RU2621547C2 - Method for remote electromagnetic multiwave radio neuroengineering of human brain - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method for remote electromagnetic multiwave radio neuroengineering of human brain comprises the following steps: a) design and layout by complex diagnostic by means of brain MRI study, MRI tractography of brain damage zones (DZ) pathways, MRI angiography of brain vessels, brain positron emission tomography (PET) or whole body PET, brain computer tomography (CT), cerebral electroencephalographic mapping (EEG) and/or brain magnetoencephalography (MEG) to create individual 3D-map of nerve tissue (NT) damage simulation by a programmed multilevel merge of diagnostics data for subsequent determination of NT DZ by marking on the patient's head skin using a stereotactic radiotherapy and radiosurgery apparatus to determine tilt angles and effective radii of the subsequent non-ionizing stereotactic effect of focused ultrasound (FUS) on NT; b) NT DZ vascular bed resimulation using focused ultrasound under control of MRI ionizing radiation (IR) or structurally-resonance therapy (SRT); c) cell restoration of NT DZ by directed intervention of autologous mesenchymal stromal stem cells (MSSCs) mobilized in peripheral blood, hematopoietic stem cells (HSCs) and progenitor cells (PCs) into the NT DZ; d) NT DZ vegetative supply correction by means of combined exposure to electromagnetic non-ionizing radiation in the form of SRT with simultaneous or sequential exposure to FUS; e) dynamic integration of somatic and vegetative components by combining FUS exposure with simultaneous or subsequent SRT exposure; f) rehabilitation of damaged NT DZ functional state by combined application of SRT and FUS.

EFFECT: method provides remote, non-invasive, focused, directed restoration of brain NT in treatment of a range of nervous and mental diseases at a stepwise combined exposure to different types of electromagnetic radiation, which eliminates disadvantages and complications from the use of these known methods of FUS, IR, SRT separately at minimum sufficient cellular intervention into the patient's brain.

6 cl, 2 dwg, 7 tbl, 2 ex

Description

The invention relates to medicine, in particular to methods for treating diseases and injuries of the human brain (GM). The invention is intended for remote multi-wave electromagnetic radio neuroengineering (DMV EM RNI) of human nervous tissue (HT) GM and can be used in the complex treatment of various nervous and mental diseases in neurology, psychiatry, neurosurgery, neurooncology and regenerative medicine.

The relevance of the development and socio-economic need for this invention is due to the threatening growth trends in the number of neurological and psychiatric patients with organic diseases and injuries of GM in the world over the past 50 years and the very low efficiency of modern treatment of nervous and mental diseases. According to the World Health Organization (WHO) for 2013, every third person on Earth suffers from a brain disease. This was due to the fact that the natural outcome of the modern many months, and in some cases many years, treatment of the majority of patients with severe diseases and brain injuries in almost all leading clinics of the world is a high mortality rate of patients, a pronounced neurological deficit and the outcome of a severe neurological disease in decay, disintegration of mental activity and dementia, as well as deep disability and desocialization of neurological and psychiatric patients after their treatment complete maladjustment this group of patients in the community. Despite the low efficiency of brain damage, the cost of their treatment is constantly growing. For example, treating brain diseases alone costs 80 billion euros annually for just one EU (Human Brain Project, 2012). In other words, the modern treatment of nervous and mental diseases in practice is still ineffective and unsuccessful, it is very expensive and takes from several weeks to several tens of years.

Currently, the modern standard for the treatment of human brain diseases includes mainly various pharmacological preparations and known methods of rehabilitation and rehabilitation treatment (physiotherapeutic procedures, physiotherapy exercises, hyperbaric oxygenation, massage, acupuncture, etc.). The search for new treatments for nervous diseases and psychiatric disorders and methods of brain neurorestoration is ongoing.

Over the past 20 years, repeated but ineffective attempts have been made to restore the damaged human brain through neurosurgical reconstructive treatment. The main methods of this treatment were large open reconstructive and reconstructive neurosurgical operations, tissue engineering technologies and methods of implantation of neuroengineering systems and devices into the brain. To date, there is not a single standard or officially approved protocol for neurorestoration in the world, and all existing medical technologies for the reconstruction of damaged GM humans and mammals are mostly neurosurgical and microsurgical "improvisational" schemes for large or small operations on the brain and its vessels or reconstructive operations on tissue engineering of the brain using stem cells (SC) and various biopolymer matrices.

In the global clinical practice of reconstructing a damaged brain, there are also attempts to use various methods for restoring the morphological structure of the brain, based on standard approaches to the application of technologies for interventional x-ray anneurology and functional neurosurgery. They are based on methods of neuronavigation and minimally invasive neurosurgical interventions (balloon angioplasty of cerebral vessels, stereotactic radio and cryodestruction of neural tissue, implantation of neurostimulants, etc.) and standard manipulations of vascular surgery (sympathectomy, blockade of sympathetic ganglia, programmed pharmaceutical perfusion. e.) used in modern vascular neurosurgery, functional neurosurgery, neuroendoscopic surgery and x-ray surgery. All microneurosurgical technologies, regardless of their degree of invasiveness, have so far not allowed anyone in the world to achieve complete cure for nervous and mental diseases, as well as to obtain real morphofunctional restoration of damaged GM in humans, regardless of the etiology and pathogenesis of the pathological process in the brain.

The efforts of neurosurgeons and neuroreanimatologists to introduce high-tech methods of treating nervous diseases led to a sharp increase in the number of surviving patients after suffering brain injuries that are almost incompatible with life (brain injuries, strokes, intoxications) with massive damage to brain tissue and a brain defect. The flip side of these fantastic "victorious successes" in the survival of acute neurological patients with brain injuries incompatible with life, and the obvious achievements of modern resuscitation and anesthesiology medicine was a significant increase in the number of neuropsychiatric patients with extremely severe organic brain lesions. A feature and specificity of this contingent of patients with organic brain pathology is their clinical futility in therapy with existing methods of pharmacological treatment and the inability to restore the productive intellectual life of patients at the present stage of neuroscience development. As a rule, the most frequent outcome of a serious neurological disease or brain injury is a chronic vegetative state in the form of an apallic syndrome or akinetic mutism syndrome (locked-up person syndrome) or dementia (dementia). For the most part, patients who survived after such severe brain injuries are deeply disabled people with complete labor and social maladjustment in the family, life and society.

It is assumed that a significant breakthrough in the effectiveness of the treatment of organic diseases of GM may be achieved in the next 10 years as a result of the introduction of modern technologies of regenerative medicine (tissue engineering, cell neurotransplantation and cell therapy) into modern neurology and neurosurgery. In 2012-2013 alone, more than 80 state institutes of regenerative medicine were opened in the EU countries for the treatment of neurological and mental patients, and more than 300 similar institutes were established in the United States. The U.S. Department of Defense has formed a military institute of regenerative medicine (IRM) at Wake-Forest University and two scientific consortia (each of which consists of 16 state universities) to solve this problem and allocated more than 300 million US dollars for research. The functional responsibilities of these innovative institutions include the creation of innovative technologies of regenerative medicine and, inter alia, the development of various neurotechnologies for the restoration of damaged brain. In recent years, this direction in medicine has received a new name - neurorestoration. The International Association for Neurorestoration (IANR) has been created, which considers invasive neurosurgical technologies of cell transplantation and tissue engineering and bioengineering of GM as the main tools and methods of neurorestoration.

Neurorestoration is a rapidly developing multidisciplinary surgical field of bioengineering science, defined as an innovative field of medicine engaged in the creation of “artificial tissues” and restoration of tissue defects. In this new scientific medical field, a new medical specialty is identified - regenerative medicine (RM), which describes tissue engineering as a surgical specialty that uses cells, engineering materials and suitable biochemical factors to improve or replace biological functions for the development of medicine.

The creation of an implantable bioconstruction or artificial tissue prosthesis (including nerve tissue) in modern bioengineering and tissue engineering of organs makes us decide on the optimal biomaterial, on the type of cells used, how they are cultured in vitro in bioreactors, on the development of matrices and the ability to integrate a living bioengineered design to the brain in vivo. At the same time, it is obvious that it is impossible to create a universal construction a priori that would completely repeat the finest balance of structural and biological properties of natural matrices and cellular tissue systems. Many fabrics viewed at high magnification have random organization. However, nature functions in such a way that everything has its own systemic organizational structure. For this reason, the creation of a new biological organization in an artificial tissue-engineering system allows scientists to hope for the restoration or replacement of the lost function of an organ or tissue. This fully applies to any methodology for the restoration of human GM.

It should be recognized that over the more than 30-year history of the existence of a scientifically based methodology and technology of cell transplantation and tissue engineering, no real organs and tissues have yet been created that are structurally and functionally consistent with natural organs and human tissues. The existing artificial “similarities” or “equivalents” of a person’s organs (bladder, trachea or bone) are still a weak imitation of the natural structure of human and animal organs, and in functional terms they generally require very serious refinement. Despite the fact that many of them are already “transplanted” to humans, they are still far from perfect and a lot of time will pass when they will be close to their natural prototypes.

Currently, neuroengineering is one of the fastest growing trends in the fundamental sections within the biotechnological platform of bioengineering and tissue engineering of human GM. Wikipedia interprets neuroengineering as a scientific discipline that is part of biomedical engineering and uses various engineering methods to study, restore, replace or strengthen the nervous system. Neuroengineering solves various unique problems on the problems of combining living neural structures and non-living electronic structures.

Another global trend in the development and creation of innovative methods of treating GM diseases is aimed at creating wireless, mobile, contactless and mainly remote neurotechnologies and developing information and communication platforms for the treatment of damaged GM people. These innovative strategies of modern neuroscience, clinical neurology and psychiatry are reflected in the materials of the global international research projects Brain Initiation (USA) and Human Brain Project (European Union). As part of the American Brain Initiation research project, in December 2013, the United States Defense Advanced Research Projects Agency (DARPA) announced multimillion-dollar grants for two new developments to create a new methodology and technology for a wireless device that can cure neurological disorders, as well as device that restores active memory. The first grant is aimed at working with the so-called neural technologies of subnets (SUBNETS), in particular, at creating a new wireless device that can cure such neurological disorders as post-traumatic stress, severe depression or chronic pain. The second grant will be given to scientists who are able to restore active memory (RAM). It is planned to develop separate wireless devices that repair GM damage and restore memory. The program includes the return of not only motor memory, but also complex hierarchical memories. Despite the fact that these developments were originally intended for injured fighters of the American army, they can be used to help the civilian population suffering from memory loss, stress disorders, dementia and other neurological and mental illnesses.

A number of experts and researchers in the US and Europe consider this DARPA non-contact approach to treating neurological patients as unrealistic, almost insane, and practically unfeasible. However, the very fact that DARPA, the main generator of new scientific ideas and a leading producer of most of the world innovations and innovative technologies in all fields of science and technology, pays so close attention to the problem of treating this contingent of military and civilian patients with a neurological and mental profile once again confirms the real the lack of treatment technologies for acute and chronic functional and organic pathology of GM, and their technical conditions for the development and creation of these devices set a very high requirements for the creation and implementation of high-tech methods for the treatment of diseases and injuries of GM, which is very difficult to meet without modern equipment and a decent methodological and technological base.

Over the past 25 years, quite a lot of experience has been gained in the development, creation and clinical application of regenerative medicine technologies in the treatment of pain pathology of the human brain and the use of transplantations of fetal nerve cells (FNC) in 550 patients, the use in the clinic of autologous hematopoietic stem cells mobilized to peripheral blood (HSC) ) and progenitor cells (PC) of bone marrow in 5230 (five thousand two hundred and thirty) patients with organic diseases of the central nervous system (CNS). About 12.5 years have been used in animal experiments and in clinical trials in humans, innovative methods of tissue engineering of GM using biomaterial FNK and biopolymer matrices (46 patients with damage to SM). An autologous cell-biopolymer neuroendoprosthetic system (patent RU 2394593 C2) was created, patented and successfully implanted to a person (52 patients with severe spinal cord injury). C1).

Closest to the present invention (prototype) in terms of essential features is the well-known bioengineering method for restoring brain functions described in patent RU 2152038 C1, IPC G01N 33/68, А61В 17/00, А61Р 25/00, 2000. This patent was A method for neurorestoration of the nervous tissue of a damaged human brain by means of algorithmized stepwise surgical use of minimally invasive technologies, radiopaque instruments and supplies (implantable cylinders, stents, perfusers, conductors, etc.) is disclosed. entgenohirurgii functional stereotactic neurosurgery and cell transplantation, implantation neurostimulators, neyrosistem and electronic devices. The very idea of a multi-stage software reconstruction of a damaged HT brain in a human being proved to be viable. The known method includes the implementation of a number of successive stages of the biotechnological process of minimally invasive bioengineering: 1) design stages, 2) stages of vascular bed remodeling, 3) stages of cell transplantation, 4) stages of dynamic integration of somatic and vegetative components, 5) stages of rehabilitation.

At the design stage, in the known prototype method, the lesion site in the GM and the spinal cord (SM) is identified by visual analysis of CT and MRI data of the brain and this focus becomes the main object of restoration of the GM or SM. The stage of remodeling of the vascular bed in the known method is carried out by surgical transposition (surgical movement) of the omentum on vascular connections to the restoration area of GM or SM or by means of x-ray minimally invasive intra-arterial intervention, performed by puncture of the femoral vein, placement of the introducer and the intra-arterial close-fusion surgical unit to the zone of brain damage in the projection of the reconstructed vascular pool carrying out within 1-2 days of program regional perfusion vasoactive pharmacological agents (vazoprostan, papaverine, no-spa, etc.). This allowed to increase the total area of the capillary network of the restoration zone by 5-6 times. At the stage of cell transplantation in the known method, the lost cell composition at the site of damage to the GM and SM is compensated using stereotactic functional neurosurgical or open surgical neurotransplantation of cells into the brain parenchyma. The restoration of the cellular composition of the nervous tissue at the site of damage is carried out by direct cell transplantation, which ensures the restoration of quantitative parameters of the content of cells in the reconstruction zone and the restoration of broken synaptic connections between neurons inside the nervous tissue. This stage is carried out by transplantation of cell preparations from fetal cells using neurosurgical devices (apparatus for stereotaxis and neuronavigation system) or using intraventricular and intrathecal cytotransfusion of fetal cell preparations. The stage of dynamic integration of somatic and autonomic components in the known method is performed by conducting open mini-surgical operations on the autonomic nodes or interventional manipulations on the autonomic nervous system autonomic structures. For this, sympathectomy operations are used on the side of damage to the GM, novocaine blockade of the regional sympathetic nodes or transplantation of nerve cells into the sympathetic ganglia on the side of the brain lesion. To restore vegetative and cellular-tissue relations at the site of damage at this stage, subdural or intracerebral implantation of standard neurostimulators in the projection of the tissue reconstruction zone of GM and SM was used. The rehabilitation stage is carried out by applying standard modern methods of rehabilitation treatment of neurological patients (physical rehabilitation on simulators, physiotherapy, physiotherapy, massage, etc.).

The effectiveness of the application of the known prototype method was tested by military personnel in the conditions of the Branch No. 3 (32 Central Naval Clinical Hospital) GVKG them. N.N. Burdenko is clinically proven in conditions of warfare by the Armed Forces of Russia during various local military conflicts (Afghanistan, Chechnya, Abkhazia, Nagorno-Karabakh). The use of this minimally invasive neurosurgical technology in military medicine for the entire period of the second Chechen military conflict in comparison with the results of treating a battle brain injury in the first Chechen local conflict allowed us to reduce mortality in wounded with a military brain injury by 15%, and to reduce disability in wounded by 35%, and also by 10.5% reduce mortality from acute traumatic ischemic damage to GM.

However, despite the very positive results of applying the known prototype method in the clinical practice of military medicine, the main unsolved problem was a large number of formidable iatrogenic surgical complications (subarachnoid and subdural hemorrhages in HT GM and SM and ischemic strokes, purulent-septic meningitis and meningoencephalitis, coma conditions, septic complications, etc.) that occur at almost all stages. It was a large number of surgical complications that became the main reason for limiting the use of this known method in civilian healthcare. The risk of a large number of surgical complications in a war is unacceptable in civilian life, especially when providing high-tech medical care to civilians.

Another disadvantage of the known prototype method was that the method took into account only the large morphological substrate of damage to the GM and SM, which was visually revealed during MRI and CT studies, and absolutely did not take into account small damage to HT and the neurophysiological, metabolic and functional features of brain damage, which play a large role in impaired brain function.

Another serious disadvantage of the prototype method is the extremely high cost of surgical minimally invasive treatment of brain pathology. The cost of modern x-ray and neuronavigation medical equipment and specialized consumables (catheters, angioplasty cylinders, stents, etc.) for interventional x-ray surgery and a number of sequential brain bioengineering operations is constantly growing in arithmetic progression due to the use of innovative foreign implant materials and mini implants. The high cost of consumables determines the correspondingly high cost of surgical work with these materials. The problem of reducing the cost of treating GM injuries also makes us look for new import-substituting alternative and less costly treatments for these patients.

