Nanosensitive optical coherence tomography for detecting structural changes in stem cells.

Mesenchymal stromal cells (MSCs) are adult stem cells that have been widely investigated for their potential to regenerate damaged and diseased tissues. Multiple pre-clinical studies and clinical trials have demonstrated a therapeutic response following treatment with MSCs for various pathologies, including cardiovascular, neurological and orthopaedic diseases. The ability to functionally track cells following administration in vivo is pivotal to further elucidating the mechanism of action and safety profile of these cells. Effective monitoring of MSCs and MSC-derived microvesicles requires an imaging modality capable of providing both quantitative and qualitative readouts. Nanosensitive optical coherence tomography (nsOCT) is a recently developed technique that detects nanoscale structural changes within samples. In this study, we demonstrate for the first time, the capability of nsOCT to image MSC pellets following labelling with different concentrations of dual plasmonic gold nanostars. We show that the mean spatial period of MSC pellets increases following the labelling with increasing concentrations of nanostars. Additionally, with the help of extra time points and a more comprehensive analysis, we further improved the understanding of the MSC pellet chondrogenesis model. Despite the limited penetration depth (similar to conventional OCT), the nsOCT is highly sensitive in detecting structural alterations at the nanoscale, which may provide crucial functional information about cell therapies and their modes of action.

Accessing depth-resolved high spatial frequency content from the optical coherence tomography signal.

Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. Conventional intensity-based OCT provides depth-resolved imaging with a typical resolution and sensitivity to structural alterations of about 5-10 microns. It would be desirable for functional biological imaging to detect smaller features in tissues due to the nature of pathological processes. In this article, we perform the analysis of the spatial frequency content of the OCT signal based on scattering theory. We demonstrate that the OCT signal, even at limited spectral bandwidth, contains information about high spatial frequencies present in the object which relates to the small, sub-wavelength size structures. Experimental single frame imaging of phantoms with well-known sub-micron internal structures confirms the theory. Examples of visualization of the nanoscale structural changes within mesenchymal stem cells (MSC), which are invisible using conventional OCT, are also shown. Presented results provide a theoretical and experimental basis for the extraction of high spatial frequency information to substantially improve the sensitivity of OCT to structural alterations at clinically relevant depths.