Vol 44, No 2 (2016)

Background: This is a theoretical and experimental study of the thermomechanical effects of laser radiation with a wavelength of 1.06 microns on the eye tissues during a laser surgery on the secondary cataract (pupillary membrane). Its relevance is related to the rates of complications after laser surgery of the eye associated with the choice of energy and time parameters of the laser irradiation. These parameters are related to the occurrence of such factors as unstable fields of thermal stress and pressure that are difficult to take into account and indirectly lead to adverse events when removing the secondary cataract. Aim: To minimize side effects and to optimize the existing technology of laser removal of the secondary cataract. Materials and methods: Samples of a  normal lens capsule and of lens capsules with various types of opacities taken during a  cataract surgery, with various optic characteristics and thickness, were treated with an infrared laser (Nd:YAG laser, 1064 nm). We performed morphometric measurements and built up a  theoretical model of the processes in a continuous medium under the effects of impulse laser irradiation. Results: The results of numerical modelling with this newly developed theoretical model are in satisfactory agreement with the experimental data on development of deformities obtained with the autopsy materials (posterior capsule of the human lens with various optical characteristics and thickness, from thin transparent membranes to more thick opaque samples). Conclusion: This study would allow for optimization of the technology of laser treatment for secondary cataracts by changing the irradiation parameters during the procedure. 

Background: Photodynamic therapy (PDT) is a  modern minimally invasive technique for treatment of a wide range of diseases, including malignancies. One of directions for PDT development is the individualization of exposure modes that can be achieved with effective treatment monitoring. There are a  number of approaches employing imaging techniques, the most promising of them being optical ones. Aim: To analyze factors affecting clinical outcomes of PDT in non-melanoma skin tumors, and to evaluate the prospects of optical imaging techniques for PDT planning and monitoring. Materials and methods: We retrospectively analyzed various aspects of the results PDT obtained in 855 patients with non-melanoma skin tumors. PDT was performed with systemic chlorine photosensitizers. As a  source of irradiation, the laser at a wavelength of 662 nm was used following exposure modes: mean power density 0.3 W/cm², the laser irradiation dose of 200 J/cm² for basal cancer and 300 J/cm² for squamous cell carcinoma. Clinical evaluation was performed based on tumor response according to RECIST criteria, by the presence or absence of recurrence during long term follow up and by the presence or absence of cosmetic defects. Fluorescence imaging and optical coherence tomography were used as non-invasive imaging techniques. Results: It was found that clinical predictors of treatment failure included tumor recurrence, squamous type of tumor, and advanced exophytic or infiltrative component. Fluorescence imaging showed an association between clinical outcomes of PDT and fluorescence characteristics of the photosensitizer. The best clinical outcomes were achieved in 147 patients with a combination of high contrast fluorescence (FC>1.2) and a high degree of photobleaching of the agent (ΔIt/IN >25%): the number of complete tumor responses was 94% (138 of 147), with recurrence seen in 3 (2%) patients only with the follow up from 6 to 53 month duration. Clinical predictors of PDT cosmetic failures are tumor recurrence and tumor stage above T2. The most vulnerable zones are the outer ear and nose wings; this fact is related to an involvement of the cartilage located directly beneath the thin skin in the photodynamic reaction. This was demonstrated by optical coherence tomography. Conclusion: Presence of clinical predictors of PDT failure justifies correction of light exposure modes that can be optimally implemented with techniques for objective evaluation of the tumor borders, photosensitizer accumulation and photobleaching. Dynamic non-invasive monitoring of PDT procedure with fluorescence imaging and optical coherence tomography seems promising for implementation of an individual approach resulting in optimal oncological and functional outcomes.

Background: Laser fluorescence spectroscopy (LFS) is widely used in various medical areas, oncology being the most known of them. In general, the LFS is used for in vivo diagnostics of tumors. Recent studies have shown that this method could be used for diagnostics of local inflammation, induced by thermal or mechanical injury. It is of interest if LFS could be used for assessment of soft biological tissue injury caused by radiation exposure. Aim: To study fluorescence of an exogenous photosensitizer and its changes over time in the radiation injury area by LFS method in vivo. Materials and methods: The experiment was done in 12 outbred SHK mice whose right hind limbs were irradiated using a gamma-therapy device ROKUS-AM (source, 60Co, at dose of 15 Gy). Before irradiation, the photosensitizer Photosens was administered to all animals intraperitoneally at dose of 2.5 mg/kg. For 21 days fluorescence was assessed in vivo with a laser diagnostic system LAKK-M in the “fluorescence” operation mode, with an excitation wavelength of 635 nm. At days 7 and 21, tissue samples from the irradiated areas of the model animals were studied histologically and differential blood cell counts were assessed simultaneously. Results: The LFS method showed an increase in the accumulation of the photosensitizer in the affected area, compared to an intact contralateral area, with higher signal intensity from the irradiated limb. The changes in the fluorescence signal from the affected over time had two characteristic peaks at days 3 and 14, probably reflecting the stage of local radiation injury. Conclusion: The use of LFS with an exogenous photosensitizer has a potential for a personalized assessment of radiation reactions in radiology.