The lack of effectiveness of modern tissue engineering and brain bioengineering technologies in the prototype method is also related to the fact that the existing cytotransfusion technologies for allogeneic fetal cells, autologous HSCs and hematopoietic progenitor cells are generally uncontrolled or, more precisely, generally uncontrolled. Most of the expensive fetal, haploidentical, or autologous cellular biomaterial used for treatment that can have a regenerative, neurotrophic, stimulatory, proliferative, or regulatory effect on damage zones in GM, when intrathecal is administered, settles on the membranes of the brain or enters the systemic circulation and bone marrow or various organs, and the other part of the cell preparation is simply lysed with aggressive cerebrospinal fluid. With intravenous and intraarterial administration, the cell preparation cannot enter the patient’s GM reconstruction zones due to the existing physiological protective impermeability of the blood-brain barrier (BBB) for the regulatory mononuclear cell elements of blood, stem cells (SC) and progenitor cells (PC) and most neurotropic pharmacological preparations . This creates the impossibility of overcoming the BBB by hematopoietic stem cells (HSCs), hematopoietic precursor cells (HSCs), stromal mesenchymal SCs and other biologically active substances (BAS) molecules. These therapeutic agents are not physically able to get in sufficient quantities into the area of brain reconstruction. As a rule, most of the cell systems of the preparation obtained from HSCs and PCs of bone marrow mobilized into peripheral blood settle in various organs and tissues or again go into the niches of the bone marrow. This phenomenon is well known and has been repeatedly demonstrated in the experiment and clinic.

An irrefutable scientific fact is the biological phenomenon of the fact that in the zone of brain reconstruction it is necessary to ensure the maximum concentration of the cell preparation, and this serves as a fundamental key element for tissue restoration and regulation of its functional properties and qualities. Today, in tissue engineering of organs, this is achieved surgically by maximizing the retention of cell systems in biopolymer heterogeneous matrices implanted at the site of restoration of GM or SM. The efforts of specialists to ensure the maximum concentration of SC in the reconstruction zone is a basic element of the entire replacement system of the affected cell systems.

Currently, the search for means of targeted vector delivery of molecular components of a pharmacological or cellular preparation to the site of damage or restoration of GM or SM tissue is predominantly done by the biochemical method (liposomes, biopolymer capsules around the cell, nanostructure, etc.) and (or) the immunochemical method (immunoliposomes , multicomponent vectors that are created by “sewing” to cells and to molecules of antigens or antibodies). But these approaches are not physiological, on the contrary, they become sufficiently traumatic for the internal structure and tissue homeostasis. The “garbage” remaining in the tissues after their application, in the form of nanoconstruction residues, liposome fragments, antibody elements or microparticles of biopolymer and metal balls, is technically impossible and practically impossible to remove from the intercellular structure of human organs and tissues.

Another equally important problem and the clinical paradox of regenerative medicine in general and the prototype method, in particular, is the problem of the "structure and function" of the reconstructed area of the nervous tissue. Many years of experience in neurosurgical reconstruction of a damaged brain showed that even complete neurosurgical restoration of the anatomical integrity of the nerve tissue at the site of injury and, in some cases, even moderate neurophysiological restoration of the electrical conductivity of the newly reconstructed portion of the GM in most cases (56.2%) does not fully restore the impaired function of the GM . At the same time, in a number of other cases, the minimal effect (2-3 transfusions of a cell preparation) of stem cells on a chronic, morphologically coarse scar-commissural or cystic defect of the GM nervous tissue, without restoring its anatomical integrity, allows the patient to launch impaired walking function, restore sensitivity and establish the function of copulative (sexual) function or absent function of the pelvic organs (defecation and urination). The reason for this unusual clinical phenomenon is considered to be problems in the formation of new synaptic contacts (synapsogenesis) between the axons of damaged neurons. This scientific fact of “neosynapsogenesis” is one of the well-known and convincingly proven biological phenomena that explain one of the basic fundamental mechanisms of action of cell preparations in the brain. Therefore, due to good neosynapsogenesis, the restoration of electrical conductivity in the damaged area of the brain is absolutely real and can be feasible due to the molecular neurotrophic secretory action of the cell preparation on local synaptogenesis and, accordingly, restoration of the physiological sequence of the passage of the electrical signal between neurons. But this does not solve the problem in essence, since, despite the largest possible restoration of the quantitative parameters of electrical conductivity along the nerves of HT, neuroregeneration of HT does not guarantee a complete restoration of the quality of information transfer of the restored signal to HT and this does not provide restoration of impaired functions of the damaged brain.

Another equally important and unresolved problem of the prototype method is the compensatory formation of a sufficiently stable morphofunctional cicatricial cystic transformation of the tissue and the insufficiency of the vascular-cellular structure of the nervous tissue in the damage zone. The newly formed abnormal vascular-cellular connections in the area of the damaged brain are very strong due to the glious connective tissue scar degeneration of the damaged HT. Such connections, although they do not provide the function of this tissue site, are quite stable and resistant to any external influences of microenvironment cells, which does not allow them to be destroyed by the usual regulatory signal of transplanted intact SCs and PCs.

All the described disadvantages of the prototype method can be overcome by applying the methods of remote (non-contact, i.e., without direct contact of the surgeon’s hands and surgical instruments with human HT brain) multilevel electromagnetic wave exposure to human GM with the aim of its directed morphofunctional reconstruction and neurorestoration. All methods of restoration of the effect on the brain are well known and described in the scientific literature, therefore, in the process of creating the present invention, it was necessary to systematize all known facts and experimental data on the effects of various types of electromagnetic radiation on NT GM and to create a new theory and general concept of non-contact remote reconstruction of a damaged brain .

A fundamentally new solution to the problem of non-surgical reconstruction of brain nerve tissue is possible only in an unconventional, asymmetric and non-linear way, that is, by radically changing the basic principles of treatment and the existing methodology and technology of the approach to brain reconstruction. The task of remote restoration of the impact on the nervous tissue of the GM can be solved on the basis of a fundamentally new biotechnological method. Such an innovative and innovative methodological approach and an alternative principle for the development and creation of a new neurotherapeutic strategy for treating brain pathology can only be remote combined and algorithmized electromagnetic multi-wave ionizing radiation (II) and non-ionizing radiation (NII), that is, software reconstructive radiation exposure of damaged human NT human electromagnetic emissions of different wavelengths.

Thus, the objective of the present invention is to develop a fundamentally new way of restoring the functions of human GM (tissue engineering method) using remote multilevel combined effects of various types of electromagnetic radiation on GM.

The solution to this problem is achieved by the fact that according to the present invention, a method for remote multi-wave electromagnetic radio neuroengineering of the brain, comprising the following stages carried out sequentially:

a) the stage of design and layout, including:

- conducting complex diagnostics, including high-resolution MRI examination of the brain (GM), MRI tractography of the pathways of the affected areas of GM, MRI angiography of GM vessels, positron emission tomography (PET) of GM or PET of the whole patient’s body, computed tomography (CT) GM with a resolution of at least 32 slices, cerebral electroencephalographic mapping (EEG) and / or magnetoencephalography (MEG) GM;

- creation of an individual 3D map for modeling damage to nerve tissue (NT) by multi-level software merging of the obtained data from the comprehensive diagnostics for the subsequent determination of areas of NT damage;

- marking the zones of damage to the nervous tissue (NT) of the GM on the scalp of the patient by using the apparatus of stereotactic radiotherapy and radiosurgery with the determination of the tilt angles and radii of the subsequent non-ionizing stereotactic effects of focused ultrasound (FUS) on NT GM;

b) the stage of remodeling of the vascular bed of NT damage zones, including, depending on the etiopathogenesis of brain disease:

- in case of tumors, microaneurysms, malformations, hemorrhages - devascularization of the zone of NT damage in the brain by destruction of the supply vessels using the ablative electromagnetic effect of the FUS of high intensity on the vessels of the zone of NT damage under MRI and subsequent electromagnetic exposure by stereotactic ionizing radiation (AI) in ablation mode , coagulation and necrotization of blood vessels;

- in case of NT ischemia, NT atrophy, NT fiber demyelination, hypervascularization of the NT lesion zone in the brain by remote microcirculatory remodeling of the brain using NT using structural resonance therapy (CRT) in standard “microcirculation” modes and the simultaneous use of low intensity FUS in the regime uniform mechanical vibration of NT in the zones of NT damage;

c) the stage of cell restoration of NT lesion zones, carried out by targeted cell intervention in autologous mesenchymal stromal stem cell (MSCC), hematopoietic stem cell (HSC) and progenitor cell (PC) mobilized into the zone of damaged NT tract and including:

- mobilization of MSCC, HSC and PC from the bone marrow into the peripheral blood of the patient, carried out using granulocyte colony stimulating factor (G-CSF);

- activation of GM regeneration in the area of NT damage and temporary opening of the blood-brain barrier (BBB) for the penetration of MSCC, HSC and PC into the zone of NT damage by stereotactic irradiation of this zone with small doses of AI no more than 2 Gray;

d) the stage of correction of the vegetative provision of the NT damage zone by combining exposure to the NT damage zones with electromagnetic non-ionizing radiation in the form of CPT in the vegetative exposure modes of “sympathetic” or “parasympathetic” with simultaneous or sequential exposure to low intensity FUS in the mode of moderate NT stimulation;

e) the stage of dynamic integration of somatic and vegetative components by combining the effects of low intensity FUS on the NT damage zone in the GM with the simultaneous or subsequent exposure to CPT in moderate “synchronization” modes and

f) the stage of rehabilitation of the functional state of the damaged NT GM by using a combination of electromagnetic non-ionizing effects of CPT in the "scanning" mode and stimulating effects of low intensity FUS.

In addition, according to the present invention, it is possible to prolong the positive effect of cellular effects on damaged NTs by the fact that, in step c) after mobilization of HSCs and PCs, mobilized bone marrow stem cells are additionally collected, standardized and cryopreserved for their intrathecal, intraventricular, intravenous or intraarterial introducing into the patient's body during his next hospitalizations.

In addition, it is possible to increase the permeability of the BBB by the fact that at stage c) before irradiation or during it, an intravenous infusion of an ozonized 0.9% saline solution is additionally carried out.

The BBB permeability can also be increased by the fact that at stage c) after irradiation, additional low-intensity FUSs are additionally affected.

In addition, at stage c), in the area of NT damage, CPT (structural resonance therapy) can be used to increase the safety and efficiency of the penetration of autologous MSCCs, HSCs and PCs into this zone.

The impacts of FUS, AI and SRT are carried out according to the present invention mainly using a helmet assembled on the basis of a stereotactic neurosurgical apparatus equipped with holders for “finger” ultrasound sensors that provide focused ultrasound exposure.

The main technical result achieved in the present invention is that the stepwise combination of simultaneous or sequential effects of different types of electromagnetic radiation (FUS, II, SRT) on human GM in the combinations described above destroys or at least eliminates, i.e. reduces, softens, smoothes, minimizes the shortcomings and complications from the use of each type of radiation separately.

The authors of the present invention believe that the proposed method can be attributed specifically to neuroengineering technologies, and the use of modern medical devices and devices for conducting stereotactic ionizing effects (stereotactic radiation therapy and radiosurgery) and electromagnetic wave exposure (structural resonance therapy) and ultrasound therapy in the present the invention allows us to talk about remote reconstructive focused multilevel molecular-cellular and systemic m multi-wave radio-bioengineering effects on the nerve tissue of the brain or on the radio-bio-engineering method of restoration of damaged nervous tissue of human GM. It can also be said that the present invention proposes an alternative to modern surgery, radiotherapy reconstructive technology of remote stereotactic software multi-wave neuroengineering, which can be used to treat a number of nervous and mental diseases of a person.

The technically proposed method for the treatment of nervous and mental diseases solves the problem of restoring damaged brain NT by means of focused focused and (or) generalized (systemic) effects of electromagnetic radiation of different wavelengths on the brain. The restoration effect in the damaged nerve tissue arises due to the initiation of certain neurobiological effects of individual radiation or wave methods of exposure (FUS or CPT) on GM, as well as due to combination combinations (II + FUS, II + CPT, CPT + FUS) due to the simultaneous use of multilevel and multiwave stereotactic and systemic effects on damaged NT GM, ensuring the emergence in a certain area of NT required neuromorphological and molecular biological x effects.

The present invention proposed an alternative to modern surgery, the way of restoration of NT damaged GM. The authors of the present invention found that the best results of the application of cellular technologies and tissue engineering of GM occur when a minimum sufficient amount of direct or indirect neurosurgical or transfusion cell intervention in the patient's brain has been carried out. The fewer additional surgical damage to the brain tissue during reconstructive neurosurgery or interventions on damaged GM can be achieved during its restoration, the better the long-term clinical results of the treatment were obtained. The best results of the treatment of neurological and psychopathological disorders of GM using regenerative medicine technologies were obtained by the authors of the present invention not from high-tech neurosurgical operations for tissue engineering of the brain, but from intrathecal transfusions (stem cell transfusions) of the HSC preparation (almost 55.4% of positive results) in subarachnoid space of patients with damaged GM.

It is obvious that the unique abilities required for the reconstruction of GM tissue are predominantly due to the radiation effects of various types of electromagnetic radiation (EMR) on human GM. In assessing the effects of the interaction of electromagnetic radiation with various biological objects, it is customary to separate the radiation into ionizing radiation (II) and non-ionizing radiation (NII). Usually, such electromagnetic oscillations (optical, x-ray, gamma radiation) are attributed to the AI, the energy quantum of which is so large that, for example, breaks in intermolecular bonds or ionization of the atom are possible. Longer-wave electromagnetic oscillations with a small value of the energy quantum belong to the Institute of Nuclear Research.

The nature of the interaction of an electromagnetic wave with a biological object is determined both by the radiation parameters (frequency or wavelength, propagation velocity, oscillation coherence, polarization of the wave) and the physical properties of the biological object as the medium in which the electromagnetic wave propagates (dielectric constant, electrical conductivity), and also parameters depending on these quantities (electromagnetic wavelength in the tissue, penetration depth, reflection coefficient from the boundary air is cloth). Thus, a decrease in the wave amplitude during its penetration into the tissue can be characterized by the penetration depth O — the distance at which the amplitude of the oscillations decreases by ~ 2.72 times. For example, at X = 10 cm (vibration frequency 3 GHz), the penetration depth in muscle tissue and skin is 15 cm, and at X = 8 mm (frequency 37.4 GHz), σ = 0.3 mm. A tendency toward a decrease in σ with a decrease in K is observed until the wavelength in the medium substantially exceeds the size of the cells or the organelles entering into them. At very high frequencies, the permeability of tissues to electromagnetic waves begins to increase again. For example, hard x-rays and gamma radiation penetrate soft tissues with little or no attenuation. A typical example of the energy effect of radiation on the body is hyperthermia, when a useful effect is achieved when the energy of electromagnetic radiation is converted into heat. But it is also possible such an effect of electromagnetic radiation on the body, in which the temperature increase is insignificant (<0.1 degrees) and it does not turn out to be the main factor in achieving a beneficial effect. In such cases, one usually speaks of the controlling or informational effect of electromagnetic radiation of low or non-thermal intensity. Studies have shown that the EMR of the millimeter wavelength range at this low power flux density of fractions or units of milliwatts per 1 cm ^{2 of the} irradiated surface (radiation wavelength in free space from 1 to 10 mm) has this property.

The most studied and described in detail in the literature today are the neurobiological effects of the influence of electromagnetic radiation of an ionizing (λ = 10-0.0001 nm) nature (AI) on human GM and SM. The obtained scientific facts of the impact of AI on the brain have become a fundamental and fundamental scientific and practical basis for their use in medical radiology. It is generally accepted in radiobiology that morphological radiation damage to the central nervous system is possible only with local exposure to the brain in doses> 10-50 Gy. Radiation necrosis of the brain is observed with local irradiation of the brain in doses> 70 Gy, after which the development of radiogenic dementia (dementia) is possible. Gamma radiation at a dose of 87.5 Gy in the ancient cerebral cortex of white rats causes a complex of typical nonspecific morphofunctional rearrangements, which include phase changes in the ratio of various cellular forms of neurocytes, their number, body volume, nucleus and nucleolus of neurons, the development of borderline, destructive and compensatory-adaptive changes in nerve cells, a change in bioenergetic metabolism and BBB permeability. The nature and severity of changes depend on the time after the cessation of exposure to factors. Apparently, the increase in the number of hypochromic forms of neurocytes observed in the post-radiation period occurs as a result of hypochromic transformation of normo- and hyperchromic neurons by intensive utilization of ribonucleoproteins in the metabolism of neurons. Phase changes in the volume of the body, nucleus, and nucleolus of neurocytes are probably due to cyclical changes in the intensity of intracellular metabolism, leading to the formation of a polar changing osmotic gradient in the cell hyalo- and nucleoplasm. Under the influence of AI, the most pronounced dystrophic and necrotic changes develop in the nervous tissue. AI causes multidirectional changes in the activity of aerobic pathways of bioenergetic metabolism in nerve cells, and also leads to disruption of the transport function of the BBB of the NT brain.

Pronounced morphological manifestations of CNS cell damage are observed, as a rule, only after exposure in doses approaching 50 Gy and higher. The earliest changes are found in synapses - the adhesion of synaptic vesicles in clusters that appear in the central part of presynaptic terminals or in the active zone. Under light microscopy, 2 hours after irradiation, at such doses, cell swelling, pycnosis of the nuclei of granular cells of the cerebellum, less often other neurons, the phenomena of vasculitis, meningitis, choroidal plexitis with granulocytic infiltration are detected. Maximum changes occur on the first day after exposure. At higher doses, early brain tissue necrosis may occur. When irradiated in doses of 10-30 Gy in the CNS cells of the nervous system, inhibition of oxidative phosphorylation is detected. The latter is associated with ATP deficiency consumed in the process of repair caused by irradiation of DNA breaks.

