Synopsis

Eighty-three patients with 100 histologically diagnosed hepatocellular carcinomas (HCCs) who preoperatively underwent diffusion-weighted (DW) imaging at any of 6 institutes were retrospectively studied. Receiver-operating characteristic analysis revealed that quantitative measurements such as the relative contrast ratio (RCR) and the contrast-to-noise ratio (CNR) between lesion and liver parenchyma on DW images were superior to the apparent diffusion coefficient (ADC) in predicting poorly differentiated HCCs, and intraclass correlation coefficients for the RCR tended to be greater than for the CNR and the ADC.

Introduction

Histological grade is one of the prognostic factors in patients with hepatocellular carcinoma (HCC)^1-4. Accurate radiological stratification of HCC grade is helpful for predicting the prognosis and selecting the therapeutic strategy.

The apparent diffusion coefficient (ADC), which is the most commonly used index in diffusion-weighted MR imaging (DWI), has been used for quantitative assessment of malignant tumors. Several studies have evaluated the correlation between the ADC and histological grade of HCC^5-14 but yielded conflicting results. Recently, some studies showed that non-ADC parameters, i.e., the relative contrast ratio (RCR) or contrast-to-noise ratio (CNR) of HCC to the surrounding liver parenchyma on DW images, were superior to the ADC in predicting the grade of HCC.^{6, 7, 9} However, they were single-center studies using single magnetic resonance (MR) units, and the inter-observer reproducibility of these measurements has not been reported.

The aim of this study was to evaluate the usefulness and the reproducibility of DW parameters, including RCR, CNR and ADC using multi-vendor MR units for predicting grade of HCC.

Methods

This multi-center, retrospective, multi-vendor study included patient data from 6 institutions. The study protocol was approved by the institutional review boards at 3 institutions. The other 3 Institutions did not have ethical review committees so delegated approvals to the main institution. The requirement for informed consent was waived.

Eighty-three patients with 100 histologically diagnosed HCCs who underwent preoperative liver DW imaging with b = 0 and 1000 s/mm² at any of 4 institutions (49 patients with 58 HCCs) or b = 0 and 800 s/mm² at any of 2 institutions (34 patients with 42 HCCs) were included. Two radiologists independently measured the ADC of the lesion as well as the RCR and the CNR between the lesion and the liver parenchyma on high b-value DW images. The diagnostic performance of the DW parameters in discriminating poorly differentiated HCCs was compared using receiver-operating characteristic (ROC) analysis. Inter-observer agreement between the radiologists was assessed using the intraclass correlation coefficient (ICC).

Results

The areas under the ROC curves for the CNR (86.4% [95% confidence interval (CI) 77.2–95.6] and 83.9% [95% CI 71.2–96.6] for b = 1000 and 800 s/mm², respectively) and the RCR (85.3% [95% CI 75.5–94.8] and 83.5% [95% CI 70.5–96.4]) tended to be superior to the ADC (71.1% [95% CI 56.9–85.2] and 75.7% [95% CI 55.1–96.2]; p < 0.05 for CNR vs ADC for b = 1000 s/mm2, but not significant for other parameters) for discrimination of poorly differentiated HCCs.

The ICCs for the RCR (0.93 [95% CI 0.88–0.96] and 0.87 [95% CI 0.77–0.93]) tended to be greater than for the CNR (0.81 [95% CI 0.70–0.88] and 0.63 [95% CI 0.41–0.78]) and the ADC (0.65 [95% CI 0.28–0.82] and 0.75 [95% CI 0.36–0.89]).

Discussion

HCC is known to increase T2 elongation and to restrict diffusion with increasing histological grade.^{6, 15, 16} The signal intensities of DWI, which are presented as the RCR and the CNR, are influenced by T2 elongation as well as restriction of diffusion. Therefore, the RCR and CNR might be more appropriate for predicting the histological grade of HCC than measurement of the ADC alone.

ROC analyses revealed that the RCR and CNR on b = 1000 s/mm² tended to be superior to the RCR and CNR on b = 800 s/mm² for discrimination of pHCCs. Restriction of diffusion is more strongly related to the contrast in DWI on b = 1000 s/mm² than on b = 800 s/mm² and is considered to be a more important reflection of histological grade. A previous study that used methods similar to those in the present study showed that the AUCs of ADC on b = 0 and 1500 s/mm² were greater than those on b = 800–1000 s/mm² in the present study.⁶

There are several limitations to this study, in particular its retrospective design and small patient population. Further prospective studies in large cohorts are needed. Another limitation is that the reproducibility of RCR and CNR among the different magnetic field strengths and respiratory motion compensation techniques available is unknown. Further assessment of the reproducibility of RCR and CNR using other measurement methods under various conditions of MRI acquisition might be needed.

Conclusion

Acknowledgements

References

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