CN207532377U - A kind of photoacoustic microscope - Google Patents

A kind of photoacoustic microscope Download PDF

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Publication number
CN207532377U
CN207532377U CN201720425684.9U CN201720425684U CN207532377U CN 207532377 U CN207532377 U CN 207532377U CN 201720425684 U CN201720425684 U CN 201720425684U CN 207532377 U CN207532377 U CN 207532377U
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pulse laser
lens
signal
acquisition control
diamond shaped
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聂立铭
吴志友
李宏辉
赵庆亮
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Xiamen University
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Xiamen University
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Abstract

The utility model discloses a kind of photoacoustic microscopes, including microscopic system, signal acquisition control system and drive system, the light microscope combines the characteristics of optical imagery high contrast harmony studies image height resolution ratio, due to the low scattering properties of acoustic signal propagation in the tissue, have has deeper penetration depth than traditional optical imaging method;And the processing such as histotomy need not be carried out, have it is non-invasive, can realize long term monitoring, and the opto-acoustic microscopic imaging equipment can realize the imaging of a variety of anatomical locations.

Description

A kind of photoacoustic microscope
Technical field
The utility model belongs to medicine and the field of medical instrument technology, and in particular to a kind of photoacoustic microscope.
Background technology
For a long time, microvesicle diagnoses contrast medium as a kind of efficient, cheap, good biocompatibility ultrasonic imaging always. Since microvesicle has higher acoustic scattering characteristic and the nonlinear interaction to incident ultrasound wave, clinically there are many should With, such as to assessment etc. that coronary artery disease, revascularization, inflammation and tumour are formed.Under normal circumstances, these clinics should With only by the acoustic impedance of microvesicle carrying out ultrasonic imaging, and have ignored the other utilization valency of this unique texture of microvesicle Value.
The main method for observing oncotherapy effect is detected by imaging means.Traditional optical microscopy imaging side Method can observe the blood vessel around tumour, but need histotomy, have it is invasive, be unfavorable for realize long term monitoring;It is and sharp Tumor tissues can be carried out with ultrasonic imaging non-invasively imaged, but its relatively low image resolution ratio can not effectively observe tumour The variation of blood vessels caliber.
Utility model content
For overcome the deficiencies in the prior art, the utility model provides a kind of photoacoustic microscope, photoacoustic microscope profit The characteristics of with optoacoustic micro-imaging technique high contrast and high-resolution, observes biology in spatial resolution level in the micron-scale The blood vessel feature of tissue achievees the purpose that monitor microvesicle explosion with this;Using the bubble structure of microvesicle, when using high-energy ultrasound When carrying out explosion treatment to microvesicle, the impact force of microvesicle explosion will bring tissue blood vessel certain physics fragmentation effect, thus The photoacoustic microscope can be applied to the treatment of monitoring tumor locus.
Technical solution is used by the utility model solves its technical problem:
A kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, signal acquisition control The information of system control drive system acquisition microscopic system, and collected data are stored and analyzed;Drive system The position of corresponding assembly is driven, is realized to microscopical adjustment.
The microscopic system includes pulse laser, and pulse laser generates short-pulse laser, and short-pulse laser lures It leads biological tissue and generates optoacoustic effect, i.e., instantaneous expanded by heating sends out ultrasonic wave;It is set gradually along short-pulse laser direction of advance There are the combination of the first beam expanding lens, the combination of the first microcobjective, fiber coupler, single mode optical fiber, collimator, the second beam expanding lens, reflection Pulse laser is sent out in mirror, the second microcobjective, beam resolution element, acoustic lens, sink and article carrying platform, the combination of the first beam expanding lens The short-pulse laser gone out is expanded, and when making its first microcobjective surface of arrival, can more completely cover the first micro- object Lens on mirror realize preferable focusing effect;First microcobjective is focused short-pulse laser, reduces focal beam spot Size, makes it through fiber coupler and enters the loss of optical fiber and be preferably minimized;Single mode optical fiber transmission can further reduce loss; After short-pulse laser goes out single mode optical fiber, light beam can be in divergent state, be parallel by diverging light collimation by the adjustment of collimator Light;The combination of second beam expanding lens again expands short-pulse laser, can more completely cover on the second microcobjective Lens, realize preferable focusing effect, reduce the size of focal beam spot;Second microcobjective is focused light beam, makes coke Point is located on receptor;Acoustic lens by the ultrasonic signal that optoacoustic effect generates to being focused so that optical focus is confocal with area for sound,focal When, reach best lateral resolution effect;Sink is convenient for acoustical coupling, and bottom of gullet is thin film, by being applied to animal The couplant on surface can be preferably bonded animal surface, and the effect of water is also as a kind of couplant, ensures sound wave by giving birth to In object energy attenuation will not be caused between acoustic lens because of by air.
