Hyperplasia / Hypertrophy, Cirrhosis, Diagnostic procedure, MR, CT-Angiography, CT, Liver, Abdomen /ecr2012/C-2202

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1 Hepatic nodules showing ring-like enhancement on hepatobiliary phase of Gd-EOB-DTPA enhanced MRI can be divided into two subtypes based on blood supply: FNH and NRH-like nodules Poster No.: C-2202 Congress: ECR 2012 Type: Scientific Exhibit Authors: K. Kozaka 1, N. Yoneda 1, S. Kobayashi 1, A. Kitao 1, Y. Ryu 1, T. Minami 1, W. Koda 1, T. Gabata 2, O. Matsui 1 ; 1 Kanazawa/JP, 2 Kanazawa City/JP Keywords: DOI: Hyperplasia / Hypertrophy, Cirrhosis, Diagnostic procedure, MR, CT-Angiography, CT, Liver, Abdomen /ecr2012/C-2202 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 14

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3 Purpose Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), which is a new MR contrast agent and works both an extracellular and hepatocytespecific contrast agent, has been proved to be highly effective in the detection and characterization of hepatic mass lesions. Most of hepatic cancers including hepatocellular carcinoma, cholangiocellular carcinoma and metastatic liver cancer are shown as hypointense nodules on the hepatobiliary (HB) phase of Gd-EOB-DTPA enhanced MRI (EOB- MRI). On the other hand, we often encounter the ring-like enhanced nodules on HB phase of EOB-MRI in the patient with various liver disease includes viral related cirrhosis, alcoholic liver disease, idiophathic portal hypertension or normal liver. The purpose of this study was to elucidate the subtypes of the hepatic nodules showing ring-like enhancement on HB phase of EOB-MRI based on intranodular blood supply evaluated by angiography-assisted CT and their prognosis. Methods and Materials Definition of "ring-like enhancement" on HB phase of EOB-MRI An entirely hyperintense nodule relative to the surrounding liver parenchyma with hypointense central portion was defined as "ring-like enhancement. However, the shape of the central hypointense portion was not always round but scar -like in some cases. In addition, the thickness of the peripheral enhanced portion was variable. Therefore, "donut-like enhancement" was also included in the definition. (Fig. 2, 3) Materials A total of 130 hepatic nodules showing ring-like enhancement on HB phase of EOB-MRI in 20 patients who also received both CT during arterial portography (CTAP) and CT during hepatic arteriography CTHA) were subjected to the study (Table 1). The patients were divided into three groups based on the nature of the background liver, namely liver cirrhosis (cirrhosis group, n=92), idiopathic portal hypertension (IPH group, n=30) and normal liver (normal group, n=8). Methods MR Imaging All individuals underwent MR imaging of the liver using a 1.5- or 3-Tesla MR system (Signa HDx; GE Healthcare, Milwaukee, Wis., USA). Each patient received an Page 3 of 14

4 intravenous bolus injection of Gd-EOB-DTPA (gadoxetic acid; Bayer Schering Pharma, Osaka, Japan) as contrast agent at a dose of 25 µmol/kg body weight at a flow rate of 2 ml/sec, followed by a 20-mL saline flush. Dynamic as well as delayed imaging were performed using a fat-suppressed 3D T1-weighted GRE sequence employing parallel imaging (LAVA EFGRE ASSET breathhold: TR/TE=3.1 msec/1.4 msec; flip angle, 15 ; field of view, cm; matrix, , interpolated to ; thickness, 4 mm; overlap 2 mm; ASSET acceleration, 2.0). HB phase was obtained 20 min. after the contrast injection. CTAP and CTHA Examinations A 4-French catheter was selectively placed in the superior mesenteric artery for CTAP or in the common or proper hepatic artery for CTHA. Scanning parameters were as follows: number of detector rows, 64; section thickness, 0.5 mm; table feed per rotation, 7.2 mm; reconstruction intervals, 3 mm; gantry rotation time, 400 msec; tube voltage, 120 kvp; and tube current, 400 ma. For CTAP, helical CT scanning began 24 sec after an infusion of 50 ml of iohexol (320 mg of iodine/ml) (Omnipaque; Daiichi, Tokyo, Japan) at 1.8 ml/sec was begun. Immediately before the injection of contrast medium, 5 µg of prostaglandin E1 (Palux; Taisyo, Tokyo, Japan) was injected into the superior mesenteric artery. Approximately 10 min after CTAP was performed, CTHA was obtained with 3-mm reconstruction intervals. CTHA began 7 sec after injection of iohexol (320 mg iodine/ml) at 2 ml/sec was begun. Image analysis Hepatic nodules showing above defined "ring-like enhancement on HB phase of EOB- MRI were depicted from the radiological records of Kanazawa University Hospital by two experienced radiologists and the intranodular blood supply in each nodule was analyzed by CTAP and CTHA. Pathological analysis The pathological diagnosis was performed only in the limited cases. Follow up for nodules in cirrhosis group Possible malignant transformation (transformation to the typical hypervascular HCC) was analyzed by follow-up study. Images for this section: Page 4 of 14

