Qungang Shan1, Jingbiao Chen1, Ronghua Yan1, Yao Zhang1, Hao Yang1, Xin Li2, Zhongping Zhang3, Yunhong Shu4, Churong Lin, Tianhui Zhang1, Bingjun He1, Zhuang Kang1, Xi Long1, and Jin Wang1
1Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), Guangzhou, People's Republic of China, 2GE Healthcare MR Research China, Guangzhou, People's Republic of China, 3MR Research China,GE Healthcare, Beijing, 4Mayo Clinic
Synopsis
HCC is the second cause of cancer-related deaths and
most HCC patients are accompanied with hepatitis B virus-related cirrhosis in China. Ki67 is a protein reflecting the proliferative activity of HCC and
could be used as a predictor of prognosis. We assessed the value of the texture
parameters in evaluating the expression of Ki67of HBV-related HCCs by whole
tumor analysis. Our results showed that Dclusterprominence showed
best diagnostic performance among all texture parameters. ADC and IVIM derived texture
parameters might be used as useful and noninvasive biomarkers for evaluating
the expression of Ki67 of HBV-related HCCs.
Introduction
Hepatocellular
carcinoma (HCC) is the most common primary malignancy of the liver worldwide1.Surgery
resection and liver transplantation have been considered the only curative
treatments. However, the prognosis remains still poor due to the high rate of recurrence.
Ki67 is a protein which reflects the proliferative activity of HCC. High
expression of Ki67 is a strong predictor of recurrence and poor prognosis in
HCC patients after surgery2,3.Intravoxel incoherent motion (IVIM)
has been used for evaluating histologic grade of HCC4, assessing therapeutic
effect and predicting prognosis5,6.However, the utility of
evaluating the expression of Ki67 using IVIM in HBV-related HCCs is not clear. This
study aimed to evaluate the value of IVIM texture parameters in predicting the
expression of Ki67in HBV-related HCCs.Methods
The study was approved by the institutional review board of our hospital
and 154 patients with chronic HBV infection who were diagnosed with HCC
pathologically after surgical resection or liver transplantation were included initially.
93 patients were excluded: (a) 18 received previous transarterial chemoembolization
(TACE), (b) 11 had no lesion larger than 1cm in size, (c) 2 had distinct motion artifacts and 6 had slice misregistration,
(d) 56 did not have available information on the expression of Ki67. A total of
61 patients (53 males and 8 females; age range, 25-75 years; mean, 54 years)with
61 HCCs were enrolled finally. In patients with multiple tumors, the largest one
was analyzed. Immunohistochemistry was used to test the expression of Ki67.Ki-67
of 10% was considered positive expression. The patients
were classified into two groups: Ki67 positive (n=48) and Ki67 negative (n=13).
All subjects underwent MRI exam on a 3.0T whole-body MRI scanner (Discovery
MR750, GE Healthcare, Milwaukee, WI). Respiratory-triggered diffusion-weighted
imaging (DWI) were performed using 11 b values (b=0, 30, 50, 100, 150, 200,
300, 500, 800, 1000, 1500 sec/mm2).Regions of interests (ROIs) were manually
placed on each axial image of ADC maps to encompass as much lesion as possible
using T2W images as a reference. Afterwards, volumes of interests (VOIs) which encompass
the whole tumor were generated automatically by summing all ROIs using a manufacturer
developed tool (Omni-Kinetics, GE Healthcare). The VOIs were then
transferred to other parameter maps automatically. Apparent diffusion
coefficient (ADC), diffusion coefficient (D), pseudodiffusion coefficient (D*)
and perfusion fraction (f) derived texture parameters of the HCCs were
calculated based on histogram and grey level co-occurrence matrix (GLCM) algorithm7.
The differences between the Ki67 (+) and Ki67 (-) group were compared using the
Student t test or Mann-Whitney test according to the statistical distribution
of the data. Receiver operating characteristic (ROC) analysis was performed to assess
the diagnostic performance of these parameters for evaluating the expression of
Ki67 of HCCs.Results
ADCcluster prominence and Dcluster
prominence, of the Ki67(+) group were significantly higher than those of Ki67(-)
group (P=0.022 and 0.013, respectively). ADC25%,ADCcorrelation,Dmedian,D10%
and D25% of the Ki67(+) group were significantly lower than those of
the Ki67(-) group ( P=0.044, 0.039, 0.023,0.029 and 0.021, respectively). The
area under the ROC curve (AUC-ROC) of the above texture parameters in
predicting the positive expression Ki67 was 0.708, 0.726, 0.65, 0.688, 0.67,
0.663 and 0.672, respectively.Discussion
In this study, ADC and IVIM texture parameters of
the whole tumor were calculated. Texture analysis could reflect the tumor heterogeneity
and the whole tumor analysis might provide a better approach for extracting
information of tumors7.Our
study showed that the ADC and IVIM derived texture parameters have the
potential value for predicting the expression of Ki67 of HBV-related HCCs.
According to ROC analysis, Dclusterprominence showed best diagnostic
performance among all texture parameters. However, the AUC of texture
parameters was relatively low, which might be due to the small sample size. Larger
sample size and prospective studies are further needed to investigate the value
of texture parameters of ADC and IVIM as biomarkers for evaluating the
expression of Ki67 of HBV-related HCC.Conclusion
In summary, texture parameters of ADC and IVIM could
be used as useful and noninvasive biomarkers for predicting the expression of Ki67 of HBV-related HCCs and might be helpful when selecting
more appropriate treatment and predicting prognosis.
Acknowledgements
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