Optical clearing and multimodality fluorescence and magnetic resonance imaging in cancer models

Abstract

Optical clearing (OC) increases the depth of light penetration and improves the outcomes of optical imaging measurements in situ and in vivo. In vivo OC protocols have to be biocompatible and should result in transient effects with minimal long-term damage to the tissues. The effects of various OC compositions in vivo were previously studied by using primarily optical imaging. Multimodality registration of optical and magnetic resonance imaging (MRI) signals in the same voxels of live tissue could be useful for improving accuracy of optical image reconstruction. We investigated OC effects on fluorescence intensity (FI) imaging of red fluorescent TagRFP protein marker in tumor cells and combined it with MRI. The OC effects of diamagnetic glycerol/DMSO/water and a paramagnetic magnetic resonance (MR) imaging agent (gadobutrol) and its mixtures were measured by using whole body FI, a single-photon counting FI setup and three MRI pulse sequences: 1) T2-weighted fast spin-echo; 2) diffusion-weighted and 2) 3D gradient-echo. A time-dependent increase of TagRFP FI resulted in tumor FI/skin ratio improvement at 15-30 min after OC. 0.7M solution of gadobutrol in DMSO/water was more efficient than 1.M gadobutrol (30-35% vs.15-20% increase of FI). The observed MRI signal intensity changes were most likely due to a combination of several effects, i.e. 1) longitudinal proton relaxation time shortening in subcutaneous tumor; 2) magnetic susceptibility effects of gadobutrol; 3) transient increase of T1w signal due to gadobutrol penetration through the skin and dilution in extracellular volume. The obtained results indicate that MRI can be instrumental in enabling mechanistic studies of OC effects in the skin and peripheral subcutaneous tissue.