CN111790060A

CN111790060A - Device for treating brain diseases based on pulse semiconductor laser external irradiation technology

Info

Publication number: CN111790060A
Application number: CN202010294979.3A
Authority: CN
Inventors: 穆力越; 杨冰; 贺大林; 鲁怀安; 魏周文; 孟涛; 刘启; 刘琦; 陈荣
Original assignee: Xi'an Blue Top Medical Electronic Technology Co ltd
Current assignee: Xi'an Blue Top Medical Electronic Technology Co ltd
Priority date: 2020-04-15
Filing date: 2020-04-15
Publication date: 2020-10-20

Abstract

The invention relates to a device for treating brain diseases, in particular to a device for treating brain diseases based on a pulse semiconductor laser external irradiation technology, which solves the problems that the irradiation light of the existing device can not effectively penetrate through a skull, the irradiation treatment can be carried out on skull deep brain cells, and the irradiation treatment can not be carried out on the skull deep brain cells, and the adverse effect can not be generated due to overhigh temperature. The device comprises a helmet, at least one pulse type laser generator, a power supply and a main control box; it is characterized in that: the helmet comprises a helmet outer layer, a helmet middle layer and a helmet inner layer; the inner layer of the helmet is made of transparent material; the light-emitting end of the pulse type laser generator is fixed on the inner side of the middle layer of the helmet, and the laser penetrates through the inner layer of the helmet to meet the conditions: the peak power density is 1-500W/cm²The mean power density is less than 500mW/cm²The diameter of the laser spot is not less than 3mm, the laser pulse width is 1ps-10ms, and the wavelength is 600-1400 nm.

Description

Device for treating brain diseases based on pulse semiconductor laser external irradiation technology

Technical Field

The invention relates to a device for treating brain diseases, in particular to a device for treating brain diseases based on a pulse semiconductor laser external irradiation technology.

Background

Tissue pain within 30cm below human skin has been treated using Low-power laser therapy (LLLT) for decades. To date, researchers all over the world have completed over 500 various clinical trials and over 4000 laboratory animal studies, confirming that such red and infrared light with a wavelength of 600-. The biophysical principle is as follows: medium and low power density (mW/cm) using red to near infrared wavelengths with narrow band spectra²) And a large energy density (J/cm)²) In a non-destructive and non-thermal manner, to produce Photobiomodulation (PBM) at the cell level. PBM uses low-intensity narrow-band light to perform non-invasive or non-invasive irradiation on human tissues, and regulates a series of biochemical actions at a cell level, including improving the main treatment effects of cytochrome oxidase activity, cellular oxygen consumption, nitric oxide generation and the like, and promoting the vasodilatation of an irradiated area, improving blood flow, improving the speed of cellular rehabilitation and nerve rehabilitation and other subsequent treatment effects. The light sources used by the PBM are all narrow-band light sources, including lasers, LEDs, bulbs with narrow-band filters, and the like.

It is currently accepted that the mechanism of PBM is closely related to Cytochrome C Oxidase (CCO) key proteins. The protein is located at the end of cell mitochondria, is an endogenous neuron photoreceptor, belongs to a part of a mitochondrial respiratory chain in cells, is responsible for catalyzing the reduction of oxygen molecules in glucose metabolism into water molecules, and is coupled with the function of a proton pump. Cytochrome oxidase is present in all human cells and is more abundant in neurons with high energy requirements. CCO is the primary photoreceptor for light in the red to near infrared region of the absorption spectrum. When COO is stimulated by light, it not only increases the activity of the electron transport chain in the cell mitochondria, but also regulates Nitric Oxide Synthesis (NOS). NOS catalyzes Arginine (Arginine) in cells to produce Nitric Oxide (NO). NO is a highly lipophilic gas, which is thawed with Soluble guanylate Cyclase (sGC), converting Guanosine Triphosphate (GTP) into Cyclic Guanosine Monophosphate (cGMP), and increasing the expression of cGMP in cells. A study by Poyton et al (2011) shows that PBM is likely to produce NO in two ways: 1) when the cytochrome oxidase is light-stimulated, NO may be transiently released from the cytochrome oxidase catalytic site; 2) when oxygen levels are reduced, i.e., hypoxia inducible factor (HIF-1 α) is increased, cytochrome oxidase activity itself may produce NO. Cytochrome oxidase enzymes function to catalyze the formation of water at high oxygen levels and the formation of NO at low oxygen levels of nitrate. Thus, under light stimulation, the increase in NO in turn increases cGMP expression in the cell, which can cause vasodilation and increase blood flow. It is believed that hypoxic injury or dead body cells cause nerve cells to produce excess NO and inhibit the enzymatic activity of CCO. However, photons of red and near infrared light are able to separate out excess NO, restoring physiological levels of NO that enable the mitochondrial membrane to better metabolize oxygen and glucose, thereby producing more Adenosine Triphosphate (ATP). ATP is the major source of cellular energy in the regulation of cellular processes.

CCO is a terminal enzyme located in the electron transport chain of the outer mitochondrial membrane. Through a series of redox reactions, electron transport chains facilitate the transfer of electrons across the inner mitochondrial membrane. The end result of these electron transfer steps is the generation of a proton gradient across the mitochondrial membrane, driving the activity of ATP synthase (ATP Synthesis). ATP synthase produces ATP from Adenosine Diphosphate (ADP). CCO mediates electron transfer from cytochrome c to molecular oxygen. CCO is a complex protein consisting of 13 different polypeptide subunits, also containing two heme centers and two copper centers. Both the heme center and the copper center can be oxidized or reduced, yielding sixteen different oxidation states. Each oxidation state has a slightly different absorption spectrum, but CCO is almost the only one in biomolecules with significant absorption in the red and near infrared spectra. According to current studies, absorption of red and near infrared light by biological tissues of more than 50% can be attributed to CCO. During PBM, light not only increases mitochondrial membrane potential (Δ Ψ) and proton gradient (Δ pH), but also alters mitochondrial optical properties, increases ADP/ATP exchange, ribonucleic acid (RNA) and protein synthesis in the mitochondria, and increases oxygen consumption. A plurality of researches find that PBM has certain wavelength specificity on the influence of mitochondria of different tissues, and CCO has stronger light absorption at 665nm and 810nm in terms of brain nervous tissues.

In 2019 Nobel physiologically or medically awarded leading Kaelin, Ratcliffe and Semenza et al discovered in the last 90 th century that cells sense and adapt to the supply of oxygen through the interaction of VHL, hypoxia inducible factor (HIF-1 α), and hydroxyl (OH). Yueh-Ling Hsieh, a Taiwan scholarian in 2012, discovered that low-power laser irradiation can regulate HIF-1a activity, improve tissue hypoxia/ischemia and neurofascial inflammation, and promote nerve regeneration. Hamblin university scholars Hamblin also mentioned BPM down-regulation of HIF-1a levels in 2013. HIF-1 α is scarcely contained in the cells when oxygen levels are high. However, when oxygen levels are low, HIF-1 α levels increase. The down-regulation of HIF-1a levels by BPM indicates an increase in oxygen levels in the cell.

Since brain cells require a large amount of energy for their activities, cytochrome oxidase is more abundant in brain neuronal cells. Since cytochrome oxidase plays an important role in cellular respiration, the expression of cytochrome oxidase is therefore also a sensitive marker of neuronal activity. Photons from the action of PBM not only accelerate the catalytic activity and oxygen consumption rate of cytochrome oxidase, increasing ATP production in the brain, but also induce a number of secondary cellular effects. These subsequent secondary effects include activation of gene expression in cells, increased metabolic capacity of neurons, and increased cell survival.

PBM can enhance the activity of the electron transport chain in brain cells while also modulating NOS. NOS is typically activated by glutamatergic receptors (AMPAR and NMDAR) to produce NO, which acts as a second messenger regulating cytochrome oxidase activity, further regulating cellular respiration. A study by Uozumi et al (2010) indicated that after 5 minutes of PBM irradiation treatment, there was a peak increase in NO followed by a decrease. As cerebral blood flow increases, a local increase in NO leads to vasodilation and hemodynamic response.

There are many kinds of brain diseases, including neuron degeneration brain diseases, traumatic encephalopathy sequelae, vascular encephalopathy sequelae, infectious encephalopathy sequelae, metabolic encephalopathy, psychopsychological encephalopathy, etc. Some brain diseases are known causes or known partial causes, such as vascular brain diseases, i.e., cerebral infarction, cerebral hemorrhage, hypoxic brain injury, atherosclerotic stroke, embolic stroke, ischemic stroke, acute traumatic brain injury, chronic traumatic brain injury, neurodegenerative diseases, depression, parkinson's disease, etc., and there are many diseases for which the true cause is not known at present, such as Alzheimer's Disease (AD). Many brain diseases can lead to dementia. Dementia can be broadly classified into congenital dementia and acquired dementia. Including senile dementia, brain injury dementia and the like, which belong to acquired dementia caused by degenerative brain diseases. AD patients are generally accompanied by senile dementia of different strengths. Current research has found that PBM is beneficial to some extent in brain diseases other than congenital dementia.

Alzheimer's disease is a common, chronic progressive neurodegenerative disease, gradually leading to dementia, is a degenerative disease of the nervous system mostly occurring in the elderly, and is clinically characterized by progressive memory impairment, language disorder, impairment of visual spatial function, bradycardia, attention deficit and affective disorder, etc. Its etiology and pathogenesis are complex with many genetic and environmental risk factors, including stress and insulin resistance. Typical pathologies are characterized by amyloid deposition, neurofibrillary tangles, neuronal loss and abnormalities of axons and synapses, particle vacuolization, and the like. The up-regulation of the expression of many genes and of various pathogenic pathway factors leads to the down-regulation of amyloid beta peptide (a β) deposition, tau hyperphosphorylation tangles, inflammation, reactive oxidative stress, Reactive Oxygen Species (ROS), mitochondrial disease, insulin resistance, methylation defects, and neuroprotective factors. Although the pathological features of AD, namely β -amyloid plaques and tau tangles, are well established, many of the associated causes are still unclear and require extensive research.

In addition to cancer, AD and senile dementia may be one of the most alarming health problems facing the world today. With the gradual increase of the aging population of the society, the incidence rate of AD is in a gradually rising trend. According to statistics of World Alzheimer Report2018, nearly 5000 million AD patients exist in the World in 2018, and the number of the AD patients is estimated to increase to 1.52 hundred million people by 2050. The published data shows that about 1000 million people suffer from Alzheimer disease in China, and the number of the Alzheimer disease is the most serious country in the world. With the aging of population accelerating, it is expected that the number of patients in China will reach 4000 million in 2050 years. There are very few drugs that can be effectively used to treat AD and dementia at present. Over the past few decades, numerous clinical trials of the drug tested have failed to reverse, improve, and even stabilize the progressively declining cognitive function of dementia patients.

