Персона: Савельева, Татьяна Александровна
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Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
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- ПубликацияТолько метаданныеEvaluating the dynamics of brain tissue oxygenation using near-infrared spectroscopy on various experimental models(2019) Kustov, D. M.; Sharova, A. S.; Makarov, V. I.; Borodkin, A. V.; Savelieva, T. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор Борисович© 2019 Astro Ltd.In this paper we consider a method for researching the dynamics of blood flow in the cerebral cortex, on an optical phantom that reproduces the parameters of real human and mice brain structures, through the use of near and infrared ranges of laser radiation. For the investigation of real tissue we chose a laboratory mouse brain in vivo. An algorithm for non-invasive diagnostics of the degree of oxygenation was identified and optimal parameters of installation components were selected for taking information about hemodynamic indicators. Output was verified by the reference method for assessing oxygenation by degree of absorption of hemoglobin in the visible range, which indicates that data have a high correlation with classical methods. With further development, this algorithm can be used in various areas of research and diagnostics.
- ПубликацияТолько метаданныеThe optical estimation of glioma cell composition using fluorescence lifetime imaging(2020) Maklygina, Y. S.; Romanishkin, I. D.; Savelieva, T. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичGliomas are one of the most common brain tumors occurring in children and adults. Gliomas are primary, diffusely infiltrating brain tumors. There are few effective therapies for these type of cancer, and patients with malignant glioma fare poorly, even after aggressive surgery, chemo- and radiotherapy.
- ПубликацияТолько метаданныеRaman spectroscopy for the development of a method for glial brain tumors diagnostics(2020) Bikmukhametova, L. R.; Romanishkin, I. D.; Savelieva, T. A.; Orlov, A. V.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичReducing the frequency of relapses after surgical removal of glial tumors is a non-trivial task due to their infiltrative growth. The main way to solve this problem is fluorescent intraoperative navigation. However, in the absence of accumulation of a fluorescent marker in the tumor tissues, other diagnostic parameters are required to find the boundaries of such tumors. Raman spectroscopy has the advantages of optical spectroscopy such as speed and non-invasiveness. With an exhaustive database of reference spectra of those components that can be expressed in glial tumors, Raman scattering spectroscopy allows multivariate diagnosis of such tumors and their intraoperative demarcation.
- ПубликацияТолько метаданныеSpontaneous raman spectroscopy for intracranial tumors diagnostics ex vivo(2020) Romanishkin, I. D.; Bikmukhametova, L. R.; Goryaynov, S. A.; Kosyrkova, A. V.; Savelieva, T. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор Борисович© 2020 Russian Photodynamic Association. All rights reserved.Neurosurgery of intracranial tumors, especially of glial origin, is a non-trivial task due to their infiltrative growth. In recent years, optical methods of intraoperative navigation have been actively used in neurosurgery. However, one of the most widely used approaches based on the selective accumulation of fluorescent contrast medium (5-ALA-induced protoporphyrin IX) by the tumor cannot be applied to a significant number of tumors due to its low accumulation. On the contrary, Raman spectroscopy, which allows analyzing the molecular composition of tissues while preserving all the advantages of the method of fluorescence spectroscopy, does not require the use of an exogenous dye and may become a method of choice when composing a system for intraoperative navigation or optical biopsy. This work presents the first results of using the principal component method to classify Raman spectra of human glioblastoma with intermediate processing of spectra to minimize possible errors from the fluorescence of both endogenous fluorophores and photosensitizers used in fluorescence navigation. As a result, differences were found in the principal component space, corresponding to tissue samples with microcystic components, extensive areas of necrosis, and foci of fresh hemorrhages. It is shown that this approach can serve as the basis for constructing a system for automatic intraoperative tissue classification based on the analysis of Raman spectra.
