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Table. Detection Rates for Identification of Hepatic Metastases Size of lesons Helical CT MRI Helical CT+ MRI < cm 8/28 (64) 8/28 (64) 023/28 (82)* 2 cm 26/33 (79) 28/33 (85) 28/33 (85) > 2 cm 30/3 (97) 29/3 (94) 03/3 (00) Total 74/92 (80) 75/92 (82) 82/92 (89) Note. -Numbers in parentheses are the percentages. * Corresponds to statistically significant difference (p = 0.036) by McNemar test. a b c Fig.. A 50-year-old woman with sigmoid colon cancer a. Helical CT scan during portal venous phase shows no definite focal lesion in the liver. b. T2- weighted MR image shows a tiny lesion with subtle high signal intensity in segment- of the liver (arrow). c. On Mn-DPDP enhanced T-weighted images, the lesion shows low signal intensity (arrow). The lesion was confirmed as metastasis at histopathologic examination. a b c Fig. 2. A 59-year-old man with sigmoid colon cancer. a. CT scan shows a hypoattenuating nodule (arrow) in segment of the liver. b. On Mn-DPDP enhanced MRI, the nodule is not defined. This nodule was missed on interpretation of MRI alone. c. On T2-weighted image, the nodule shows subtle high signal intensity. The lesion was confirmed as metastasis at histopathologic examination. - -

Table 3. Interobserver Variability in Confidence Ratings ( -values) Table 2. Mean Az Values for Each Imaging Technique for Differentiating Malignant lesions from Benign Lesions Size of lesions Helical CT MRI Helical CT+ MRI < cm 0.603 0.08 0.807 0.06 0.848 0.05 2 cm 0.807 0.06 0.883 0.05 0.92 0.04 > 2 cm 0.932 0.06 0.927 0.05 0.955 0.04 Note. Date are mean SD Statiscally significant difference (p<0.05) compared with CT Size of Lesions Helical CT MRI Helical CT+ MRI < cm 0.62 0.72 0.83 2 cm 0.82 0.9 0.93 > 2 cm 0.92 0.96 Note. -values 0 >, positive correlation; 0 0.4, positive but poor agreement; 0.4 0.75, good agreement; > 0.75,excellent agreement : consensus of opinions in all nodules a b Fig. 3. A 67-year-old man with sigmoid colon cancer a. Helical CT scan during portal phase shows two small hypoattenuating nodules that are too small to characterize in liver segment- and - (arrows). b. On T2-weighted image, segment lesions (arrows) in segment- show very high signal intensity suggesting hepatic cysts. However segment- lesion is not defined. c. On Mn-DPDP enhanced T-weighted images, segment- lesion (arrowhead) shows low signal intensity. The lesion in segment- VI was confirmed as metastasis at histopathologic examination. c - 2 -

Table 4. False Positive Rates Size of lesions Helical CT MRI Helical CT+ MRI < cm 5/53 (28) 5/53 (9) 3/53 (6) 2 cm 08/53 (5) 3/53 (6) 3/53 (6) 2 cm > 0/53 (0) 2/53 (4) 0/53 (0) Note. Numbers in parentheses are the percentage of patients with at least one false positive lesions. Statiscally significant difference (p<0.05) compared with MRI, CT-MRI a b c Fig. 4. A 58-year-old woman with rectal cancer (A) Mn-DPDP enhanced MRI shows a nodule with low signal intensity in segment of the liver (arrow), which is not defined on T2-weighted image (B). The lesion was interpreted as metastasis on interpretation of MRI alone. (C). On CT images, no focal lesion is seen in corresponding area. On combined CT-MRI reading, the lesion was correctly interpreted as artifact probably caused by partial volume averaging of an adjacent colon loop. - 3 -

