CN111281343A - Wearable multi-modal imaging device and imaging method thereof - Google Patents

Wearable multi-modal imaging device and imaging method thereof Download PDF

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Publication number
CN111281343A
CN111281343A CN202010099239.4A CN202010099239A CN111281343A CN 111281343 A CN111281343 A CN 111281343A CN 202010099239 A CN202010099239 A CN 202010099239A CN 111281343 A CN111281343 A CN 111281343A
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imaging
module
animal
wavelength division
division multiplexer
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杨志刚
顾振宇
张建国
屈军乐
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Shenzhen University
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Shenzhen University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6802Sensor mounted on worn items
    • 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
    • A61B5/0062Arrangements for scanning
    • A61B5/0064Body surface scanning
    • 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
    • A61B5/0062Arrangements for scanning
    • A61B5/0066Optical coherence imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026Measuring blood flow
    • A61B5/0261Measuring blood flow using optical means, e.g. infrared light
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1072Measuring physical dimensions, e.g. size of the entire body or parts thereof measuring distances on the body, e.g. measuring length, height or thickness
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1075Measuring physical dimensions, e.g. size of the entire body or parts thereof for measuring dimensions by non-invasive methods, e.g. for determining thickness of tissue layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1079Measuring physical dimensions, e.g. size of the entire body or parts thereof using optical or photographic means
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14542Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40Animals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00Evaluating a particular growth phase or type of persons or animals
    • A61B2503/42Evaluating a particular growth phase or type of persons or animals for laboratory research

Abstract

The invention discloses a wearable multi-modal imaging device and an imaging method thereof, wherein the imaging device comprises: the device comprises an optical coherence tomography module, a photoacoustic imaging module, a laser speckle imaging module, a wavelength division multiplexer and an imaging probe, wherein the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module are respectively connected with the imaging probe through the wavelength division multiplexer; the wavelength division multiplexer receives the optical signals respectively output by the imaging modules and irradiates the optical signals to an imaging area of the animal to be detected through the imaging probe; the imaging probe receives a signal returned by the animal to be detected, and the returned signal is respectively sent to the corresponding optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module through the wavelength division multiplexer for collection, so that a corresponding imaging image is obtained. By implementing the invention, the change of blood flow of the blood vessel can be monitored for a plurality of times and for a long time under the waking state of the animal, and the multi-parameter tissue structure information of the blood vessel can be obtained simultaneously.

Description

Wearable multi-modal imaging device and imaging method thereof
Technical Field
The invention relates to the technical field of optical imaging, in particular to a wearable multi-modal imaging device and an imaging method thereof.
Background
With the development of optical imaging technology, optical imaging technology also plays a crucial role in the field of medical imaging. It has wide application in the research fields of hemodynamics, oncology, ophthalmology, cardiovascular disease detection, pharmacological analysis and the like. In the optical imaging research of the brain region, a plurality of scientific research institutions have conducted more intensive research. For example, various optical imaging techniques are used to perform hemodynamic experimental studies related to angiography, blood oxygen saturation measurement, cerebral ischemia model monitoring, stimulated neural response, and the like.
However, due to the limitation of various imaging principles and the limitation of the overlarge volume of the existing imaging device, in the actual imaging process, when the skin or the head blood vessel of the mouse is imaged, the mouse needs to be anesthetized by drugs and then fixed below the imaging probe for imaging. Different doses of anesthetic are used for mice with different weights, so that the dose of the anesthetic is difficult to control, and the mice cannot be fully anesthetized due to too small anesthetic amount, so that the progress of an experiment is influenced; excessive anesthesia can lead to over-anesthesia and death of the mice. And the nervous activity of the mouse can be influenced when the mouse is in an anesthesia state, so that the research on the nervous activity of the mouse in a normal activity state is not facilitated.
Disclosure of Invention
In view of this, embodiments of the present invention provide a wearable multi-modality imaging apparatus and an imaging method thereof, so as to solve the technical problem that the imaging apparatus in the prior art is not favorable for developing research on animals.