- ПубликацияТолько метаданныеIntraoperative vascular fluorescence in cerebral glioblastomas and vascular histological features Intraoperatsionnaia fluorestsentsiia sosudov v strukture glioblastom golovnogo mozga i ikh gistologicheskaia kharakteristika(2019) Potapov, A. A.; Chobulov, S. A.; Nikitin, P. V.; Okhlopkov, V. A.; Savel'eva, T. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор Борисович5-ALA intraoperative fluorescence is widely used in surgery of brain tumors for intraoperative demarcation of boundaries and more total resection because 5-ALA metabolites are not accumulated in the intact brain and vascular tissues. Given this fact, it was hypothesized that fluorescence of vessels in the immediate vicinity of a brain tumor may indicate their infiltration by tumor cells as a potential pathway for their dissemination and as a factor for continued tumor growth after surgery and adjuvant therapy. PURPOSE: Identification of fluorescent vessels located near cerebral gliomas, with a histological description of their structure, relationships with the tumor, and potential invasion of the walls by tumor cells. MATERIAL AND METHODS: A prospective cohort study included 14 patients with malignant supratentorial gliomas, aged 20 to 78 years. Five patients were operated on due to continued tumor growth. Two hours before surgery, all patients received 5-ALA orally. During surgery, a microscope (Carl Zeiss OPMI Pentero, Germany) with a fluorescent module (BLUE-400) was used. In all cases, molecular-genetic and immunohistochemical examinations of the tumor material were performed. During surgery, fluorescent vessels, after evaluating their functional significance, were also resected for histological examination. RESULTS: Glioblastoma and anaplastic astrocytoma were verified in 10 and 4 patients, respectively. In 4 out of 10 glioblastoma cases, vessels with homogeneous or fragmentary fluorescent walls were detected in the tumor bed after resection of most of the tumor; in patients with anaplastic astrocytomas, vascular fluorescence was not observed. In the four vascular samples with intraoperatively detected wall fluorescence, tumor invasion into the vascular layers was revealed in all cases. These patients underwent an immunohistochemical examination with monoclonal antibodies to the glial GFAP marker, which clearly identified areas of ingrowth of tumor cells into the vascular wall. CONCLUSION: 5-ALA intraoperative fluorescence is a fundamentally new approach in the rapid diagnosis of tumor-infiltrated blood vessels. Invasion of tumor cells to intact vessels may be a mechanism of tumor progression and dissemination. Additional resection of fluorescent vessels may affect the radicalness of surgical treatment, but requires a mandatory assessment of their functional significance. Интраоперационная флуоресценция с использованием 5-аминолевулиновой кислоты (5-АЛК) широко используется в хирургии опухолей головного мозга с целью интраоперационной демаркации границ и увеличения радикальности удаления, поскольку накопление ее метаболита отсутствует в интактных тканях мозга и сосудов. С учетом этого факта высказана гипотеза о том, что флуоресценция сосудов, расположенных в непосредственной близости от опухолей мозга, может указывать на их инфильтрацию опухолевыми клетками как на потенциальный путь их диссеминации и фактор продолженного роста опухоли после операции и адъювантной терапии. Цель исследования - выявление флуоресцирующих сосудов, расположенных вблизи глиом головного мозга, с гистологическим описанием их структуры, взаимоотношений с опухолью и возможной инвазии стенок опухолевыми клетками. Материал и методы. В проспективное когортное исследование включены 14 пациентов в возрасте от 20 до 78 лет со злокачественными супратенториальными глиомами. У 5 больных операция проведена в связи с продолженным ростом опухоли. Все пациенты за 2 ч до операции получали 5-АЛК внутрь. Во время операции использовали микроскоп OPMI Pentero (Carl Zeiss Meditec AG, Германия) с флуоресцентным модулем (BLUE-400). Во всех случаях проведены молекулярно-генетическое и иммуногистохимическое исследования опухолевого материала. В ходе хирургического вмешательства дополнительно для гистологического исследования резецировали флуоресцирующие сосуды после оценки их функциональной значимости. Результаты. У 10 пациентов верифицирована глиобластома, у 4 - анапластическая астроцитома. В 4 из 10 наблюдений c глиобластомами после удаления основной массы опухоли в ложе удаленной опухоли выявлены сосуды с гомогенно или фрагментарно флуоресцирующими стенками, у пациентов с анапластическими астроцитомами флуоресценции сосудов не отмечалось. Во всех четырех образцах сосудов, в которых интраоперационно определена флуоресценция стенки, выявлена инвазия опухоли в васкулярные слои. У данных пациентов проведено иммуногистохимическое исследование с использованием моноклональных антител к глиальному маркеру GFAP. Это позволило четко выделить участки врастания опухолевых клеток в сосудистую стенку. Выводы. Интраоперационная флуоресценция с применением 5-АЛК является принципиально новым подходом в экспресс-диагностике сосудов, инфильтрированных опухолью. Инвазия опухолевыми клетками ранее интактных сосудов может являться механизмом, посредством которого осуществляются прогрессирование и диссеминация опухолевого процесса. Дополнительная резекция флуоресцирующих сосудов может влиять на радикальность хирургического лечения, однако необходима обязательная оценка их функциональной значимости.
