A Distinctive MRI-Based Absolute Bias Correction Protocol for the Potential Labelling and In Vivo Tracking of Stem Cells in a TBI Mice Model

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability. The condition is difficult to treat owing to its heterogeneous nature and complex biological pathways. Stem cell transplantation is an emerging self-deliverable therapeutic modality which could immensely improve the invigorating management of the problem. The synergistic interaction of the stem cells with the paracrine niche molecules at the site of injury is an end point that decides the cells’ effective tissue-forming regenerative response. Thus, noninvasive monitoring and tracking of the infused stem cells is quite decisive after transplantation. Here, we have designed and validated a distinctive in vivo magnetic resonance imaging protocol to monitor the transplanted mesenchymal stem cells (MSCs) longitudinally in TBI-induced mice. We have further described the synthesis of improved transverse relaxivity contrast agent, a protocol for the efficient labelling of MSCs, preparation of a TBI model system in mice, and the imaging and tracking of the implanted stem cells at the injury site through 7T MRI. MGE-T2∗ imaging in association with relaxometry-based quantitative assessment using absolute bias correction provided a suitable mechanism to monitor and track the infused labelled stem cells at the TBI site. High transverse relaxivity negative contrast agent synthesis, MSC labelling procedure, and quantitative T2∗ time measurement normalized with absolute bias correction are the key features of this protocol. This procedure has immense application potential and could therefore be extrapolated to stem cell tracking during the treatment of various diseases.