RESULTS

Total 63 patients (M:F = 54:9, mean age 55.8±9.5 years) were included in this study. Patients were pathologically confirmed HCCs after surgical resection wedge resection: 19, segmentectomy: 15, sectionectomy: 14, hemihepatectomy: 13, extended hemihepatectomy: 1, total hepatectomy: 1). The underlying causes of cirrhosis (as determined from available pathological/laboratory data and hepatology clinical notes) included viral hepatitis B (n=52), viral hepatitis C (n=3), and alcohol abuse (n=8).

A. Tumor Size

Mean tumor size was 3.4± 2.4cm [1.0-14.0] on basis of the pathologic reports. Regarding gross pathologic diameter as standard reference, the mean and standard error of the measurement error of tumor measured on each phase/sequence by novices and experts are summarized in Table 2. There were no statistical significances on the measurement errors in each CT phases by novice or experts with ANOVA. The measurement errors on MR were slightly smaller than CT, but there were no statistical significances by novices (P=0.29) or experts (P=0.62).

There were no statistical significances on the measurement errors in each MR phases by novices or experts.

B. Major Imaging Features

Table 3 shows the frequency of LI-RADS major imaging features and inter-observer agreement. Inter-observer agreement on AP hyperenhancement was moderate in CT and MR (к=0.566, 0.475). Inter-observer agreement on washout

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appearance was fair in CT (к= 0.364) and substantial in MR (к=0.630). Inter-observer agreement on capsule appearance was moderate in CT (к=0.491) and fair in MR (к=0.303).

C. Ancillary Imaging Features

In only two cases, novice used ancillary imaging feature from LI-RADS 3 lesions to LI-RADS 4 lesions on CT. There was no case in expert’s reading used ancillary imaging feature on CT. In two cases on MR, novice used ancillary imaging features from LI-RADS 3 lesions to LI-RADS 4 lesions. In only one case on MR, expert used ancillary imaging features from RADS 3 lesion to LI-RADS 4 lesion.

D. LI-RADS Categorization

Figure 2 shows the distribution of LI-RADS category in each reader. ICC for LI-RADS category in CT between individual readers was 0.574 with 95% CI of [0.393, 0.755]. ICC for LI-RADS category in MR between individual readers was 0.318 with 95% CI of [0.098, 0.537]. Overall inter-observer agreement was better when measured by CT than by MR.

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Table 1. MR Imaging Sequences and Parameters

Parameters TR/TE

gap (mm) Matrix size Reduction factor

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Table 2. Measurement errors of hepatocellular carcinomas (HCCs) size measured by novice and experts

Novices Experts

Mean SE Mean SE P value

CT

Unenhanced 0.58 0.08 0.54 0.08

0.752

AP 0.55 0.09 0.56 0.08

PVP 0.57 0.08 0.50 0.06

DP 0.56 0.09 0.52 0.07

MR

Unenhanced 0.43 0.06 0.47 0.06

0.750

AP 0.45 0.06 0.49 0.07

PVP 0.46 0.06 0.52 0.07

HBP 0.47 0.06 0.46 0.06

SE : standard error

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Table 3. Inter-observer agreement of LI-RADS major imaging features by CT and MR

CT MR CT

agreement

MR

agreement Arterial hyperenhancement

Novice 58(92.1%) 57(90.5%)

Expert 58(92.1%) 61(96.8%) к=0.566 к=0.475 Portal venous or delayed washout

Novice 45(71.4%) 40(63.5%)

Expert 50(79.4%) 48(76.2%) к=0.364 к=0.630 Capsule appearance

Novice 34(54.0%) 43(68.3%)

Expert 32(50.8%) 34(54.0%) к=0.491 к=0.303

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Figure 1. Image from a 36- year-old man with hepatocellular carcinoma (HCC) in segment VII of the liver

A. Contrast enhanced arterial phase CT image shows a HCC with nodule-in-nodule appearance with indistinct margin. B. Contrast enhanced delayed phase CT image shows a HCC with indistinct margin. C. Gadoxetic acid-enhanced arterial phase MR image shows a HCC with nodule-in-nodule appearance. D. Gadoxetic acid-enhanced HBP MR image shows a HCC with clear outline with surrounding parenchyma.

