Purpose: The purpose of this study was to investigate the feasibility and sensitivity of cellular magnetic resonance imaging (MRI) with ferumoxytol nanocomplex-labeled macrophages at ultrahigh magnetic field of 7 T.
Materials and methods: THP-1-induced macrophages were labeled using self-assembling heparin + protamine + ferumoxytol nanocomplexes which were injected into a gelatin phantom visible on both microscope and MRI. Susceptibility-weighted imaging (SWI) and balanced steady-state free precession (bSSFP) pulse sequences were applied at 3 and 7 T. The average, maximum intensity projection, and root mean square combined images were generated for phase-cycled bSSFP images. The signal-to-noise ratio and contrast-to-noise ratio (CNR) efficiencies were calculated. Ex vivo experiments were then performed using a formalin-fixed pig brain injected with ~100 and ~1,000 labeled cells, respectively, at both 3 and 7 T.
Results: A high cell labeling efficiency (>90%) was achieved with heparin + protamine + ferumoxytol nanocomplexes. Less than 100 cells were detectable in the gelatin phantom at both 3 and 7 T. The 7 T data showed more than double CNR efficiency compared to the corresponding sequences at 3 T. The CNR efficiencies of phase-cycled bSSFP images were higher compared to those of SWI, and the root mean square combined bSSFP showed the highest CNR efficiency with minimal banding. Following co-registration of microscope and MR images, more cells (51/63) were detected by bSSFP at 7 T than at 3 T (36/63). On pig brain, both ~100 and ~1,000 cells were detected at 3 and 7 T. While the cell size appeared larger due to blooming effects on SWI, bSSFP allowed better contrast to precisely identify the location of the cells with higher signal-to-noise ratio efficiency.
Conclusion: The proposed cellular MRI with ferumoxytol nanocomplex-labeled macrophages at 7 T has a high sensitivity to detect <100 cells. The proposed method has great translational potential and may have broad clinical applications that involve cell types with a primary phagocytic phenotype.
Keywords: ultrasmall superparamagnetic iron oxide nanoparticles, ultrahigh field, balanced steady-state free precession, cellular magnetic resonance imaging, self-assembling nanocomplexes, 7 T

摘要视频链接：Phase-cycled bSSFP of ferumoxxytol nanocomplex-labeled macrophages at 7T