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Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Characterization of the inflammatory response in a photothrombotic stroke model by MRI: implications for stem cell
Caroline Vandeputte1, Debby Thomas, Tom Dresselaers
1Division of Nuclear Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Purpose:
The aim of this study was to evaluate the specificity of magnetic resonance imaging (MRI) contrast in a photothrombotic (PT) stroke model with and without engraftment of superparamagnetic iron oxide (SPIO)-labeled stem cells.
Procedures:
We monitored animals with PT stroke versus animals with PT stroke and stem cell engraftment by T(2)/T(2)*w MRI 4-8 h and 2, 4, 6/7 and 14 days after PT induction. Results were correlated with immunohistochemistry.
Results:
T(2)*w MRI images showed hypointense contrast due to the accumulation of inflammatory cells and corresponding iron accumulation and glial scar formation in the border zone of the lesion, similar as what was observed for SPIO-labeled cells. Histological analysis was thus indispensable to distinguish between labeled transplanted cells and immune cells.
Conclusion:
These results raise caution regarding the non-invasive monitoring of SPIO-labeled transplanted stem cells by MRI in models that result in a strong inflammatory response.
Insights
Magnetic resonance imaging (MRI) contrast in photothrombotic (PT) stroke models can be misleading. Histology is essential to differentiate SPIO-labeled stem cells from inflammatory cells in PT stroke models.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Regenerative Medicine
Background:
- Photothrombotic (PT) stroke models are used to study stroke pathophysiology.
- Superparamagnetic iron oxide (SPIO)-labeled stem cells are investigated for cell tracking in vivo.
- Magnetic resonance imaging (MRI) is a key tool for non-invasive monitoring of cell therapies.
Purpose of the Study:
- To evaluate the specificity of MRI contrast in a PT stroke model.
- To assess MRI contrast with and without SPIO-labeled stem cell engraftment.
- To determine if MRI can reliably distinguish SPIO-labeled cells from endogenous cells.
Main Methods:
- Animals underwent PT stroke induction.
- T(2)/T(2)*-weighted MRI was performed at multiple time points post-induction.
- Animals were either engrafted with SPIO-labeled stem cells or not.
- MRI results were correlated with immunohistochemistry.
Main Results:
- T(2)*-weighted MRI showed hypointense contrast in the lesion border zone.
- This hypointensity was attributed to inflammatory cell accumulation and iron deposition.
- Similar signal changes were observed with SPIO-labeled cells, complicating interpretation.
- Histological analysis was crucial for differentiating SPIO-labeled cells from immune cells.
Conclusions:
- MRI contrast in PT stroke models with stem cell engraftment can be confounded by inflammation.
- Non-invasive monitoring of SPIO-labeled stem cells using MRI requires careful interpretation in inflammatory settings.
- Histological validation is indispensable for accurate assessment of cell engraftment and distribution.
