Synopsis

Keywords: Cancer, Liver

Vessels encapsulating tumor clusters (VETC) is a powerful predictor of a poor prognosis in patients with hepatocellular carcinoma (HCC) .Therefore, preoperative radiologic prediction of these histopathological results can allow optimized management of HCC and help improve long-term survival for patients.However,to our knowledge, no published studies have investigated preoperative VETC patten of HCC using IVIM parameters and comparing with DWI. Our study indicated that IVIM-derived D* provides a non-invasive analytical approach for preoperative predicting VETC of HCC.ADC value were not predictive for VETC.

Introduction

Vessels encapsulating tumor clusters (VETC) is a powerful predictor of a poor prognosis in patients with hepatocellular carcinoma (HCC) ^1,2, because it provides the route for tumor cells to access the portal or systemic circulation. Unfortunately, information regarding VETC status and tumor differentiation is not routinely available preoperatively, thus, limiting their clinical utility in decision making. Therefore, preoperative radiologic prediction of these histopathological results can allow optimized management of HCC and help improve long-term survival for patients. Conventional DWI supposes the Gaussian water diffusion, and thus cannot distinguish between the diffusion of water molecules and the perfusion of blood. Specifically, intravoxel incoherent motion (IVIM) DWI can simultaneously quantify the diffusion of water molecules and microcirculation perfusion in living tissues. Therefore, it can compensate the limitations of conventional DWI³. It has been reported that IVIM can Improve tumor characterization and grading compared with traditional DWI⁴. However, to our knowledge, no published studies have investigated preoperative VETC patten of HCC using IVIM parameters and comparing with DWI. The aim of this study was to prospectively evaluate the diagnostic efficacy of IVIM in predicting VETC of HCC with comparison to the conventional DWI.

Methods

The prospective study was approved by our Medical Ethics Committee. 104 patients with HCC confirmed by histopathological results were recruited between March 2021 to April 2022. All patients underwent preoperative routine MR and IVIM sequence examination on a 3T MRI scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with a 16 channel body coil. Besides conventional T1WI and T2WI sequences, a research application multi-b DWI using single-shot echo-planner imaging with integrated-shimming sequence was performed with breath navigation under free breathing. The parameters were as follows: 8 b-values: 0 , 20 , 50 , 100 , 150 , 200 , 600 and 1000 s/mm2; TR: 4900 ms, TE: 57ms, FOV: 380 mm × 261 mm, matrix: 88×128, layer thickness: 5.0mm, bandwidth: 2442 Hz/pixel, acceleration factor: 2. The apparent diffusion coefficient (ADC) map and IVIM-derived parameters maps of molecular diffusion coefficient (D), perfusion fraction (f), and perfusion-related diffusion coefficient (D*) were calculated from all 8 b-values. All the quantitative images were analyzed by two independent radiologists who were blinded to the histopathological results. The radiologist drew freehand ROI to outline the tumor around the tumor margin on the original DW images (b = 1000 s/mm2) on whole tumor volume，which was the largest lesion, and tried to avoid the obvious hemorrhage, calcified and necrotic areas. The ROIs then were copied to all other quantitative maps. The mean value of each parameter for the whole tumor was used for further statistical analysis. The surgically resected hepatic specimens were used for the pathological evaluation. Regarding the CD34 evaluation, unequivocal immunoreactivity of a continuous lining around tumor clusters was defined as VETC. The area of VETC was semi-quantitatively evaluated, and 55% was applied as the optimal cutoff value to further divide HCC patients into the VETC+ (Fig. 1) or VETC− (Fig. 2) group as previously reported ². Continuous variables were firstly checked for homogeneity by using F test, and independent sample t test or t′ test was used for the continuous variables. Interobserver agreement toward the diffusion parameters were checked by using the intra-class correlation coefficient (ICC) with the two-way random method. Receiver operating characteristics (ROC) curve analyses were performed to evaluate the diagnostic efficiency for predicting VETC. All statistical analyses were performed by using a statistical software package SPSS 23.0 (SPSS Inc.).

Results

Results were reported in Table 1. Of all the 104 HCCs, VETC was present (VETC+) with 46 (44.2%) HCCs and absent (VETC-) with 58 (55.8%) HCCs. Only the D* value was significantly higher in the VETC+ group than that in the VETC− group (all p < 0.001, Fig.1 and Fig.2). No statistical significance was observed for ADC, D, and f (p>0.05) between the two groups. The D* value for VETC of HCC showed an area under ROC curves of 0.863 (95% CI, 0.782–0. 0.923) (Fig. 3).

Discussion

Our study indicated that D* from IVIM parameters superior to ADC in detecting VETC of HCC. According to IVIM theory, each IVIM parameter represents a specific biological property in a tissue; D stands for tissue cellularity, f for the fractional volume of microcapillary perfusion, and D* for flow velocity that is defined by flow velocity and the mean capillary segment length ⁵. VETC+ and VETC- correspond to morphologic features of micro-vessels in two very different tumors, respectively. Immunohistochemical and immunofluorescent staining show that vascular endothelial cells forms a wider lumen⁶, which indicates faster blood flow or longer segment length and may lead to a higher D* of VETC+ tumors, as shown in our study. However, no significant differences in the f value were found between VETC+ and VETC-. This might be because the D* value and the f value represent different aspects of perfusion, with D* representing the flow rate of blood in the microvessels and the f value representing the blood-carrying capacity of the capillaries ⁷. And D can not reflect the changes in the vascular microstructure compared to the D*.

Conclusion

IVIM-derived D* provides a non-invasive analytical approach for preoperative predicting VETC of HCC. ADC value were not predictive for VETC.

Acknowledgements

No acknowledgement found.