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3 Table 1. Detection Accuracy in Liver Metastases and Hepatocellular Carcinomas Early (95% CI of Area) Delay (95% CI of Area) p value Reader 1 Mets (n=69) ( ) ( ) > 0.1 HCC (n=37) ( ) ( ) > 0.1 Reader 2 Mets (n=69) ( ) ( ) > 0.1 HCC (n=37) ( ) ( ) > 0.1 Mets: metastases, HCC: hepatocellular carcinomas, CI: confidence interval Table 2. Comparison of Lesion Conspicuity between Mn-DPDP enhanced Early and Delay MR Images Early > Delay Early = Delay Early < Delay p value Reader 1 Mets (n=63) < HCC (n=31) < Reader 2 Mets (nn=56) < 0.01 HCC (n=30) < Mets: metastases, HCC: hepatocellular carcinomas Wilcoxon s signed rank test A B C Fig. 1. A 70-year-old man with liver metastasis from colon cancer. Precontrast T1-weighted MR image (A) shows a 2.5 cm hypointense metastatic mass in segment VII of liver, which reveals thin and faint ring enhancement (arrowhead) on Mn-DPDP-enhanced early MR image (B). On postcontrast delay MR image (C), more prominent and thicker ring enhancement is demonstrated in the periphery of the metastatic mass. 301

4 정재준 외: Mangafodipir Trisodium 조영 후 간 MR 영상에서 전이성 간암의 진단을 위해 지연기 영상은 꼭 필요한가? 주변의 정상간에 비해 어둡게 보인다(8). 전이성 간암의 발견 율을 높이기 위해 Gd-DTPA와 Mn-DPDP를 포함한 여러 가 지 조영제들이 간의 MR 검사에서 독립적으로 사용되어 왔지 만, 간 병소의 발견 민감도에 있어서 어떤 조영제가 다른 조영 제보다 특별히 우월하다는 보고는 없는 실정이다(5, 6, 16, 17). Mn-DPDP 투여 후 조영증강 영상에서 어떤 병소의 신호강 도가 중등도 이상으로 높게 증가되거나 정상간과 동일하면 이 병소는 간세포성(고분화 간세포암, 간선종, 국소 결절성 과증 식 등)일 가능성이 높다(6). 과혈관성 전이암들은 Mn-DPDP 조영증강 영상에서는 망간의 축적이 안 되는 것으로 알려져 있 지만, 췌장의 과혈관성 도세포 종양(islet cell tumor)에서 전 연기 영상에서 증가하였으나, 간세포암의 경우 두 판독자 모두 에서 초기와 지연기 영상 사이에 차이를 보이지 않았다 (Table 3). 고 찰 Mn-DPDP를 정맥주사하면 약 20분 내로 탈인산화 대사 과정을 거치고, 부분적으로 분자 중 망간이 내인성 아연이온과 치환반응을 일으키며, 아연과의 치환반응을 통해 방출된 망간 이온이 간으로 유입되어 조영효과를 나타내는데(6, 15), T1강조영상에서 정상간은 망간이 축적되어 밝게 보이고, 전이성 간암에는 망간이 축적되지 않아 신호강도의 변화가 거의 없이 Table 3. Comparison of Ring Enhancement Grade between Mn-DPDP enhanced Early and Delay MR Images Reader 1 Mets (n=63) Early > Delay Early = Delay Early < Delay p value < HCC (n=31) Reader 2 Mets (n=56) HCC (n=30) NA < > 0.1 Mets: metastases, HCC: hepatocellular carcinomas, NA: not available, Wilcoxon s signed rank test A B Fig. 2. A 74-year-old man with liver metastasis from colon cancer. Precontrast T1-weighted MR image (A) shows a 2.1 cm hypointense metastatic mass in segment VIII of liver dome, which reveals no definite ring enhancement on Mn-DPDP-enhanced early MR image (B). On postcontrast delay MR image (C), overt ring enhancement is demonstrated in the periphery of the metastatic mass. C 302

