CN106580267B - Imaging system of human body microvascular three-dimensional ultrastructure based on sidestream dark field imaging technology - Google Patents

Imaging system of human body microvascular three-dimensional ultrastructure based on sidestream dark field imaging technology Download PDF

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CN106580267B
CN106580267B CN201710054004.1A CN201710054004A CN106580267B CN 106580267 B CN106580267 B CN 106580267B CN 201710054004 A CN201710054004 A CN 201710054004A CN 106580267 B CN106580267 B CN 106580267B
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CN106580267A (en
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董蒨
于綦悦
魏宾
夏楠
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Affiliated Hospital of University of Qingdao
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0077Devices for viewing the surface of the body, e.g. camera, magnifying lens

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Abstract

The invention relates to an imaging system of a human body microvascular three-dimensional ultrastructure based on a lateral flow dark field imaging technology, which at least comprises: a light source module for emitting a linearly propagating columnar light; an aperture module for making the light irradiated on the surface of the measured object into circularly polarized light with unchanged irradiation position and changed irradiation angle; a light splitting unit; a dark field objective lens for intensively irradiating light onto the surface of the object to be measured; an imaging unit for imaging; and a presentation module for presenting the image. Through the aperture module rotating regularly, the incident light entering the dark field objective lens is annular incident light and passes through a special light system inside the dark field objective lens, so that the outgoing light irradiates the surface of the measured object in the form of an inverted cone, the irradiation of the microvascular ultrastructure inside the measured skin at the same position by the incident light at different angles is realized, the principle of photometric three-dimensional imaging is met, three-dimensional imaging is realized, and the microvascular density of a longitudinal section and the microvascular ultrastructure are accurately quantified in a digital mode.

Description

Imaging system of human body microvascular three-dimensional ultrastructure based on sidestream dark field imaging technology
Technical Field
The invention relates to a medical instrument for medical diagnosis by utilizing an optical imaging technology, in particular to an imaging system of a human body microvascular three-dimensional ultrastructure based on a lateral flow dark field imaging technology.
Background
Microcirculation refers to the place where blood and tissue cells between the arterioles and venules exchange substances. The integrity of the function, morphology and metabolism of the microcirculation is an indispensable condition for maintaining the normal functions of human organs. Through the research of microcirculation, the special functions of various organs of the human body can be further known, the pathogenesis of the cognitive diseases is facilitated, and the disease prevention, diagnosis and treatment are facilitated. Various disease states including diabetes, hypertension, coronary heart disease and the like can cause the pathological conditions of microcirculation, including the changes of parameters such as the tube diameter of a micro-blood vessel, the density of the micro-blood vessel, the ultrastructural speed of the micro-blood vessel in the micro-blood vessel and the like, and can also observe the endothelial cells of the micro-blood vessel and the blood cells flowing in the micro-blood vessel. Therefore, the microcirculation quality is grasped by knowing the ultramicro structure of the micro blood vessels, and the method has extremely important effects on diagnosis and treatment of various diseases. The microvascular ultrastructural condition is important for health and disease diagnosis and treatment, and high-precision digital quantification is carried out on the microvascular ultrastructural condition, so that the accurate diagnosis and treatment is necessary. In order to realize accurate diagnosis and treatment by utilizing the micro-vascular ultrastructure, a 'noninvasive dynamic micro-vascular ultrastructural observation system' capable of carrying out real-time high-definition imaging and digitalization on the micro-vascular ultrastructure under the noninvasive condition is required to be indispensable.
In the medical field, there are many ways of non-invasively imaging the interior of the body through the skin, such as Computed Tomography (CT) techniques, and Magnetic Resonance Imaging (MRI) techniques, among others. Although these techniques have been developed and developed earlier, they are not suitable for use in microvascular ultrastructural imaging due to the large size of the device, low resolution, poor real-time performance, etc. Among them, lateral flow dark field (SDF) imaging techniques and Orthogonal Polarization Spectroscopy (OPS) imaging techniques are two common techniques for imaging microvascular ultrastructures.
