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We previously demonstrated that the ribonuclease Regnase-1 (Reg1) in keratinocytes plays a role in mitigating skin inflammation by down-regulating pro-inflammatory cytokines. Here, we explored whether Reg1 also has a protective role against skin carcinogenesis. The chemically-induced two-stage carcinogenesis protocol revealed that epidermis-specific Reg1-deficient (Reg1-cKO) mice developed skin tumors with a shorter latency and more multiplicity than control mice. Also, repeated ultraviolet B irradiation readily provoked solar keratosis-like lesions in Reg1-cKO mice. Increased levels of COX-2, whose mRNA (Ptgs2) is reportedly a target of Reg1, have been known to be associated with the development of squamous cell carcinomas (SCCs). Indeed, Ptgs2 mRNA levels were upregulated in the skin of Reg1-cKO mice after treatment with the tumor promoter, TPA. The level of prostaglandin E2 was higher in TPA-treated Reg1-cKO mouse skin than in control mice. Moreover, in vivo inhibition of COX-2 attenuated the TPA-induced epidermal thickening in Reg1-cKO mice. Finally, REG1 knock-down in human SCC lines enhanced PTGS2 mRNA levels after TPA treatment. In conclusion, epidermal Reg1 plays a regulatory role not only in skin inflammation but also in tumor promotion through the down-regulation of COX-2. Therefore, forced expression of Reg1 under inflammatory conditions may be relevant to preventing skin cancer.

Background The effectiveness of four-dimensional (4D) flow magnetic resonance imaging (MRI) for assessing hemodynamic changes before and after balloon-occluded retrograde transvenous obliteration (BRTO) remains unclear. Purpose To evaluate the feasibility of 4D flow MRI for assessing hemodynamic changes in the portal venous system before and after BRTO. Material and Methods We included 10 patients (7 men, 3 women; mean age = 67 years) with liver cirrhosis who had a high risk of gastric variceal bleeding or hepatic encephalopathy. Non-contrast 4D flow MRI of the upper abdomen was performed before and after BRTO. In addition, we compared the blood flow rates in the portal vein (PV), superior mesenteric vein (SMV), splenic vein (SV), left renal vein, and inferior vena cava before and after BRTO. Moreover, the flow directions of the SMV and SV before and after BRTO were assessed using both portography and 4D flow MRI. Results There was a significant post-BRTO increase in the blood flow rate in the PV and SV ( P < 0.05). There was no significant post-BRTO change in the blood flow rates in the SMV, inferior vena cava, and left renal vein. In four patients, portography confirmed that hepatofugal flow in the SV and SMV changed to hepatopetal flow after BRTO. Moreover, 4D flow MRI correctly assessed the flow directions in the SMV and SV in 70%–100% of the patients. Conclusion 4D flow MRI can be used to detect hemodynamic changes in the portal venous system before and after BRTO.

Schwannomas in and around the porta hepatis (porta hepatic schwannomas) are rare benign tumors easily misdiagnosed as other pathologies, including malignancies. We aimed to evaluate their imaging features on ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), andWe performed a multi-institutional retrospective study by reviewing the clinical and imaging findings of pathologically proven eight porta hepatic schwannomas (mean age, 55 years; range, 38-80 years; one male and seven females). Preoperative imaging included three ultrasonography, eight CT, eight MRI, and two FDG-PET/CT.All patients were asymptomatic. The mean tumor size was 61.9 mm (range, 30-180 mm), and all tumors demonstrated well-defined lesions on ultrasonography and their solid components showed soft tissue attenuation on non-contrast CT. MRI showed two distinct components in all cases: the component with T1-weighted hypointensities and T2-weighted hyperintensities with poor enhancement (suggestive of Antoni B histology); the component with T2-weighted hypointensities with gradually increasing enhancement (suggestive of Antoni A histology), resulting in a heterogeneous pattern on post-contrast CT or MRI (8/8, 100%). The separated deviation of surrounding bile ducts and vessels without obstruction allowed the recognition of extrahepatic localization and their benign nature. A ginger root-like morphology (2/8, 25%) seemed to be suggestive of extension along the Glisson's sheath, although this finding was not seen frequently.Recognizing imaging features such as extrahepatic location, benign nature with internal structures suggestive of Antoni A/B histology, and characteristic tumor extension may provide key diagnostic clues for porta hepatic schwannomas.