Gonzalez-Lima et al (1998) and Valla et al (2001) demonstrated that cognitive impairment and neurodegeneration associated with dementia manifest as a local deficit in brain metabolism early in the disease. For example, in patients at risk for AD, an early decrease in metabolic activity of the brain, in particular a decrease in cytochrome oxidase activity, can be detected. Likewise, phenotypic expression of diseases such as major depression and post-traumatic stress disorder is associated with decreased metabolic capacity of the frontal lobe forebrain region. PBMs are expected to enhance the metabolic capacity of those areas exhibiting functional defects, thereby increasing the functional connectivity of the brain neural network.

Many studies have found that mitochondrial dysfunction, insufficient ATP supply and oxidative stress are contributing factors to almost all forms of brain disease. Several neurological disorders, including major depressive disorder, brain trauma, Parkinson's disease, and AD are associated with these several factors.

In the context of PBM molecular studies, Lu et al (2017) demonstrated that PBM can improve mitochondrial dynamics, increase mitochondrial membrane potential, reduce oxidized mitochondrial DNA, inhibit apoptosis, increase expression of mitochondrial antioxidants, increase CCO activity and ATP levels, inhibit a β -induced reactive gliosis, inflammation and tau hyperphosphorylation. Lee (2017) et al suggested that NO release due to PBM is responsible for increased cerebral blood flow. NO is a major neuronal signaling molecule and has the ability to trigger vasodilation, among other functions. For this purpose, it first stimulates soluble guanylate cyclase to form cyclic GMP (cGMP). cGMP then activates protein kinase G, resulting in Ca²⁺And calcium activates the opening of potassium channels. Ca²⁺The decreased concentration prevents the myosin light chain kinase from phosphorylating myosin molecules, thereby relaxing smooth muscle cells of the vascular and lymphatic walls. This vasodilation then promotes blood circulation, which in turn improves the oxygenation process of the brain.

Oxidative stress occurs when there is an imbalance between the production of Reactive Oxygen Species (ROS) and the body's ability to resist. When the active oxygen is excessive, they become harmful by the antioxidant. Many studies have found that oxidative stress is associated with various neurological disorders, such as major depression and traumatic brain injury, cardiovascular disease and AD. PBM can regulate the balance of ROS at the cellular level, alleviating the condition.

PBMs can achieve improved metabolic function at the cellular level by increasing intracellular ATP production. There is a great deal of research evidence that PBM can protect nerves at the cellular level, protect cells from damage, promote their survival, prolong life span, and reverse apoptotic signals. One study by Oron et al (2006) found that transcranial pbm (tpbm) stimulated nerve cell growth. At the tissue level, several studies have demonstrated that tPBM enhances cerebral blood flow and oxygenation processes and also exhibits certain anti-inflammatory effects.

Similar to the results achieved by physical exercise, tPBM promotes the regeneration and relaxation of microvasculature in the brain, improving blood circulation. These improvements in blood flow functionality can effectively reduce the probability of microvascular rupture in the brain of elderly patients, reduce the mortality of brain cells due to microvascular rupture, reduce the probability of dementia and delay the onset of dementia.

Pbm (lllt) has long used red or near infrared light for wound healing, pain relief, treatment of inflammation and prevention of tissue death. In recent years, there have been many high-level studies abroad to treat various brain diseases by irradiating red light or near infrared light to the head (tPBM) in a non-invasive manner through animal experiments, human clinical trials, and the like. Experimental animals with brain diseases (mice or rats) treated with tPBM by Ando et al (2011) and Salehpour et al (2017) were found to have increased amounts of ATP in their brains. De Taboada et al (2011) irradiated the head of amyloid beta protein precursor (A beta PP) transgenic mice with a 810nm laser at different irradiation doses (3 times per week for 6 months) and found a significant reduction in the number of A beta plaques in the brains of the mice. PBM can cause dose-dependent reduction in amyloid burden, soluble a β PP α, and encephalitis markers. ATP levels and mitochondrial function are both increased. The cognitive function measured by the morris water maze in mice was also improved.

Hamblin (2016), Hennessy and Hamblin (2016), Thunshelle and Hamblin (2016) used the tPBM approach to treat a variety of brain diseases, including sudden disorders (stroke, traumatic brain injury, TBI, cerebral vascular ischemia), neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, dementia) and psychiatric disorders (depression, anxiety, post-traumatic stress disorder), confirming that tPBM is not only effective, but also does not have any observable side effects.

Saltmarche et al (2017) reported a human clinical trial of a small sample of tPBM for the treatment of AD. The clinical trial included 5 cases diagnosed with mild to moderate severe dementia (Mini-Mental State Exam, MMSE score 10-24). The study used Neuroalpha (810nm, 10Hz pulsed LED) PBM therapy from Vielight corporation in combination with transcranial and intranasal PBM to treat default network cortical nodules of the brain (bilateral medial prefrontal cortex, anterior neurite/posterior cingulate gyrus, horn gyrus and hippocampus). Each patient was treated with transcranial tPBM/intranasally PBM weekly in the office and daily at home for 12 weeks of treatment. Follow-up was carried out 4 weeks after 12 weeks, during which time no treatment was given. At 12 weeks, all patients were found to have significantly enhanced cognitive function (MMSE and ADAS-cog), improved sleep, and reduced restlessness, anxiety and loitering mood. No adverse side effects were found. However, these improved effects were observed to decline rapidly during the 4-week follow-up period. This indicates that in order to continuously improve and alleviate dementia, patients need to be treated with transcranial tPBM weekly or even daily.

Although the safety and effectiveness of tPBM are confirmed by a plurality of animal experiments, a plurality of phenomena inconsistent with the animal experiment results are still encountered when the tPBM is used in human clinical treatment. The Henderson and Morries research group (2019) considered that the use of LEDs or low power lasers was not effective for irradiating deep tissues of the brain, such as the hippocampus and parahippocampus, due to the blocking and absorption of light by the hair, and the absorption and scattering of light by various tissues including the scalp, skull, and near the outer layers of the brain. The hippocampus of a normal adult is located about 5-10cm from the skull, and the specific distance varies depending on the measurement location and the individual. As measured from the skull bone, about 7cm or so on average. The hippocampus is an important organ in the default network of the brain, playing a critical role in short-term memory function. Such tpbms can be difficult to achieve good clinical results if the photons of the LED or low power laser (less than 0.5W) do not reach the hippocampus and hippocampal lateral return tissues in significant amounts, or other vital organs in the default network. The research group of Henderson and Morries suggests that effective tPBM should use a near-infrared laser with a power of several watts, and especially should use a pulsed laser.

In order to effectively irradiate laser to the inside of the brain, Maksimovich et al (2004-. Specifically, under local anesthesia, the common femoral artery was punctured and placed into a catheter of 6-7Fr in diameter according to the Seldinger technique, and then an optical fiber of 25-100 μm in diameter was introduced into the catheter, and a low power 632.8nm wavelength helium neon laser was used to transmit through the optical fiber and irradiate the distal end of the anterior cerebral artery and the middle artery. Although the results of the Maksimovich et al study demonstrated the short-term and long-term effectiveness of PBM in the treatment of ischemic brain diseases (brain degeneration, senile dementia, cognitive impairment, cerebral arteriosclerosis, chronic cerebrovascular dysfunction, etc.) and degenerative brain diseases (alzheimer's disease), such traumatic surgery has not received wide medical acceptance.

By utilizing the safety and the effectiveness of PBM in treating brain diseases, a plurality of related products and patents exist at home and abroad. A relatively representative product abroad is the transcranial and intranasal PBM illumination from Vielight, canada, using LED light sources; an LED light source helmet from photomodex, USA; helmet transcranial irradiation with LED light source from the company THOR Photomedicine, uk; an LED light source helmet from cognitolate, ireland, etc. The domestic products are products such as those which are irradiated to the brain acupuncture points by the Riley laser technology Limited company in Tianjin, or those which are irradiated to the head by the ears by the laser of other companies. The light sources in these above products are low power light sources with an optical power of less than 5W.

U.S. Pat. No. US8,535,361B2, U.S. patent application Nos. US2014/0358199A1, and US2018/0256917A9 are all inventions by doctor Lew Lim, Vielight corporation. In these three patents, Lim doctor discloses a device that uses a battery-powered light source of no more than 20mW placed in a nostrils. The nasal cavity irradiation device can irradiate light to brain parts such as hippocampus and the like from an nasal cavity channel through a thin skull. The invention of the three us patents has the advantage of light design and can use the lower price LED as the light source. It is also clear that the low power of the LED light source does not penetrate the skull efficiently, effectively illuminating brain cells deep within the skull to achieve the desired effect. According to Henderson et al (2019), the depth of transnasal LED illumination typically does not exceed 2 cm.

Luis De Taboada et al, and the company Phototera, in the United states and Europe, have filed several patents including U.S. Pat. No. 7,303,578B2, U.S. Pat. No. 7,309,348B2, U.S. Pat. No. 7,575,589B2, U.S. Pat. No. 8,308,784B2, U.S. Pat. No. 10,188,872B2, U.S. Pat. No. 10,357,662B2, and European patent application No. EP2,489,403A2, among others. In these patents, De Taboada et al disclose the treatment of brain diseases by irradiating the head with red to near-infrared laser light, respectively, which is largely classified into three types, the first is to irradiate the head with laser light coupled with one or more optical fibers fixed on a helmet with a plurality of holes through a complicated emitting head with optical lenses. The second method is to fix a plurality of semiconductor lasers to a specific helmet and irradiate the head with the semiconductor lasers. The third is to direct the laser through a fiber into a device with multiple fibers, called a blanket, to irradiate the head. The first and second designs require a very complex set of optical, mechanical, heat dissipation and electronic control devices due to the direct laser irradiation on the head, and do not have a laser safety automatic protection device, so that a human patient who is not trained professionally cannot be treated. Third, although the helmet is lightweight by using an optical fiber to guide the laser into the optical blanket, the helmet is lightweight because: 1) The helmet is free of a light feedback detection and interlocking device, and when the optical fiber is accidentally broken in the using process or the local laser irradiation is too strong, the helmet can cause injury to a patient; 2) continuous emission (CW) laser is used, when the laser power is high, the laser can damage the external tissues of the head, such as hair, scalp and the like, and when the laser power is too low, the laser can not irradiate the deeper area of the brain; 3) no indicating light exists under the infrared irradiation condition, and an intelligent electric control device does not exist, so that a person who is not trained professionally cannot treat the patient. In summary, the inventions disclosed in the series of patents to Luis De Taboada et al have many design deficiencies, high manufacturing costs, insecurity and technical problems that are difficult to implement.

Massachusetts institute of technology Li-Huei Tsai et al, in a series of patent applications, US20170304584A1, US20190105509A1, US20190126062A1, US20190240443A1, disclose the use of weak light having a frequency of 10-100Hz for stimulating the eyes and head, sound having a frequency of 10-100Hz for stimulating the ears, and mechanical vibration having a frequency of 10-100Hz for stimulating the brain for the treatment of AD and dementia. The invention is based on the principle that optical signals or electromagnetic wave signals, acoustic signals or mechanical vibration signals stimulate and resonate brain waves, belongs to the theory and mechanism of Optogenetics (Optogenetics), and is not based on the PBM energy biomedical principle (including promoting nerve cell repair, regeneration, improving cerebral blood flow and cerebral blood oxygen content and the like) with certain energy to treat AD, dementia and other cerebral diseases.

