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Inhibition Effects of High Mechanical Index Ultrasound Contrast on Hepatic Metastasis of Cancer in a Rat Model

Posted Oct 31, 2010 Updated Apr 7, 2023
By Hua Zhong MD , Rui Li MD , Ying-xue Hao MD , Yan-li Guo MD , Xing Hua MD , Xiao-hang Zhang MD , Zhao-hui Chen MD
6 min read

Rational and Objectives

The liver is the most common organ for tumor metastasis. The development of new methods to depress hepatic metastasis is of great importance in improving survival. The aim of this study was to observe the effects of high–mechanical index ultrasound contrast on hepatic metastasis of colorectal cancer.

Materials and Methods

Hepatic metastasis models were established by injecting human colon carcinoma LoVo cells into the spleens of Sprague-Dawley rats. The rats were divided into a control group, a microbubble plus ultrasound group, a simple ultrasound group, and a simple microbubble group. The ultrasound contrast agent SonoVue (1 mL/kg) was injected via the tail vein, and high–mechanical index ultrasound contrast (frequency, 1.5 MHz; mechanical index, 1.7) was performed on the spleen intermittently for 2 minutes. The animals were sacrificed after 10 days, and the sizes and number of hepatic metastases were measured and compared. Histologic pathology and splenic ultrastructure were observed.

Results

The number and sizes of hepatic metastases patently decreased in rats in the microbubble plus ultrasound group ( P < .01). There were no obvious differences among the control group, simple ultrasound group, and simple microbubble group in hepatic metastases ( P > .05). Histologic pathology showed that the number of tumor cells in the spleens decreased considerably, and massive necroses, hemorrhages, and thrombi were observed in the tumor and spleen tissues of rats in the microbubble plus ultrasound group. Transmission electron microscopy showed that the mitochondria of tumor cells and endothelial cells were clearly swelled, and there were gaps among endothelial cells and platelets aggregated in capillary vessels.

Conclusion

This research shows that intermittent high–mechanical index ultrasound contrast may inhibit the hepatic metastasis of cancer in a rat model.

Hepatic metastasis of malignant tumors is accomplished mainly by diffusion metastasis, lymphatic metastasis, blood-route metastasis, and implantation metastasis caused by malignant cell shedding. The liver is the largest parenchymatous organ in the human body and is considered the major location of many malignant tumor metastases because of its double blood supply. Hepatic metastasis is commonly seen in the blood-route metastasis of colon cancer. It was reported that in patients with colorectal cancer, about 10% to 25% were found to have hepatic metastases when they underwent primary surgery, another 25% were found to have hepatic metastases during follow-up, and >50% had hepatic metastasis . Therefore, the inhibition of hepatic metastasis is of great importance for the improvement of survival.

Compared to enhanced computed tomography and magnetic resonance imaging, ultrasound contrast is a new diagnostic technique. In recent years, with the development of the ultrasound contrast technique and the application of new ultrasound contrast agents, the effects of microbubble contrast agents on human tissues and organs have aroused great concern. Ultrasound contrast has been extensively used in the diagnosis of liver diseases and has made great progress . Yumita et al found that ultrasound cavitation caused by ultrasound contrast could damage tumor cells.

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Materials and methods

Materials and Equipment

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Cell Culture

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Establishment of the Animal Model

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Empirical Method

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Statistical Analysis

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Results

Tumor Growth

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Figure 1, (a) Many metastases (diameter, 2–5 mm) appeared in the liver in the control group (arrows). (b) The number and sizes of hepatic metastases (diameter, 1–2 mm) decreased considerably in the microbubble plus ultrasound group (arrow).

Table 1

Comparison of the Number and Sizes of Liver Metastases Among the Study Groups

Group Number Diameter (mm) Control 10.33 ± 4.62 3.75 ± 1.29 Microbubbles plus ultrasound 3.42 ± 1.38 ∗ 1.58 ± 0.67 ∗ Simple ultrasound 9.58 ± 3.42 † 3.58 ± 1.24 † Simple microbubbles 11.33 ± 3.73 † 3.75 ± 1.22 †

Data are expressed as mean ± standard deviation.

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Histopathologic Changes

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Figure 2, (a) Most tumor cells were circular or oval in shape and distributed in mass in the control group. (b) In the microbubble plus ultrasound group, massive hemorrhages and necroses were found in spleen. (c) In the microbubble plus ultrasound group, thrombi were found in the spleen tissue (arrow). Hematoxylin and eosin staining, 200×.

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Transmission Electron Microscopy

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Figure 3, (a) The conjunctions between endothelial cells were tight and the mitochondria were normal in the control group (blue arrow). (b) The endothelial cells had diversified shapes and swelling mitochondria (arrowhead), and the conjunctions broke off (blue arrow) in the microbubble plus ultrasound group. (c) The mitochondria of tumor cells in the microbubble plus ultrasound group were swollen (blue arrow). (d) Platelets aggregated in the capillary vessels (blue arrow) in the microbubble plus ultrasound group.

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Discussion

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Conclusions

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References

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Academic Radiology, Volume 17, Issue 11
Journals General Radiology
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