Gadoxetic Acid-enhanced Magnetic Resonance Imaging Research Articles

Hepatic Arterial Phase on Gadoxetic Acid-Enhanced Liver MR Imaging: A Randomized Comparison of 0.5 mL/s and 1 mL/s Injection Rates

ObjectiveTo compare gadoxetic acid injection rates of 0.5 mL/s and 1 mL/s for hepatic arterial-phase magnetic resonance (MR) imaging.Materials and MethodsIn this prospective study, 101 consecutive patients with suspected focal liver lesions were included and randomly divided into two groups. Each group underwent dynamic liver MR imaging using a 3.0-T scanner after an intravenous injection of gadoxetic acid at rates of either 0.5 mL/s (n = 50) or 1 mL/s (n = 51). Arterial phase images were analyzed after blinding the injection rates. The signal-to-noise ratios (SNRs) of the liver, aorta, portal vein, hepatic vein, spleen, and pancreas were measured. The contrast-to-noise ratios (CNRs) of the hepatocellular carcinomas (HCC) were calculated. Finally, two experienced radiologists were independently asked to identify, if any, HCCs in the liver on the images and score the image quality in terms of the presence of artifacts and the proper enhancement of the liver, aorta, portal vein, hepatic vein, hepatic artery, spleen, pancreas, and kidney.ResultsThe SNRs were not significantly different between the groups (p = 0.233-0.965). The CNRs of the HCCs were not significantly different (p = 0.597). The sensitivity for HCC detection and the image quality scores were not significantly different between the two injection rates (p = 0.082-1.000).ConclusionImage quality and sensitivity for hepatic HCCs of arterial-phase gadoxetic acid-enhanced MR were not significantly improved by reducing the contrast injection rate to 0.5 mL/s compared with 1 mL/s.

Gadoxetic acid-enhanced MRI for hepatocellular carcinoma and hypointense nodule observed in the hepatobiliary phase

The aim of our study was to evaluate the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (MR) imaging both in the detection of hepatocellular carcinoma (HCC) and precancerous lesions and in the assessment of their evolution. A retrospective study was undertaken on 56 patients with chronic liver disease and suspected liver lesions. We evaluated the number, size and signal intensity of the nodules on dynamic and hepatobiliary MR images. Follow-up studies were carried out every 3 months. Statistical analysis was performed using the Fisher's exact test. A total of 120 nodules were identified in 41 patients. Of these, 92/120 nodules (76.6%; mean diameter 18.4 mm) showed the typical HCC vascular pattern: 90/92 nodules appeared hypointense and 2/92 were hyperintense on hepatobiliary phase images. An additional 28/120 hypointense, nonhypervascular nodules (23.3%; mean diameter 11 mm) were detected on hepatobiliary phase images, 15 of which showed hypointensity also on the equilibrium phase images. During the 3- to 12-month follow-up, 14/28 nodules (mean diameter 13.3 mm) developed the typical vascular pattern of HCC. Gadoxetic acid-enhanced MR imaging is useful for detecting HCC as well as hypovascular nodules with potential progression to HCC. Lesions measuring more than 10 mm in diameter are at higher risk of developing into HCC (p = 0.0128).

Ectopic pancreas in upper gastrointestinal tract: MRI findings with emphasis on differentiation from submucosal tumor

