Кластерный анализ результатов интраоперационной оптической спектроскопической диагностики в нейрохирургии глиальных опухолей головного мозга

The paper presents the results of a comparative study of methods of cluster analysis of optical intraoperative spectroscopy data during surgery of glial tumors with varying degree of malignancy. The analysis was carried out both for individual patients and for the entire dataset. The data were obtained using combined optical spectroscopy technique, which allowed simultaneous registration of diffuse reflectance spectra of broadband radiation in the 500–600 nm spectral range (for the analysis of tissue blood supply and the degree of hemoglobin oxygenation), fluorescence spectra of 5‑ALA induced protoporphyrin IX (Pp IX) (for analysis of the malignancy degree) and signal of diffusely reflected laser light used to excite Pp IX fluorescence (to take into account the scattering properties of tissues). To determine the threshold values of these parameters for the tumor, the infltration zone and the normal white matter, we searched for the natural clusters in the available intraoperative optical spectroscopy data and compared them with the results of the pathomorphology. It was shown that, among the considered clustering methods, EM‑algorithm and k‑means methods are optimal for the considered data set and can be used to build a decision support system (DSS) for spectroscopic intraoperative navigation in neurosurgery. Results of clustering relevant to thepathological studies were also obtained using the methods of spectral and agglomerative clustering. These methods can be used to postprocess combined spectroscopy data.В работе представлены результаты сравнительного исследования методов кластерного анализа данных оптической интраоперационной спектроскопии при проведении операций по удалению глиальных опухолей различной степени злокачественности. Анализ проведен как для отдельных пациентов, так и для всей совокупности данных. Данные были получены методом комбинированной оптической спектроскопии, регистрирующим спектр диффузного отражения широкополосного излучения в диапазоне спектра 500–600 нм (с целью анализа кровенаполненности тканей и степени оксигенации гемоглобина), спектр флуоресценции индуцированного 5‑аминолевулиновой кислотой протопорфирина IX (с целью анализа степени изменения тканей) и сигнал диффузно отраженного лазерного излучения, использовавшегося для возбуждения флуоресценции (с целью учета рассеивающих свойств тканей). Для определения пороговых значений указанных параметров для опухоли, зоны инфильтрации и нормального белого вещества был проведен поиск естественных кластеров в имеющихся интраоперационных данных оптической спектроскопии и их сопоставление с результатами патоморфологической экспертизы. Было показано, что среди рассмотренных методов кластеризации ЕМ‑алгоритм и метод k‑средних оптимальны для рассмотренного набора данных и могут быть использованы для построения системы поддержки принятия решений при спектроскопической интраоперационной навигации в нейрохирургии. Релевантные результатам патоморфологических исследований модели были также получены с помощью методов спектральной и агломеративной кластеризации. Эти методы могут быть использованы для постобработки данных комбинированной спектроскопии

Cluster analysis of the results of intraoperative optical spectroscopic diagnostics In brain glioma neurosurgery

The paper presents the results of a comparative study of methods of cluster analysis of optical intraoperative spectroscopy data during surgery of glial tumors with varying degree of malignancy. The analysis was carried out both for individual patients and for the entire dataset. The data were obtained using combined optical spectroscopy technique, which allowed simultaneous registration of diffuse reflectance spectra of broadband radiation in the 500–600 nm spectral range (for the analysis of tissue blood supply and the degree of hemoglobin oxygenation), fluorescence spectra of 5‑ALA induced protoporphyrin IX (Pp IX) (for analysis of the malignancy degree) and signal of diffusely reflected laser light used to excite Pp IX fluorescence (to take into account the scattering properties of tissues). To determine the threshold values of these parameters for the tumor, the infltration zone and the normal white matter, we searched for the natural clusters in the available intraoperative optical spectroscopy data and compared them with the results of the pathomorphology. It was shown that, among the considered clustering methods, EM‑algorithm and k‑means methods are optimal for the considered data set and can be used to build a decision support system (DSS) for spectroscopic intraoperative navigation in neurosurgery. Results of clustering relevant to thepathological studies were also obtained using the methods of spectral and agglomerative clustering. These methods can be used to postprocess combined spectroscopy data

Sevanol and Its Analogues: Chemical Synthesis, Biological Effects and Molecular Docking

Among acid-sensing ion channels (ASICs), ASIC1a and ASIC3 subunits are the most widespread and prevalent in physiological and pathophysiological conditions. They participate in synaptic plasticity, learning and memory, as well as the perception of inflammatory and neurological pain, making these channels attractive pharmacological targets. Sevanol, a natural lignan isolated from Thymus armeniacus, inhibits the activity of ASIC1a and ASIC3 isoforms, and has a significant analgesic and anti-inflammatory effect. In this work, we described the efficient chemical synthesis scheme of sevanol and its analogues, which allows us to analyze the structure–activity relationships of the different parts of this molecule. We found that the inhibitory activity of sevanol and its analogues on ASIC1a and ASIC3 channels depends on the number and availability of the carboxyl groups of the molecule. At the structural level, we predicted the presence of a sevanol binding site based on the presence of molecular docking in the central vestibule of the ASIC1a channel. We predicted that this site could also be occupied in part by the FRRF-amide peptide, and the competition assay of sevanol with this peptide confirmed this prediction. The intravenous (i.v.), intranasal (i.n.) and, especially, oral (p.o.) administration of synthetic sevanol in animal models produced significant analgesic and anti-inflammatory effects. Both non-invasive methods of sevanol administration (i.n. and p.o.) showed greater efficacy than the invasive (i.v.) method, thus opening new horizons for medicinal uses of sevanol