Zhijun Geng1, Yunfei Zhang2, Hui Li1, Jing Zhao1, Sihui Zeng1, Cheng Zhang1, Chuanmiao Xie1, and Yongming Dai2
1Sun Yat-sen University Cancer Center, Guangzhou, China, 2United Imaging Healthcare, Shanghai, China
Synopsis
Tightly correlated with the prognosis, microvascular invasion (MVI) serves as one significant predictor determining the clinical management. Abnormal angiogenesis, one typical character during carcinogenesis, can lead to the abnormal micro-vessel manifestations including micro-hemorrhage and more, which may correlate with another abnormal vascular manifestations—MVI. Hence, this research aims to predict the MVI via visualizing the intra-tumor hemorrhage with susceptibility weighted imaging (SWI) widely proven to be powerful for imaging hemorrhage and IVIM hypothesized to be effective for visualizing the hemorrhage via quantifying the abnormal perfusion. The results displayed that visualizing the micro-hemorrhage holds great potential for predicting MVI of HCC.
Introduction
Being tightly
correlated with the prognosis of hepatocellular carcinoma (HCC) such as
recurrence and poor response to therapy as well as playing a significant role
for the subsequent clinical management, MVI has attracted the attention of
innumerable researchers.1-3 As
another abnormal vascular manifestations, angiogenesis, serving as one
representative character during carcinogenesis, is the main cause of many
abnormal micro-vessel changes containing intra-tumoral hemorrhage,
hyper-vascularity and so on.4 Therefore, we hypothesized that visualizing the intra-tumoral
hemorrhage may be enlightening for predicting the MVI as they are all sourced
from the abnormal micro-vessel, which may overcome the disadvantages of the
histopathological examination, current gold standard, such as the sampling
bias, invasiveness and so on. With the ability of quantifying the perfusion, we
speculated that D* (pseudo diffusion coefficient) and f (perfusion fraction)
obtained from IVIM parametric maps may be helpful for sensitively visualizing
the micro-vessel hemorrhage related to the abnormal perfusion in the molecular
dimension.5 Differently, due to the fact that SWI applies the phase information
to enhance the contrast of susceptibility change with “intrinsic contrast
agents”, some paramagnetic substances, such as deoxygenated hemoglobin and so
on, SWI (Susceptibility Weighted Imaging) is able to offer the macroscopical
visibleness of abnormal micro-vessel manifestations including micro-hemorrhage
and so on.6,7 Since
IVIM and SWI can respectively reflect the micro-vessel changes in the
microscopic dimension with high sensitivity and in the macroscopic dimension
with high specificity, respectively, this research aims to predict the MVI via
visualizing the intra-tumor hemorrhage with the assistance of SWI and IVIM. As
far as we are aware, neither have the SWI and IVIM been combined for clinical
application, nor have the visualization of micro-vessel hemorrhage been applied
for predicting the MVI of HCC.Methods
The number of
patients recruited into this research was 28, in total. One 3T MR scanner (uMR
780, United Imaging Healthcare Co Ltd) was utilized for completing all MR
examinations. The main MR sequences in this research included T2WI sequence, SWI
sequence and IVIM sequence. Detailed parameters of SWI sequence were as the
followings: TR/TE/FA: 120 ms/10 ms/30°, Rows*Columns: 303*384 and
slice thickness: 5 mm. Detailed parameters of IVIM
sequence were as the followings: TR/TE/FA: 4294 ms/ 67.1 ms/90°, Rows*Columns:
256*202, slice thickness: 5 mm and b values: 0, 10, 20, 30, 40, 60, 80, 100,
200, 400, 600, 800 s/mm2. The parametric maps of IVIM were
calculated according to the most-widely used fitting model. One
experienced radiologist with more than 8 years’ experience was asked to define
the ROI in IVIM parametric maps and SWI images. The histogram metrics of the whole
tumor lesion were extracted for subsequent statistics. Patients
were classified into MVI positive termed as MVI(+) and MVI negative termed as
MVI(-) according to whether there existed MVI in the tumor according to the
histopathological results. Besides, micro-hemorrhage in the tumor was also assessed
according to the histopathological examination. Mann-Whitney
U test was performed to see whether there existed significant difference (p < 0.05) between MVI(-) and MVI(+)
HCC patients for each histogram metrics extracted from IVIM and SWI images. ROC
analysis was performed to evaluate the diagnostic performance. Results
Representative IVIM parametric images and SWI images were
displayed in Figure 1 together with
the images of tumor specimens. Interestingly, the areas of micro-hemorrhage in
tumor specimens well matched the corresponding areas of SWI and IVIM parametric
images in MVI(+) HCC patient with abnormal image manifestations. Heat map in Figure 2 showed that Dmean,
Dkurtosis, SWIMean, SWI70% Percentile, SWI75%
Percentile, SWI80% Percentile, fmean, f70%
Percentile, Dp Kurtosis and Dp 75% Percentile in MVI(-)
group were significantly different from those of MVI(+) group (p < 0.05). Detailed values and
comparisons were exhibited in Figure 3.
Interestingly, the proportion of patients pathologically diagnosed having
micro-hemorrhage in MVI (-) group was significantly lower than that of MVI(+)
group (15% vs 78%, p < 0.05). The
diagnostic performance of each index having significant difference between
MVI(-) and MVI(+) patients for discriminating MVI(+) patients from MVI(-)
patients from good to bad were f70% Percentile (AUC = 0.797), SWI80%
Percentile (AUC = 0.754), SWI75% Percentile (AUC = 0.736), SWI70%
Percentile (AUC = 0.723), DKurtosis (AUC = 0.723), SWIMean(AUC
= 0.718), fMean (AUC = 0.705), Dp Kurtosis (AUC = 0.700),
Dp 75 Percentile (AUC = 0.667) and DMean (AUC = 0.600).Discussion
For MVI(+) patients, the probability of suffering
micro-hemorrhage was much higher than that of MVI(-) group, which indicates
that micro-hemorrhage may serve as a predictive marker for diagnosing MVI.
Besides, the result of that f70% Percentile and SWI80%
Percentile have the best diagnostic performance may be explained by the
following points: 1) The abnormal micro-vessel manifestations including MVI and
micro-hemorrhage were tightly correlated to each other. 2) f value is able to
sensitively reflect the abnormal tissue perfusion.8 3) With the help of
endogenous “contrast agents” such as deoxygenated hemoglobins,
SWI can sensitively visualize the micro-hemorrhage area with specific
hypo-intensity.9Conclusion
Visualizing the micro-hemorrhage of HCC via the
combination of SWI and IVIM holds great potential for accurately predicting the
MVI.Acknowledgements
No acknowledgements.References
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