The invention discloses a Chinese patent with an authorized publication number of 'CN 201768276U', and discloses a treatment device for stimulating acupuncture points on the head by using LED light, wherein a near-infrared LED lamp is aligned to corresponding acupuncture points on the head of a patient, and the LED light can penetrate through the scalp and the skull to reach damaged brain cells, so that the treatment purpose is achieved through the comprehensive action of acupuncture point stimulation and photobiological regulation. This patent, similar to the other treatments using LEDs described above, has the advantages of a simple design and low cost, but also has the disadvantage that the low power of the LED light source does not effectively penetrate the skull, effectively irradiating the deep brain cells within the skull to achieve the desired effect. This is because, as mentioned above, any LED has a low brightness and low optical power compared to a laser, and cannot allow enough photons to reach brain tissue over 2cm deep. If multiple LED arrays are used, heat dissipation means, such as a fan, is necessary for the LED arrays, making the overall helmet cumbersome. In addition, the plurality of LED arrays can only increase the irradiation area, and cannot increase the irradiation depth.

The invention discloses a near infrared light therapeutic apparatus for treating brain diseases, which is a Chinese patent with the application publication number of CN 104162233A, and discloses a near infrared light therapeutic apparatus.A plurality of near infrared LED light sources are fixed on a helmet-shaped hemispherical support, and the main light distribution design principle of the near infrared light therapeutic apparatus is similar to the first or second design of Luis De Taboada and the like. However, in terms of the light source, the invention also uses an LED, and even if the LED is operated in a blinking mode, the peak power of the light is very low, and the LED cannot irradiate tissues with a depth of 2cm or more in the brain. Because the design belongs to the close fitting type design, if the LED is replaced by the semiconductor laser, the laser spot on the hair or the scalp is too small, and the laser power density is too large to damage the hair or the scalp.

The invention discloses a wearable photoelectric integrated autism therapy instrument, and Chinese patent with application publication number of CN 109432607A, which discloses a method for treating brain diseases such as autism by irradiating a brain with LEDs with multiple wavelengths from red light to near infrared and combining 2Hz or 40Hz pulse current stimulation. Chinese patent entitled "a red helmet" entitled "CN 204890973U" describes another helmet that uses a plurality of red LEDs for illuminating the brain. Both of application publication No. CN109432607 a and publication No. CN 204890973U use LEDs as light sources, and as described above, the design using LEDs has the advantages of simple design and low cost, but also has the disadvantage of using LEDs for irradiation, i.e., the deep brain cells in the skull cannot be effectively irradiated to achieve the desired effect.

The invention discloses a brand-new earphone type laser health care therapeutic instrument with multiple working wavelengths, and a Chinese patent with the application publication number of CN 106730404A, and discloses a method for irradiating ear tissues and brain blood flowing through the ear by multi-wavelength laser transmitted by optical fibers so as to achieve the specific therapeutic purpose. The invention is similar to the technology of nasal cavity irradiation, the area irradiated by the ear is limited, therefore, the brain area and volume of the effective irradiation area are limited, and the expected treatment effect is difficult to achieve. The ear irradiation laser and the nasal cavity irradiation laser are similar, and the laser power cannot be too high, so that thermal damage can be caused to the irradiation part.

The invention discloses an intelligent photodynamic hair growing helmet, and discloses a helmet for treating alopecia and stimulating hair growth by utilizing PBM or LLLT, belonging to Chinese patent with the application publication number of CN 110141797A. In order to avoid covering the scalp by the hair in the prior art, the invention uses a plurality of needle-shaped light guide channels to bypass the hair and directly irradiate the scalp with the light. Since the laser used for treating alopecia is a low power continuous mode (CW) laser, the power emitted by a single laser is generally less than 20mW, and the laser cannot effectively penetrate through brain tissue, and therefore cannot be effectively used for treating brain diseases.

The invention relates to a hair-growing device, and the Chinese patent with the application publication number of CN 108114378A discloses a hair-growing device which uses a plurality of small-power lasers, such as a plurality of red lasers with the wavelength of 700nm and the power of 620 mW and the power of 700nm, and irradiates on the scalp to generate 1-20mW/cm²The irradiation power density of the helmet, and the flexible self-adaptive helmet hair-growing device can be output in a pulse mode so as to enhance the development of hair. The disadvantage of this invention is that since the laser sources are fixed to a flexible helmet which limits the heat dissipation of each laser source, only a very low power laser source, for example a 5mW laser source, can be used, even in the case of pulses, producing no more than 20mW/cm on the scalp²The laser irradiation power density of (1). This power density may produce PBM effects on the scalp portion, but is insufficient to penetrate the skull to produce an effective effect on the deep brain cells. The results of the present study show that even with the use of LED light sources, it should be possible to generate an optical power density of at least several tens of milliwatts per square centimeter at the scalp site, for example, the Neuro Alpha product, clinically validated by Vielight, has a power density index of 25-150 mW/cm²。

The invention discloses a wearable photoelectric integrated autism therapy instrument, and discloses a device for treating autism by directionally irradiating a brain area related to autism with red and near-infrared LED light, wherein the Chinese patent with the application publication number of CN 109432607A is named as 'a wearable photoelectric integrated autism therapy instrument'. This device is similar to the patent by doctor Lew Lim, but emphasizes the specificity of the illuminated area.

The invention discloses an acupuncture point positioning cover for laser treatment of brain diseases, and an authorized publication number of Chinese patent CN 204121616U. Such a positioning cap is similar to the helmet described in the Luis De Taboada et al series of patents, which helmet has a plurality of holes left therein for fixing the light source. The invention discloses a Chinese patent with the application publication number of CN 107998516A, which is named as a helmet type therapeutic instrument and discloses a device based on acupoint irradiation and magnetic therapy. The design of the device is not adapted to PBM treatment of deep brain cell tissue.

The invention discloses a handheld low-level laser instrument and a low-level laser beam generation method, and a Chinese patent with the application publication number of CN 108325090A. The invention relates to a handheld low-level laser treatment device, and discloses another handheld low-level laser treatment device in Chinese patent with the application publication number of CN 102573991A. Both of these inventions beam-shape the treatment laser through one or more corrective lenses to achieve the desired irradiation parameters for treatment, and the operator needs to treat the patient in a hand-held manner.

Since the discovery of the brain Default Network (the brain's Default model Network) in 2001 taught by Raichle, university of st louisis washington, usa, 3000 academic studies have discussed the application and contribution of the brain Default Network in neuroscience, cognitive science, brain disease research, neurophysiology and cytology worldwide. The default network of the brain consists of brain organs such as medial prefrontal cortex, posterior parietal subcortical, splenic posterior cortex, hippocampus, hippocampal juxtapose, cingulate posterior cortex, and adjacent anterior process nerves and horny gyrus. For normal adults, these organs are mostly at a depth of at least 3cm below the scalp, with both the hippocampus and the hippocampal paradox located in the midbrain exceeding a depth of 5 cm. However, the existing therapeutic device based on continuous light irradiation of brain can not effectively penetrate the brain tissue above 5 cm.

Disclosure of Invention

The invention aims to provide a device for treating brain diseases based on a pulse semiconductor laser external irradiation technology, which aims to solve the technical problems that irradiation light emitted by the existing treatment device cannot effectively penetrate through a skull to carry out irradiation treatment on brain cells at the deep layer of the skull, and how to realize the irradiation treatment on the brain cells at the deep layer of the skull without generating adverse effects due to overhigh temperature.

On the way from the laser light emitting point to the irradiated tissue inside the brain, the laser light is reflected, refracted, absorbed and scattered by many objects on the light path. For the sake of brevityOnly the laser power density I (W/cm) after absorption and scattering by the tissue is considered²) A change in (c). According to the universal Beer-lambert (Beer-Lamber) law shown in the following formula (1):

in the formula (1), I₀Is the incident laser power density; alpha is alpha_ɑAbsorption coefficient (1/cm) of light for human tissue; alpha is alpha_sScattering coefficient (1/cm) for human tissue to light; d is depth (cm); i is the laser power density at depth D. The absorption coefficient and scattering coefficient of light at different wavelengths may also be different for the same substance. In the case of tPBM, the laser light is absorbed and scattered by different substances in the light path, such as hair, scalp, skull, water, blood, meninges, cerebral gray matter, white matter, etc. The laser power density at a certain depth D of the head is a value after all the substances on the optical path are absorbed and scattered, and the value can be obtained by an integral equation shown in the following formula (2):

in the formula (2), I_D(λ) is the laser power density at depth D at wavelength λ; i is₀(λ) is the incident laser power density at wavelength λ; the range of the light wavelength lambda is 600-1400 nm; i is one of the substance types, namely hair, scalp, skull, water, blood, meninges, cerebral gray matter, white matter and the like; n is the total number of all species on the optical path; alpha is alpha_iɑ(z, λ) is the optical absorption coefficient for substance i at position z at a wavelength λ; alpha is alpha_is(z, λ) is the light scattering coefficient for substance i at position z at wavelength λ. It can be seen that as the depth D increases, the attenuation of light intensity by various substances in the light path decreases exponentially. As far as is known, the intensity of light passing through the hair, the skull, only, is less than 1% of the intensity of the incident light. In view of the inability to carry out I on living human body_DOf the optimum irradiation intensity I₀There is no clear understanding. For a particular subject to be treatedThe parameters of specific parts in the brain, such as the hippocampus 5-7cm in the skull, in the irradiation light path are basically fixed values, and for effective tPBM irradiation, the incident laser power density I must be increased₀So that there is sufficient I on the hippocampus_D。

To effectively use tPBM to treat brain diseases, such as ischemic brain diseases and degenerative brain diseases, it is necessary to have enough photons reach the organs of the default network and be absorbed by the cells in the default network. In order to enable red to near infrared laser to penetrate through brain tissues with the depth of more than 10cm, the invention provides a novel design, which is technically characterized in that:

1) using one or more lasers as light sources within a treatment helmet, each light source having a maximum peak power in excess of 5W;

2) the laser light source may be a vertical emitting VCSEL semiconductor laser generator, a side emitting semiconductor laser generator, or a fiber coupled laser generator. The semiconductor laser generator package may be a surface mount package, a TO package, a C package, a COS package, or other type of package.

3) The light source with the same wavelength or a plurality of light sources with different wavelengths in the treatment helmet can be spatially arranged in a pre-designated mode, and one or a plurality of lasers with specific wavelengths are output according to treatment requirements in an electronic control mode;

4) each laser luminous point in the treatment helmet is spaced from the irradiation surface by a certain distance, so that the diameter of a laser spot on hair or scalp is not less than 3 mm.

