ORIGINAL ARTICLES
The difficulty of intraoperative delineation of glial tumors is due to the peculiarities of their growth along vessels and nerve fibers with infiltration of healthy white matter. Insufficiently complete removal of tumor tissues leads to recurrences, and excessive removal is fraught with neurological complications. Optical spectroscopy methods are characterized by high speed, accuracy and non-invasiveness, which determines the prospects of their use for intraoperative demarcation of the boundaries of such tumors. Fluorescence and diffuse reflectance spectroscopy have found wide application in intraoperative neuronavigation, mainly for detecting the edges of diffuse gliomas. At the same time, in recent years the direction of <i>ex vivo</i> spectral analysis of tumor samples using a combination of various optical spectroscopy methods, including both elastic and inelastic scattering spectroscopy, has been actively developed. Obviously, the ability to obtain spectra intraoperatively and on fresh specimens is different. The present article compares the results of the analysis of optical-spectral characteristics of intracranial tumors at intraoperative diagnosis and <i>ex vivo</i> analysis and proposes a mathematical model for interpretation of the observed dependencies.
In an in vivo pilot study, the efficiency of noninvasive fractional laser photothermolysis (NFLP) as a transdermal system for application photosensitization of mouse skin before photodynamic therapy (PDT) was studied. For NFLP, a laser (λ = 970 nm) with an average power of 4 W and a pulse frequency of 50 Hz was used. An area of the skin of the anterior abdominal wall of mice was irradiated. After NFLP, a photosensitizer (PS) based on chlorin e6 in the form of a gel (0.5%) was applied to the skin with an application time of 30 min. Then, laser PDT (λ = 662 nm) was performed with a power of 2 W in a scanning pulse-periodic mode with a frequency of 5 Hz and a light spot area on the skin of 1.2 mm². The results of histological examination, confocal and electron microscopy showed the features of transdermal distribution of chlorin e6 after NFLP. PS fluoresces in all skin layers and the subcutaneous fat layer, indicating its deep penetration into the hypodermis after NFLP compared to conventional cutaneous application. The advantages of NFLP as a transport system for successful penetration of the gel form of chlorin e6 through all skin layers are demonstrated. Electron microscopy showed transdermal transport of PS in the form of nanosized microspheres and particles absorbed by macrophages and fibroblasts. It was also shown for the first time that pulsed PDT after NFLP leads to the formation of nanosized foci of photodestruction up to the border of the reticular layer of the skin and the hypodermis.
The antitumor effectiveness of sonodynamic therapy (SDT) with a chemotherapeutic drug and a photosensitizer (PS) of the chlorine series was studied in an in vivo experiment. The work was performed on 60 white nonlinear rats, divided into 2 series of 30 individuals each. Pliss lymphosarcoma, transplanted subcutaneously, was used as a tumor strain. Photolon was administered intravenously in a single dose of 2.5 mg/kg 2.5-3 hours before ultrasound exposure, and doxorubicin was administered intraperitoneally in a single dose of 5 mg/kg 0.5 hours before ultrasound exposure performed using the «Phyaction U» apparatus, generating radiation with a frequency of 1.04 MHz, intensities of 0.5 and 1.5 W/cm² and lasting 5 minute. The study groups in each series included 5 rats: control, ultrasound, doxorubicin, photolon + ultrasound, doxorubicin + ultrasound, photolon + doxorubicin + ultrasound. To assess antitumor effectiveness, criteria generally accepted in experimental oncology were used: average volume of tumors (Vav., cm³), absolute tumor growth rate (K, units), tumor growth inhibition coefficient (TGI, %), frequency of complete tumor regressions (CR, %), the average life expectancy of rats (ALE, days), the coefficient of increase in the average life expectancy of rats (%) and the median overall survival (days). Differences were considered statistically significant at a significance level of p<0.05. In the first and second series of experiments, the most effective modes were the use of photolon, doxorubicin and ultrasound with a frequency of 1.04 MHz and intensities of 0.5 and 1.5 W/cm², respectively. The proposed combination of therapeutic interventions made it possible to statistically significantly (p˂0.05) increase the indicators of TGI, PR and ALE compared to the control and each of the components of the method separately. SDT methods developed and tested in in vivo experiments are characterized by high antitumor efficacy.
LITERATURE REVIEWS
Photodynamic therapy has traditionally been used and approved in many countries for the treatment of intraepithelial forms of cutaneous squamous cell carcinoma and precancer – actinic keratosis and Bowen’s disease. However, recently a number of studies have been conducted that suggest a possible expansion of the boundaries of photodynamic therapy for cutaneous squamous cell carcinoma. Several authors have suggested a therapeutic effect of photodynamic therapy for superficial, microinvasive and well-differentiated cutaneous squamous cell carcinoma. We reviewed publications on the website https://pubmed.ncbi.nlm.nih.gov devoted to this problem. Analysis of the research results shows that photodynamic therapy can achieve high efficiency and good cosmetic results in patients with microinvasive cutaneous squamous cell carcinoma, and in some cases even with an invasive form, and can be considered as an alternative to surgical treatment in patients with contraindications to surgery.
To reduce the frequency of relapses after surgical removal a brain tumor, it is critically important to completely remove all affected areas of the brain without disrupting the functionality of vital organs. Therefore, intraoperative differential diagnostics of micro-areas of tumor tissue with their subsequent removal or destruction is an urgent task that determines the success of the operation as a whole. Optical spectroscopy has shown its advantages over the past decade when used as a tool for intraoperative metabolic navigation. And one of the most promising options for the development of this technology is spectrally-resolved imaging. Currently, methods of spectrally-resolved imaging in diffusely reflected light have been developed, for example, mapping the degree of hemoglobin oxygen saturation, as well as fluorescence visualization systems, for both endogenous fluorophores and special fluorescent markers. These systems allow rapid analysis of tissue by the composition of chromophores and fluorophores, which allows the neurosurgeon to differentiate tumor and normal tissues, as well as functionally significant areas, during surgery. No less mandatory are the methods of using spectrally resolved visualization based on mapping characteristics obtained from Raman spectra, but due to the smaller cross-section of the process, these methods are used ex vivo, as a rule, for urgent analysis of fresh tissue samples. In this paper, we focus on both the physical foundations of such methods and a very important aspect of their application – machine learning (ML) methods for image processing and tissues’ classification.