5 Table 1: Main clinical features. Page 5 of 14

6 Results Results 1. The intranodular blood supply evaluated by angiography assisted CT (CTAP and CTHA) The angiography assisted CT findings was summarized in Fig. 1. On CTAP, almost the same or increased intranodular portal supply relative to the surrounding liver was shown in all of 130 nodules seen in cirrhosis and IPH groups. In 85/93 nodules in cirrhosis group and 25/30 nodules in IPH group, tiny portal venules distributed from the central portion of the nodule were identified on CTAP. In contrast, all 8 nodules in normal group showed portal perfusion defect on CTAP. On CTHA, all of the nodules in cirrhosis and IPH groups showed the same or decreased intranodular arterial supply compared with surrounding liver. In contrast all nodules in normal group demonstrated increased arterial supply with not less frequently strong central spotty enhancement on CTHA. Result 2. Pathologic features #Cirrhosis group Two nodules were diagnosed as hyperplastic lesion without cellular atypia by fine needle biopsy. #IPH group One nodule was diagnosed as hyperplastic lesion without cellular atypia by fine needle biopsy and other nodules was surgically resected during splenectomy and proven as nodular regenerative nodule (NRH) #Normal group Two nodules were diagnosed as hyperplastic nodule by fine needle biopsy, but the limited specimen could not to be affirmed as focal nodular hyperplasia (FNH) because definite central scar was not evident. However, in conjunction with imaging features, they were diagnosed as FNH. Result 3. Follow up study of the nodules in cirrhosis group 90/92 nodules in cirrhosis group were followed-up. Observation period was 468±282, range days. Imaging modality was variable (angiography assisted CT 1, dynamic CT 5, dynamic MRI (Gd-EOB-DTPA) 3). 2 nodules were treated by radiofrequency ablation therapy at the time of detection. No malignant transformation (arterial hypervascularization) were found. Images for this section: Page 6 of 14

7 Fig. 1: The intranodular blood supply evaluated by angiography assisted CT (CTAP and CTHA). Page 7 of 14

8 Fig. 2: 52 year-old male with fatty liver. A. EOB-MRI revealed a hyper-intensity nodule (arrow) in segment 6 sized 14mm in diameter with central hypo-intensity scar (dashed arrow). B. CTAP showed distinctly portal defect. C. CTHA 1st phase. The nodule was clearly enhanced with central feeding arteries. D. H-E stain. The pathologic specimen from fine needle biopsy. The nodule was consisted of multi-thickened hepatocytes without cellular atypia. Though this specimen didn't include the focus of central scar but the nodule was diagnosed as focal nodular hyperplasia in conjunction with pathologic and radiologic findings. Page 8 of 14

9 Fig. 3: 78 year-old male with normal liver. A. EOB-MRI revealed a hyper-intensity nodule in segment * sized in diameter. (arrow). B. CTAP showed distinctly portal defect. C. CTHA 1st phase. The nodule was clearly enhanced with central feeding arteries. The nodule was diagnosed as focal nodular hyperplasia based on imaging findings. Page 9 of 14

10 Fig. 4: 78 year-old male with idiopathic portal hypertension (IPH) without HCC burden. A. Hepatobiliary phase of EOB-MRI revealed a hyperintense nodule in segment 2 with central hypointensity sized 17mm in diameter (arrow). B. CTAP showed hyperattenuation relative to the surrounding liver parenchyma indicating increased intranodular portal supply. Tiny portal venules were identified in the nodule. C. The nodule demonstrated hypo-attenuation relative to surrounding hepatic parenchyma on CTHA. Histological diagnosis was nodular regenerative hyperplasia (not shown). Note: There were many nodules with the same blood supply and Gd-EOB-DTPA uptaking here and there (dashed arrow in Fig. 4a.). Page 10 of 14

