BE1031381B1 - INTERVENTIONAL OPTICAL STIMULATION DEVICE - Google Patents

Abstract

The present invention relates to the interdisciplinary field of biological photonics and relates to an interventional optical nerve stimulation device. This device comprises a transmission guide module, an optical stimulation terminal module, a light source generation module used for producing a light source of specific wavelength, power, pulse period and pulse width according to actual needs, coupled in the transmission guide module which is intermediate between the light source generation module and the optical stimulation terminal module, to receive the laser beam produced by the light source generation module, guide it to a specific brain area of the target organism; the optical stimulation terminal module is used for fixing the laser beam transmitted by the transmission guide module in a predetermined specific brain area of the target organism.

Description

1 BE2024/5425

INTERVENTIONAL OPTICAL STIMULATION DEVICE

Technical field

The present invention relates to the interdisciplinary field of biological photonics in biology, relating to an interventional optical stimulation device.

Prior art

Biological photonics is a discipline that studies the interaction, generation, and use of light (photons) with living organisms for imaging, sensing, and manipulating biological materials. In this field, the scientific community has extensively studied various methods of neuronal regulation in the form of light, electricity, magnetism, sound, etc., and applied them clinically to treat functional neurological diseases such as mental disorders, drug-resistant epilepsy, neurodegenerative diseases, etc. In light-based neuronal regulation methods, optogenetics and near-infrared modulation have seen significant development in recent years.

Optogenetics involves introducing exogenous light-sensitive proteins into specific living cells using viruses, and then using light stimulations of specific wavelengths, powers, pulse periods, and pulse widths to regulate neuronal activity, control the behavior of cells or even animals. This technology has exceptional characteristics such as high sensitivity, low toxicity, temporal precision in the order of milliseconds, and spatial precision at the cellular or even subcellular level, thus providing researchers with a method to explore the functional interactions between different brain areas, thus opening new fields for neuroscience and neurobiology.

Near-infrared modulation is a promising clinically applicable regulation method, having a modulatory effect on neuronal signals and behavior, and exhibiting non-thermal, long-range, and reversible characteristics. This technology has been demonstrated to inhibit cancer cell migration and glycolysis, and research results have shown acceleration of associative learning in mice and modulation of neuronal activity in zebrafish larvae, demonstrating great research potential.

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Currently, the implementation of optical stimulation or near-infrared modulation in optogenetics requires special manipulations such as surgical opening of the animal skull, opening of the skull or thinning of the skull, thus causing significant damage to the laboratory animals, which hinders the performance of in vivo experiments and the obtaining of stable and reliable experimental data, and fails to provide long-term, stable and sustainable experimental conditions.

Statement of the invention

The present invention provides an interventional optical stimulation device to solve the difficult implementation problems of existing optical neural stimulation conditions, thereby providing an experimental platform for optical neural stimulation and other biological photonics research.

To achieve the above-mentioned objectives, the present invention uses the following technical scheme:

An interventional optical stimulation device, comprising a light source generation module, a transmission guidance module and an optical stimulation terminal module;

The light source generation module is used to generate light source of specific wavelengths, powers, pulse periods and pulse widths according to actual needs, coupled into the transmission guide module;

The transmission guide module serves as an intermediary for connecting the light source generation module and the optical stimulation terminal module, receiving the laser beam generated by the light source generation module and guiding it to a specific target brain area of the living organism;

The optical stimulation terminal module is used to fix the laser beam transmitted by the transmission guidance module into a predefined specific brain area of the living organism.

In an improved embodiment, the light source generation module comprises a light source, an attenuation portion and a coupling portion; the light source, the attenuation portion and the coupling portion are connected by a collimated optical path: the light source emits a laser beam of wavelength,

3 BE2024/5425 of specific pulse period and pulse width, obtains a specific power laser beam after the attenuation part, and is coupled in the transmission guide module to the coupling part.

In an improved embodiment, the light source and the dimming portion are removably connected.

In an improved embodiment, the coupling portion is a mechanical device fixing the end of the transmission guide module, with a groove structure inside, a protruding surface fitting the end of the transmission guide module, fixed horizontally with a nut.

In an improved embodiment, the transmission guidance module comprises an optical fiber layer, a support layer and a protective layer; the support layer and the protective layer tightly wrap the optical fiber layer from the inside to the outside, thereby forming a transmission guidance module which is implanted along a pre-designed path in the blood vessels of the brain of the organism, combining at its end with the optical stimulation terminal module.

