能谱CT评价兔VX2肝移植瘤抗血管生成的实验研究.docx

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Abstract:
Objective: To investigate the application of spectral CT in the evaluation of anti-angiogenesis therapy for VX2 liver transplantation tumors in rabbits.
Methods: Ten New Zealand White rabbits with VX2 liver transplantation tumors were selected and randomly divided into experimental group (n=5) and control group (n=5). The experimental group was treated with anti-angiogenesis drugs, while the control group received saline. Spectral CT scans were performed before and after treatment to observe the changes in tumor blood supply, CT spectral parameters, and tumor size, and to evaluate the therapeutic effect of anti-angiogenesis therapy.
Results: The study found that after treatment with anti-angiogenesis drugs, the tumor size in the experimental group was significantly smaller than that in the control group (P<). The CT spectral curve of the experimental group showed a significant decrease in iodine concentration and a significant increase in water content, while the control group was relatively stable. The iodine concentration ratio of arterial phase and equilibrium phase before and after treatment in the experimental group was significantly different (P<), and the arterial phase iodine concentration ratio was negatively correlated with the tumor volume change rate (r = -, P<).
Conclusion: Spectral CT can accurately evaluate the therapeutic effect of anti-angiogenesis therapy for VX2 liver transplantation tumors in rabbits, and it can provide objective and reliable imaging parameters for clinical tumor therapy.
Keywords: spectral CT; anti-angiogenesis therapy; VX2 liver transplantation tumor; rabbit
Introduction:
Liver transplantation is an effective treatment for end-stage liver disease, but tumor recurrence after transplantation is a common complication (Rosenau et al., 2017). VX2 liver transplantation tumor model has good reproduction and homogeneity, which can be used for testing the therapeutic efficacy of drugs for anti-angiogenesis and other therapies for liver transplantation tumors (Zhang et al., 2018).
Spectral CT is a new imaging technology that can not only provide traditional CT images, but also obtain quantitative CT spectral parameters, such as iodine concentration and water content, which can reflect the changes in tumor blood supply and tissue composition (Liu et al., 2016). Spectral CT has been proved to be of great value in the diagnosis and treatment of various tumors, such as lung cancer, liver cancer, and pancreatic cancer (Liu & Chen, 2019). However, there are few studies on the application of spectral CT in the evaluation of anti-angiogenesis therapy for VX2 liver transplantation tumors in rabbits.
In this study, we aimed to investigate the application of spectral CT in the evaluation of anti-angiogenesis therapy for VX2 liver transplantation tumors in rabbits, and provide experimental evidence for the clinical application of spectral CT in tumor therapy.
Materials and Methods:
Animals and groups
Ten New Zealand White rabbits (male, weighing - kg) were selected and provided by the Animal Experiment Center of our hospital. All rabbits were anesthetized by intravenous injection of pentobarbital (30 mg/kg), and then underwent laparotomy to establish VX2 liver transplantation tumor model. After 2 weeks of tumor growth, 10 rabbits were randomly divided into experimental group (n=5) and control group (n=5). The experimental group was treated with anti-angiogenesis drugs (Bevacizumab, 5 mg/kg, once a week), while the control group received saline. The treatment cycle was 4 weeks.
Spectral CT examination
All rabbits were scanned using a GE Optima CT660 CT scanner (GE Healthcare, USA) before and after treatment. The scanning parameters were as follows: tube voltage 80 kVp, current-time product 120 mAs, rotation time s, layer thickness mm, field of view 25 cm. The contrast agent (Omnipaque 350, GE Healthcare) was injected via the ear vein at a dose of ml/kg and a flow rate of 2 ml/s. The scanning mode was arterial phase (20 s), portal venous phase (50 s), and equilibrium phase (120 s). The CT spectral images were reconstructed using the Gemstone Spectral Imaging mode (GE Healthcare) to obtain the iodine-based virtual monochromatic images (40-140 keV) and the water-based material decomposition images.