Purpose: This study aims to identify the hallmarks of gadoxetate disodium-enhanced magnetic resonance imaging distinguishing hepatocellular carcinoma (HCC) from hypervascular liver metastases (HLMs). Methods: Between January 2008 and October 2020, among patients who underwent gadoxetate disodium-enhanced MRI, those who met the following criteria were retrospectively included: without chronic hepatitis or liver stiffness ≤ 2.5 kPa on magnetic resonance elastography or F0/F1 on pathological assessment. Two blinded radiologists reviewed the imaging findings to judge the presence or absence of the enhancing capsule, nonperipheral washout, corona enhancement, hypointensity in the transitional/hepatobiliary phase (HBP), hyperintensity on T2-weighted/diffusion-weighted imaging (DWI), mosaic architecture, and blood products/fat in mass. The lesion-to-liver signal intensity ratios in HBP and DWI were also calculated. Univariate and multivariate analyses were performed to identify the imaging hallmarks distinguishing HCC from HLM. Interobserver agreement was calculated using kappa values and intraclass correlation coefficients (ICCs). Results: The final study cohort comprised 72 lesions in 44 patients (mean age, 65.0±11.9 years). Univariate analysis revealed higher frequencies of the following features in HCC than in HLM (P < .10): nonperipheral washout, corona enhancement, transitional phase hypointensity, mosaic architecture, and fat in mass (P = .002-.073). Multivariate analysis revealed that nonperipheral washout and mosaic architecture favored the diagnosis of HCC over that of HLM with odds ratios of 7.66 and 14.6, respectively (P = .038 and .029, respectively). The interobserver agreement for each item was moderate or substantial (kappa or ICC = .447-.792). Conclusion: Peripheral washout and mosaic architecture may be reliable imaging hallmarks for distinguishing HCC from HLM.

Background Effect of decreased injection flow rate of contrast agent at the same iodine dose and delivery rate on aortic enhancement has not been clearly elucidated. Purpose To evaluate the effect of decreased injection flow rate of contrast agent on aortic peak enhancement in a dynamic flow phantom and on aortic enhancement in clinical dynamic 80-kVp computed tomography (CT) with contrast dose reduction. Material and Methods In the dynamic flow phantom experiment, the effect of a decreased injection flow rate at the same total iodine dose and delivery rate on simulated aortic peak enhancement was evaluated. In the clinical retrospective study, we searched 312 patients with renal dysfunction who underwent an 80-kVp abdominal dynamic CT with 40% reduction of contrast agent from a standard 120-kVp protocol and measured the aortic enhancement at the level of the hepatic hilum. Independent predictors for aortic enhancement were determined by multiple linear regression analysis, and after adjustment of significant predictors, independent variables for acquiring optimal aortic enhancement, ≥300 HU, were determined by multiple logistic regression analysis. Results In the phantom experiment, decreased flow rate showed a significant but small descent effect (6%–9%) on simulated aortic peak enhancement. In the multiple linear regression analysis, only age was an independent predictor of aortic enhancement; there was no independent predictor for optimal age-adjusted aortic enhancement of ≥300 HU. Conclusions Decreased injection flow rate had a small influence on aortic enhancement in vitro but had no significant effect on the aortic enhancement in clinical dynamic 80-kVp CT.

Purpose In contrast-enhanced abdominopelvic CT (CE-APCT) for oncologic follow-up, ultrahigh-resolution CT (UHRCT) may improve depiction of fine lesions and low-dose scans are desirable for minimizing the potential adverse effects by ionizing radiation. We compared image quality and radiologists’ acceptance of model-based iterative (MBIR) and deep learning (DLR) reconstructions of low-dose CE-APCT by UHRCT. Methods Using our high-resolution (matrix size: 1024) and low-dose (tube voltage 100 kV; noise index: 20–40 HU) protocol, we scanned phantoms to compare the modulation transfer function and noise power spectrum between MBIR and DLR and assessed findings in 36 consecutive patients who underwent CE-APCT (noise index: 35 HU; mean CTDIvol: 4.2 ± 1.6 mGy) by UHRCT. We used paired t-test to compare objective noise and contrast-to-noise ratio (CNR) and Wilcoxon signed-rank test to compare radiologists’ subjective acceptance regarding noise, image texture and appearance, and diagnostic confidence between MBIR and DLR using our routine protocol (matrix size: 512; tube voltage: 120 kV; noise index: 15 HU) for reference. Results Phantom studies demonstrated higher spatial resolution and lower low-frequency noise by DLR than MBIR at equal doses. Clinical studies indicated significantly worse objective noise, CNR, and subjective noise by DLR than MBIR, but other subjective characteristics were better (P Conclusion Image quality, except regarding noise characteristics, and acceptance by radiologists were better by DLR than MBIR in low-dose CE-APCT by UHRCT. Graphical abstract

To evaluate the feasibility of folded image training strategy (FITS) and the quality of images reconstructed using the improved model-based deep learning (iMoDL) network trained with FITS (FITS-iMoDL) for abdominal MR imaging.This retrospective study included abdominal 3D T1-weighted images of 122 patients. In the experimental analyses, peak SNR (PSNR) and structure similarity index (SSIM) of images reconstructed with FITS-iMoDL were compared with those with the following reconstruction methods: conventional model-based deep learning (conv-MoDL), MoDL trained with FITS (FITS-MoDL), total variation regularized compressed sensing (CS), and parallel imaging (CG-SENSE). In the clinical analysis, SNR and image contrast were measured on the reference, FITS-iMoDL, and CS images. Three radiologists evaluated the image quality using a 5-point scale to determine the mean opinion score (MOS).The PSNR of FITS-iMoDL was significantly higher than that of FITS-MoDL, conv-MoDL, CS, and CG-SENSE (P 0.001). The SSIM of FITS-iMoDL was significantly higher than those of the others (P 0.001), except for FITS-MoDL (P = 0.056). In the clinical analysis, the SNR of FITS-iMoDL was significantly higher than that of the reference and CS (P 0.0001). Image contrast was equivalent within an equivalence margin of 10% among these three image sets (P 0.0001). MOS was significantly improved in FITS-iMoDL (P 0.001) compared with CS images in terms of liver edge and vessels conspicuity, lesion depiction, artifacts, blurring, and overall image quality.The proposed method, FITS-iMoDL, allowed a deeper MoDL reconstruction network without increasing memory consumption and improved image quality on abdominal 3D T1-weighted imaging compared with CS images.