However, in the conventional Orthogonal Polarization Spectrum (OPS) imaging technology, since the reflection capability of the polarizing plate for the orthogonal polarized light has an upper limit, the polarized reflected light cannot be filtered out by 100% to cause excessive background noise in imaging, and in order to solve this problem, a lateral flow dark field (SDF) imaging technology was proposed in 2007, the principle of which is shown in fig. 1.
In the lateral flow dark field imaging technology, annular LED illumination is firstly adopted to surround the imaging microscope lens, and the light source emitted by the LED is light with a special wavelength but not polarized light like the OPS imaging technology. The LED light is irradiated from the periphery of the micro lens to the skin in a ring shape, and scattered inside the skin while being scattered on the surface of the skin. Because the micro lens is very close to the skin, the light which is annularly irradiated on the skin and reflected back is difficult to enter the lens for imaging, and the irradiation direction of internal scattered light is random, and a part of the light irradiates the micro lens for imaging on the CCD. This avoids direct imaging of microvascular ultrastructures by skin surface reflection.
However, conventional lateral flow dark field imaging techniques can only achieve two-dimensional imaging. Although the analysis of two-dimensional imaging can quantitatively digitize the flow velocity of the ultramicro structure of the micro-blood vessels, the diameter of the micro-blood vessels and the density of the micro-blood vessels on the cross section, the two-dimensional imaging cannot acquire depth information, so that the analysis of the density of the micro-blood vessels on the longitudinal section and the shape of the micro-blood vessels cannot meet the requirements. At this time, the imaging device needs to be improved, so that the imaging device has three-dimensional measurement capability, can perform three-dimensional measurement on the microvascular ultrastructure to acquire depth information, and accurately performs digital quantification on the microvascular density of the longitudinal section and the microvascular ultrastructure.
Disclosure of Invention
In view of the above-mentioned shortcomings, it is an object of the present invention to provide an imaging system for three-dimensional ultrastructural of human microvasculature based on lateral flow dark field imaging techniques.
In order to achieve the above purpose, the technical scheme of the invention is as follows: an imaging system of a human body microvascular three-dimensional ultrastructure based on a lateral flow dark field imaging technology at least comprises:
a light source module for emitting a linearly propagating columnar light;
an aperture module for making the light irradiated on the surface of the measured object into circularly polarized light with unchanged irradiation position and changed irradiation angle;
a light-splitting unit for partially transmitting and partially reflecting light;
a dark field objective lens for intensively irradiating light onto the surface of the object to be measured, wherein scattered light transmitted when irradiated onto the surface of the skin and backscattered at micro-blood vessels inside the skin is received and imaged by the dark field objective lens;
an imaging unit for imaging;
and a presentation module for presenting the image.
Preferably, it is: the light source module comprises a light source and a collimation unit which is positioned in the irradiation direction of the light source and is used for converting emergent light into columnar linear propagation.
Preferably, it is: the aperture module comprises an opaque baffle plate capable of blocking emergent light and a driving rotating device for driving the aperture to rotate, wherein light holes are formed in the edges of the opaque baffle plate, and a dimming unit is arranged in the light holes.
Preferably, it is: the dimming unit is a 1/4 wavelength plate or a 1/4 phase difference module.
Preferably, it is: and protection devices are arranged on two sides of the dimming unit.
Preferably, it is: the two sides of the protection device are coated with an anti-reflection coating.
Preferably, it is: the light splitting unit is any one of a semi-transparent mirror and a non-polarized light splitter.
Preferably, it is: the side part of the light splitting unit is provided with a light shielding plate for blocking the light transmitted through the light splitting unit.
Preferably, it is: and a right-angle reflecting plane mirror is arranged between the collimating unit and the light splitting unit.
Preferably, it is: the periphery of the light source module, the aperture module, the light splitting unit, the dark field objective lens, the imaging unit and the imaging module is provided with a fixed frame.