5 대한영상의학회지 2004;51: 방간이나 간경변에 의해 전이성 간암이 잘 보이지 않을 수도 있다. CT 검사는 최근 나선형 CT나 다중절편 CT 등의 발달 로 국소적 병소의 발견율과 진단율이 많이 향상되었지만, 아직 도 조영제 주입 후 역동적 검사가 불가능한 CT를 이용하여 검 사하는 경우가 많아 다음 검사로 복부 MR 검사를 하게 되는 데, 그 동안 주로 이용되어 온 Gd-DTPA 조영제를 이용한 복 부 MR 검사도 작은 전이성 간암을 발견하는데 제한이 있는 것 으로 보고되고 있다(8, 21, 22). 전이성 간암은 조영증강 역동적 CT나 Gd-DTPA 조영증강 MR 영상에서 자주 관찰되는 바와 같이 종양 주변의 환형 조 영증강이 Mn-DPDP 조영증강 MR 영상에서도 관찰되는 것으 로 알려져 있지만, 중심부 괴사를 동반한 간세포암이나 간농양 등에서도 환형 조영증강이 관찰된다는 보고들(12, 13)이 있어 이들간의 감별이 필요하며 이를 위해 12시간 이상의 지연기 영상이 필요한 것으로 생각한다. 따라서 대상 환자들은 모두 입원 환자로 국한하여 검사를 시행해야 일정 시간이 지난 후 에 지연기 영상을 얻을 수 있고, 외래 환자의 경우 겪을 수 있 는 번거로움을 피할 수 있다. 간 병소의 환형 조영증강 여부를 판정하는 기준은 Mn-DPDP 이된 전이성 간암에는 망간의 축적이 보고되어 있다(18-20). 이 연구에서 두 판독자의 간 병소 발견율이 전이성 간암은 각각 63개(91.3%)와 56개(81.2%), 원발성 간세포암은 각각 31개(83.8%)와 30개(81.1%)로 비교적 높지 않게 나타났는 데, 병소의 크기가 작아 발견하지 못한 이유 외에도, 전이성 간 암의 경우 작은 간낭종을 전이성 간암으로 판독한 경우가 많 았고, 간세포암의 경우 주변의 간경변성 결절들 때문에 간세포 암을 인식하지 못 하거나 간경변성 결절 자체를 간세포암으로 인식한 경우가 있었다. 우리 나라에서 비교적 흔한 위암이나 최근 발생빈도가 증가 하고 있는 대장암 등의 가장 좋은 치료방법은 종양의 수술적 제거이지만 이들 종양의 진단 시에 이미 간에 전이되어 수술 을 못하는 경우가 많이 있다. 하지만 간에 전이된 종양이 한 개이거나 한 개 이상이더라도 간의 한 구역에 모여있으면 간 의 구역절제술을 통해 제거할 수 있으므로, 수술 전 초음파나 CT 검사를 통해 전이성 간암의 개수와 위치를 정확히 진단하 는 것이 환자의 예후를 결정하는데 있어서 매우 중요하다. 하 지만 초음파 검사는 시술자의 능력이나 병소의 위치 및 크기 에 따라 병소의 발견율에 차이가 많고 가성 병소가 많으며, 지 A B Fig. 3. A 56-year-old man with hepatocellular carcinoma (HCC). Precontrast T1-weighted MR image (A) shows a 5.2 cm lobulated and hypointense HCC in segment IV of liver, which reveals slightly irregular ring enhancement (arrowheads) on Mn-DPDPenhanced early MR image (B). On postcontrast delay MR image (C), an irregular ring enhancement (arrowheads) is still demonstrated in the periphery of the metastatic mass without interval change. C 303

6 1. Earls JP, Bluemke DA. New MR imaging contrast agents. Magn Reson Imaging Clin N Am 1999;7: Young SW, Simpson BB, Ratner AV, Matkin C, Carter EA. MRI measurement of hepatocyte toxicity using the new MRI contrast agent manganese dipyridoxal diphosphate, a manganese/pyridoxal 5-phosphate chelate. Magn Reson Med 1989;10: 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 1998;16: Ni Y, Marchal G. Enhanced magnetic resonance imaging for tissue characterization of liver abnormalities with hepatobiliary contrast agents: an overview of preclinical animal experiments. Top Magn Reson Imaging 1998;9: Helmberger T, Semelka RC. New contrast agents for imaging the liver. Magn Reson Imaging Clin N Am 2001;9: Hahn PF, Saini S. Liver-specific MR imaging contrast agents. Radiol Clin North Am 1998;36: Liou J, Lee JK, Borrello JA, Brown JJ. Differentiation of hepatomas from nonhepatomatous masses: use of Mn-DPDP-enhanced MR images. Magn Reson Imaging 1994;12: Helmberger TK, Laubenberger J, Rummeny E, Jung G, Sievers K, Dohring W, et al. MRI characteristics in focal hepatic disease before and after administration of Mn-DPDP: discriminant analysis as a diagnostic tool. Eur Radiol 2002;12: Marti-Bonmati L, Lonjedo E, Poyatos C, Casillas C. Mn-DPDP enhancement characteristics and differentiation between cirrhotic and noncirrhotic livers. Invest Radiol 1998;33: King LJ, Burkill GJ, Scurr ED, Vlavianos P, Murray-Lyons I, Healy JC. Mn-DPDP enhanced magnetic resonance imaging of focal liver lesions. Clin Radiol 2002;57: Coffin CM, Diche T, Mahfouz A, Alexandre M, Caseiro-Alyes F, Rahmouni A, et al. Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging. Eur Radiol 1999;9: Kane PA, Ayton V, Walters L, Beniamin I, Heaton ND, Williams R, et al. Mn-DPDP-enhanced MR imaging of the liver. Correlation with surgical findings. Acta Radiol 1997;38: ,,,,. Gadolinium chelatemangafodipir trisodium :. 2002;46: Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1983;148: Rummeny EJ, Marchal G. Liver imaging. Clinical applications and future perspectives. Acta Radiol 1997;38: Semelka RC, Worawattanakul S, Kelekis NL, John G, Woosley JT, Graham M, et al. Liver lesion detection, characterization, and effect on patient management: comparison of single-phase spiral CT and current MR techniques. J Magn Reson Imaging 1997;7: Kettritz U, Schlund JF, Wilbur K, Eisenberg LB, Semelka RC. Comparison of gadolinium chelates with manganese-dpdp for liver lesion detection and characterization: preliminary results. Magn Reson Imaging 1996;14: Wang C, Ahlstrom H, Eriksson B, Lonnemark M, McGill S, Hemmingsson A. Uptake of mangafodipir trisodium in liver 304