- ПубликацияТолько метаданныеOptical biopsy: Fundamentals and applications in neurosurgery(2021) Romanishkin, I. D.; Maklygina, Yu. S.; Borodkin, A. V.; Tsarukaev, B. A.; Savelieva, T. A.; Grachev, P. V.; Kalyagina, N. A.; Orlov, A. V.; Loschenov, V. B.; Савельева, Татьяна Александровна; Калягина, Нина Анатольевна; Лощенов, Виктор Борисович© 2021 Institute of Physics Publishing. All rights reserved.Currently, there is a significant increase in the incidence of cancer of the central nervous system. Determination of the boundaries of intracerebral and intramedullary tumors is especially difficult. The urgency of the problem of determining the boundaries of astrocytic tumors is due to the peculiarities of their growth along myelinated nerve fibers and vessels, leading to the infiltration of healthy white matter by tumor cells, which affects the high frequency of postoperative relapses. The complexity of surgery for intramedullary tumors of the spinal cord is that the tumor does not always have a clear border and the risk of injury is high due to the smaller size of the operated area compared to the brain. Reliable information regarding the volume of the resected tumor should be obtained by intraoperative imaging. The solution to this problem is implemented mainly in three directions: the use of intraoperative computed tomography, magnetic resonance imaging and ultrasound scanning, and various combinations of these methods. Unfortunately, all these methods of intraoperative diagnostics do not allow real-time examination of tissues in an operating wound and/or do not provide a simultaneous analysis of both structural and metabolic changes. The limitations of intraoperative navigation methods in neurosurgery have led to the relevance of the development of an accurate spectroscopic method for in vivo determination of the content of specific metabolic markers and structural changes accompanying the development of the tumor process in the nervous tissue. Various approaches to intraoperative navigation based on optical spectroscopy are called optical biopsy. In this article, we present the methods and tools developed in recent years for spectroscopic guidance in neurooncology. First of all, this, of course, concerns the analysis of spectral dependences recorded before, during and after tumor removal. We have used such modalities of optical spectroscopy as fluorescence, diffuse reflectance spectroscopy and spontaneous Raman scattering. An equally important issue on the way to increasing the efficiency of tumor resection is the development of new instrumentation; therefore, we have developed a number of new devices, which are a combination of well-known neurosurgical instruments and laser and fiber-optic technologies. Last but not least is the issue of rapid classification of the studied tissues based on the recorded signals, which was solved by us using machine learning methods.
- ПубликацияТолько метаданныеFiltering Raman spectral features of glial tumor sites based on biochemical correlates(2022) Savelieva, T. A.; Romanishkin, I. D.; Orlov, A. V.; Kosyrkova, A. V.; Shugaj, S. V.; Goryajnov, S. A.; Golbin, D. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичRaman spectroscopy is a sensitive and fast tool for analyzing the molecular composition of tissues, so we used it to differentiate glial tumor and normal tissues during surgery. The structure of Raman spectra motivated us to implement the feature selection technique, based on the filtering of those points of the spectrum for which statistically significant differences were found between the groups. Finally they were matched to the main biochemical components of the studied tissues, and new vectors of Raman features of a smaller dimension were formed. © 2022 IEEE.