5) The peak power density I of the laser light source in the helmet is enabled by driving the laser light source synchronously or asynchronously through a pulse current source or other control modes₀Can reach 10W/cm²Above, the maximum can reach 500W/cm²；

6) The average power density of the incident laser on the irradiation surface is less than 500mW/cm by adjusting the duty ratio of the laser pulse²Avoiding damage of the laser to any tissue on the irradiated light path, including hair;

7) the pulse width of the laser in the helmet can be between 1ps and 10ms by electronically controlling the pulse width of a pulse current source or adopting pulse laser modulated by photoelectricity;

8) by using the physical principle that the laser pulse width and the laser peak power are in inverse proportion under the condition of the same laser pulse frequency and the same laser average power, the laser peak power can be changed by changing the laser pulse width, and then the effective depth irradiated by the tPBM is adjusted. Generally, the higher the peak power of the laser, the deeper the depth to which the laser can effectively reach;

9) a part of light sources in the treatment helmet can emit laser to irradiate specific target organs in the brain in an electronic control mode, and meanwhile irradiation on non-target brain tissues is avoided;

10) by adopting a multi-point covering irradiation mode, two or more than two laser light sources in the treatment helmet irradiate a certain part of the deep layer of the brain in a directional manner, so that the organs at the part are treated by sufficient tPBM;

11) the laser light sources with different wavelengths can be used according to specific requirements to arrange the spatial distribution of the laser light sources in the treatment helmet by utilizing the fact that the penetration depths of the lasers with different wavelengths in human brain tissues are different and the internal organs of the brain which need to be mainly treated by different patients are different;

12) the treatment helmet can adopt an active heat dissipation mode to reduce any discomfort of a treated person caused by laser heating, and the active cooling mode can be water cooling or air cooling;

the design principle of the invention is that the pulse laser with high peak power and low average power is used for irradiating the human brain, and PBM is used for treating non-congenital brain diseases, including ischemic brain diseases and degenerative brain diseases. The laser may be a semiconductor laser. Semiconductor lasers are characterized by being driven by high pulse currents to produce relatively high energy laser pulses in a short period of time. The laser pulse width can be in the range of 1ns-10ms, and the laser pulse width can be adjusted through the electric pulse width of a pulse current source and can also be generated through other photoelectric modes. The laser peak power P_pIs defined by the following formula (3):

in formula (3), E is the laser pulse energy (J, Joule); τ is the pulse width (s, sec); laser peak power P_pIn units of watts (W). The energy and width of the laser pulse can be adjusted by adjusting the intensity and width of the drive current pulse. Peak power density of the laser equal to P_p/(spot area). Under the condition of a certain wavelength, the effective penetration depth of the laser in human tissues is in direct proportion to the peak power density of the pulse, and the effective irradiation range is in direct proportion to the area of a light spot. While tPBM irradiation passes through a variety of tissues from the upper hair, scalp, blood, water, skull, meninges, gray matter, white matter, etc., the specific effective depth of irradiation, area, volume are also related to many other individual factors, high peak power means deeper penetration depth. In order to effectively irradiate the tissue PBM with the depth of 5-10cm by the laser, the peak power density of the laser designed by the invention can reach up to 500W/cm²。

The wavelength range of the semiconductor laser is 600-1400 nm. Laser light in this wavelength range is absorbed by human tissue and generates heat. According to the principle of conservation of energy, all of the laser energy incident on the head is substantially completely absorbed and converted into heat energy, heating the head. According to the mechanism of PBM treatment, heat does not provide a benefit to a series of biochemical effects such as ATP production by cells, but excessive heat may cause discomfort to the person to be irradiated. Laser heating is a cumulative effect, proportional to the average power of the laser. Thus, the present invention contemplates a low laser average power to reduce the laser heating effect of the treatment helmet on the patient. Average power P of laser_avgCalculated using the following formula (4) or (5):

P_avg＝Ef (4)；

P_avg＝P_pD_c(5)；

(4) wherein f is the repetition frequency of the laser pulse. (5) In the formula, D_cIs the duty cycle of the laser pulse over a time period. Lowering f or lowering D_cAll can beThe average laser power is reduced. At D_cIs 0.1% and the laser peak power density is 500W/cm²In the case of (2), the average power density of the laser beam at the irradiation spot was only 0.5W/cm². Such low average power densities are safe for hair, skin and skull. Less than about 1% of the energy after passing through the skull, i.e. less than 5mW/cm²Can be used for illumination of the PBM, so that low optical power densities are also safe for various soft tissues in the brain without any thermal effects.

Many brain diseases, including ischemic brain diseases and degenerative brain diseases, involve multiple brain tissues, such as the default network of the brain, extending almost throughout various depths. In order to make the laser irradiate at a specific depth, the invention designs that the peak power P of the laser is adjusted_pThe effective illumination depth is adjusted. P_pCan be adjusted by varying the pulse width τ alone, the laser pulse energy E, or both. The invention designs that a plurality of laser generators with different wavelengths are simultaneously arranged in a treatment helmet by utilizing the different penetration depths of the laser with different wavelengths in the brain tissue, and the laser generators can emit the laser with a certain specific wavelength according to the required treatment depth during treatment. Due to the combined effect of water and blood on laser absorption and scattering, the laser wavelength will penetrate deeper into soft tissue at 800-. In order to make the laser irradiate the tissues of a specific area, the invention designs that the laser generator of the specific area is opened according to the treatment requirement, and the laser generators of other areas in the helmet are closed.

The invention adopts the technical scheme that a device for treating brain diseases based on a pulse semiconductor laser external irradiation technology comprises a helmet, at least one pulse laser generator, a power supply and a main control box; it is characterized in that:

the helmet comprises a helmet outer layer, a helmet middle layer and a helmet inner layer; the middle layer of the helmet is made of a heat-conducting material; the inner layer of the helmet is made of transparent materials;

the light emitting ends of the pulse type laser generators are all fixed on the inner side of the middle layer of the helmet;

the laser emitted by the light emitting end of the pulse type laser generator penetrates through the inner layer of the helmet (namely the laser reaching the surface of the skin), and the following conditions are met: the peak power density is 1-500W/cm²The mean power density is less than 500mW/cm²The diameter of the laser spot is not less than 3mm, the laser pulse width is 1ps-10ms, and the wavelength is 600-1400 nm.

Further, the pulsed laser generator is a semiconductor laser generator, and the semiconductor laser generator is a VCSEL semiconductor laser generator;

and an air space of 10-30mm is arranged between the light emitting end of the VCSEL semiconductor laser generator and the inner layer of the helmet.

Further, the pulsed laser generator is a semiconductor laser generator, and the semiconductor laser generator is a TO-packaged pulsed semiconductor laser generator.

Further, the pulse type laser generator is a semiconductor laser generator, and the semiconductor laser generator is a C-packaged semiconductor laser generator or a COS-packaged semiconductor laser generator;

and the light outlet end of the C-packaged semiconductor laser generator and the light outlet end of the COS-packaged semiconductor laser generator are both provided with protective covers with light outlet windows.

Further, the pulsed laser generator is a fiber-coupled laser generator;

the optical fiber coupled laser generator comprises at least one semiconductor laser tube;

the laser emitted by the semiconductor laser tube is coupled into one or more optical fibers after being optically shaped, and the output end of each optical fiber is the light emitting end of the pulse type laser generator;

the average power of the laser output by the semiconductor laser tube is 0.1-2W, and the peak power of the output laser is 1-200W;

the optical fiber is a multimode optical fiber, the core diameter of the optical fiber is between 100 and 600 mu m, and the numerical aperture NA of the optical fiber is more than 0.2; the distance between the output end of the optical fiber and the inner layer of the helmet is more than 25 mm; the average power of the laser output by each optical fiber is not more than 2W, and the peak power of the pulse is not more than 200W.

Further, the pulse laser generator is an optical fiber coupled laser generator, and the optical fiber coupled laser generator is a solid laser generator or an optical fiber laser generator with electric pulse modulation, acousto-optic Q-switch modulation, electro-optic Q-switch modulation or mode-locked modulation.

Further, a water cooling device or an air cooling device is arranged in the helmet.

Further, the device also comprises a working state indicating unit;

the working state indicating unit is a visible light semiconductor laser tube arranged in the pulse laser generator or an LED lamp arranged in the helmet;

the wavelength range of the visible indicating light output by the working state indicating unit is 400-700nm, and the power range is 1-200 mW.

Further, the helmet outer layer is made of a hard material;

the other surfaces of the inner side of the middle layer of the helmet, except the light outlet end of the fixed pulse type laser generator, are provided with a reflecting material or a reflecting film for reflecting red light to near infrared light;

the inner layer of the helmet is made of hard or semi-hard material;

the helmet also comprises a flexible shading belt arranged at the edge of the inner side of the helmet.

Further, the helmet also comprises a switch element for controlling the pulse type laser generator to work and a detection feedback unit arranged in the helmet;

the switching element comprises an interlocking power switch and a signal sensor; the signal sensor is a helmet fixing belt buckle type interlocking device or a pressure sensor used for sensing the pressure between the helmet and the head top in the helmet;

the detection feedback unit is used for detecting the working condition of the pulse type laser generator and the temperature in the helmet.

The invention has the beneficial effects that:

(1) the pulse laser generator is adopted to generate pulse laser with the wavelength of 600-1400nm, high peak power and low average power to irradiate the brain of a human body, so that deep tissues of the brain exceeding 7cm can be effectively irradiated, and adverse effects caused by heating the brain by high average power density are avoided; therefore, the invention solves the technical problems that the irradiating light emitted by the existing treatment device can not effectively penetrate the skull to irradiate and treat brain cells at the deep layer of the skull, and how to realize the irradiating and treating of the brain cells at the deep layer of the skull without generating adverse effect due to overhigh temperature.

(2) Compared with the LED in the prior art, the photoelectric conversion efficiency of the semiconductor laser with the wavelength of 600-1400nm is generally over 35%, for the VCSEL semiconductor laser with the wavelengths of 808nm, 850nm and 940nm, the photoelectric conversion efficiency can reach 45%, which is far higher than 10-25% of the photoelectric conversion efficiency of the LED with the wavelength of 810nm, so that under the condition of outputting the same optical power, the heat dissipation required by the VCSEL semiconductor laser is much smaller than that of the LED. More importantly, even if the LED is driven by a pulse current, the light output power of the LED is not high, and the peak power thereof is difficult to reach 1W or more. Therefore, the present invention has significant advantages over LEDs in terms of photoelectric conversion efficiency and pulse peak power using pulsed lasers, especially pulsed semiconductor lasers used in consumer electronics.

(3) The pulse laser generator is preferably a VCSEL semiconductor laser generator, the VCSEL semiconductor laser generator emits light beams with conical shapes, and the divergence angle is about 20 degrees. VCSEL laser units are typically very small, with light emitting units between 1 micron and tens of microns in diameter. The pumping current is also very small between microamperes and milliamperes. The output power of the laser unit is in the micro watt level. Therefore, the laser power density of the laser light emitting surface of the VCSEL is low, and the VCSEL can be used in daily common air without damaging the laser light emitting surface of the VCSEL. Most of VCSEL semiconductor laser generators commonly used in the market are formed by closely arranging a plurality of VCSEL laser units and can output watt-level laser power. However, even with a watt level of laser output, the laser power density is as low as a single VCSEL laser unit. Since the light emitting area of the VCSEL semiconductor laser generator is generally 2 to 4 ten thousand times larger than that of other semiconductor laser generators with the same power, the laser power density of the light emitting surface is 2 to 4 ten thousand times lower. Therefore, the VCSEL semiconductor laser generator is suitable for operation in ordinary air without worrying about damage to the laser light emitting surface due to light contamination.