The invention has the beneficial effects that:
(1) Through the aperture module rotating regularly, the incident light entering the dark field objective lens is annular incident light and passes through a special light system inside the dark field objective lens, so that the outgoing light irradiates the surface of the measured object in the form of an inverted cone, the irradiation of the microvascular ultrastructure inside the measured skin at the same position by the incident light at different angles is realized, the principle of photometric three-dimensional imaging is met, three-dimensional imaging is realized, and the microvascular density of a longitudinal section and the microvascular ultrastructure are accurately quantified in a digital mode.
(2) Through the cooperation of rotatory light ring module and dark field objective, only need an imaging system, it is realized that a plurality of two-dimensional imaging system combinations are realized to have avoided in the traditional three-dimensional imaging system for this system structure is simple small and exquisite, convenient operation, and the cost is reduced, and this is very important in practical application popularization in-process.
(3) The linearly polarized light is changed into circularly polarized light through the light adjusting unit of the aperture module part, so that the light utilization efficiency is increased, the imaging definition is improved, the three-dimensional imaging is ensured, and the real-time three-dimensional measurement of the microvascular ultrastructure is possible.
(4) The device can carry out real-time three-dimensional measurement on the microvascular ultrastructure, has clear imaging effect, and is a revolutionary invention for preventing, diagnosing and treating certain diseases.
Drawings
FIG. 1 is a schematic diagram of an apparatus in accordance with the background of the invention;
FIG. 2 is a schematic light ray diagram of embodiment 1 of the present invention;
FIG. 3 is a schematic structural view of embodiment 1 of the present invention;
FIG. 4 is a schematic light ray diagram of embodiment 2 of the present invention;
FIG. 5 is a schematic structural view of embodiment 2 of the present invention;
FIG. 6 is a schematic view of the structure of the baffle plate of the present invention;
fig. 7 is a schematic structural view of the aperture module of the present invention.
In the figure, 1-a light source; a 2-collimation unit; 3-baffle plates; 4-a light splitting unit; 5-dark field objective lens; 6-a light shielding plate; 7-a presentation module; 8-driving a rotating device; 9-fixing the frame; 10-right angle reflecting plane mirror; 11-light holes; a 12-imaging unit; 13-protection device.
Detailed Description
The invention will be further illustrated with reference to specific examples.
The invention relates to an imaging system of a human body microvascular three-dimensional ultrastructure based on a lateral flow dark field imaging technology, which at least comprises: a light source module for emitting a linearly propagating columnar light; an aperture module for making the light irradiated on the surface of the measured object into circularly polarized light with unchanged irradiation position and changed irradiation angle; a light-splitting unit for partially transmitting and partially reflecting light; a dark field objective lens for intensively irradiating light onto the surface of the object to be measured, wherein scattered light transmitted when irradiated onto the surface of the skin and backscattered at micro-blood vessels inside the skin is received and imaged by the dark field objective lens; an imaging unit for imaging; and a presentation module for presenting the image.
Wherein the two embodiments are specifically described according to whether a right angle reflecting plane mirror is provided or not.
Example 1
The imaging system of the three-dimensional ultrastructure of human microvasculature based on the lateral flow dark field imaging technique shown in fig. 2-3 at least comprises:
a light source module for emitting a linearly propagating columnar light;
an aperture module for making the light irradiated on the surface of the measured object into circularly polarized light with unchanged irradiation position and changed irradiation angle;
a light-splitting unit for partially transmitting and partially reflecting light;
a dark field objective lens for intensively irradiating light onto the surface of the object to be measured, wherein scattered light transmitted when irradiated onto the surface of the skin and backscattered at micro-blood vessels inside the skin is received and imaged by the dark field objective lens;
an imaging unit for imaging;
and a presentation module for presenting the image.
Further, the light source module comprises a light source and a collimation unit which is positioned in the irradiation direction of the light source and is used for converting the emergent light into columnar linear propagation.