- ПубликацияТолько метаданныеDifferentiation of glioblastoma tissues using spontaneous Raman scattering with dimensionality reduction and data classification(2022) Romanishkin, I.; Savelieva, T.; Orlov, A.; Loschenov, V.; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичThe neurosurgery of intracranial tumors is often complicated by the difficulty of distinguishing tumor center, infiltration area, and normal tissue. The current standard for intraoperative navigation is fluorescent diagnostics with a fluorescent agent. This approach can be further enhanced by measuring the Raman spectrum of the tissue, which would provide additional information on its composition even in the absence of fluorescence. However, for the Raman spectra to be immediately helpful for a neurosurgeon, they must be additionally processed. In this work, we analyzed the Raman spectra of human brain glioblastoma multiforme tissue samples obtained during the surgery and investigated several approaches to dimensionality reduction and data classificatin to distinguish different types of tissues. In our study two approaches to Raman spectra dimensionality reduction were approbated and as a result we formulated new technique combining both of them: feature filtering based on the selection of those shifts which correspond to the biochemical components providing the statistically significant differences between groups of examined tissues (center of glioblastoma multiforme, tissues from infiltration area and normally appeared white matter) and principal component analysis. We applied the support vector machine to classify tissues after dimensionality reduction of registered Raman spectra. The accuracy of the classification of malignant tissues (tumor edge and center) and normal ones using the principal component analysis alone was 83% with sensitivity of 96% and specificity of 44%. With a combined technique of dimensionality reduction we obtained 83% accuracy with 77% sensitivity and 92% specificity of tumor tissues classification.
- ПубликацияТолько метаданныеInvestigation of a combined absorption-fluorescence-Raman spectroscopy approach to brain tumor tissue differentiation ex vivo(2022) Romanishkin, I. D.; Savelieva, T. A.; Poletaeva, I. Yu.; Shugai, S. V.; Goryaynov, S. A.; Golbin, D. A.; Loschenov, V. B.; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичIn this work, we used a combined absorption-fluorescence-Raman approach to the optical investigation of brain tissue. The proposed approach allowed taking into account the blood fill, oxygenation, accumulation of fluorescent biomarker, and Raman signal to estimate a degree of malignancy of the tissue. © 2022 IEEE.
- ПубликацияТолько метаданныеOptical Spectral Approach to Breast Tissue Oxygen Saturation Analysis for Mastectomy Perioperative Control(2022) Kustov, D. M.; Krivetskaya, A. A.; Savelieva, T. A.; Loschenov, V. B.; Кривецкая, Анна Александровна; Савельева, Татьяна Александровна; Лощенов, Виктор БорисовичThe purpose of our research is to study the ability of the developed method of hemoglobin detection, based on the fiber-optic spectral analysis in visible region, to determine the level of blood supply to breast tissues before surgical treatment, intraoperatively and during observation of the patient in the postoperative period, when breast tissue is healing. The significant effect of subcutaneous adipose tissue on the shape of diffuse reflectance spectra due to scattering leads to a decrease in the accuracy of determining hemoglobin oxygen saturation and hemoglobin concentration from them. The variability of the subcutaneous adipose tissue layer is quite high, which also leads to a high variability of the spectra within a class of tissues that are in the same physiological state, which implies that the intraclass variability due to this factor should be assessed for a specific problem, not considering it random. For this purpose, in our work, we constructed optical phantoms simulating various thicknesses of the subcutaneous adipose tissue in order to determine the effect of its light scattering on the diffuse reflectance spectrum and to select the optimal configuration of optical fibers. © 2022 by the authors.