A tolerant dose to the brain is considered to be 55-65 Gy, and a tolerant fractional dose is 2 Gy. Primary damage to the central nervous system during whole-body irradiation is considered possible only at doses> 100 Gy (cerebral form of acute radiation sickness or abbreviated ARS), and secondary radiation damage to the central nervous system at 50-100 Gy (toxemic form of ARS). The threshold for the occurrence of radiation-induced neuroanatomical changes is considered a dose of 2-4 Gy of total exposure. At the same time, in experimental studies, morphological changes in neurons were already detected at doses of 0.25-1 Gy of total exposure, and a dose of 0.5 Gy was considered threshold for radiation damage to the central nervous system with primary neuronal damage. Persistent changes in cerebral electrical activity had a threshold of 0.3-1 Gy and increased in proportion to the absorbed radiation dose. Violation of the central nervous system is possible when exposed to radiation in relatively small doses. Irradiation modifies neurotransmission, which leads to multiple cerebral and behavioral effects, which are largely dependent on the radiation dose. After general irradiation in doses of 1-6 Gy, a slowly progressing central nervous system radiation disease was described. A 1982 UNSCEAR report (UNSCEAR Report, 1982) indicates that after irradiation in doses of 1-6 Gy, progressive degeneration of the cerebral cortex develops. It has been shown that the subchronic exposure to ¹³⁷ Cs in doses comparable to the doses resulting from the Chernobyl accident (Chernobyl nuclear power plant) leads to molecular modifications of the pro- and anti-inflammatory cytokines and NO-ergic pathways in the brain. Neuroinflammatory reactions can explain the electrophysiological and biochemical abnormalities observed with chronic exposure to ¹³⁷ Cs.

Although no conclusive evidence has been obtained in systematic reviews of the dependence of the risk of brain and cardiovascular diseases on radiation doses in the range of 0-5 Sv, in a published English epidemiological study in workers associated with sources of ionizing radiation (nuclear workers), a male patient showed a dose-dependent increase mortality from diseases of the circulatory system (ERR per 1 Sv = 0.65 (90% CI: 0.36-0.98)), and the excess was significantly manifested at cumulative doses> 300 mSv. In the USA, the maximum permissible annual dose of artificial radiation for a population of 0.1 m ³ / year has already been established.

Possible threshold doses of long-term cerebral radiation damage are small doses of 0.1-1.3 Gy per brain in childhood. The radiation-associated effects in adults have been established at doses> 0.15-0.25 Sv. Dose-dependent neuropsychiatric, neurophysiological, neuropsychological and neuroimaging abnormalities were detected after irradiation at doses> 0.3 Sv, and neurophysiological and neuroimaging markers at doses> 1 Sv. Thus, there are quite contradictory points of view regarding the radiocerebral effects of AI.

Irradiation of the brain with AI modulates the expression pattern of 1574 genes, of which 855 abnormalities are observed more than 1.5 times. Changes in about 30% of the genes are dose-dependent, including genes that are affected exclusively at doses of 0.1 Gy. About 60% of the genes change depending on the time after irradiation, with most of the genes being broken at the 30th minute compared to 4 hours after exposure to radiation. Early changes include signal transduction, ion regulation, and synaptic signaling. Later disorders are represented by changes in metabolic functions, namely the synthesis of myelin and protein. Small doses of radiation also modulate the expression of genes responsible for stress response, cell cycle control, and DNA synthesis and repair. A dose of 0.1 Gy causes changes in gene expression that are qualitatively different from those upon exposure to 2.0 Gy. The data obtained indicate that low-dose irradiation of GM induces the expression of genes responsible for protective and reparative functions, while genes with reduced modulation are involved in neuronal signaling. Changes in the GM gene profile after irradiation are complex and depend both on the time after exposure to radiation and on the radiation dose. The radiation response of progenitor cells from the zone of the hippocampal dentate gyrus and impaired neurogenesis can play a significant, if not causal, role in radiation-induced cognitive impairment.

Analysis of the transcriptome profiles of GM mice after irradiation of the whole body showed that exposure to small doses of radiation (0.1 Gy) induces genes that are not affected by radiation in large doses (2 Gy). It has been established that genes that respond to low-dose irradiation are associated with unique neuronal pathways and functions. The molecular response of GM mice a few hours after exposure to low-dose ionizing radiation involves downregulation of the neuronal pathways that are associated with cognitive dysfunction. Such a downregulation is observed with normal human aging and Alzheimer's disease.

Today, there is new evidence of the radiation-induced molecular and cellular basis of cerebral effects due to the effects of AI in small doses: impaired neurogenesis in the adult hippocampus, changes in the gene expression profile, neuroinflammatory reactions, neurosignalization alterations, apoptotic cell death, cell death and damage from secondary lesions and others. These disorders, together with the long and well-known “vascular-glial union”, probably explain the pathogenesis of the radiation pore Genesis GM. On the other hand, it was shown that the use of small doses of AI can be used to stimulate tissue regeneration, transient short-term changes in the state and permeability (opening and closing) of the BBB in the nerve tissues of GM.

Thus, 1 Gy should be considered the minimum safe therapeutic regimen for the use of ionizing electromagnetic radiation exposure on the human brain, and 0.1 Gy as a tolerant fractional dose. It is these modes that the authors of the present invention consider reasonable and appropriate to apply to solve the problems of the invention.

Hypersensitivity of the nervous system to the effects of electromagnetic radiation of the non-ionizing range (NII) is also well known. This is evidenced by the facts of neuropsychic disorders in individuals who have been in contact with radiation sources for a long time. The interaction of electromagnetic NII with the biological environment at various levels of its organization has also been well studied - from individual atoms or molecules to simple structures, such as membranes or cell infrastructures.

The action of the magnetic component of the electromagnetic radiation can be associated with the paramagnetic orientation of the molecules, as well as with a change in the trajectory of a moving charged particle under the action of the Lorentz force. The action of the electrical component is associated with the oscillatory movement of free charges (electrons, ions). The electrical component can change the orientation of molecules having an initial dipole moment. Since the medium has electrical resistance and viscosity, energy losses occur in it. Although these processes may depend on the frequency of radiation, they are unlikely to exhibit such a high criticality to it, which is characteristic of biological experiments.

When irradiating molecules of nerve cells, the energy of the NeII is spent on transitions of molecules from one energy state to another. Transitions of electrons between energy states correspond to the optical range. The microwave range corresponds to rotational transitions or vibrational transitions, if we consider relatively large structures. If the radiation frequency coincides with the rotation frequency of the polar molecules, resonant transfer of the radiation energy of the molecules is possible. With this interaction, the structure of the molecule does not change, but its rotational kinetic energy increases. For energy exchange efficiency, it is important that this process is long and energy dissipation is minimal. In the case of water molecules, as already indicated, the resonant transfer of energy is accompanied by its rapid dissipation due to collisions of molecules. Therefore, the resonant nature of the interaction is not visually possible to observe in experiments.

When analyzing the dynamics of molecular proteins of NT cells, one can also distinguish vibrations of individual fragments with frequencies lying in the millimeter and submillimeter ranges, however, these movements are anharmonic and after several periods of vibration are interrupted by thermal fluctuations. Therefore, external electromagnetic radiation cannot have a significant effect on such molecular motions.

In medicine, electromagnetic waves are used as a therapeutic and diagnostic tool. The EMR scale used in modern medicine is presented in Table 1.

The use of EMR lasers in scientific and practical medical activities is widely known. Based on various types of lasers, surgical and therapeutic laser equipment has been developed. Methods have been developed for the treatment of many diseases, for example, long non-healing trophic ulcers and wounds, many types of skin diseases, cardiac ischemia, etc. Laser acupuncture methods have begun to be mastered in the treatment of a number of diseases. In oncology clinics, microwave hyperthermia begins to be widely used - focused electromagnetic radiation, which locally heats tumors at a fixed frequency (approximately to a temperature of 42-45 ° C), acts as an additional therapeutic factor. Inhibition of growth and resorption of the tumor are associated both with heating and with an increase in the action of the main therapeutic factors - chemotherapeutic drugs and x-rays.

In contrast to the above examples of the use of highly informative coherent oscillations in infrared radiation, the role is played not by external (from an artificial source), but by the proper thermal (incoherent) electromagnetic radiation of a biological object. The maximum thermal radiation of the human body at wavelengths is about 104 nm. For this infrared part of the spectrum, very sensitive detectors based on semiconductor compounds, cooled by liquid nitrogen, and based on them, the so-called thermal imaging equipment, have been created. In thermal imagers, the thermal field of the human skin is converted into a visible image on the screen of the tube. From this image, the deviation of thermal fields from the norm can be determined in degrees. Such observations provide sufficient information for the diagnosis of a number of diseases, for monitoring the dynamics of their development and the course of treatment.

It is shown that external (electrical and electromagnetic) EMP signals with frequency characteristics of certain biological rhythms affect various levels (cellular, organ, systemic) and regulation pathways (nervous, humoral, energy). With the aim of selective remote exposure of EMR to various levels of the body, a method of structural resonance electromagnetic therapy (CRT) was proposed. This method of exposure to electric current and electromagnetic radiation of ultra-low intensity, the frequency parameters of which correspond to the endogenous biorhythms of a healthy person and are resonant, in which the therapeutic effect is enhanced due to the synchronization of the rhythms of the acting factor and the corresponding functional system. The essence of biological resonance is to multiply the effect of exposure when the exposure frequency coincides with the natural frequency of the biological object. The uniqueness of CPT therapy lies in the correct physiological effect on the human body with an alternating electric current of a specific shape, amplitude and frequencies selected based on the frequencies of spontaneous biopotential activity of human organs and tissues. As a result, the conditions are created for the restoration of their own, genetically determined rhythms of the human body in accordance with the law of resonance. In this regard, the therapeutic possibilities of the technique are extremely wide, and the absence of heating and stimulation elements reduces the likelihood of side effects and complications.

The CPT method was developed by the staff of the Central Medical Center No. 165 of the FMBA of Russia and the Clinical Pharmacology Laboratory of the Moscow Medical Academy. Sechenov and the Department of Theoretical Problems of Non-Drug Therapy of the Research Institute of Traditional Methods of Treatment and Diagnosis. For the general systemic low-intensity impact, the REMATERP apparatus is used, for local impact, the KELSI-01-MCC and RADOMYS-MCC apparatuses are used. The frequency range used in REMATERP devices from 0.026 Hz to 360,000 Hz allows you to affect all levels of structural organization - cellular, tissue, organ, system. The therapeutic effects of low-frequency magnetotherapy - anti-inflammatory, analgesic, regenerative, immunocorrective - are fully inherent in the electromagnetic version of CPT. CPT is also one of the non-surgical ways to overcome the problem of microcirculation disturbance in the area of damage to the brain NT, capable of exerting a normalizing and regulating effect on the existing cellular-vascular microcapillary network of the zone of damage to NT.

The mechanism of action of CPT on the damaged human brain is well understood. A group of domestic researchers (O.P. Kuzovlev, I.L. Blinkov, L.V. Khazina) analyzed the known bioeffective frequencies - their own experimentally found and calculated (according to the method of E.N. Chirkova) resonance frequencies of various organs and tissues of the human organism, which allowed to create a single system (a kind of periodic system of structural resonance frequencies for various organs and tissues), on the basis of which specialized equipment was created that implements the principles of structural resonance electromagnetic Apia in humans. According to the researchers, the periodic system of structurally resonant frequencies of human organs and tissues is the matrix of the program for managing all physiological processes of life. All processes are controlled by physical processes that carry information-electromagnetic signals of the corresponding frequency, amplitude, shape and other characteristics. Having received such a signal, the GM begins to work in accordance with the natural algorithm of the organ. For example, using the microcirculatory regime of a structurally resonant effect on the patient’s GM, this group of researchers using the physiotherapy apparatus “REMATER” and the physiotherapy apparatus “REKELSI” electrostimulator to act on the damaged spinal cord of a patient with corresponding frequency characteristics from 5836.09 Hz to 8454, 144 Hz to 12681.22 Hz and a period of 93 seconds proved the possibility of changing the geometry and volume of the vascular bed of various organs and tissues and patented this phenomenon.

Existing methods of conducting SRT GM are implemented by devices with the action of an electric current contact (on the skin) or the magnetic component of the electromagnetic field - non-contact (by means of inductors through clothes). Both from the point of view of the impact on the singularity zones that control the rhythmic wave-like processes, and from the point of view of the energy power (at or less than the power of the Earth’s magnetic field), CPT with a non-contact mode of action refers to informational influences and allows the following reconstructive effects on NTs:

- Ultra-low-intensity EMR on human tissue has a microvascular effect, reveals a microcapillary network in the area of damage;

- EMR, the frequency parameters of which correspond to the endogenous biorhythms of a healthy person and are resonant, has a regulatory effect on NT GM and SM;

- the therapeutic effect of EMR is enhanced due to the synchronization of the rhythms of the acting factor and the corresponding functional system, which leads to biological resonance, the essence of which is to repeatedly enhance the effect of exposure when the acting frequency coincides with the natural frequency of the biological object;

- upon irradiation of millimeter-wave EMI with a low power flux density of fractions or units of milliwatts per 1 cm ^{2 of the} irradiated surface (radiation wavelength in free space from 1 to 10 mm), SCs can provide informational, regulatory and control effects on damaged tissue by directed non-ionizing electromagnetic radiation of low or non-thermal intensity.

Another direction of non-ionizing effects on the brain, which can be used for remote radiation restoration of NT GM, is ultrasound. The lower limit of the ultrasonic range is called elastic vibration with a frequency of 18 kHz. The upper limit of ultrasound is determined by the nature of the elastic waves, which can propagate only if the wavelength is much greater than the mean free path of the molecules (in gases) or interatomic distances (in liquids and gases). In gases, the upper limit is 106 kHz, in liquids and solids - 1010 kHz. As a rule, frequencies up to 106 kHz are called ultrasound. Higher frequencies are called hypersound. Ultrasonic waves by their nature do not differ from waves in the audible range and obey the same physical laws. But ultrasound has specific features that have determined its widespread use in science and technology: 1. Small wavelength. For the lowest ultrasonic range, the wavelength does not exceed a few centimeters in most media. The short wavelength determines the radiation pattern of the propagation of ultrasonic waves. Near the emitter, ultrasound propagates in the form of beams in size close to the size of the emitter. When it encounters inhomogeneities in the medium, the ultrasonic beam behaves like a light beam, undergoing reflection, refraction, and scattering, which allows the formation of sound images in optically opaque media using purely optical effects (focusing, diffraction, etc.); 2. A small period of oscillations, which allows you to radiate ultrasound in the form of pulses and to carry out in the medium an accurate temporary selection of propagating signals; 3. The ability to obtain high values of vibrational energy with a small amplitude, because the vibrational energy is proportional to the square of the frequency. This allows you to create ultrasound beams and fields with a high level of energy, without requiring large equipment; 4. In the ultrasonic field significant acoustic currents develop. Therefore, the effect of ultrasound on the medium gives rise to specific effects - physical, chemical, biological and medical, such as cavitation, sound-capillary effect, dispersion, emulsification, degassing, disinfection, local heating and many others.

Therapeutic ultrasound can be conditionally divided into ultrasound of low and high intensities. The main task of applying low-intensity ultrasound is non-damaging heating or any non-thermal effects, as well as stimulation and acceleration of normal physiological reactions in the treatment of injuries. At higher intensities, the main goal is to cause controlled selective destruction in the tissues. The first area includes most applications of ultrasound in physiotherapy and some types of cancer therapy, the second - ultrasound surgery.

Innovative solutions for the use of ultrasound in the treatment of nervous diseases have been the development of focused ultrasound technology (FUS), combined with magnetic resonance imaging (MRI). Thanks to the FUZ-MRI technology, a new medical discipline appears - non-invasive functional neurosurgery. In July 2006, the ExAblate system was installed at the University Hospital of Zurich, Switzerland, together with an MRI 3 Tesla, designed for targeted exposure to focused ultrasound on pathways in the GM. The first patients for non-invasive neurosurgical treatment of FUS-MRI were people suffering from severe neurogenic pain, motor disorders, Parkinson's disease and epilepsy. By the summer of 2009, the first 10 patients were treated. FUZ-MRI is a modern alternative to surgical removal of tumors and organs. This is a completely non-invasive, easily tolerated outpatient procedure that can be repeated many times if necessary. To ablate brain tumors without opening the skull, a special ultrasound emitter in the form of a helmet with an external cooling system and a device for stereotactic fixation of the head have been developed. At Harvard Clinic Brigham and Women's Hospital (Boston, USA), several patients with glioblastoma underwent transcranial FUS-MRI tumor ablation. The first positive results were obtained. Clinical trials are ongoing in four clinics in the United States, Canada and Israel. In Russia, FUZ-MRI - the unit is located at the N.I. National Medical and Surgical Center Pirogov (Moscow).

Actually, the FUZ-MRI procedure consists in treating a brain tumor or zone of interest in the brain with successive pulses of focused ultrasound. The entire allocated tumor volume is covered by rows of closely spaced slots. The system keeps track of all temperature effects on the patient. After each produced FUS impulse, the volume of the treated tissue, where it was heated above the “coagulation threshold,” is marked in blue. This creates a "dosimetric map" of the procedure, allowing you to control the correctness of the procedure. During the procedure, the main vital signs of the patient are constantly monitored, who is in direct voice contact with the staff and holds the emergency stop button in the hand. Immediately upon completion of the procedure, a control MRI scan is performed with the introduction of a contrast agent, which allows visualization of the "zone without perfusion" inside the tumor formation. On MRI images taken after administration of a contrast medium, areas of lack of contrast absorption are displayed, which indicates devascularization and tissue necrosis. The effectiveness of the FUS-MRI procedure is assessed by measuring the volume of the “zone without perfusion” that appears in the treated brain tumor, or the zone of interest in the brain.

It is believed that the FUZ-MRI technology creates a new therapeutic paradigm, in fact a new form of surgery. The Israeli company InSightec (InSitek), the manufacturer of the ExAblate system, founded in 1999 as a joint venture between Elbit Medical Imaging and General Electric Medical Systems, has become a world leader in the development of new medical technologies. In 2000, Business Week magazine (USA) named the ExAblate system one of 25 ideas designed to change the world.

