Laser-induced fluorescent visualization and photodynamic therapy in surgical treatment of glial brain tumors.

High-grade gliomas have a diffuse and infiltrative nature of the growth of tumor cells, due to which the achievement of radical resection is difficult. Surgical resection completeness of brain tumors is an important factor in prolonging the life of patients. An accurate definition of tumor boundaries and residual fluorescent regions is impossible due to imperfections of the equipment used for fluorescent imaging. 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) in humans and is clinically used to detect and treat tumors. Currently, fluorescence-guided surgery with PpIX used a surgical microscope with an excitation wavelength in the blue spectrum range. Because of its low ability to penetrate into biological tissue, blue light is ineffective for providing high-quality fluorescent navigation. Also, when performing an operation using radiation in the blue spectrum range, the photosensitizer's surface layer (PS) often bleaches out, which leads to frequent errors. The use of red light emission makes it possible to slow down the PS bleaches out due to the absorption properties of PpIX, but this task is technically more complicated and requires highly sensitive cameras and specialized optical filters. The new two-channel video system for fluorescent navigation has a radiation source in the red range of the spectrum, the penetration depth of which is greater than the blue light, which makes it possible to increase the depth of probing into biological tissues. The study's clinical part involved 5 patients with high grade glioma and 1 patient with low grade glioma: grade III oligodendrogliomas (2), grade IV glioblastomas (3), and grade II diffusion astrocytoma (1).

Theoretical and experimental modeling of interstitial laser hyperthermia with surface cooling device using Nd3+-doped nanoparticles.

To improve methods of laser hyperthermia for the treatment of bulk malignant neoplasms, an urgent task is the development of techniques and devices that automatically control heating at a given tissue depth and ensure its uniformity. The article proposes the concept of a system for performing hyperthermia with real-time spectroscopic temperature control and surface cooling, which allows to record spectra of diffusely scattered radiation and fluorescent signal from various depths of biological tissues by the means of the variation of the angle and distance between the fiber source of laser radiation and the receiving fiber. Theoretical and experimental modeling of the spatial distribution of diffusely scattered radiation and temperature inside the tissue with a fiber optic device providing surface cooling of the irradiated tissue, and recording spectral information from a given depth in real time, is presented. Simulation of radiation propagation in biological tissues, depending on the distance between the source and the receiver and the angle of their tilt, was carried out using the Monte Carlo method. Modeling of the temperature distribution inside the tissues was carried out by means of a numerical solution of the heat conduction equation. Experimental modeling was carried out on phantoms of biological tissues simulating their scattering properties as well as accumulation of the investigated nanoparticles doped with Nd3+ ions. It was shown that inorganic nanoparticles doped with rare-earth Nd3+ ions can be used as temperature labels for feedback to the therapeutic laser. According to the results of the theoretical simulation, optimal configurations of the relative arrangement of the fibers were chosen, as well as the optimum surface cooling temperatures for the given power densities. The heating of the phantom of the neoplasm containing the investigated nanoparticles doped with Nd3+ ions by laser radiation with an 805-nm wavelength and power density of 1 W/cm2 up to 42 °C at a depth of 1 cm while maintaining the surface temperature within the limits of the norm was demonstrated.

[Intraoperative combined spectroscopy (optical biopsy) of cerebral gliomas]. / Intraoperatsionnaia kombinirovannaia spektroskopiia (opti-cheskaia biopsiia) gliom golovnogo mozga.

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.

[Intraoperative fluorescent visualization and laser spectrosopy in intrinsic brain tumor surgery].

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.

[First experience of photodynamic diagnosis and laser spectroalanysis in surgery of intracranial meningiomas].

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.