In this further optimized technical scheme, the support layer is made of titanium alloy with a contractible lattice structure, with a diameter less than 0.8 mm in the contracted state; the protection layer is a 1 mm diameter microtube; the optical fiber layer is an optical fiber of the IRF-Se series with a diameter of 100 um, with a numerical aperture index of 0.27 for selenium infrared optical fibers.

In this further optimized technical scheme, the optical stimulation terminal module comprises an optical fiber end and a support frame, the optical fiber end being fixed inside the support frame, where the optical fiber end is the terminal part of the optical fiber layer, and the support frame is a titanium alloy lattice structure with extensible and contractile properties.

In this even more optimized technical scheme, the support frame has a contraction diameter smaller than the internal diameter of the protective layer.

In this further optimized technical scheme, the output power Pour at the light end of the interventional optical stimulation device satisfies:

4 BE2024/5425

For = Pin * (04, Be NPA) + 10770

Pout WHERE and P, respectively represent the output power and the power of the input optical fiber layer; element 1052 describes the attenuation of the light beam in the optical fiber layer, a representing the loss coefficient of the optical fiber; (ny, bn, 2) describes the attenuation of the coupling process of the light source at the input of the optical fiber layer, for the case of Gaussian beam incidence, can be expressed as: erf [ezen] (ny, bn, 2) = Cerf] *n where Ony represents the near field width of the laser beam, à is the wavelength of the beam, 8, represents the numerical aperture angle of the optical fiber, erf is the Gaussian error function, n represents the reflection loss at the end of the optical fiber;

The loss coefficient a comes from transmission losses due to optical materials and manufacturing, as well as bends during use, due to the need for the transmission guide module to penetrate the blood vessels of the target brain area of the body, it is necessary to take into account macroscopic bending losses: ak? 2 (2 — n2K2)2 a exp [2 |B? — nzköa 37 N] (RVB? = n2kga2ké (n? — n3) where a is the radius of the core, andn, and n, are the refractive indices of the optical fiber core and cladding respectively, and k and ko are the wave vectors of light in the optical fiber and in vacuum respectively, B is the propagation constant, R is the bending radius of the optical fiber.

Unlike existing technology, the above technical scheme has the following advantages: the invention provides an interventional optical stimulation device which, by its interventional mode, can realize optical stimulation of specific brain areas of living organisms under microsurgery conditions. The interventional mode reduces the damage to living organisms for optical stimulation compared with existing technology, and the stimulation is performed inside the brain areas of the organisms, thus ensuring the effectiveness of stimulation and the accuracy of subsequent data collection; by following a pre-established path along the blood vessels of the brain area of the organisms, the light beam 5 is precisely directed to the specific area; the light source and the attenuation device can be replaced according to actual needs, emitting light beams of specific wavelengths, powers, pulse periods and pulse widths, suitable for optical stimulation experiments under different conditions; The transmission guide module has certain extensibility, and its specifications with the optical stimulation terminal module can be adjusted within a certain range, suitable for biological experiments on different brain structures, with high versatility; in addition, the titanium alloy bracket has good biocompatibility, reducing the exclusivity of biological tissues.

Brief description of the drawings

Figure 1 is a structural diagram of the interventional optical stimulation device;

Figure 2 is a schematic diagram of the light source generation module;

Figure 3 is a schematic of the transmission guidance module;

Figure 4 is a cross-sectional diagram of the transmission guide module;

Figure 5 is a schematic of the optical stimulation terminal module;

Figure 6 is a top-view schematic of interventional optical stimulation through the blood vessels of a sheep's brain.

Reference signs:

Light source generation module 1; Light source 11; Attenuation part 12; Coupling part 13; Transmission guide module 2; Optical fiber layer 21; Support layer 22; Protective layer 23; Optical stimulation terminal module 3; Optical fiber end 31; Support frame 32.

Detailed description of the embodiments

To explain in detail the technical content, construction features, objectives and achieved effects of the technical solution, examples of specific embodiments are described below, accompanied by detailed explanations and references to the drawings.