Ectopic pancreas can frequently be mistaken for other submucosal masses. Ectopic pancreas may follow the signal intensity of mother pancreas on various magnetic resonance (MR) sequences, which might be helpful for differentiation between ectopic pancreas and other submucosal tumors in upper gastrointestinal (UGI) tract. To evaluate the value of MR imaging (MRI) in differentiating ectopic pancreases from submucosal tumors in UGI tract. Fifteen patients with ectopic pancreas and 26 patients with UGI submucosal tumors were included. All patients underwent abdominal MRI with diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced MRI. Qualitative (location, contour, growth pattern, lesion border, and presence of intralesional cystic portion and duct-like structure) and quantitative (long diameter [LD], short diameter [SD], LD/SD ratio, signal intensities and apparent diffusion coefficients [ADC], and signal intensity - and ADC ratios of UGI submucosal lesions to pancreas) parameters were compared between ectopic pancreases and UGI submucosal tumors using Fisher's exact test, the Mann-Whitney U test, and receiver-operating characteristic (ROC) analysis. Duodenum was the most common location for ectopic pancreas (12/15, 79.9%), and the gastric body for UGI submucosal tumors (15/26, 57.7%) (P = 0.005). Round shape was an imaging feature more common in UGI submucosal tumors (12/26, 46.2%) than in ectopic pancreas (1/15, 6.7%; P = 0.021). On all of the various pulse sequences of MR images, ectopic pancreas showed isointensity comparable to that of pancreas more frequently than did sequences of UGI submucosal tumors (P < 0.01).The means (0.95 ± 0.09, 0.99 ± 0.06, 1.07 ± 0.08) of the signal intensity ratio of ectopic pancreas to pancreas on fat-suppressed unenhanced T1-weighted, arterial, and portal phase images were significantly higher than those (0.60 ± 0.09, 0.62 ± 0.28, 0.86 ± 0.27) of UGI submucosal tumors (P < 0.05). In contrast, the means (1.05 ± 0.12, 0.93 ± 0.18) of the signal intensity ratios of ectopic pancreas on T2-weighted images and DW images (b = 800 s/mm(2)) were significantly lower than those (1.82 ± 0.39, 2.35 ± 0.94) of UGI submucosal tumors (P < 0.001). On ROC analysis, if absolute value of difference between 1.0 and signal intensity ratio of submucosal lesions to the pancreas on T1-weighted images is <0.21, the sensitivity and specificity reach 100.0% for diagnosis ectopic pancreas from submucosal tumors. Abdominal MRI with DWI can be a valuable tool for differentiating ectopic pancreases from UGI submucosal tumors.

Liver Fibrosis: Histopathologic and Biochemical Influences on Diagnostic Efficacy of Hepatobiliary Contrast-enhanced MR Imaging in Staging

To evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with diffuse chronic liver diseases (CLDs) and to investigate the factors that may influence the results. With the approval of the Hospital Ethics Committee and waiver of the informed consent requirement, data in 102 patients with histologically proven liver fibrosis (classified according to the METAVIR system) of various underlying causes were retrospectively analyzed. Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of the liver was defined by using region of interest measurements before contrast material injection and in the hepatobiliary phase (20 minutes after contrast material administration), and relative enhancement was calculated. Univariate and multivariate regression analyses were applied to identify variables associated with relative enhancement measurements, and the performance of relative enhancement measurements in the staging of liver fibrosis was assessed by using area under the receiver operating characteristic curve (AUC) analysis. At analysis of the relationship between enhancement measurements and histologic parameters, the relative enhancement values correlated strongly with liver fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P = .05). In multivariate analysis, only liver fibrosis stage independently influenced relative enhancement values (P < .001). The measurements performed well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and 0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels were independent predictors of false-negative results. The presence of hepatic fibrosis can be assessed with good discrimination by using gadoxetic acid-enhanced MR imaging, but assessment can be confounded in the setting of abnormal aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

Hilar Cholangiocarcinoma: Value of Adding DW Imaging to Gadoxetic Acid–enhanced MR Imaging with MR Cholangiopancreatography for Preoperative Evaluation

To assess the benefit of adding diffusion-weighted (DW) imaging to gadoxetic acid-enhanced magnetic resonance (MR) imaging and MR cholangiopancreatography in the preoperative evaluation of hilar cholangiocarcinoma. The institutional review board approved this retrospective study and waived the requirement for informed consent. The study included 52 patients (36 men, 16 women; mean age, 63.4 years) with surgically confirmed hilar cholangiocarcinoma who underwent gadoxetic acid-enhanced MR imaging and DW imaging at 3.0 T between August 2010 and December 2011. Two observers independently reviewed two image sets--a gadoxetic acid set, including images from MR cholangiopancreatography, and a combined gadoxetic acid set and DW imaging set--to evaluate the tumor involvement of each biliary confluence and vascular and liver invasion by using receiver operating characteristic (ROC) curve analysis. For each observer, area under the ROC curve (Az) values for tumor involvement of the biliary confluence were 0.965 and 0.957 for the gadoxetic acid set and 0.980 and 0.975 for the combined set, respectively (P > .05). For detecting 105 biliary confluences with tumor involvement, the sensitivities with the combined set (97.1% [102 of 105] and 98.1% [103 of 105]) were higher than those with the gadoxetic acid set (91.4% [96 of 105] for both observers) (P = .029 and P = .016), although the specificities were similar with both image sets (P > .05). For the detection of liver invasion, the combined set (75.0% [15 of 20] for both observers) yielded better sensitivity than the gadoxetic acid set (50.0% [10 of 20] and 45.0% [nine of 20]) (P = .016 and P = .031). For evaluation of vascular invasion, the two image sets showed similar diagnostic performance. In the preoperative evaluation of hilar cholangiocarcinoma, the addition of DW imaging to gadoxetic acid-enhanced MR imaging could improve sensitivity in the evaluation of tumor extent along the bile duct and liver invasion.