(4) The invention preferably adopts a TO packaged pulse type semiconductor laser generator. The TO-packaged pulse type semiconductor laser generator has the advantages of treating brain diseases: 1) the TO packaged pulse type semiconductor laser generator can be easily welded on a metal part on the inner side of the middle layer of the helmet; 2) the existing TO-packaged pulse type semiconductor laser generator can generate laser pulse peak power of 120W, the pulse width can be 100ns or shorter, and the average laser power under the 0.1% duty ratio is only 120 mW; 3) the pulse type semiconductor laser generators capable of being packaged by the TO can be used for covering and irradiating certain organs in the deep part of the brain, such as a hippocampus and a hippocampus, from different directions, the high peak power of the pulse type semiconductor laser generators can enable laser photons TO reach the deep part area of the brain, meanwhile, the extremely low average power of the pulse type semiconductor laser generators can be used for irradiating for a long time, such as irradiation for more than 30 minutes, and other human tissues in an irradiation light path cannot be damaged.

(5) The pulse laser generator is preferably a laser generator coupled with optical fibers, laser is transmitted to a part needing to be treated through the optical fibers, and the laser generator is completely separated from the part needing to be treated by the laser, so that heat generated by the laser generator cannot influence the part needing to be treated.

Drawings

FIG. 1 is a schematic structural view of a helmet according to an embodiment 1 of the present invention;

FIG. 2 is a schematic structural view of a helmet according to an embodiment 2 of the present invention;

FIG. 3 is a schematic diagram of the process by which the mechanism of PBM treatment is red and near infrared light which can lead to a cascade of intracellular pleiotropic effects;

FIG. 4 is a schematic diagram of the main brain area and its division of labor;

FIG. 5 is a schematic structural diagram of an embodiment of the present invention when the pulsed laser generator is a semiconductor laser generator according to the present invention;

FIG. 6 is a schematic diagram of the design of liquid cooling within the helmet of the present invention;

FIG. 7 is a schematic diagram of the design of heat pipe transport cooling within the helmet of the present invention;

FIG. 8 is a schematic structural diagram of an embodiment of the present invention when the pulsed laser generator is an optical fiber coupled laser generator;

FIG. 9 is a schematic view of a partial design of the middle and inner layer optomechanical structures of the single wavelength semiconductor laser-based helmet of the present invention;

FIG. 10 is a schematic view of a partial design of the middle and inner layer optomechanical structures of the multi-wavelength semiconductor laser-based helmet of the present invention;

FIG. 11 is a schematic illustration of beam divergence characteristics of two different types of semiconductor laser generators and a beam divergence characteristic of a fiber coupled laser generator;

FIG. 12 is a graph showing the relationship between the peak power density of the illumination light and the effective illumination depth;

FIG. 13 is a schematic diagram of multi-spot blanket irradiation of deep brain tissue;

FIG. 14 is a schematic diagram of selective illumination of the right region of the brain;

FIG. 15 is a graph of the dose profile of laser PBM treatment for Arndt-Schulz;

FIG. 16 is an electrical schematic of the main control box of an embodiment of the present invention;

FIG. 17 is a laser waveform diagram for operation in a continuous light extraction mode according to an embodiment of the present invention;

FIG. 18 is a laser waveform diagram of an embodiment of the present invention operating in a chopped light mode;

FIG. 19 is a laser waveform diagram of the embodiment of the present invention operating at low duty cycle in the chopping light emitting mode;

FIG. 20 is a laser waveform diagram for operation in any of the pulsed light extraction mode and the intermittent light extraction mode in accordance with embodiments of the present invention;

FIG. 21 is a schematic diagram of an embodiment 1 of the fiber-coupled laser generator of the present invention;

FIG. 22 is a schematic diagram of an embodiment 2 of the fiber-coupled laser generator of the present invention;

FIG. 23 is a schematic diagram of an embodiment 3 of the fiber-coupled laser generator of the present invention;

FIG. 24 is a schematic diagram of an embodiment 4 of the fiber-coupled laser generator of the present invention.

The reference numerals in the drawings are explained as follows:

100-helmet, 101-helmet outer layer, 102-cooling liquid, 103-heat pipe, 105-helmet middle layer, 106-reflective material or reflective film, 109-helmet inner layer, 110-helmet fastening band, 115-helmet fastening band snap-in interlock, 116-helmet interlock connection, 125-pressure sensor, 126-pressure sensor connection, 130-temperature sensor, 135-helmet inner temperature sensor connection, 170-flexible shading band, 180-helmet bus, 200-light emitting region, 203-semiconductor laser welding base, 206-air gap, 210-semiconductor laser generator, 220-semiconductor laser beam, 221-semiconductor laser power supply line, 224-semiconductor laser beam divergence angle, 225-semiconductor laser spot, 240-fiber output end, 241-fiber, 242-fiber output end interface, 243-fiber coupled laser output beam, 244-fiber coupled laser output beam divergence angle, 245-fiber coupled laser output spot, 300-fiber coupled laser generator, 305-semiconductor laser base and heat sink, 306-visible semiconductor laser base and heat sink, 310-semiconductor laser tube, 312-visible semiconductor laser tube, 313-visible semiconductor laser collimator, 315-fast axis collimator, 316-slow axis collimator, 317-collimator, 320-beam reflector, 325-polarization beam splitter PBS, 326-wavelength combiner, 330-focusing mirror, 340-fiber coupler, 350-optical fiber coupled semiconductor laser generator air cooling device, 400-power supply and main control box, 405-main control electronic system and optical fiber coupled laser generator connecting line, 410-main control electronic system, 420-medical direct current power supply, 421-AC alternating current power supply connecting line, 422-AC alternating current power supply, 425-main control electronic system and medical direct current power supply connecting line, 430-Internet of things module and external communication module, 435-main control electronic system and Internet of things module and external communication module connecting line, 441-semiconductor laser pulse current source and main control electronic system connecting line, 442-semiconductor laser pulse current source, 445-main control electronic system and human-machine control interface connecting line, 450-photoelectric detector, 455-photoelectric detector and main control electronic system connecting line, 460-interlocking power switch, 465-interlocking power switch connecting line, 480-intelligent PBM parameter automatic output device, 485-intelligent PBM parameter automatic output device and main control electronic system connecting line, 500-man-machine control interface, 510-manual control interface, 511-irradiation area manual setting interface, 512-pulse parameter manual setting interface, 600-pulse waveform input end, 700-heat exchanger, 710-connecting line of heat exchanger and main control electronic system, 920-hippocampus.

Detailed Description

The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

The following detailed description is provided to illustrate various embodiments of the present invention for the purpose of describing the principal technical features, embodiments and technical advantages of the present invention. The core technical content of the present invention includes but is not limited to the examples provided below. Those skilled in the art, having the benefit of the teachings of this invention, may effect numerous modifications thereto without departing from the scope or spirit of the invention in its aspects.

The core technical content of the invention is that a pulse laser generator with the wavelength of 600-1400nm is arranged inside a helmet for treating the brain diseases, and the brain diseases are treated by utilizing the principle of photobiological modulation (PBM). In order to effectively irradiate red or near-infrared laser to deeper brain organs, the invention adopts a plurality of pulse type laser generators with high peak power as light sources, and uses a pulse generation mode with low duty ratio to obtain the irradiation effect with high peak power and low average power. Wherein the peak power density of the laser irradiated on the skin surface by each light source can be 1-500W/cm²And the average laser power density is less than 500mW/cm². The device based on the invention can treat, recover or relieve stroke, traumatic brain injury TBI, cerebral vascular ischemia, Alzheimer's disease, Parkinson's disease and dementiaThe brain diseases such as depression, anxiety, post-traumatic stress disorder and the like can also help users to improve the cerebral blood flow and promote the generation of brain cells, brain microgrooves and brain microvasculature so as to improve the brain health and improve the attention and cognitive ability.

Referring to fig. 1 and 2, the device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology of the present invention comprises a helmet 100, at least one pulsed laser generator, and a power supply and main control box 400. The helmet 100 includes a helmet outer layer 101, a helmet middle layer 105, and a helmet inner layer 109; the middle layer 105 of the helmet is made of a heat-conducting material; the helmet inner layer 109 is made of a transparent material; the light emitting ends of the pulse laser generators are all fixed on the inner side of the middle layer 105 of the helmet; after the laser emitted from the light emitting end of the pulse laser generator penetrates through the inner layer 109 of the helmet (i.e. the laser reaching the skin surface), the following conditions are satisfied: the peak power density is 1-500W/cm²The mean power density is less than 500mW/cm²The diameter of the laser spot is not less than 3mm, the laser pulse width is 1ps-10ms, and the wavelength is 600-1400 nm.

Fig. 1 is a schematic structural view of a helmet according to an embodiment 1 of the present invention. The helmet 100 comprises a helmet made of hard material, a laser light source, a photoelectric and temperature detecting sensor, a cooling and heat dissipating device of the laser light source, and the like. The helmet 100 has a three-layer structure, and the material of the helmet outer layer 101 is a hard material, such as a flame retardant PVC material. The material of the middle layer 105 of the helmet is a thermally conductive material, such as a metallic material. The material of the inner layer 109 of the helmet is a hard or semi-hard transparent material, and is transparent to the wavelength of 600-1400 nm. The material of the inner layer 109 of the helmet may be transparent PMMA, or other organic material with light transmittance > 80% and characteristics that meet the medical safety requirements of human body contact. A plurality of semiconductor laser generators 210 or optical fiber output ends 240 of the optical fiber coupled laser generator 300 are fixed in a light emitting area 200 in the direction of one side of the middle layer 105 close to the head of the helmet, and a reflective material or a reflective film 106 for reflecting red light to near infrared light is arranged on the vacant surface except the optical fiber output ends 240 for fixing the semiconductor laser generators 210 and the optical fiber coupled laser generator 300. The reflective material or film 106 may be a smooth aluminum, copper or other metal material, or a metal film or dielectric film. The helmet 100 is secured to the head of a patient by helmet strap 110, and two sections of helmet strap 110 are connected together by helmet strap snap-in interlocks 115, or helmet strap 110 is connected directly to the helmet. The helmet 100 takes laser safety into account, and the helmet mount strap snap-in interlock 115 not only securely secures the helmet 100 to the patient's head, but also incorporates an interlock switch to prevent laser output without a snap-on fastening. One or more temperature sensors 130 are mounted on the skin side of the helmet 100 to ensure that the patient does not experience discomfort from excessive temperatures for a given exposure time, typically the skin side of the helmet 100 is no higher than 41 degrees celsius. The electric wire or optical fiber connected to the laser light source in the helmet 100, the connection wire of the helmet fixing band buckle type interlock 115, the connection wire 135 of the temperature sensor in the helmet, the cooling water conduit of the middle layer 105 of the helmet, the optical fiber and the water pipe are connected to the power supply and the main control box 400 through the helmet bus 180. To further ensure the safety of the laser, the inside of the helmet 100 is provided with a pressure sensor 125. In the case where the head of the person to be irradiated stands upright, the switch of the pressure sensor 125 is closed by natural gravity, and the closing electric signal is connected to the power supply and the main control box 400 through the pressure sensor connection line 126. The pulsed laser generator is enabled to emit laser light only after the power supply and main control box 400 receives a switch close signal from the pressure sensor 125. In order to prevent therapeutic light from leaking from the helmet inner layer 109 and irradiating to the eyes of a patient or an operator, and to ensure the laser safety of the device for treating brain diseases, a flexible light-shielding tape 170 made of black knitted material is installed at the inner side edge of the helmet inner layer 109. The flexible shade band 170 made of black knitted material not only prevents laser leakage from the helmet 100, but also improves comfort of the patient using the helmet 100.