But to destroy is simpler and easier than to create and build. The authors of the present invention believe that the reconstructive capabilities of the clinical use of ultrasound are much wider than its destructive properties. The effect of ultrasound on the brain changes the permeability of the BBB in the brain. This neurobiological effect was shown by studies of Perfusion Technology from Andover (Massachusetts, USA). Scientists from around the world have been studying the BBB and how to overcome it for many years. Overcoming the BBB of the brain is the overcoming of the natural protection of GM tissues from the penetration of potentially dangerous substances. But it is the BBB that prevents not only the entry of unwanted bacteria and substances into the GM departments, but also the transport of drugs, regulatory cell systems and SCs to the GM when necessary. The method of increasing BBB permeability by ultrasound, developed by Perfusion Technology, is simpler and cheaper. Instead of opening the BBB in a single place, the ultrasonic perfusion method uses specially designed headphones to open the entire brain to low-intensity ultrasound waves for an hour-long course of treatment.

Perfusion Technology is developing headphones that distribute ultrasound waves throughout GM, allowing cancer drugs or other large molecules to shrink and pass through the BBB. Studies of the monkey brain after treatment using the device showed that it allowed a chemical marker (brown) to enter the brain.

It is obvious that already today in modern medicine each of the described methods of ionizing and non-ionizing EMR for the treatment of pathologies of GM is very widely used. The methods of this effect and medical equipment for their implementation are allowed for clinical use in Russia and most highly developed countries of the world (USA, England, Canada, Great Britain, Germany, etc.). However, each of these methods of remote action on the brain is applied to a very limited pathology of the brain, fragmented and isolated to the nature of damage to the NT (only tumors or tremors) as a way of a very specific local neurobiological effect on the NT GM or SM. In this case, the systemic neurobiological mechanisms of the combined effect of various types of radiation on NTs, which can provide a programmed restoration effect on it, are ignored.

It should also be noted that there are a number of important problems that limit the wide therapeutic replication of various methods of using ionizing EMR in medicine. Among the current problems of world radiobiology and radiological protection that limit the wide dissemination of the achievements of these sciences in medicine, two problems are most relevant. The first of them is the effect of small doses of ionizing radiation on human health in general and the possibility of damage to the brain NT, in particular, and the second is more than a century of sharp discussion about the radiosensitivity / radio infection of human GM. The combination of these unresolved scientific questions - whether small doses of ionizing radiation affect the human brain - is an extremely controversial problem. In accordance with the classical principles of cancer radiation therapy established by the French radiotherapists Bergonie and Tribondeau (1906), the sensitivity of cells to radiation is directly dependent on their reproductive activity and inversely proportional to the degree of their differentiation. Accordingly, mature neural tissue is considered as an exceptional example of a “closed static population”, and, due to its fixed postmitotic state, this cell population is considered “the most radio-stable”. At the same time, data showing a central nervous system radiosensitivity have recently dramatically increased. Moreover, there were again reports of the beneficial effects of small doses of radiation on human health, interpreted as a "radiation-adaptive response." In addition, it was believed that the “vascular-glial union” is the cerebral basis of the post-radiation damage to GM, while neurons were considered outside the pathogenesis of radiation damage. In accordance with this, the white matter of GM was supposed to be more radioactive than gray. However, recent advances in understanding the mechanisms of radiation damage to the central nervous system make us reconsider these seemingly well-established provisions. It has now become clear that the central nervous system is the main dose-limiting system in clinical radiotherapy, and that the central nervous system is radiosensitive.

The present invention did not aim at the final solution to these problems, but further expanding the possibilities of using AI and Non-III in the reconstruction of human GM requires reducing the potential risk of possible complications from the use of EMR of various wavelengths in the clinic. The authors of the present invention believe that overcoming the main contradictions and further discussions on the problem of radiosensitivity / radioactivity GM when using small doses of ionizing EMR for therapy and morphofunctional reconstruction of brain damage can be achieved by combining local and systemic use of small doses of various types of electromagnetic (AI and NII) effects on human NT cells NT. It is this new aspect of the combined use of EMR for restoration of the human brain that avoids a large number of possible complications from the isolated use of these technologies in the clinic and implements the strategy of interstitial reconstruction of NT GM. The principle of the combined (combined) effects of different types of electromagnetic radiation on human NT human hypertrophies was the basis of the present invention. The combined programmatic effect on NT of different types (ionizing and non-ionizing) EMR allows achieving the required combinations of neurobiological effects in the area of damage of NT GM. For example, a combination of AI and low-intensity FUS in a certain place of NT can cause mutually reinforcing and mutually correlating neurobiological effects:

1. Temporarily increase the permeability of the BBB NT for bioactive drugs, bone marrow SC and PC and tissue-specific SC.

2. Create in the zone of NT damage the concentration gradient of inflammation for the directed transport of SC and PC into this zone.

3. To reduce the negative effects and side effects of the selective use of small doses of AI on NT human NT cells.

The combined effects of CPT and FUS contribute to a significant increase in microcirculation precisely in the area of NT damage to the brain due to the general systemic microcirculatory effect of CPT on the NT of the entire brain of the patient and to the enhancement of the local microcirculatory effect by focused ultrasound “massaging” effect on the NT and the elimination of local angiospastic and angioparalic effects on microcapillaries disturbed vascular autonomic provision of arteries and veins in the area of NT brain damage. The simultaneous combined effect of low doses of AI and SRT on damaged human NT human genitals in rehabilitation modes promotes activation of the bioelectrical activity of GM without the presence of classical post-radiation molecular-biological effects from the use of AI, as well as the destruction by the AI of systemic pathological connections in the damaged nervous tissue of human GM and the imposition by CPT resonance-wave frequencies of the physiological range of NT.

In the modern scientific medical literature, a number of experimental scientific facts are described of the positive and mutually correcting use of the combined use of various types of EMR, which for some reason have not yet found their direct application in modern medicine and are practically not used in clinical practice. For the first time, the thesis about the possibility of a positive effect on biological systems exposed to ionizing radiation from other non-ionizing electromagnetic fields of weak or non-thermal intensity, which in this context acquire the meaning of information signals, was formulated in the book of the Moscow biophysicist A.S. Presman's "Electromagnetic fields and wildlife", Moscow, 1968. Today it is well known that the adverse effects of medium and small doses of ionizing radiation on human health can be significantly offset by the action of non-ionizing electromagnetic waves of an extremely high range and structurally resonant electromagnetic effects. It is believed that this positive effect of non-ionizing EMR on the side effects of ionizing EMR can be due to biological resonances of EMR and a change in the frequency of modulation of EMR, which is the information frequency that carries the bulk of the relevant information. EMR modulation is a change in a certain law of the amplitude, frequency or phase of harmonic oscillation to introduce the required information into the oscillatory process. Information transfer using electromagnetic waves due to their modulation is possible only in the low-frequency range of these waves, corresponding to the frequency range of the functional systems of the body (from 1 to 10 Hz). The imposition of the physiological resonance frequencies of the brain tissue affected by ionizing electromagnetic radiation on the brain using normal methods of SRT practically corrects the negative post-radiation molecular biological effects of small doses of AI in this tissue and makes this effect practically safe. In combination with x-rays or anticancer drugs, EM waves always act as a protector.

But there is another no less significant aspect of the simultaneous combination effect on the brain of different types of EMP. The combined (combined) use of small doses of various types of AI with FUS allows you to purposefully control at the same time various post-radiation neurobiological effects. For example, as noted above, with the combined effect of low-frequency HF and low doses of AI on the area of NT damage in the brain, two extremely important neurobiological effects can be simultaneously achieved in reconstructed NT: focused ultrasound will super-selectively increase the BBB permeability in the area of NT damage for HSCs for several hours and (or) mesenchymal SC, and irradiation of the NT damage zone with small doses of AI will create an aseptic inflammation zone in it and the corresponding concentration gradient of cytokines and factors is inflamed capable of providing targeted migration and homing of SK and PC from peripheral blood and bone marrow to the area of NT damage. The degree of each neurobiological phenomenon can be regulated by using additional methods of radiation diagnostics (MRI contrasts, thermometry of NTs, PET studies of glucose metabolism of NTs, etc.) Thus, the combination of the stereotactic simultaneous effects of FUS and AI in the area of NT brain damage solves a number of very important tasks of targeting SC in the area of NT damage and their unhindered access to the site of NT damage through the BBB with subsequent (about an hour later) restoration of the barrier functions of the BBB of the brain.

Low-intensity NII (SRT) and low-frequency ultrasound contribute to a more rapid restoration of vital processes in tissues when they are damaged. This is due to an increase in the proliferative activity of the SC of the hematopoietic system, which, in turn, leads to an increase in the mitotic activity of bone marrow cells. The effect of low-intensity EMR on bone marrow cells was also shown in in vitro experiments (L.P. Ignasheva and EI Soboleva, 1991), namely, it was shown that non-thermal low-intensity EMR has a positive effect on hematopoietic stem cells cryopreserved bone marrow, contributes to the survival of lethally irradiated recipients after myelotransplantation and may be one of the ways to increase the repopulation ability of cryopreserved bone marrow. A group of scientists led by V.I. Govallo, on the basis of the Central Research Institute of Traumatology and Orthopedics, together with the Istok Scientific Research Institute, studies were conducted and it was shown that under the influence of EHF waves, human lymphocytes and fibroblasts in vitro produce factor phytokine, which enhances the growth and functional activity of similar cells.

The simultaneous use of CPT and FUS in the area of damage to the brain NT can significantly improve the overall synchronization of the work of elements of damaged tissue due to the activating effect on the nerve cells and the massage effect of the FUS of low frequency on the NT and the imposition of physiological rhythms of the brain throughout the brain and in the area of damage to the NT with appropriate modes CPT.

Thus, certain combinations of various types of EMR, acting simultaneously on the damaged area of NT GM, are capable of exerting specific and fairly stable neurobiological effects that can be used to accomplish the tasks of reconstructing NT brain. The radio-reconstructive combined effect of these radiations on NT GM can realize all the morphofunctional changes in it required for restoration, but not surgically, as described in the prototype method, but remotely.

Once again, it is worth noting the important scientific fact of the proposed invention, namely, that the emergence of the necessary (software) neurobiological effects in NT was carried out by simultaneous combined focused effects of various types of AI and NII of low power and intensity with different wavelengths. This ensured the formation in NT of the damaged brain by launching specific restoration molecular-biological mechanisms - microcirculation or aplasia of the microvascular bed, neuroregeneration or neurodegeneration of nerve cells, activation or depression of the speed of nerve impulses, homing and pathotropism of cell systems, aseptic inflammation or radiation necrosis, etc. . These neurobiological effects of NT in the case of programmed and programmed use led to a multilevel restoration of the main elements of NT due to improved microcirculation of the zone of interest, activation of the regulatory qualities of the SC of the patient’s bone marrow, restoration of autonomic autonomic support and normalization of NT functioning biorhythms. As a result of the application of the proposed method, the problems of replenishing the quantitative and qualitative restoration of the cellular composition of the NT damage zone in the brain (neurons, oligodendrocytes, microglia, fibers, synapses, etc.) were solved, the BBB permeability was controlled, vascular remodeling of the NT damage zone was provided (reduction or increased vascular geometry and volume of the microvasculature), regulation of synaptogenesis in damaged NTs and remodulation of autonomic autonomic provision of NTs in the e damage HT (corresponds to change tone of the sympathetic or parasympathetic nervous system), held synchronization main backbone NT components.

Thus, the proposed bioengineering method for treating brain pathology provides remote interstitial restoration of the morphofunctional structure of the damaged NT of the human brain during neuropsychiatric diseases and craniocerebral injuries without the use of neurosurgical operations and minimally invasive interventional technologies of x-ray surgery and excludes the complete contact of any neurosurgery of the patient’s brain and neuro surgical instruments.

In the present invention, the same stages of restoration of the damaged brain are implemented as in the prototype method, but at a new technological level of multi-wave electromagnetic exposure.

In FIG. 1 is a front view of a photograph of a stereotaxic device modified according to the present invention with sensors fixed thereto for multi-wave focal exposure;

in FIG. 2 - the same side view.

The method of the present invention is as follows.

The design and marking stages (a) of the proposed method are aimed at the diagnosis of lesion foci (zones of NT damage) in the brain. An important problem in the reconstruction of damaged NT is the analysis of the degree of its morphological damage and the determination of the localization of the zones of functional damage to NT in GM. To assess the reconstruction volume, very accurate data on the nature of NT damage are needed. These data are able to provide high-resolution MRI of the GM (1.5 T or 3 T), which allows to study the resonance-wave characteristics of the inductance of the NT in the zone of damage.

The data of the analysis of metabolic changes in various sections of the GM make it possible to obtain the technology of modern positron emission tomography (PET). The combination of PET data with computed tomography (CT) of the GM allows you to clearly link the data of metabolic disorders of the pathological focus to its localization in organs and tissues. Therefore, the combined PET / CT technology opens up great prospects for the diagnosis of morphofunctional changes and their topical binding to a specific anatomical formation in the brain. Magnetization of NTs as a functional parameter of NT damage in various regions of the brain can be obtained using magnetoencephalography (MEG) data. The data of three-dimensional EEG mapping make it possible to obtain localization of the bioelectric activity of the GM cortex.

Comparison and software merging of these data in the bioinformation mapping tables of the patient’s GM with MRI and CT data allows us to obtain the integral characteristic and maximum reliability of the personified data of this biological information, as well as to use these arrays of biological information using modern IT technologies and mathematical modeling methods. Thus, using these ultramodern data of radiation diagnostics of human GM, you can design your restoration efforts in the field of neuroengineering, determine the main directions and information levels of GM reconstruction and correctly plan the amount of necessary biomaterials and tools. The use of specialized professional software for multyfusion technology of MRI, CT, PET, EEG mapping and MEG data makes it possible to compile a multidimensional table of parameters of various brain regions, compare it with the table of the average statistical rate and see those injuries and functional disorders that were left unattended by the doctor with visual inspection of the image.

The obtained multilevel information on the state of the patient’s brain should be provided to patients for bio-information analysis on modern information media (laser disks, flash cards, etc.) and recorded using the basic software for reading and processing them in the standard of unified computer programs DICOM . The level of requirements for certain neuroscience studies at this stage is as follows:

1. MRI study of GM, it must be carried out on a high-resolution magnetic resonance imager (from 1.5 T and above);

2. MRI tractography of the conducting paths of the zone of damage to the GM;

3. MRI angiography of cerebral vessels;

4. Positron emission tomography (PET) of the GM or PET of the whole body of the patient;

5. Computed tomography of the GM, mainly on a spiral CT scan with a resolution of at least 32 slices;

6. Cerebral mapping of EEG on an EEG hardware complex that has software for 3D local modeling of GM bioelectric activity; and / or

7. Magnetoencephalography (MEG) GM with 3D modeling of the results.

The time difference between the dates of the various results of computer beam diagnostics should not exceed more than a week. All research data should be presented on information media (laser disks, flash cards, etc.) in a single DICOM format. All tomographic studies performed at this stage to examine the patient can be used at the next stage to monitor the effectiveness of the treatment. Using information technologies of 3D tomographic data processing allows them to be combined into 3D brain maps using the specialized software “Multimodalfusion 3D”, which exists on the supercomputer stereotactic hardware complex CyberKnife (USA) or a similar hardware complex for stereotactic radiation therapy from other manufacturers. This allows you to get a three-dimensional (3D) multi-level mapped model of the information structure of the damaged nervous tissue of a patient’s GM in the form of a set of tables of local brain data, “link” or correlate them with anatomical formations in the brain and create a personalized 3D map of existing pathological changes and injuries of a specific person’s NT and animal. This 3D disease map can be the basis for marking and stereotactic targeted therapeutic radio-bioengineering effects of AI on the patient’s GM.

At this stage, the subsequent radio-bioengineering effects on the patient’s brain are also marked.

Stages of preparation for remote radiation therapy (using the Clinac 2300 (3D CRT) stereotactic radiosurgical apparatus as an example:

1. The patient is consulted by a radiologist.

1a. Medical documentation is being examined, a patient is being examined and

indications for remote radiation exposure are established.

1c. The treatment tactics, the technique of remote radiation therapy, the type of radiation, the use of radio modifying agents, the fixation of the patient are determined. In the event of a change in the treatment plan or a forced interruption, a repeated consultation is carried out with an entry in the outpatient card of the patient or in the inpatient medical history.

1. Topometric preparation begins in the beam topometry group, in the computed tomography room.

2a. The radiologist doctor, together with the radiologist and the x-ray laboratory technician, select the desired and convenient position of the patient on the table of the computer tomograph, select fixing devices to reproduce the patient's identical placement. During stereotactic radiation therapy sessions, a thermoplastic mask is applied to the patient's head or body.

2c. Data on the parameters of the fixing devices by the x-ray laboratory assistant are entered in the sheet of fixing devices.

2g Computed tomography is performed on the estimated volume of exposure, the resulting images are sent to a workstation for contouring volumes. In order to clarify the amount of exposure, magnetic resonance imaging is additionally performed.

3. In the three-dimensional planning system, the radiologist selects the amount of radiation (GTV, CTV, PTV), coordinates them with the consultant, sends the images in digital format to the planning system for the medical physicist, fills out the technological map (indicating the ROD, SOD, apparatus, energy , the number of fractions, localization, the presence of fixing devices).

4. The medical physicist, according to the terms of reference, selects the optimal number of radiation fields, their directions, energy, dose, determines the necessity of using tissue-equivalent boluses, wedge-shaped filters.

4a. After calculating the three-dimensional irradiation program in order to determine the center point, setting fields are created to check the reference point.

4c. The irradiation program with the application of dose-volume histograms of the target and critical organs is coordinated with the radiologist and senior researcher, printed and issued to the radiologist.

