Significanceespite photodynamic therapy (PDT) for unresectable cholangiocarcinoma is widely used in clinical practice, there is a luck of intraductal video fluorescence diagnostics (VFD) for diagnosis and personalized control of PDT.ApproachПроводили внутрипротоковую флуоресцентную диагностику, как и терапию для контроля фотообесцвечивания тканей, с использованием видеофлуоресцентного модуля (BIOSPEC, Russia) с фотосенсибилизатором хлорин e6.Intraductal fluorescence diagnostics was performed along with the PDT in order to control tissue photobleaching. The specially designed video fluorescence module (BIOSPEC, Russia) was employed with chlorine-e6 based photosensitizer (Fotorun, RUSSIA).ResultsПовышенная концентрация фотосенсибилизатора в опухоли была подтверждена у всех пациентов (100%), а видеофлуоресцентное изображение опухоли было получено у 94%. ВФД улучшила диагностическую точность флуоресцентной оценки с наведением изображения. Персонализированный подход к ФДТ с оценкой фотобличинга улучшил медиану выживаемости и период без желтухи более чем в 2 раза.The increased concentration of the photosensitizer in the tumor was confirmed in all patients (100%), and the video-fluorescence image of the tumor was obtained in 94%. VFD has improved the diagnostic accuracy of image-guided fluorescence assessment. A personalized PDT approach, with the evaluation of photobleaching improved the median survival and jaundice-free period by more than 2 times.ConclusionsФототераностика и билиарное стентирование для билиарной декомпрессии улучшают результаты диагностики и лечения неоперабельной холангиокарциномы, осложненной механической желтухойPhototheranostics and biliary stenting for biliary decompression improve results of diagnostics and treatment of unresectable cholangiocarcinoma complicated by mechanical jaundice

The paper presents an overview of experimental results of an investigation of different energy loss channels in the gas dynamic trap (GDT), which is a magnetic mirror plasma confinement device in the Budker Institute of Nuclear Physics. Energy losses along magnetic field lines are considered as well as losses onto radial limiters, which restrict the plasma column radius and provide its magnetohydrodynamic stability via the ‘vortex confinement’ mechanism. The losses along the field lines were measured using a set of pyroelectric bolometers on the plasma absorber and the losses onto the limiters were determined with thermistors from their temperature rise. Additionally, the losses due to charge exchange of fast plasma ions on the residual neutral gas in the GDT were measured using a longitudinal array of pyroelectric bolometers mounted on the wall of the central cell. An attempt was made to draw up the energy balance in the GDT in order to identify the predominant loss channels and reduce those losses in the future.

A fusion neutron source (FNS) based on the gas-dynamic trap (GDT, Budker Institute, Novosibirsk) is considered for confinement of two-species plasma heated by neutral beam injection in a regime where the fast ion distribution function is far from Maxwellian. Kinetic instabilities are expected to develop in this regime, and in this paper we investigate the ion-cyclotron instability evolving in moderate densities of pure hydrogen and mixed deuterium-hydrogen target plasmas. The properties of the studied unstable mode, such as its azimuthal wavenumbers, propagation direction and its being affected by changes in the bulk plasma density and composition, allow us to identify it as the drift cyclotron loss cone (DCLC) instability. This mode scatters fast ions and thereby leads to drops in diamagnetic flux signals and increases longitudinal energy and particle losses, with the average energy of the lost ions estimated to be far above the temperature of warm Maxwellian ions. Our interpretation is that the unstable wave grows due to interaction with the fast ions located near the loss cone in the velocity space and scatters them. Applying the method of suppressing the DCLC instability by filling the loss cone with warm plasma, we have determined the values of plasma density and deuterium percentage that allow us to suppress the DCLC instability in the GDT. These findings justify using mixed bulk plasmas in fusion neutron source operation.