Fig. 2 is a schematic structural view of a helmet in accordance with an embodiment 2 of the present invention. In contrast to fig. 1, fig. 2 contains two laserbuminescent regions 200 for illuminating the brain through the ear and face. The advantage of illuminating the brain through the face is that absorption of the laser by the hair can be avoided, and discomfort of placing the laser illuminator into the mouth can also be avoided.

FIG. 3 is a schematic diagram of the process by which the therapeutic mechanism of PBM is the cascade of intracellular pleiotropic effects caused by red and near infrared light. In the PBM process, photons are absorbed by cytochrome c oxidase due to its unique spectral properties, photon energy catalyzes a series of redox reactions, and electron transport chains facilitate the transfer of electrons across the inner mitochondrial membrane. The specific steps are that NAD-NADH proportion is increased and mitochondrial membrane potential (delta psi) is increased, which in turn leads to increased ATP and free Radical (ROS) content. While the enhancement of the activity of the electron transport chain regulates NO synthesis (NOS) in cytochrome oxidase. Then calcium ion release, cyclic adenosine monophosphate (cAMP), increased expression of cyclic guanosine monophosphate cGMP in the cells occur, eventually leading to vasodilation and increased blood flow. Secondary results are increased cellular energy metabolism, decreased apoptosis and cellular inflammation.

Fig. 4 is a schematic diagram of the main brain area and its division. The tPBM can be specifically performed on the treatment region by selectively turning on the semiconductor laser generator 210 or the optical fiber output terminal 240 above the treatment region in the helmet 100 through the power supply and the main control box 400.

FIG. 5 is a schematic structural diagram of an embodiment of the present invention when the pulsed laser generator is a semiconductor laser generator. Because the vertical light emitting VCSEL semiconductor laser generator has extremely low power density of the light emitting surface, the vertical light emitting VCSEL semiconductor laser generator can be used in ordinary unclean air without worrying about the damage of the light emitting surface of the laser, and the ordinary VCSEL semiconductor laser generator is a good choice for the design under the condition that the pulse peak power is not required to be more than 100W. The laser emission average power of a single light emitting group of the VCSEL laser is between 0.1 and 5W, and the laser emission power of each light emitting point in the light emitting group is in the order of micro watt to milliwatt. Under the drive of a pulse current source, the peak power P emitted by a single light-emitting group of VCSEL laser_pCan reach 1-50W. The single emitting group of VCSEL lasers is packaged on an aluminum-based circuit board. The aluminum-based circuit board is fixed on the inner side of the middle layer of the metal helmet in a heat conduction mode. Multiple VCSEL semiconductors can be arranged according to the heat dissipation capability of the metal helmetA laser generator. Under the condition of pulse current driving, the plurality of VCSEL semiconductor laser generators can emit laser with the total average power of 5-100W, the total pulse laser power exceeds 500W, and the heat dissipation power required by the integral metal helmet does not exceed 200W. A TO-packaged side-emitting pulsed semiconductor laser generator or a TO-packaged VCSEL pulsed semiconductor laser generator is a good choice when higher peak laser power is required. The TO package can be a 5.6mm diameter TO56 package, a 9mm diameter TO9 package, or other specification TO packages. One or more pulsed semiconductor laser generators 210 may be contained within the helmet 100. Pulsed semiconductor laser generator 210 may be a conventional VCSEL vertical emission semiconductor laser generator, a TO-packaged side-emitting or VCSEL vertical emission semiconductor laser generator, or other types of packaged (e.g., C-packaged or COS-packaged) semiconductor laser generators, or a combination of these types of semiconductor laser generators. When the semiconductor laser generator packaged by the C package or the semiconductor laser generator packaged by the COS is adopted, the laser light emitting point area of the semiconductor laser generator packaged by the C package is small, the power density of the laser light emitting point is high, and in order to prevent the laser from being damaged in the using process, the semiconductor laser generator packaged by the C package or the COS package is required to be provided with a protective cover with a light emitting window. The laser wavelength of the semiconductor laser generators 210 is between 600 nm and 1400nm, and may be a single wavelength or multiple wavelengths. The plurality of semiconductor laser generators 210 are respectively fixed on the welding bases 203 of the plurality of semiconductor lasers by means of effective thermal conduction, and then fixed on the helmet middle layer 105 made of metal material by means of effective thermal conduction. A reflecting material or film 106 made of metal or dielectric film is added on the inner side of the middle layer 105 of the helmet in the area where the semiconductor laser generator 210 is not fixed, and the reflecting material or film 106 is used for reflecting various stray light to the skin surface of a human body to enhance the PBM efficiency. Since the area of the emitting point of the semiconductor laser generator 210 is small and the divergence angle of the emitted light beam is small, the emitting point of the semiconductor laser generator 210 and the inner layer 109 of the helmet are prevented from damaging the hair or scalp due to too small light spot on the hair or scalp and too high average laser power densityWith an air gap 206 of 10-30mm between them, so that the spot diameter on the hair or scalp is greater than 3 mm. The 10-30mm air gap 206 also prevents the light emitting point of the semiconductor laser generator 210 from contacting any object and causing damage to the light emitting point. The helmet inner layer 109 is made of a transparent hard or semi-hard material. The helmet 100 of the present embodiment includes a visible light laser generator or a visible light LED (not shown) for indicating light, in addition to the semiconductor laser generator 210 for treatment; the wavelength of the visible light source is between 400 and 700nm, and the output power range is between 1 and 200 mW. The semiconductor laser power supply lines 221 of the plurality of semiconductor laser generators 210 are connected to a power supply and main control box 400.

In order to dissipate heat of the semiconductor laser generator 210 within the helmet 100, a heat pipe may be fixed at each heat generating point. The end of the heat pipe connected with the heating point is a hot end, and the other end of the heat pipe is a cold end. And the cold ends of all heat pipes are connected to a heat sink for heat dissipation. The heat sink may be a heat exchanger of heat pipe and coolant, or a heat exchanger of heat pipe and air. The temperature of the liquid heat exchanger or the air heat exchanger is controlled by the power supply and main control box 400 in order to keep the temperature of the heat pipe within 41 degrees celsius. Semiconductor refrigeration equipment (TEC) may be used to cool a liquid or air heat exchanger. And a forced air cooling device can also be adopted for heat dissipation. Figure 6 is a schematic diagram of the design of liquid cooling within the helmet of the present invention. The cooling liquid 102 within the helmet 100 may be water. The cooling liquid 102 is connected to a power supply and main control box 400 through a water pipe. For the design of fig. 6, power and main control box 400 contains a heat sink (not shown) that includes a water tank, a water pump, and a heat exchanger for water and air. The advantage of the design of fig. 6 is that it ensures that the temperature within helmet 100 is stable over a range that is comfortable for the subject at any PBM treatment laser power. Fig. 7 is a schematic diagram of the structure of the heat pipe transmission cooling design in the helmet of the present invention. The heat pipe 103 may be provided with a plurality of individual welding or other effective heat conducting means fixed on the outside of the middle layer 105 of the helmet, and the specific welding points or fixing points are the back of the welding base 203 of the corresponding semiconductor laser. All heat pipes 103 converge in a heat exchanger 700 and dissipate heat through the heat exchanger 700. The heat exchanger 700 is connected to the power and main control box 400, and the temperature of the helmet 100 is controlled by a temperature control subsystem inside the power and main control box 400.

FIG. 8 is a schematic structural diagram of an embodiment of the present invention when the pulsed laser generator is a fiber-coupled laser generator. The laser energy transmission through the optical fiber is a common medical laser energy transmission mode, and one of the advantages of the laser energy transmission is that the laser generator can be completely separated from the laser treatment part, so that the heat generated by the laser generator cannot influence the treatment part. Semiconductor laser, solid laser or fiber laser with the wavelength of 6001400nm can be effectively coupled into the multimode fiber with the core diameter of 100-600 μm, and the laser energy is transmitted to the PBM irradiation part. In this embodiment, the following concrete steps are performed: the fiber-coupled laser generator 300 has one or more laser sources, which are coupled into one or more optical fibers 241 after certain optical shaping, and the corresponding fiber output end 240 of the optical fiber 241 is fixed in the fiber output end interface 242 in the helmet 100, and finally the laser is output from the fiber output end 240. The laser output direction and the helmet middle layer 105 are in the normal direction. A plurality of fiber output interfaces 242 are secured to the helmet middle layer 105 as needed for treatment. The fiber coupled laser generator 300 is of modular design, and may be a single module, or multiple modules; can be placed in the main control box or outside the main control box. The optical fiber 241 is a multimode optical fiber with a core diameter of 100-600 μm. The average power of the laser light output through each optical fiber 241 is not more than 2W, and the peak power of the pulse is not more than 200W. If the fiber-coupled laser generator 300 has N fiber outputs, the total average power of the laser outputs in the helmet does not exceed Nx2W, and the total pulse peak power does not exceed Nx 200W. Since the semiconductor laser tube capable of being driven by the pulse current has the advantages of small volume, large pulse energy, low cost, etc., the semiconductor laser tube is the first choice of the fiber-coupled laser generator 300. The semiconductor laser tube can output the average laser power of 0.1-2W and also can output the peak laser power of 1-200W in a pulse mode. The physical structure of the semiconductor laser tube can be a single-tube semiconductor laser with a single luminous source or a bar semiconductor laser with more than two luminous units. In some cases, the fiber coupled laser generator 300 may be a solid state laser generator or a fiber laser generator with electrical pulse modulation, acousto-optic Q-switch modulation, electro-optic Q-switch modulation, mode-locked modulation, or other electro-optical pulse output. The wavelength of the laser emitted by the solid laser generator is between 600-1400nm, and the laser can be near infrared wavelength laser such as Nd: YAG, Nd: YLF and the like. The pulse width of the output laser of the solid laser generator and the fiber laser generator can be between 1ps and 10 ms. In order to avoid too small a laser spot on the head, the numerical aperture NA of the optical fiber 241 is generally greater than 0.2, and the distance from the output end of the optical fiber 241 to the helmet inner layer 109 is greater than 25 mm. Under the condition, the diameter of a light spot irradiated on a treatment part can reach more than 5 mm. The inner helmet layer 109 is made of a relatively hard transparent material. In order to simultaneously meet the requirements of light transmission at the wavelength of 600-1400nm and medical safety, the transparent material, such as PMMA (polymethyl methacrylate) and other organic materials, has the light transmittance of more than 80 percent and meets the medical safety requirement of human body contact.

