Abstract

The poor prognosis for patients with high-grade glioma is partly due to the invasion of tumor cells into surrounding brain tissue. The goal of the present work was to develop a mouse model of glioma that included the potential to track cell invasion using MRI by labeling GL261 cells with iron oxide contrast agents prior to intracranial injection. Two types of agents were compared with several labeling schemes to balance between labeling with sufficient iron to curb the dilution effect of cell division while avoiding overwhelming signal loss that could prevent adequate visualization of tumor boundaries. The balanced steady-state free precession (bSSFP) pulse sequence was evaluated for its suitability for imaging glioma tumors and compared to T(2)-weighted two-dimensional fast spin echo (FSE) and T(1)-weighted spoiled gradient recalled echo (SPGR) at 3 T in terms of signal-to-noise ratio and contrast-to-noise ratio efficiencies. Ultimately, a three-dimensional bSSFP protocol consisting of a set of two images with complementary contrasts was developed, allowing excellent tumor visualization with minimal iron contrast when using pulse repetition time = 6 ms and alpha = 40 degrees, and extremely high sensitivity to iron when using pulse repetition time = 22 ms and alpha = 20 degrees. Quantitative histologic analysis validated that the strong signal loss seen in balanced steady state free precession pulse sequence images of iron-loaded tumors correlated well with the presence of iron.

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