Purpose To determine the optimal combination of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) findings for the diagnosis of hepatocellular carcinoma (HCC) and to compare its diagnostic ability to that of dynamic computed tomography (CT) in patients with chronic liver disease. Methods This multi-institutional study consisted of two parts: Study 1, a retrospective study to determine the optimal combination of gadoxetate disodium-enhanced MRI findings (decision tree and logistic model) to distinguish HCC (n = 199) from benign (n = 81) or other malignant lesions (n = 95) (375 nodules in 269 patients) and Study 2, a prospective study to compare the diagnostic ability of gadoxetate disodium-enhanced MRI to distinguish HCC (n = 73) from benign (n = 15) or other malignant lesions (n = 12) with that of dynamic CT (100 nodules in 83 patients). Two radiologists independently evaluated the imaging findings (Study 1 and 2) and made a practical diagnosis (Study 2). Results In Study 1, rim or whole enhancement on arterial phase images, signal intensities on T2-weighted/diffusion-weighted/portal venous/transitional/hepatobiliary phase images, and signal drop on opposed-phase images were independently useful for differential diagnosis. In Study 2, the accuracy, sensitivity, negative predictive value, and negative likelihood ratio of the CT decision tree (reader 2) were higher than those of MRI Model 2 (P = 0.015-0.033). There were no other significant differences in diagnostic ability (P = 0.059-1.000) and radiologist-made practical diagnosis (P = 0.059-1.000) between gadoxetate disodium-enhanced MRI and CT. Conclusion We identified the optimal combination of gadoxetate disodium-enhanced MRI findings for HCC diagnosis. However, its diagnostic ability was not superior to that of dynamic CT.

OBJECTIVE To evaluate the effect of ultra high-resolution computed tomography (UHRCT) and model-based iterative reconstruction (MBIR) on the detectability of simulated submillimeter artery. METHODS A small vessel phantom ranging from 0.4 to 2.0 mm in diameter and edge phantoms of low to high attenuation values were scanned by UHRCT (super-high-resolution mode and normal-resolution-mode) and conventional CT, and data were reconstructed by MBIR and filtered back projection (FBP). Vessel detectability was assessed subjectively and the effective size at which 50% of response was achieved (ES50 [mm]) was calculated. Modulation transfer function (MTF) was calculated by an edge spread function method. RESULTS ES50 of super high-resolution mode (0.36 mm for MBIR and 0.50 mm for FBP) was significantly smaller than those of normal-resolution mode (P < 0.01). In the MTF analysis, the MTF of MBIR improved as the edge phantom attenuation increased, whereas that of FBP was stable. CONCLUSIONS Both UHRCT and MBIR are effective for the detectability of simulated submillimeter artery.

To compare the quality of dynamic imaging between stack-of-stars acquisition without breath-holding (DISCO-Star) and the breath-holding method (Cartesian LAVA and DISCO).This retrospective study was conducted between October 2019 and February 2020. Two radiologists performed visual assessments of respiratory motion or pulsation artifacts, streak artifacts, liver edge sharpness, and overall image quality using a 5-point scale for two datasets: Dataset 1 (n = 107), patients with Cartesian LAVA and DISCO-Star; Dataset 2 (n = 41), patients with DISCO and DISCO-Star at different time points. Diagnosable image quality was defined as ≥ 3 points in overall image quality. Whether the scan timing of the arterial phase (AP) was appropriate was evaluated, and results between the pulse sequences were compared. In cases of inappropriate scan timing in the DISCO-Star group, retrospective reconstruction with a high frame rate (80 phases, 3 s/phase) was added.The overall image quality of Cartesian LAVA was better than that of DISCO-Star in AP. However, noninferiority was shown in the ratio of diagnosable images between Cartesian LAVA and DISCO-Star in AP. There was no significant difference in the ratio of appropriate scan timing between DISCO-Star and Cartesian LAVA; however, the ratio of appropriate scan timing in DISCO-Star with high frame rate reconstruction was significantly higher than that in Cartesian LAVA in both readers. Overall image quality scores between DISCO and DISCO-Star were not significantly different in AP. There was no significant difference in the ratio of appropriate scan timing between DISCO-Star with high frame rate reconstruction and DISCO in both readers.The use of DISCO-Star with high frame rate reconstruction is a good solution to obtain appropriate AP scan timing compared with Cartesian LAVA. DISCO-Star showed equivalent image quality in all phases and in the ratio of appropriate AP scan timing compared with DISCO.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used as a first-line procedure for the definitive diagnosis of pancreatic solid tumor. Adverse events associated with the EUS-FNA procedure include acute pancreatitis, bleeding, infection, and duodenal perforation. Rarely, pancreatic tumors disseminate in the peritoneal cavity or seed in the gastric wall via the biopsy needle tract after EUS-FNA. Such seeding has been noted primarily in cases of adenocarcinomas and has not been associated with solid pseudopapillary neoplasm (SPN), a rare and potentially malignant tumor of the pancreas. This is the first report of a case of tumor seeding in the gastric wall after EUS-FNA of pancreatic SPN.