5. On the electron accelerator using the “OBI” - On Board Imaging system, which includes two subsystems: CBCT - (Con-Beam CT) - computed tomography in kilovolt radiation and planar images - flat images in kilovolt radiation, a radiation plan is simulated .

5a. A radiologist, together with X-ray laboratory assistants, an engineer, and a medical physicist, put the patient on the treatment table of the device for remote radiation therapy, in the previously selected position, according to the list of fixing devices, select the installation field, check the correct location of the reference point.

5c. Wedges, tissue-equivalent boluses are installed, if any, in the irradiation program, and the installation is checked by performing kilovolt portal images.

5g The irradiation volume is recorded in digital form and on paper from each treatment field, with the exception of oncoming fields (for example, with a four-field technique - boxing, the accelerator head was fixed at 90 °, rotation of the same zone at 270 ° is not necessary to be fixed).

5d Verification of the accuracy of patient placement using computed tomography in a conical beam of CBTS is carried out before the start of each stage of radiation ionizing exposure.

6. Checking the accuracy of patient placement using megavolt portal images is carried out weekly.

6a. At the first laying of the patient, the presence of a medical physicist and engineer is mandatory in order to check the laser anti-collision system;

6b. After the patient’s first laying, the x-ray laboratory technician takes a photograph of the patient’s position on the table of the electron accelerator with the inclusion of fixing devices in the frame and prints this image on a printer.

7. After checking the patient’s position, the x-ray laboratory technicians set the exposure parameters and monitor the patient’s condition on the monitors.

8. After the procedure is completed, x-ray assistants help the patient to rise from the treatment table and take him out of the canyon to the waiting room.

Mandatory set of documents included in the 3D ray card:

1) consultation of a radiologist;

2) informed consent of the patient;

3) a sheet of parameters of fixing devices;

4) routing with design parameters;

5) a map of the dose distribution of each volume of exposure, signed by a medical physicist, radiologist and consultant;

6) a dose-volume histogram of all radiation targets and critical organs, certified by the signature of a medical physicist, radiologist and consultant;

7) a photograph of the position of the patient on the table of the electron accelerator with the inclusion of fixing devices in the frame;

8) a radiation diary (each area is signed daily), is certified by the signature of an x-ray laboratory assistant and radiologist;

9) portal images obtained using kilovolt radiation (on paper), all volumes of exposure;

10) epicrisis of radiation therapy, after completion of treatment.

Thus, the marking is carried out taking into account the 3D radiation chart of the patient’s disease on a standard radiotherapeutic (radiosurgical) stereotactic hardware complex, for example, Clinac 2300 (3D CRT).

As a result of marking, specific “radio tags” are made on the patient’s scalp to further fix the stereotactic apparatus on the patient’s head and conduct a directed stereotactic effect of AI and NII on the patient’s brain and determine the main vertical and horizontal tilt angles and azimuths of the directed NII influence on the brain for stereotactic use of CPT and FUZ with the help of special sensors fixed in the latches of the stereotactic apparatus.

To illustrate and verify the therapeutic possibilities of the proposed principle of remote radio-bioengineering effects on damaged human NT human NT, the inventors proposed a demo sample of a stereotactic device for simultaneous multi-wave effects on the brain, into which diagnostic and therapeutic sensors of NII were mounted, connected to a standard therapeutic ultrasound device and a standard device for CPT therapy. For these purposes, the well-known stereotactic method of pointing to the subcortical structures of the brain was used, which was implemented on the basis of the existing, but modified stereotactic apparatus.

In accordance with the classical concepts in neurosurgery, the stereotactic method is a set of tools and techniques in which the practical task of ensuring the possibility of low-traumatic surgical access to any parts of the brain is solved on the basis of mathematical techniques and largely depends on a correct understanding of the geometric properties of the x-ray image. The stereotactic method, or abbreviated stereotaxis (from the Greek stereos - volumetric, spatial and taxis - location) is a combination of techniques and calculations that allow using special instruments and methods of x-ray and functional control to accurately insert the cannula (electrode) into a predetermined deep located the structure of GM or SM for influencing it for therapeutic purposes. Since the present invention does not use a surgical effect on NT GM, in this case, the main thing in stereotactic marking on a radiosurgical stereotactic complex was to determine the main tilt angles and zones on the brain for multi-wave exposure from different types of EMR sensors.

The main methodological method of stereotaxis is to compare the conditional coordinate system of the brain with the coordinate system of a stereotaxic device. According to the present invention, the conditional coordinate system of NT damage zones in the brain was the marking carried out by a radiologist on a radiosurgical apparatus, and the coordinate assignment for non-research institutes (FZU and SRT). To conduct simultaneous focused targeted electromagnetic ionizing and non-ionizing effects on specific areas of damaged NT, a stereotactic apparatus adapted to reconstruction problems was used, in which, regardless of its designs, the basic principle of the stereotactic method is preserved - comparing the coordinate system of the brain with the coordinate system of the stereotactic device. Despite the variety of stereotactic apparatus systems, and therefore stereotactic calculations, comparisons (“bindings”) between the coordinate system of the brain and such apparatus are based on the same principle of three-dimensional orthogonal and polar projections. Various devices use both a rectangular and a polar coordinate system. Rectangular coordinates involve calculations in three planes of space located at right angles to each other. This method has several advantages, in particular, it allows you to accurately determine the magnification of the object as a result of parallax of x-rays, and also to reinstall the device in exactly the same position if the operation is performed in two stages. The essential disadvantages of apparatuses based on a system of rectangular coordinates are also obvious - this is the complexity of the design, the difficulty of fixing the apparatus on the head and laborious calculations that require a lot of time. The most common devices in our time are based on a polar coordinate system. The principle of their action is that the electrode cannula is introduced into the brain in the direction of the target point at certain angles. These angles are determined using lines that draw from the end entered to a considerable depth of the brain in images in both projections. It is these angles established during radiosurgical marking that were used in the proposed method to create focal effects of various ultrasound sensors.

From a practical point of view, all existing devices can be divided into two groups: 1. Devices of a relatively simple design, fixed in a small trepanation hole in the bones of the skull. Fixation of these devices does not require preliminary x-ray control and is carried out according to external cranial landmarks; 2. Apparatuses of complex construction and large sizes, in which the patient’s head is fixed under x-ray control using sharp stops screwed into the bones of the skull. For the purposes of the present invention, it is advisable to use a second type of stereotactic apparatus.

Obviously, for stereotactic neurosurgical operations, complex and bulky devices of the second type, which require a lot of time for installation and stereotactic calculations, do not justify themselves in practice and are inconvenient in the operating room. But for the purposes of radio neuroengineering and remote neurorestoration and reconstruction of damaged NT GM, these devices are quite convenient and reliable and, with their corresponding refinement and simplification, they can be widely used in brain bioengineering. The use of these devices makes the process of radio neuroengineering quite mobile. The device can be installed both in the treatment room or physiotherapy room and carry out combined focal CPT and focal ultrasound exposure, and can be used in the operating room of the radiosurgery room of the radiotherapy department. At the same time, it is obvious that the simplicity and convenience of practical application cannot be achieved at the cost of reducing the accuracy of the apparatus, that is, the accuracy of pointing and falling into a given subcortical structure. The accuracy of hitting the target with a multi-wave focal effect in the subcortical structures is ensured by calculating and simulating hitting the target with a computerized radiotherapy (radiosurgical) stereotactic apparatus, which will provide the necessary effect of AI on the NT damage zone. Ultrasound exposure sensors are fixed on the stereotactic apparatus fixators and positioned at predetermined angles of inclination to the skull in accordance with the marking that ensures the focusing of ultrasound rays in the area of neuroengineering plastic surgery of the brain (i.e., in the area of NT damage), and the structural-resonance inductors are strengthened to plexiglass frame stereotactic apparatus in the frontal and occipital part. To monitor the effectiveness and safety of neuroengineering, a helmet is put on the patient’s head to install electrodes to fix the bioelectric activity of the patient’s GM brain in time. In FIG. 1-2 are photographs of a stereotaxic device modified according to the present invention with sensors fixed thereto for multi-wave focal exposure.

Stage remodeling of the vascular bed of the zones of damage to NT (b). Depending on the etiopathogenesis of the brain disease and the specific tasks of this stage, two vascular remodeling strategies can be implemented: 1) the neovascularization of the zone of damage to the NT in the brain (for tumors, microaneurysms, malformations, hemorrhages, etc.) and 2) hypervascularization of the zone of damage to the NT brain (NT ischemia, NT atrophy, demyelination, etc.). The neovascularization of the zone of damage to NT in the brain has long been resolved by applying destruction of the supply vessels with focused ultrasound under the control of MRI as the first stage of complex treatment using the FUZ-MRI device. Vascular ablation with focused ultrasound provides complete occlusion of the tumor supply arteries or neoplasms in type plus tissue. Another strategy for remodeling the vascular bed, aimed at increasing its geometry and increasing blood flow volume, is implemented by opening microcapillaries and microvenules of the zone of NT damage in the brain. It is solved by remote hypervascularization and microcirculatory remodeling effects on the brain using medical equipment for electromagnetic CPT, described, for example, in patent RU 2317116 C2 for a device for electromagnetic therapy, and the use of FUS using standard equipment for ultrasound therapy. The authors of this patent proposed to use the device for electromagnetic therapy in microcirculatory mode. The possibility of the microcirculatory effect of EMR on human tissue was proved in an experiment, since a method of remote action on the brain according to patent RU 2067879 C1 has already been developed. In this method, organ and tissue are stimulated with an electric current or an alternating magnetic field, and the stimulation frequency range is calculated based on an empirical ratio. This method is improved and designated as structural resonance therapy (CRT). The essence of CPT is to involve the magnetic moments of the body’s structures in resonant “swinging”, while damaged structures having an asymmetric moment will be unbalanced with the removal of pathological ingredients into the general homeostasis system, and tissues released from them or initially healthy tissues remain unchanged. The search for resonant, highly effective frequencies of the treatment signal has been carried out empirically for over 25 years under the control of clinical and instrumental methods for analyzing the dynamics of the disease. CPT is based on the well-known standard value of the fluctuation frequency of atomic cosmic hydrogen - the primary driving information generator for the development of all types of physical structures - 1420817336 Hz. To build the starting points (left row) of the bifurcation of the rhythm cascades, use the octave law with a coefficient of 2, and to build the end points (right row) of the bifurcation, use the golden ratio rule by multiplying the value of the starting point by a factor of 1.5 or use the sum of the values of the initial frequencies of the same rhythm cascade and the previous (lower frequency). The difference in frequency values at the bifurcation points of the rhythm cascades in the CPT method is only from 3.7 A% to 4.7 A%.

CPT for the microcirculation mode in the brain can be implemented using devices of various types, in particular, using the electrostimulator according to RU 24636 U1 (KELSI and RADOMYS devices), a device for cutaneous exposure using conductive rubber (RU 2082449 C1 on “Electrode for feeding on the skin of an electric current during physiotherapy ”), a knitted graphitized cloth UVIS-TR or a silver-plated polymer (article 56041 TU-8378-491-365445028-00), devices for affecting the mucous membranes with biopsy forceps (author’s witness GUSTs SU 1159282 A1) or rubber conductive cable (Inventor's Certificate SU 1367980 A1) and contactlessly by using inducers of the stranded wire in the form of flat belts device for electromagnetic treatment (the above patent RU 2317116 C2).

Considering the fact that pathology, as a rule, violates evolutionarily expedient connections between different organs and systems, there is a need for consistent "debugging" of each level of organization known by rhythm cascades, the pathology of which can be identified by well-known diagnostic methods. When implementing the proposed method, it is possible to use the so-called “scanning” mode, when after a certain time, the envelope frequency characteristic (“address”) for a particular organization level is sequentially pumped carrier frequencies from the minimum trinar through all possible actual biorhythms of structural and functional units up to to the cellular and subcellular levels with a return to the initial trinar.

CPT can be performed on the standard equipment of the REKELSI contact electric stimulator, on which the action is carried out by a rectangular bipolar pulse current (filling), formed into triangular symmetrical equal-bored modulations (envelope). Options for combining the envelope and fill frequencies are implemented in nine modes of operation of the electric stimulator. The new model of the electric stimulator was developed taking into account the latest requirements using a modern elemental base and can operate in automatic and manual stimulation modes. The device is controlled from the touch panel. The device has a user-friendly interface and does not require special training for conducting modes 2-7 "microcirculation" (see Table 2).

When using the apparatus for CPT "REMATER", the effect is carried out by means of an inductor with a rectangular bipolar pulse current (filling), formed into triangular equidistant symmetrical modulations (envelope). Options for combining envelope and fill frequencies are implemented in eight modes of operation. The new model of the device was developed taking into account the latest requirements using a modern elemental base and can operate in automatic and manual modes. The device is controlled from the touch panel. The device has a user-friendly interface and does not require special training. The therapeutic possibilities of using CPT are implemented in several modes of operation of the REMATER apparatus.

To simulate the focal ultrasonic effect on the area of NT brain damage, standard ultrasound “finger” (“pencil”) sensors were used, used for ultrasound research in neurosurgery in the study of transcranial main vessels of the head and neck, or the sensors that were routinely attached to a therapeutic ultrasound device. Ultrasonic exposure to ultrasound sensors mounted in a stereotactic apparatus and focused on intracerebral focused exposure was carried out by connecting them to a standard ultrasound therapy device UZT-107F or UZT 1.01F device. The universal ultrasound therapeutic apparatus UZT-107F with microprocessor control is intended for the treatment of various diseases of the peripheral nervous system by ultrasound. Distinctive features of the device are a smooth adjustment of intensity and a more accurate dosage of radiation. The device is powered from an alternating current network of voltage 220 ± 10% V, frequency 50 Hz. Power consumption - no more than 45 watts. The frequency of ultrasonic vibrations, MHz - 0.88 ± 0.1%. The effective area of the emitters is 0.88 cm ² . The operating mode is continuous, pulsed. The adjustment of the power output is stepwise. The intensity of ultrasonic vibrations in steps, W / Kb. cm from 0 to 1 in increments of 0.1. The pulse duration is 2.4 and 10 ms ± 20%. The pulse repetition rate is 50 Hz. The apparatus kit includes an electronic unit, three emitters, a spatula, cable, fuses. The emitters IUT 0.88 05.10F, IUT 0.88 1.06F, IUT 0.88 1.090, IUT 0.88 2.07C, and IUT 0.88 2.08U were used to simulate stereotactic focused effects. For direct and close contact of ultrasound sensors with the patient’s head, a standard ultrasound gel was used. The time of the FUS procedure was from 10 to 30 minutes and coincided in time with the time of the CPT procedure.

Stage of cellular restoration of the zones of damage to NT (s). The target delivery of SC and PC cell systems in the present invention was ensured by using fundamental neurobiological features and patterns of migration of human HSCs and human GPs. In other words, there was no artificial attraction of these cells to the NT damage zone (magnetic induction, use of the antigen-antibody mechanism, vector immunoliposomal delivery, etc.), but the genetic mechanisms of HSC pathotropism underlying the self-regulation and sanogenesis were used. The proposed method was based on a number of fundamental neurobiological molecular-cellular phenomena of migration of human and mammalian SCs and PCs (the phenomenon of homing, pathotropism, cell adhesion and the “nearby” effect). For this, we used the well-known method for the release of HSCs and mesenchial SC and PC into the peripheral vascular bed during bone marrow stimulation with granulocyte colony-stimulating factor molecules for 5 days, as well as a number of basic biophysical phenomena of the interaction of different types of AI and non-III waves with different types of NT cells.

Cell transplantation was realized by remote directed migration of SC from the bone marrow to the damaged areas of NT GM using the known and approved for clinical use technology of mobilization of HSCs for their collection during bone marrow transplantation and treatment of the effects of traumatic injuries of the spinal cord (patent RU 2383119 C1). The main methods of cell delivery and cell intervention in the damaged areas of the patient’s GM were mobilization of HSC and PC into the patient’s systemic bloodstream using granulocyte colony stimulating factor (G-CSF) (neupogen, physostigmine, granocyte, etc.), as well as intravenous and intrathecal cytotransfusion of cryopreserved HSCs, intravenous or intraarterial infusions of haploidentical (closely related) mesenchymal stromal bone marrow stem cells or autologous neural SCs. It is proved that 4 days after the use of G-CSF in the patient’s blood, a significant number of leukocytes circulate (about 30 × 10 ⁶ -50 × 10 ⁶ ), of which 1-1.2% are HSCs and mesenchymal stem cells with CD cell surface markers 34+ CD45-. The main objective of this stage of restoration was to create a targeting vector for autologous SC and PC and create conditions for their migration to the areas of NT damage and create in these zones the maximum concentration of stem and progenitor cell systems. At this stage, a neurological or psychiatric patient began to mobilize stem and progenitor cells of the bone marrow using the introduction of granulocyte colony stimulating factor (G - CSF) for 4 days in the form of preparations of neurogen, granocyte, physostigmine intramuscularly 2 times a day (morning and evening) ) with daily monitoring of a clinical blood test.

Human bone marrow stem PCs (HSCs and mesenchymal stromal SCs) are able to restore the pathological lesion in human and mammalian mammalian NTs if they are mobilized into the peripheral blood by granulocyte colony stimulating factors (G-CSF) with the highest concentration of stimulation on day 5 SCs and PCs in peripheral blood are either transplanted into the patient’s parenchyma or introduced by systemic intrathecal, intraventricular, intravenous or intraarterial transfusion of a human or in a mammal. Human and mammalian HSCs and MSCCs that are implanted and circulating in the blood have a number of specific features: a) they always migrate to the pathological zone of NT regardless of the origin of the pathological process (inflammation, hemorrhage, tumor, ischemia, degeneration, etc.) according to the gradient of the concentration of inflammation and edema due to the phenomenon of directional migration, homing or pathotropism; b) HSCs, PCs, and MCCCs adhere to pathological cells of the NT lesion zone due to the SC cell adhesion phenomenon; c) they have a regulatory, neurotrophic or stimulating effect on pathological cells in the area of NT damage according to the type of by stander effect phenomenon (nearby phenomenon); d) regeneration of NT tissue cells in human GM can be realized by replacing damaged cells in tissue in the NT damage zone or by combining (fusion) with them as a result of direct fusion of these cells or by establishing new synaptic contacts between transplanted donor cells and recipient nerve cells .