The technical scheme provided by the invention is as follows:
a first aspect of embodiments of the present invention provides a wearable multimodal imaging apparatus, comprising: the device comprises an optical coherence tomography module, a photoacoustic imaging module, a laser speckle imaging module, a wavelength division multiplexer and an imaging probe, wherein the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module are respectively connected with the imaging probe through the wavelength division multiplexer; the wavelength division multiplexer receives optical signals respectively output by the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module, and irradiates the optical signals to an imaging area of an animal to be detected through the imaging probe; the imaging probe receives a signal returned by the animal to be detected, and the returned signal is respectively sent to the corresponding optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module through the wavelength division multiplexer for collection, so that a corresponding imaging image is obtained.
Optionally, the imaging probe comprises: the optical fiber connector comprises a main body, a support, a fixed substrate and a combined signal wire, wherein the main body is detachably connected to the first surface of the support, and the combined signal wire is arranged inside the main body and used for transmitting the optical signal and the returned signal; the fixed substrate is detachably connected to a second surface, opposite to the first surface, of the support, and the imaging probe is fixed to an animal to be tested through the fixed substrate.
Optionally, the body is connected to the first surface of the support by a snap groove.
Optionally, the fixed base is threadedly connected with the support.
Optionally, the imaging probe further comprises: the mobile module is arranged in the main body, and the light-gathering assembly and the photoacoustic conversion assembly are arranged on the mobile module; the light condensing assembly is connected with the combined signal line and is used for receiving the optical signals output by the wavelength division multiplexer through the combined signal line and receiving the signals returned by the animal to be detected and respectively sending the signals to the corresponding optical coherence tomography module and the corresponding laser speckle imaging module through the wavelength division multiplexer; the photoacoustic conversion assembly is used for receiving a signal returned by an animal to be detected, converting the signal into an electric signal and sending the electric signal to the photoacoustic imaging module through the wavelength division multiplexer.
Optionally, the light focusing assembly comprises: the self-focusing lens receives the optical signal output by the wavelength division multiplexer through a combined signal line and outputs the optical signal through the micro-reflector, the double-axis MEMS micro-scanning vibrating mirror and the focusing lens in sequence.
Optionally, the micro-mirror is arranged right below the self-focusing lens at an angle of 45 degrees with the bottom of the main body; the double-axis MEMS micro-scanning galvanometer is arranged on the right side of the micro-reflector and is parallel to the micro-reflector; the focusing lens is arranged right below the biaxial MEMS micro-scanning galvanometer and is parallel to the bottom of the main body.
Optionally, the fixed substrate comprises a tightening strip and a flexible bottom surface, the flexible bottom surface is detachably connected to the second surface of the support, and the imaging probe is fixed on the animal to be tested through the tightening strip.
Optionally, the wearable multi-modality imaging apparatus further comprises: the support transparent cover is matched with the support.
A second aspect of the embodiments of the present invention provides an imaging method of a wearable multi-modality imaging apparatus, which is applied to the wearable multi-modality imaging apparatus according to any one of the first aspect and the first aspect of the embodiments of the present invention, and includes the following steps: fixing an imaging probe on an animal to be detected; respectively starting the light sources of the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module, so that light signals output by the light sources are incident on an animal to be detected through the wavelength division multiplexer and the imaging probe; moving a moving module in the imaging probe according to a preset imaging area until optical signals output by the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module reach a preset position through the wavelength division multiplexer and the imaging probe; rotating the double-shaft MEMS micro-scanning galvanometer to perform two-dimensional scanning on a preset imaging area; and obtaining corresponding imaging images according to the signals returned by the animal to be detected, which are received by the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module.
The technical scheme of the invention has the following advantages:
the wearable multi-modal imaging device provided by the embodiment of the invention can be stably worn on the animal body and moves along with the animal, the animal does not need to be fixedly anesthetized, the change of blood flow of the blood vessel can be monitored for a long time for a plurality of times in the waking state of the animal, and the wearable imaging device can be worn on any part of the animal and is not limited to a specific part. Therefore, the wearable multi-modality imaging device provided by the embodiment of the invention can solve the technical problem that the imaging device in the prior art is not beneficial to researching animals in a normal state.
