Laboratory for Molecular Imaging

Scientific results:

1. We have installed and launched into operation a a scientific non-cryogenic  device for pre-clinical MRI.
2. The Laboratory has conducted research to develop a new technology for the multimodal registration of optical and MRI images in the same volume of tissue in vivo, which can be ensured by using contrast agents for MRI  with the optical clearing effect.
3. Our researchers have studied the effects of clinical magnetic resonance (MR)-contrasting with the use of gadobutrol (Gadovist^TM) and its combinations and effects of the optical clearing of gadobutrol for efficient fluorescence imaging in vivo when applied both locally and systemically.
4. For the first time lentiviral vector carriers for the doxycycline-regulated expression of chimeric proteins have been created on the basis of a catalytically inactive mutant of the Cas9 endonuclease (dCas9).
5. Experiments have been conducted to study co-expression and localization in the nuclei of cells of chimeric proteins on the basis of dCas9 orthologs. The novelty of the research lies in the development of methods of multi-purpose tagging of the nuclear DNA of cells to find co-localized and (or) interacting dCas9-FP chimeras on the basis of the FRE effect.
6. Induced doxycycline-regulated expression of chimeric proteins on the basis of dCas9 orthologs has also been demonstrated in vivo using fluorescence imaging methods relying on the technology of optical clearing in subcutaneous tumor xenograft in mice.
7. We have described the double effect of gadobutrol as an optical clearing agent and as an MR contrast agent to visualize tumor perfusion, which confirms the importance of multimodal experiments in imaging.
8. Using a scientific non-cryogenic device for pre-clinical MRI, we have conducted a research of the distribution of mixtures that clear the surface of skin in subcutaneous tissues.
9. We have developed and tested non-invasive approaches to studying particularities of the biodegradation of composite materials based on co-polymers with the use of microscopic and multimodal (tomographic and fluorescence) methods. These polymers are designed for creating triboelectric devices to generate weak electrical stimuli for tissues or cells that can be implemented both into tissue or onto its surface. The proposed devices will be later studied as potential candidate for efficient conversion of biomechanical energy (i. e. heartbeat, respiratory movements of the chest, movements of limbs and blood pulsations) to electricity. We are expecting such nanogenerators to extend the operation life of biosensors recording vitally important indicators of the organism.

Implemented results of research:

1. A method has been developed for imaging biological tissues and (or) organs that includes immersion the optical clearing of biological tissue or an organ. The method is characterized by a technique in which an immersion agent based on gadolinium is injected into tissue or an organ, then the diffusion of the agent into the studied region is monitored using MRI and one of the optical methods, the region with higher contrast is determined and in this region MRI images of the tissue or the organ are registered, an optical clearing region are determined, an optical image is registered in that region, then the MRI image is spatially bound to the main structures and organs for subsequent overlaying of MRI in the region with higher contrast with optical images in the region of optical clearing.
2. The Laboratory obtained the patent for an invention No. РСТ/RU2019/050259 «A method of visualizing biological tissues and (or) organs» (authors: Valeriy V. Tuchin, Daria K. Tuchina, Alexandr P. Savitskiy, Aleksey A. Bogdanov). The invention belongs to the realm of medicine, namely to methods of obtaining images using optical clearing of biological tissues and organs and using magnetic resonance imaging (MRI). A method has been proposed for studying biological tissues and organs by bimodal visualization with the use of immersion optical clearing of biological or organs on the basis of contrast MRI agents.
3. Relying on the developed non-invasive approaches, the Laboratory researches processes of the biodegradation of composite materials based on copolymers with the use of microscopy and multimodal (tomography and fluorescence) methods. The research is conducted within the project of the Ministry of Science and Higher Education of the Russian Federation in the form of a subsidy from the federal budget to ensure the conduct of scientific research by Russian scientific institutions and (or) higher education organizations in collaboration with organizations from EU member states within the multilateral cooperation in the program «Horizon 2020», including the ERA-NET initiative within measures of support of the implementation of the program of bi- and multilateral scientific and technological cooperation (2021–2023) «Bioresorbable implantable devices based on triboelectric nanogenerators». Processes of the degradation of composite materials based on copolymers are studied using microscopy and bimodal (tomography and fluorescence) methods.

Education and career development:

