JOURNAL OF MAGNETIC RESONANCE IMAGING 39:42–50 (2014)

Original Research

Hepatic Steatosis: Effect on Hepatocyte Enhancement With Gadoxetate Disodium-Enhanced Liver MR Imaging Hiromitsu Onishi, MD, PhD,1,2* Daniel Theisen, MD,1 Olaf Dietrich, PhD,3 Maximilian F. Reiser, MD,1 and Christoph J. Zech, MD1 Key Words: magnetic resonance imaging; liver; steatosis; gadoxetate disodium (Gd-EOB-DTPA); Dixon technique J. Magn. Reson. Imaging 2014;39:42–50. C 2013 Wiley Periodicals, Inc. V

Purpose: To investigate the effect of hepatic steatosis on enhancement of liver parenchyma with gadoxetate disodium-enhanced MR imaging. Materials and Methods: Gadoxetate disodiumenhanced MR images of 166 patients were analyzed. Liver–spleen contrast and liver–spleen relative enhancement ratio on three-dimensional gradient echo T1weighted images with fat suppression 20 minutes after injection of gadoxetate disodium were evaluated in correlation with fat signal fraction using the Pearson correlation coefficient and also compared between patients with normal liver parenchyma (n ¼ 115) and with liver steatosis (n ¼ 51) using the Student t-test.

NONALCOHOLIC FATTY LIVER disease is the most common chronic liver disease in the United States (1– 3). Hepatic steatosis, which is the initial process in nonalcoholic fatty liver disease (3–5), reduces hepatocellular functional reserve in association with the changes of the metabolism and also influences microcirculation due to obstruction of the sinusoidal space caused by an increase in cell volume (6–8). Moreover, hepatic steatosis can lead to liver cirrhosis and hepatocellular carcinoma (3–5). Gadoxetate disodium (Primovist) is a liver-specific MR imaging contrast agent taken up by hepatocytes (9–11) and facilitates accurate detection of focal liver lesions on MR images during the hepatobiliary phase (12–20). Recently, several studies have reported that liver function and liver fibrosis were well correlated with signal intensities of the liver on gadoxetate disodium-enhanced MR images (21–27). Because hepatic steatosis changes the hepatic metabolism and also can cause fibrosis, hepatic steatosis, and fatty liver disease may affect the enhancement of gadoxetate disodiumenhanced MR imaging in the hepatobiliary phase. Several studies investigated the enhancement pattern of fatty liver diseases in gadoxetate disodium-enhanced MR images in animal models (28–31). They reported that the maximum hepatobiliary enhancement in the nonalcoholic steatohepatitis (NASH) group was higher and the period for the maximum enhancement and the half-life period in the NASH group were prolonged in comparison with the simple fatty liver and control groups (28–31). To the best of our knowledge, however, no study has evaluated the effect of fatty liver disease on enhancement of liver parenchyma with gadoxetate disodium-enhanced MR imaging in human beings. Therefore, the purpose of this study was to retrospectively investigate the effect of hepatic steatosis on enhancement of liver parenchyma with gadoxetate disodium-enhanced MR imaging in humans.

Results: The liver–spleen contrast at hepatobiliary phase showed inverse correlations with the fat signal fraction (r ¼ 0.36; P < 0.01), while the liver–spleen relative enhancement ratio showed no statistical correlation with the fat signal fraction (P ¼ 0.80). The liver–spleen contrast in the group with steatotic liver was significantly lower than that in the group with normal livers (P < 0.001). There was no significant difference in the relative enhancement ratio between the two groups (P ¼ 0.85). Conclusion: Our results may suggest that hepatic steatosis does not affect the uptake of gadoxetate disodium into hepatocytes and are considered crucial as background knowledge in extending the use of gadoxetate disodium-enhanced MR imaging to quantitate liver function.

