Introduction . Preoperative fMRI often shows a reduced BOLD response in the areas located perifocal to brain tumors caused by pathological vasoreactivity as a result of neurovascular uncoupling. The aim of this study was an accurate identification of the eloquent cortical areas near brain tumors by measuring vasoreactivity using the breath holding test. Material and methods. 23 patients with brain tumors located near eloquent cortical areas underwent fMRI mapping of the language and / or motor cortical areas depending on the location of the tumor. Breath hold test was  also included, the design of which coincided with motor and language block paradigms. Results . A statistical dependency between motor, speech tasks and breath-hold BOLD-response was included into the BOLD analysis using coherence. fMRI activation maps generated by this method showed activation in the eloquent areas adjacent to brain tumors which were not detected by the standard analysis. This study shows that neurovascular uncoupling affects the accuracy of BOLD fMRI in brain tumors. Conclusion. The results of fMRI mapping can be partially improved by the incorporating vasoreactivity measurements into a standard analysis.

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.

Purpose: to assess correlation between Ki-67/MIB-1 LI and WHO grade brain gliomas and parameters of diffusion kurtosis MRI (DK-MRI) in the tumor. Patients and methods. The study includes 84 patients with supratentorial brain gliomas (35 gliomas with low grade malignancy, 20 gliomas with the 3-rd grade and 29 gliomas with the 4-th grade of malignancy). The study appraised correlation links between absolute and normalized parameters of diffusion tensor (mean, axial and radial (MD, AD, RD), fractional and relative anisotropy (FA and RA) and diffusion kurtosis (mean, axial and radial (MK, AK, RK), kurtosis anisotropy (KA)) with Ki-67/MIB-1 LI and WHO glioma grade in the most malignant regions (p < 0.05, Spirman coefficient). Results. DK-MRI parameters showed statistically significant correlation with Ki-67/MIB-1 LI and WHO glioma grades. Presence of oligodendroglioma (ODG) component in gliomas and oligoastrocytomas (OASs) did not affect the correlation between DK-MRI parameters and Ki-67/MIB-1 LI. However it affected correlation between DK-MRI parameters and WHO glioma grades. When studying correlation between parameters of DK-MRI and Ki-67/MIB-1 LI in IV grade gliomas maximum correlation was detected in case of normalised kurtosis anisotropy (KA). Conclusion. DK-MRI proved high sensitivity in detecting structural changes in gliomas, which are observed when WHO grade and Ki-67/MIB-1 LI tumors change. DK-MRI parameters depend on WHO grade and Ki-67/MIB-1 LI gliomas. Presence of oligodendroglioma component in gliomas does not affect the correlation between DK-MRI parameters and Ki-67/MIB-1 LI, but affect the correlation between DK-MRI parameters and WHO glioma grade. Complex analysis of DK-MRI parameters in gliomas with due account for WHO glioma grade, Ki-67/MIB-1 LI and presence of oligodendroglioma component in the tumor carried out in our study made it possible to study in depth the dynamics of DK-MRI parameters during various pathological processes developing in the tumor.

Нейрохирургия, сравнительно молодая и одна из сложнейших областей медицинской практики, за столетие своего развития в качестве автономного направления достигла невероятных успехов во многом благодаря тому, что интегрировала достижения научно-исследовательской деятельности, совершенствования медицинской техники и операционных методов. Вместе с тем нейрохирургия всегда сама была источником фундаментальных знаний о нервной системе и не только черпала информацию из таких разделов, как генетика, биохимия и физиология, но и обогащала их данными о патологических и нормальных состояниях и функционировании нервной системы. Этот процесс взаимного обогащения, стимулируемый появлением всё новых технологических возможностей, не только демонстрирует продуктивность исследований, лежащих на пересечении фундаментальных и практико-ориентированных дисциплин, но и позволяет надеяться на увеличение положительной статистики по числу спасённых и возвращённых к нормальной жизнедеятельности больных с различными травмами и органическими заболеваниями, в частности, благодаря методам нейропротекции и стимуляции нейрогенеза, или, по крайней мере, на улучшение качества жизни в случае неизлечимых заболеваний, в том числе с использованием методов нейромодуляции.

The review analyzes the current state of the problem of diagnosis and therapy of high-grade gliomas on the basis of the most promising present-day approaches. The diagnostic and treatment perspectives of the molecular genetic analysis of glioblastoma markers located on the tumor cell surface are considered. Gene therapy and the use of dendritic cells and oncolytic viruses are considered as the most interesting approaches to therapy of high-grade gliomas.