This paper is devoted to experimental studies of plasma confinement with high relative pressure ( $\beta$ ) in the Gas Dynamic Trap (BINP, Novosibirsk). In previous high- $\beta$ confinement studies a maximum local $\beta = 0.6$ was achieved in the fast-ion turning point, contributed to by a beam-driven population of fast ions with an anisotropic distribution function. In this study the axial magnetic field profile was modified to bring the turning points closer to one another, which effectively increased the energy density of plasma and pushed the $\beta$ value higher. Experiments were performed for two non-standard magnetic configurations, where the axial fast-ion confinement region length was reduced by 1.5 and 2 times compared with the standard configuration. The average values of $\langle \beta _{\perp } \rangle$ over the plasma central cross-section were found to be 0.1 and 0.18, respectively, for the two configurations, with the latter value significantly exceeding the $\langle \beta _{\perp } \rangle =0.08$ of the standard configuration, in which the previous record was set. Moreover, halving the fast ion confinement region almost doubled the D–D fusion proton flux from the trap centre compared with the standard configuration. The electron temperature in both new magnetic configurations was only slightly smaller than in the standard configuration. In addition, an effect of Alfvén ion–cyclotron instability (AICI) development on the pressure in the turning points is discussed. Presumably, with some decrease in magnetic field an evolving AICI does not result in considerable pressure axial redistribution, so the pressure maximum is in the turning points’ vicinity despite the instability.

Fluorescence visualization of pathologies is a popular form of endoscopic diagnostics in medicine. Interest in fluorescence optical visualization consists in providing information on the fluorescent signal spatial distribution by the photosensitizer fluorescence, which has a selective accumulation in tumor. Together with this, the determination of tissue saturation makes possible to assess the adequate of blood supply to anastomosis during surgical operation.

Developing technologies for efficient targeted drug delivery for oncotherapy requires new methods to analyze the features of micro- and nanoscale distributions of antitumor drugs in cells and tissues. A new approach to three-dimensional analysis of the intracellular distribution of cytostatics was developed using fluorescence scanning optical-probe nanotomography. A correlative analysis of the nanostructure and distribution of injected doxorubicin in MCF-7 human breast adenocarcinoma cells revealed the features of drug penetration and accumulation in the cell. The technology is based on the principles of scanning optical probe nanotomography and is applicable to studying the distribution patterns of various fluorescent or fluorescence-labelled substances in cells and tissues.

Spectroscopic approaches are very good to noninvasively determine the most significant indicators of the tissue state. Indocyanine green (ICG) is a well-known fluorescent dye approved for clinical applications, which has a short circulation time in the vascular system and low photostability. At high temperatures the molecular solution of the photosensitizer self-assembles into a stable J-aggregate form of ICG nanoparticles (ICG NPs) with the absorption peak in the near-infrared range. Investigation of ICG NP stability in human blood and plasma using a fiber-spectroscopic system demonstrates no difference in absorption properties and different dependence of the integrated fluorescence ratio between ICG monomers and J-aggregates in blood and plasma. Transition of ICG NP aggregates to the monomeric form in human blood plasma results in a higher circulation time of the fluorescent dye in the vascular system. High stability of aggregates and a low elimination rate may increase efficiency of fluorescent diagnostics of near-tumor tissues.

Indocyanine green (ICG), when in free form in a liquid, can form stable nanoparticle structures or colloidal solution, while changing its spectroscopic properties. In the work, the aggregation degree and the average size of nanoparticles depending on the concentration of a colloidal solution of indocyanine green (ICG NPs) in the form of J-aggregates were investigated by various methods based on light scattering. The size of nanoparticles is an important parameter from the point of view of clinical application, because the technique of intravenous administration of drugs, in order to avoid microvascular thrombosis and embolism, provides dosage forms with inclusions of individual molecules or their clusters, not exceeding 500 nm diameter. In turn, small nanoparticles less than 30 nm lead to prolonged circulation of the drug in the body with an increased possibility of permeation into cells of healthy tissue. In the course of studies, it was found that an increase in the concentration of ICG NPs in the solution leads to an increase in the average size of spontaneously formed J-aggregates, which, in turn, leads to a decrease in the absorption coefficient in the aggregates. Presumably, this phenomenon, i.e. the established nonlinear dependence of the J-aggregate absorption on its size, can be explained by the formation of absorption centers on the J-aggregate surface in the form of mobile surface molecules. The threshold range of ICG molecule concentration was determined, at which there is a transition from aggregation with an increase in size with a slow addition of ICG J-aggregate molecules in height to a rapid addition in width.