The inferior mesenteric artery arising from the superior mesenteric artery is an extremely rare anatomic variation. We report a case with this variation demonstrated with 3-dimensional contrast-enhanced computed tomography, which later was confirmed at surgery. The ordinary inferior mesenteric artery arising from the aorta was absent. Previously reported cases with this variation are reviewed. 3-dimensional contrast-enhanced computed tomography is useful for in vivo visualization of aberrant arterial anatomy. Keywords: Anatomy, Inferior mesenteric artery, Superior mesenteric artery, Variation, 3D-CT

The amount of an iodinated contrast agent can be effectively reduced by using a lower-tube voltage peak in clinical CT imaging while maintaining image quality by state-of-the-art iterative reconstruction techniques. The use of a lower-tube voltage peak in clinical CT imaging has advantages and disadvantages we need to know.

Aims To evaluate the association between contrast patterns on gadoxetic acid-enhanced hepatobiliary phase (HBP) MR images and transporter expression in surgically resected hypovascular hepatocellular nodules including early hepatocellular carcinomas (HCCs). Methods Forty-two hypovascular hepatic nodules and 43 hypervascular HCCs as a control were included in this retrospective study. Contrast of the nodules on HBP images was graded as hypo-, iso-, or hyperintense. Histopathological assessment was performed in the context of multistep hepatocarcinogenesis. Immunohistochemical staining of organic anion transporter 1B3 (OATP1B3) and multidrug resistance protein 2 (MRP2) was performed. Cramer’s coefficient was used to determine the linear relationship between contrast grades and transporter expression, and the Cochran-Armitage trend test was used to determine the relationship between transporter expression and progression of multistep hepatocarcinogenesis. Results Moderate linear relationships between contrast grades and OATP1B3 expression were observed for both hypo- and hypervascular nodules. OATP1B3 expression was negatively correlated with the progression of multistep hepatocarcinogenesis. MRP2 expression was not associated with the contrast grades or histopathological results. Conclusion OATP1B3 expression was associated with contrast grades of hepatocellular nodules observed in HBP image of gadoxetic acid-enhanced MRI in the hypovascular hepatocellular nodules and was negatively correlated with hepatocarcinogenesis.

Purpose To compare the abilities of three intravoxel incoherent motion (IVIM) imaging approximation methods to discriminate the histological grade of hepatocellular carcinomas (HCCs). Methods Fifty-eight patients (60 HCCs) underwent IVIM imaging with 11 b-values (0-1000 s/mm2). Slow (D) and fast diffusion coefficients (D*) and the perfusion fraction (f) were calculated for the HCCs using the mean signal intensities in regions of interest drawn by two radiologists. Three approximation methods were used. First, all three parameters were obtained simultaneously using non-linear fitting (method A). Second, D was obtained using linear fitting (b = 500 and 1000), followed by non-linear fitting for D* and f (method B). Third, D was obtained by linear fitting, f was obtained using the regression line intersection and signals at b = 0, and non-linear fitting was used for D* (method C). A receiver operating characteristic analysis was performed to reveal the abilities of these methods to distinguish poorly-differentiated from well-to-moderately-differentiated HCCs. Inter-reader agreements were assessed using intraclass correlation coefficients (ICCs). Results The measurements of D, D*, and f in methods B and C (Az-value, 0.658-0.881) had better discrimination abilities than did those in method A (Az-value, 0.527-0.607). The ICCs of D and f were good to excellent (0.639-0.835) with all methods. The ICCs of D* were moderate with methods B (0.580) and C (0.463) and good with method A (0.705). Conclusion The IVIM parameters may vary depending on the fitting methods, and therefore, further technical refinement may be needed.

Background Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. Purpose To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. Study Type A retrospective study at a single institution. Population In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0–F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. Field Strength/Sequence 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. Assessment Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. Statistical Tests The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. Results Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90–91% [108–9/120]), ≥F3 (79–81% [95–97/120]), and F4 (82–85% [98–102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). Data Conclusion MRE can be an alternative to liver biopsy for fibrosis staging. Level of Evidence: 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