al. Hepatic metastases from colorectal cancer: preoperative detection and assessment of respectability with helical CT. Radiology 200;28:55-60 5.van Erkel AR, Pijl ME, van den Berg-Huysmans AA, Wasser MN, van de Velde CJ, Bloem JL. Patients with Colorectal Cancer: Relationship between Size of metastases, standard of reference, and detection rates. Radiology 2002;224:404-409 6.Haider MA, Amitai MM, Rappaport DC, ÒMalley ME, Hanbidge AE, Redston M, et al. Multidetector row helical CT in preoperative assessment of small (<.5 cm) liver metastases: is thinner collimation better? Radiology 2002;225:37-42 7.Semelka RC, Martin DR, Balci C, Lance T. Focal liver lesions: comparison of dual-phase CT and multisequence multiplanar MR imaging including dynamic gadolinium enhancement. J Magn Reson Imaging 200;3:397-40 8.Seneterre E, Taourel P, Bouvier Y, Pradel J, Van Beers B, Daures JP, et al. Detection of hepatic metastases: ferumoxidesenhanced MR imaging versus unenhanced MR imaging and CT during arterial portography. Radiology 996;200:785-792 9.Ward J, Naik KS, Guthrie JA, Wilson D, Robinson. Hepatic lesion detection: comparison of MR imaging after the adminis- tration of superparamagnetic iron oxide with dual-phase CT by using alternative free response receiver operating characteris- analysis. Radiology 999;20:459-466 tic 0.Reimer P, Jahnke N, Fiebich M, Schima W, Deckers F, Marx C, et al. Hepatic lesion detection and characterization: value of nonenhanced MR imaging, superparamagnetic iron oxide-enhanced MR imaging, and spiral CT-ROC analysis. Radiology 2000;27():52-58.Arbab AS, Ichikawa T, Sou H, Araki T, Nakajima H, Ishigame K, et al. Ferumoxides-enhanced double-echo T2-weighted MR imaging in differentiating metastases from nonsolid benign lesions of the liver. Radiology 2002;225():5-58 2.Kim KW, Kim AY, Kim TK, Park SH. Kim HJ, Lee YK, et al. Small(<2cm) hepatic lesions in colorectal cancer patients: detection and characterization on Mangafodipir Trisodium-en- hanced MRI. AJR Am J Roentgenol 2004;82:233-240 3.Helio J, Braga HJ, Choti MA, Lee VS, Paulson EK, Siegelman ES, et al. Liver lesions: manganese enhanced MR and dual phase helical CT for preoperative detection and characterization-comparison with receiver operating characteristic analy- sis. Radiology 2002:223:525-53 4.Imam K, Bluemke DA. MR imaging in the evaluation of hepatic metastases. Magn Reson Imaging Clin N Am 2000;8:74-756.Hughes KS, Rosenstein RB, Songhorabodi S, Adson MA, Ilstrup DM, Fortner JG, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of longterm survivors. Dis Colon Rectum 988;3():?4 2.Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, et al. Liver resection for colorectal metastases. J Clin Oncol 997;5:938-946 3.Kuszyk BS, Bluemke DA, Urban BA, Choti MA, Hruban RH, Sitzmann JV, et al. Portal-phase contrast-enhnaced helical CT for the detection of malignant hepatic tumors: sensitivity based on comparison with intraoperative and pathologic findings. A- JR Am J Roentgenol 996;66:9-95 4.Valls C, Andia E, Sanchez A, Guma A, Figueras J, Torras J, et 5.,,,,,. Mangafodipir Trisodium MR?:. 2004;5:299-305 6.Federle M, Chezmar J, Rubin DL, Weinreb J, Freeny P, Schmiedl UP, et al. Efficacy and safety of mangafodipir trisodium (MnD-PDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials?efficacy of early imaging. J Magn Reson Imaging 2000;2(5):689-70 7.Oudkerk M, Torres G, Song B, Konig M, Grimm J, Fernandez- Cuadrado J, et al. Characterization of Liver Lesions with - 4 -