FIG. 9 is a schematic view of the partial design of the middle and inner layer optomechanical structures of the single wavelength semiconductor laser-based helmet of the present invention. In order to effectively utilize the light energy emitted by the semiconductor laser, a layer of reflective material or film 106 made of metal or dielectric film is provided inside the layer 105 in the helmet for reflecting various stray light to the skin surface of the human body to enhance the PBM efficiency. The laser beam 220 emitted from the semiconductor laser generator 210 passes through the helmet inner layer 109 and then irradiates the treatment site. FIG. 10 is a schematic view of the partial design of the middle and inner layer optomechanical structures of the helmet based on multiple wavelength semiconductor lasers according to the present invention. In order to effectively irradiate the PBM of a specific brain organ, the laser with different wavelengths can be irradiated on one treatment point. The three semiconductor laser generators 210 respectively emit laser beams 220 of three different wavelengths. The lasers with different wavelengths can be emitted simultaneously or not. Sometimes, TO achieve optimal PBM illumination, the three semiconductor laser generators 210 may also be differently packaged pulsed semiconductor laser sources, such as TO-packaged semiconductor laser generators, C-packaged semiconductor laser generators, COS-packaged semiconductor laser generators.

PBM efficacy is closely related to the peak and average power density of the therapeutic light at the surface of the treatment site. Due to the optical characteristics of different laser light sources, the helmet 100 may have different peak and average power densities when using different light sources. FIG. 11 is a schematic illustration of beam divergence characteristics of two different types of semiconductor laser generators and a beam divergence characteristic of a fiber coupled laser generator. In FIG. 11, semiconductor laser spot 225 of VCSEL vertical emission semiconductor laser generator 210 on the left side is circular and semiconductor laser beam 220 has a semiconductor laser beam divergence angle 224 that is generally between 10 and 25 degrees. The semiconductor laser spot 225 of the central side-emitting semiconductor laser generator 210 is elongated with a semiconductor laser beam divergence angle 224 of the semiconductor laser beam 220 in the fast axis direction generally between 20-40 degrees and the slow axis direction generally between 8-15 degrees. The output beam characteristics of the right fiber-coupled laser generator are related to the beam characteristics of the input laser itself and the numerical aperture NA of the transmission fiber. For a medically commonly used multimode fiber-coupled laser generator, the fiber-coupled laser output spot 245 output from the fiber output end 240 is circular, and the fiber-coupled laser output beam divergence angle 244 of the fiber-coupled laser output beam 243 is generally determined by the NA of the fiber. For an optical fiber with NA of 0.22, the divergence angle is about 12.5 degrees. For all types of laser light sources, the size of the light spot is proportional to the vertical distance L from the light emitting point to the irradiation surface H.

Fig. 12 is a graph showing the relationship between the peak power density of the irradiated light and the effective irradiation depth. The effective penetration depth of human tissue to red and near infrared laser light is not only related to the wavelength, but also to the peak power density of the laser light. According to beer-lambert law, the higher the peak power density of a laser, the deeper its effective penetration depth.

High peak power density lasers do irradiate deep brain tissue, but when their average power density is low, the irradiated organs receive a low dose. In order to achieve an optimum dose of irradiation effectively in a certain time, it is necessary to cover-irradiate the irradiated organs from different directions simultaneously with a plurality of high peak density pulsed lasers. FIG. 13 is a schematic diagram of multi-point coverage irradiation of deep brain tissue. In order to irradiate the hippocampus 920 with a certain dose, which is about 7cm deep, part of the semiconductor laser generator 210 in the helmet 100 is selectively turned on, so that the semiconductor laser beam 220 can be coveringly irradiated in the hippocampus 920 after being absorbed and scattered by various head and brain tissues in the light path. Other laser light sources in the helmet 100 can also be selectively turned on for blanket irradiation if it is desired to irradiate other target tissues in the brain. For a particular patient, it is sometimes desirable to enhance tPBM irradiation of a functional area in the brain. In this case, part of the laser light source in the helmet 100 may be turned on, and fig. 14 is a schematic diagram of selectively illuminating the right region of the brain.

FIG. 15 is a graph of the dose profile of laser PBM treatment for Arndt-Schulz. The Arndt-Schulz dose curve is a universal dose curve and is often used to describe the efficacy of drug therapy. Through many studies by researchers with PBM researchers, this dose curve is also suitable for PBM treatment as well. The dose of light irradiation is generally expressed in unit area (cm)²) In units of laser energy (joules), i.e. J/cm². When the light irradiation dose is too small, the light stimulation treatment effect of the PBM on the brain tissue is not obvious, but when the light irradiation dose is too large, the PBM has no light stimulation on the brain tissue, but has photoinhibition to achieve the treatment effect. The light irradiation dose is calculated by multiplying the light power density by the light irradiation time. Thus, the semiconductor laser generator 210 or the fiber-coupled laser generator 300 emits the peak power P of the laser light_PAnd the average power P_avgIt is required to meet the treatment requirements. After the set irradiation time has elapsed, the light irradiation dose to the brain can be made within the optimal region in fig. 15.

FIG. 16 is an electrical schematic diagram of the main control box of an embodiment of the present invention. The power and host control box 400 contains a host electronic system 410. The main control electronic system 410 is composed of one or more Central Processing Units (CPUs), electronic components for controlling the laser generators, and hardware and software related to the embedded control system. The power supply of the master electronic system 410 is provided by a medical dc power supply 420. The medical dc power supply 420 may be built-in or external, and is connected to the medical dc power supply via a connection 425 of the main control electronic system. The medical dc power supply 420 and the AC power supply 422 are connected by an AC power supply line 421. Master electronic system 410 controls one or more semiconductor laser pulse current sources 442 via semiconductor laser pulse current source and master electronic system connection 441. The semiconductor laser pulse current source 442 supplies power to a corresponding plurality of semiconductor laser generators 210 located within the helmet 100 via semiconductor laser supply lines 221.

In order to monitor the illumination of the laser light source in the helmet 100, one or more photodetectors 450 are provided in the helmet 100. The photodetector 450 may be a photodiode. The output signal of the photodiode is input to the host electronic system 410 through the photodetector and host electronic system connection line 455.

In order to ensure the laser safety of the device for treating brain diseases, a helmet fixing band snap-type interlock 115 and/or a pressure sensor 125 are provided on the helmet 100. The output signals of the helmet interlock switch 460 are all switch electrical signals and are respectively connected to the interlock power switch by the helmet interlock connection 116 and/or the pressure sensor connection 126. The interlock power switch 460 controls the on and off of the semiconductor laser pulse current source 442 through the interlock power switch connection 465, which in turn controls the laser output of the semiconductor laser generator 210. The temperature sensor 130 in the helmet 100 is connected with the main control electronic system 410 through the helmet temperature sensor connecting line 135. After the detected temperature of the temperature sensor 130 exceeds 41 degrees celsius, the host electronic system 410 automatically reduces the average laser power emitted by the semiconductor laser generator 210. The power reduction may be achieved by reducing the semiconductor laser drive current or reducing the duty cycle in the case of chopping, pulsing, or turning off the semiconductor laser generator 210.

The power and main control box 400 may further include an internet of things module and an external communication module 430, and is connected to the main control electronic system 410 through a connection 435 between the main control electronic system and the internet of things module and the external communication module. The internet of things module and the external communication module 430 are designed to allow the device for treating brain diseases to receive input of treatment parameters from a doctor, and also to output the working conditions and the use history thereof to a central computer, so that the central computer can analyze the use conditions of the devices for treating brain diseases, provide the use conditions of each user for the treating doctor, or provide big data analysis. The internet of things module and the external communication module 430 may be connected to the lan through a network cable, or may be connected to the lan through WiFi or bluetooth or other wireless methods.

An operator of the apparatus for treating brain diseases can operate the power supply and the operation of the main control box 400 through the human-machine control interface 500. On the human-machine control interface 500 are an operator manual control interface 510, an irradiation area manual setting interface 511, and a pulse parameter manual setting interface 512. The operator can manually set the desired irradiation parameters including parameters such as average power of the laser output, pulse peak power, pulse frequency, pulse duty cycle, pulse width, laser wavelength, laser irradiation time, irradiation area, etc. The human-machine control interface 500 may be connected to the power supply and main control box 400 through the connection 445 between the main control electronic system and the human-machine control interface, or may be connected to the power supply and main control box 400 through wireless means such as WiFi or bluetooth. In addition to setting treatment parameters using the human machine interface 500, the operator may also use the manual control interface 510 to set treatment parameters, or use the intelligent PBM parameter auto-outputter 480 to allow the physician to set treatment parameters remotely via the Internet or to invoke the operator's previously stored parameter settings. As shown in the Arndt-Schulz dose graph of FIG. 15, the effect of PBM is not significant if the dose of red and near infrared light applied to the affected part is too small, but the effect of PBM is inhibited if the dose applied to the affected part is too large. The irradiation dose to the affected part should be set at its optimum interval. In view of the difference in the disease condition of each patient and the difference in the color of the scalp, the color, length and density of the hair, the operator should set the optimal irradiation parameters under the guidance of the doctor. As a result of the research known at present, the absorption of human skull to 810nm is small, and the use of 810nm laser is a good choice, but other wavelengths of laser have different penetration depths to different tissues, so the invention proposes to use a multi-wavelength light source to achieve the best treatment effect. Another parameter related to the depth of transmission, in addition to wavelength, is the peak power density. For human tissue, the higher the peak power density, the deeper the penetration depth and vice versa. In order to effectively ingest deeper brain organs, such as the hippocampus, the operator may set a high peak power pulse output, i.e., a short pulse time, high brightness laser output. To avoid unnecessary heating of the head by the red and near infrared lasers, the operator may set a low duty cycle, i.e., low average laser power mode parameter, or intermittent laser mode parameter.

The apparatus for treating brain diseases may also be connected to one or more external devices, such as a pulse waveform input 600. The input pulse waveform may be a waveform and frequency simulating a brain wave, such as an Alpha wave of 8-14Hz, a Beta wave of 12.5-28Hz, or a Gamma wave of 25-100Hz (usually 40Hz), or directly inputting the waveform of the brain wave of the person to be irradiated to the power supply and main control box 400 through the pulse waveform input terminal 600, and finally generating the desired laser output waveform at the semiconductor laser generator 210.