The wearable multi-modal imaging device provided by the embodiment of the invention couples optical coherence tomography, photoacoustic imaging and laser speckle imaging together, thereby realizing the technical effect that the three imaging modes work simultaneously. Meanwhile, the wearable multi-modal imaging device provided by the embodiment of the invention can make up for the defect of a single imaging mode and obtain the multi-parameter tissue structure information of the blood vessel. The optical coherence tomography can provide information of tissues with scattering characteristics, can obtain the caliber and depth data of the capillary, the photoacoustic imaging can provide information of tissues with absorption characteristics, can obtain the data of blood oxygen saturation and hemoglobin concentration, and the laser speckle imaging can obtain the caliber data and flow rate data of the capillary. Therefore, the wearable multi-modal imaging device provided by the embodiment of the invention has wide research prospect and application value.
The imaging method of the wearable multi-modal imaging device provided by the embodiment of the invention can be used for continuously acquiring signals of biological tissue structures. After the imaging is finished once, when the area is replaced for acquisition, the computer is only required to drive the mobile module to select the required imaging area for signal acquisition. When needing to wait for a long time and then collecting, the main body of the probe can be taken down, and when needing to be tested next time, the main body is installed again. When the biological tissue needs to be subjected to surgical treatment, the fixing nut for connecting the support and the flexible bottom surface can be unscrewed, the tightening belt is loosened, and then the whole imaging probe is taken down.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a block diagram of a wearable multi-modality imaging apparatus according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a wearable multi-modality imaging apparatus according to an embodiment of the present invention;
FIG. 3 is a schematic structural diagram of an imaging probe of the wearable multi-modality imaging apparatus according to the embodiment of the invention;
fig. 4 is a flowchart of an imaging method of the wearable multi-modality imaging apparatus according to the embodiment of the present invention.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; the two elements may be directly connected or indirectly connected through an intermediate medium, or may be communicated with each other inside the two elements, or may be wirelessly connected or wired connected. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
An embodiment of the present invention provides a wearable multi-modality imaging apparatus, as shown in fig. 1, the imaging apparatus including: the system comprises an optical coherence tomography module 100, a photoacoustic imaging module 200, a laser speckle imaging module 300, a wavelength division multiplexer 12 and an imaging probe 400, wherein the optical coherence tomography module 100, the photoacoustic imaging module 200 and the laser speckle imaging module 300 are respectively connected with the imaging probe 400 through the wavelength division multiplexer 12; the wavelength division multiplexer 12 receives optical signals respectively output by the optical coherence tomography module 100, the photoacoustic imaging module 200 and the laser speckle imaging module 300, and irradiates the optical signals to an imaging area of an animal to be detected through the imaging probe 400; the imaging probe 400 receives a signal returned by the animal to be detected, and the returned signal is respectively sent to the corresponding optical coherence tomography module 100, the photoacoustic imaging module 200 and the laser speckle imaging module 300 through the wavelength division multiplexer 12 for collection, so as to obtain a corresponding imaging image.
The wearable multi-modal imaging device provided by the embodiment of the invention can be stably worn on the animal body and moves along with the animal, the animal does not need to be fixedly anesthetized, the change of blood flow of the blood vessel can be monitored for a long time for a plurality of times in the waking state of the animal, and the wearable imaging device can be worn on any part of the animal and is not limited to a specific part. Therefore, the wearable multi-modality imaging device provided by the embodiment of the invention can solve the technical problem that the imaging device in the prior art is not beneficial to researching animals in a normal state.
The wearable multi-modal imaging device provided by the embodiment of the invention couples optical coherence tomography, photoacoustic imaging and laser speckle imaging together, thereby realizing the technical effect that the three imaging modes work simultaneously. Meanwhile, the wearable multi-modal imaging device provided by the embodiment of the invention can make up for the defect of a single imaging mode and obtain the multi-parameter tissue structure information of the blood vessel. The optical coherence tomography can provide information of tissues with scattering characteristics, can obtain the caliber and depth data of the capillary, the photoacoustic imaging can provide information of tissues with absorption characteristics, can obtain the data of blood oxygen saturation and hemoglobin concentration, and the laser speckle imaging can obtain the caliber data and flow rate data of the capillary. Therefore, the wearable multi-modal imaging device provided by the embodiment of the invention has wide research prospect and application value.
