Verification of multistep nature in development of hepatocellular carcinoma in the LEC rat using MR imaging method

本研究的目的是通过对Long Evans Cinnamon（LEC）大鼠肝脏病变的MRI纵向研究，阐明LEC大鼠肝脏病变的发展过程。在纵向研究之前，我们测量了11只老年LEC大鼠的MR图像与病理相关性，以表征各种肝脏病变。因此，我们可以区分肿瘤/异型增生结节，紫癜肝，胆管纤维化和囊肿的成像。分别于60、75、90、100周龄对同一12只LEC大鼠进行重复成像，最后一次测量后处死动物，经苏木精/伊红（H & E）和酸性六亚甲基四胺银（PAM）染色后进行组织病理学诊断。在12只大鼠中，共发现4个肿瘤/不典型增生结节，24个肝硬化，7个胆管纤维化，4个胆管扩张和3个囊腺瘤。其中28个病灶至少随访了两个不同的时间段。它们的成像特征，如T2弛豫时间和图像强度比的病变，肝实质在T1加权图像前和注射Gd后保存良好，在每个病灶，除了延长T2弛豫时间观察囊腺瘤，因为它的增长。通过纵向观察每个病灶的体积来评估病灶的生长速度。假设呈指数增长，我们计算出肿瘤/异型增生结节、肝硬化、胆管纤维化、胆管扩张和囊腺瘤的平均倍增时间分别为4.1、5.8、20.3、8.7和4.6周。单个病变的准确生长率只能通过非侵入性成像方法（如MR成像）获得。

The purpose of this study is to elucidate the developing process of hepatic lesions in the Long Evans Cinnamon (LEC) rat by a longitudinal study of the same animals using MR imaging method. Prior to the longitudinal study we measured MR images of eleven aged LEC rats with pathologic correlation in order to characterize various hepatic lesions. As a result we can discriminate neoplastic/dysplastic nodules, peliosis hepatis, cholangiofibrosis and cyst by imaging. Then, we performed repeated imaging on the same twelve LEC rats at 60, 75, 90 and 100-weeks old.After the final measurement the animals were sacrificed and the hepatic lesions were histopathologically diagnosed after hematoxylin/eosin (H & E), and periodic-acid methenamine silver (PAM) staining. We have identified 4 neoplastic/dysplastic nodules, 24 peliosis hepatis, 7 cholangiofibrosis, 4 bile duct dilatation and 3 cystadenoma altogether in 12 rats. Among them 28 lesions were followed up at least two different time stages. Their imaging characteristics such as the T2 relaxation time and the image intensity ratio of lesion to liver parenchyma in T1-weighted images before and after Gd injection were well preserved in each lesion except for the prolonged T2 relaxation time observed in cystadenoma as it grows. The growth rate of lesions was also evaluated by following up the volume of each lesion in the longitudinal observation. Assuming an exponential growth we calculated the average doubling time of neoplastic/dysplastic nodule, peliosis hepatis, cholangiofibrosis, bile duct dilatation, and cystadenoma as 4.1, 5.8, 20.3, 8.7, and 4.6 weeks, respectively. This exact growth rate on individual lesions can only be obtained by a noninvasive imaging method like MR imaging.