Iron imaging reveals tumor and metastasis macrophage hemosiderin deposits in breast cancer
(a) Multi-gradient echo (MGE) MRI image (first-echo) showing variation of contrast with increasing concentration of iron(III) (0-0-0.25 mg g-1). (b) Quantitative MRI measurements of signal relaxation rates R2* (= 1/ T2*) for the MGE image series as a function of iron(III) concentration (solid-line linear fit, dashed lines 95% confidence interval). (c) Parametric iron(III) maps generated for the standards, and H2O (dashed circle). (d) Iron MRI maps of whole blood, transferrin (Tfn, ~20μg iron/mL), macrophage hemosiderin from mouse spleen, superparamagnetic iron oxide (SPIO) nanoparticles in aqueous solution (200μg/mL), and in vivo in mammary tumors, livers (no tumor), and spleens (no tumor) of the MMTV-PyMT breast cancer models. Upper scale bar, 1mm, lower scale bar 2mm. Expansions show high-iron pixel cluster regions indicative of hemosiderin deposition. Scale bar 200μm. High-iron(III) MRI clusters quantified automatically by (e) counting the total number of high iron pixel clusters in the iron MRI images (0.15–0.3 mg iron(III) g-1 range), and (f) measuring the average cross-sectional areas of the clusters (mm2). Points are individual animals (mean±s.e.m.; n = 8 animals; n.s. not significant p>0.05, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 two-tailed unpaired t-test).