of pathogenesis remain incompletely understood. The X-linked inhibitor of apoptosis (XIAP) protein was originally described as an anti-apoptotic protein that directly binds and inhibits caspases-3, 7, and 9. Here, we investigated the function of XIAP in hepatocytes in vitro using gain and loss-of-function approaches. We noted an XIAP-dependent increase in caspase activation as well as increased inflammatory markers and pro-inflammatory EV release from hepatocytes in vitro. Primary hepatocytes (PMH) from Xiap Alb.Cre and Xiap loxP mice exhibited higher cell death but surprisingly, lower expression of inflammation markers. Conditioned media from these isolated Xiap deleted PMH further decrease inflammation in bone marrow-derived macrophages. Also, interestingly, when administered an ethanol plus Fas-agonist-Jo2 model and an ethanol plus CCl4 model, these animals failed to develop an exacerbated disease phenotype in vivo. Of note, neither Xiap Alb . Cre nor Xiap AAV8.Cre mice presented with aggravated liver injury, hepatocyte apoptosis, liver steatosis, or fibrosis. Since therapeutics targeting XIAP are currently in clinical trials and caspase-induced death is very important for development of ALD, we sought to explore the potential basis of this unexpected lack of effect. We utilized scRNA-seq and spatially reconstructed hepatocyte transcriptome data from human liver tissue and observed that XIAP was significantly zonated, along with its endogenous inhibitor second mitochondria-derived activator of caspases (SMAC) in periportal region. This contrasted with pericentral zonation of other IAPs including cIAP1 and Apollon as well as caspases 3, 7, and 9. Thus providing a potential explanation for compensation of the effect of Xiap deletion by other IAPs. In conclusion, our findings implicate a potential zonallydependent role for SMAC that prevented development of a phenotype in XIAP knockout mice in ALD models. Targeting SMAC may also be important in addition to current efforts of targeting XIAP in treatment of ALD.

Liver Imaging and Data System (LI-RADS) Version 2018 and Other Imaging Features in Intrahepatic Cholangiocarcinoma in Chinese Adults with vs. without Chronic Hepatitis B Viral Infection.

Purpose: To describe liver imaging reporting and data system (LI-RADS) version 2018 and other MRI imaging features in intrahepatic mass-forming cholangiocarcinoma (iCCA) in Chinese adults with vs. without chronic hepatitis B viral (HBV) infection. Methods: We retrospectively enrolled 89 patients with pathologically proven iCCA after multiphase imaging performed between 2004 and 2017 at a tertiary medical center in southern China. Based on whether patients had chronic HBV, iCCA was divided into two subgroups: HBV-positive (n = 50 patients, including 9 with cirrhosis) vs. HBV-negative (n = 39 patients, including 14 with hepatolithiasis and 25 with no identifiable risk factor for iCCA; none had cirrhosis). Two independent abdominal radiologists in consensus reviewed the largest mass in each patient to assign LI-RADS v2018 features; they also scored each observation's shape and location. Imaging features were compared using chi-square or Fisher's exact tests. Results: Most iCCAs in HBV-positive (88% (44/50)) and HBV-negative (97% (38/39)) patients had at least one LR-M feature. Compared to iCCAs in HBV-negative patients, iCCAs in HBV-positive patients were more likely to have at least one major feature of HCC (46% (23/50) vs. 8% (3/39), P < 0.001) and more likely to be smooth (42% (21/50) vs. 10% (4/39), P = 0.001). Six of 50 (12%) iCCAs in HBV-positive patients and 1/39 (3%) iCCAs in HBV-negative patients had at least one major feature of HCC without any LR-M feature. Conclusions: In this retrospective single-center study in Chinese adults, iCCAs in HBV-positive patients were more likely to resemble HCCs than iCCAs in HBV-negative patients.

The role of lesion hypointensity on gadobenate dimeglumine-enhanced hepatobiliary phase MRI as an additional major imaging feature for HCC classification using LI-RADS v2018 criteria.