6 BE2024/5425

As shown in Figure 1, structural diagram of the interventional optical stimulation device. The interventional optical stimulation device provided by the present invention comprises a light source generation module 1, a transmission guide module 2 and an optical stimulation terminal module 3 connected in sequence. The light source generation module 1 is used for generating a light source of specific wavelengths, powers, pulse periods and pulse widths according to actual needs, coupled in the transmission guide module 2. The transmission guide module 2 serves as an intermediary for connecting the light source generation module and the optical stimulation terminal module, receiving the laser beam generated by the light source generation module and guiding it to a specific target brain area of the living organism. The optical stimulation terminal module 3 is used for fixing the laser beam transmitted by the transmission guide module in a predefined specific brain area of the living organism.

The light source generation module 1 comprises a light source 11, an attenuation part 12 and a coupling part 13.

The transmission guidance module 2 comprises an optical fiber layer 21, a support layer 22 and a protection layer 23.

The optical stimulation terminal module 3 comprises an optical fiber end 31 and a support frame 32.

As shown in Figure 2, a schematic diagram of the light source generation module. The light source generation module 1 comprises a light source 11, an attenuation part 12, and a coupling part 13. The light source 11 is a tunable laser selected according to actual needs for different wavelengths, pulse periods, and pulse widths; the attenuation part 12 is a device for attenuating the laser beam according to actual power needs, such as an attenuation blade or a power adjustment device integrated with the laser; the coupling part 13 is a mechanical device fixing the end of the transmission guide module 2, with a groove structure inside, a protruding surface fitting the end of the transmission guide module 2, fixed horizontally with a nut.

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The light source 11, the attenuation part 12 and the coupling part 13 are connected by a collimated optical path: the light source 11 emits a laser beam of specific wavelength, which, after the attenuation part 12, becomes a laser beam of specific power, and is coupled in the optical fiber layer 21 of the transmission guide module 2 to the coupling part 13. The light source 11 and the attenuation part 12 are detachable and can be replaced according to actual needs.

In this example, the light source 11 uses a quantum cascade mid-infrared laser with a wide wavelength range and easy integration to generate a mid-infrared beam, the attenuation part 12 uses an attenuation blade to obtain an output power of the light beam from the end of the optical fiber in the mW range, and the coupling part 13 is a mechanical device fixing the end of the transmission guide module 2, with a groove structure inside, a protruding surface fitting the end of the transmission guide module 2, fixed horizontally with a nut. The light source 11 and the attenuation part 12 are detachable and can be replaced according to actual needs. Actual needs refer to the optical parameters required when using this device for optical neural stimulation.

As shown in Figure 3, schematic diagram of the transmission guide module. The specifications of the optical fiber layer 21, the support layer 22 and the protection layer 23 of the transmission guide module 2 can be customized according to actual needs; in this example, the support layer 22 is made of titanium alloy with a lattice structure that can be contracted, with a diameter of less than 0.8 mm in the contracted state, the protection layer 23 is a microtube with a diameter of 1 mm, the optical fiber layer 21 is an optical fiber of the IRF-Se series with a diameter of 100 um, with a numerical aperture index of 0.27 for selenium infrared optical fibers. As shown in Figure 4, a cross-sectional diagram of the transmission guidance module, the support layer 22 and the protection layer 23 tightly wrap the optical fiber layer 21 from the inside to the outside, thereby forming a transmission guidance module 2 which is implanted along a pre-designed path in the blood vessels of the body's brain, combining at its end with the optical stimulation terminal module 3, thereby enabling the end of the optical fiber 31 to be close to the specific brain area.

8 BE2024/5425

The transmission guide module 2 comprises an optical fiber layer 21, a support layer 22 and a protection layer 23. The optical fiber layer 21 is an optical fiber selected according to actual needs, with a specific operating window and supporting a specific mode; the support layer 22 is made of titanium alloy, connecting to the end of the support frame 32; the protection layer 23 is a microtube whose diameter is larger than the contracted diameter of the support frame 32. The transmission guide module 2 has a certain extensibility to adapt to the nonlinear structure of cerebral blood vessels.

As shown in Figure 5, schematic of the optical stimulation terminal module.

The support frame 32, with its metal lattice structure, fits the blood vessel wall of the body's brain, with an internal groove fixing the optical fiber end 31; the optical fiber end 31 emits a laser beam propagated from the optical fiber layer 21 with a defined angle, stimulating a specific brain area. The optical stimulation terminal module 3 comprises an optical fiber end 31 and a support frame 32. The optical fiber end 31 is the terminal portion of the optical fiber layer 21, and the support frame 32 is a titanium alloy lattice structure with expandable and contractile properties.

