Amide proton transfer-weighted (APTw) MR imaging has attracted increasing attention in the field of molecular imaging as a novel contrast mechanism in MRI. The purpose of the study was to prospectively evaluate the potential role of APTw-MRI and morphologic features in predicting the histological grade of hepatocellular carcinoma (HCC). We enrolled 32 HCC patients who underwent routine liver sequences and APTw sequence on a 3.0-T MRI scanner. Our results showed higher APTw values and larger tumor size are potential predictive biomarkers for high-grade HCC.
Introduction
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the histological grade of HCC can predict long-term survival before local treatment or liver transplantation .1,2 Previous studies reported,3,4 several MRI technical could not accurately and non-invasively predict the histological grade of HCC. Therefore it is desirable to develop a novel imaging method that complements other MR methods and thus improves accuracy in grading HCC. Some preliminary studies 5,6 have applied APTw imaging in glioma grading and got significant results, which makes us speculate on the value of APT in predicting the histological grade of HCC. And, some previous studies 7,8 have shown that APTw imaging can detect liver composition changes between after-meal and over-night-fast statuses and assess the scan-rescan reproducibility in the liver scanning. However, no studies were designed to evaluate the clinical potential of APTw MRI in grading HCC.The study evaluated the differences of APTw values, clinical characteristics and MR morphologic features between low-grade and high-grade groups of HCC and screened independent risk factors at multivariate logistic regression analysis. The results suggest that an increased APTw value and larger tumor size are significantly correlated with high-grade HCC. Furthermore, according to AUC analysis, the combination with both may yield better diagnostic performance in predicting histological grade of HCC in comparison with tumor size alone. Therefore, our current study demonstrated the feasibility and capability of APTw MRI and morphologic features in predicting the histological grade of HCC. Prior to our study, Deng 8 and Chen 7 had demonstrated the feasibility and repeatability of APTw-MR imaging for normal liver tissue. Other phantom experiment 5 showed the APT signal was positively correlated with the bovine serum albumin (BSA) concentration. In our study, we found a significant increase in APTw values in the high-grade HCC: the APTw values in high-grade HCC (grade 3 and 4, 2.8+0.9%) were higher than in the low-grade HCC (grade 1 and 2, 1.6+0.7%).
In the present study ,we found that as tumor size increased, the incidence of low-grade tumors decreased and the incidence of high-grade tumors increased (P=0.017). We use 7.6cm as the critical value of tumor size to identify high- and low- grade HCC. And tumor size was confirmed as a reliable predictor of high-grade HCC among those morphologic features. Our results are slightly different from the results of previous study9 that found that HCC tumors larger than 5 cm has a certain correlation with poor prognosis ,due to the high incidence of advanced histologic grade. However, their study finally suggested that increase in tumor diameter is not a reliable factor in predicting histologic grade. Therefore, we need to further expand the sample to confirm the results of the present study.
1.Clark T, Maximin S, Meier J, et al. Hepatocellular Carcinoma: Review of Epidemiology, Screening, Imaging Diagnosis, Response Assessment, and Treatment. Curr Probl Diagn Radiol .2015;44(6):479-486.
2.Parkin DM. Global cancer statistics in the year 2000. LANCET ONCOL. 2001;2(9):533-543.
3. Kogita S, Imai Y, Okada M, et al. Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow. EUR RADIOL. 2010;20(10):2405-2413.
4. Heo SH, Jeong YY, Shin SS, et al. Apparent diffusion coefficient value of diffusion-weighted imaging for hepatocellular carcinoma: correlation with the histologic differentiation and the expression of vascular endothelial growth factor. KOREAN J RADIOL .2010;11(3):295-303.
5. Choi YS, Ahn SS, Lee S, et al. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. EUR RADIOL. 2017;27(8):3181-3189.
6. Togao O, Yoshiura T, Keupp J, et al. Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro Oncol. 2014;16(3):441-448.
7. Chen SZ, Yuan J, Deng M, et al. Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla. EUR RADIOL. 2016;26(6):1792-1800.
8. Deng M, Chen S, Yuan J, et al. Chemical Exchange Saturation Transfer (CEST) MR Technique for Liver Imaging at 3.0 Tesla: an Evaluation of Different Offset Number and an After-Meal and Over-Night-Fast Comparison. MOL IMAGING BIOL. 2016;18(2):274-282.
9.Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11(9):1086-1092.