Purpose To compare the occurrence of transient respiratory motion (TM) artifacts between 0.05 mmol/kg and 0.025 mmol/kg gadoxetic-acid on arterial phase MRI intra-individually for evaluating dose-dependence of gadoxetic acid. Materials and Methods This retrospective study involved 91 patients who underwent dynamic MRI at 1.5T at different times, one time with 0.05 mmol/kg and the other 0.025 mmol/kg gadoxetic-acid. Examinations with 0.05 mmol/kg totaled 91 scans, and examinations with 0.025 mmol/kg totaled 375 scans (due to multiple exams for several patients). The scan with 0.025 mmol/kg closest in time to the 0.05 mmol/kg scan was selected to minimize temporal effects. Two radiologists graded TM artifacts in the arterial phase images using a four-point scale: no, mild, moderate, and severe artifacts. Results were compared between the two protocols (0.05 mmol/kg versus all 0.025 mmol/kg and 0.05 mmol/kg versus selected 0.025 mmol/kg), and the odds ratio for moderate-to-severe artifacts was calculated. Results Significantly more TM artifacts were observed in the double dose (16/91 [17%]) scans compared with either all (17/375 [4%]; P

Although single-component Class 2 CRISPR systems, such as type II Cas9 or type V Cas12a (Cpf1), are widely used for genome editing in eukaryotic cells, the application of multi-component Class 1 CRISPR has been less developed. Here we demonstrate that type I-E CRISPR mediates distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5′-ARG protospacer adjacent motif (PAM), without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation can be used to introduce functional gene knockouts and knock-ins. As an example of potential therapeutic applications, we show Cas3-mediated exon-skipping of the Duchenne muscular dystrophy (DMD) gene in patient-induced pluripotent stem cells (iPSCs). These findings broaden our understanding of the Class 1 CRISPR system, which may serve as a unique genome editing tool in eukaryotic cells distinct from the Class 2 CRISPR system., Class 1 CRISPR systems are not as developed for genome editing as Class 2 systems are. Here the authors show that Cas3 can be used to generate functional knockouts and knock-ins, as well as Cas3-mediated exon-skipping in DMD cells.

To compare the estimated quantity of intratumor gadoxetic acid retention using T1 mapping of gadoxetic acid-enhanced magnetic resonance imaging (MRI) versus conventional processing methods for the differential diagnosis of focal liver lesions.Seventy patients with hepatic lesions (colorectal metastasis (CRM) [n = 28], hepatocellular carcinoma (HCC) [n = 20], hemangioma [n = 12], and intrahepatic cholangiocarcinoma (ICC) [n = 10]) underwent gadoxetic acid-enhanced MRI, including pre- and post-contrast T1-weighted imaging and T1 mapping. Quantitative analyses included the lesion-to-liver signal intensity ratio (SIR) on hepatobiliary phase images, the pre- and post-contrast lesion T1 value difference (ΔT1 [ms]), and the lesion retention index (LRI [%]), which was the estimated intralesional gadoxetic acid retention calculated on pre- and post-contrast T1 maps using a two-compartment pharmacokinetic model. Results were compared between the four subcategories of focal liver lesions using the Kruskal-Wallis test, followed by the post-hoc Dunn's test and receiver operating characteristic (ROC) analysis to distinguish between pairs of the four lesion subcategories.This study identified significant differences in the LRI of the four lesion subcategories (p 0.01), without significant differences in ΔT1 or SIR. Post-hoc analysis demonstrated significant differences in CRM vs. hemangioma (p 0.01), hemangioma vs. ICC (p 0.01), and HCC vs. ICC (p = 0.047) for the LRI.The quantity of intratumor gadoxetic acid retention estimated using pre- and post- contrast T1 mapping could distinguish focal liver lesions, unlike conventional processing methods, and captured unique lesion characteristics.

Purpose To evaluate the effect of imaging sequence (spin-echo echo-planar imaging [EPI] and gradient-echo [GRE]) and postprocessing method (two-dimensional [2D] and 3D inversion algorithms) on liver MR elastography (MRE) and to validate the diagnostic performance of EPI-MRE3D versus conventional GRE-MRE2D for liver fibrosis staging. Materials and Methods Three MRE methods (EPI-MRE3D, EPI-MRE2D, and GRE-MRE2D) were performed on soft and mildly stiff phantoms and 58 patients with chronic liver disease using a 3 Tesla clinical MRI scanner, and stiffness values were compared among the three methods. A validation study comprised 73 patients with histological liver fibrosis (F0–4, METAVIR system). Areas under the receiver operating characteristic curves (AUCs) and accuracies for diagnosing significant fibrosis (F3–4) and cirrhosis (F4) were compared between EPI-MRE3D and GRE-MRE2D. Results Stiffness values of the soft and mildly stiff phantoms were 2.4 kPa and 4.0 kPa by EPI-MRE3D; 2.6 kPa and 4.2 kPa by EPI-MRE2D; and 2.7 kPa and 4.2 kPa by GRE-MRE2D. In patients, EPI-MRE3D provided significantly lower stiffness values than other methods (P

To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule’s initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p

Purpose To evaluate the usefulness of magnetic resonance elastography (MRE) in detecting the clinical progression of cirrhosis from Child-Pugh class A to B in patients with hepatitis C. Materials and Methods We reviewed the data of 101 consecutive patients with type C viral hepatitis and clinically suspected cirrhosis who fulfilled the all following criteria: available MRE at 1.5 Tesla (T) or 3.0T and laboratory tests within a month, Child-Pugh class A, platelet count less than 155 × 103/μL, no clinical history of hepatocellular carcinoma, and ≥6 months of follow-up after MRE. We longitudinally analyzed the incidence of cirrhosis progression as defined by the clinical progression from Child-Pugh class A to B at two subsequent follow-up points. Risk of cirrhosis progression was assessed by Cox analyses and Kaplan-Meyer methods. Results Cirrhosis progression was noted in 25 patients during the follow-up period. Liver stiffness (hazard ratio [HR] by 1 kPa increase = 1.397; P = 0.0074), Child-Pugh score of 6 versus score 5 (HR of 3.085; P = 0.0276), and treatment responses to anti-viral therapy versus nonresponse (HR of

Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). The aim of this study was to investigate the morphophenotypical changes of this sequence and their potential translational significance.We scored the vascular profile, ductular reaction/stromal invasion and overexpression of five biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC).The score separated the four groups of nodules as individual entities (p0.01). In the sequence, biomarker's overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p0.05). For diagnosis, the application of four and five biomarkers (rather than the usual three) improved the sensitivity of the assay for the detection of eHCC (76% and 93% vs. 52%); biomarkers in alternative combinations, and also increased the sensitivity of the assay (GS+CHC+EZH2: 76%; GS+CHC+EZH2+HSP70: 90%).This study supports the multistep nature of human hepatocarcinogenesis, and suggests that eHCC is more heterogeneous than previously thought. This provides further information of the potential translational significance into clinical practice.

PURPOSE We investigated the added value of the hypointensity on hepatocyte-phase (HP) imaging of gadoxetic acid-enhanced MRI (EOB-MRI) in the 2014 version of the Liver Imaging Reporting and Data System (LI-RADS) for distinguishing hepatocellular carcinoma (HCC) from benign hepatic lesions in patients with chronic liver disease. METHODS We retrospectively evaluated targeted lesions (111 HCCs, 28 benign hepatic lesions) of 139 patients (101 men, 38 women; aged 18 to 89 years, mean age, 68 ± 11 years) with chronic liver disease. EOB-MRI and dynamic contrast-enhanced computed tomography (CECT) were performed within 3 months. Two abdominal radiologists independently reviewed 3 imaging datasets: (1) EOB-MRI without an HP image using the LI-RADS system (MR imaging without HP); (2) EOB-MRI with an HP image using a modified version of the LI-RADS system in which hypointensity on the HP image was used as an additional major criterion of malignancy (MR imaging with HP); and (3) dynamic contrast-enhanced computed tomography (CECT) images using the LI-RADS system. We evaluated intra- and inter-reader agreement with kappa statistics along with 95% confidence intervals and compared diagnostic sensitivity and specificity of the 3 imaging datasets with McNemar's test. RESULTS The sensitivities of MR imaging were statistically higher with HP (Reader 1, 95% [107/111]; Reader 2, 95% [106/111]) than without HP (Reader 1, 84% [93/111], P = 0.002; Reader 2, 86% [96/111], P = 0.002). Specificity was comparably high between MR imaging with HP (Reader 1, 96% [27/28]; Reader 2, 96% [27/28]) and dynamic CECT (Reader 1, 100% [28/28], P = 0.317; Reader 2, 100% [28/28], P = 0.317) and MR imaging without HP (Reader 1, 96% [27/28], P = 1.00; Reader 2, 100% [28/28], P = 0.317). CONCLUSION The use of an HP image from EOB-MRI as an additional major criterion improved the sensitivity of LI-RADS to distinguish HCCs from benign hepatic lesions while retaining high specificity.

PURPOSE We evaluated the validity and reliability of magnetic resonance elastography (MRE) for staging hepatic fibrosis in patients with chronic hepatitis B. METHODS The study included 73 patients with chronic hepatitis B and confirmed stages of pathological fibrosis. Two radiologists measured liver stiffness using MRE in all cases. We compared the area under the receiver operating characteristic (ROC) curve (Az) for distinguishing stages of fibrosis compared with MRE liver stiffness measurements and serum fibrosis markers. We used intraclass correlation coefficients to analyze interobserver agreement for measurements of liver stiffness and 2 one-sided t-tests to test the equivalence of the measurements by the 2 observers. RESULTS ROC analyses revealed the significantly superior discrimination abilities of MRE for liver fibrosis staging (Az = 0.945 to 0.978 [Observer 1] and 0.936 to 0.967 [Observer 2]) to those of serum fibrosis markers (0.491 to 0.742) for both observers (P < 0.0004). The intraclass correlation coefficient between the 2 observers was excellent (ρ = 0.971), and the measurements of liver stiffness by the 2 observers were statistically equivalent within a 0.1-kPa difference (P = 0.0157)CONCLUSION: MRE is a valid and reliable technique for discriminating the stage of hepatic fibrosis in patients with chronic hepatitis B.

