Figure 4
Hypointense MR signals in livers of alb-myctg mice correspond to highly tumorigenic tissue sections with strong proliferation. (A) T1-weighted liver MR image of a 65 weeks old male alb-myctg mouse after i.v. application of gadoxetic acid disodium. Sharply demarcated multiple hypointense foci become obvious within hepatic lobes due to contrast uptake of surrounding hepatic tissue (indicated by arrows); one lesion (white circle) was followed up in subsequent analyses. (B) Macroscopic appearance of explanted liver showing multifocal and sometimes multinodular tumor growth characterized by enhanced vascularisation, discoloration, and destruction of liver segments. (C) Paraffin-embedded section of the complete mouse liver shown in (B). Please note that these serial sections were performed in the same transversal orientation as performed for the MR imaging shown in (A). White circle: macroscopically visible tissue abnormality corresponding to hypointense signal as highlighted in (A). (D) Hematoxylin/eosin staining of the liver section shown in (C). White circle highlights one selected neoplastic lesion surrounded by normal liver tissue. Scale bar indicates diameter of the lesion (mm). (E) Enlarged view (200× original magnification) of mouse liver section with lesions after staining with hematoxylin/eosin. (G) PCNA staining (brown nuclei) of liver tissue as a marker for cell proliferation demonstrates DNA synthesis only in areas identified as HCC and (H) close-up view (200× original magnification) of tumorous areas in PCNA staining. Black arrows indicate PCNA positive nuclei; dashed black line separates healthy liver tissue from tumor nodule; Orientation labeling: R: right; L: left.