In vivo application of magnetic resonance imaging contrast agents for tissue optical clearing (Conference Presentation)

Abstract

Solving the problem of limited depth penetration of light in vivo remains important due to the innate high scattering of light in the tissues. One way to reduce tissue scattering is to apply immersion optical clearing using chemical agents. This reversible process is based on partial replacement of tissue intercellular fluid with clearing agents, which leads to matching of refractive indices between tissue components as well as tissue dehydration and consequently to more regular packing of tissue structural elements. Earlier we discovered that low molecular weight MRI contrast agents have the ability of optical clearing [1]. This was shown for the first time in the case of mouse skin samples ex vivo. The next logical step included an in vivo study. The expected advantages of using MRI contrast agent compositions as optical clearing agents are: 1) their biocompatibility; 2) the possibility of combining the areas of enhanced contrast of MRI and optical images in time and space. The effect of optical clearing was obtained when MRI contrast agents were applied to the surface of mouse skin in vivo. We used the following MRI contrast agents: Gadavist (Bayer HealthCare Pharmaceuticals, Germany), Magnevist (Bayer HealthCare Pharmaceuticals, Germany) and Dotarem (Guerbet, France). The Spectral Radar OCT System OCP930SR 022 (Thorlabs Inc., United States) with a wavelength of 930 nm was used to quantify the change in the optical properties of the skin. After hair removal from the mouse skin, a B-scan of the intact skin region with OCT was recorded. Then, the selected MRI agent was applied topically to the target skin area. Skin OCT scans were recorded every 5-10 min during the exposure of the skin area to an MRI agent. The solution was removed each time before scanning and applied again after scanning. OCT showed an increase in the penetration depth of the light beam into the tissue and resulted in more contrast images of the skin by reducing skin scattering for each of the used MRI agents. OCT data were processed to quantify the diffusion coefficients of MRI agents in the skin and the effectiveness of optical clearing of skin using these agents. The obtained results show the possibility of not only improving the quality of optical imaging, but also open the way for the implementation of a new approach to multimodality, when synchronization in time and space of regions with increased contrast of both the optical image and MRI image is automatically ensured since the same agent enables both effects simultaneously.