Multicolor spectral photon counting CT monitors and quantifies therapeutic cells and their encapsulating scaffold in a model of brain damage

Abstract

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.

Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke

“…[ 55 ] In addition, SPCCT was recently shown to be very promising for monitoring and quantifying gold‐labeled macrophages in rat brain. [ 56 ] More data are needed to fully assess the safety profile of NanoGd, especially with regards to a potential brain accumulation. Provided that those data confirm the absence of long‐term toxicity, NanoGd‐enhanced SPCCT may become an alternative imaging approach for the cellular and molecular imaging of inflammatory responses.…”

In Vivo Molecular K-Edge Imaging of Atherosclerotic Plaque Using Photon-counting CT

“…Even pre-injection imaging with CT would not be satisfactory because of strong artifacts surrounding the calcifications that could mask small focal enhancement. Therefore, a need exists for a specific imaging technique, such as PCCT k-edge imaging, that, as demonstrated by several proof-of-concept studies, has the capacity to specifically detect and quantify contrast materials (5,(9)(10)(11)(15)(16)(17)27,28). An ideal PCCT contrast material for the evaluation of coronary arteries needs to combine macrophage specificity and a high payload of an element suitable for k-edge imaging, such as ytterbium, gadolinium, or gold nanoparticles, among others (27)(28)(29).…”

“…In addition, gold nanoparticles are highly biocompatible, are extremely dense, and have low viscosity, which is important for in vivo applications (11). To date, PCCT has shown encouraging results for cardiovascular imaging in phantoms, animals, and human studies (7,(12)(13)(14), including proof of concept of k-edge imaging for assessing atherosclerotic change (9,(15)(16)(17)(18)(19).…”

DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

“…[ 26 ] In the last decade, a better understanding of tumor biology and synthesis of versatile nanomaterials such as polymers and polymer gels, lipids, inorganic NPs, and biomacromolecular scaffolds has aided the development of novel theranostic platforms for cancer. [ 11,14,21b,27 ] The development of such materials is very diverse and extensively reviewed elsewhere. [ 28 ]…”