Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

AIM: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS: We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS: The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION: History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

Early detection of hypervascularization in hepatocellular carcinoma (≤2 cm) on hepatic arterial phase with virtual monochromatic imaging: Comparison with low-tube voltage CT.

This study aims to assess the diagnostic value of virtual monochromatic image (VMI) at low keV energy for early detection of small hepatocellular carcinoma (HCC) in hepatic arterial phase compared with low-tube voltage (80 kVp) CT generated from dual-energy CT (DE-CT). A total of 107 patients with 114 hypervascular HCCs (≤2 cm) underwent DE-CT, 140 kVp, blended 120 kVp, and 80 kVp images were generated, as well as 40 and 50 keV. CT numbers of HCCs and the standard deviation as image noise on psoas muscle were measured. The contrast-to-noise ratios (CNR) of HCC were compared among all techniques. Overall image quality and sensitivity for detecting HCC hypervascularity were qualitatively assessed by three readers. The mean CT numbers, CNR, and image noise were highest at 40 keV followed by 50 keV, 80 kVp, blended 120 kVp, and 140 kVp. Significant differences were found in all evaluating endpoints except for mean image noise of 50 keV and 80 kVp. Image quality of 40 keV was the lowest, but still it was considered acceptable for diagnostic purposes. The mean sensitivity for detecting lesion hypervascularity with 40 keV (92%) and 50 keV (84%) was higher than those with 80 kVp (56%). Low keV energy images were superior to 80 kVp in detecting hypervascularization of early HCC.

Liver parenchymal changes detected by MR elastography and diffusion-weighted imaging after stereotactic body radiotherapy for hepatocellular carcinoma.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a local treatment option for hepatocellular carcinoma (HCC). SBRT-induced focal reactions on the liver parenchyma have not been thoroughly evaluated using quantitative magnetic resonance imaging (MRI). PURPOSE: To quantitatively evaluate liver parenchymal changes caused by SBRT for HCC using magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). METHOD: We retrospectively evaluated 22 adult patients who received SBRT for HCC and 27 who received locoregional therapy other than SBRT (controls). Liver stiffness by MRE and apparent diffusion coefficient (ADC) values by DWI of the liver parenchyma were measured before and after SBRT. Regions of interest (ROIs) were drawn on the two areas of radiation dose distribution levels, > 30 Gy and ≤ 30 Gy; a ROI was drawn in the control group. The two indices were compared before and after SBRT using a Wilcoxon matched-pairs signed-rank test. RESULTS: Liver stiffness and ADC values were significantly increased after SBRT in the dose areas of > 30 Gy compared with those before SBRT (4.05 vs 4.85 kPa; p < 0.05 in liver stiffness, and 1.10 vs 1.40 ×10-3 s/mm2; p < 0.05 in ADC values). In the dose area of ≦ 30 Gy, liver stiffness showed a significant increase in one reader (p = 0.033) but not in another reader (p = 0.085); ADC value showed no significant difference before and after SBRT as per both readers (p > 0.05). The control group demonstrated no significant differences before and after treatment (p > 0.05). CONCLUSION: MRE and DWI can be used to detect SBRT-induced liver parenchymal changes.

Inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein from bland thrombus using gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: To assess inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein (TIV) from bland thrombus on gadoxetic acid-enhanced magnetic resonance imaging (Gx-MRI). Secondarily, to determine whether a multi-feature model improves accuracy compared to LI-RADS. METHODS: We retrospectively identified consecutive patients at risk for hepatocellular carcinoma with venous occlusion(s) reported on Gx-MRI. Five radiologists independently classified each occlusion as TIV or bland thrombus using the LI-RADS TIV criterion (enhancing soft tissue in vein). They also evaluated imaging features suggestive of TIV or bland thrombus. Intra-class correlation coefficient (ICC) was calculated for individual features. A multi-feature model was developed based on consensus scores of features with > 5% consensus prevalence and > 0.40 ICC. Sensitivity and specificity of the LI-RADS criterion and of the cross-validated multi-feature model were compared. RESULTS: Ninety-eight patients with 103 venous occlusions (58 TIV, 45 bland thrombus) were included. The LI-RADS criterion provided 0.63 ICC and, depending on the reader, 0.62-0.93 sensitivity and 0.87-1.00 specificity. Five other features had > 5% consensus prevalence and > 0.40 ICC, including three LI-RADS suggestive features and two non-LI-RADS features. The optimal multi-feature model incorporated the LI-RADS criterion and one LI-RADS suggestive feature (occluded or obscured vein contiguous with malignant parenchymal mass). After cross-validation, the multi-feature model did not improve sensitivity or specificity compared to the LI-RADS criterion (P = 0.23 and 0.25, respectively). CONCLUSION: Using Gx-MRI, the LI-RADS criterion for TIV provides substantial inter-observer agreement, variable sensitivity, and high specificity for differentiating TIV from bland thrombus. A cross-validated multi-feature model did not improve diagnostic performance.

Effect of a combination of pemafibrate and a mild low-carbohydrate diet on obese and non-obese patients with metabolic-associated fatty liver disease.

BACKGROUND AND AIM: Recently, pemafibrate and a low-carbohydrate diet (LCD) have each been reported to improve fatty liver disease. However, it is unclear whether their combination improves fatty liver disease and is equally effective in obese and non-obese patients. METHODS: In 38 metabolic-associated fatty liver disease (MAFLD) patients, classified by baseline body mass index (BMI), changes in laboratory values, magnetic resonance elastography (MRE), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were studied after 1 year of combined pemafibrate plus mild LCD. RESULTS: The combination treatment resulted in weight loss (P = 0.002), improvement in hepatobiliary enzymes (γ-glutamyl transferase, P = 0.027; aspartate aminotransferase, P < 0.001; alanine transaminase [ALT], P < 0.001), and improvement in liver fibrosis markers (FIB-4 index, P = 0.032; 7 s domain of type IV collagen, P = 0.002; M2BPGi, P < 0.001). Vibration-controlled transient elastography improved from 8.8 to 6.9 kPa (P < 0.001) and MRE improved from 3.1 to 2.8 kPa (P = 0.017) in the liver stiffness. MRI-PDFF improved from 16.6% to 12.3% in liver steatosis (P = 0.007). In patients with a BMI of 25 or higher, improvements of ALT (r = 0.659, P < 0.001) and MRI-PDFF (r = 0.784, P < 0.001) were significantly correlated with weight loss. However, in patients with a BMI below 25, the improvements of ALT or PDFF were not accompanied by weight loss. CONCLUSIONS: Combined treatment with pemafibrate and a low-carbohydrate diet resulted in weight loss and improvements in ALT, MRE, and MRI-PDFF in MAFLD patients. Although such improvements were associated with weight loss in obese patients, the improvements were observed irrespective of weight loss in non-obese patients, indicating this combination can be effective both in obese and non-obese MAFLD patients.

Effect of decreased contrast injection flow rate on aortic enhancement in 80-KV peak CT with contrast dose reduction.

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.

An Intra-individual Comparison between Free-breathing Dynamic MR Imaging of the Liver Using Stack-of-stars Acquisition and the Breath-holding Method Using Cartesian Sampling or View-sharing.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Four-dimensional flow magnetic resonance imaging for assessment of hemodynamic changes in the portal venous system before and after balloon-occluded retrograde transvenous obliteration: a pilot feasibility study.

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.

Keratinocyte Regnase-1, a Downregulator of Skin Inflammation, Contributes to Protection against Tumor Promotion by Limiting Cyclooxygenase-2 Expression.