In one embodiment, the optical coherence tomography module 100 includes a broadband light source unit, an interferometric system unit, a spectral analysis unit, and a data acquisition unit.
As shown in fig. 2, the broadband light source unit includes a light emitting diode 1 and an optical isolator 2 connected by an optical fiber. The light emitting diode may be a superluminescent light emitting diode with a wavelength of 835 nm. When the super-radiation light emitting diode is adopted, the formed spectrum width is larger, the coherence length is shorter, interference signals can be generated only when the optical path difference is in a very small range, and the closer the optical path difference is to zero, the higher the contrast of the formed interference fringes is, and the higher the positioning precision is. Therefore, the superluminescent light emitting diode is adopted as the light source, so that higher positioning precision can be realized. The optical isolator 2 may be selected from optically passive devices that allow only one-directional light to pass through. Optical isolator 2 is added in emitting diode 1's exit, can improve the transmission efficiency of light wave outside the light source with the optical isolation that reflects back in the optic fibre, can play the effect of protection light source simultaneously.
As shown in fig. 2, the interferometric system unit includes a fiber coupler 3, a first polarization controller 6, a second polarization controller 7, a first fiber collimator 4, and a plane mirror 5 connected by optical fibers. The optical fiber coupler 3 can select 90: 10, 2 x 2 fiber coupler. Light generated by the light emitting diode 1 can be proportionally divided into two beams through the optical fiber coupler 3, wherein 10% of the light enters a reference arm consisting of the first optical fiber collimator 4 and the plane mirror 5, and 90% of the light enters a sample arm (namely, the light irradiates an imaging area of an animal to be detected through the wavelength division multiplexer and the imaging probe). Because the polarization state of light changes when the light is transmitted in the optical fiber, the polarization states of the reference light and the sample light can be matched by adjusting the first polarization controller 6 and the second polarization controller 7, and the contrast of interference fringes can be improved.
As shown in fig. 2, the spectral analysis unit includes an achromatic collimator lens 8, a transmissive grating 9, a near-infrared achromatic lens 10, and a CMOS 11. The transmission grating 9 may be a 1200 line pair (lines per mm) grating, or another line pair may be selected, and the center wavelength of the transmission grating 9 is 830 nm. The data acquisition unit may optionally include a multifunctional data acquisition card 46 and a computer 47.
When the optical coherence tomography module 100 works, broad spectrum light generated by the light emitting diode 1 is incident into the optical fiber coupler 3 through the optical isolator 2 and is divided into two paths, one path is incident into the plane reflector 5 through the first polarization controller 6 and the first optical fiber collimator 4, and the original path is reflected by the plane reflector 5 and returns to the optical fiber coupler 3 as reference light; the other path of light is incident into the imaging probe through the second polarization controller 7 and the wavelength division multiplexer 12, and finally is incident onto the animal to be detected, the light signal scattered and returned by the animal to be detected is returned to the optical fiber coupler 3 through the original path of the wavelength division multiplexer 12 to be used as sample light, the reference light and the sample light received in the optical fiber coupler 3 are interfered, the generated interference signal is collimated through the achromatic collimating mirror 8, the light is split through the transmission grating 9, and finally the interference signal is focused on the CMOS11 through the near-infrared achromatic lens 10 to be converted into an electric signal. The multifunctional data acquisition card 46 can acquire the electrical signals and process the electrical signals by the computer 47, and the OCT (optical coherence tomography) image can be reconstructed by the computer 47.
In one embodiment, as shown in fig. 2, the photoacoustic imaging module 200 includes a pulse laser 13, a first neutral filter 14, a first light beam expanding system 15, a second fiber collimator 16, an ultrasonic amplifier 44, a multifunctional data acquisition card 46, and a computer 47. The pulse laser 13 may be a laser with a wavelength of 532nm, and the first neutral filter 14 may be an optical attenuator, which can attenuate light beams. The first light beam expanding system 15 may be specifically composed of two lenses, or may be selected from other beam expanding devices.
