Functional dynamic contrast-enhanced magnetic resonance imaging in an animal model of brain metastases: a pilot study.

Background: Brain metastasis is a common disease with a poor prognosis. The purpose of this study is to test feasibility and safety of the animal models for brain metastases and to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to enhance detection of brain metastases.

Methods: With approval from the institutional animal ethics committee, 18 New Zealand rabbits were randomly divided into three groups: Group A received an intra-carotid infusion (ICI) of mannitol followed by VX2 cells; group B received successive ICI of mannitol and heparin followed by VX2 cells; and group C received an ICI of normal saline. The survival rate and clinical symptoms were recorded after inoculation. After two weeks, conventional MRI and DCE-MRI were performed using 3.0 Tesla scanner. The number of tumors and detection rate were analyzed. After MRI measurements, the tumors were stained with hematoxylin-eosin.

Results: No rabbits died during the procedure. The rabbits had common symptoms, including loss of appetite, lassitude and lethargy, etc. at 10.8±1.8 days and 8.4±1.5 days post-inoculation in group A and B, respectively. Each animal in groups A and B re-gained the lost weight within 14 days. Brain metastases could be detected by MRI at 14 days post-inoculation in both groups A and B, with metastases manifesting as nodules in the brain parenchyma and thickening in the meninges. DCE-MRI increased the total detection of tumors compared to non-contrast MRI (P<0.05). The detection rates of T1-weighted image, T2-weighted image and DCE-MRI were 12%, 32% and 100%, respectively (P<0.05). Necropsy revealed nodules or thickening meninges in the gross samples and VX2 tumor cytomorphologic features in the slides, which were consistent with the MRI results.

Conclusions: The VX2 rabbit model of brain metastases is feasible, as verified by MRI and pathologic findings, and may be a suitable platform for future studies of brain metastases. Functional DCE-MRI can be used to evaluate brain metastases in a rabbit model.