Background: During the follow-up of patients with chronic liver disease, hypervascular hepatocellular carcinomas (HCCs) can develop either from pre-existing high-risk nodules or by de novo hepatocarcinogenesis. The purpose of this study was to evaluate, by retrospective analysis, the detectability and signal intensity on previous hepatocyte-phase gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) of hypervascular HCC initially detected on current EOB-MRIs. Methods: We examined 50 initially detected hypervascular HCCs that showed typical enhancement features on EOB-MRI in 39 patients whose previous EOB-MRI images obtained 6-19 months earlier were available. The detectability of each hypervascular HCC on the hepatocyte phase images of previous EOB-MRIs was assessed. The imaging features on hepatocyte-phase images of previous EOB-MRIs at the locations where hypervascular HCCs were found on the current EOB-MRI images were classified as detectable or undetectable. The signal intensities of detectable nodules (defined as group A) on hepatocyte-phase images of previous EOB-MRIs were classified as hypo-, iso-, or hyperintensity. Nodules undetectable on the hepatocyte-phase images of previous EOB-MRIs were assigned to group B. Results: Twenty-two (22/50, 44%) hypervascular HCCs were detectable on the earlier hepatocyte phase images (group A). In contrast, 28 (28/50, 56%) hypervascular HCCs were not detectable on the hepatocyte phase of earlier EOB-MRI images (group B). Conclusion: When the previous EOB-MRI images were used as the reference, more than half (28/50, 56%) of hypervascular HCCs initially appearing on the current EOB-MRI images were found not to have developed from nodules detectable on the previous MRIs through the traditionally accepted process of multistep carcinogenesis. Instead, they seemed to have developed via an “imaging-occult” process of carcinogenesis in patients with chronic liver diseases.

Objectives To compare the diagnostic accuracies of magnetic resonance elastography (MRE) and transient elastography (TE) for hepatic fibrosis. Materials and Methods This retrospective study was approved by the institutional review board and included 113 patients (mean age, 63.1 ± 12.2 years; 84 men and 29 women) with chronic liver disease who underwent liver biopsy or resection, histopathologic assessment (METAVIR scoring system), and TE within 6 months of MRE. Diagnostic accuracies of MRE and TE were compared using receiver operating characteristic curve analysis. Appropriate cutoff values of the two methods determined by maximum positive and minimum negative likelihood ratios were used to calculate the positive and negative predictive values for discriminating significant fibrosis (≥ F2) from F0–F1 or cirrhosis (F4) from F0–F3. Results Mean (95% confidence interval) area under the receiver operating characteristic curve values of MRE for cirrhosis (F4) (0.97 [0.93–0.99] vs. 0.93 [0.87–0.96]; P = 0.0308), clinically significant fibrosis (≥ F2) (0.98 [0.94–0.99] vs. 0.87 [0.79–0.92]; P = 0.0003), and any fibrosis (≥ F1) (0.97 [0.92–0.99] vs. 0.87 [0.76–0.93]; P = 0.0126) were significantly higher than those of TE. By using the cutoff values derived from the maximum positive likelihood ratio, the positive and negative predictive values for ≥ F2 were 98.8% and 83.9%, respectively, by MRE and 98.2% and 44.8%, respectively, by TE; and for F4, 97.0% and 86.3%, respectively, by MRE and 95.8% and 77.5%, respectively, by TE. Conclusion MRE has better diagnostic accuracy than TE for staging hepatic fibrosis.

Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy.To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard.A retrospective study at a single institution.In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle.2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used.Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard.The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test.Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017).MRE can be an alternative to liver biopsy for fibrosis staging.3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275.

To compare the occurrence of transient respiratory motion (TM) artifacts between 0.05 mmol/kg and 0.025 mmol/kg gadoxetic-acid on arterial phase MRI intra-individually for evaluating dose-dependence of gadoxetic acid.This retrospective study involved 91 patients who underwent dynamic MRI at 1.5T at different times, one time with 0.05 mmol/kg and the other 0.025 mmol/kg gadoxetic-acid. Examinations with 0.05 mmol/kg totaled 91 scans, and examinations with 0.025 mmol/kg totaled 375 scans (due to multiple exams for several patients). The scan with 0.025 mmol/kg closest in time to the 0.05 mmol/kg scan was selected to minimize temporal effects. Two radiologists graded TM artifacts in the arterial phase images using a four-point scale: no, mild, moderate, and severe artifacts. Results were compared between the two protocols (0.05 mmol/kg versus all 0.025 mmol/kg and 0.05 mmol/kg versus selected 0.025 mmol/kg), and the odds ratio for moderate-to-severe artifacts was calculated.Significantly more TM artifacts were observed in the double dose (16/91 [17%]) scans compared with either all (17/375 [4%]; P 0.01) or selected (3/91 [3%]; P = 0.01) standard dose scans. The odds ratio of the moderate-to-severe artifacts with the higher dose was 4.99-5.33.There appears to be dose-dependence of gadoxetic-acid and the occurrence of TM artifacts.3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:433-438.

Purpose To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). Materials and Methods This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. Results D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). Conclusion IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging. J. Magn. Reson. Imaging 2015;42:204–210. © 2014 Wiley Periodicals, Inc.

