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Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T

This study uses quantitative T2* imaging to track ferumoxides–protamine sulfate (FEPro)‐labeled MDA‐MB‐231BR‐Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro‐labeled, unlabeled or tumor necrosis factor‐related apoptosis‐inducing ligand(TRAIL)‐treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3–4 weeks using gradient multi‐echo and turbo spin‐echo pulse sequences at 3 T with a solenoid receive‐only 4‐cm‐diameter coil. Quantitative T2* maps of the whole brain were obtained by the application of single‐exponential fitting to the signal intensity of T2* images, and the distribution of T2* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T2* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro‐labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T2* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T2* values in the ranges 10–35 ms (Q1), 36–60 ms (Q2) and 61–86 ms (Q3) from 1 day to 3 weeks post‐infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T2* obtained from serial MRI in rats receiving unlabeled or TRAIL‐treated cells or saline. Histologic analysis demonstrated isolated Prussian blue‐positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T2* analysis of FEPro‐labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T2*‐weighted images. Published in 2010 by John Wiley & Sons, Ltd.