Volume 71, Issue 5, Pages 432-437 (May 2016) Heterogeneity of non-cancerous liver parenchyma on gadoxetic acid-enhanced MRI: an imaging biomarker for hepatocellular carcinoma development in chronic liver disease  Y. Asayama, A. Nishie, K. Ishigami, Y. Ushijima, Y. Takayama, D. Okamoto, N. Fujita, K. Morita, M. Obara, H. Honda  Clinical Radiology  Volume 71, Issue 5, Pages 432-437 (May 2016) DOI: 10.1016/j.crad.2016.01.023 Copyright © 2016 The Royal College of Radiologists Terms and Conditions

Figure 1 A 65-year-old man with hepatitis C. The Child–Pugh class was A. HCC was found in segment 6 (not shown). (a) The ROI was placed on the right lobe of the liver on an HBP image. The increase ratio of LMR was 0.79. (b) Histogram of the signal intensity of NLP demonstrated a peaked distribution with high kurtosis (3.195) and low skewness (−1.279). This case was categorised into the highK/lowS category. Clinical Radiology 2016 71, 432-437DOI: (10.1016/j.crad.2016.01.023) Copyright © 2016 The Royal College of Radiologists Terms and Conditions

Figure 2 A 57-year-old man with hepatitis C. The Child–Pugh class was A. HCC was not identified. (a) The ROI was placed on the right lobe of the liver on an HBP image. The increase ratio of LMR was 0.620. (b) The histogram of signal intensity of the NLP demonstrated a positive distribution but relatively lower kurtosis (0.522) and high skewness (0.056). This case was categorised into the lowK/highS category. Clinical Radiology 2016 71, 432-437DOI: (10.1016/j.crad.2016.01.023) Copyright © 2016 The Royal College of Radiologists Terms and Conditions

Figure 3 Scatterplot of kurtosis and skewness in all cases. With a cut-off value of 0.547 for kurtosis and −0.1185 for skewness, the four categories and HCC development were significantly correlated (p=0.0374). (○) HCC cases; (●) non-HCC cases. Clinical Radiology 2016 71, 432-437DOI: (10.1016/j.crad.2016.01.023) Copyright © 2016 The Royal College of Radiologists Terms and Conditions

Figure 4 Schematic diagram of changes from baseline (broken line) to the histographic pattern typical of the highK/lowS category (solid line). The histogram of the highK/lowS category shows a peaked distribution with a loss of the shoulder accompanied by a longer and thicker left tail. In the highK/lowS category, hepatocytes (or groups of them) with less contrast medium uptake ability form a longer and thicker tail at the left. In contrast, highly functional hepatocytes (or groups of them) with greater contrast uptake ability build a sharper peak. In such conditions, these accelerated or hyperplastic hepatocytes could have many opportunities to undergo oncogene mutation. Clinical Radiology 2016 71, 432-437DOI: (10.1016/j.crad.2016.01.023) Copyright © 2016 The Royal College of Radiologists Terms and Conditions