The targeted transport of bone marrow SCs mobilized into peripheral blood on the 5th day of bone marrow stimulation was implemented as follows. To overcome the BBB by cellular systems circulating in the peripheral bed after stimulation in a given region of NT GM and their penetration into the parenchyma of the nervous tissue in the proposed method of treatment, small doses of AI on the human brain were used (1 Gy, tolerant fractional dose of 0.1 Gy) . The following scientific facts served as the fundamental basis for the use of these doses of AI. Doses of 0.1 Gray are able to: a) stimulate tissue regeneration in the area of local interaction of AI with human and animal tissues and activate the proliferation of SC and PC bone marrow of humans and mammals; b) cause aseptic microinflammation and micro-edema in the area of local contact of small doses of AI with brain tissues of humans and animals; c) temporarily disrupt the BBB of NT at the site of AI penetration into the brain and provide in this place a short-term “gateway” for direct penetration of cellular systems, proteins and antibodies from the systemic bloodstream into NT; d) cause instability of the entire informational structure of NT and GM cells in the tissue irradiation zone; e) also cause instability of the genome of the cellular elements of this tissue, which can lead to destabilization of the magnetization, inductance and transient variability of the electromagnetic field of the tissue. Therefore, to activate regeneration in the zone of damage to NTs of GMs, to temporarily open the BBB for penetration of HSCs, GPCs, MCCS and their directed migration to the zone of damage to NTs, to destabilize established pathological intercellular connections in NTs and to form intracellular genetic instability in NT cell systems, as well as to change inductance NT in the zone of its damage, stereotactic irradiation of the zone of NT damage was used with small doses of AI in combination with FUS.

On the 6th day of the patient’s bone marrow stimulation in the morning, using a blood separator of the SpectraCoba type (USA), leukocytopheresis and standard collection, standardization and cryopreservation of mobilized bone marrow SC were performed. The main task of the stage of remote cell transplantation is to ensure unhindered superselective entry of circulating SCs from the bloodstream of peripheral blood into specific areas of NT damage identified at the design stage. Under standard conditions for the functioning of GM, the penetration of HSCs, PCs, and MSCCs from the bloodstream into the nervous tissue is physiologically impossible, since an unchanged BBB prevents this.

According to the literature and our own studies of the authors of the present invention, the threshold doses of cerebral radiation damage to nerve tissue are small doses of 0.1-1.3 Gy per brain in childhood, and radiation-associated neurobiological effects in adults are established at doses> 0.15-0 , 25 Sound Dose-dependent neuropsychiatric, neurophysiological, neuropsychological and neuroimaging abnormalities were detected after irradiation at doses> 0.3 Sv, and neurophysiological and neuroimaging markers at doses> 1 Sv. Thus, the permissible total dose of AI should be a dose of not more than 0.3 Sv. This dose of III radiation is capable of providing genetic instability of nerve cells of the NT damage zone and transient (temporarily up to 6 hours) BBB permeability for cellular mononuclear blood systems (HSC, PC, MCCC, etc.), monoclonal antibodies and biologically active protein molecules from peripheral blood. Using the equipment of modern complexes for stereotactic radiosurgery (CyberKnife, GammaKnife, Navartis, etc.) for local irradiation of NT GM allows you to concentrate this dose superselectively directly in the areas of NT brain damage. The use of AI irradiation on NT GM using these radiosurgical complexes at a concentration level of HSC, PC, and MCCC in the patient’s peripheral blood will ensure their unhindered exit through the capillary network at the sites of stereotactic exposure. To increase the effect of the disclosure of the BBB in the patient’s GM during the period of GM irradiation, it is advisable to carry out intravenous infusion of an ozonized 0.9% saline solution or use FUS during the entire period. These procedures will significantly increase the permeability of the BBB in the brain by one hour, will guarantee the saturation of the NT with oxygen in the areas of NT damage, and will enhance the effect of the temporary opening (up to 1 hour) of the BBB in the GM. The delayed effects of increased BBB permeability after irradiation with AI and FUS will occur immediately after a multi-wave exposure, increase within an hour or an hour and a half after exposure, and will stay for about 12 hours, which will also contribute to the further release of stem and progenitor systems in NT and cellular saturation of the areas of brain NT damage .

The stage of correction of the vegetative provision of the NT damage zone (d). The need for this stage is due to the fact that the main autonomic components of tissue support, for example, the body and synapse of nerve cells located in the autonomic ganglia of the sympathetic and parasympathetic nervous system, are among the first to suffer in the formation of a pathological process in the tissue. Degeneration and wrinkling of nerve cells, pycnocytosis, fatty degeneration of neutral structures in the vegetative ganglia occur. According to the present invention, for the correction of the predominance of sympathetic innervation in the patient, the “sympathetic” mode was used (frequency numbers 7-13 on the REMATER apparatus). When parasympathetic innervation dominated in the clinical picture of the process, the “parasympathetic” mode was used (frequency numbers 14-15 on the REMATER apparatus). Also, in parallel with conducting CPT in the regimes of the indicated vegetative support, the regime of complex simultaneous FUS was applied as an ultraphonophoresis to the area of the stellate node on the affected side with a 1% solution of novocaine or lidecaine.

The stage of dynamic integration of somatic and vegetative components (e) was carried out according to the present invention by combining FZU and SRT in destabilization modes. The use of the CPT destabilization regime corresponded to the envelope frequency (F envelope) of 194 Hz, the filling frequency (= carrier) (F rec.) Of 12500 Hz, 75000 Hz, 150,000 Hz. These effects of CPT led to the disintegration of the damage zone of the NT GM, and subsequently, the synchronization of the elements of the NT damage zone was ensured by the influence of the FUS. At present, the backbone and regulatory-combining capabilities of ultrasound for the restoration of brain NT are well known. The principle of action of focused ultrasound is the same as that of traditional ultrasound - a directed beam of energy, penetrating through tissues, is focused at a small point, causing a local increase in temperature. By focusing ultrasonic energy at a certain depth in the tissues of the body, you can cause a wide variety of effects, ranging from local non-invasive destruction of a given volume of tissue and ending with the effects of activation of nerve structures.

American scientists from Columbia University found that the impact of FUS with an intensity close to critical, but not causing irreversible changes in the structure of the brain, can significantly activate and synchronize the neural networks of the brain. In Europe and the USA, focused ultrasound is already used in the treatment of pain with bone and joint metastases, in the treatment of fibroadenoma and breast cancer, prostate cancer, many neurological diseases, in particular, essential tremor in Parkinson's disease.

Focused ultrasonic fields have four main features: 1. The field width is determined by the same beam divergence angle as in the far field of the non-focusing transducer; 2. The narrowing of the field occurs only in the area where the near field was before focusing, and the far field cannot be focused; 3. The width of the field in focus and behind it is inversely proportional to the diameter of the transducer; 4. The field intensity decreases rather rapidly with distance from the focal region. Therefore, the extent of the focused field is limited. The beam width W at the focal point of the transducer or in the far field is defined as W = ahZ / D, where h is the dominant wavelength of the transmitted acoustic energy; Z is the axial distance from the transducer; D is the width of the transducer (diameter for a circular transducer); and - a constant depending on the geometric shape of the transducer. For circular transducers or piston transducers, a = 1.22, and for rectangular transducers, 1.0. Focusing is carried out using plastic lenses or phase-shifting elements. Plastic lenses are relatively cheap and give good results. They are obtained using an optical system developed by Schlieren that makes ultrasonic waves visible. With strong focusing, the field concentrates in focus and does not extend far. On the contrary, when the ultrasound transducer of the same diameter is weakly focused, the near field extends over a rather considerable distance. The focusing of the ultrasound beam in an electronic phase-shifting system is achieved through a combination of spherical and linear spatio-temporal relationships of pulses arriving at the transducers. As a result of such electronic signal processing, the ultrasonic field is focused at a given distance and propagates at a specific azimuth angle.

Focusing systems, including plastic lenses or phase-shifting elements, have found wide application in various diagnostic ultrasonic medical devices, see, for example, http://meduniver.com/Medical/Physiology/1792.html MedUniver.

The stage of rehabilitation of the functional state of the damaged NT GM (f) according to the present invention is also implemented by means of CPT on NT GM and the stimulating effects of FUS. Due to the fact that the treatment signal for CPT is based on a biologically sound code of the morphogenetic field, its use is safe and does not require special operator qualifications. Exposure to the effects of CPT not only does not have strict restrictions, but on the contrary, the longer and more often the sessions, the faster the patient is rehabilitated, especially in the acute phase and in severe cases of the disease.

Non-contact electromagnetic exposure (contains in the general spectrum of the treatment signal a range of system regulatory frequencies from 0.026 to 0.048 and up to 50,000 Hz) has the advantage in cases when it is necessary to restore normal regulation, harmonize the basic biorhythms of a person, stop various pathologies of hollow organs at the organ frequency level, stabilize the general condition of the body in the pathology of arterioles, capillaries, venous and lymphatic systems, with serositis, synovitis and bursitis, with allergic lesions s various organs, including the toxic-allergic hepatitis and pancreatitis, angioedema, eczema, atopic dermatitis, hives, hay fever, and psoriasis. Apply the CPT scan mode.

Rehabilitation or restoration of the function of damaged NT NT can be carried out by non-contact, transdermal exposure to electric current (frequencies ≥200 Hz are represented in the general spectrum of the treatment signal), which is advantageous in treating organs located far from the skin surface or organs that do not have their own spontaneous biopotential activity, as well as with degeneration and inflammation of the facial nerve, neuritis, radiculitis, neuralgia, with metabolic syndromes of various origins, in the treatment of benign natural tumors (with careful monitoring by medical specialists).

The effects of local relaxing and sedative rehabilitation effects of CPT can be enhanced by simultaneous local exposure to FUS, which significantly improves the rehabilitation and recovery properties of therapeutic effects. The main task of applying low-intensity ultrasound is non-damaging heating or any non-thermal effects, as well as stimulation and acceleration of normal physiological reactions in the treatment and rehabilitation of damage.

Thus, the present invention provides a new medical biotechnology of remote electromagnetic multi-wave radio bioengineering of damaged NT GM. The invention implements the principles of stereotactic non-contact and wireless effects on the molecular-cellular mechanisms of various neurobiological pathological processes in the brain by software combining the electromagnetic wave non-ionizing and ionizing radiation component of radiation therapy to repair damaged NT GM. Bioengineering of neural tissue in this invention is based on sequential multi-stage program combination and use of various methods of radiosurgical, radiotherapeutic, structural resonance, ultrasonic regulatory multi-wave and cellular effects on the structure and function of damaged NT human hypertension known and approved for clinical use. As part of the innovative concept of non-contact and wireless neurorestoration and restoration of molecular-cellular mechanisms of functioning of the structure of the damaged brain, an innovative methodology of selective (selective) phased reconstruction of NRT was applied using cell and tissue-engineering technologies, stereotactic technologies of radiation therapy, bioresonance therapy and ultrasound therapy. Regeneration and (or) replacement of damaged NT cells in this method is carried out by targeted plastic treatment of the required NT sites with autologous HSCs mobilized into the patient’s peripheral blood or transplantation of donor haploidentical (closely related) HSCs, mesenchymal stromal stem cells (MSCCs) and bone marrow hematopoiesis the patient. These basic elements of the technology made it possible to create a new highly effective and innovative multi-wave radio bioengineering method for the restoration of damaged nervous tissue of GM in various nervous and mental diseases.

Each of the methods of the method of the present invention of ionizing and non-ionizing electromagnetic wave effects of various types of radiation on human NT can be independently used for clinical use, officially approved for clinical use in humans in the Russian Federation and used to treat individual neurological diseases as one of methods of physiotherapy or radiotherapy. But the local clinical application of these methods in the restoration of NT GM, limited by purely narrow physiotherapeutic use, does not allow us to achieve the required clinical effect of NT reconstruction in the treatment of these diseases. Today these technologies are only auxiliary methods in the complex ineffective pharmacological treatment of nervous and mental diseases, and when used correctly, they can become the main tools for restoring the damaged structure and function of damaged nervous tissue of GM and SM. The proposed method of remote electromagnetic radio neuroengineering allows you to overcome all the main disadvantages of minimally invasive surgical technology and perform all stages of the restoration of human and mammalian GM without touching the nervous tissue of the patient’s GM. The reconstructive and reconstructive effect on a specific damaged morphofunctional tissue structure of a patient’s GM in the proposed method is technically implemented by combining systemic and local effects of AI and NeII EMR and regulating and controlling the molecular-cellular and wave mechanisms of NT homeostasis in the damaged zone of NT GM.

The regulation of the morphological structure of a damaged NT is regulated using medical devices and hardware approved for clinical use in the Russian Federation for remote multi-wave and ionizing effects on cells of a damaged human NT (CPT devices, devices for stereotactic radiotherapy and radiosurgery) without invasive surgical methods for influencing NT. At the same time, the following basic software algorithms for bioengineering technology and the logic of step-by-step reconstruction of NTs were implemented:

1. All the basic technological solutions of the morphological and functional restoration of NT through remote bioengineering of the brain are implemented in practice, providing various stages of brain restoration.

2. Super-accurate software and computer diagnostics of all personal morphofunctional characteristics (CT, MRI, PET, MEG, EEG) of the areas of damage to NT GM was carried out.

3. Targeted targeting and targeted transport of SK and PC cellular systems or native autologous tissue-specific SK and PCs to the tissue engineering zone are provided.

4. Implemented a stimulating and reconstructive effect on NT.

5. A change was made in the geometry of the vascular bed of the pathology zone, taking into account all the existing problems of reconstruction.

6. Management (opening and closing) of the BBB of a human GM is provided at the right time, for the right time and in the right place of the GM.

7. Provided remote synchronization of somatic and vegetative components of NT in the zone of damage.

8. The restoration and activation of the impaired function of the damaged section of NT GM was ensured.

The effectiveness of the proposed method was evaluated in a clinical setting in patients with severe organic diseases of the nervous system (10 patients with consequences of a brain injury, 2 patients with amyotrophic lateral syndrome and 3 patients with multiple sclerosis).

The proposed method of radio neuroengineering can be widely used for the rapid non-drug relief of post-stress (neurosis-like, psychogenic and reactive) disorders and to increase the working capacity of military personnel of the Ministry of Defense of the Russian Federation and the Ministry of Emergencies of the Russian Federation on the battlefield or natural disaster areas. From the standard modules of diagnostic and therapeutic radiation equipment, unique biotechnological platforms for managing new generation stereotactic radio-bioengineering medical equipment complexes that can be used for accelerated treatment of nervous and mental diseases will be created.

Further, the method of the present invention is illustrated by examples.

Example 1

Patient V., born on 10/31/1956, was in the clinic on 10/07/2014 with a clinical diagnosis: Consequences of combined trauma. A severe brain contusion with diffuse axonal damage, the consequences of compression of the left hemisphere by acute subdural hydroma in the early period after an injury (02.15.2010). Condition after resection craniotomy in the left frontotemporal region, removal of subdural hydroma. The consequences of pneumothorax on the left; fracture of 5, 6, 7 ribs on the left; fracture of both ankles of the left lower leg, subluxation of the foot; fracture of the right tibia, fracture of the right patella. Tracheotomy (02/18/2010); epicystostomy (03/30/2010). Condition after catheterization of the right common carotid artery through the superficial temporal (prolonged intracarotid infusion of drugs (November 2010). Removal of the epicystostomy (09.2011). Removal of the tracheostomy tube (02.03.2012). Condition after plastic surgery of the tracheostomy opening (01/17/2013, Central Clinical Hospital UDP, Moscow) Cystolithotomy (Elista, 06/06/2013) Condition after repeated intrathecal cytotransfusions MACK.

Complaints: independently does not show due to the peculiarity of the underlying disease.

Anamnesis of the disease: it is known that after an accident on 02/15/2010 (while driving, he was in the front seat next to the driver and delivered to the hospital by a passing vehicle), a severe brain injury was diagnosed with compression of the left hemisphere with an acute subdural hematoma. As a result of the examination, the following treatments were identified and carried out: pneumothorax on the left; fracture of 5, 6, 7 ribs on the left; fracture of both ankles of the left lower leg, subluxation of the foot; fracture of the right tibia, fracture of the right patella. Resection craniotomy was performed in the left frontotemporal region, removal of subdural hydroma 02.16.2010; tracheostomy 02/18/2010; epicystostomy 03/30/2010. For a month I was in the hospital, then I received treatment on an outpatient basis. From November 9, 2010 to December 15, 2010 he received treatment at the Institute of the Human Brain of the Russian Academy of Sciences, where catheterization of the right common carotid artery through the superficial temporal lobe with prolonged intracarotid infusion of drugs was performed. Orchoepididimectomy was also performed there due to the acute development of right-sided epididymitis with the development of bacterial toxic shock. Subsequently, the patient was sent to the NeuroVita clinic in a planned manner to carry out rehabilitation measures according to an individually developed program in the clinic. The patient was admitted as planned to continue the complex therapy: rehabilitation, symptomatic treatment, intrathecal cytotransfusion MACK. During the observation, after the first hospitalization, there is a positive trend: it recognizes relatives, responds positively to doctors, fixes the gaze on the person entering the room, shakes hands, opens upon request - closes his mouth, blinks, correctly answers questions of any complexity, showing with his right hand on the tablets with the correct answers in such subjects as physics, higher mathematics. Such manipulations as planting, verticalization, - tries to actively participate and help caregivers, tries to fix the knee joint at the request of the instructor during verticalization, is engaged in an exercise bike (passive, active mode).

