Article
Manganese (Mn)-enhanced magnet resonance imaging (MRI) for in vivo assessment of tissue regeneration following neuronal precursor cell transplantation after cervical spinal cord injury in rats
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Authors
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Moritz Scherer
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Alexander Younsi
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Lennart Riemann
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Guoli Zheng
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Thomas Skutella
- Universitätsklinikum Heidelberg, Institut für Anatomie, Heidelberg, Deutschland
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Manfred Jugold
- Deutsches Konsortium für Translationale Krebsforschung (DKTK), Abteilung Medizinische Bildverarbeitung, Heidelberg, Deutschland
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Andreas W. Unterberg
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Klaus Zweckberger
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | June 18, 2018 |
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Outline
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Objective: Stem cell therapy holds the possibility to leverage functional recovery after spinal cord injury (SCI). In animal models of SCI, MnMRI has been shown to enable in vivo assessment of the spinal cord after injury. Mn-uptake is dependent on intact neurons and correlates with functional repair. This study sought to evaluate if MnMRI is suitable for stem-cell treatment monitoring following a cervical spinal cord injury in rats.
Methods: Female Wistlar rats were exposed to a cervical clip-contusion/compression injury at level C5 (28g clip-force for 60s, n=15). On day 10 after injury, n=10 animals received transplantation of neuronal precursor cells (NPC) bilaterally ±2mm from lesion (4x105 NPCs). Treadmill training was applied to n=5 NPC animals (Group1). No special treatment was applied to the remaining 5 (Group2). Further n=5 animals received saline vehicle transplantation after SCI(Group3). Sham animals (n=5) received neither SCI nor NPCs. 8 weeks after injury, all animals were examined in a conventional 1.5 tesla MRI using a special rodent coil. As a contrast agent, 80mcl 0.8mM MnCl2 was injected into the cisterna magna 48h prior to scanning. Signal-to-noise ratios (SNR) in the ±4mm rostral and caudal peri-lesional areas were compared between groups.
Results: All animals were examined without difficulty with sufficient image quality showing the Mn-enhanced spinal cord in axial and sagittal T1 sequences. An intramedullary cyst could be observed in SCI animals (Group1-3). MnMRI enabled fair visual discrimination of spinal cord condition. SNR was significantly reduced caudal to the lesion compared to rostral in all groups (Groups1,2,sham: mean -0.74±0.33, p<0.05). Reduction was most pronounced in injured but untreated animals (Group3: mean -1.04±0.24, p<0.01) suggesting extensive persisting tissue damage in this group. Among SCI animals, there was no significant difference in SNR rostral to the lesion. NPC transplanted animals had significantly higher caudal SNR compared to vehicle (Group 1+2 vs. 3, p<0.01). Treadmill training had no additional effect on caudal SNR.
Conclusion: MnMRI enabled in vivo evaluation of SCI in rats. NPC treatment correlated with reduced SNR decay across the lesion site compared to vehicle, while treadmill training had no measurable effect on SNR. However, at 1,5 tesla changes in SNR were too discrete for reliable visual discrimination, which limits the applicability of MnMRI at this field strength.
