Abstract
.Significance: Stem cell therapies are of interest for treating a variety of neurodegenerative diseases and injuries of the spinal cord. However, the lack of techniques for longitudinal monitoring of stem cell therapy progression is inhibiting clinical translation.Aim: The goal of this study is to demonstrate an intraoperative imaging approach to guide stem cell injection to the spinal cord in vivo. Results may ultimately support the development of an imaging tool that spans intra- or postoperative environments to guide therapy throughout treatment.Approach: Stem cells were labeled with Prussian blue nanocubes (PBNCs) to facilitate combined ultrasound and photoacoustic (US/PA) imaging to visualize stem cell injection and delivery to the spinal cord in vivo. US/PA results were confirmed by magnetic resonance imaging (MRI) and histology.Results: Real-time intraoperative US/PA image-guided injection of PBNC-labeled stem cells and three-dimensional volumetric images of injection provided feedback necessary for successful delivery of therapeutics into the spinal cord. Postoperative MRI confirmed delivery of PBNC-labeled stem cells.Conclusions: The nanoparticle-augmented US/PA approach successfully detected injection and delivery of stem cells into the spinal cord, confirmed by MRI. Our work demonstrated in vivo feasibility, which is a critical step toward the development of a US/PA/MRI platform to monitor regenerative spinal cord therapies.
Highlights
In spite of great potential and substantial research, few stem cell therapies have reached clinical implementation
Our work demonstrated in vivo feasibility, which is a critical step toward the development of a US/PA/magnetic resonance imaging (MRI) platform to monitor regenerative spinal cord therapies
The bolus of PBNClabeled mesenchymal stem cells (MSCs) was visible at similar locations in intraoperative US/PA [Fig. 2(c)] and postoperative MR [Fig. 2(e)] images, which were spatially correlated at a qualitative level
Summary
In spite of great potential and substantial research, few stem cell therapies have reached clinical implementation. The lack of real-time longitudinal imaging feedback during procedures limits therapy development, making it challenging to evaluate outcomes from a research and clinical standpoint. Stem cell therapies of the spinal cord could benefit from intra- and postoperative image guidance.[1,2,3,4,5] In a recent clinical study, amyotrophic lateral sclerosis patients received stem cell treatments through direct injection into the spinal cord, which is appealing due to better outcomes in spite of high risk associated with the invasive surgical procedure.[2,5,6,7,8] Realtime intraoperative image guidance of needle insertion is desired to improve procedure safety and guide stem cell delivery to the tissue target to validate success prior to completing the Neurophotonics.
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