Hyperpolarized 129 Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept study using superparamagnetic iron oxide nanoparticles

Abstract

Purpose: To measure regional changes in hyperpolarized ¹²⁹ Xe MRI signal and apparent transverse relaxation ( $T_2^{\ast }$ ) because of instillation of SPION-labeled alveolar-like macrophages (ALMs) in the lungs of rats and compare to histology.

Methods: MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION-labeled ALMs into either the left or right lung. $T_2^{\ast }$ maps were calculated from 2D multi-echo data at each time point and changes in $T_2^{\ast }$ were measured and compared to control rats receiving 4 million unlabeled ALMs. Histology of the ex vivo lungs was used to compare the regional MRI findings with the locations of the SPION-labeled ALMs.

Results: Regions of signal loss were observed immediately after instillation of unlabeled and SPION-labeled ALMs and persisted at least 1 h in the case of the SPION-labeled ALMs. This was reflected in the measurements of $T_2^{\ast }$ . One hour after the instillation of SPION-labeled ALMs, the $T_2^{\ast }$ decreased to 54.0 ± 7.0% of the baseline, compared to a full recovery to baseline after the instillation of unlabeled ALMs. Histology confirmed the co-localization of SPION-labeled ALMs with regions of signal loss and $T_2^{\ast }$ decreases for each rat.

Conclusion: Hyperpolarized ¹²⁹ Xe MRI can detect the presence of SPION-labeled ALMs in the airways 1 h after instillation. This approach is promising for targeting and tracking of stem cells for the treatment of lung disease.

Keywords: SPIONs; alveolar-like macrophages; hyperpolarized; lung; xenon.