MONITORING OF OPTICAL CLEARING EFFECTS BY FLUORESCENCE AND MAGNETIC RESONANCE IMAGING IN VIVO
Alexei A. Bogdanov Jr.1,2 , Natalia I. Kazachkina 2, Victoria V. Zherdeva2, Irina G. Meerovich 2, Ilya D. Solovyev 2, Daria K. Tuchina 2,3,4, Alexander P. Savitsky 2, Valery V. Tuchin 2,3,4,5
1 University of Massachusetts Medical School, Radiology, Worcester, Massachusetts, United States of America
2 A.N.Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, Russian Federation
3 Saratov State University, Saratov, Russian Federation
4 Tomsk State University, Tomsk, Russian Federation
5 Institute of Precision Mechanics and Control of the Russian Academy of Sciences, Saratov, Russian Federation
Abstract
Optical clearing is an efficient strategy for increasing the depth of light penetration into the non-transparent biological tissues in experimental optical imaging. The effects of optical clearing (OC) compositions, i.e.: 1) diamagnetic glycerol/DMSO/water; 2) concentrated paramagnetic magnetic resonance (MR) imaging agent (gadobutrol); 3) diluted paramagnetic 75%gadobutrol/5%DMSO/water were studied by measuring fluorescence intensity (FI) and magnetic resonance signal changes in the tissues in vivo before and after topical application of OC compositions. Mouse models of subcutaneous tumor expressing endogenous TagRFP red fluorescent protein marker were used for comparing the changes of FI measured over several tumor foci before and after OC application onto the skin surface. By using a macroscopic CCD camera imaging as well as tumor foci microscopy with a TCSPC detector setup we observed time dependent increase of the overall TagRFP FI. Both diamagnetic and paramagnetic OC compositions resulted in a similar level of tumor FI/skin ratio improvement at 15-30 min after OC application. By using OC containing 100% gadobutrol we observed up to 15-20% increase of FI and 30-35% increase of tumor/skin ratio in the case of gadobutrol/DMSO/water mixture. The tracking of 1T MR signal intensity changes within selected regions of interest (ROI) located close to the skin surface before, during and after OC was performed by using two pulse sequences: 1) T2-weighted (T2w) fast spin-echo pulse sequences in the case of diamagnetic glycerol-containing OC mixtures and 2) 3D GRE pulse sequences for imaging paramagnetic gadobutrol-induced changes of MR signal. We observed significant quantitative differences between Gaussian noise-normalized MRI signal intensities before and after OC. The interpretation of observed changes was made in view of a potential transient change of the peripheral tumoral microenvironment induced by glycerol/DMSO/water mixture resulting in: 1) shortening of mean proton relaxation times within the voxels of subcutaneous tumor (i.e. T2w hypointensity increase); 2) decrease of T1w signal in the skin due to high concentration of gadobutrol in OC resulting in magnetic susceptibility effects; 3) transient increase of T1w signal in subdermal layer due to gadobutrol penetration through the skin. The latter was observed only in the case of 75% gadobutrol OC composition. The obtained results indicate that MRI is important modality enabling mechanistic studies of OC effects in the skin and peripheral subcutaneous tissue. A combination of optical imaging and MRI with registration of optical and MR signal change in the same voxels of live tissue could potentially be useful for improving accuracy of image reconstruction and for multimodality imaging.
Speaker
Alexei Bogdanov, Jr
UMASS, Worcester, MA and FBRC RAS, Moscow Russia
Russia
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