1 Institute for Clinical Radiology, Ludwig Maximilians-University Hospital Munich, Germany 2 Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan 3 Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Ludwig Maximilians-University Hospital Munich, Germany Dr. Zech’s present address is Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Switzerland; Contract grant sponsor: Japanese Society for Magnetic Resonance in Medicine. Contract grant sponsor: Japan Society for the Promotion of Science; Contract grand number: 24591761. *Address reprint requests to: H.O., Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan, Yamadaoka 2-2, Suita, Osaka, 565–0871, Japan. E-mail: [email protected] Received October 22, 2012; Accepted February 26, 2013 DOI 10.1002/jmri.24136 View this article online at wileyonlinelibrary.com. C 2013 Wiley Periodicals, Inc. V

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MATERIALS AND METHODS Study Population This study was performed in accordance with the principles of the Declaration of Helsinki (32). The ethics committee at our institution deemed that approval of this study was unnecessary due to the retrospective character of the evaluation. Consecutive 533 patients who underwent gadoxetate disodium-enhanced liver MR imaging for the evaluation of liver diseases between April and September, 2010, were eligible for the study. However, 367 (69%) of these patients were excluded from the study population for the following reasons; (a) lack of total bilirubin data in blood test (n¼64), (b) hyperbilirubinemia (higher than 1.0 mg/dL, n¼209), (c) suspected of having liver cirrhosis (n¼30), (d) states after splenectomy (n¼9), (e) having huge and/or diffuse liver tumors or diseases other than steatosis (n¼22), (f) severe imaging artifacts (n¼3), and (g) use of nonstandard MR acquisition protocols (n¼30). The patients with hyperbilirubinemia or suspected of having liver cirrhosis were excluded to prevent the effect of bilirubin or fibrosis on liver enhancement with gadoxetate disodium-enhanced MR imaging (23,25,33). In the present study, the suspicious of having liver cirrhosis was determined with reference to the morphological change of the liver on MR images and the blood test data (i.e., aspartate aminotransferase-to-platelet ratio index). The remaining 166 patients (82 men and 84 women; mean age, 58 years; range, 18–84 years) constituted the study population (Fig. 1). MR Imaging MR imaging was performed with a 1.5 Tesla (T) system (n¼116) (Magnetom Avanto; Siemens Healthcare, Erlangen, Germany) or a 3.0T system (n ¼ 50) (Magnetom Verio; Siemens Healthcare) with body array coils. For contrast enhancement, 10 mL of gadoxetate disodium (Primovist; Bayer-Schering Pharma AG, Berlin, Germany) was administered intravenously with a mechanical power injector at 1 mL/s through a catheter inserted into an arm vein, followed by 20 mL of a saline flush. The standard MR acquisition protocol for liver assessment using gadoxetate disodium in our institution included in-phase and out-of-phase gradient

Figure 1. Flowchart of patient enrollment.

echo T1-weighted images, gadoxetate disodiumenhanced dynamic images (precontrast, arterial, and portal venous dominant phase), and hepatobiliary phase images 20 min after injection of the contrast agent using three-dimensional (3D) gradient echo T1weighted images, which were evaluated in the present study. Acquisition parameters are listed in Table 1.

Quantitative Image Analysis The regions of interest (ROIs) for the liver and spleen parenchyma were drawn from the same axial images for each sequence by an abdominal radiologist (blinded data) with 15 years of experience using a

Table 1 MR Imaging Sequences and Parameters Acquisition 1.5T T1 in-phase T1 out-of-phase Dynamic & HBP 3.0T T1 in-phase T1 out-of-phase Dynamic & HBP

Sequence

TR (ms)

TE (ms)

Flip angle (degrees)

Matrix size

Thickness (mm)

Fat suppression

2D GRE 2D GRE 3D GRE

120 110 3.35

4.76 2.50 1.19

70 70 15

320 x 168 320 x 168 256 x 154

6 6 3

Not used Not used Used

2D GRE 2D GRE 3D GRE

115 120 3.67

2.46 3.69 1.30

50 50 12

320 x 216 320 x 216 320 x 224

5 5 3

Not used Not used Used

TR ¼ repetition time; TE ¼ echo time; 2D ¼ two-dimensional; 3D ¼ three-dimensional; GRE ¼ gradient echo; HBP ¼ hepatobiliary phase image.