With the design of multiple semiconductor laser generators 210 within the helmet 100, the semiconductor laser generators 210 generate a certain amount of heat during operation. This heat can be dissipated to the ambient air through the area of the helmet 100 itself, or can be carried to the exterior of the helmet, such as the power supply and main control box 400, through a heat exchanger 700. The heat exchanger 700 is connected to the power supply and main control box 400 by a connection 710 between the heat exchanger and the main control electronics. The connection 710 between the heat exchanger and the host electronics system may be a water line or other heat transfer connection. The temperature of the semiconductor laser generator 210 may be controlled by a power supply and a main control box 400.

The complex tissue morphology, tissue structure and cellular characteristics of the human brain result in the need for a relatively large laser power output range for the device to treat brain diseases to meet the required irradiation dose of tPBM. In order to achieve the desired tPBM treatment effect, the device for treating brain diseases can be operated in a continuous light emitting mode, and the laser output waveform thereof is shown in fig. 17. The continuous light pattern is effective for superficial brain tissue. But for deeper brain tissues that require PBM treatment, such as organs on the default network of the brain, the continuous light extraction mode is not sufficient. If the laser power density in the continuous light-emitting mode is too high, the laser photons can reach the brain organs, but other brain tissues in the photon path can cause the treatment effect to fall into the inhibition area of the Arndt-Schulz dose curve due to too high light irradiation dose, and even damage the head or the brain tissues. To avoid these disadvantages, the pulsed laser brain disease treatment apparatus may output laser light in a chopped light-emitting mode, and the output waveform is as shown in fig. 18. Fig. 19 is a waveform of laser light when operating at low duty cycle in a chopped light extraction mode, where the peak power of the laser light is much higher than the average power. Fig. 20 is a laser waveform diagram in operation in any of the pulse light emission mode and the intermittent light emission mode, except for the chopper mode. Such an arbitrary pulse pattern may be a preset pulse waveform, such as a waveform and frequency simulating a certain brain wave, or a waveform of the brain wave of the irradiated person is directly inputted to the power supply and the main control box 400 through the pulse waveform input terminal 600, and finally a desired laser output waveform is generated at the semiconductor laser generator 210. When a laser modulated by Q-switch or mode-locked is used as a tPBM light source, the pulse waveform is determined by the pulse characteristics of the laser. In the case of generating laser pulses using pulsed current drive, the operator can also adjust the peak power density with the pulse width to adjust for different depths of illumination.

One design of the present invention is to use a fiber coupled laser generator as the light source. FIG. 21 is a schematic diagram of an embodiment 1 of the fiber-coupled laser generator of the present invention. In this embodiment 1, the fiber-coupled laser generator 300 couples the energy emitted from the semiconductor laser tube 310 into the optical fiber 241 by using the core components such as the semiconductor laser tube 310 with the wavelength of 600-1400nm and the optical element. Specifically, semiconductor laser tube 310 is secured to a semiconductor laser base and heat sink 305. to effectively dissipate heat, semiconductor laser base and heat sink 305 is secured by thermal conduction to a fiber-coupled semiconductor laser generator air cooler 350. Laser beams emitted by the semiconductor laser tube 310 are focused on a fiber coupler 340 capable of fixing the optical fiber through optical elements such as a fast axis collimating mirror 315, a slow axis collimating mirror 316, a beam reflecting mirror 320, a focusing mirror 330 and the like, and finally laser energy of the semiconductor laser tube 310 is input into the optical fiber 241. Whereas the wavelength of the semiconductor laser tube 310 may be invisible near infrared light, such as laser light with a wavelength above 800nm, the fiber-coupled laser generator 300 may also contain a visible semiconductor laser as the indicator light inside the helmet 100. Specifically, a visible light semiconductor laser tube 312 with a wavelength of 400-700nm, such as 450 ± 20nm, 520 ± 20nm, 635 ± 20nm, etc., is fixed on the visible light semiconductor laser base and heat sink 306, and its emission light beam passes through the visible light semiconductor laser collimating mirror 313 and irradiates on the beam reflecting mirror 320. The beam reflector 320 is a wavelength combiner, and may not coat the emission wavelength of the visible light semiconductor laser tube 312. For example, both surfaces of the beam reflector 320 may be coated with an anti-reflection film for reducing the laser energy loss of the visible light semiconductor laser tube 312, and the side facing the semiconductor laser tube 310 may be coated with a high-reflection film for reducing the emission wavelength of the semiconductor laser tube 310. The combined laser beam is coupled into the optical fiber 241 by the focusing mirror 330. The optical fiber 241 contains a near infrared laser for treatment and a visible laser for indication. The output laser power of the visible light semiconductor laser tube 312 ranges from 1 mW to 200 mW. The fiber coupled laser generator 300 is connected to the power and main control box 400 via the main control electronics and fiber coupled laser generator connection 405. The power and main control box 400 provides the required power and electronic control for the fiber-coupled laser generator 300. For the sake of simplicity, parts of the pulse current source are not particularly shown in fig. 21 to 24.

FIG. 22 is a schematic diagram of embodiment 2 of the fiber-coupled laser generator of the present invention. In this embodiment 2, the use of two semiconductor laser tubes 310 can increase the laser output power of the fiber-coupled laser generator 300 or output two different laser wavelengths. The two semiconductor laser tubes 310 with the wavelength of 600-1400nm may have the same wavelength or different wavelengths. The two semiconductor laser tubes 310 are respectively fixed on the two semiconductor laser bases and the heat dissipation device 305 in the polarization directions perpendicular to each other, pass through respective collimating lenses 317, are combined by a polarization beam splitter PBS325, and are finally coupled into an optical fiber 241. The collimating lens 317 may be a single lens, such as an aspheric lens, or may be a combination of a fast axis collimating lens 315 and a slow axis collimating lens 316 similar to those shown in fig. 21. Similarly, the combination of the fast axis collimator 315 and the slow axis collimator 316 in fig. 21 can be replaced by a single collimator 317 in fig. 22.

FIG. 23 is a schematic diagram of an embodiment 3 of the fiber-coupled laser generator of the present invention. In this embodiment 3, more than 2 semiconductor laser tubes 310 are contained in the fiber-coupled laser generator 300. The plurality of semiconductor laser tubes 310 have different laser emission wavelengths λ a to λ n. The emission beams of the semiconductor laser tubes 310 are collimated by the corresponding collimating mirrors 317, then combined by the polarization beam splitter PBS325 and the wavelength beam combiners 326, and incident on the focusing mirror 330 coated with antireflection films for the wavelengths λ a to λ n, and finally the laser beams of the semiconductor laser tubes 310 are coupled into the optical fiber 241.

FIG. 24 is a schematic diagram of an embodiment 4 of the fiber-coupled laser generator of the present invention. In this embodiment 4, more than 2 semiconductor laser tubes 310 are contained in the fiber-coupled laser generator 300. The emission wavelengths of the plurality of semiconductor laser tubes 310 may be the same or different. The emission beams of the plurality of semiconductor laser tubes 310 are collimated by the combination of the corresponding fast axis collimator 315 and slow axis collimator 316, or by the corresponding collimator 317 (not shown in fig. 24), and then reflected by the corresponding beam reflector 320 to the corresponding focusing mirror 330, and finally output by the plurality of corresponding optical fibers 241.

Claims

1. A device for treating brain diseases based on pulse semiconductor laser external irradiation technology comprises a helmet (100), at least one pulse laser generator, a power supply and a main control box (400); the method is characterized in that:

the helmet (100) comprises a helmet outer layer (101), a helmet middle layer (105) and a helmet inner layer (109); the middle layer (105) of the helmet is made of a heat-conducting material; the helmet inner layer (109) is made of a transparent material;

the light emitting ends of the pulse type laser generators are all fixed on the inner side of a middle layer (105) of the helmet;

the laser emitted by the light emitting end of the pulse type laser generator penetrates through the inner layer (109) of the helmet, and the following conditions are met: the peak power density is 1-500W/cm²The mean power density is less than 500mW/cm²The diameter of the laser spot is not less than 3mm, the laser pulse width is 1ps-10ms, and the wavelength is 600-1400 nm.

2. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 1, characterized in that:

the pulsed laser light generator is a semiconductor laser light generator (210), and the semiconductor laser light generator (210) is a VCSEL semiconductor laser light generator;

an air space (206) of 10-30mm is arranged between the light emitting end of the VCSEL semiconductor laser generator and the inner layer (109) of the helmet.

3. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 1, characterized in that:

the pulsed laser generator is a semiconductor laser generator (210), and the semiconductor laser generator (210) is a TO-packaged pulsed semiconductor laser generator.

4. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 1, characterized in that:

the pulse type laser generator is a semiconductor laser generator (210), and the semiconductor laser generator (210) is a C-packaged semiconductor laser generator or a COS-packaged semiconductor laser generator;

5. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 1, characterized in that:

the pulsed laser generator is a laser generator (300) coupled by an optical fiber;

the fiber-coupled laser generator (300) comprises at least one semiconductor laser tube (310);

laser emitted by the semiconductor laser tube (310) is coupled into one or more optical fibers (241) after being subjected to optical shaping, and the output end of each optical fiber (241) is the light emitting end of the pulse type laser generator;

the average power of the laser output by the semiconductor laser tube (310) is 0.1-2W, and the peak power of the output laser is 1-200W;

the optical fiber (241) is a multimode optical fiber, the core diameter of the optical fiber is between 100 and 600 mu m, and the numerical aperture NA of the optical fiber is more than 0.2; the distance between the output end of the optical fiber (241) and the inner layer (109) of the helmet is more than 25 mm; the average power of the laser output by each optical fiber (241) is not more than 2W, and the peak power of the pulse is not more than 200W.

6. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 1, characterized in that:

the pulse type laser generator is an optical fiber coupled laser generator (300), and the optical fiber coupled laser generator (300) is a solid laser generator or an optical fiber laser generator which is modulated by electric pulses, acousto-optic Q-switch, electro-optic Q-switch or mode-locked.

7. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to any one of claims 1 to 6, characterized in that: a water cooling device or an air cooling device is also arranged in the helmet (100).

8. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 7, is characterized in that:

the device also comprises a working state indicating unit;

the working state indicating unit is a visible light semiconductor laser tube (312) arranged in the pulse type laser generator or an LED lamp arranged in the helmet (100);

9. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 8, characterized in that:

the helmet outer layer (101) is made of a hard material;

the other surfaces except the light outlet end of the pulse laser generator fixed on the inner side of the middle layer (105) of the helmet are provided with a reflecting material or a reflecting film (106) for reflecting red light to near infrared light;

the helmet inner layer (109) is made of a hard or semi-hard material;

the helmet (100) further comprises a flexible shade strip (170) disposed at an inside edge of the helmet.

10. The device for treating brain diseases based on the pulsed semiconductor laser external irradiation technology according to claim 9, characterized in that:

the helmet also comprises a switching element for controlling the pulse type laser generator to work and a detection feedback unit arranged in the helmet (100);

the switching elements include an interlock power switch (460) and a signal sensor; the signal sensor is a helmet fixing belt buckle type interlock (115) or a pressure sensor (125) used for sensing the pressure between the helmet (100) and the head top in the helmet (100);

the detection feedback unit is used for detecting the working condition of the pulse type laser generator and the temperature in the helmet (100).