Background: The impedance rheocardiography is a  simple, inexpensive, noninvasive method of assessment of central hemodynamics that can be used for detection of cardiovascular remodeling and thus promote an improvement of cardiovascular mortality. Modern mathematical methods of data management could help to discover new possibilities of rheographic signal analysis. Aim: To demonstrate the potential of a  wavelet-analysis of rheocardiograms for identification of myocardial remodeling of patients with cardiovascular disorders. Materials and methods: The proposed method was validated in 12  healthy men aged from 20  to 25  years and 14  patients with arterial hypertension. We used a  polyreocardiograph, which records simultaneously the impedance (ICG), the electrocardiogram (ECG) and the phonogram (PCG). The function of the cardiovascular system was assessed based on the two-dimensional time-frequency distributions of wavelet transformed coefficients of differential rheogram curves. Results: The results of an isometric load test confirm the adequacy of stroke volume estimation based on the amplitude of wavelet coefficients and the scale of the E wave. In this technique, ISTI parameter was defined as the time interval between the R wave in the ECG and the maximum of the E wave in the wavelet image. The simultaneous time-frequency analysis of both the pulse and respiratory component of an ICG signal can be a basis for the development of complex functional respiratory tests. Conclusion: The approach proposed demonstrates the possibility to obtain the characteristics of the diastolic phase of the cardiac cycle, and allows for a more precise determination of the stroke volume. Data management is done automatically. These advantages are expected to be used for producing a mobile cardiograph for screening diagnostic.

Background and aim: The volume of reconstructive surgery in traumatology in recent decades has increased significantly due to an increase in traumas, numbers of affected in local military conflicts, and environmental deterioration. This has led to an increase in demand for plastic materials, and the need to create modern high technologies to meet this need, including alternative sources of bone implants. Any solution to this problem would involve an in-depth study of bone biophysical properties with innovative techniques to develop requirements to elaboration of new effective implants based on natural bone, as well as on natural or synthetic analogues. This study aimed exactly at these aspects. Materials and methods: We studied human bone samples taken from various parts of the skeleton aged from 3 to 89 years and animal (bovine) bone samples aged from 1.5 to 2 years. Biophysical characteristics of the studied materials were assessed at the stage of sample preparation with original author's methods of physical and mechanical processing, in the process of analysis of patterns of normal changes in the bone structure and function, as well as during changes in its composition with age, anisotropy of the material and the level of structural organization. Structure patterns were studied by classical (light, scanning electron microscopy) and advanced (acoustic microscopy) techniques. Methods of engineering biomechanics were used to assess functional changes in macro and micro volumes of bone samples. Results: The main study results involve the development of innovative methods of sample preparation and structural and functional analysis. First of all, these are the methods of mechanical processing of bone fragments based on the use of hollow cylindrical milling cutters in the environment of limited amounts of mineralized biological tissues, as well as on the application of hydrodynamic cutting ensuring a delicate and highly efficient bone cut. Another distinctive feature of the study is the elaborated methodology for morphological and mechanical analysis of bone samples at the macro and micro levels, with consideration of real physical and chemical condition of samples. To ensure sample sterility, the authors proposed innovative techniques using of ozone-oxygen mixtures. The study results gave a  complex of quantitative characteristics describing age-related compositional changes of the human bone, anisotropy of its physical and mechanical characteristics, osteon parameters and physical and mechanical characteristics of bone tissue depending on its composition. Conclusion: The use of the proposed methodology allowed for obtaining of new data on biophysical properties of bone tissue that are of interest for bioimplantology, biomaterial science and expands basic information on the bone as a natural biocomposite. They can be the basis for development of practical guidelines on optimization of the choice of bone fragments for manufacture of implants based on the detected patterns of changes in macro- and microstructure, physical and mechanical characteristics and bone composition in the studied age range.

Background: Lichen planus rubrum (LPR) belongs to the group of papulosquamous dermatoses. Pathophysiology of this most common lichenic dermatosis is related to autoimmune destruction of basal keratinocytes. Treatment of LPR includes systemic corticosteroids, cytotoxic agents, immunosuppressants, aromatic retinoids, PUVA-therapy, as well as biological preparations (rituximab, efalizumab), which all are insufficiently effective and associated with multiple side effects and complications. Aim: To evaluate efficacy of extracorporeal photochemotherapy (EPCT) in generalized typical and atypical LPR. Materials and methods: We performed a prospective active-controlled cohort study. Thirty three patients with different types of LPR treated with EPCT were divided into 2 groups. Group 1 included 19 patients with typical generalized (including subacute and chronic) LPR, group 2, 14 patients with atypical (pigmented, follicular, hypertrophic, erosive ulcerated, vulvovaginal/ gingival syndrome) LPR. At 2 hours before a EPCT session patients were administered 8-methoxypsoralen, then mononuclear cells were isolated with a cell separator Haemonetics MCS+ and treated with UV A radiation (at a wavelength from 320 to 400  nm), then monocyte mass was reinfused to the patient. The treatment course consisted of 4  sessions performed every other day. Results: Positive clinical effect and satisfactory tolerability of EPCT were demonstrated in all 33 patients. In patients with generalized subacute typical LPR, EPCT promoted activation of natural immunosuppressive mechanisms (there was no correlation between CD8+ and HLA-DR+ , as well as between CD8+ and CD11b+: r=0.52 (р>0.05) and r=0.35 (р>0.05), respectively). In patients with generalized chronic LPR the treatment led to restoration of immune tolerance to genuine body antigens (correlation between CD16+ and CD11b+ was preserved and correlation between CD16+ and HLA-DR+ was lower: r=0.77 (p<0.05) and r=0.62 (p>0.05), respectively). Conclusion: The data obtained confirms high clinical efficacy of EPCT and its pathophysiological effects at early and later stages of generalized typical LPR.