We previously showed that the ribonuclease Regnase-1 (Reg1) in keratinocytes plays a role in mitigating skin inflammation by downregulating proinflammatory cytokines. In this study, 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-knockout [Reg1-cKO]) mice developed skin tumors with shorter latency and more multiplicity than control mice. In addition, repeated UVB irradiation readily provoked solar keratosis-like lesions in Reg1-cKO mice. Increased levels of cyclooxygenase 2, whose mRNA (Ptgs2) is reportedly a target of Reg1, have been known to be associated with the development of squamous cell carcinomas. Indeed, Ptgs2 mRNA levels were upregulated in the skin of Reg1-cKO mice after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. The level of prostaglandin E2 was higher in 12-O-tetradecanoylphorbol-13-acetate‒treated Reg1-cKO mouse skin than in control mice skin. Moreover, in vivo inhibition of cyclooxygenase 2 attenuated the 12-O-tetradecanoylphorbol-13-acetate‒induced epidermal thickening in Reg1-cKO mice. Finally, REG1 knockdown in human squamous cell carcinomas lines enhanced PTGS2 mRNA levels after 12-O-tetradecanoylphorbol-13-acetate treatment. In conclusion, epidermal Reg1 plays a regulatory role not only in skin inflammation but also in tumor promotion through the downregulation of cyclooxygenase 2. Therefore, forced expression of Reg1 under inflammatory conditions may be relevant to preventing skin cancer.

Model-based Deep Learning Reconstruction Using a Folded Image Training Strategy for Abdominal 3D T1-weighted Imaging.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Adult-onset Langerhans cell histiocytosis changing CNS lesion from pituitary to suprasellar extension.

Summary: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of abnormal Langerhans cells in various tissues and organs, including bone, skin, the lungs, and the pituitary gland. Hypothalamic-pituitary lesions in LCH often cause central diabetes insipidus (CDI), but the natural course of LCH in the CNS remains to be elucidated. In this study, we report an interesting case of altered LCH lesions in the CNS from the pituitary to the hypothalamus in a 45-year-old woman. She developed symptoms of polyuria and was diagnosed with CDI with lymphocytic hypophysitis due to an enlarged pituitary gland with stalk thickening shown on MRI. Short-term glucocorticoid therapy cured pituitary enlargement, but serum prolactin levels gradually increased. Six years later, the immunohistological findings of a skin biopsy revealed positive for leukocyte common antigen, S-100, and CD1a expression, indicating a diagnosis of LCH. MRI revealed a new lesion in the hypothalamus without pituitary involvement, likely due to LCH. Chemotherapy improved LCH lesions both in the skin and hypothalamus, but therapy was stopped on the patient's request. Although adult-onset LCH is rare, it should be considered as a differential diagnosis in cases of CDI as the primary disease. The clinical course in the present case indicated that LCH lesion was altered from pituitary to suprasellar extension; where such changes were observed, the possibility of LCH should be considered. Learning points: Diagnosing the primary disease of CDI is challenging; therefore, careful observation is necessary in pathologically unknown cases. Enhanced MRI should be performed in cases with suspected hypothalamic lesions, such as elevated serum prolactin. Although adult-onset LCH is rare, it should be considered a differential diagnosis in cases of CDI as the primary disease. The direction of changing CNS lesion from pituitary to suprasellar extension might be a unique MRI finding in LCH.

Schwannoma in and around the porta hepatis: radiological features in eight cases and literature review.

PURPOSE: 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), and 18F-fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT). METHODS: We 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. RESULTS: 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. CONCLUSION: 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.

Distinction Between Hepatocellular Carcinoma and Hypervascular Liver Metastases in Non-cirrhotic Patients Using Gadoxetate Disodium-Enhanced Magnetic Resonance Imaging.

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.

Image quality and radiologists' subjective acceptance using model-based iterative and deep learning reconstructions as adjuncts to ultrahigh-resolution CT in low-dose contrast-enhanced abdominopelvic CT: phantom and clinical pilot studies.

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 < 0.001 for all). Compared with the routine protocol, subjective noise was similar or better by DLR, and other subjective characteristics were similar or worse by MBIR. CONCLUSION: Image quality, except regarding noise characteristics, and acceptance by radiologists were better by DLR than MBIR in low-dose CE-APCT by UHRCT.

Uptake of gadoxetic acid in hepatobiliary phase magnetic resonance imaging and transporter expression in hypovascular hepatocellular nodules.

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.