Optical clearing of mouse skin samples using MR and X-ray agents
Nikita S. Chikalkin1, Daria K. Tuchina,1,2 Olga A. Sindeeva,1 Alexander P. Savitsky,3
Alexei A. Bogdanov, Jr. 3,4 Valery V. Tuchin1,2,5
1Saratov State University, Saratov, Russia;
2National Research Tomsk State University, Tomsk, Russia;
3Federal Research Center of Biotechnology, Russian Academy of Sciences, Moscow, Russia;
4University of Massachusetts Medical School, Worcester, MA, USA;
5Institute of Precision Mechanics and Control, Russian Academy of Sciences, Saratov, Russia
Abstract
One of the goals of biomedical optics is the development of methods for probing biological tissues with visible and near infrared (NIR) radiation, which enables visualization of their fine structure. The interest in developing these methods stems from the potential of optical imaging in developing safe and multiparametric diagnostics of biological tissues. Currently, the transparency window in the wavelength range from 650 to 1200 nm is used for optical sensing of biological tissues.
The penetration of light into the tissue at greater depths allows to obtain valuable information about the structure, physiological state and tissue pathology. Due to multiple scattering and absorption of light by tissue components/inclusions the light beam expands and weakens as it travels through the tissue thereby complicating gathering of such information. However, light scattering in biological tissues can be significantly reduced by using optical clearing agents (OCAs).
In this work, we investigated the possibility of using MRI and X-ray contrast agents: Gadovist, Magnevist, Dotarem and Visipaque, as OCAs. The use of these contrast agents may potentially facilitate multimodality imaging, i.e. bi- or tri-modal imaging including optical, MRI and CT simultaneously or sequentially.
Mouse skin samples were used as model biological tissue. The experimental study included measuring the collimated transmission of light at different wavelengths through the samples using a USB4000-Vis-NIR spectrometer (Ocean Optics, USA). OCA application was compared to 0.9% NaCl as control.
Based on the results of light transmission measurements the following conclusions were made: significant optical clearing was obtained using MRI and X-ray contrast agents. The application of clinical paramagnetic MR contrast agent Gadovist (gadobutrol) resulted in transmission increase by 5 times in 70 min, and the use of Magnevist (GdDTPA dimeglumine) resulted in the same level of optical clearing but required longer applications (180 min).
Dotarem and Magnevist during the course of their action on skin samples led to tissue swelling and showed the greatest weight gain in comparison to other agents. The weight of the samples immersed in Dotarem and Magnevist increased by 31% and 33%, respectively. Visipaque and Gadovist did not result in any significant swelling (measured as the increase of skin sample mass). In conclusion, our experiments show that concentrated paramagnetic and iodine-containing contrast agents available for clinical use are efficient as OCA of model tissue and may be useful for multimodality imaging that combines optical with magnetic resonance or CT imaging.
Acknowledgment. This work was supported by the Government of the Russian Federation (grant no 14.W03.31.0023 to support scientific research projects implemented under the supervision of leading scientists at Russian institutions and Russian institutions of higher education).
Speaker
Nikita Chikalkin
Saratov state University
Russia
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