Functional Dynamic Contrast-Enhanced Magnetic Resonance Imaging in an Animal Model of Brain Metastases: A Pilot Study

Abstract

BackgroundBrain 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.MethodsWith 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.ResultsNo 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.ConclusionsThe 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.

Image-guided surgery of head and neck carcinoma in rabbit models by intra-operatively defining tumour-infiltrated margins and metastatic lymph nodes

“…Animal experiments were performed in compliance with the policy on animal use and ethics established by the Ethics Committee of Shanghai Ninth People's Hospital. VX2 tumour models were established according to procedures in our previous study with slight modifications [12]. Briefly, VX2 tumours were initially grown in the right hind limb of a donor rabbit (maintained at our institute).…”

Radiotherapy in Preclinical Models of Brain Metastases: A Review and Recommendations for Future Studies

“…Animal models for BM encompass diverse species, including mice [30,38,41,43,49,56,[60][61][62][63][64][65] , rats [48,72,77,112,113] , monkeys [114] , dogs [115] , rabbits [116] , and chick embryos [117][118][119] , with mice being predominantly the predominant ones used (Figure 3A). The organ tropism of tumor cells in chick embryos was recently found to be consistent with that in mice [118] .…”

Development of Rabbit Brain Tumor Model Using VX2 Cells and Verification with the MRI in Neuroradiologic Research

“…중심부 괴사가 크고 종양 주변에는 부종이 생기며 아주 급격히 자라고 침범하며 주변 뇌 조직으로 작은 군집을 만들며 자라 나가기 때문이다( 3 16 ). 또한 혈관이 풍부한 특성 때문에 혈관신생 연구( 6 17 )에, 그리고 신경영상의학과 영역의 뇌종양의 영상화( 1 18 19 ), 중재시술( 20 ) 등의 연구에 잘 사용된다. 임상적인 관점에서는 항암제 요법, 면역치료, 방사선 요법 및 수술 등의 복합 치료에 대한 연구를 이 모델로 할 수 있다는 의의가 있다.…”