OBJECTIVES: To determine the value of lesion hypointensity in the hepatobiliary phase (HBP) on gadobenate dimeglumine-enhanced MRI as an additional major imaging feature for diagnosis of hepatocellular carcinoma (HCC) using LI-RADS v2018 criteria. METHODS: Between March 2016 and August 2018, 235 patients with 250 hepatic nodules at high risk of HCC underwent gadobenate dimeglumine-enhanced MRI. Two radiologists independently evaluated the imaging features and classified the nodules based on LI-RADS v2018 criteria, and their consensus data were used to calculate the diagnostic performance of LI-RADS categories. Two modified LI-RADS definitions were as follows: (1) LI-RADS-m1: HBP hypointensity as an additional major feature; (2) LI-RADS-m2: HBP hypointensity as an alternative to "enhancing capsule" as an additional major feature. The diagnostic performance of LR-5 categories was compared using McNemar's test. RESULTS: The sensitivity and specificity for LR-5 classification using original LI-RADS v2018 criteria were 78.1% and 96.3%, respectively. Significantly improved sensitivity (82.7%; p = 0.004) with unchanged specificity (96.3%; p = 1.00) was seen for LR-5 classification using LI-RADS-m1. Similar sensitivity and specificity (82.7% and 96.3%, respectively) were also seen using LI-RADS-m2. Significantly improved sensitivity (79.5% vs. 64.0%; p = 0.031) with unchanged specificity (96.2% vs. 96.2%, p = 1.00) was seen using both LI-RADS-m1 and LI-RADS-m2 compared to the original LI-RADS v2018 for 39 HCC nodules measuring 10-19 mm. CONCLUSIONS: Lesion hypointensity on gadobenate dimeglumine-enhanced HBP MRI may improve sensitivity for LR-5 classification beyond that achievable using conventional LI-RADS v2018 criteria. Lesion hypointensity may prove a suitable alternative imaging feature to enhancing capsule for accurate LR-5 classification. KEY POINTS: • Including lesion hypointensity in the HBP as an additional major feature improved sensitivity for LR-5 classification on gadobenate dimeglumine-enhanced MRI. • Lesion hypointensity in the HBP can replace "enhancing capsule" as an additional major feature for LR-5 classification without impairing specificity.

Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer.

PURPOSE: To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS: The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0 T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram. RESULTS: PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60 Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90 Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60 Hz]; 0.975 vs. 0.904, P = 0.060 [90 Hz], respectively). CONCLUSIONS: MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

Accuracies of Chemical Shift In/Opposed Phase and Chemical Shift Encoded Magnetic Resonance Imaging to Detect Intratumoral Fat in Hepatocellular Carcinoma.

BACKGROUND: Magnetic Resonance Imaging (MRI) being a noninvasive modality may help in preoperative evaluation of intratumoral fat in hepatocellular carcinoma (HCC) using chemical shift encoded (CSE) MRI and in-/opposed-phase (IOP) imaging sequences. PURPOSE: To compare the diagnostic accuracy of chemical shift encoded fat fraction at three different flip angles (FAs) using quantitative chemical shift encoded MRI (CSE-MRI) with in-/opposed phase (IOP) imaging to evaluate intratumoral fat in HCC. STUDY TYPE: Retrospective. POPULATION: Eighty-six patients with 87 pathology proven HCCs. FIELD STRENGTH/SEQUENCE: IOP (LAVA-Flex) and CSE-MRI (IDEAL IQ) a three-dimensional spoiled gradient-echo pulse sequences acquired at 3 T. ASSESSMENT: Regions of interest (ROIs) were manually drawn by two observers in the tumors to measure mean fat fractions. Surgical specimens were reassessed for intratumoral fat content. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed for CSE-MRI sequence at FA 3°, 8°, and 9°. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was expressed in terms of inter- and intra-observer agreements. Receiver operating characteristic curve analysis was performed for the diagnostic performance followed by combined metric of both. SNR/CNR were analyzed by Kruskal-Wallis test. RESULTS: Excellent inter- and intra-observer agreements (ICC >0.95, P < 0.001) were observed for both IOP and CSE-MRI. IOP (86.4%) showed higher sensitivity than CSE-MRI at FA 3° (72.5%), FA 8° (76.4%) and FA 9° (76.3%). In contrast, the specificity for CSE-MRI at FA 3° (86%), FA 8° (87%), and FA 9° (87%) were greater than IOP (72%). A combined metric of IOP and CSE-MRI derived fat fractions at FA 8° gave highest AUC of 87% and accuracy of 86%. SNR and CNR for CSE-MRI were significantly higher at FA 8° and FA 9° than FA 3° (P < 0.05). DATA CONCLUSION: IOP and quantitative CSE-MRI are both feasible methods to detect intratumoral fat in HCC with higher accuracy and SNR for CSE-MRI at FA 8° and 9°. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Increasing the sensitivity of LI-RADS v2018 for diagnosis of small (10-19 mm) HCC on extracellular contrast-enhanced MRI.