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picture archiving and communication system (Syngo Imaging, Siemens Healthcare). For measuring signal intensities, two ROIs, each 1.0 cm2 or larger, were placed in the right and left lobe of the liver as well as in the spleen, excluding large vessels. To prevent disturbing effects of receiver coils sensitivity or B1 inhomogeneity, the ROIs were carefully placed at the same

place of the anatomy among the different sequence images for each patient. The fat deposition in the liver parenchyma was evaluated using the signal intensities on in-phase and out-of-phase MR images. Fat signal fraction was calculated according to the following equation (3,34); Fat signal fraction (%)

 SI in-phase; liver =SI in-phase; spleen –SI out -of -phase ; liver =SI out-of -phase ; spleen  ¼  100 2 SI in-phase ; liver =SI in -phase ; spleen

SI: signal intensity Because the in- and out-of-phase images were not simultaneously acquired in the present study, signal intensities of liver parenchyma were divided by that of spleen in each phase to correct and the slightly different repetition times in two acquisitions (34). When the

Liver –spleen Liver –spleen

contrast contrast

Liver –spleen

relative

calculated value was lower than 0, the fat signal fraction was treated as 0. For assessment of the effect on the enhancement degree of liver parenchyma, liver–spleen contrast (signal ratio) and liver–spleen relative enhancement ratio were calculated according to the following equations (22,23);

ðprecontrast Þ ¼ SIpre; liver =SIpre ; spleen ðhepatobiliary phase Þ ¼ SI HBP; liver =SIHBP; spleen  SIHBP; liver =SIpre; liver  enhancement ratio ¼ SI HBP; spleen =SIpre; spleen

HBP: hepatobiliary phase Qualitative Image Analysis The fat distribution patterns whether homogeneous or not were determined based on the findings on inphase and out-of-phase images. In the patients with a steatotic liver with inhomogeneous or nonuniform fat distribution, comparing hepatobiliary phase images with the corresponding in- and out-of-phase T1weighted images, the differences of hepatobiliary enhancement of the liver parenchyma between at the fat deposition area and the sparing area were visually analyzed. Two blinded radiologists reviewed the MR images and evaluated the signal intensity at these areas on the hepatobiliary phase images by consensus. Statistical Analysis The Pearson correlation coefficient was used to evaluate the liver–spleen contrast and liver–spleen relative enhancement ratio in correlations with the fat signal fraction, respectively. In the present study, patients with less than 6% of the fat signal fraction were assigned to the normal liver group and the patients with 6% or more to the steatotic liver group (2,35). The liver–spleen contrast and liver–spleen relative enhancement ratio were compared using Student t-test between the two groups. Statistical analyses were performed for all patients and also for the subgroups of patients who underwent MR examination at different magnetic field strengths,

1.5T and 3.0T. A P value of less than 0.05 indicates a significant difference. RESULTS In the 166 patients, 51 patients (31%) were assigned to the steatotic liver group. Patients’ backgrounds in each group are shown in Table 2. The liver–spleen contrast at precontrast and hepatobiliary phase showed inverse correlations with the fat signal fraction (r ¼ 0.46, 0.36, P < 0.01 and .01, respectively; Fig. 2a, b), while the liver–spleen relative signal enhancement ratio showed no statistical correlation with the fat signal fraction (r ¼ 0.02; P ¼ 0.80; Fig. 2c). Table 2 Patient Backgrounds Characteristics Gender Male Female Age (years) Body weight (kg)a Total bilirubin (mg/dL) MR system 1.5T 3.0T Fat signal fraction (%) a

Normal liver group (n ¼ 115)

Steatotic liver group (n ¼ 51)

n ¼ 58 n ¼ 57 58 6 13 (18–84) 72 6 12 0.60 6 0.20

n ¼ 24 n ¼ 27 58 6 13 (27–80) 77 6 17 0.63 6 0.23

n ¼ 87 n ¼ 28 1.4 6 1.9

n ¼ 29 n ¼ 22 17.4 6 8.5

P values

¼ 0.69 ¼ 0.97 ¼ 0.28 ¼ 0.46

< 0.05 < 0.001

Patients’ body weight was evaluated for 39 patients in the normal and for 17 in the steatotic liver group within the extent that the data were available.

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Figure 2. Scatter plots for all patients. The liver–spleen contrast at precontrast (a) and hepatobiliary phase (b) showed inverse correlations with the fat signal fraction (r ¼ 0.46; P < 0.01; r ¼ 0.36, P < 0.01, respectively), whereas the liver–spleen relative signal enhancement ratio did not show a statistical correlation with the fat signal fraction (c).