Mangafodipir Trisodium?enhanced MR Imaging: multicenter Study Comparing MR and Dual-Phase Spiral CT. Radiology 2002;223(2):57-24 8.Schwartz LH, Gandras EJ, Colangelo SM, ErcolaniMC, Panicek DM. Prevalence and importance of small hepatic lesions found at CT in patients with cancer. Radiology 999;20:7-74 9.Ward J, Chen F, Guthrie JA, Wilson D, Lodge JP, Wyatt JI, et al. Hepatic lesion detection after superparamagnetic iron oxide enhancement: comparison of five T2-weighted sequences at.0 T by using alternative-free response receiver oprating characteristic analysis. Radiology 2000;24():59-66 20.Mann GN, Marx HF, Lai LL, Wagman LD. Clinical and Cost Effectiveness of a New Hepatocellular MRI Contrast Agent, Mangafodipir Trisodium, in the Preoperative Assessment of Liver Resectability. Annals of Surgical Oncology 200;8:573-579 2.Harned RK II, Chezmar JL, Nelson RC. Recurrent tumor after resection of hepatic metastases from colorectal carcinoma-location and time of discovery as determined by CT. AJR Am J Roentgenol 994;63;93-97 22.Pedro MS, Semelka RC, Braga L. MR imaging of hepatic metastases. Magn Reson Imaging Clin N Am 2002;0:5-29 23.Vidiri A, Carpanese L, Annibale MD, Caterino M, Cosimelli M, Zeuli M, et al. Evaluation of hepatic metastases from colorectal carcinoma with MR-superparamagnetic iron oxide. J Exp Clin Cancer Res. 2004 Mar;23():53-60 24.Soyer P, Elias D, Zeitoun G, Roche A, Levesque M. Surgical treatment of hepatic metastases: impact of intraoperative ultrasound. AJR Am J Roentgenol 993;60:5-54 25.Soyer P, Levesque M, Elias D, Zeitoun G, Roche A. Detection of liver metastases from colorectal cancer: comparison of interoperative US and CT during arterial portography. Radiology 992;83:54-544 26.Young SW, Simpson BB, Ratner AV, Matkin C, Carter EZ. MRI measurement of hepatocyte toxicity using the new MRI contrast agent managanese dipyridoxal diphosphate, a manganese/pyridoxal 5-phosphate chelate. Magn Reson Med 989;0:-3 27.Jung G, Heindel W, Krahe T, Kugel H, Walter C, Fischbach R, et al. Influence of the hepatobiliary contrast agent mangafodipir trisodium(mn-dpdp) on the imaging properties of abdominal organs. Magn Reson Imaging 998;6:925-93 - 5 -

Preoperative Detection of Hepatic Metastases from the colorectal Cancers: Comparison of Dual-phase CT scan, Mn-DPDP enhanced MRI, and combination of CT and MRI Kyung Min Shin, M.D., Hun Kyu Ryeom, M.D., Jong Yeol Kim, M.D., Gyu Seok Choi, M.D. 2, Hye Jeong Kim, M.D., Jong Min Lee, M.D., Yongmin Chang, Ph.D., Yong Seon Kim, M.D., Duk Sik Kang, M.D. Department of Radiology, School of Medicine, Kyungpook National University 2 Department of Surgery, School of Medicine, Kyungpook National University Purpose : To determine the usefulness of additional Mn-DPDP MRI for preoperative evaluation of the patients with colorectal cancers by comparison of dual-phase CT scan, Mn-DPDP enhanced MRI and combination of CT and MRI. Materials and Methods : Fifty-three colorectal cancer patients with 92 metastatic nodules underwent dualphase (arterial and portal) helical CT scan and Mn-DPDP MRI prior to surgery. The indication of MRI was presence or suspected of having metastatic lesions at CT scan and/or increased serum carcinoembryonic antigen (CEA) levels (0 ng/ml or more). The diagnosis was established by the combination of findings at surgery, intraoperative ultrasonography, and histopathologic examination. Two radiologists interpreted CT, MRI, and combination of CT-MRI at discrete sessions and evaluated each lesion for location, size, and intrinsic characteristics. The lesions were divided into three groups according to their diameter; cm <, 2 cm, and > 2 cm. Diagnostic accuracy was evaluated using the alternative-free response receiver operating characteristic method. Detection and false positive rate were also evaluated. Results : In the lesions smaller than cm, detection rate of combined CT-MRI was superior to CT or MRI alone (82%, p = 0.036). The mean accuracy (Az values) of combined CT and MRI was significantly higher than that of CT in the lesions smaller than 2 cm ( cm <, p=0.034; 2 cm, p=0.045). However, there was no significant difference between MRI and combined CT-MRI. The false positive rate of CT was higher than those of combined CT-MR in the lesions smaller than cm (28 %, p=0.023). Conclusion : Additional MRI using Mn-DPDP besides routine CT scan was helpful in differentiating the hepatic lesions (< 2 cm) and could improve detection of the small hepatic metastases (< cm) from colorectal carcinoma. Index words : Liver neoplasms, CT Liver neoplasmamms, MR Magnetic resonance (MR), contrast media Address reprint requests to : Hun Kyu Ryeom, Department of Radiology, School of Medicine, Kyungpook National University 50, 2Ga, Samduk-dong, Jung-gu, Taegu 700-72, Korea. Tel. 82-53-420-5390 Fax. 82-53-422-2677 E-mail: hkryeom@knu.ac.kr - 6 -