Quantitative monitoring of adenocarcinoma development in rodents by magnetic resonance imaging

Purpose: Accurately following the time course of tumor progression and response to therapy in animal models of cancer is key to the development of better chemopreventive and chemotherapeutic agents. The goal of this work was to monitor quantitatively the development and progression of adenocarcinoma in a time course study of mice treated with the carcinogen urethane using in vivo small-animal magnetic resonance imaging (MRI). Experimental Design: Mice treated with a single dose of urethane were imaged at four time points beginning 8 months after treatment. High-resolution images of mouse lung were obtained in vivo using respiratory-gated MRI methods. Individual tumors were manually segmented and their volumes calculated. At the end of the study, mice were euthanized and MRI tumor quantification was validated by histology and histopathology. Results: Tumors as small as 0.4 mm in diameter can be detected and quantitatively measured in mice by in vivo MRI. Total tumor burden increased consistently in all mice studied, whereas the growth rate of individual tumors varied widely. The positions and diameters of individual tumors as measured by MRI correlated well with histology results. Histologic study of large, rapidly growing tumors showed that these were adenocarcinomas, whereas small, slowly growing lesions were predominantly adenomas. Conclusions: Longitudinal in vivo MRI is a powerful modality that can be of great aid in elucidating the factors that control the onset of lung tumors and can serve as a platform for the development and preclinical testing of novel therapies having a high likelihood of efficacy in human clinical trials.