The liver–spleen contrast at precontrast and hepatobiliary phase images in the steatotic liver group was significantly lower than in the normal liver group, respectively (P < 0.001 and 0.001, respectively). However, there was no statistically significant difference in the liver–spleen relative signal enhancement ratio between the two groups (P ¼ 0.85). For the subgroup of patients examined at 1.5T, the liver–spleen contrast at precontrast and hepatobiliary phase in the steatotic liver group was significantly

lower than in the normal liver group, respectively (P < 0.001 and 0.001, respectively). For the subgroup of patients who underwent MR imaging at 3.0T, there was no statistically significant difference in the liver– spleen contrast at hepatobiliary phase between two groups. The detailed results are shown in Table 3. The scatter plots for the subgroup data are also shown in Figures 3 and 4. For the qualitative analysis, inhomogeneous or nonuniform fat distribution in the liver was recognized in

Table 3 Relationship of Liver–Spleen Contrast and Relative Enhancement Ratio With Hepatic Steatosis

All MR imaging (n ¼ 166) Liver-spleen contrast (precontrast) Liver-spleen contrast (hepatobiliary phase) Liver-spleen relative enhancement ratio MR imaging at 1.5T (n ¼ 116) Liver-spleen contrast (precontrast) Liver-spleen contrast (hepatobiliary phase) Liver-spleen relative enhancement ratio MR imaging at 3.0T (n ¼ 50) Liver-spleen contrast (precontrast) Liver-spleen contrast (hepatobiliary phase) Liver-spleen relative enhancement ratio

Normal liver group

Steatotic liver group

P values

1.43 6 0.25 2.24 6 0.52 1.57 6 0.26

1.20 6 0.21 1.87 6 0.38 1.56 6 0.22

< 0.001 < 0.001 ¼ 0.85

1.51 6 0.23 2.37 6 0.51 1.57 6 0.26

1.30 6 0.16 2.00 6 0.37 1.53 6 0.25

< 0.001 < 0.001 ¼ 0.49

1.20 6 0.15 1.86 6 0.31 1.56 6 0.25

1.07 6 0.19 1.70 6 0.33 1.60 6 0.16

< 0.001 ¼ 0.08 ¼ 0.53

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DISCUSSION The use of gadoxetate disodium-enhanced liver MR imaging has extended to the quantitative evaluation of liver function (21–27). The advantages of the evaluation with gadoxetate disodium-enhanced liver MR imaging are that it is a noninvasive method and can denote regional hepatic function. However, more basic knowledge about the various factors that can affect the hepatobiliary enhancement other than fibrosis

Figure 3. Scatter plots for patients examined at 1.5T. The liver–spleen contrast at precontrast (a) and hepatobiliary phase (b) showed inverse correlations with the fat signal fraction (r ¼ 0.41, P < 0.01, r ¼ 0.29, P < 0.01, respectively), whereas the liver–spleen relative signal enhancement ratio did not show a statistical correlation with the fat signal fraction (r ¼ 0.01; P ¼ .94) (c).

seven patients (Figs. 5 and 6). Among these seven patients, three patients had homogeneous and the remaining four patients inhomogeneous enhancement of the liver parenchyma in the hepatobiliary phase images. Of the four patients with inhomogeneous liver enhancement, the signal intensity decreased in the area fat deposition in three patients, while it increased in one patient (Figs. 5 and 6)

Figure 4. Scatter plots for patients examined at 3.0T. The liver–spleen contrast at precontrast (a) and hepatobiliary phase (b) showed inverse correlations with the fat signal fraction (r ¼ 0.44, P < 0.01, r ¼ 0.35, P < 0.05, respectively), whereas the liver–spleen relative signal enhancement ratio did not show a statistical correlation with the fat signal fraction(r ¼ 0.03, P ¼ 0.81) (c).

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Figure 5. MR images of inhomogeneous severe hepatic steatosis at 3.0T. In-phase image (a), out-of-phase image (b), precontrast fat-suppressed 3D gradient echo T1-weighted image (c), and hepatobiliary phase image (d). The signal intensity of the liver on the hepatobiliary phase image is decreased inhomogeneously depending on the fat distribution.