When the photoacoustic imaging module 200 works, pulse laser generated by the pulse laser 13 attenuates the intensity of the laser through the first neutral filter 14, is expanded by the first light beam expanding system 15, enters the second optical fiber collimator 16, enters the imaging probe through the wavelength division multiplexer 12, and finally enters animal tissues to be measured. The animal tissue to be measured absorbs light to generate instant temperature rise to cause thermal expansion, a photoacoustic signal is excited, the photoacoustic signal can be converted into an electrical signal through the imaging probe 400, the electrical signal is amplified and filtered by the ultrasonic amplifier 44, and then the electrical signal can be collected by the multifunctional data acquisition card 46 and processed by the computer 47 to reconstruct a photoacoustic image.
In one embodiment, as shown in fig. 2, the laser speckle imaging module 300 includes a laser 17, a second neutral filter 18, a second light beam expanding system 19, a beam splitter 20, a third fiber collimator 21, a filter 22, a CCD23, a multifunctional data acquisition card 46, and a computer 47. The laser 17 may be a He-Ne laser having a wavelength of 632 nm. The central wavelength of the optical filter 22 is 632nm, so that the optical signal returned by the animal to be measured can pass through the optical filter 22, and stray light with other wavelengths is filtered.
When the laser speckle imaging module 300 works, laser generated by a laser 17 is reflected by a second neutral optical filter 18, a second light beam expanding system 19 and a beam splitter 20 and enters a third optical collimator 21, then enters an imaging probe through a wavelength division multiplexer 12 which is in optical fiber connection with the third optical collimator 21, finally irradiates on animal tissues to be detected, and returns back through the original path of backscattered light signals of the animal tissues to be detected, and passes through the third optical collimator 21, the beam splitter 20 and the optical filter 22 again, and returned signals are collected by a CCD23 and are processed by a computer 47 to obtain speckle images.
In one embodiment, the multifunctional data acquisition card 46 and the computer 47 in the optical coherence tomography module 100, the photoacoustic imaging module 200, and the laser speckle imaging module 300 may share the same acquisition card and computer to reduce the volume of the imaging device.
In one embodiment, the wavelength division multiplexer 12 may be a three wavelength division multiplexer, i.e., the input of the wavelength division multiplexer may mix three different wavelengths 532nm, 632nm and 835nm and output from a single output fiber.
In one embodiment, as shown in FIG. 3, an imaging probe 400 includes: a main body 24, a support 25, a fixed substrate 26, and a combined signal line 40, the main body 24 being detachably attached to a first surface of the support 25, the combined signal line 40 being disposed inside the main body 24 for transmitting an optical signal and a return signal; the fixed substrate 26 is detachably attached to a second surface of the support 25 disposed opposite to the first surface, and the imaging probe is fixed to the animal to be measured through the fixed substrate 26.
In one embodiment, as shown in FIG. 3, the body 24 may be coupled to the first surface of the support 25 via a slot 33. The support 25 may be provided with a fixing edge 31 protruding outward, a fixing hole 32 is formed on the fixing edge 31, and a screw 29 protruding upward is formed on the fixing base 26, and when the fixing base and the support 25 are coupled, the screw 29 may be aligned with the fixing hole 32 and coupled and fixed using a nut 30.
Alternatively, as shown in fig. 3, the fixing substrate 26 may include a tightening band 27 and a flexible bottom surface 28, the flexible bottom surface 28 is detachably connected to the second surface of the support 25 by a screw, and the imaging probe is fixed to the animal to be tested by the tightening band 27. Specifically, the flexible bottom surface 28 may be made of a flexible material, a middle portion thereof may be provided as an opening, and both ends of the flexible bottom surface 28 may be sewn with the tightening band 27 as a single body. The tightening band 27 may be formed by an adhesive tape.