01/17/2013 in the Central Clinical Hospital of the UDP in Moscow, suturing of the tracheostomy opening was performed; 06/06/2013. cystolithotomy (Elista city).

Somatic status: General condition - moderate, stable. Correctly shows colors, considers and can show the right answer with his right hand, selects from the cards being shown, at the request he can perform actions: open his mouth, show his tongue, move his tongue in the oral cavity; a predetermined number of times to blink eyes, blows out a lit match. He chews rough food. Physique normosthenic, moderate nutrition. No bedsores. HELL 120/80 mm RT. Art., pulse 71 beats / min. The position is passive. The skin is pale, moist, clean (multiple postoperative scars as a result of trauma and surgical interventions on the anterior abdominal wall and limbs). Sclera - visible, mucous, normal color. Edema is absent, pastiness is not observed. Independent breathing, through natural paths, he himself expectorates the accumulated sputum. Percussion: percussion sound above the pulmonary fields of the pulmonary. Auscultatory: in the lungs, hard breathing, weakened in the lower sections; conductive wheezing. Heart sounds are muffled, the rhythm is correct. The abdomen is of the usual form, participates in the act of breathing, painless, mild, the symptoms of Shchetkin-Blumberg, Courvoisier are negative. The liver is not palpable, painless. The gall bladder is not palpable, painless. The spleen is not palpable, painless. Stool, urine: not completely in control.

NEUROLOGICAL STATUS: No meningeal signs. Cranial innervation: I olfactory nerve - difficult to evaluate; II optic nerve - photoreaction is reduced, vision is difficult to evaluate, does not follow the subject; independent eyeball movements saved. The patient occasionally fixes his gaze on a person entering the ward, relatives, acquaintances, presented objects. III, IV, VI - oculomotor, block, abducent nerves - pupils D = S, palpebral fissures D = S; V trigeminal nerve - sensitivity on the face is difficult to assess due to the severity of the condition; VII - the facial nerve - the face is symmetrical, mimic tests are satisfactory, VIII - the vestibulo-cochlear nerve - it is difficult to evaluate because of the severity of the condition; IX, X - glossopharyngeal, vagus nerves - palatine curtain symmetrical, uvula in the midline, pharyngeal reflexes high. Swallowing is the norm, the patient chews food chopped in a blender. The positive symptoms of oral automatism, XI - additional - are difficult to evaluate due to the vegetative state, XII - deviation of the tongue to the right.

The limb holds the awning: the leg is upright when supporting the foot on the bed, the forearm is resting on the shoulder. Muscle tone in the limbs is high, slightly higher on the right. Participates in planting, moving within the bed. Tendon reflexes: medium vividness, without a clear difference of sides. Pathological signs are positive - a symptom of Babinsky, Oppenheim, Pusep. Sensitivity is difficult to assess due to the severity of the condition. Coordination tests are difficult to evaluate because of the severity of the condition. Pelvic function does not control. Higher nervous functions according to complex (clinical, paraclinical signs) are partially preserved.

Blood and urine tests without pathology. ECG. Conclusion: Sinus rhythm, horizontal position of EOS, heart rate of 67 beats per minute. ECG in dynamics, without negative dynamics.

ELECTROENCEPHALOGRAPHIC RESEARCH

Alpha rhythm irregular: Frequency: 8 counts / sec; amplitude: up to 60 μV; severity index: 60% in the left hemisphere and 35% in the right; maximum severity - in the occipital-parietal sections. Zone differences saved. Modulations are fuzzy. Beta activity. Frequency 18-23 counts / sec, amplitude up to 14 μV; It is expressed mainly in the frontotemporal. Pathological slow activity: polymorphic low-amplitude diffuse theta oscillations, index 10%. Paroxysmal phenomena: no. Other EEG phenomena: no. Functional tests: Activation reaction: adequate. Photostimulation of 2-24 Hz, without significant effect. Hyperventilation (3 min): not performed. Conclusion: Epileptiform activity was not detected. Interhemispheric asymmetry was revealed: the alpha rhythm is better expressed in the left hemisphere. Moderate diffuse disturbances in the bioelectric activity of the brain of a regulatory nature are noted.

QUANTITATIVE EEG ANALYSIS

The following characteristics of the bioelectrical activity of the brain were revealed by the method of spectral analysis: The peak of spectral power is observed in the alpha theta range at a frequency of 7.5 Hz, in the left hemisphere and at a frequency of 9 Hz in the right hemisphere. The obtained data indicate the formed alpha rhythm in both hemispheres of the brain with signs of desynchronization in the activity of deep pacemakers of the bioelectric activity of the brain.

SOMATOSENSOR CALLED CAPACITIES

Stimulation - n. Tibialis at the level of the medial ankle (electrical stimuli lasting 0.3 ms and a frequency of 0.5 Hz); Registration - 1) Cz - Fpz sensory cortical projection.

Conclusion: During stimulation of both lower limbs, pronounced dysfunctions of the pathways of the somatosensory analyzer were revealed.

SOMATOSENSOR CALLED CAPACITIES

Stimulation - n. Ulnaris at wrist level; Registration - C3's / C4's-Fpz sensory cortical projection.

Conclusion: During stimulation of both upper limbs, pronounced dysfunctions of the pathways of the somatosensory analyzer were revealed.

With prior informed consent, the patient underwent intrathecal MACK cytotransfusion - twice; the procedure was satisfactorily transferred. Consultation of a neurosurgeon. The state of minimal consciousness. The consequences of CCI, severe brain contusion with diffuse axonal damage, compression of the left hemisphere with acute subdural hydroma in the early period after injury. Condition after resection craniotomy in the left frontotemporal region, removal of subdural hydroma 16/02/10. According to the obtained neuroimaging data of the brain and based on the conclusions of the neuroophthalmologist: intracranial pressure is within normal values, there is no risk of developing intracranial pressure - it is recommended that the patient undergo plastic surgery: (close) the trepanation window in a planned manner, in a specialized hospital.

The patient was disassembled at a consultation of doctors of the clinic, the diagnosis: “The consequences of polytrauma. The condition after a severe bruise of the brain, removal of an intracranial hematoma of the frontoparietal region of the right hemisphere of the brain with the outcome in a chronic vegetative state in the form of an apallic syndrome (locked-in person syndrome). ” It is anamnestically known that patient B., after a serious automobile injury, underwent several life-saving neurosurgical operations on the brain. In the process of neurosurgical treatment, he was in a coma for more than 11 months. The outcome of the treatment of brain damage to patient B. was a chronic vegetative state in the form of an appal syndrome or “locked man” syndrome. Due to the inefficiency of further conventional treatment, the patient was discharged from the academic medical institution for home care, but the patient's relatives decided to continue the struggle to recover after removing him from this state and restoring his consciousness. The consultation was faced with the question of verification of the main areas of damage to the brain NT, requiring restoration in the process of bioengineering. Together with the specialists of the PET department of the Federal State Budgetary Institution RONC RAS and the specialists of LLC Cyberknife, we have developed a technology for multilevel merging of data from all tomographic studies. The results of examining the patient’s GM fusion of this information data and obtaining a 3D map of the morphofunctional structure of the patient’s GM are presented. The patient underwent 4 radio neuroengineering sessions with the collection of mobilized bone marrow stem cells and intrathecal injections of autologous hematopoietic stem cells. Patient V., after a course of radio neuroengineering, regained consciousness, began to understand conversations, followed instructions for closing his eyes, raised a hand at the command, and moved his fingers. He began to consciously manifest emotional reactions, actively participating in the rehabilitation process. Speech has not yet recovered, but emits emotionally colored sounds, periodically cries, gets angry at his wife. The patient was given a course of an individually designed rehabilitation and massage program, verticalization on specialized simulators with the elimination of gravity; a course of vascular, nootropic metabolic therapy. In connection with the end of the planned period of stay in the clinic, a patient in a compensated state is discharged for outpatient treatment under the supervision of a neurologist and general practitioner at the place of residence. Recommended by:

• Continue taking: aspirin cardio 50 mg 1 t n / n - constantly; baclofen 25 mg * 3 r / day (with an increase in spasticity in the limbs, it is possible to add the table. Sirdalud 2 mg * 3 r / day - starting the first three days at night with 2 mg). Finlepsin tablets 100 mg 1 tablet at night.

• Repeated courses of vascular and nootropic therapy: Cerakson's solution intramuscularly, solution Actovegin intravenously No. 10; Vazobrala solution per os., tablets Thioctacid 600 mg per day, Trental tablets 800 mg / day.

• Periodically perform a control study of blood tests, urine tests - for the prevention of exacerbation of urolithiasis, it is recommended, in agreement with the urologist, to take a course: the urological collection is brewed in bags up to 3 times a day, 2 tablets of conefron 3 times a day, 3 phytolysin paste 3 -4 times a day to dissolve in water - alternate reception.

• For the prevention of urinary tract infections or with exacerbation of chronic cystitis. Recommended: tablets Palin 400 mg * 2 r / day -14 days.

• Continue exercise therapy under the supervision of an instructor.

• Re-hospitalization after 3 months.

Example 2

Patient S., 64, was in the clinic on 08/07/2014. until 02.09.2014, was hospitalized for the first time in a planned manner with a clinical diagnosis: Main diagnosis: Motor neuron disease (reliable ALS) debut, sporadic form: flaccid tetraparesis, mainly in the upper extremities. Dyscirculatory encephalopathy on the background of hypertension, common atherosclerosis of the main arteries. Reconvalescent Epstein-Barr virus. Concomitant diseases: Stage 2 hypertension, AH 2 degree, medium risk. Violation of the rhythm and conduction of the heart: single and paired polymorphic ventricular extrasystole, polytopic supraventricular extrasystole. Imbalance: dyslipidemia, hypercholesterolemia. Atherosclerosis of the brachiocephalic arteries, initial manifestations. Chronic obstructive bronchitis. DN II-III degree, Chronic superficial gastritis, remission. Chronic calculous prostatitis. Nodular prostatic hyperplasia. Mild myopathy, complex myopic astigmatism in both eyes.

Anamnesis of the disease: in the anamnesis of frequent gastrointestinal tract diseases (in his youth he was engaged in boxing), frequent psychophysical stress at work. From youth, a periodic increase in blood pressure from 170/100 mm Hg is disturbing. Art. against the background of psychoemotional stress. "Working" HELL 120-130 / 80-90 mm RT. Art. The last 2 months constantly takes Valz 80 mg * 2 p. / Day, periodically with an increase in blood pressure, 25 mg capoten is added. On October 28, 2014, he suffered an accident when he was driving his own car, as a result of sharp braking he hit the steering wheel with his chest, in the following months the patient did not notice any deterioration in health. The patient himself noted a deterioration since January 2014, when twitching of certain muscle groups began to appear, muscle mass and body weight gradually decreased. Since April 2014, he began to notice growing weakness and awkwardness in the limbs, more in the hands, blurred speech, false urge to urinate and a decrease in the pressure of the stream. He went to the clinic where an MRI of the brain was performed (04.24.2014): in the white matter of the occipital, frontal and parietal lobes, periventricular and subcortical, a few foci of a discirculatory nature (up to 9 × 6 mm). Moderate replacement mixed hydrocephalus. An MRI of the cervical spine and brain was performed - multiple posterior protrusions at the thoracic level (up to 2 mm). For further examination and maintenance therapy, he was hospitalized in the Health for You MC in Moscow, signs of the current generalized neuronal (anterogy) process with a predominance of denervation (2-3 B stage of DRP) were revealed by ENMG (needle EMG) at the bulbar, cervical and lumbar levels ), signs of the breakdown of muscle fibers, revealed generalized motor axonopathy (most pronounced - from the side of the median nerve tested), sensory conduct intact. A consultation was held in conjunction with the head. Department of Nervous Diseases, MD, prof. Gubsky L.V., diagnosed with Motor neuron disease. The therapy was carried out with Berlition 600 mg, Actovegin 10 ml, cardiomagnyl 75 mg, 80 mg diovan. From June 16, 2014 to July 2, 2014, he was treated at the UMMC MC Health with specialists from the CTM (12 LTM, 12 foot massage, additional program), intravenous heptral No. 7, cerebrolysin No. 7, neuromultivitis 1 table. × 3 r / day, Sirdalud 2 mg × 2 r / day, Riluzole 50 mg × 2 r / day, Valsartan 160 mg in the morning, Arifon retard 1.5 mg in the morning.

Real hospitalization for further examination and the choice of tactics for further treatment according to the radio neuroengineering program. Anamnesis of life: grew and developed according to age. In mental and physical development did not lag behind. Frequent CCW. Tuberculosis, syphilis, hepatitis, veins. denies the disease. Smokes 1 pack of cigarettes per day. Alcohol is not abused. Allergic reactions: according to the patient, not noted. In somatic status at the time of inspection - negative dynamics were not noted: general condition - moderate, stable. The skin is dark, warm, moist, tissue turgor is reduced. Groups of peripheral lymph nodes of soft-elastic consistency, not enlarged, painless on palpation. Mixed breathing, NPV - 18 per minute. Heart sounds are moderately muffled, the pulse is 80 per minute, satisfactory filling. HELL 135/85 mm RT. Art. The abdomen is not enlarged, soft, painless. There are no symptoms of peritoneal irritation. Intestinal noises are heard. Urination system: urination is free, painless. Palpation of the kidney area is painless. The symptom of striking is negative on both sides. The chair is regular. Pelvic function controls. Neurological status: In the mind, oriented in place and time. There are no cognitive impairments. The pupils are symmetrical. Photoreactions saved. The movement of the eyeballs in full. There are no bulbar disorders. Pharyngeal, cough, swallowing reflexes are slightly reduced. Reflexes of oral automatism. Upper flaccid paraparesis with an emphasis on the left in the proximal muscle group, weakness in the hand is more pronounced on the left. Caused by fibrillation in the muscles of the upper limbs. Hypotrophy of the upper muscles, distal parts. There are no sensitive violations. Tendon reflexes of the upper and lower extremities are enlivened, without a pronounced difference in sides. Pathological wrist marks (a symptom of Tremner) are caused. Coordination tests are performed with intention. No pelvic abnormalities. There are no meningeal symptoms.

RESULTS OF INSTRUMENTAL, LABORATORY RESEARCH METHODS.

Blood and urine tests - without pathology. Immunological status is within normal limits.

ELECTROENCEPHALOGRAPHIC RESEARCH

Alpha rhythm is irregular. Frequency: 10-12 count / sec; amplitude: up to 50 μV; severity index: 30%; dominates in the occipital-parietal regions of both hemispheres, zonal differences are smoothed, and modulations are fuzzy. A distinct lateralization of the alpha rhythm is not traced. Beta activity. Frequency 17-20 counts / sec, amplitude up to 12 μV; well expressed in all leads. Pathological slow activity: no. Paroxysmal phenomena: not detected. Other EEG phenomena: none.

Functional tests: Activation reaction (opening of the eyes): adequate. Photostimulation 2-24 Hz: no significant effect. Hyperventilation (3 min): the EEG pattern does not change.

Conclusion:

1. No typical epileptiform activity was detected.

2. There are no signs of focal lesions of the cerebral cortex.

3. Significant interhemispheric asymmetry is not observed.

4. Revealed moderate diffuse disorders of the bioelectric activity of the brain associated with dysfunction in the activity of the diencephalic stem structures.

QUANTITATIVE EEG ANALYSIS

By the method of spectral analysis, the following characteristics of the bioelectrical activity of the brain were revealed: The peak of the spectral power of the main EEG rhythm (alpha rhythm) is determined in the occipital region at a frequency of 10.5 Hz, expanded, deformed, no significant asymmetry in the hemispheres is noted. An additional peak was detected at a frequency of 9 Hz in the frontal region. The data obtained may indicate the presence of disintegration in the activity of the main pacemakers of cortical rhythm while maintaining the overall level of functional activity of neocortex neurons in both hemispheres of the brain.

PROTOCOL OF NEEDLE ELECTROMIOGRAPHIC (EMG) SURVEY

The patient is sent for an EMG examination with a preliminary diagnosis: motor neuron disease for verification. When EMG examination with concentric needle electrodes, the following data were obtained, see Table 7.

Conclusion: The data obtained indicate a current generalized disease of spinal cord motor neurons, which is more pronounced in the distal muscles of the hands. Stage of denervation-reinnervation process: 2-3. Signs of breakdown of muscle fibers are noted.

ELECTRONEUROMYOGRAPHIC RESEARCH

The study of motor fibers:

The study of sensitive fibers (antidromic):

F-wave: upon stimulation at the distal point (20 stimuli):

Right ulnar nerve: abs. Left ulnar nerve: 55% blocks, min latency - 27.7 ms, max latency - 30.2 ms, average latency - 28.4 ms. Stereotype of the F-wave is noted.

The study of motor fibers:

The study of sensitive fibers (antidromic):

F-wave: upon stimulation at the distal point (20 stimuli): Right tibial nerve: 5% blocks; min latency - 45.6 ms, max latency - 50.8 ms, average latency - 48.1 ms. Left tibial nerve: blocks 0%; min latency - 44.5 ms, max latency - 50.7 ms, average latency - 47.5 ms.

Conclusion: According to the results of the study, pronounced dysfunctions of both peroneal nerves (motor fibers), gross disorders of the median nerves (motor fibers) and the right ulnar nerve according to the axonal type were revealed.

ECG: Sinus rhythm. The vertical position of the EOS. Heart rate - 90 beats per minute.