Specifically, the light source is 1 a polarization film-plated LED or a semiconductor laser capable of emitting linearly polarized light. As is well known, light emitted from an LED is unpolarized light, and in order to convert the LED into circularly polarized light by a light control unit, a polarizing film layer is coated on the surface of a light emitting portion of the LED, and the light emitted from the LED first passes through the polarizing film layer to become polarized light. The LED using the plating polarization film has the advantages of long service life, uniform irradiation and no speckle noise. The disadvantage is that the light rays emitted by the light emitting diode have poor linear propagation property. Therefore, a semiconductor laser is preferable, and the price of the current semiconductor laser has been almost equivalent to that of a high-performance high-power LED, so that the use of such a semiconductor laser light source hardly increases the cost of the apparatus, and the semiconductor laser has excellent polarization characteristics and linear propagation characteristics.
The collimator unit 2 is an aspherical lens or a plano-convex lens. The aspheric lens is a double-cemented achromatic lens and comprises a concave-convex lens and a double-convex lens which are sequentially arranged along the irradiation direction of the light source, and the curvature radius of the double-convex lens is smaller than that of the concave-convex lens; the plano-convex lens is a plane and a convex surface along the irradiation direction of the light source; since the double cemented achromatic lens has small spherical aberration relative to the plano-convex lens and achieves high light collimation accuracy, the double cemented achromatic lens is preferable.
Further, as shown in fig. 6-7, the aperture module includes an opaque plate 3 capable of blocking the outgoing light and a driving rotation device 8 for driving the aperture to rotate, a light hole 11 is provided at an edge of the opaque plate 3, and the light hole 11 is provided with a dimming unit.
The driving rotation device is any one of an ultrasonic driving rotation device and a motor driving rotation device. The driving rotation device 8 is arranged through the aperture module, so that columnar light sequentially irradiates light beams at different positions of the incident aperture of the dark field objective lens along the ring shape, forms emergent light after entering the dark field objective lens 5, sequentially irradiates the emergent light, and intensively irradiates the surface of an observed object, namely, due to the rotation time difference of the aperture module, the same positions of the surface of the detected object irradiated by emergent light with different angles are formed, and the three-dimensional images of the detected object and the micro-vascular ultrastructure in the skin are formed after the three-dimensional images are respectively imaged and taken and processed.
Wherein, the dimming unit is a 1/4 wavelength plate or a 1/4 phase difference module. The incident linearly polarized light can be adjusted to circularly polarized light with stronger penetrating power and clearer imaging effect. Among them, a 1/4 retardation film is preferable. The 1/4 phase difference film is also called as a 1/4 polymer phase delay film, is made of a highly durable birefringent polymer sheet, can modify the polarization state of transmitted light, has the function of a 1/4 wavelength plate, is durable and low in cost, and greatly enhances the maintainability of equipment and reduces the cost. Specifically, referring to Table 1, the alignment of the 1/4 wavelength plate and the 1/4 retardation film was performed.
Table 1 1/4 wavelength plate or 1/4 retardation film
1/4 wavelength plate 1/4 phase difference film
Shape of material Round shape Square shape
Area of material [ mm] 76.2 (diameter) 100×100
Material of material Crystal Birefringent polymers
Transmittance of light >98% >90%
Thickness [ mm ]] 9 0.075
Price of ¥16462.5 ¥142.5
As can be seen from Table 1, the price of the 1/4 retardation film is far lower than that of the 1/4 wavelength plate under the condition of ensuring that the imaging effect is not greatly different, so that the maintenance and use cost of the device can be greatly reduced by adopting the 1/4 retardation film. On the other hand, the 1/4 retardation film has almost no thickness, and the thickness of the 1/4 wavelength plate is approximately 1cm, and the 1/4 retardation film is superior to the 1/4 wavelength plate in terms of its effect of being mounted on the front end of the present apparatus. The incident light is changed into circularly polarized light from linearly polarized light through the dimming unit, so that the light utilization efficiency is improved, and the light transmission capacity and the transmission imaging definition are improved.
As a preferred embodiment, both sides of the dimming unit are provided with protection means. Wherein the protective device may be optical glass or other transparent material.
As a preferred embodiment, both sides of the protection device are coated with an anti-reflection coating.