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Figure 2. Distribution of LI-RADS category by imaging modality

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IV. Discussion

Our study results show the tumor size measurement varies with imaging modalities and each phase. It is still debate which phase should be used to measure the exact size of tumor. The Organ Procurement and Transplantation Network (OPTN) protocol recommends size measurements in the late hepatic arterial or early portal venous phase.(13) On the other hand, LI-RADS allows to measure the size in the most visible phase.(3) The American Association for the Study of Liver Diseases (AASLD) practice guidelines does not specify size measurement methods.(11) Our results showed that the measurement errors of tumor diameter measured by MR were smaller than those measured by CT. It indicates that MR is favorable for size measurement, especially in beginners. Interestingly, there were no statistical significances of the measurement errors between novices and experts on both CT and MR.

Davenport MS et al. reported an inter-observer agreement of the major imaging features in MR, substantial agreement for arterial hyperenhancement (κ = 0.67), moderate for washout appearance (κ = 0.48), and moderate for capsule appearance (κ = 0.52).(8) In contrast, the degree of inter-observer agreement demonstrated in this study was moderate (к = 0.475) for AP hyperenhancement, substantial (к = 0.630) for washout appearance, and fair (к = 0.303) for capsule appearance. These results are lower than those of previous reports, which can be explained in relation to the characteristics of gadoxetic acid. In MR imaging using gadoxetic acid, which shows not only hepatocyte uptake and also biliary excretion, the hepatic AP may appear less intense than with conventional agents.(14) These characteristics of gadoxetic acid can affect low inter-observer agreement in

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assessing arterial hyperenhancement. In HBP, normal liver parenchyma appears uniformly bright on T1- weighted images because gadoxetic acid accumulates in the extracellular space.(14) Enhanced normal parenchyma can obscure capsule and it could be a cause of low inter-observer agreement.

Comparing the major imaging features, the inter-observer agreement was higher in CT (к = 0.566) than in MR (к = 0.475) for arterial enhancement. When reviewed by expert, the arterial enhancement was better detected in MR than in CT (96.8% vs. 92.1%). Novice’s readings showed a frequency of arterial enhancement similar to that of expert (92.1%) in CT, but revealed a significantly lower detection rate in MR, compared to that of expert’s (90.5% vs. 96.8%). It might be due to characteristics of gadoxetic acid. Since gadoxetic acid may show less intense enhancement in the AP than other contrast agents, it is important to familiarize with the images using gadoxetic acid.

In terms of washout appearance, the inter-observer agreement was higher in MR (к = 0.630) than in CT (к = 0.364) and it might be caused by higher tissue contrast in MR than in CT.

In capsule appearance, the inter-observer agreement was lower in MR (к = 0.303) than in CT (к = 0.491). Specifically, the frequency of capsule appearance in CT and MR was similar (50.8%, 54.0%) in expert, however, there was a significant difference in the frequency of capsule appearance between CT and MR (54.0%, 68.3%) in novice. It suggests that sufficient experience in MR imaging using gadoxetic acid is needed for precise image reading in GAeMR. The frequency of capsular appearance was higher in MR than in CT, not only in expert but also in novice. Strong association between the imaging features of subjective washout and

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capsule in hypervascular liver nodules may be partially derived from an optical illusion and/or reader predisposition.(15) Therefore, the inter-observer agreement could be lower in capsule appearance.

Ancillary imaging features that favor HCC in LI-RADS includes mild to moderate T2 hyperintensity, restricted diffusion, corona enhancement, mosaic architecture, nodule-in-nodule architecture, intra-lesional fat, lesional iron sparing, lesional fat sparing, blood products, diameter increase less than threshold growth, distinctive rim, HBP hypointense rim, HBP hypointensity.(3) But in our study, limited numbers of cases used ancillary imaging features, because we already knew pathological results. Because there are no standard guidelines, the use of ancillary features may cause bias by radiologist’s discretion.

There was no significant difference between expert and novice in the frequency of final categorization of LI-RADS. When evaluating the value of ICC, it was found that the inter-reader agreement of MR was lower than that of CT (ICC:

0.574 in CT, 0.318 in MR). Although not significant, there was a trend toward increased proportion of LI-RADS 5 lesions at MRI compared to CT.