The support frame 32, when not deployed, is wrapped inside the protective layer 23. Before optical stimulation, by pulling the protective layer 23 laterally, the support frame 32 naturally deploys, adapting to the blood vessel wall of the body's brain, with an internal groove fixing the end of the optical fiber 31; the end of the optical fiber 31 emits a laser beam propagated from the optical fiber layer 21 to this location, stimulating a specific brain area.

The specifications of the transmission guide module 2 and the optical stimulation terminal module 3 can be customized within a certain range; in the application of the invention, individual organisms have anatomical differences, with different cerebral vascular structures, distributions and diameters, and specific locations in the brain for the specific experiments, and can be adapted according to actual needs. Actual needs refer to the specific parameters required to achieve the stimulation target area.

9 BE2024/5425 neuronal and meet the requirements of vascular structures and applications when using this device.

In practical application, the optic nerve stimulation effect is closely related to the wavelength and light power; once the wavelength of the light source 11 is determined, the selection of the light source 11, the attenuation portion 12 and the optical fiber layer 21 should prioritize the final output power.

For the problem of output power attenuation of optical fibers, the interventional optic nerve stimulation device satisfies the output power For final at the end 31 of the optical fiber:

Pout = Pn * (ny, On, A) * 102 where P,ut and P, represent the output power and the power of the optical fiber layer 21 respectively; 107% < describes the attenuation of the light beam in the optical fiber layer 21, a representing the loss coefficient of the optical fiber; (ny; 027 2) describes the attenuation of the coupling process from the light source 11 to the optical fiber layer 21, for an incident Gaussian beam, can be expressed as erf [Eze] (ny, bn, 2) = erf] *n

WHERE w,y represents the near-field width of the laser beam, α is the beam wavelength, δ represents the numerical aperture angle of the optical fiber, erf is the Gaussian error function, n represents the reflection loss at the end of the optical fiber.

The loss coefficient a arises from transmission losses due to optical materials and manufacturing, as well as bending during use. Since the transmission guide module 2 must penetrate the cerebral blood vessels of the target organism, macro bending losses must be taken into account, for a multimode optical fiber: ak? 2 (82 — n2k2)2 a mm + exp [2 [ß? — nîk?a > gr 8

Striped? — nîkga?k$(n7 — n3)

10 BE2024/5425 where a is the radius of the fiber core, n, and n, are the refractive indices of the core layer and the cladding respectively, k and ko are the wave vectors in the optical fiber and in vacuum respectively, B is the propagation constant, R is the radius of curvature of the fiber, similar results are obtained for a single-mode optical fiber.

In this example, the target organism of the chosen optic nerve stimulation is a sheep. Using the light source generation module 1, a light beam is coupled into the transmission guidance module 2 according to the optical parameters required by the experiment, and then guided along a specified path previously implanted in the sheep's cerebral blood vessels to reach a specific brain area. The optical stimulation terminal module 3 deploys a titanium alloy support frame to fit against the vascular wall, fixing the end of the light beam near the specified brain area, allowing the light beam to act on the target brain area at a specified angle.

As shown in Figure 6, a bird's eye view for interventional optic nerve stimulation through the blood vessels of the sheep brain. After selecting the sheep brain area requiring optic nerve stimulation, based on the vascular structure of the sheep brain area obtained from angiography, the path by which the transmission guide module 2 will reach the blood vessels near the sheep brain area is determined; an incision is made at the location of the specified blood vessels, the transmission guide module 2 is inserted into the blood vessels from this incision, sticking against the vascular wall along the specified path to reach the target position.

As illustrated in Figure 6, once the microcatheter is removed, the support frame 32 of the optical stimulation terminal module 3 opens naturally, fitting tightly against the vascular wall, with the end of the optical fiber 31 emitting a light beam at a specified angle, acting on a specific brain area of the sheep.

It should be noted that in this document, relationship terms such as "first" and "second" are simply used to distinguish one entity or operation from another, without necessarily implying an actual relationship or order between those entities or operations. In addition, the terms "include," "contain," or any other variation are intended to include, but are not limited to, processes, methods, articles, or

11 BE2024/5425 terminal devices comprising a series of elements are not limited to these elements, but also include other elements not explicitly listed, or elements inherent in these processes, methods, articles or terminal devices. In the absence of further restrictions, the elements defined by the expressions "comprise." or "contain." are not exclusive and may include other elements in the processes, methods, articles or terminal devices comprising said elements. Furthermore, in this document, the terms "greater than", "less than", "exceeding" are understood as not including the number in question; "above", "below", "within" are understood as including the number in question.