7 metastases from endocrine tumors. J Magn Reson Imaging 1998;8: Kettritz U, Semelka RC. Contrast-enhanced MR imaging of the pancreas. Magn Reson Imaging Clin N Am 1996;4: Mathieu D, Coffin C, Kobeiter H, Casciro-Alves F, Mahfouz A, Rahmouni A, et al. Unexpected MR-T1 enhancement of endocrine liver metastases with mangafodipir. J Magn Reson Imaging 1999;10: Martin DR, Semelka RC. Imaging of benign and malignant focal liver lesions. Magn Reson Imaging Clin N Am 2001;9: Pedro MS, Semelka RC, Braga L. MR imaging of hepatic metastases. Magn Reson Imaging Clin N Am 2002;10: Semelka RC, Hussain SM, Marcos HB, Woosley JT. Perilesional enhancement of hepatic metastases: correlation between MR imaging and histopathologic findings-initial observations. Radiology 2000;215: Oudkerk M, Torres CG, Song B, Konig M, Grimm J, Fernandez- Cuadrado J, et al. Characterization of liver lesions with mangafodipir trisodium-enhanced MR imaging: multicenter study comparing MR and dual-phase spiral CT. Radiology 2002;223: Martin DR, Semelka RC, Chung JJ, Balci NC, Wilber K. Sequential use of gadolinium chelate and mangafodipir trisodium for the assessment of focal liver lesions: Initial observations. Magn Reson Imaging 2000; 18: Sahani DV, O Malley ME, Bhat S, Hahn PF, Saini S. Contrast-enhanced MRI of the liver with mangafodipir trisodium: imaging technique and results. J Comput Assist Tomogr 2002;26: Are the Delay Images Necessary to Evaluate the Liver Metastatic Lesions on Mangafodipir Trisodium Enhanced Liver MRI?: Comparison with Hepatocellular Carcinomas 1 Jae-Joon Chung, M.D. 1, 2, Hee Chul Yang, M.D. 2, Myeong-Jin Kim, M.D., Jong Tae Lee, M.D., Hyung Sik Yoo, M.D., Ki Whang Kim, M.D. 1 Department of Diagnostic Radiology, Yonsei University College of Medicine, Research Institute of Radiological Science, Yonsei University 2 Department of Diagnostic Radiology, NHIC Ilsan Hospital Purpose: To assess whether ring enhancements of liver metastases on Mn-DPDP enhanced, early MR images were well visualized on delayed images, as compared with those of hepatocellular carcinomas (HCC), and to investigate the detection accuracy and conspicuity of each tumor. Materials and Methods: Twenty patients with liver metastases and 15 with HCC were studied by Mn-DPDP enhanced, T1-weighted MR images. Peripheral ring enhancement and conspicuity were investigated. Differences in detection accuracy and frequency of ring enhancement in liver metastases and HCC were assessed. Results: In liver metastases (n=69), 44 cases (63.8%) without ring enhancement and 25 (36.2%) with were noted on early images. Sixteen cases (23.2%) without ring enhancement, 38 (55.1%) with ring enhancement similar to the early images, and 15 (21.7%) with prominent ring enhancement were noted on delayed images. In HCC (n=37), 36 cases (97.3%) without ring enhancement and 1 case (2.7%) with were noted on early images. There was no difference of detection accuracy in liver metastases or HCC between the 2 readings. Ring enhancement and conspicuity of each tumor were superior on delayed images. Ring enhancement in liver metastases was better seen on delayed images. Conclusion: Ring enhancement in liver metastases was well presented on Mn-DPDP enhanced, delayed MR images, which was useful to differentiate liver metastases from HCC. Index words : Liver, neoplasms Liver, MR Mangnetic resonance (MR) Magnetic resonance (MR), contrast enhancement Address reprint requests to : Jae-Joon Chung, M.D., Department of Diagnostic Radiology, YUMC, 134 Shinchon-dong, Seodaemun-gu, Seoul , Korea. Tel Fax jjchung@yumc.yonsei.ac.kr 305

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