There are several limitations in our study. First, shrinkage factor after formalin fixation should be considered when reporting tumor size. The tumor size may slightly larger in vivo condition, and that may differ according to the various imaging modalities. So we used the gross pathological size of HCC as reference standard. Second, in our institution, the pathological specimens are usually sectioned in the sagittal or coronal plane, coronal and sagittal images are not always available in retrospective study with CT and GAeMR. Accordingly, we used mainly axial images. Third, we measured the size of each phases of one HCC at the same session, bias could exist. The differences between each phases was very small. It is difficult to measure the size of the HCC with irregular peritumoral

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enhancement on AP, but it is easier than that to measure the size of HCC with clear outline on HBP image.

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V. CONCLUSION

In conclusion, the measurement errors of tumor diameter measured by MR were smaller than that measured by CT and MR is favorable for size measurement, especially in beginners. The inter-observer agreement of arterial hyperenhancement and capsule appearance was higher in CT than in MR and in terms of washout appearance, that was higher in MR than in CT. LI-RADS showed fair to moderate agreement for diagnosis of HCC on CT and GAeMR.

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2. Purysko AS, Remer EM, Coppa CP, Leao Filho HM, Thupili CR, Veniero JC. LI-RADS: a case-based review of the new categorization of liver findings in patients with end-stage liver disease. Radiographics. 2012;32(7):1977-95.

3. Quality and safety resources: Liver Imaging–Reporting and Data System [Internet]. 2012. Available from: http://www.acr.org/Quality-Safety/Resources/LIRADS.

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5. Doo KW, Lee CH, Choi JW, Lee J, Kim KA, Park CM. "Pseudo washout" sign in high-flow hepatic hemangioma on gadoxetic acid contrast-enhanced MRI mimicking hypervascular tumor. AJR Am J Roentgenol. 2009;193(6):W490-6.

6. Ahn SS, Kim MJ, Lim JS, Hong HS, Chung YE, Choi JY. Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology. 2010;255(2):459-66.

7. Kim SH, Kim SH, Lee J, Kim MJ, Jeon YH, Park Y, et al. Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol. 2009;192(6):1675-81.

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8. Davenport MS, Khalatbari S, Liu PS, Maturen KE, Kaza RK, Wasnik AP, et al.

Repeatability of diagnostic features and scoring systems for hepatocellular carcinoma by using MR imaging. Radiology. 2014;272(1):132-42.

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12. Zhang YD, Zhu FP, Xu X, Wang Q, Wu CJ, Liu XS, et al. Liver Imaging Reporting and Data System:: Substantial Discordance Between CT and MR for Imaging Classification of Hepatic Nodules. Acad Radiol. 2016;23(3):344-52.

13. Policy 9: Allocation of livers and liver-intestines [Internet]. 2017. Available from:

https://optn.transplant.hrsa.gov/governance/policies.

14. Goodwin MD, Dobson JE, Sirlin CB, Lim BG, Stella DL. Diagnostic challenges and pitfalls in MR imaging with hepatocyte-specific contrast agents. Radiographics.

2011;31(6):1547-68.

15. Sofue K, Sirlin CB, Allen BC, Nelson RC, Berg CL, Bashir MR. How reader

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perception of capsule affects interpretation of washout in hypervascular liver nodules in patients at risk for hepatocellular carcinoma. J Magn Reson Imaging. 2016;43(6):1337-45.

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우 MR에서는 우수한 일치도(к=0.630)를 보인 반면 CT에서는 보통의 일치도(к

=0.364)를 보였다. 피막의 경우에는 CT에서 우수한 일치도(к=0.491)를 보였으며, MR에서는 보통의 일치도(к=0.303)를 보였다. LI-RADS 카테고리의 비율은 전공의 와 전문의 비율 간의 큰 차이는 없었고, CT에서의 판독자간 일치도는 우수한 (Intraclass correlation coefficients (ICC) = 0.574) 반면 MR에서는 보통의 일치도 (ICC = 0.318)를 보였다.

연구 결론: 간세포암 종양의 크기 측정에 있어 MR이 CT에 비해 조금 더 정확했으며, 특히 초심자에게 MR이 유리하였다. 판독자간 일치도는 동맥기 조영증강과 피막의 경 우 CT가 MR에 비해 높았으며, 세척 효과의 경우 MR이 CT에 비해 높았다. LI-RADS 카테고리 평가의 판독자간 일치도는 CT와 Gadoxetic-acid 조영증강 MR에서 보통에서 우수한 정도의 일치도를 보였다.

핵심어: 간세포암, Gadoxetic aicid 조영증강 MRI, LI-RADS, 판독자간 일치도