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Hyperpolarized 129 Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept
Vlora Riberdy1,2, Michael Litvack1, Elaine Stirrat1
1Translational Medicine Program, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada.
Purpose:
To measure regional changes in hyperpolarized 129 Xe MRI signal and apparent transverse relaxation ( ) 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. maps were calculated from 2D multi-echo data at each time point and changes in 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 . One hour after the instillation of SPION-labeled ALMs, the 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 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.
Insights
Hyperpolarized 129Xe MRI detected SPION-labeled alveolar-like macrophages (ALMs) in rat lungs for up to 1 hour. This technique shows promise for tracking stem cells in lung disease treatment.
Area of Science:
- Pulmonary Imaging
- Biomedical Engineering
- Nanomedicine
Background:
- Hyperpolarized 129Xe MRI offers unique insights into lung function.
- Superparamagnetic iron oxide nanoparticles (SPIONs) can be used for MRI contrast enhancement.
- Alveolar-like macrophages (ALMs) are being investigated for therapeutic applications in lung diseases.
Purpose of the Study:
- To assess regional changes in hyperpolarized 129Xe MRI signal and apparent transverse relaxation (T2*) after instilling SPION-labeled ALMs in rat lungs.
- To compare these MRI changes with histological findings.
- To evaluate the potential of this method for tracking SPION-labeled cells.
Main Methods:
- Mechanically ventilated rats underwent MRI before and after instillation of SPION-labeled or unlabeled ALMs.
- 2D multi-echo data were used to calculate T2* maps.
- Changes in MRI signal and T2* were quantified and compared to controls.
- Ex vivo histology was performed to correlate MRI findings with cell distribution.
Main Results:
- Signal loss and decreased T2* were observed immediately after instilling both unlabeled and SPION-labeled ALMs.
- SPION-labeled ALMs caused a persistent T2* decrease to 54.0 ± 7.0% of baseline at 1 hour.
- Unlabeled ALMs resulted in full T2* recovery to baseline.
- Histology confirmed co-localization of SPION-labeled ALMs with MRI signal abnormalities.
Conclusions:
- Hyperpolarized 129Xe MRI can detect SPION-labeled ALMs in rat airways up to 1 hour post-instillation.
- This MRI technique is a promising tool for targeting and tracking stem cells for lung disease therapy.
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