In one embodiment, as shown in fig. 3, the imaging probe 400 further comprises: the main body 24 is internally provided with a moving module 45, and the light-gathering assembly and the photoacoustic conversion assembly are arranged on the moving module 45; the light condensing assembly is connected with the combined signal line 40 and is used for receiving the optical signals output by the wavelength division multiplexer 12 through the combined signal line 40 and receiving the signals returned by the animal to be detected and respectively sending the signals to the corresponding optical coherence tomography module and the corresponding laser speckle imaging module through the wavelength division multiplexer 12; the photoacoustic conversion component is used for receiving a signal returned by the animal to be tested, converting the signal into an electric signal and sending the electric signal to the photoacoustic imaging module 300 through the wavelength division multiplexer 12. When the imaging probe 400 is in operation, the computer can control the moving module 45 to move three-dimensionally, so as to observe the imaging effect and find the optimal imaging position.
In one embodiment, as shown in fig. 3, the light focusing assembly comprises: the self-focusing lens 34 receives the optical signal output by the wavelength division multiplexer 12 through a combined signal line 40 and outputs the optical signal through the micro-mirror 35, the biaxial MEMS micro-scanning galvanometer 36 and the focusing lens 37 in sequence.
Alternatively, as shown in fig. 3, the self-focusing lens 34 may be mounted on the upper left portion of the top of the imaging probe body 24, a screw hole for fixing the self-focusing lens 34 by a screw may be provided on the top of the self-focusing lens 34, and an optical fiber may be mounted on the tail portion of the self-focusing lens 34. The micromirror 35 is disposed right under the self-focusing lens 34 at an angle of 45 ° with the bottom of the body 24; the biaxial MEMS micro scanning galvanometer 36 is arranged at the right side of the micro mirror 35 and is parallel to the micro mirror 35; the focusing lens 37 is disposed directly below the biaxial MEMS micro-scanning galvanometer 36, parallel to the bottom of the body 24.
Specifically, the scanning frequency and the scanning range of the dual-axis MEMS micro-scanning galvanometer 36 can be controlled by a computer, and when the dual-axis MEMS micro-scanning galvanometer 36 works, the light beam scans the animal to be detected in the form of linear light, and the three-dimensional information of the animal to be detected can be obtained at the same time. Compared with the traditional scanning mirror, the biaxial MEMS micro-scanning galvanometer 36 is made of monocrystalline silicon, adopts a non-universal joint design, and has the advantages of small size, low cost, high scanning frequency, high response speed, low power consumption and the like.
In an embodiment, as shown in fig. 3, the photoacoustic conversion assembly includes: the light transmitting sheet 38 transmits light beams emitted by the light condensing assembly, and reflects photoacoustic signals returned by the animal to be detected to the ultrasonic transducer 39; the ultrasonic transducer 39 receives the photoacoustic signal and converts it into an electrical signal. The light-transmitting sheet 38 is horizontally arranged on the bottom of the main body 24, the light-transmitting sheet 38 can be made of a light-transmitting anti-sound material, and the bottom is a hollow structure, so that a photoacoustic signal excited by an animal to be detected can enter the light-transmitting sheet 38 for reflection and is received by the ultrasonic transducer 39; the ultrasonic transducer 39 is installed at the upper right of the light-transmitting sheet 38 and is connected to the ultrasonic amplifier 44 through an ultrasonic signal line 43.
In an embodiment, the wearable multimodal imaging apparatus further comprises: a transparent cover of the support, which matches the support 25. Specifically, when the probe needs to be detected at a longer interval, the main body 24 of the imaging probe can be detached, the support 25 is left, and then the support 25 is covered with the transparent cover of the support to seal the support; when experimental probing is required again, the transparent cover of the support can be removed, and the main body 24 of the probe is reinstalled for experimental probing. In addition, when the imaging probe operates, the inside of the seat 25 may be filled with an ultrasonic coupling medium, and optionally, the ultrasonic coupling medium may be water or other materials, which is not limited in the present invention.
An embodiment of the present invention further provides an imaging method of a wearable multi-modality imaging apparatus, as shown in fig. 4, the imaging method is applicable to the wearable multi-modality imaging apparatus according to the above embodiment, and the imaging method includes the following steps:
step S101: fixing an imaging probe on an animal to be detected; alternatively, the test animal may be treated prior to fixing the imaging probe. Taking the skin tissue of the mouse as an example, the skin area to be imaged of the mouse can be depilated first, and a model of the scald of the skin of the mouse is made.