and cirrhosis is absolutely essential to apply its potential to functional imaging widely in the clinical practice (36). In particular, to investigate the effect of hepatic steatosis is considered crucial because of the high prevalence of hepatic steatosis (i.e., 31–33% in the United States) (1,2). The liver–spleen contrast at precontrast images and at hepatobiliary phase images 20 min after injection of gadoxetate disodium showed an inverse correlation with the fat signal fraction and the steatotic liver group demonstrated significantly lower liver–spleen contrast than the normal liver group. However, the liver–spleen relative signal enhancement ratio showed no statistical correlation with the fat signal fraction and was not significantly different between the steatotic and nonsteatotic group. In consideration of the result that the liver–spleen contrast on the precontrast images using a 3D gradient echo sequence with fat suppression showed an inverse correlation with the fat signal fraction, the liver–spleen contrast at hepatobiliary phase may be affected mainly by the change of precontrast signal intensity of the liver due to the fat deposition rather than the change of liver function to take up gadoxetate disodium into hepatocytes. It can be assumed that in the patients with liver

steatosis the lower signal intensity of the liver was responsible for the lower liver–spleen contrast on the 3D gradient echo sequence with fat suppression. The lower signal intensity of the liver will also reduce the contrast between hepatic lesions and liver parenchyma at hepatobiliary phase images. This may adversely affect the evaluation of liver tumors in clinical studies. In the subgroup analyses of 1.5T and 3T MR systems, there were no significant differences in the liver–spleen contrast at hepatobiliary phase between normal patients or patients with liver steatosis at 3.0T MRI examinations. One of the reason for the discrepancy between the results at 3.0T and 1.5T may be B1 inhomogeneity at 3.0T body MR imaging (37). The patient-to-patient variability in the signal change due to B1 inhomogeneities is considered to eliminate the contrast differences at 3.0T between the two patient groups. In addition, longer T1 of water at 3.0T would make fat fraction higher at 3.0T due to T1 bias (38). However, in-phase and out-ofphase two-dimensional T1-weighted imaging were acquired with longer TR (i.e., 115–120 ms) in the present study. This might reduce the influence of T1 bias in this study (38).

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Figure 6. MR images of nonuniform hepatic steatosis at 1.5T. In-phase image (a), out-of-phase image (b), precontrast fat-suppressed 3D gradient echo T1-weighted image (c), and hepatobiliary phase image (d). The signal intensity on the hepatobiliary phase image increased at the fat distribution area (*) in this patient.

In the qualitative analysis, the fat distribution areas in the inhomogeneous steatotic liver demonstrated variable signal intensities on the hepatobiliary phase images compared with the areas less involved by fat deposition. This variability may be caused by underlying pathological or molecular biological conditions of liver parenchyma developed in association with fat deposition. On the basis of the negative correlation between liver fibrosis score and signal intensities of the liver on gadoxetate disodium-enhanced MR images (23,25), the enhancement ratio may be decreased in patients with NASH, which present with liver fibrosis and inflammatory conditions. However, Sonoda et al reported in their study using a rabbit model that the maximum enhancement ratio in NASH group was higher than that in normal liver group or fatty liver group (29). More investigations including the issue of the effect of inflammation are needed to resolve this discrepancy. In clinical practice, inhomogeneous distribution of fat in the liver can cause diagnostic confusion by mimicking neoplastic, inflammatory, or vascular conditions (39). Although in-phase and out-of-phase MR imaging is widely accepted as a standard method for diagnosis of fat deposition, it might be difficult to

distinguish focal fat deposition from fat containing tumors in some conditions (3). Gadoxetate disodiumenhanced MR imaging is often used for the differential diagnosis of the focal liver lesions (16–20). Our results on the spectrum of gadoxetate disodium-enhanced MR image findings in the patients with liver steatosis may help the accurate diagnosis in difficult cases with unusual fat distribution pattern. The present study has various limitations. First, the hepatic steatosis was not proved histologically and our study population could include various steatotic liver diseases (i.e., simple steatosis, alcoholic steatohepatitis, nonalcoholic steatohepatitis, etc.). Each disease may potentially show different results in the gadoxetate disodium enhancement. Second, in- and out-of-phase MR imaging, not MR spectroscopy, was used to obtain the fat signal fraction as the reference standard. Although MR spectroscopy is considered the most accurate MR method for liver fat quantification, the in- and out-of-phase MR imaging also provide the fat signal fraction well correlated with that obtained by the MR spectroscopy (2,34,35,40,41). Third, an influence of patients’ body weight may be a potential limitation in this study, because a fixed dose of gadoxetate disodium was injected for each patient.

