Translation. Region: Russian Federation –
Source: Novosibirsk State University – Novosibirsk State University –
Laboratory of Nuclear Innovative Medicine Faculty of Physics, Novosibirsk State University received new equipment for digitalization of morphological studies and full automation of tissue preparation technology. The latest scientific equipment acquired by NSU within the framework of Priority 2030 programs, opens up fundamentally new research opportunities for scientists in a number of socially significant nosologies, such as neurodegenerative diseases and oncological processes, making it possible to significantly shorten the path from laboratory stages to the clinical use of innovative methods of early diagnosis and therapy.
Now the Laboratory of Nuclear and Innovative Medicine has several lines of such devices. The synthetic hardware series is used in the design of new forms of chemical compounds, allowing to significantly increase the effectiveness of the drugs used, to solve the issue of targeted delivery of active complexes in the composition of liposomes, to create nanoparticles. This opens up new prospects and horizons for the use of already known binary technologies, such as neutron capture therapy and hyperthermia.
— Binary technologies have been known for a long time, research on the possibilities of their application, for example, in oncological practice has been conducted for many decades. However, due to the absence of local impact methods, for example, with hyperthermia, only general warming of the body was used, which is very traumatic and unsafe for the subjects. At present, medical capabilities and equipment have changed significantly and allow for therapeutic thermal impact based on other physical principles.
In this case, the decisive role belongs to the applied therapeutic drug, its chemical properties, the possibility of selective accumulation in the affected tissue, which ultimately determines the effectiveness. The situation is similar with the prospects of neutron capture therapy of tumors, which have been widely discussed in recent years. It is the possibility of synthesizing such compounds that the new hardware base will provide in the near future. Moreover, the available equipment potentially allows producing drugs, the use of which gives a chance to merge the process of both diagnostics and therapy of a number of diseases, i.e. to enter the sphere of so-called theranostics, – said the head of the Laboratory of Nuclear and Innovative Medicine of NSU, Associate Professor Vladimir Kanygin.
Today, there are a large number of synthesized compounds with specified properties, but not every one of them can even be a potential candidate for the preclinical stage of testing, not to mention use in hospital practice. The situation with binary methods is even more complicated, since it is necessary to evaluate the effectiveness and safety of both the drug itself and the hardware station, both in an isolated mode of operation and in the synergy mode, which is the essence of these methods. For this reason, both the synthesis of compounds with targeted functional properties and their differentiation are a fairly complex and multi-stage task. The equipment available in the laboratory allows us to solve the key issue of targeting, i.e. targeted delivery of active substances to the lesion, as required in neutron capture therapy or hyperthermia.
— Previously, we have conducted successful experiments to obtain substances containing the necessary carrier – boron, and all kinds of nanoparticle suspensions. Currently, two such drugs are known that are used in practice, have already undergone comprehensive in-depth studies and a number of preclinical trials. A huge number of drugs described in research articles have a number of limitations. This is due to their physicochemical and toxic properties. The approaches that we develop and apply in the laboratory are aimed at eliminating these negative consequences. Candidate drugs for neutron capture therapy should have high bioavailability, low toxicity, high ability to emulate in the areas that are of interest to us, and, having the listed properties, should be fairly easily excreted from a living organism after the experiment. Potentially, the scientific community classifies nanoparticles as such drugs. We have a number of completed studies in this area. At the moment, under my supervision, a master's thesis on the synthesis and modification of silicon oxide nanoparticles applicable in hyperthermia is being carried out at the NSU Physics Department. We are also considering the possibilities of artificial intelligence technologies in the search for an ideal drug for neutron capture therapy of oncological pathologies, – said Alfiya Tsygankova, Senior Researcher, PhD in Chemistry.
For a number of years, the laboratory's scientists have been testing neutron capture therapy on animals – cats, rabbits and dogs. The models of spontaneous tumors were used as a basis. The individuals involved in the research were identified in collaboration with veterinarians who actively participated in the selection of four-legged patients, according to certain parameters that met the scientists' requests. Last year, NSU purchased a computer tomograph for diagnosing tumors in animals, which opened up new opportunities for the team.
During the research work of the LYAIM to evaluate the effectiveness of neutron capture therapy for tumors of various localizations and histologies, about a hundred animals were exposed within the walls of the nuclear reactor of Tomsk Polytechnic University (TPU) and more than 20 at the G.I. Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences.
