In vivo imaging of endogenous neural stem cells in the adult brain

Abstract

The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3’-deoxy-3’-[¹⁸F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.

Keywords: Neural stem cells, Positron emission tomography, Magnetic resonance imaging, 3’-deoxy-3’-[¹⁸F]fluoro-L-thymidine, [¹¹C]PK11195

Core tip: Endogenous neural stem cells (eNSCs) in the adult mammalian brain can be mobilized by, e.g., pharmacological methods to facilitate regeneration and enhance functional recovery in neurological disease. In order to translate experimental approaches into the clinical setting, non-invasive imaging of eNSCs is required to monitor their fate in vivo. This review summarizes current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as Positron-Emission-Tomography, placing emphasis on the specificity of the signal obtained, as well as on their potential for clinical translation.