Liver Failure after Major Liver Resection: Risk Assessment by Using Preoperative Gadoxetic Acid–enhanced 3-T MR Imaging

To determine if gadoxetic acid-enhanced magnetic resonance (MR) imaging with measurement of relative liver enhancement (RLE) on hepatobiliary phase images can allow preoperative assessment of the risk of liver failure after major liver resection. The local institutional review committee approved this retrospective analysis and waived written informed consent. The study included 73 patients (39 men; median age, 64.4 years) who underwent gadoxetic acid-enhanced 3-T MR imaging before resection of three or more liver segments. RLE was calculated as the ratio of signal intensity measurements of the liver parenchyma before and 20 minutes after intravenous administration of gadoxetic acid. RLE was assessed in each liver segment and the mean value of all segments was used for analysis. Posthepatectomy liver failure was defined according to the "50-50 criteria" (ie, prothrombin time <50% and serum bilirubin >50 µmol/L on postoperative day 5) and the International Study Group of Liver Surgery (ISGLS) classification. The association of RLE and liver failure was tested with univariate and multivariate logistic regression analysis. In addition to RLE, the latter also included demographic, clinical, operative, and histologic variables. Patients with liver failure according to the 50-50 criteria (n = 3) had significantly lower RLE (54.5%) than those without (125.6%) (P = .009). According to ISGLS criteria, RLE was 112.5% in patients with grade A liver failure (n = 20), 88.4% in patients with grade B (n = 7), 41.7% (n = 2) in patients with grade C, and 136.5% (P < .001) in those without liver failure. In a logistic regression analysis, RLE was inversely related to the probability of liver failure according to the 50-50 (P = .02) and ISGLS (P < .001) criteria. In a multivariate analysis, RLE was independently associated with a higher probability of liver failure according to ISGLS classification (P = .003). Gadoxetic acid-enhanced MR imaging can help with the assessment of the risk for liver failure after major liver resection.

Infiltrative hepatocellular carcinoma on gadoxetic acid-enhanced and diffusion-weighted MRI at 3.0T

To determine imaging features of infiltrative hepatocellular carcinoma (HCC) on 3T magnetic resonance imaging (MRI) including gadoxetic acid-enhanced and diffusion-weighted imaging (DWI). Eighteen patients with infiltrative HCC underwent liver MRI that consisted of T1- and T2-weighted image (T2WI), gadoxetic acid-enhanced arterial, portal, 3-min late and 20-min hepatobiliary phase (HBP), and DWI. Two reviewers evaluated in consensus tumor characteristics and lesion conspicuity using a 4-point scale. The tumor-to-liver contrast ratio was also measured. Most of the tumors (n = 16, 88.9%) were seen as irregular permeative masses (4.0-23.0 cm, mean 10.5 cm in diameter) and the remaining two as poorly defined amorphous infiltration among thrombosed portal veins. Internal reticulation within the tumor was characteristic and was most frequently observed on 3-min late phase (n = 18), followed by HBP (n = 15). Tumor conspicuity and tumor-to-liver contrast ratio was highest with b-800 DWI, which was significantly higher than those of other images (P < 0.05). DWI provides the highest conspicuity for infiltrative HCC compared to unenhanced T1- and T2WI and gadoxetic acid-enhanced MRI. The gadoxetic acid-enhanced 3-min late image is useful in characterizing infiltrative HCC, as it clearly depicts internal reticulation in all tumors.

Organ-focused mutual information for nonrigid multimodal registration of liver CT and Gd–EOB–DTPA-enhanced MRI

Accurate detection of liver lesions is of great importance in hepatic surgery planning. Recent studies have shown that the detection rate of liver lesions is significantly higher in gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) than in contrast-enhanced portal-phase computed tomography (CT); however, the latter remains essential because of its high specificity, good performance in estimating liver volumes and better vessel visibility. To characterize liver lesions using both the above image modalities, we propose a multimodal nonrigid registration framework using organ-focused mutual information (OF-MI). This proposal tries to improve mutual information (MI) based registration by adding spatial information, benefiting from the availability of expert liver segmentation in clinical protocols. The incorporation of an additional information channel containing liver segmentation information was studied. A dataset of real clinical images and simulated images was used in the validation process. A Gd-EOB-DTPA-enhanced MRI simulation framework is presented. To evaluate results, warping index errors were calculated for the simulated data, and landmark-based and surface-based errors were calculated for the real data. An improvement of the registration accuracy for OF-MI as compared with MI was found for both simulated and real datasets. Statistical significance of the difference was tested and confirmed in the simulated dataset (p<0.01).

