International Journal of Nanomedicine (Jul 2018)
Improved sensitivity of cellular MRI using phase-cycled balanced SSFP of ferumoxytol nanocomplex-labeled macrophages at ultrahigh field
Abstract
Yelong Shen,1,2 Lirong Yan,1 Xingfeng Shao,1 Bin Zhao,2 Jinlun Bai,3 Wange Lu,3 Danny JJ Wang1 1Laboratory of FMRI Technology (LOFT), Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA; 2Shandong Medical Imaging Research Institute, School of Medicine, Shandong University, Jinan, Shangdong, China; 3Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA 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