Purpose To evaluate the effect of hepatitis activity on liver stiffness measurements and the role of serum alanine aminotransferase (ALT) in liver fibrosis staging by MR elastography (MRE). Materials and Methods We measured liver stiffness (kPa) in 135 patients by MRE and histologically assessed fibrosis and hepatitis activity within 2 months. Stepwise multiple linear regression was performed to determine the maximum adjusted R2 against liver stiffness, after adjusting for nothing (model 1), ALT/upper limit of normal categories (model 2), and hepatitis activity (A grade) by METAVIR (model 3). Logistic regression was used to identify independent factors associated with pathologically proven cirrhosis. Results Platelet count and METAVIR F score were strongly associated with liver stiffness. The adjusted R2 value of model 3 (0.7026) was higher than those of models 1 (0.6472) and 2 (0.6564), showing that hepatitis activity affected liver stiffness measurement. High ALT levels (odds ratio, 0.0066; P = 0.0003) as well as MRE (odds ratio, 9.91; P

Objective: After much debate, the International Consensus Group for Hepatocellular Neoplasia (ICGHN) has recently arrived at a conclusion regarding the pathological criteria for early hepatocellular carcinoma (HCC). They have stated that stromal invasion should be recognized as the most important pathological finding for precisely diagnosing and differentiating early HCC from dysplastic nodules (DN). Methods: We conducted a review of the imaging findings from multi-imaging modalities of early HCC cases diagnosed according to the pathological criteria of the ICGHN. The multi-imaging modalities included gadoxetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI), abbreviated as EOB-MRI, contrast-enhanced CT (CE-CT), CT during arterioportography (CTAP), and CT during hepatic arteriography (CTHA). It has been shown that EOB-MRI is the only imaging modality that has sufficient resolution for the detection and classification of early HCC. Results: The most significant imaging feature for diagnosing early HCC was hypointensity on hepatobiliary-phase (HP) images of EOB-MRI; all of the cases of early HCC that were detected on HP images of EOB-MRI showed hypointensity, while all of the images of DN showed isointensity or hyperintensity compared with the liver parenchyma. The results of the diagnostic performance analysis showed that EOB-MRI had excellent sensitivity (97%) for detecting early HCC and outstanding specificity (100%) for distinguishing early HCC from DN. Conclusions: Considering the results from imaging-pathologic correlations and follow-up studies indicating that many early-stage hepatocellular nodules showing hypointensity on HP images of EOB-MRI tend to develop hypervascularization during a relatively short follow-up period, it is beginning to be accepted that such nodules may be treated as early HCC. However, hepatologists and radiologists should also recognize that some cases of early HCC may show isointensity or hyperintensity on HP images of EOB-MRI, making it impossible to differentiate early HCC from DN, although the low prevalence of such nodules may be unlikely to affect the generally accepted follow-up protocols for cirrhotic patients. Our results and other recent reports have indicated that signal-intensity patterns on HP images of EOB-MRI for DN and early HCC directly correlate with the degree of expression of the organic anion transporting polypeptide (OATP) 1B3 in the nodules. Thus, the diagnostic performance of pathological analyses for early HCC cases may be dramatically improved, nearly up to that of EOB-MRI, by incorporating an OATP1B3 staining method.

Purpose To identify magnetic resonance imaging (MRI)-based parameters associated with gastroesophageal varices (GEVs) in patients with chronic liver disease. Materials and Methods Ninety-three patients were divided into three groups based on endoscopic findings: group 1 with no GEVs (n = 49), group 2 with mild GEVs (n = 30), and group 3 with severe GEVs (n = 14). We used a multivariate logistic regression analysis to assess liver stiffness, aspartate aminotransferase-to-platelet ratio index, spleen stiffness and volume, portal vein velocity, cross-sectional area, and flow volumes potential independent associators of any (mild and severe) GEVs or severe GEVs. Results The analysis showed that spleen and liver stiffness and spleen volume were independently associated with any GEVs (spleen stiffness, odds ratio [95% confidence interval], 1.25 [1.04–1.68], P = 0.018; liver stiffness, 1.52 [1.13–2.17], P = 0.006; spleen volume, 1.01 [1.00–1.01], P = 0.016), whereas spleen stiffness was associated with severe GEVs (1.82 [1.25–2.95]; P = 0.005). Conclusion: Liver and spleen stiffness and spleen volume are associated with GEVs in patients with chronic liver disease. Compared with liver stiffness and spleen volume, spleen stiffness is more strongly associated with severe GEVs. J. Magn. Reson. Imaging 2015;41:117–124. © 2013 Wiley Periodicals, Inc.

To assess the value of hepatic arterial-phase (HAP) imaging with a low tube voltage (80 kVp), using non-helical, volumetric acquisition with a 320-detector-rows area-detector CT (ADCT) scanner for evaluating hypervascular hepatocellular carcinoma (HCC) compared with routine 120-kVp HAP imaging. This study enrolled 128 patients with 148 HCCs. Seventy-six patients with 79 HCCs underwent HAP imaging with 80 kVp obtained using a 320-detector-rows ADCT scanner. The remaining 52 patients with 69 HCCs underwent routine HAP imaging with 120 kVp obtained by 64-slice helical acquisition. Image noise and tumor to liver contrast-to-noise ratio (CNR) of the two sets of images were compared. Three radiologists evaluated both sets of images using receiver operating characteristic analyses. Although there was a two-fold increase in the mean image noise with 80 kVp over that with 120 kVp (p