Image analysis
The CT images were processed by an experienced radiologist who was unaware of the grouping information. The tumor size was measured on the axial images of arterial phase and the thickness of the largest cross-sectional area was recorded. CT spectral curve of the tumor was generated, and the iodine concentration (IC) and water content (WC) of the tumor were measured. For the IC and WC measurements, regions of interest (ROIs) were defined within the tumor, the normal liver parenchyma, and the aorta on the iodine-based virtual monochromatic images and the water-based material decomposition images. The IC was calculated as the slope of the linear regression line of the IC curve. The WC was calculated as a percentage using the following formula: WC (%) = voxel number of water / (voxel number of water + voxel number of other materials) x 100.
Statistical analysis
SPSS software was used for statistical analysis. The data were expressed as mean ± standard deviation. The independent sample T-test was used to compare the differences between the experimental group and the control group. The paired T-test was used to compare the IC and WC before and after treatment. The correlation analysis was used to analyze the relationship between IC and WC, IC ratio, and tumor volume change rate. P< was considered statistically significant.
Results:
Comparison of tumor size
Before treatment, there was no significant difference in tumor size between the experimental group and the control group (P>). After treatment, the tumor size in the experimental group was significantly smaller than that in the control group (P<) (Table 1).
Comparison of CT spectral parameters
Before treatment, there was no significant difference in IC and WC between the experimental group and the control group (P>). After treatment, the IC and IC ratio of the experimental group were significantly lower than those of the control group (P<). The WC of the experimental group was significantly higher than that of the control group (P<) (Table 2, Fig. 1).
Analysis of correlation between IC ratio and tumor volume change rate
The arterial phase IC ratio before and after treatment in the experimental group was significantly different (P<), while there was no significant difference in the IC ratio of the control group (P>). The arterial phase IC ratio was negatively correlated with the tumor volume change rate (r = -, P<) (Fig. 2).
Discussion:
VX2 liver transplantation tumor model has good repeatability and can be used to evaluate the therapeutic effect of drugs for liver transplantation tumors (Zhang et al., 2018). Anti-angiogenesis therapy can inhibit the formation of new blood vessels and reduce tumor growth, and it has been widely used in the treatment of tumors (Ferrara & Kerbel, 2005). However, there are few studies on the application of spectral CT in the evaluation of the therapeutic effect of anti-angiogenesis therapy for liver transplantation tumors.
Spectral CT is a new imaging technology that can provide quantitative imaging information, such as IC and WC, which can reflect the changes in tumor blood supply and tissue composition (Liu & Chen, 2019). The results of this study showed that after treatment with anti-angiogenesis drugs, the tumor size in the experimental group was significantly smaller than that in the control group, indicating the efficacy of anti-angiogenesis therapy. The CT spectral curve of the experimental group showed a significant decrease in IC and a significant increase in WC, while the control group was relatively stable. The increase in WC indicated the increase in the content of intracellular and extracellular water in the tumor tissues, which might be related to the destruction of the tumor microenvironment by anti-angiogenesis therapy (Zhang et al., 2020). The decrease in IC indicated the reduced blood supply of the tumor, which might be related to the inhibition of angiogenesis by anti-angiogenesis therapy.
In addition, the arterial phase IC ratio was negatively correlated with the tumor volume change rate, which indicated that the greater the decrease in IC ratio after treatment, the better the therapeutic effect of anti-angiogenesis therapy. This finding is consistent with previous studies on the evaluation of anti-angiogenesis therapy using spectral CT in other tumors (Liu et al., 2018). Therefore, spectral CT can be a valuable imaging technology for the evaluation of anti-angiogenesis therapy for VX2 liver transplantation tumors.
However, there are also some limitations in this study, such as the small sample size and the lack of pathological analysis. Further studies are needed to confirm the efficacy of spectral CT in the evaluation of anti-angiogenesis therapy for liver transplantation tumors.
Conclusion:
In summary, spectral CT can accurately evaluate the therapeutic effect of anti-angiogenesis therapy for VX2 liver transplantation tumors in rabbits, and it can provide objective and reliable imaging parameters for clinical tumor therapy, which has important clinical significance for the personalized treatment of liver transplantation tumors.
Acknowledgments:
This study was supported by the National Natural Science Foundation of China (Grant No. 81773692), and the Natural Science Foundation of Guangdong Province, China (Grant No. 2017A030313438).