Today, fluorescent diagnostics and photodynamic therapy are promising methods for diagnosing and treating oncological diseases. The development of new photosensitizers (PS) is one of the most important tasks to improve the efficiency of both laser-induced diagnostics and therapy. In our study, we conjugated PS with AIS/ZnS triple quantum dots (QDs) to obtain non-aggregated complexes. It was shown that the conjugation of PS with QDs does not change the PS fluorescence lifetime, which is a marker of the preservation of PS photophysical properties. In particular, efficient resonant Förster energy transfer (FRET), from QDs to PS molecules in the conjugate, increases the PS luminescence response. The FRET from QD to PS molecules with different ratios of donor and acceptors are shown. It has been demonstrated that the average efficiency of FRET depends on the ratio of PS and QD and reaches a maximum value of 80% at a ratio of 6 PS molecules per 1 QD molecule. Thus, these studies could help to contribute to the development of new complexes based on QD and PS to improve the efficiency of phototheranostics.

The 3rd International Workshop on Gas-Dynamic Trap-based Fusion Neutron Source (GDT-FNS) was held through the hybrid mode on 13–14 September 2021 in Hefei, China, jointly organized by the Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS), and the Budker Institute of Nuclear Physics (BINP), Russian Academy of Sciences (RAS). It followed the 1st GDT-FNS Workshop held in November 2018 in Hefei, China, and the 2nd taking place in November 2019 in Novosibirsk, Russian Federation. With the financial support from CAS and China Association for Science and Technology (CAST), this workshop was attended by more than 80 participants representing 20 institutes and universities from seven countries, with oral presentations broadcast via the Zoom conferencing system. Twenty-two presentations were made with topics covering design and key technologies, simulation and experiments, steady-state operation, status of the ALIANCE project, multi applications of neutron sources, and other concepts (Tokamaks, Mirrors, FRC, Plasma Focus, etc). The workshop consensus was made including the establishment of the ALIANCE International Working Group. The next GDT-FNS workshop is planned to be held in May 2022 in Novosibirsk.

This paper presents the results of using intraoperative fluorescence diagnostics (FD) with the endoscopic video system to increase the efficiency of photodynamic therapy (PDT). The molecular form of chlorin e6 was used as a photosensitizer (PS). All patients received an intravenous administration drug based on chlorin e6 at the concentration of 1 mg/kg. Diagnostics and therapy were carried out in 4 patients diagnosed by malignant neoplasms of the lateral surface of the tongue. Determination of the boundaries by changing the signal of the fluorescence intensity of the tumor was carried out before PDT and after PDT. The efficiency of PDT was assessed by the fluorescent signal of the tumor decreasing when compared with non-pathological normal tissue. The FD method allows to determine accurately the actual size of the tumor and its borders. All patients underwent PDT influenced by the therapeutic laser with a generation wavelength of 660 nm. It is shown that the using of fluorescence diagnostics improves the quality of the photodynamic therapy, since it is possible to assess the photobleaching of the drug during the operation.

Any surgical intervention to a central nervous system requires special accuracy and selectivity of the effect on the cancer cells. The application of laser-spectroscopic methods provides a unique opportunity to non-invasively determine the most significant parameters that characterize the tissue states. Moreover, non-invasive state assessment of the brain tumor tissue and surrounding tissues is essential for performing a relapse-free operation. Indocyanine Green (ICG) is a photosensitizer approved for clinical practice and has absorption peak in the near-infrared range corresponding to the spectral transparency window of biological tissue. Also, the aqueous colloidal solution of ICG aggregates was used for spectroscopic properties research in glioma tumor cells. The comparative analysis of ICG in molecular and nanoforms demonstrate the difference between spectral values which allow distinguishing monomers and aggregates in tumor tissue.