— When organizing this work, we encountered a number of problems, the most important of which is the lack of adequate verification of spontaneous formations in animals (primarily histological, although tomography was no better at first) in our region. In Moscow and St. Petersburg, the method is developed and widely used, but on our side of the Urals, the situation is sad. And objective and timely morphological diagnostics is, in fact, the basis of everything else. Neither tomographic descriptions (which, by the way, became available only after the launch of the tomograph and our training of the relevant specialists in the zoological profile), nor any preclinical studies in the field of therapy of oncological and neurodegenerative diseases are feasible without clear, timely and reliable histological verification of biopsy materials or surgically removed formations. In this regard, the capabilities of the unique diagnostic equipment recently purchased by the University, which formed the second hardware line of LYAIM, are difficult to overestimate, — Vladimir Kanygin explained.
The second line of devices is designed for the analysis of histological preparations, with the help of which the effectiveness of any therapeutic effect, the safety of a drug or physical method for healthy or pathologically altered tissue are assessed, and the diagnoses themselves are established based on samples taken as a result of a biopsy or surgery.
— The laboratory has received modern equipment of fairly high quality. Its presence significantly modifies the process of obtaining and staining tissue samples, dramatically increases the speed of the researcher's work, and significantly expands his capabilities. If on the previous equipment it took more than a day to conduct a histological examination of a section, then here we are talking about a few hours. In addition, the digitalization of the process provides opportunities for consultative communication with specialists from other cities and scientific organizations, — explained the head of the laboratory of molecular mechanisms of pathological processes of the Federal Research Center for Fundamental and Translational Medicine (FRC FTM), Doctor of Biological Sciences Elena Koldysheva.
The digital scanner received by LYAM this year is an optical microscope providing 40x magnification with a built-in digital camera connected to a computer adapted for processing and storing the resulting images. Scanning glass with a microslide allows you to obtain a digital image displayed on the screen in high quality, calibrated for sharpness. You can scan either the entire slice or its individual parts. The camera’s capabilities make it possible to minimize cut defects; the system “recognizes” the image of a microspecimen and can scan only it or a selected area of arbitrary shape in order to reduce the resulting file volume. Also, due to the camera optics, high resolution is achieved and the quality of even the smallest structures, micrometers in size, is not affected. Everything can be adjusted depending on the needs of the researcher. The resulting images can be shared via online conferences with experts from different locations. Digital copies of histological preparations solve the problems of storage and loss of originals and make it possible to organize a digital archive of images. But the most promising thing is both the creation of our own databases for artificial intelligence and the immediate use of existing digital scan storages. This dramatically speeds up the work of the morphologist, qualitatively expands the availability of remotely used case archives, and allows problematic images to be broadcast to experts and discussed through teleconferences with competent teams. In the near future – computer analysis of images using existing software modules, as well as their improvement for specific tasks using artificial intelligence.
“The capabilities of light microscopy make it possible to assess how pronounced certain tissue features are with various staining methods, what processes occur at the molecular-cellular level, and with their help it is possible to analyze markers characteristic of a number of pathologies. Digitizing an image obtained at a forty-fold magnification, displaying it on a computer screen, calibrating sharpness depending on needs and setting high image quality, the ability to select and work with a specific section area can significantly speed up the examination of each microslide. Isn’t this an obvious advantage of the device?! For example, detecting signs of atrophy and dystrophic changes in tissues and cells, calculating areas of necrosis, assessing the density of cells presented in a preparation, with the ability to calculate their area, become much faster when using built-in programs for working with images. Evaluation of marker expression based on the results of immunohistochemistry of tumor sections allows one to determine the effectiveness of the therapy or select personalized treatment at the initial stage. Moreover, adapting and improving image processing software to specific tissue types will facilitate the study of a variety of pathologies. We will use this equipment for the primary diagnosis of tumors in animals, with the possibility of developing the direction of personalized treatment in veterinary medicine, as well as to study the effectiveness of neutron capture therapy. In general, histology is the most accurate way to make a diagnosis based on pathological changes in the tissue,” explained Nikolai Kanygin, laboratory assistant at the Lyamim FF NSU.
It should be emphasized that the emergence of such equipment allows us to talk about real telemedicine, the widespread use of AI and qualitatively different opportunities for professional expertise and specialized consultations, an innovative format for training specialists and students. Of course, this will revolutionize the accuracy of the resulting morphological diagnosis (which underlies the medical diagnosis), and will dramatically save precious time on obtaining it.
— Although the acquired equipment is of medical class, LYAIM plans to use it primarily in research on animal models, where the demand for such equipment is difficult to overestimate. We can talk about a whole range of pathological conditions and diagnoses that are part of the laboratory's scientific interests. In particular, having the previously acquired CT scanner in our arsenal, we will be able to closely approach the preclinical assessment of the effectiveness of existing and developed methods of treating neurodegenerative diseases. Although, of course, cancer search remains our priority. And in conclusion, it is worth announcing the uniqueness of the direction in the region for the needs of the zooveterinary link. Of course, they will be taken into account by us, especially against the background of the growing clinical capabilities of colleagues in veterinary hospitals, — said Vladimir Kanygin.
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