1. CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
2. Department of Radiology, University of Pennsylvania, Pennsylvania, United States
3. CREATIS, CNRS UMR 5220 - INSERM U1206 - University of Lyon 1 - INSA Lyon, Lyon, France
4. Hospices Civils de Lyon, Radiology Department, Lyon, France
5. VOXCAN, 1 avenue Bourgelat, 69280 Marcy l'Etoile, France
6. LAGEPP, University of Lyon 1, CNRS UMR 5007, 43 bd 11 Novembre, 69622 Villeurbanne, France
Rationale & aim: Various types of cell therapies are currently under investigation for the treatment of ischemic stroke patients. To bridge the gap between cell administration and therapeutic outcome, there is a need for non-invasive monitoring of these innovative therapeutic approaches. Spectral photon counting computed tomography (SPCCT) is a new imaging modality that may be suitable for cell tracking. SPCCT is the next generation of clinical CT that allows the selective visualization and quantification of multiple contrast agents. The aims of this study are: (i) to demonstrate the feasibility of using SPCCT to longitudinally monitor and quantify therapeutic cells, i.e. bone marrow-derived M2-polarized macrophages transplanted in rats with brain damage; and (ii) to evaluate the potential of this approach to discriminate M2-polarized macrophages from their encapsulating scaffold.
Methods: Twenty one rats received an intralesional transplantation of bone marrow-derived M2-polarized macrophages. In the first set of experiments, cells were labeled with gold nanoparticles and tracked for up to two weeks post-injection in a monocolor study via gold K-edge imaging. In the second set of experiments, the same protocol was repeated for a bicolor study, in which the labeled cells are embedded in iodine nanoparticle-labeled scaffold. The amount of gold in the brain was longitudinally quantified using gold K-edge images reconstructed from SPCCT acquisition. Animals were sacrificed at different time points post-injection, and ICP-OES was used to validate the accuracy of gold quantification from SPCCT imaging.
Results: The feasibility of therapeutic cell tracking was successfully demonstrated in brain-damaged rats with SPCCT imaging. The imaging modality enabled cell monitoring for up to 2 weeks post-injection, in a specific and quantitative manner. Differentiation of labeled cells and their embedding scaffold was also feasible with SPCCT imaging, with a detection limit as low as 5,000 cells in a voxel of 250 × 250 × 250 µm in dimension in vivo.
Conclusion: Multicolor SPCCT is an innovative translational imaging tool that allows monitoring and quantification of therapeutic cells and their encapsulating scaffold transplanted in the damaged rat brain.
Keywords: multicolor spectral photon-counting CT, regenerative medicine, cell therapy, cell tracking, neurology