Specifically, when the imaging probe is fixed, the middle hollow part of the flexible bottom surface can be aligned to the position of a mouse scalding skin, so that the position of the mouse scalding skin can be observed through the middle hollow part of the flexible bottom surface, then the flexible bottom surface and the body of the mouse are stably fixed by using the tightening belts on two sides of the flexible bottom surface, then the fixing holes of the support and the screws on the flexible bottom surface are aligned, placed and installed, and fixed by using nuts; and finally, fixing the main body of the probe and the support part through a clamping groove.
Step S102: respectively starting light sources of the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module, so that light signals output by the light sources are incident on the animal to be detected through the wavelength division multiplexer and the imaging probe; specifically, three light source superluminescent light emitting diodes, a pulse laser, and a He-Ne laser generate excitation lights of three different wavelengths, which are mixed by a wavelength division multiplexer and output from a single output optical fiber into an imaging probe. The self-focusing lens of the imaging probe outputs exciting light in a form of parallel light, the exciting light is incident to the center of the micro-reflector and then reflected to the double-shaft MEMS micro-scanning galvanometer, the exciting light passes through the focusing lens and is converged by the light-transmitting sheet, and light spots are focused on a certain imaging area of the animal tissue to be measured. Step S103: moving a moving module in the imaging probe according to a preset imaging area until optical signals output by the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module reach a preset position through the wavelength division multiplexer and the imaging probe; specifically, the movement of the moving module may be controlled by a computer to determine the optimal imaging position.
Step S104: rotating the double-shaft MEMS micro-scanning galvanometer to perform two-dimensional scanning on a preset imaging area; specifically, the rotation of the double-shaft MEMS micro-scanning galvanometer can be controlled by a computer, and the range and the frequency of scanning light of the double-shaft MEMS micro-scanning galvanometer can be controlled by operating the computer, so that the biological tissue is scanned in two dimensions, and signals of the biological tissue in the whole scanning area are acquired.
Step S105: and obtaining corresponding imaging images according to signals returned by the animal to be detected and received by the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module. The OCT signal and the laser speckle signal generated by the excitation of the animal tissue to be detected return to the original path and pass through the wavelength division multiplexer again, the sample light carrying the OCT signal interferes with the reference light returned by the plane mirror, and the interference signal is received by the CMOS; the laser speckle signal passes through a beam splitter and an optical filter, and the signal is received by the CCD; the photoacoustic signal generated by the excitation of the animal tissue to be detected is received by the ultrasonic transducer, amplified and filtered by the ultrasonic amplifier and collected by the multifunctional data acquisition card, and simultaneously, the multifunctional data acquisition card receives the signals output by the CMOS and the CCD and processes and reconstructs OCT, photoacoustic and laser speckle images of a scanning area by a computer.
The imaging method of the wearable multi-modal imaging device provided by the embodiment of the invention couples optical coherence tomography, photoacoustic imaging and laser speckle imaging together, and the designed imaging probe can be stably installed at any position on an animal body due to the advantages of small size and detachable structure, so that the multi-modal imaging detection of the animal can be carried out under the state of waking free movement, the operability of the experiment can be simplified, meanwhile, the animal detection can be continuously carried out for a long time, and the survival rate of the animal is improved.
The imaging method of the wearable multi-modal imaging device provided by the embodiment of the invention can be used for continuously acquiring signals of biological tissue structures. After the imaging is finished once, when the area is replaced for acquisition, the computer is only required to drive the mobile module to select the required imaging area for signal acquisition. When needing to wait for a long time and then collecting, the main body of the probe can be taken down, and when needing to be tested next time, the main body is installed again. When the biological tissue needs to be subjected to surgical treatment, the fixing nut for connecting the support and the flexible bottom surface can be unscrewed, the tightening belt is loosened, and then the whole imaging probe is taken down.
Although the present invention has been described in detail with respect to the exemplary embodiments and the advantages thereof, those skilled in the art will appreciate that various changes, substitutions and alterations can be made to the embodiments without departing from the spirit and scope of the invention as defined by the appended claims. For other examples, one of ordinary skill in the art will readily appreciate that the order of the process steps may be varied while maintaining the scope of the present invention.
Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present invention, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed, that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present invention. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

Claims (10)

1. A wearable multi-modality imaging apparatus, comprising: an optical coherence tomography module, a photoacoustic imaging module, a laser speckle imaging module, a wavelength division multiplexer and an imaging probe,
the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module are respectively connected with the imaging probe through the wavelength division multiplexer;
the wavelength division multiplexer receives optical signals respectively output by the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module, and irradiates the optical signals to an imaging area of an animal to be detected through the imaging probe;
the imaging probe receives a signal returned by the animal to be detected, and the returned signal is respectively sent to the corresponding optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module through the wavelength division multiplexer for collection, so that a corresponding imaging image is obtained.
2. The wearable multimodal imaging apparatus of claim 1, wherein the imaging probe comprises: a main body, a support, a fixed substrate and a combined signal wire,
the main body is detachably connected to the first surface of the support, and the combined signal line is arranged inside the main body and used for transmitting the optical signal and the returned signal;
the fixed substrate is detachably connected to a second surface, opposite to the first surface, of the support, and the imaging probe is fixed to an animal to be tested through the fixed substrate.
3. The wearable multimodal imaging apparatus of claim 2, wherein the body is attached to the first surface of the mount by a snap-in groove.
4. The wearable multi-modality imaging apparatus of claim 2, wherein the stationary base is threadably connected with the mount.
5. The wearable multimodal imaging apparatus of claim 2, wherein the imaging probe further comprises: the mobile module is arranged in the main body, and the light-gathering assembly and the photoacoustic conversion assembly are arranged on the mobile module;
the light condensing assembly is connected with the combined signal line and is used for receiving the optical signals output by the wavelength division multiplexer through the combined signal line and receiving the signals returned by the animal to be detected and respectively sending the signals to the corresponding optical coherence tomography module and the corresponding laser speckle imaging module through the wavelength division multiplexer;
the photoacoustic conversion assembly is used for receiving a signal returned by an animal to be detected, converting the signal into an electric signal and sending the electric signal to the photoacoustic imaging module through the wavelength division multiplexer.
6. The wearable multimodal imaging apparatus of claim 5 wherein the light focusing assembly comprises: the self-focusing lens receives the optical signal output by the wavelength division multiplexer through a combined signal line and outputs the optical signal through the micro-reflector, the double-axis MEMS micro-scanning vibrating mirror and the focusing lens in sequence.
7. The wearable multi-modality imaging apparatus of claim 6, wherein the micro-mirror is disposed directly below the self-focusing lens at a 45 ° angle to the bottom of the body; the double-axis MEMS micro-scanning galvanometer is arranged on the right side of the micro-reflector and is parallel to the micro-reflector; the focusing lens is arranged right below the biaxial MEMS micro-scanning galvanometer and is parallel to the bottom of the main body.
8. The wearable multimodal imaging apparatus of claim 2, wherein the fixed base comprises a strap and a flexible bottom surface, the flexible bottom surface being removably attached to the second surface of the support, the imaging probe being secured to the test animal by the strap.
9. The wearable multi-modality imaging apparatus of claim 2, further comprising: the support transparent cover is matched with the support.
10. An imaging method of a wearable multimodal imaging apparatus, applied to the wearable multimodal imaging apparatus according to any one of claims 1 to 9, comprising the steps of:
fixing an imaging probe on an animal to be detected;
respectively starting the light sources of the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module, so that light signals output by the light sources are incident on an animal to be detected through the wavelength division multiplexer and the imaging probe;
moving a moving module in the imaging probe according to a preset imaging area until optical signals output by the optical coherence tomography module, the photoacoustic imaging module and the laser speckle imaging module reach a preset position through the wavelength division multiplexer and the imaging probe;
rotating the double-shaft MEMS micro-scanning galvanometer to perform two-dimensional scanning on a preset imaging area;
and obtaining corresponding imaging images according to the signals returned by the animal to be detected, which are received by the optical coherence tomography imaging module, the photoacoustic imaging module and the laser speckle imaging module.
CN202010099239.4A 2020-02-18 2020-02-18 Wearable multi-modal imaging device and imaging method thereof Pending CN111281343A (en)

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