Hepatocyte Enhancement in Steatosis

However, the influence on the hepatic enhancement can be corrected to some degree by means of dividing the signal intensity of the liver by that of the spleen, because the enhancement of the liver, as well as that of the spleen, is expected to decrease inversely with the body weight. Finally, because of the retrospective analyses using the images in the standard MR protocol, hepatic iron deposition was not assessed. Hepatic iron deposition can cause overestimation of the fat signal fraction at 3.0T and underestimation at 1.5T in the in- and out-of-phase MR imaging. This might lead to misclassification of the subjects with iron overload to the groups and potentially contribute the different prevalence of steatotic liver between 1.5T and 3.0T in this study. In conclusion, our results demonstrate that there is no significant difference in the enhancement ratio of the liver between patients with normal liver and the patients with hepatic steatosis, although signal intensity of the liver in patients with hepatic steatosis is significantly lower than that in normal patients on precontrast and hepatobiliary phase gadoxetate disodium-enhanced T1-weighted 3D gradient echo MR images with fat suppression. These findings may suggest that hepatic steatosis does not affect the uptake function of gadoxetate disodium into hepatocytes, although further investigations considering aspects of pathology and molecular biology will be needed, and are crucial as background knowledge in extending the use of gadoxetate disodium-enhanced MR imaging to quantitate liver function.

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REFERENCES 1. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395. 2. Szczepaniak LS, Nurenberg P, Leonard D, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005;288:E462–E468. 3. Reeder SB, Sirlin C. Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am 2010;18:337– 357. 4. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116: 1413–1419. 5. Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA, Boparai N, Younossi ZM. Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Hum Pathol 2004;35:196–199. 6. Imber CJ, St. Peter SD, Handa A, Friend PJ. Hepatic steatosis and its relationship to transplantation. Liver Transpl 2002;8:415– 423. 7. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl 2003;9:651–663. 8. Guiu B, Petit JM, Capitan V, et al. Intravoxel incoherent motion diffusion-weighted imaging in nonalcoholic fatty liver disease: a 3.0-T MR study. Radiology 2012;265:96–103. 9. Schuhmann-Giampieri G, Schmitt-Willich H, Press WR, Negishi C, Weinmann HJ, Speck U. Preclinical evaluation of Gd-EOBDTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology 1992;183:59–64. 10. Weinmann HJ, Schuhmann-Giampieri G, Schmitt-Willich H, Vogler H, Frenzel T, Gries H. A new lipophilic gadolinium chelate as a tissue-specific contrast medium for MRI. Magn Reson Med 1991;22:222–228. 11. Tsuboyama T, Onishi H, Kim T et al. Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced

21.

22.

23.

24.

25.

26.

27.

28.

29.

MR imaging – correlation with expression of sinusoidal and canalicular transporters and bile accumulation. Radiology 2010;255: 824–833. Onishi H, Kim T, Imai Y, et al. Hypervascular hepatocellular carcinomas: detection with gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT. Eur Radiol 2012;22:845– 854. Sano K, Ichikawa T, Motosugi U, et al. Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging. Radiology 2011;261:834–844. Di Martino M, Marin D, Guerrisi A, et al. Intraindividual comparison of gadoxetate disodium-enhanced MR imaging and 64-section multidetector CT in the detection of hepatocellular carcinoma in patients with cirrhosis. Radiology 2010;256:806–816. Ichikawa T, Saito K, Yoshioka N, et al. Detection and characterization of focal liver lesions: a Japanese phase III, multicenter comparison between gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced computed tomography predominantly in patients with hepatocellular carcinoma and chronic liver disease. Invest Radiol 2010;45:133–141. Grazioli L, Bondioni MP, Haradome H, et al. Hepatocellular adenoma and focal nodular hyperplasia: value of gadoxetic acidenhanced MR imaging in differential diagnosis. Radiology 2012;262:520–529. Purysko AS, Remer EM, Coppa CP, Obuchowski NA, Schneider E, Veniero JC. Characteristics and distinguishing features of hepatocellular adenoma and focal nodular hyperplasia on gadoxetate disodium-enhanced MRI. AJR Am J Roentgenol 2012;198:115– 123. Bieze M, van den Esschert JW, Nio CY, et al. Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium. AJR Am J Roentgenol 2012;199:26–34. Motosugi U, Ichikawa T, Onohara K, et al. Distinguishing hepatic metastasis from hemangioma using gadoxetic acid-enhanced magnetic resonance imaging. Invest Radiol 2011;46:359–365. Sun HY, Lee JM, Shin CI, et al. Gadoxetic acid-enhanced magnetic resonance imaging for differentiating small hepatocellular carcinomas (< or ¼2 cm in diameter) from arterial enhancing pseudolesions: special emphasis on hepatobiliary phase imaging. Invest Radiol 2010;45:96–103. Yamada A, Hara T, Li F, et al. Quantitative evaluation of liver function with use of gadoxetate disodium-enhanced MR imaging. Radiology 2011;260:727–733. Motosugi U, Ichikawa T, Sou H, et al. Liver parenchymal enhancement of hepatocyte-phase images in Gd-EOB-DTPAenhanced MR imaging: which biological markers of the liver function affect the enhancement? J Magn Reson Imaging 2009;30:1042–1046. Motosugi U, Ichikawa T, Oguri M, et al. Staging liver fibrosis by using liver-enhancement ratio of gadoxetic acid-enhanced MR imaging: comparison with aspartate aminotransferase-to-platelet ratio index. Magn Reson Imaging 2011;29:1047–1052. Cho SH, Kang UR, Kim JD, Han YS, Choi DL. The value of gadoxetate disodium-enhanced MR imaging for predicting posthepatectomy liver failure after major hepatic resection: a preliminary study. Eur J Radiol 2011;80:e195–200. Watanabe H, Kanematsu M, Goshima S, et al. Staging hepatic fibrosis: comparison of gadoxetate disodium-enhanced and diffusion-weighted MR imaging-preliminary observations. Radiology 2011;259:142–150. Katsube T, Okada M, Kumano S, et al. Estimation of liver function using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Invest Radiol 2011;46:277–283. Kim T, Murakami T, Hasuike Y, et al. Experimental hepatic dysfunction: evaluation by MRI with Gd-EOB-DTPA. J Magn Reson Imaging 1997;7:683–688. Tsuda N, Okada M, Murakami T. Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol 2007;42:242–247. Sonoda A, Nitta N, Ohta S, et al. The Possibility of differentiation between nonalcoholic steatohepatitis and fatty liver in rabbits on Gd-EOB-DTPA-enhanced open-type MRI scans. Acad Radiol 2011;18:525–529.

