Quantitative evaluation of MRI-based tracking of ferritin-labeled endogenous neural stem cell progeny in rodent brain

Endogenous neural stem cells have the potential to facilitate therapy for various neurodegenerative brain disorders. To increase our understanding of neural stem and progenitor cell biology in healthy and diseased brain, methods to label and visualize stem cells and their progeny in vivo are indispe...

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Bibliographic Details
Published in:NeuroImage (Orlando, Fla.) Fla.), 2012-08, Vol.62 (1), p.367-380
Main Authors: Vande Velde, Greetje, Raman Rangarajan, Janaki, Vreys, Ruth, Guglielmetti, Caroline, Dresselaers, Tom, Verhoye, Marleen, Van der Linden, Annemie, Debyser, Zeger, Baekelandt, Veerle, Maes, Frederik, Himmelreich, Uwe
Format: Article
Language:English
Subjects:
Animals
Atoms & subatomic particles
Bias field correction
Brain
Cell adhesion & migration
Cell division
Cell tracking
Cell Tracking - methods
Computer simulation
Contrast agents
Contrast Media
Endogenous neurogenesis
Female
Ferritin
Ferritins
Image Enhancement - methods
Image processing
Magnetic Resonance Imaging - methods
Medical imaging
Mice
Mice, Inbred C57BL
MRI
Neural stem cells
Neurons - cytology
Olfactory Bulb - cytology
Reporter gene
Reproducibility of Results
Sensitivity and Specificity
Staining and Labeling
Stem cells
Stem Cells - cytology
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Summary:Endogenous neural stem cells have the potential to facilitate therapy for various neurodegenerative brain disorders. To increase our understanding of neural stem and progenitor cell biology in healthy and diseased brain, methods to label and visualize stem cells and their progeny in vivo are indispensable. Iron oxide particle based cell-labeling approaches enable cell tracking by MRI with high resolution and good soft tissue contrast in the brain. However, in addition to important concerns about unspecific labeling and low labeling efficiency, the dilution effect upon cell division is a major drawback for longitudinal follow-up of highly proliferating neural progenitor cells with MRI. Stable viral vector-mediated marking of endogenous stem cells and their progeny with a reporter gene for MRI could overcome these limitations. We stably and efficiently labeled endogenous neural stem/progenitor cells in the subventricular zone in situ by injecting a lentiviral vector expressing ferritin, a reporter for MRI. We developed an image analysis pipeline to quantify MRI signal changes at the level of the olfactory bulb as a result of migration of ferritin-labeled neuroblasts along the rostral migratory stream. We were able to detect ferritin-labeled endogenous neural stem cell progeny into the olfactory bulb of individual animals with ex vivo MRI at 30weeks post injection, but could not demonstrate reliable in vivo detection and longitudinal tracking of neuroblast migration to the OB in individual animals. Therefore, although LV-mediated labeling of endogenous neural stem and progenitor cells resulted in efficient and stable ferritin-labeling of stem cell progeny in the OB, even with quantitative image analysis, sensitivity remains a limitation for in vivo applications. ► Ferritin (FerrH) as a reporter gene for MRI. ► Lentiviral vector injection to label endogenous neural stem cells with ferritin. ► Ferritin-labeled neuroblasts migrated into olfactory bulb can be detected by MRI. ► Intensity inhomogeneity correction is prerequisite for unbiased quantification.
ISSN:1053-8119
1095-9572
DOI:10.1016/j.neuroimage.2012.04.040