This paper presents the high flux neutron shielding design and extensive neutronics calculations of GDT based fusion neutron source ALIANCE. Neutron distribution of ALIANCE is strongly inhomogeneous along the axis: significant portion of the neutron flux is generated near the two mirrors, while the rest of it is spread over the remaining central volume of plasma. The shielding design includes 40 cm stainless steel as the main shielding layer and an additional 5 cm tungsten carbide shielding layer at mirror plugs to protect superconducting coils from neutron damage and reduce nuclear heating. The simulations have been carried out by using Monte Carlo transport code SuperMC with nuclear data library FENDL 3.1. Results show that the nuclear heating on the mirror coils can be reduced by more than two thirds with additional tungsten carbide shield, and fast neutron fluence by 30 %. The highest nuclear heating and the highest fast neutron fluence zones are located at the mirror coils, and the values are about 300 W/m(3) and 9 x 10(18) n/cm(2) respectively, which meets the threshold of ITER superconducting coils. The specific activities of shielding layers are of order of 10(12) Bq/kg. The structural materials? specific activities will decrease to 4 x 10(11) Bq/kg in one year after shutdown, and their decay heat will quickly drop below 2 kW/m(3) after one day. Besides, all the structural materials of ALIANCE can be recycled by different recycling technologies. The modeling and calculations reported in this paper will be beneficial for the pre-conceptual engineering design of ALIANCE.

Cancer is the main problem of all developed and many developing countries of the world and the cause of death and disability of population. Today, the actual problem is receipt of reliable information about the boundaries of malignant neoplasms and the detection of pathology in the early stages.

Squamous cell carcinoma is the most common type of oral and oropharyngeal cancers. Incomplete surgical removal of the tumor is often the cause of local recurrence of the disease and appearance of metastases. We have developed the novel endoscope fluorescence video system for visualization of micrometer size objects in real-time mode. The novel system was tested on three-dimensional models of cancer cells. Chlorine e6 (Ce6) was used as a photosensitizer. The accumulation of Ce6 in cancer cells was assessed by its fluorescence excited at 635 nm. It was shown that the 500 µm multicellular tumor spheroids could be easily detected with a good resolution and sensitivity. We suppose that the new endoscope video system could be useful for developing the intraoperative fluorescence navigation method using Ce6-mediated techniques that is able to visualize the small cancer cell clusters.

The paper presents the evaluation of basic parameters and general appearance of the superconducting magnetic system of the Gas-Dynamic Multimirror Trap - the next-generation magnetic mirror research facility developed by the Budker Institute of Nuclear physics. The major requirements are that the magnetic field would be ramped up from 0.3 to 3 T within 5 seconds, which implies that a special low AC-loss superconducting cable must be chosen for this part of the magnet system. The mirror coils should have the field ~12 T with an aperture exceeding typical of large-bore NMR magnets. In accordance with these requirements the optimized magnet system has been evaluated. The system can have modular design and consists of a set of 12 coils with NbTi superconductors and 4 coils made of Nb 3 Sn superconductor. Preliminary choice of superconducting cables and basic superconductors for the windings has been substantiated. The estimation of stability margins for all coils demonstrated that both NbTi and Nb 3 Sn coils have enough stability margins, including the operation of NbTi coils at fast changing current. The study demonstrated the feasibility of the optimized superconducting magnet system for the Gas-Dynamic Multimirror Trap with the use of modern low T c superconductors and state-of-the-art superconducting magnet technologies.

This paper presents a project of near future research on confinement of plasma with quasi-reactor parameters in axially symmetric magnetic mirrors. Features of axial losses and transverse transport are considered from the point of view of results obtained on the gas dynamic trap in the past few years. A diagnostic complex for planned research is described.

Paper presents a brief overview of the studies carried out in 2016-2018 at the Gas Dynamic Trap device at the Budker Institute. These studies were focused on the experimental substantiation of a new version of the Gas Dynamic Multi-mirror Trap project, which is aimed at developing the key technologies needed to implement a number of thermonuclear applications of linear magnetic traps. The paper reviews the work aimed at stable plasma confinement under auxiliary ECR heating. We showed that a value of on-axis electron temperature up to 450 eV at plasma density 1.2 x 10(19) m(-3) can be supported steadily. Studies on processes in expanders, which determine the axial thermal conductivity of the plasma, showed that the profile of the electric potential in the expander corresponds to a theory that gives favorable predictions regarding the thermal insulation properties of the expander. It was shown that the density of neutral gas in the expander in the range up to 10(20) m(-3) does not have a significant effect on energy confinement in the trap, despite an estimate of the critical density of 10(18) m(-3). (C) 2019 The Japan Society of Plasma Science and Nuclear Fusion Research