Hepatocellular carcinoma 20mm or smaller in cirrhosis patients: early magnetic resonance enhancement by gadoxetic acid compared with gadopentetate dimeglumine.

To evaluate the differences in enhancement pattern of hepatocellular carcinoma (HCC) 20mm or smaller and enhancement effects of hepatic vessels on early dynamic contrast-enhanced magnetic resonance imaging (MRI) obtained with gadoxetic acid and gadopentetate dimeglumine in the same patients with cirrhosis. We reviewed MR images using gadoxetic acid and gadopentetate dimeglumine in the same 34 patients with 42 histologically confirmed HCCs (median diameter, 14.5mm). The percentage enhancements (PEs) of HCC, the hepatic artery and portal vein and relative contrasts (RCs) between HCC and the liver were calculated and analyzed statistically. The PEs of HCC, the hepatic artery and portal vein were significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p=0.0256 for HCC, p<0.0001 for hepatic artery) and portal phase (p<0.0001 for HCC, portal vein). The RC between HCC and the liver was significantly lower for gadoxetic acid in comparison with gadopentetate dimeglumine in the arterial phase (p=0.0422), but was not significantly different in the portal phase (p=0.1133). Forty-one of the 42 (97.62%) nodules showed arterial hypervascularization. Of these, 31 (75.61%) nodules were hypointense in the portal phase for gadoxetic acid, and 22 (53.66%) were hypointense for gadopentetate dimeglumine (p=0.038). Compared with gadopentetate dimeglumine, gadoxetic acid-enhanced MRI demonstrated a different enhancement pattern of inferior arterial enhancement and was more rapidly hypointense in the portal phase for HCC. It showed markedly lower enhancement for hepatic artery and portal vein in the patients with cirrhosis.

Is Liver-Specific Gadoxetic Acid-Enhanced Magnetic Resonance Imaging a Reliable Tool for Detection of Hepatocellular Carcinoma in Patients with Chronic Liver Disease?

Gadoxetic acid is a recently developed hepatobiliary-specific contrast material used for magnetic resonance imaging (MRI) which enables highly sensitive detection of hepatocellular carcinoma (HCC). We performed a meta-analysis of all available studies of the diagnostic performance of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for detection of HCC in patients with chronic liver disease. Databases including MEDLINE and EMBASE were searched for relevant original articles published from January 2000 to April 2012. Pooled estimation and subgroup analysis data were obtained by statistical analysis. Across 10 studies of 570 patients, Gd-EOB-MRI sensitivity was 0.91 (95 % CI 0.77, 0.97) and specificity was 0.93 (95 % CI 0.85, 0.97). Overall, LR+ was 13.6 (95 % CI 5.6, 33.2), LR- was 0.10 (95 % CI 0.04, 0.27), and DOR was 140.36 (95 % CI 28, 696). Among patients with high pre-test probabilities, MRI enabled confirmation of HCC; among patients with low pre-test probabilities, MRI enabled exclusion of HCC. Worst-case-scenario (pre-test probability, 50 %) post-test probabilities were 93 and 9 % for positive and negative MRI results, respectively. In studies in which both Gd-EOB-MRI and contrast enhanced computed tomography (CE-CT) were performed, Gd-EOB-MRI was more sensitive than CE-CT (0.93 vs. 0.78; p < 0.05). Subgroup analysis suggested average lesion size (<2 vs. >2 cm) did not affect the diagnostic accuracy of the test (p > 0.05). A limited number of small studies suggest Gd-EOB-MRI has good diagnostic performance in the detection of HCC among patients with chronic liver disease. It is also confirmed to be a reliable tool for evaluation of small early-stage HCC.

Liver Fibrosis: Histopathologic and Biochemical Influences on Diagnostic Efficacy of Hepatobiliary Contrast-enhanced MR Imaging in Staging

To evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with diffuse chronic liver diseases (CLDs) and to investigate the factors that may influence the results. With the approval of the Hospital Ethics Committee and waiver of the informed consent requirement, data in 102 patients with histologically proven liver fibrosis (classified according to the METAVIR system) of various underlying causes were retrospectively analyzed. Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of the liver was defined by using region of interest measurements before contrast material injection and in the hepatobiliary phase (20 minutes after contrast material administration), and relative enhancement was calculated. Univariate and multivariate regression analyses were applied to identify variables associated with relative enhancement measurements, and the performance of relative enhancement measurements in the staging of liver fibrosis was assessed by using area under the receiver operating characteristic curve (AUC) analysis. At analysis of the relationship between enhancement measurements and histologic parameters, the relative enhancement values correlated strongly with liver fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P = .05). In multivariate analysis, only liver fibrosis stage independently influenced relative enhancement values (P < .001). The measurements performed well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and 0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels were independent predictors of false-negative results. The presence of hepatic fibrosis can be assessed with good discrimination by using gadoxetic acid-enhanced MR imaging, but assessment can be confounded in the setting of abnormal aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

Focal nodular hyperplasia: characterisation at gadoxetic acid-enhanced MRI and diffusion-weighted MRI

The aim of this study was to assess the enhancement patterns of hepatic focal nodular hyperplasia (FNH) on gadoxetic acid-enhanced MRI and diffusion-weighted (DW) MRI. This retrospective study had institutional review board approval. Gadoxetic acid-enhanced and DW MR images were evaluated in 23 patients with 30 FNHs (26 histologically proven and 4 radiologically diagnosed). The lesion enhancement patterns of the hepatobiliary phase images were classified as heterogeneous or homogeneous signal intensity (SI), and as dominantly high/iso or low SI compared with those of adjacent liver parenchyma. Heterogeneous (any) SI lesions and homogeneous low SI lesions were categorised into the fibrosis group, whereas homogeneous high/iso SI lesions were categorised into the non-fibrosis group. Additionally, lesion SI on T2 weighted images, DW images and apparent diffusion coefficient (ADC) values were compared between the two groups. The lesions showed heterogeneous high/iso SI (n=16), heterogeneous low SI (n=5), homogeneous high/iso SI (n=7) or homogeneous low SI (n=2) at the hepatobiliary phase MR images. The fibrosis group lesions were more likely to show high SI on DW images and T2 weighted images compared with those in the non-fibrosis group (p<0.05). ADC values tended to be lower in the fibrosis group than those in the non-fibrosis group without significance. FNH showed variable enhancement patterns on hepatobiliary phase images during gadoxetic acid-enhanced MRI. SI on DW and T2 weighted images differed according to the fibrosis component contained in the lesion. FNH shows a wide spectrum of imaging findings on gadoxetic acid-enhanced MRI and DW MRI.

Hypervascular hepatocellular carcinomas showing hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging: a possible subtype with mature hepatocyte nature

We evaluated molecular features of hypervascular hepatocellular carcinoma (HCC) that shows iso- or hyperintensity (hyperintense HCC) in the hepatobiliary phase (HB phase) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). We investigated 89 surgically resected cases. Patients were divided into two groups according to the signal intensity in the HB phase of EOB-MRI: hyperintense HCCs (n=18) and hypointense HCCs (n=71). We performed immunohistochemical staining for uptake transporter of gadoxetic acid: organic anion transporter polypeptides (OATP8); tumor markers: alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II); hepatic stem cell markers: epithelial cell adhesion molecule (EpCAM), cytokeratin 19 (CK19), and neural cell adhesion molecule (NCAM); biliary marker: CK7; hepatocyte marker: hepatocyte paraffin 1 (HepPar1); markers of HCC differentiation: glypican-3; signaling: beta-catenin, and the respective grade was semiquantitatively determined. Histopathologically, hyperintense HCCs showed significantly weaker expression of AFP (p<0.05), PIVKA-II (p<0.01), EpCAM (p<0.005), glypican-3 (p<0.005) relative to the hypointense HCCs, whereas OATP8 (p<0.0001), HepPar1 (p<0.05), and beta-catenin (p<0.001) were overexpressed in hyperintense HCCs compared with hypointense HCCs. Hyperintense HCC expressed OATP8 and showed a feature of mature hepatocytes with a weak expression of stem cell characteristics immunohistochemically. In addition, this type of HCC demonstrated a weaker expression of the poorer prognosis markers including, AFP, PIVKA-II, EpCAM, CK19, and glypican-3.

Oxaliplatin‐related sinusoidal obstruction syndrome mimicking metastatic liver tumors

A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.