PURPOSE: To evaluate whether the LI-RADS v2018 LR-5 criteria can be modified to increase sensitivity without reducing specificity for diagnosing small (10-19 mm) HCC. METHODS: 167 consecutive high-risk patients with 174 small observations reported clinically on extracellular contrast-enhanced MRI from 2014 to 2018 were retrospectively studied. The best available reference standard was applied for each observation. Blinded to the reference standard, two radiologists scored LI-RADS imaging features retrospectively and assigned each observation a LI-RADS category using LI-RADS v2018 and each of four modified LI-RADS versions (mLI-RADS I to IV) with successively more expansive LR-5 criteria. Per-observation sensitivity and specificity of LR-5 for small HCC using each version were assessed. Each modified version was compared to v2018 (McNemar test). RESULTS: The 174 observations included 135 HCC, 8 non-HCC malignancies, and 31 benign entities. Using LI-RADS v2018, LR-5 provided 70% (both readers) sensitivity and 95% (both readers) specificity for small HCC. Expanding the LR-5 criteria to include nonrim APHE plus at least one additional major feature (mLI-RADS I) or no APHE plus at least two additional major features (mLI-RADS II) significantly increased sensitivity (reader 1/reader 2: 75%/75% vs. 70%, p = 0.016/0.031; 78%/79% vs. 70%, p = 0.001/0.001) without significantly reducing specificity (reader 1/reader 2: 90%/92% vs. 95%, p = 0.500/1.000 for both). mLI-RADS III and IV further increased sensitivity (reader 1/reader 2: 80%/81% vs. 70%, p < 0.001/< 0.001; 94%/92% vs. 70, p < 0.001/< 0.001) but with trend-level (reader 1/reader 2: 85%/80% vs. 95%, p = 0.125/0.063) or significant (reader 1/reader 2: 64%/62% vs. 95%, p < 0.001/< 0.001) specificity reductions. CONCLUSIONS: Expanding the v2018 LR-5 criteria to include nonrim APHE plus at least one additional major feature or no APHE plus at least two additional major features significantly increases sensitivity without significantly reducing specificity for small HCC. Confirmation is warranted in multi-center prospective studies.

Quantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models.

OBJECTIVES: To determine the potential of bi-parametric dual-frequency hepatic MR elastography (MRE) for predicting portal pressure (PP) in mouse models of portal hypertension (PHTN) with the presence of varying hepatic fibrosis. METHODS: We studied 73 wild-type male mice, including 22 mice with hepatic congestion, 20 mice with cholestatic liver injury, and 31 age-matched sham mice. Hepatic shear stiffness (SS) and volumetric strain (VS) were calculated by 3D MRE acquired at 80 and 200 Hz. We measured PP immediately after MRE. Liver fibrosis was verified by hydroxyproline assay. We predicted PP by fitting generalized linear models with single- and dual-frequency SS and VS, respectively. The relationship between predicted and actual PP was evaluated by Spearman's correlation. We compared the prediction accuracy of portal hypertension for all models with DeLong tests at a significance level of 0.05. RESULTS: Animals with congestive or cholestatic liver disease developed significant PHTN and hepatic fibrosis to varying degrees. In both models, SS increased, while VS decreased significantly compared with shams. All bi-parametric models had high diagnostic accuracy for PHTN. The dual-frequency models (AUCs: 0.90 [81-95%], 0.91 [81-95%]) had substantially or significantly higher accuracy than single-frequency ones (AUCs: 0.83 [71-91%], and 0.78 [66-87%]). The predicted PP of dual-frequency models also showed stronger correlations with actual PP than single-frequency predictions. CONCLUSIONS: The bi-parametric dual-frequency model improved the diagnostic accuracy of liver MRE in diagnosing PHTN in preclinical models. This technical advance has the potential to monitor PHTN progression and treatment efficacy in the presence of varying fibrosis. KEY POINTS: • Bi-parametric hepatic MR elastography can predict portal pressure. • The prediction models of shear stiffness and volumetric strain with dual-frequency measurements demonstrate high diagnostic accuracy (AUCs > 0.9) in two different portal hypertension mouse models with varying fibrosis.