50 30. Tsuda N, Matsui O. Signal profile on Gd-EOB-DTPA-enhanced MR imaging in non-alcoholic steatohepatitis and liver cirrhosis induced in rats: correlation with transporter expression. Eur Radiol 2011;21:2542–2550. 31. Tsuda N, Okada M, Murakami T. New proposal for the staging of nonalcoholic steatohepatitis: evaluation of liver fibrosis on Gd-EOB-DTPA-enhanced MRI. Eur J Radiol 2010;73:137–142. 32. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Organ 2001;79:373–374. 33. Higaki A, Tamada T, Sone T, et al. Potential clinical factors affecting hepatobiliary enhancement at Gd-EOB-DTPA-enhanced MR imaging. Magn Reson Imaging 2012;30:689–693. 34. Cowin GJ, Jonsson JR, Bauer JD, et al. Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging 2008;28:937–945. 35. Noworolski SM, Lam MM, Merriman RB, Ferrell L, Qayyum A. Liver steatosis: concordance of MR imaging and MR spectroscopic data with histologic grade. Radiology 2012;264:88–96.

Onishi et al. 36. Sahani DV, Agarwal S, Chung RT. The double-edged sword of functional liver imaging. Radiology 2012;264:621–623. 37. Merkle EM, Dale BM. Abdominal MRI at 3.0 T: the basics revisited. AJR Am J Roentgenol 2006;186:1524–1532. 38. Hansen KH, Schroeder ME, Hamilton G, Sirlin CB, Bydder M. Robustness of fat quantification using chemical shift imaging. Magn Reson Imaging 2012;30:151–157. 39. Hamer OW, Aguirre DA, Casola G, Lavine JE, Woenckhaus M, Sirlin CB. Fatty liver: imaging patterns and pitfalls. Radiographics 2006;26:1637–1653. 40. Reeder SB, Robson PM, Yu H, et al. Quantification of hepatic steatosis with MRI: the effects of accurate fat spectral modeling. J Magn Reson Imaging 2009;29:1332–1339. 41. Kim H, Taksali SE, Dufour S, et al. Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL. Magn Reson Med 2008;59:521–527.

Hepatic steatosis: effect on hepatocyte enhancement with gadoxetate disodium-enhanced liver MR imaging.

To investigate the effect of hepatic steatosis on enhancement of liver parenchyma with gadoxetate disodium-enhanced MR imaging...
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