Towards registration of optical and MR signal changes in subcutaneous tumor volume in vivo after optical skin clearing

Abstract

The goal of this research was in testing magnetic resonance imaging (MRI) pulse sequences for monitoring local changes of proton relaxation times after the local application of skin optical clearing (OC) compositions in vivo. We used xenograft mouse models of cancer, i.e. nu/nu mice bearing subcutaneous tumors expressing endogenous TagRFP red fluorescent protein marker and tested the changes in fluorescence intensity and lifetime (FL) of the subcutaneous tumor foci after OC application (70% glycerol, 5% DMSO, 25% water) onto the skin. By using time-correlated single photon counting within 20-30 min after the OC we observed: 1) 30-40% increase in the overall photon numbers output; 2) 50 ps increase in the median FL of TagRFP. We subsequently performed tracking of MR signal intensity changes within selected regions of interest (ROI) located close to the skin surface before, during and after OC. The analysis of 1T MR T2-weighted (T2w) fast spin-echo images showed significant quantitative differences between Gaussian noise-normalized MRI signal intensities (Mann-Whitney test, p<0.05). Our results suggest that the application of OC may cause: 1) a transient change of the peripheral tumoral microenvironment and as a consequence, FL increase and shortening of mean proton relaxation times within the voxels of subcutaneous tumor (i.e. T2w hypointensity increase); 2) potential microviscosity change due to the permeability for the OC components resulting in shortening of tissue water proton relaxation times. The results suggest that T2w 1T MRI was useful for semi-quantitative monitoring of MR signal intensity longitudinal changes in the subcutaneous space during and after OC thereby enabling registration of optical and MR signal fluctuations in the same voxels of live tissue.