1. The Laboratory has developed and taught the lecture course «Basics of molecular imaging in living systems» at the Faculty of Bioengineering and Bioinformatics of Moscow State University (Russia) and for postgraduate students of the Research and Education Center of Biotechnology of the Russian Academy of Sconces (Russia).
2. We has developed and taught the lecture course «Tissue optics and optical clearing of tissues and cells» (São Paulo School of Advanced Science on Modern Topics in Biophotonics, Brazil, 2019).
3. We organized the 3^rd school ADFLIM (advanced fluorescence imaging methods) to provide academic training to young researchers and professionals (Saratov, Russia, 2018).
4. We organized the international youth school on optics, laser physics and biophotonics «Saratov Fall Meeting» 2018 (Saratov, Russia, 2018).
5. Participation in the judging panel for the evaluation of works (project teams) by young researchers in the section «Medicine and pharmacology» at the 3^rd International Scientific Conference «Science of the Future» and the 4^th All-Russian Forum «Science of the Future – Science of the Youth».
6. We conducted the 4^th International School on Advanced Fluorescence Imaging Methods ADFLIM on the grounds of Saratov State University from 23 to 27 September 2019 in conjunction with the 23^rd International school for students and young researchers on optics, laser physics and biophotonics. The attendees of the research and education schools also participated in the work of the International symposium «Optics and biophotonics 7» that was staged by Saratov State University and the Federal Research Center of Biotechnology of the Russian Academy of Sconces from 24 to 27 September 2019.
7. Since the creation of the Laboratory of Molecular Imaging it has organized internships for at least 10 students of Moscow and federal universities and young professionals. Students of First Moscow State Medical University, the Faculty of Biology of Moscow State University, Moscow Polytechnic University, postgraduate students of Moscow State University, the Federal Research Center of Biotechnology of the Russian Academy of Sconces prepared their theses on the grounds of the Laboratory. 7 graduates: 3 bachelors, 1 specialist, 1 Candidate of Sciences in Chemistry  (supervised by Prof., Doctor of Sciences in Chemistry Alexandr P. Savitskiy on the basis of the Federal Research Center of Biotechnology of the Russian Academy of Sconces), 2 Candidate of Sciences in Physics and Mathematical Sciences (supervised by corresponding member of the Russian Academy of Sciences Valeriy V. Tuchin on the basis of Saratov State University) have been prepared on the grounds of the Laboratory. Two young researchers enrolled are currently studying in the postgraduate school of the Federal Research Center of Biotechnology of the Russian Academy of Sconces and the Institute of General Genetics of the Russian Academy of Sciences. Graduates of the bachelor’s degree school of First Moscow State Medical University and Polytechnic Institute are working on master’s degree theses.
8. The leading scientist Alexey A. Bogdanov participated in in the judging panel for the evaluation of works (project teams) by young researchers in the section «Medicine and pharmacology» at the 3^rd International Scientific Conference «Science of the Future» and the 4^th All-Russian Forum «Science of the Future – Science of the Youth» that was held In Sochi in 2019.

Other results:

In late May 2019, as part of our work on the project supported by the Ministry of Science and Higher Education of Russia, in the premises of the Laboratory of Molecular Imaging of the  Bach Institute of Biochemistry the state-of-the-art М3™ device for pre-clinical magnetic resonance imaging (MRI) was installed and launched into operation. The device is designed for the visualization of details of the anatomy and physiology of experimental animals (rodents weighing up to 30 grams).

М3™ MRI was designed on the basis of a compact highly efficient permanent magnet with a magnetic field strength of 1 Tesla that does not require cryogenic support. This MRI device is the only, as of now, system in Russia, and one of about 100 pre-clinical MRI systems installed in leading research and R&D centers of the world. 

Collaborations:

Laboratory of Laser Diagnostics of Technical and Living Systems of the Institute of Precision Mechanics and Control of the Russian Academy of Sciences (Russia), Laboratory of Biophotonics of the Research and Education Institute of Optics and Biophotonics of Saratov State University: joint research and publications.

The 4^th International school on advanced methods of fluorescence imaging ADFLIM was conducted on the grounds of Saratov State University from 23 to 27 September 2019 in conjunction with the 23^rd International school for students and young researchers on optics, laser physics and biophotonics. In 2019, 421 registered users from more than 20 countries visited the SFM website. More than 500 people participated in the events (including the audience). The participants of the Symposium delivered 18 plenary lectures, including two via Internet, as well as 30 invited lectures (of which 18 were delivered online), 127 oral presentations, 232 poster presentations and 22 Internet presentations. 

In 2020, as part of the International symposium «Optics and Bioinformatics – 8», which was part of «Saratov Fall Meeting» 2020 (SFM’20), 14 conferences and seminars were conducted, including the conference «Towards Optical and Multimodal Translational Imaging» (TOMTI’20). The staging of this conference had been initiated by leaders of the academic team created on the basis of the Laboratory for Molecular Imaging (Prof. Alexey A. Bogdanov) and the Laboratory of Physical Biochemistry  (Prof. Alexandr P. Savitskiy) of the Federal Research Center of Biotechnology of the Russian Academy of Sconces, as well as the Department of Optics and Biophotonics of Saratov State University (corresponding member of the Russian Academy of Sciences Valeriy V. Tuchin). The conference was conducted with support of the Ministry of Science and Higher Education of Russia, the Federal Research Center of Biotechnology of the Russian Academy of Sciences, Saratov State University. It was held in the online format using the Zoom platform, which turned out to be an advantage, as foreign researchers widely known in the academic community by virtue of their cutting-edge works in molecular and multimodal imaging eagerly responded to our invitation to deliver a presentation. At the TOMTI’20 conference 26 presentations were delivered, of which 5 were plenary presentations, 6 were invited oral presentations, young researchers delivered 6 oral presentations, 8 poster presentations. Authors of the presentations represented 8 Russian cities (Saratov, Kazan, Kursk, Volgograd, Moscow, Saint Petersburg, Nizhniy Novgorod, Tomsk), as well as Italy, Australia and the USA.

In 2020−2021, the Laboratory collaborated with Riga Technical University, the University of Tartu, the Rhine−Waal University of Applied Sciences. This collaboration resulted in the joint project «Bioresorbable implantable devices based on triboelectric nanogenerators» that received financial support from the Ministry of Science and Higher Education of Russia (ERA-NET Cofund).

Research devoted to the development of a technology for the tagging of nucleomes on the basis of a catalytically inactive mutant of the Cas9 endonuclease (dCas9) is conducted in collaboration with employees of the Laboratory of Functional Genomics of the Vavilov Institute of General Genetics of the Russian Academy of Sciences, the Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences. The continuation of research, envisioned by the mega-grant from the Ministry of Science and Higher Education, resulted in a Russian Science Foundation-supported project with the topic «Engineering of probes for bimodal fluorescence and magnetic resonance imaging of specific genome editing sites in living cells and tissues».