Background: To improve quality of surgery in oncology, it is necessary to completely remove the tumor, including its metastases, to minimize injury to normal tissues and to reduce duration of an intervention. Modern methods of detection based on radiological computerized tomography and magnetic resonance imaging can identify a tumor after its volume has become big enough, i.e. it contains more than 10 billion cells. Therefore, an improvement of sensitivity and resolution ability of diagnostic tools to identify early stages of malignant neoplasms seems of utmost importance. Aim: To demonstrate the potential of a new class of anti-Stokes luminescence nanoparticles for deep optical imaging with high contrast of malignant tumors. Materials and methods: Upconversion nanoparticles with narrow dispersion and a  size of 70 to 80  nm, with a  core/shell structure of NaYF4:Yb3+:Tm3+/NaYF4 were used in the study. The nanoparticles have an intensive band of anti-Stokes photoluminescence at a wavelength of 800  nm under irradiation with a  wavelength of 975  nm (both wavelengths are within the transparency window for biological tissues). The conversion coefficient of the excitation radiation into the anti-Stokes luminescence was 9%. To increase the time during which nanoparticles can circulate in blood flow of small animals, the nanoparticles were covered by a  biocompatible amphiphilic polymer shell. As a  tumor model we used Lewis epidermoid carcinoma transfected to mice. Results: We were able to obtain stable water colloids of nanoparticles covered with amphiphilic polymer that could preserve their initial size at least for one month. The use of upconversion nanoparticles with a  hydrophilic shell made of intermittent maleic anhydride and octadecene co-polymer with subsequent coating with diglycidyl polyethylene glycol ether allowed for reduction of non-specific reaction of nanoparticles with plasma proteins. In its turn, it resulted in an increased time of their circulation in blood flow of small animals for up to 1 hour. With the Lewis lung carcinoma transfected to mice model we demonstrated аn in-life transportation of upconversion nanoparticles into the tumor with a  high degree of localization due to a passive EPR effect. The contrast of luminescent signal in the tumor compared to adjacent tissues was at least 70%. The possibility of visualization of upconverted nanoparticles up to 15 mm of biological tissue was shown. Conclusion: The optical imaging techniques with anti-Stokes photoluminescent markers ensure a  high contract real-time detection of tumor tissues that allows for their use for intra-operative diagnostics.

Rationale: One of the most complicated and unresolved problems in clinical medicine is the choice of an optimal method for organ-preservation treatment of uterine fibroids in women of childbearing age. Aim: To assess clinical efficacy of robot-assisted laparoscopic myomectomy. Materials and methods: The search was performed in PubMed, Embase, Trip, Cochrane, DocMe databases by keywords: “fibroids”, “robot”, “da Vinci”, “robotic myomectomy”, “robot-assisted myomectomy”. Results: We found 25 publications on robot-assisted laparoscopic myomectomy, including 6  papers on its reproductive outcomes (levels of evidence II–IV). Duration of robot-assisted surgery ranged from 132 to 261 minutes, intraoperative blood loss was in the range from 50 to 387 mL, postoperative hospital stay ranged from 1 to  3.9  days. There was a  lower percentage of intra- and postoperative complications after the robot-assisted interventions, compared to abdominal or classic laparoscopic access, as well as a lower percentage of conversion laparotomies compared to laparoscopy. Pregnancy rates after robotic myomectomy ranged from 16.7 to 69%. Only one case of uterine rupture after robot-assisted laparoscopic myomectomy has been described in the literature. Conclusion: Due to high cost of the method, the number of conducted studies is insufficient to evaluate the role of robotic technologies in the organ-preservation approach to uterine fibroids. Nevertheless, they suggest that robot-assisted laparoscopic myomectomy is justified in women of childbearing age who are planning pregnancy, with big centripetally growing intramural nodes and deformation of the uterine cavity. This technique on its own is an independent method for fertility restoration and could be the first step before the use of assisted reproductive technology.

Methods based on accelerative and radionuclide technologies are more and more invading clinical practice of modern medicine. The aim of this review is to demonstrate the role of nuclear physics techniques for treatment and diagnostics of various disorders. We analyzed data published in the last 50 years in research papers, reports and other open sources considering particulars of electron accelerators and heavy charged particles in radiation and nuclear medicine and presenting the information on prevalence of accelerators and other high-tech medical equipment in Russia and worldwide.