Presence of a hypovascular hepatic nodule showing hypointensity on hepatocyte‐phase image is a risk factor for hypervascular hepatocellular carcinoma

To determine whether the presence of a hypovascular nodule in the liver showing hypointensity on hepatocyte-phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a risk factor for hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease. Forty-one patients with pathologically confirmed hypervascular HCC and 41 age- and gender-matched controls were retrospectively selected. These patients had undergone EOB-MRI at least twice: the latest EOB-MRI and EOB-MRI performed more than 6 months earlier. History of hypervascular HCC, presence of a hypointense hypovascular nodule in previous hepatocyte-phase MR images, percent prothrombin time, platelet count, serum levels of albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, α-fetoprotein, and protein induced by vitamin K absence-II (PIVKA-II) were variables evaluated by multivariate logistic regression analysis. Multivariate analysis revealed that serum albumin level (odds ratio [95% confidence interval], 0.19 [0.06-0.57]; P = 0.0024), history of hypervascular HCC (8.62 [2.71-32.8]; P = 0.0001), and presence of a hypointense hypovascular nodule (4.18 [1.18-17.2]; P = 0.0256) were significant risk factors for hypervascular HCC. Patients with chronic liver disease showing a hypointense hypovascular nodule in the liver on hepatocyte-phase EOB-MRI have a high risk of HCC development.

Hypovascular Hypointense Nodules on Hepatocyte Phase Gadoxetic Acid–enhanced MR Images: Too Early or Too Progressed to Determine Hypervascularity

HomeRadiologyVol. 267, No. 1 PreviousNext CommunicationsLetters to the EditorHypovascular Hypointense Nodules on Hepatocyte Phase Gadoxetic Acid–enhanced MR Images: Too Early or Too Progressed to Determine HypervascularityUtaroh Motosugi Utaroh Motosugi Author AffiliationsDepartment of Radiology, University of Yamanashi, 1110 Shiomokato, Chuo-shi, Yamanashi 409-3898, Japane-mail: [email protected]Utaroh Motosugi Published Online:Apr 1 2013https://doi.org/10.1148/radiol.13122186MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References1 Kim YK, Lee WJ, Park MJ, Kim SH, Rhim H, Choi D. Hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid–enhanced MR images in patients with cirrhosis: potential of DW imaging in predicting progression to hypervascular HCC. Radiology 2012;265(1):104–114. Link, Google Scholar2 International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 2009;49(2):658–664. [Published correction appears in Hepatology 2009; 49(3):1058.] Crossref, Medline, Google Scholar3 Kumada T, Toyoda H, Tada Tet al.. Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium–enhanced MRI. AJR Am J Roentgenol 2011;197(1):58–63. Crossref, Medline, Google Scholar4 Motosugi U, Ichikawa T, Sano Ket al.. Outcome of hypovascular hepatic nodules revealing no gadoxetic acid uptake in patients with chronic liver disease. J Magn Reson Imaging 2011;34(1):88–94. Crossref, Medline, Google Scholar5 Asayama Y, Yoshimitsu K, Nishihara Yet al.. Arterial blood supply of hepatocellular carcinoma and histologic grading: radiologic-pathologic correlation. AJR Am J Roentgenol 2008;190(1):W28–W34. Crossref, Medline, Google Scholar6 Nishie A, Tajima T, Asayama Yet al.. Diagnostic performance of apparent diffusion coefficient for predicting histological grade of hepatocellular carcinoma. Eur J Radiol 2011;80(2):e29–e33. Crossref, Medline, Google Scholar7 Muhi A, Ichikawa T, Motosugi Uet al.. High-b-value diffusion-weighted MR imaging of hepatocellular lesions: estimation of grade of malignancy of hepatocellular carcinoma. J Magn Reson Imaging 2009;30(5):1005–1011. Crossref, Medline, Google Scholar8 Regimbeau JM, Abdalla EK, Vauthey JNet al.. Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol 2004;85(1): 36–41. Crossref, Medline, Google ScholarArticle HistoryPublished online: Apr 2013Published in print: Apr 2013 FiguresReferencesRelatedDetailsCited ByHepatology International, Vol. 11, No. 4Korean Journal of Radiology, Vol. 18, No. 3Korean Journal of Radiology, Vol. 17, No. 1Digestive Diseases, Vol. 34, No. 6Journal of Magnetic Resonance Imaging, Vol. 41, No. 2Digestive Diseases, Vol. 33, No. 6Liver Cancer, Vol. 4, No. 1Hepatology Research, Vol. 44, No. 13Digestive Diseases, Vol. 32, No. 6Liver Cancer, Vol. 3, No. 3-4Oncology, Vol. 87, No. Suppl. 1Recommended Articles Validation of a Diagnostic Algorithm for Hepatocellular Carcinoma at Gadoxetic Acid–enhanced MRIRadiology2021Volume: 300Issue: 1pp. 184-186Diagnostic Performance of Gadoxetic Acid–enhanced Liver MR Imaging versus Multidetector CT in the Detection of Dysplastic Nodules and Early Hepatocellular CarcinomaRadiology2017Volume: 285Issue: 1pp. 134-146Clinical Outcomes of Radiofrequency Ablation for Early Hypovascular HCC: A Multicenter Retrospective StudyRadiology2017Volume: 286Issue: 1pp. 338-349Hepatobiliary versus Extracellular MRI Contrast Agents in Hepatocellular Carcinoma Detection: Hepatobiliary Phase Features in Relation to Disease-free SurvivalRadiology2019Volume: 293Issue: 3pp. 594-604Abbreviated Gadoxetic Acid–enhanced MRI with Second-Shot Arterial Phase Imaging for Liver Metastasis EvaluationRadiology: Imaging Cancer2019Volume: 1Issue: 1See More RSNA Education Exhibits All Manner of Things: Hepatocellular Carcinoma Imaging and TherapyDigital Posters2018Focal Liver Reaction Following Localized Radiation Therapy of Hepatocellular CarcinomaDigital Posters2020Atypical and Mimicking Hepatocellular Carcinoma: Evaluated by LI-RADS 2017Digital Posters2018 RSNA Case Collection Pseudocirrhosis of Hepatic Breast MetastasesRSNA Case Collection2020Oxaliplatin-induced focal nodular hyperplasiaRSNA Case Collection2021Radioembolization of Liver Metastasis RSNA Case Collection2020 Vol. 267, No. 1 Metrics Altmetric Score PDF download