Further, the light splitting unit is a half lens. See figures a and b of figures 2, 3, 4 and 5 for a semi-lens.
Further, a light shielding plate 6 for blocking the light transmitted through the spectroscopic unit is provided at the side of the spectroscopic unit 4. The light shielding plate 6 mainly prevents the laser light from being erroneously taken into eyes of a human body to damage the eyes. On the other hand, the laser has certain energy, and although the adopted laser is low-power laser, the laser cannot cause thermal sensation and cannot irradiate other instruments to cause instrument damage. However, whether or not the laser is harmful, it is necessary to mask the laser for safety.
Further, the light source module, the aperture module, the beam splitting unit, the dark field objective lens, the imaging unit and the imaging module are provided with fixing frames at the periphery. The whole optical instrument is formed into a whole through the fixed frame 9, and the whole device can be arranged into a handheld device due to the small size of the selected device, so that the operation and the use are convenient.
The invention also provides an imaging method of the imaging system, which comprises the following steps:
(1) Moving the lens of the dark field objective lens 5 to the surface of the object to be measured, starting the light source 1, and enabling the emergent light to pass through the collimation unit to form columnar linear light;
(2) When the linearly transmitted columnar emergent light irradiates the aperture module, only one beam of incident light passes through the light transmission hole 11 and becomes circularly polarized light through the light adjusting unit, and the rest of the incident light is blocked by the light-tight baffle plate and cannot pass through the light-tight baffle plate;
(3) The transmitted circularly polarized light is reflected by the semi-transparent mirror at right angles, and is reflected by the light splitting unit, so that along with the rotation of the aperture module, columnar light sequentially irradiates light beams at different positions of an incident aperture of the dark field objective lens along a ring shape, forms emergent light after entering the dark field objective lens 5, sequentially irradiates the emergent light, and intensively irradiates the focal position of the dark field objective lens 5 on the surface of an observed object, namely, due to the rotation of the aperture module with time difference, the emergent light irradiated at different angles is formed to irradiate the same position on the surface of the detected object, and the light is transmitted when the emergent light irradiates the surface of the skin, and is backscattered at micro-blood vessels in the skin;
(4) The scattered light part with random propagation direction enters the dark field objective lens, passes through the light splitting unit, is imaged by the imaging unit, and is displayed on the imaging module to form a two-dimensional image;
(5) The aperture module is driven to regularly rotate around the central axis of the aperture module by driving the rotating device 8, the processes of 1-4 are repeated, and a two-dimensional image is formed after the aperture module rotates for one angle;
(6) A series of two-dimensional images shot at the same position and different angles are processed, and three-dimensional imaging of the microvascular ultrastructure is realized according to the principle of photometric stereo three-dimensional measurement.
Specifically, a part of the light irradiated to the skin surface is reflected, and the incident light transmitted through the skin surface is backscattered, and the reflected light is reflected to the other end of the outgoing light of the dark field objective lens due to the relatively uniform propagation direction, so that the reflected light is rarely imaged by the dark field objective lens; the direction of travel of the back-scattered light is random, so that most of the light is imaged by the dark field objective lens. The imaging unit records imaging when a plurality of light sources with different angles irradiate, and three-dimensional imaging is carried out on the microvascular ultrastructure in the skin by utilizing a photometric stereo measurement method.
Example 2
As shown in fig. 4 to 5, unlike embodiment 1, a right angle reflecting plane mirror 10 is provided between the collimator lens 2 and the half mirror. The direction of the light source can be parallel to the direction of the imaging module through the right angle reflecting plane mirror 10, so that the whole device is more compact and attractive, and is convenient to hold, use and operate. The procedure is as in example 1.
Example 3
Unlike example 1, the spectroscopic unit is a non-polarizing beam splitter, and the rest is the same as example 1. See c and d for figures 2, 3, 4 and 5 for the drawings of the unpolarized beam splitter.
Example 4
Unlike embodiment 3, a right angle reflecting plane mirror 10 is provided between the collimator lens 2 and the non-polarizing beam splitter. The direction of the light source can be parallel to the direction of the imaging module through the right angle reflecting plane mirror 10, so that the whole device is more compact and attractive, and is convenient to hold, use and operate. The procedure is as in example 3.