11 Fig. 5: 63 year-old male with alcoholic related liver fibrosis without HCC burden. A. Hepatobiliary phase of EOB-MRI revealed multiple hyper-intense nodules (arrow) with hypo-intense central portion. In this study we excluded the nodules less than 5mm in diameter because the central hypo-intensity was difficult to evaluate. B. The nodules showed hyper-attenuation relative to the surrounding liver parenchyma on CTAP indicating abundant intranodular portal supply. Segment 4 nodule also demonstrated an intra-lesional portal venule. *; portal perfusion defect due to large A-P shunting. C. The nodules were almost iso-attenuation relative to the surrounding hepatic parenchyma on CTHA 1st phase. D. The pathologic specimen obtained by fine needle biopsy showed hyperplastic change without cellular atypia and slightly dilated hepatic sinusoids (H-E stain). We diagnosed this nodule as NRH-like nodule rather than FNH-like nodule which often arising in alcoholic liver because of the similarity with NRH as shown in Fig days follow-up showed no malignant transformation. Page 11 of 14

12 Fig. 6: 72 year-old male with HCV related cirrhosis without HCC burden. A. Hepatobiliary phase of EOB-MRI revealed a hyper-intense nodule with central scar-like hypo-intensity (included in the definition of "ring-like enhancement") sized 11.3mm in diameter in S7. B. CTAP showed hyper-attenuation relative to the surrounding liver parenchyma indicating abundant intranodular portal supply. A tiny portal venule in the nodule was depicted (white arrow). C. The nodule demonstrated hypo-attenuation relative to the surrounding hepatic parenchyma CTHA. D. The pathologic specimen obtained by fine needle biopsy showed hyperplastic change without cellular atypia and slightly dilated hepatic sinusoids (H-E stain). We diagnosed this nodule as NRH-like nodule in conjunction with both pathological and radiological findings similar to those of NRH as shown in Fig. 4. Page 12 of 14

13 Conclusion The ring-like enhanced nodules (including hyper-intense nodule with internal scar-like hypo-intensity) on HB phase of EOB-MRI in IPH with increased intranodular portal supply and normal liver with increased intranodular arterial supply were diagnosed as NRH and FNH respectively in conjunction with pathologic and radiologic findings. On the other hand, the ring-like enhanced nodules in cirrhosis showed almost the same blood supply with NRH in IPH and although there were limited cases, histological findings were also similar to those of NRH. Therefore, we diagnosed them as NRH-like nodule. The fact that these nodules demonstrated no malignant transformation in our study may support these nodules were not neoplastic but hyperplastic nodules. To date, in the cirrhotic liver, although such nodules like NRH is not well known, these are not less frequently seen on EOB-MRI. We think it is important to know such entity for correct imaging interpretation of liver imaging. In conclusion, hepatic nodules showing ring-like enhancement on HB phase can be divided into NRH-like nodules fed by portal vein and FNH fed by hepatic artery. NRH-like nodule is often seen in cirrhotic livers and may not have malignant potential. References Terminology of nodular hepatocellular lesions. International Working Party. Hepatology. 1995;22(3): MacSween RN, Burt AD, Portmann BC, Ishak KG, Scheuer PJ, Anthony PP. Pathology of the liver 5th edition Tanimoto A, Kuwatsuru R, Kadoya M, et al. Evaluation of gadobenate dimeglumine in hepatocellular carcinoma: results from phase II and phase III clinical trials in Japan. J Magn Reson Imaging. 1999;10(3): Hanna RF, Aguirre DA, Kased N, Emery SC, Peterson MR, Sirlin CB. Cirrhosisassociated hepatocellular nodules: correlation of histopathologic and MR imaging features. Radiographics. 2008;28(3): Casillas C, Marti-Bonmati L, Galant J. Pseudotumoral presentation of nodular regenerative hyperplasia of the liver: imaging in five patients including MR imaging. Eur Radiol. 1997;7(5): Personal Information Page 13 of 14

14 K. Kozaka, MD Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa , Japan. address: k- Page 14 of 14