Improved sensitivity of cellular MRI using phase-cycled balanced SSFP of ferumoxytol nanocomplex-labeled macrophages at ultrahigh field

Abstract

PurposeThe 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 methodsTHP-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 witĥ100 and ~1,000 labeled cells, respectively, at both 3 and 7 T.ResultsA 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, botĥ100 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.ConclusionThe 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.

Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI

“…However, these sequences only offer qualitative estimates of transplanted cell numbers and are vulnerable to blooming artifacts and low-signal elements like air, which impact assessment accuracy and interpretability. Preliminary progress has been made in improving FE-MRI field strength and sequence optimization for more sensitive or quantitative tracing of ferumoxytol-labeled cells [ 100 , 101 ]. Despite this, challenges in specificity, such as in vivo labeling involving multiple cell types and macrophage infiltration around implants which generate false positive signals, complicate the interpretation of FE-MRI results.…”

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利用活体成像技术判断经络穴位的存在性

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