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Diagnostic Performance of Amide Proton Transfer-Weighted MRI for Predicting Histological Grade of Hepatocellular Carcinoma
Yue Lin1, Chunmei Li1, Jinyuan Zhou2, and Min Chen1

1Beijing Hospital, Beijing, China, 2Johns Hopkins University, Baltimore, MD, United States

Synopsis

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.

Methods

Between May 2017 and April 2018, 32 consecutive patients with pathologically confirmed HCC were enrolled, who underwent routine liver sequences and APTw sequence on a 3.0-T MRI scanner. MR images were acquired in prior to pathological results. The APTw images were post-processed in an internal development software based on the Interactive Data Language (IDL) environment. Two radiologists drew ROIs independently by referring to the axial T2 images. Morphologic features of conventional MR images and clinical characteristics were also evaluated. Inter- and intra-radiologist agreement was assessed by using the intraclass correlation coefficient (ICC). Student t test was used for the continuous parameters and x2 test or Fisher exact test was used for categorical variables. Multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis were used to evaluate the relative value and diagnostic efficiency of these parameters as potential predictors of high-grade HCC.

Results

Morphological evaluation and clinical characteristics showed that larger tumor size (P =.017) and higher ALT level (P =.02) were associated with higher histologic grade. The ICC values between the inter-observer and intra-observer variability in APTw values showed excellent agreement (ICC = 0.997 and 0.955). Significant differences in the APTw values between low and high- grade HCCs were found (P<.001). At multivariate analysis, APTw value (odds ratio, 0.047; P= .027), as well as tumor size (odds ratio, 0.655; P = .040), were independent risk factors for high-grade HCC. The ROC analyses demonstrated that the diagnostic performance of APTw, tumor size and the combination with both in differentiating the low-grade HCC from the high-grade HCC, with AUCs of 0.870 for APTw, 0.709 for tumor size and 0.911 for the combination with both. Compared with the AUC of tumor size alone, the AUC of the combination with both significantly increased(P=.0112).

Discussion

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.

Conclusions

APTw imaging can be applied to predict the histological grade of HCC. Increased APTw value and larger tumor size were independent risk factors for predicting high-grade HCC.

Acknowledgements

No acknowledgement found.

References

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.

Figures

Fig. 1. Flow diagram shows inclusion and exclusion criteria for the study, HCC=hepatocellular carcinoma

Fig. 2. Examples of the definition of the regions of interest for quantitative analysis. Five ROIs were manually placed on the tumor on MTR image with the T2WI image as anatomical reference. a T2WI image and b MTR image.

Fig. 3. The APTw value of the high and low-grade HCCs for the two radiologists. Significant differences were observed between the high-grade HCCs and the low-grade HCCs for both radiologist 1 and radiologist2. *P <.001.

Fig. 4. Conventional and APTw images of typical high and low-grade HCC. a T2WI, b DWI, c APTw, and d H&Estained pathological section (original magnification x400, black arrow: tumor cells) for a 65year-old man with low-grade HCC(Edmondson-Steiner grade 2). The APTw value of the tumor was 1.12 %. e T2WI, f DWI, g APTw, and h H&E-stained pathological section (original magnification x400,the whole section : tumor cells) for an 81-year-old-male patient with high-grade HCC (Edmondson-Steiner grade 4). The APTw value of the tumor was 3.54 %.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
4346