UNLABELLED The method of fluorescent diagnosis (FD) using 5-ALA has been widely employed in surgery of primary intracerebral tumors over the last years. The issue of FD application in surgery of gliomas with continued growth has remained less studied. OBJECTIVE To investigate the efficacy of using FD with 5-ALA and laser spectral analysis in surgery of brain gliomas with continued growth. MATERIAL AND METHODS 19 patients with Grade II-IV (WHO) gliomas with continued growth of different localization were studied. All tumors localized supratentorially. 5-Aminolevulinic acid hydrochloride "Alasens" (SSC "NIOPIK", Moscow, Russia) was used in the study. The equipment used during surgery included an operating microscope with an attachment for fluorescent navigation. Apart from expert qualitative assessment of a fluorescence extent, computer analysis of the fluorescence and light scattering (diffuse reflection) spectra was performed on a LESA-01-BIOSPEK spectrum analyzer (Russia). RESULTS Detectable fluorescence was obtained in all the cases. PP IX fluorescence indices from 9.05 to 53.97 (the study was conducted in 12 cases) were determined by quantitative analysis of the spectrograms. The analysis of light scattering revealed its inverse relationship with respect to the fluorescence index. High sensitivity of the method in surgery of gliomas with continued growth requires clarification of method specificity because non-specific accumulation of PP IX in the area of post-radiation necrosis may occur in these patients. CONCLUSIONS The FD method can be used for intraoperative demarcation of tumor resection boundaries in surgery of cerebral gliomas with continued growth. However, it is necessary to be critical of the high sensitivity of the method in patients with postradiation pathomorphism due to possible non-specific accumulation of PP IX in tissues. A light scattering study may provide additional information about the structure of tissues in the surgical wound.

Fluorescent diagnosis was first proposed in the early XX century and has been used in neurosurgery for about 15 years. The method relies on selective accumulation of strongly fluorescent protoporphyrin IX in tumor cells. Over the past years, the method of intraoperative fluorescence diagnosis has occupied its niche in many neurosurgical clinics around the world and is now used for fast intraoperative diagnosis in brain tumor surgery. However, the efficiency of fluorescent intraoperative diagnosis using 5-aminolevulinic acid is 80-90% and 58.8% for surgery of Grade III-IV and I-II gliomas, respectively. One of the methods to improve the efficiency of fluorescent diagnosis is to use vector systems for delivering fluorescent drugs into the tumor. This paper reports the results of an experimental study of systems for delivering fluorescent agents (protoporphyrin IX, Alexa 488, Alexa 660) using connexin-43 antibodies in rats with transplanted C6 glioma.

Clinical studies have revealed high selectivity of 5-ALA-induced protoporphyrin IX accumulation in different brain tumors. Modern methods of evaluation of tissues visible fluorescence are based on the qualitative analysis of the images. Up-to-date methods of combined spectral analysis allow fulfilling the intraoperative quantitative evaluation of the protoporphyrin IX content, as well as the scattering and absorption properties of a tissue. This paper presents a new method of the simultaneous analysis of hemoglobin concentration in oxygenated and reduced forms, tumor marker concentration (5-ALA-induced PP IX) and a new way to analyze the changes in the scattering properties of the tissues. The method is implemented by splitting the visible spectrum into intervals where hemoglobin and protoporphyrin IX have the characteristic peaks of absorption and fluorescence. The present method shows the dependence of the fluorescence index from the tumor grade. Combined spectroscopy (optical biopsy) can detect the differences between the subtypes of gliomas that are similar in the protoporphyrin IX fluorescence index. This method complements and enhances the diagnostic capabilities of spectroscopy, which is particularly important in the non-fluorescent glioma surgery.

Photodynamic diagnosis (PDD) has been actively implemented into neurooncological practice, especially in cerebral gliomas surgery. This paper describes our first experience of PDD combined with laser spectroanalysis in intracranial meningiomas. The study included 21 patients (8 male and 13 female patients, mean age was 58 years, range--between 37 and 74 years) with intracranial meningiomas operated with PDD in Burdenko Neurosurgical Institute between 2008 and 2011. In 14 cases laser spectroanalysis was used. Tumor fluorescence was present in all but one cases (95%). Spectroanalysis demonstrated that peaks of fluorescence varied between 5 and 46 (mean level was 18.5). These data correlated with visual impression of fluorescence and confirmed that meningioma is a tumor with bright fluorescence. Radical removal (Simpson grade I-II) was achieved in 10 cases, subtotal resection was performed in the rest of the patients. Application of PDD and laser spectroanalysis allows gaining complete information about accumulation of photosensibilizer in the tissue. To our opinion, these methods may be the most useful for determination of the borders of dural and bony invasion which directly affects the surgical tactics and degree of radical removal. Further studies are needed to evaluate the influence of PDD and laser spectroanalysis on long-term surgical outcomes.

Absence of well-defined borders of the glial tumor due to their infiltrative growth is one of the main issues in neurosurgery. A number of methods for intraoperative visualization are available today. The fluorescent metabolic navigation with 5-aminolevulinic acid (5-ALA) combined with quantitative laser spectroscopy is one of the latest technique. In our series of 99 consecutive patients with brain gliomas (WHO Grade I-IV) we found that visible fluorescence was observed in 68% of cases. Additional use of the laser spectroscopy could increase method sensitivity up to 74% due to accumulation of the protoporphyrine IX in nonfluorescense tumors. It was shown that there are some differences in quantitative fluorescence not only within same tumor (glioblastoma) but also in-between low- and high-grade gliomas. Intraoperative fluorescence and laser spectroscopy are effective and very helpful methods of intraoperative imaging in of intrinsic brain tumor surgery.

Different techniques are used today in neurosurgery for intraoperative navigation, including metabolic guidance using 5-aminolevulinic acid (5-ALA). The article focuses on history of intraoperative photodynamic diagnosis (PDD), mechanisms of 5-ALA action, possibilities of its application in different areas of neurosurgery. In addition to visual assessment of fluorescence, laser biospectroscopy significantly increases the diagnostic value of PDD. Laser biospectroanalysis is described in details, wide perspectives of its application in neurosurgery are demonstrated.