Although the above examples have been described, once those skilled in the art in this field understand the basic concept, they may make further modifications and adaptations to these examples, therefore the above is only an example of the invention and does not limit the scope of patent protection of the invention, any equivalent structure or process change made by using the contents of this description and the drawings, or by applying it directly or indirectly to other related technical fields, is also included in the scope of patent protection of the invention.

Claims (9)

12 BE2024/5425 Claims 1. An interventional optical stimulation device, comprising a light source generation module, a transmission guide module and an optical stimulation terminal module; the light source generation module is used for generating, according to actual needs, a light source of specific wavelength, power, pulse period and pulse width, coupled in the transmission guide module; the transmission guide module serves as an intermediary for connecting the light source generation module and the optical stimulation terminal module, so as to receive the laser beam generated by the light source generation module and guide it to a specific target biological brain area; the optical stimulation terminal module is used for fixing the laser beam transmitted by the transmission guide module in a predefined target biological brain area. 2. The interventional optical stimulation device according to claim 1, characterized in that the light source generation module comprises a light source, an attenuation part and a coupling part; the light source, the attenuation part and the coupling part are connected by a collimated light path: the light source emits a laser beam of specified wavelength, pulse period and pulse width, obtains a laser beam of specified power after the attenuation part, and is coupled in the transmission guide module to the coupling part. 3. The interventional optical stimulation device according to claim 2, characterized in that the light source and the attenuation part are removably connected. 4. The interventional optical stimulation device according to claim 2, characterized in that the coupling part is a mechanical device fixing the front end of the transmission guide module, with an internal groove structure and a protruding surface fitting the front end of the transmission guide module, fixed horizontally with a nut. 5. The interventional optical stimulation device according to claim 1, characterized in that the transmission guidance module comprises a layer of optical fibers, 13 BE2024/5425 a supporting layer and a protective layer; the supporting layer and the protective layer tightly wrap the optical fiber layer from inside to outside, and the transmission guidance module thus formed is implanted along a pre-designed path in the biological cerebral blood vessels, combining with the end of the optical stimulation terminal module. 6. The interventional optical stimulation device according to claim 5, characterized in that the support layer is made of titanium alloy, with an expandable mesh structure in a contracted state, a diameter of less than 0.8 MM; the protective layer is a microtube of 1 mm diameter; the optical fiber layer is a wire of 100 um diameter, of the IRF-Se infrared optical fiber series with a numerical aperture of 0.27. 7. The interventional optical stimulation device according to claim 5, characterized in that the optical stimulation terminal module comprises an optical fiber end and a support frame, the optical fiber end being fixed inside the support frame, the optical fiber end being the terminal portion of the optical fiber layer, the support frame being a titanium alloy mesh structure with expandable and contractile properties. 8. The interventional optical stimulation device according to claim 7, characterized in that the contraction diameter of the support frame is less than the internal diameter of the protective layer. 9. The interventional optical stimulation device according to claim 7, characterized in that the final emission power Pour at the light end of the interventional optical stimulation device satisfies: Pour = Pin * Meng Gen, 4) + 10770 WHERE Put and P, respectively represent the output power and the power of the input optical fiber layer; 10755 describes the attenuation of the light beam in the optical fiber layer, a representing the loss coefficient of the optical fiber; (ny; 027 2) describes the attenuation of the coupling process of the light source (11) at the input of the optical fiber layer, for an incident Gaussian beam, can be expressed as: 14 BE2024/5425 erf [Eze] (ny, bn, 2) = erf] *n where Ony represents the near-field width of the laser beam, Å is the beam wavelength, 6, represents the numerical aperture angle of the optical fiber, erf is the Gaussian error function, n represents the reflection loss at the end of the optical fiber; the loss coefficient a comes from transmission losses due to optical materials and manufacturing, as well as bends during use, due to the need for the transmission guidance module to penetrate the target cerebral blood vessels, macro bending losses must be taken into account: ak? 8 - n2k2)2 a=— + exp [2 |8: nikia EN Raye? — nîkga?k$(n7 — n3) where a is the radius of the fiber core, n, and n; represent the refractive index of the core layer and the cladding respectively, k and k represent the wave vector of light in the optical fiber and in vacuum respectively, B is the propagation constant, R is the radius of curvature of the optical fiber.