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Micro-magnetic Resonance Lymphangiography in Mice Using a Novel Dendrimer-based Magnetic Resonance Imaging Contrast Agent

Metabolism Branch, Center for Cancer Research, National Cancer Institute [H. K., T. A. W., Y. T.], Renal Diagnostics and Therapeutics Unit, National Institutes of Diabetes and Digestive and Kidney Diseases [R. A. S.], and Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute [M. W. B.], NIH, Bethesda, Maryland 20892, and Department of Radiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287 [S. K.]

Major advances in cancer biology and immunology have been gained using mouse models. However, very few methods are currently available to visualize the deep lymphatic system. A new micro-magnetic resonance lymphangiography (MRL) method in mice, which uses dendrimer-based magnetic resonance imaging contrast agents, was developed. Micro-MRL imaging clearly visualized most of the mouse lymphatic system, including both lymphatics and lymph nodes. This method could detect and distinguish among dilation of lymphatic vessels in a lymphangitis model, proliferative or neoplastic lymph node swellings in a lymphoproliferative model, and inflammatory lymph node swellings in an infection/inflammation model. Changes in the lymphoid system of transgenic mice overexpressing interleukin-15 could be visualized. Abnormal enlarged lymph nodes identified by micro-MRL were selectively removed and analyzed to demonstrate their cell type, receptor expression, and clonality in individual mice. We conclude that the enhanced resolution of this noninvasive micro-MRL can detect and classify lymphatic and lymph node abnormalities in mice, which should have wide applicability to the study of immunology and cancer in both experimental animals and clinical medicine.

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