Function of external respiration. Conclusion: Decreased pulmonary volumes and ventilation reserves (III-IV Art.). Moderate obstruction of the bronchi (1 tbsp.).

USDG MAG. Conclusion: Atherosclerosis of BCA on both sides without hemodynamically significant stenosis. C-shaped tortuosity of the left ICA is hemodynamically insignificant.

Ultrasound of the vessels of the lower extremities: The investigated superficial and deep veins of the lower extremities are completely passable.

Integrated ultrasound. Conclusion: Polyp of the gallbladder. Diffuse pancreatic changes, fatty infiltration. Left kidney stone? Atherosclerosis of the abdominal aorta.

Echocardiography. Conclusion: The chambers of the heart are not expanded, myocardial hypertrophy is not. The global contractile ability of the myocardium is preserved, the local is not compromised (PV-70%). Locally not disturbed. Aorta is compacted, not expanded. Shutters MK tight. Mitral valve insufficiency ++ 2.5 m / s. Tricuspid valve insufficiency ++ 2.0 m / s. In the pericardial cavity, the volume of fluid is within normal limits. The diastolic function of the left ventricular myocardium is not impaired. The average pressure in the pulmonary artery is within normal limits.

X-ray examination of the chest organs: On the right, the average proportion is reduced in volume, compacted - the x-ray picture may be due to the median lobe syndrome. Or another reason for obstruction of the middle / lobar bronchus. The right root zone is enlarged, not compacted, but in the presence of clinical data a relapse of inflammation cannot be ruled out. Other departments unchanged.

MRI of the brain (08/14/2014). Conclusion: MP-picture of pronounced signs of vascular encephalopathy, some violations of the architectonics of the main arteries of the brain and neck. Minor changes in the sinuses.

MRI of the thoracic spine (08/14/2014). The results of the examination are recorded on a CD, the conclusion - issued on hand.

Therapist consultation. Conclusion: Stage 2 hypertension, AH 2 degree, medium risk. Violation of the rhythm and conduction of the heart: single and paired polymorphic ventricular extrasystole, polytopic supraventricular extrasystole. Imbalance: dyslipidemia, hypercholesterolemia. Atherosclerosis of the brachiocephalic arteries, initial manifestations. Chronic obstructive bronchitis. DN II-III degree. Chronic superficial gastritis, remission. Chronic calculous prostatitis. Recommendations are given.

Ophthalmologist consultation: Mild myopathy, complex myopic astigmatism in both eyes. A medical consultation was held at the clinic under the chairmanship of the clinic’s director general. professors A.S. Bryukhovetsky, as part of the deputy. gene. Medical Director Prof. Dr. med. N.G. Evseev, doctor of hematologist, professor MD G.L. Mentkevich, neurophysiologist Ph.D. A.A. Frolov, attending neurologist N.I. Kovalenko. At a medical consultation, due to the lack of treatment standards and an unfavorable prognosis of the course of the disease, it was decided to include the patient in the radio neuroengineering group of the spinal cord. The patient was consulted by an employee of the Research Institute of Dogs, Russian Academy of Medical Sciences RAMS, MD, professor G.L. Mentkevich, who determined the tactics of mobilization and separation of autologous hematopoietic stem cells. With the informed consent of the patient in the neurological department, 4 sessions of structural resonance therapy in the "microcirculation" mode were performed on the REMATERP structural-resonant electromagnetic therapy apparatus "MARS" within 4 days after the stimulation of hematopoiesis by the neupogen (GUP MOKB No. 29/23010499 / 0573-01), on the 5th day of hematopoiesis stimulation, the patient was taken to the radiation therapy department and intravenous ozone was administered, then 1 stereotactic radiation therapy was conducted on the motor zones of the cerebral cortex using CyberKnife zga on the left (0.002 zvs). After irradiation, after 2 hours, MAGSK was separated (August 22, 2014), the procedure was satisfactorily transferred. The following days (5 days) spent 6 sessions of structural resonance therapy in the mode of synchronization of nerve tissue on the apparatus "REMATER". Subarachnoid cytotransfusion of autologous hematopoietic stem cells was performed twice, with prior informed consent, in a double dose. The manipulation was satisfactory, the last time was a moderate headache after the introduction of MACK on the third day, no signs of meningism were noted. In the department, complex treatment was further carried out: symptomatic therapy: Eufillin 2.4 - 10 ml No. 5; Ribksin's solution of 10 ml No. 15; dexometasone solution 8 mg 1 time No. 20; Cerebrolysin solution 10.0 No. 15; Nootropil solution 20.0 No. 5; Ceftriaxone solution 1 gr. per day number 10 in two stages. Mildronate solution 5.0 No. 15 - intravenously in physiological saline, drip, in stages. Prozerin 1.0 solution subcutaneously No. 10 every other day; Milgamma solution 2.0 v / m No. 10; Retabolil solution 1.0 IM twice a week. Rilutec tablets 100 mg per day. Kudesan tablets 1 tablet 2 times a day. Tablets Noliprel A 5 mg 1 tablet in the morning. Tablet Concor 5 mg 1 tablet in the afternoon; rehabilitation program Total radiation exposure 0.012 mSv. The patient is discharged in a moderate state, relatively stable state under the supervision of a neurologist, general practitioner.

From the presented examples, it is clearly seen that the use of computer technology for merging data of various methods of radiation diagnostics of GM in the proposed method allows us to find morphofunctional zones for bioengineering of GMI and apply innovative reconstructive approaches to radio bioengineering to them. The proposed method for stereotactic radio neuroengineering of human tissues can be implemented only in a high-tech medical hospital equipped with standard diagnostic and treatment equipment for stereotactic radiation diagnostics and radiotherapy (devices for stereotactic radiosurgery and radiotherapy, MRI, PET / CT and magnetoencephalograph) or in a specialized front-end module; equipped with all of the above equipment or its analogues. The novelty and scientific relevance of the present invention lies in the creation of a three-dimensional (3D) model of the disease, based on MRI, MEG, PET / CT, EEG mapping and innovative software that allows you to coordinate and compare multilevel diagnostic information about the structure of NT GM neurological patient obtained on different hardware diagnostic tools, as well as the fact that the technology allows you to create a single plan for the reconstruction of the damaged area of the brain or monitor the speaker the restoration of NT GM.

Literature

1. Abrakov L.V. / Basics of stereotactic neurosurgery. L., "Medicine", 1975, p. 232.

2. Blekhman II. Synchronization in nature and technology. - M., 1981.

3. Bryukhovetsky A.S. Dmitrieva T.B., Chekhonin V.P., Zubritsky V.F., Shumakov V.I., Sharaevsky G.Yu. Bioengineering method of restoration of brain functions // Patent for the invention of the Russian Federation No. 2152038 from 06/27/2000. - 7 p.

4. Bryukhovetsky A.S., Dmitrieva TB, Chekhonin V.P., Zubritsky V.F., Shumakov V.I., Sharaevsky G.Yu. Bioengineering method for remodeling the vascular system of the brain // Patent for the invention of the Russian Federation No. 2152039 from 06.27.2000. - 6 p.

5. Bryukhovetsky A.S., Dmitrieva TB, Chekhonin V.P., Zubritsky V.F., Krasheninnikov M.E., Shumakov V.I., Sharaevsky G.Yu. A method of obtaining a preparation of human embryonic neurons for cytotransfusion // Patent for the invention of the Russian Federation No. 2146932 from 03/27/2000. - 8 p.

6. Bryukhovetsky A.S., Yarygin V.N., Mkheidze D.M., Mentkevich G.L., Zaitsev A.Yu. Patent of the Russian Federation RU No. 2283119 C1 dated 09/10/2006, “The preparation of autologous hematopoietic stem cells, the method of its production, cryopreservation and use for the treatment of traumatic disease of the central nervous system”.

7. Bryukhovetsky A.S., Sevastyanov V.I. RF patent RU №2249462 "Universal heterogeneous collagen matrix for implantation and method for its preparation" dated April 10, 2005

8. Bryukhovetsky A.S. RF patent RU No. 2283119 "The preparation of autologous hematopoietic stem cells, the method of its preparation, cryopreservation and use for a traumatic disease of the central nervous system" dated September 10, 2006.

9. Bryukhovetsky A.S., Pugachev G.R. A method of activating lost motor functions, as well as determining the effectiveness of their recovery in case of damage to the central nervous system. RF patent No. 2316334 dated February 10, 2008 - 27 p.

10. Bryukhovetsky A.S. International application PCT / RU 2009/000067 "Implantable neuroendoprosthetic system, method for its preparation and method for reconstructive neurosurgical surgery", filed February 13, 2009.

11. Bryukhovetsky A.S. Spinal cord injury: cell technology in the treatment and rehabilitation. M .: Practical medicine, 2010 .-- 341 p.: Ill.

12. Bryukhovetsky A.S. International application PCT / RU 2009/000424. The preparation of stem cells with reprogrammed cellular signaling, the method of its production and use, filed 08/20/2009

13. Bryukhovetsky A.S. Cellular technologies in neurooncology: cytoregulatory therapy of glial brain tumors. - M., RONTs Publishing Group, 2011 .-- 736 p.: Ill.

14. Kuzovlev O.P. et al. New successful rehabilitation and treatment technology (O.P. Kuzovlev, 2003 and 2005; 2005 and 2006).

15. Kuzovlev O.P. A new direction in medical rehabilitation of people with extreme professions, 2006 and 2007.

16. Kuzovlev O.P. Correction of the functional state of the cardiovascular system in arterial hypertension, 2005.

17. Kuzovlev O.P., Razumov A.N., Korchazhkina N.B. Improving reserve and adaptive capacity in healthy individuals, 2005.

18. Putilov A.A. The backbone synchronization function in nature. - Novosibirsk, 1987.

19. Fartuh D.A. et al. Allergic dermatosis treatment, 2006.

20. Laktionova L.V. Treatment of bronchial asthma and obstructive pulmonary disease, 2006.

21. Ivanova V.V., Kuzovlev O.P. Treatment of genital papillomavirus infection. 2005 and 2006.

22. Bychkov S.A. Treatment and prevention of complications in surgical dentistry, 2003.

23. Bubnov V.A. Salnikov P.S. Treatment and prevention of postoperative paresis of the gastrointestinal tract, 2003.

24. Abdurakhmanova A.Z. Rehabilitation in the early postoperative period of cholecystectomy, 2009 and 2010.

25. Kaznacheev V.P., Mikhailova L.P. Bio-informational function of natural electromagnetic fields. Novosibirsk: Science, 1985.

26. Kandel E.I. / Functional and stereotactic neurosurgery / Academy of Medical Sciences of the USSR. - M.: Medicine, 1981, 368 p.

27. Kuzovlev O.P. Correction of some cervical dorsopathy syndromes, 2005.

28. Kudelina N.Yu. Treatment of congenital visual impairment in children, 2007.

29. Goncharova O.V. Treatment of the effects of perinatal CNS hypoxia in children, 2008.

30. Marutaev M.A. Nature and music are numerical characteristics. M., 1972.

31. Petukhov S.V. Biomechanics, bionics and symmetry. M., Science, 1981.

32. Khazina L.V., Chaikina Y. Yu. Correction of the main neurological vertebro-and osteogenic neurological syndromes, 2003.

33. Rautian A.S. Biological meaning and nodal stages of the separation of processes of ontogenesis and phylogenesis // Sources of information in the phylogenetic systematics of plants. M .: Nauka, 1986, p. 68-69.

34. Rautian A.S. Paleontology as a source of information about patterns and evolutionary factors // Modern paleontology. T. 2. M .: Nedra, 1988.S. 76-118.

35. Rautian A.S. On the nature of genotype and heredity // General biological aspects of plant phylogeny. M .: Nauka, 1991.S. 91-93.

36. Rautian A.S., Rautian G.S. Some features of abnormal hair dryers // Phenetics of populations. Mater. III All-Union. conference M .: type No. 9, 1985.P. 196.

37. Bryukhovetskiy A.S. Post-Genome Technologies in Neurorestoratology: from Mapping and Profiling of Stem Cell Proteome to the Development of Personalized Cell Preparations for Regenerative Therapy of Neural Disorders - // IANR V & 9th GCNN Conference with ISCITT Symposium - 4-7 May, 2012, Xi ' an, Ch.

38. Moore X-L, Lu J., Sun L., Zhu C-J., Tan P. and M-C Wong Endothelial progenitor cells' 'homing' specificity to brain tumors //! Gene Therapy. - 2004. - 11. - P. 811-818.

39. Hill K., J. Bamber, G. Ter Haar. Ultrasound in medicine. Physical basis of application // M .: FIZMATLIT, 2008.

40. Bailey M.R., Khokhlova V.A., Sapozhnikov O.A., Karl S.G., Kram L.A. Physical mechanisms of the effect of therapeutic ultrasound on biological tissue (review) // Acoust. Zh., 2003, T. 49, No. 4, pp. 437-464.

41. Filonenko E.A., Khokhlova V.A. The effects of acoustic nonlinearity in the therapeutic effect of powerful focused ultrasound on biological tissue // Acoust. Zh., 2000, T. 46, No. 2, pp. 211-219.

42. Burov VA, Dmitrieva NP, Rudenko OV. Nonlinear ultrasound: destruction of microscopic biocomplexes and non-thermal effects on a malignant tumor // Doklady Akademii Nauk. Biochemistry, Biophysics, Molecular Biology, 2002, T. 383, No. 3, pp. 401-404.

43. Gavrilov L.R. High intensity focused ultrasound in medicine. / Ed. V.A. Akulicheva. - M., FAZIS Publishing House, 2013 .-- 656 p.

Claims (19)

1. The method of remote multi-wave electromagnetic radio neuroengineering of the brain, comprising sequentially the following stages: a) the design and layout stage, including: - conducting complex diagnostics, including high-resolution MRI examination of the brain (GM), MRI tractography of the pathways of the affected areas of GM, MRI angiography of GM vessels, positron emission tomography (PET) of GM or PET of the whole patient’s body, computed tomography (CT) GM with a resolution of at least 32 slices, cerebral electroencephalographic mapping (EEG) and / or magnetoencephalography (MEG) GM; - creation of an individual 3D map for modeling damage to nerve tissue (NT) by multi-level software merging of the obtained data from the comprehensive diagnostics for the subsequent determination of areas of NT damage; - marking the zones of damage to the nervous tissue (NT) of the GM on the scalp of the patient by using the apparatus of stereotactic radiotherapy and radiosurgery with the determination of the tilt angles and radii of the subsequent non-ionizing stereotactic effects of focused ultrasound (FUS) on NT GM; b) the stage of remodeling of the vascular bed of NT damage zones, including, depending on the etiopathogenesis of brain disease: - in case of tumors, microaneurysms, malformations, hemorrhages, the neovascularization of the zone of damage to the NT in the brain by destruction of the supply vessels using the ablative electromagnetic effect of the FUS of high intensity on the vessels of the zone of damage of the NT under the control of MRI and subsequent electromagnetic exposure by stereotactic ionizing radiation (II) in ablation mode, coagulation and necrotization of blood vessels; - in case of NT ischemia, NT atrophy, NT fiber demyelination, hypervascularization of the zone of NT damage in the brain by means of remote microcirculatory remodeling of the brain using the influence of structural resonance therapy (CPT) on NT in standard microcirculation modes and simultaneous use of low intensity FUS in the regime uniform mechanical vibration of NT in the zones of NT damage; c) the stage of cell restoration of NT lesion zones, carried out by targeted cell intervention in autologous mesenchymal stromal stem cell (MSCC), hematopoietic stem cell (HSC) and progenitor cell (PC) mobilized into the zone of damaged NT tract and including: - mobilization of MSCC, HSC and PC from the bone marrow into the peripheral blood of the patient, carried out using granulocyte colony stimulating factor (G-CSF); - activation of GM regeneration in the area of NT damage and temporary opening of the blood-brain barrier (BBB) for the penetration of MSCC, HSC and PC into the zone of NT damage by stereotactic irradiation of this zone with small doses of AI no more than 2 Gray; d) the stage of correction of the vegetative provision of the NT damage zone by combining exposure to the NT damage zones with electromagnetic non-ionizing radiation in the form of CPT in the vegetative exposure modes of “sympathetic” or “parasympathetic” with simultaneous or sequential exposure to low intensity FUS in the mode of moderate NT stimulation; e) the stage of dynamic integration of somatic and vegetative components by combining the effects of low intensity FUS on the NT damage zone in the GM with the simultaneous or subsequent exposure to CPT in moderate “synchronization” modes and f) the stage of rehabilitation of the functional state of the damaged NT GM by using a combination of electromagnetic non-ionizing effects of CPT in the "scanning" mode and stimulating effects of low intensity FUS. 2. The method according to p. 1, characterized in that they prolong the positive effect of cellular effects on damaged NT by the fact that in step c) after mobilization of HSCs and PCs, they additionally collect, standardize and cryopreserve mobilized bone marrow stem cells for intrathecal, intraventricular, intravenous or intraarterial administration into the patient’s body during his next hospitalizations. 3. The method according to p. 1, characterized in that they increase the permeability of the BBB, for which at stage c) before irradiation or during it, an intravenous infusion of an ozonized 0.9% saline solution is additionally carried out. 4. The method according to p. 1, characterized in that they increase the permeability of the BBB, for which at the stage c) after irradiation, additional low-intensity FUS is additionally affected. 5. The method according to p. 1, characterized in that they increase the safety and efficiency of the penetration of autologous MSCCs, HSCs and PCs into the NT damage zone by using CPT (structural resonance therapy) in this zone in step c). 6. The method according to any one of paragraphs. 1-5, characterized in that the effects of FUS, AI and SRT are carried out using a helmet assembled on the basis of a stereotactic neurosurgical apparatus equipped with holders for "finger" ultrasound sensors that provide focused ultrasound exposure.

Images