Claims (7)

1. An imaging method of an imaging system of a human body microvascular three-dimensional ultrastructure based on a lateral flow dark field imaging technology is characterized by comprising the following steps of: the imaging system includes at least:
a light source module for emitting a linearly propagating columnar light;
an aperture module for making the light irradiated on the surface of the measured object into circularly polarized light with unchanged irradiation position and changed irradiation angle;
a light-splitting unit (4) for partially transmitting and partially reflecting light;
a dark field objective lens (5) for intensively irradiating light onto the surface of the object to be measured, wherein scattered light transmitted when irradiated onto the surface of the skin and backscattered at micro-blood vessels inside the skin is received and imaged by the dark field objective lens (5);
an imaging unit (12) for imaging;
a presentation module (7) for presenting an image;
the aperture module comprises an opaque baffle (3) capable of blocking emergent light and a driving rotating device for driving the aperture to rotate, wherein a light hole (11) is formed in the edge of the opaque baffle (3), and a dimming unit is arranged in the light hole;
the light source module comprises a light source (1) and a collimation unit (2) which is positioned in the irradiation direction of the light source (1) and is used for converting emergent light into columnar linear propagation;
a light shielding plate (6) for blocking the light transmitted through the light splitting unit is arranged at the side part of the light splitting unit (4);
the imaging method of the imaging system comprises the following steps:
s1, moving a lens of a dark field objective lens to the surface of a measured object, starting a light source, and enabling emergent light to pass through a collimation unit (2) to form columnar linear light;
s2, when the linearly transmitted columnar emergent light irradiates the aperture module, only one beam of incident light passes through the light transmission hole and becomes circularly polarized light through the light adjusting unit, and the rest of incident light is blocked by the light shielding plate (6) and cannot pass through the light shielding plate;
s3, reflecting the transmitted circularly polarized light by the right angle of the light splitting unit, and along with the rotation of the aperture module, enabling columnar light to sequentially emit light beams at different positions of an incident aperture of the dark field objective lens along the ring shape, forming emergent light after entering the dark field objective lens, sequentially irradiating the emergent light, and concentrating the focal position of the dark field objective lens irradiated on the surface of an observed object, namely, forming emergent light irradiated at different angles on the same position of the surface of the detected object due to the rotation of the aperture module with time difference, transmitting the light when the emergent light irradiates the surface of the skin, and back scattering the micro blood vessels in the skin;
s4: the scattered light part with random propagation direction enters the dark field objective lens, passes through the light splitting unit, is imaged by the imaging unit, and is displayed on the imaging module to form a two-dimensional image;
s5: the aperture module is driven to regularly rotate around the central axis of the aperture module by driving the rotating device, the processes of S1-S4 are repeated, and a two-dimensional image is formed after the aperture module rotates for one angle;
s6: a series of two-dimensional images shot at the same position and different angles are processed, and three-dimensional imaging of the microvascular ultrastructure is realized according to the principle of photometric stereo three-dimensional measurement.
2. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 1, characterized in that: the dimming unit is a 1/4 wavelength plate or a 1/4 phase difference module.
3. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 1, characterized in that: and protection devices (13) are arranged on two sides of the dimming unit.
4. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 3, characterized in that: both sides of the protection device (13) are coated with an anti-reflection coating.
5. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 1, characterized in that: the light splitting unit (4) is any one of a semi-transparent mirror and a non-polarizing light splitter.
6. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 1, characterized in that: a right-angle reflecting plane mirror (10) is arranged between the collimation unit (2) and the light splitting unit (4).
7. The imaging method of the imaging system of the three-dimensional ultrastructure of the human microvasculature based on the lateral flow dark field imaging technique according to claim 1, characterized in that: the periphery of the light source module, the aperture module, the light splitting unit (4), the dark field objective lens (5), the imaging unit (12) and the imaging module (7) is provided with a fixed frame (9).
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