Validation of diagnostic criteria using gadoxetic acid-enhanced and diffusion-weighted MR imaging for small hepatocellular carcinoma (≤ 2.0 cm) in patients with hepatitis-induced liver cirrhosis

Gadoxetic acid and diffusion-weighted imaging (DWI) is increasingly used for the diagnosis of hepatocellular carcinoma (HCC). It is relevant to refine the diagnostic parameters for HCC, using state-of-the-art imaging techniques. To validate usefulness of magnetic resonance imaging (MRI) criteria with gadoxetic acid-enhanced MRI and DWI for diagnosis of small HCC by differentiation from dysplastic nodule (DN) or regenerative nodule (RN) in cirrhotic patients with strongly suspected small HCC. One hundred and eight patients with 102 HCCs and 29 benign nodules including 21 DNs and two large RNs (≤ 2.0 cm), and 40 patients with no HCC underwent gadoxetic acid-enhanced MRI and DWI. All patients also underwent MDCT. Index MR criteria for HCC were: (i) arterial hyperenhancement and hypointensity on hepatobiliary phase (HBP) with hyperintensity on DWI; (ii) hypovascular nodule with hyperintensity on DWI; (iii) arterial hyperenhancement and hypointensity on HBP without hyperintensity on DWI; (iv) arterial hyperenhancement and either iso- or hyperintensity on HBP, with hyperintensity on DWI; and (v) hyperintensity only on DWI. According to these criteria, MRI findings for HCCs and benign nodules were independently classified by two reviewers. On multidetector-row computed tomography, 64 HCCs (62.7%) showed typical features for HCC while 13 (12.8%) were not identified. On MRI, 84 HCCs (82.4%) showed arterial hyperenhancement and hypointensity on HBP, and hyperintensity on DWI. Eight HCCs were regarded as hypovascular HCCs with hyperintensity DWI (category 2). One HCC (0.6 cm in diameter) was demonstrated only by DWI. For each observer, 101 (99.0%) and 100 HCCs (98.0%) were discernible when applying all MRI criteria for HCC, respectively. Three DNs also fit the HCC criteria, thus the specificity was 90.9% for both observers. With the HCC criteria based on combined gadoxetic acid-enhanced MRI and DWI, it is possible to reliably diagnose small HCC including hypovascular HCCs.

Hepatocellular Carcinoma: Imaging Patterns on Gadoxetic Acid–enhanced MR Images and Their Value as an Imaging Biomarker

