Non-invasive Imaging of the In Situ Restoration of Brain Tissue Abstract Regenerative medicine is gradually merging the use of stem cells and biomaterials into tissue engineering to repair damaged tissues. Developments in tissue engineering of the brain have been slow, mostly due to accessibility of the brain and being able to monitor the ongoing process non-invasively. However, non-invasive imaging, such as MRI, provides information as to the site and extent of damage in the brain, affording image- guided injection of material for tissue engineering. However, little progress has been achieved in monitoring implanted cells, as well as biomaterial non-invasively. One major challenge is to visualize these different components non-invasively without the detection of one affecting the detection of the other, or potentially the visualization of brain damage. A significant development of non-invasive imaging is therefore needed to facilitate our ability to monitor the evolution of i situ tissue engineering inside the brain. Specifically, we here aim to: 1) develop magnetic resonance imaging-based paramagnetic chemical exchange saturation transfer (PARA-CEST) to distinguish human neural stem cells (NSCs) and human endothelial cells (ECs) and 2) establish a CEST based imaging of a de-cellularized extracellular matrix (ECM) bioscaffold without interfering with our ability to detect a stroke-induced lesion cavity. These studies will provide the framework to monitor in situ tissue engineering for stroke.

Public Health Relevance

Regenerative medicine is increasingly finding translations from the bench to the bedside. As stem cells are integrated with biomaterials for in situ tissue engineering, the complexity of the procedure is increasing and it is becoming important to monitor how these processes interact over time in vivo. Translation of this non-invasive monitoring into patients requires the development and implementation of appropriate approaches. Our proposal here aims to develop chemical exchange saturation transfer (CEST), a non-invasive MRI technique, as a core platform to visualize multiple cell types, as well as biomaterials, while maintaining our ability to characterize newly forming tissue with other MRI techniques, such as MRS, as well as diffusion and perfusion MRI. Very significant technological, as well as neurobiological challenges, however, need to be addressed before we can integrate this multi-parametric MRI into an efficient non-invasive assessment of in situ tissue engineering. The proposed studies aim to address these challenges and provide a framework within which we can eventually explore the therapeutic potential of this approach. If a newly functional tissue can be generated to replace that which is lost due to the stroke, this approach could indeed dramatically change the long-term outcome after stroke.

National Institute of Health (NIH)
Research Project (R01)
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Clinical Molecular Imaging and Probe Development (CMIP)
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Lavaute, Timothy M
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University of Pittsburgh
Schools of Medicine
United States
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Chou, Chung-Hsing; Sinden, John D; Couraud, Pierre-Olivier et al. (2014) In vitro modeling of the neurovascular environment by coculturing adult human brain endothelial cells with human neural stem cells. PLoS One 9:e106346