ORIGINAL ARTICLE 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 Tomoaki Ichikawa, MD,* Kazuhiro Saito, MD,† Naoki Yoshioka, MD,‡ Akihiro Tanimoto, MD,§ Takehiko Gokan, MD,¶ Yasuo Takehara, MD, Takeshi Kamura, MD,** Toshifumi Gabata, MD,†† Takamichi Murakami, MD,‡‡ Katsuyoshi Ito, MD,§§ Shinji Hirohashi, MD,¶¶ Akihiro Nishie, MD, Yoko Saito, MD,*** Hiroaki Onaya, MD,††† Ryohei Kuwatsuru, MD,‡‡‡ Atsuko Morimoto, MD,§§§ Koji Ueda, MD,¶¶¶ Masayo Kurauchi, MAg, and Josy Breuer, MD**** Objectives: To prospectively evaluate the safety and efficacy of combined unenhanced and gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced mag- netic resonance (MR) imaging compared with unenhanced MR imaging and triphasic contrast-enhanced spiral computed tomography (CT) for the detec- tion and characterization of focal liver lesions. Materials and Methods: The study was reviewed and approved by the institutional review board at each of the 15 centers involved in the study, and informed written consent was given by all patients. In total, 178 patients with suspected focal hepatic lesions (based, in most patients, on CT, tumor marker and ultrasound examinations) underwent combined MR imaging with a single, rapid injection of Gd-EOB-DTPA 0.025 mmol/kg, including T1- weighted dynamic and delayed MR images 20 to 40 minutes postinjection. Triphasic contrast-enhanced CT, the comparator examination, was per- formed within 4 weeks of MR imaging. Standard of references (SOR) were resection histopathology and intraoperative ultrasonography, or combined CT during arterial portography and CT hepatic arteriography; in cases where, although the major lesions were treated, some lesion(s) were not treated, follow-up superparamagnetic iron oxide-enhanced MR imaging was addi- tionally performed. All images were assessed for differences in lesion detection and characterization (specific lesion type) by on-site readers and 3, blinded (off-site) reviewers. All adverse events (AEs) occurring within 72 hours after Gd-EOB-DTPA administration were reported. Results: Overall, 9.6% of patients who received Gd-EOB-DTPA reported 21 drug-related AEs. A total of 151 patients were included in the efficacy analysis. Combined MR imaging showed statistically higher sensitivity in lesion detection (67.5%–79.5%) than unenhanced MR imaging (46.5%– 59.1%; P  0.05 for all). Combined MR imaging also showed higher sensitivity in lesion detection than CT (61.1%–73.0%), with the results being statistically significant (P  0.05) for on-site readers and 2 of 3 blinded readers. Higher sensitivity in lesion detection with combined MR imaging compared with CT was also clearly demonstrated in the following subgroups: lesions with a diameter 20 mm (lesions 10 mm: 38.0%–55.4% vs. 26.1%– 47.3%, respectively; lesions 10 –20 mm: 71.1%– 87.3% vs. 65.7%– 78.4%, respectively); in cirrhotic patients (64.5%–75.4% vs. 54.5%–70.3%, respectively); and in patients with hepatocellular carcinoma (66.6%–78.6% vs. 59.1%–71.6%, respectively). Combined MR imaging demonstrated a higher proportion of correctly characterized lesions (50.5%–72.1%) than unenhanced MR imaging (30.2%–50.0%; P  0.05 for all), whereas there were no significant differences compared with CT (49.0%– 68.1%), except for one blinded reader (P  0.05). Conclusion: In this study, hepatocyte-specific Gd-EOB-DTPA was shown to be safe and to improve the detection and characterization of focal hepatic lesions compared with unenhanced MR imaging. When compared with spiral CT, Gd-EOB-DTPA enhanced MRI seems to be beneficial especially for the detection for smaller lesions or hepatocellular carcinoma underlying cirrhotic liver. Key Words: MRI, CT, gadoxetic acid, liver, neoplasms, hepatocellular carcinoma (Invest Radiol 2010;45: 133–141) A lthough the recent evolution of diagnostic radiologic technolo- gies has changed the landscape of hepatic imaging, misdiag- noses during early disease development may prevent patients from receiving optimal treatment. There is insufficient diagnostic perfor- mance for both the early detection and the characterization of small liver lesions even with state-of-the-art computed tomography (CT) and magnetic resonance (MR) imaging techniques. As such, there is a need to improve on morphology-based CT and MR imaging using Received May 29, 2009, and accepted for publication, after revision, October 24, 2009. From the *Department of Radiology, University of Yamanashi, School of Med- icine, Yamanashi, Japan; †Department of Radiology, Tokyo Medical Univer- sity Kasumigaura Hospital, Ibaraki, Japan; ‡Department of Radiology, Uni- versity of Tokyo, School of Medicine, Tokyo, Japan; §Department of Diagnostic Radiology, Keio University, School of Medicine, Tokyo, Japan; ¶Department of Radiology, Showa University, School of Medicine, Tokyo, Japan; Department of Radiology, Hamamatsu University, School of Medi- cine, Shizuoka, Japan; **Department of Radiology, Niigata University, School of Medicine, Niigata, Japan; ††Department of Radiology, Kanazawa University, School of Medicine, Ishikawa, Japan; ‡‡Department of Radiol- ogy, Osaka University Graduate School of Medicine, Osaka, Japan; §§De- partment of Radiology, Yamaguchi University, School of Medicine, Yamagu- chi, Japan; ¶¶Department of Radiology, Nara Medical University Hospital, Nara, Japan; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; ***Department of Radiologi- cal Technology, Hirosaki University School of Health Sciences, Aomori, Japan; †††Department of Radiology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan; ‡‡‡Department of Radiology, Juntendo University, School of Medicine, Tokyo, Japan; §§§Department of Radiology, Osaka Koseinenkin Hospital, Osaka, Japan; ¶¶¶Department of Radiology, Higashiosaka Yamaji Hospital, Osaka, Japan; Clinical Development Diagnostics Imaging, Bayer Yakuhin, Ltd, Osaka, Japan; and ****Global Clinical Development Diagnos- tics, Bayer Schering Pharma AG, Berlin, Germany. Supported by Bayer Yakuhin, Ltd. (formerly Nihon Schering K.K.), Osaka, Japan. Also editorial was supported by Bayer Schering Pharma AG, Berlin, Germany. Reprints: Tomoaki Ichikawa, MD, Department of Radiology, University of Yamanashi, School of Medicine, 1110 Shimokato, Chuo, Yamanashi 409 – 3898, Japan. E-mail: ichikawa@yamanashi.ac.jp. Copyright © 2010 by Lippincott Williams & Wilkins ISSN: 0020-9996/10/4503-0133 Investigative Radiology • Volume 45, Number 3, March 2010 www.investigativeradiology.com | 133