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

Abstract

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 10-35ms (Q1), 36-60ms (Q2) and 61-86ms (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.