To investigate the patterns of imaging appearance of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance (MR) images and to assess their potential value as prognostic markers of HCC associated with tumor recurrence after surgery. The institutional review board approved this retrospective study and informed consent was waived. A total of 216 patients with 304 pathologically proved HCCs underwent gadoxetic acid-enhanced MR imaging prior to surgery and were included in the study. Two reviewers, blinded to the clinical data, evaluated in consensus the imaging patterns of HCC according to enhancement patterns on dynamic phase images and signal intensity on hepatobiliary phase (HBP) images. The association of imaging features with clinical-pathologic findings was evaluated by using the Student t test, χ(2) test, Mann-Whitney U test, and linear-by-linear association. The dependence of time to tumor recurrence (TTR) after surgery was evaluated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. HCCs with atypical enhancement pattern (P = .0167, P = .0450, P < .0001, respectively) and iso- to hyperintensity on HBP images (P = .0001, P = .0002, P < .0001, respectively) had smaller tumor size, lower histologic grade, and worse Child-Pugh class. The log-rank test (P = .0064) and Cox proportional hazards model (hazard ratio, 5.676; P = .0158) revealed that HCCs with iso- to hyperintensity on HBP images had significantly longer TTR than HCCs with hypointensity on HBP images. HCCs can be classified into several imaging patterns on gadoxetic acid-enhanced MR images, which are associated with tumor aggressiveness and outcome. In addition, iso- to hyperintensity on HBP images may be a useful imaging biomarker to indicate longer TTR after surgery. .

Hypovascular Nodules in Patients with Chronic Liver Disease: Risk Factors for Development of Hypervascular Hepatocellular Carcinoma

To identify patient characteristics and magnetic resonance (MR) imaging findings associated with subsequent hypervascularization in hypovascular nodules that show hypointensity on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with chronic liver diseases. Institutional review board approval was obtained, and informed consent was waived. At multiple follow-up gadoxetic acid-enhanced MR imaging examinations of 68 patients, 160 hypovascular nodules were retrospectively reviewed. A Cox regression model for hypervascularization was developed to explore the association of baseline characteristics, including patient factors (Child-Pugh classification, etiology of liver disease, history of local therapy for hepatocellular carcinoma [HCC], and coexistence of hypervascular HCC) and MR imaging findings (fat content, signal intensity on T2-weighted images, and nodule size). In addition, the growth rate was calculated as the reciprocal of tumor volume doubling time to investigate its relationship with subsequent hypervascularization by using receiver operating characteristic and Kaplan-Meier analyses. The prevalence of subsequent hypervascularization was 31% (50 of 160 nodules). Independent Cox multivariable predictors of increased risk of hypervascularization were hyperintensity on T2-weighted images (hazard ratio [HR] = 8.7; 95% confidence interval [CI]: 3.6, 20.8), previous local therapy for hypervascular HCC (HR = 5.0; 95% CI: 1.8, 13.6), Child-Pugh B cirrhosis (HR = 3.6; 95% CI: 1.4, 9.5) and coexistence of hypervascular HCC (HR = 2.0; 95% CI: 1.0, 3.8). The mean growth rate was significantly higher in nodules that showed subsequent hypervascularization than in those without hypervascularization. Kaplan-Meier analysis based on the receiver operating characteristic cutoff level (1.8 × 10(-3)/day [tumor volume doubling time, 542 days]) showed that nodules with a higher growth rate had a significantly higher incidence of hypervascularization (P = 5.2 × 10(-8), log-rank test). Hyperintensity on T2-weighted images is an independent and strong risk factor at baseline for subsequent hypervascularization in hypovascular nodules in patients with chronic liver disease. Tumor volume doubling time of less than 542 days was associated with a high rate of subsequent hypervascularization.

Natural Course of Hypovascular Nodules Detected on Gadoxetic Acid-enhanced MR Imaging: Presence of Fat is a Risk Factor for Hypervascularization

Hypovascular nodules that exhibit hypointensity in hepatocyte-phase images of gadoxetic acid-enhanced magnetic resonance (MR) imaging are frequently encountered in clinical practice. We investigated risk factors for the development of these nodules into hypervascular hepatocellular carcinoma (HCC). We retrospectively reviewed our institutional database and identified 302 patients who underwent gadoxetic acid-enhanced MR imaging for suspected or confirmed HCC from February 1, 2008 to January 30, 2011. We excluded patients who were examined for metastasis of other malignancies or for other hepatic tumors, such as focal nodular hyperplasia. We identified hypovascular nodules that were hypointense in hepatocyte-phase images, recorded their characteristics, and calculated the cumulative hypervascularization rate for nodules that were followed up. Of the 302 patients, 82 had hypovascular nodules (178 nodules; mean size, 9.3 mm). Sixty nodules were followed up for over 6 months, and eight progressed to hypervascular HCC. Hypervascularization occurred more frequently in nodules with fat than those without (P<0.01). The cumulative hypervascularization rate was 5.1% over a year. The presence of intralesional fat was found to be a risk factor for hypervascularization of hypovascular nodules that exhibited hypointensity in the hepatocyte-phase images of gadoxetic acid-enhanced MR imaging.