Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T.
This study uses quantitative T(2)* 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 T(2)* maps of the whole brain were obtained by the application of single-exponential fitting to the signal intensity of T(2)* images, and the distribution of T(2)* 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 T(2)* 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 T(2)* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T(2)* 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 T(2)* 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 T(2)* analysis of FEPro-labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T(2)*-weighted images.
Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA. hotsong@yuhs.ac
Ho-Taek
HT
Song
Elaine K
EK
Jordan
Bobbi K
BK
Lewis
Eric
E
Gold
Wei
W
Liu
Joseph A
JA
Frank
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003911:Dextrans / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011479:Protamines / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude
D003911:Dextrans; D058185:Magnetite Nanoparticles; D011479:Protamines; C065507:ferumoxides