The signal acquisition control system includes the ultrasonic detector, signal amplifier, the data collecting card that are sequentially connected in series And computer, beam resolution element are made of right-angle prism and diamond shaped lens, two sides of diamond shaped lens or so are both provided with silicone oil Layer, silicon layer have from light refractive index similar in lens but acoustic impedance is different, therefore can penetrate light beam in silicon layer And acoustic beam is reflected, achieve the effect that optoacoustic detaches, another side of diamond shaped lens is also equipped with one layer of silicon layer, secondary reflection Ultrasonic wave is received by ultrasonic detector, and ultrasonic detector is arranged on diamond shaped lens, ultrasonic detector via ultrasonic coupling agent with Beam resolution element combines, and converts acoustic energy into electric energy, and the information of sound wave is reached by signal amplifier, data collecting card to be calculated Machine carries out processing imaging by computer to acoustical signal.
The drive system is included through motor-driven two-dimensional translation platform, and beam resolution element is mounted on two-dimensional translation On platform, the position for changing two-dimensional translation platform is driven by motor according to experiment condition, so as to meet different experiment demands, The data of collection are stored and are analyzed by computer, pass through image reconstruction by the signal input part electrical connection computer of motor Algorithm reconstruction image.
The pulse laser is provided with synchronous triggering device, and synchronous triggering device is electrically connected data collecting card, at present Conventional way is to isolate light beam using a spectroscope, is converted to electric signal by photodiode, obtains synchronizing tactile Hair, the synchronous triggering device of the utility model are believed to the optoacoustic that data collecting card synchronous acquisition is controlled to be generated per single pulse Number.
Preferably, described first beam expanding lens combination and the combination of the second beam expanding lens by focal length for the first convex lenses of 20mm and Focal length is the second convex lens groups of 30,40 or 60mm into forming 1.5,2,3 times of amplification factor.
Using microvessel density being caused to become before and after photoacoustic microscope Imaging: Monitoring microvesicle explosion described in the utility model The method of change includes the following steps:
1) tumor region is scanned using photoacoustic microscope, obtains the tumor vessel photoacoustic signal before microvesicle explosion;
2) microvesicle is injected into animal body, scans tumor region with ultrasonic generator, make micro- in tumor region Follicular rupture;
3) after microvesicle explosion, tumor region is scanned using photoacoustic microscope, obtains the tumor vessel optoacoustic after microvesicle explosion Signal;
4) data processing is carried out to collected photoacoustic signal, the blood vessel optoacoustic of tumor region is shown before and after comparison microvesicle explosion Micro- image monitors microvesicle explosion in biological tissues with this.
The principle of this method is:Tumor tissues metabolism is fast, growth and development is fast, by physiological knowledge it is known that this is main It is because numerous blood vessels provide abundant nutritional ingredient inside tumor region.Research shows that damage blood vessel is to inhibiting tumour Growth and development has good application prospect, can play the therapeutic effect to tumour.Above-mentioned photoacoustic microscope Imaging: Monitoring is micro- Cause in the method that microvessel density changes before and after bubble explosion, using physics fragmentation effect caused by microvesicle explosion, to tumour Blood vessel causes to damage, and passes through caused Vascular change before and after opto-acoustic microscopic imaging monitoring microvesicle explosion.When pulse laser is beaten When in biological tissue, a part of luminous energy is absorbed by extinction material, is converted to thermal energy by energy deposition, extinction material is heated swollen It is swollen, and the contract on cooling after laser stops irradiation, it thus periodically expands with heat and contract with cold and generates ultrasonic wave, i.e. photoacoustic signal.Due to Photoacoustic signal reflects the light absorption distribution of organization internal, therefore can rebuild to obtain vascular distribution image by data processing, So as to assess the effect of microvesicle blast treatment tumour.
The utility model has the advantages that:
(1) the utility model method combines the characteristics of optical imagery high contrast harmony studies image height resolution ratio, due to The low scattering properties of acoustic signal propagation in the tissue, have has deeper penetration depth than traditional optical imaging method;
(2) the utility model is monitored using photoacoustic technique, without carrying out the processing such as histotomy, have it is non-invasive, It can realize long term monitoring, and the opto-acoustic microscopic imaging equipment can realize the imaging of a variety of anatomical locations;
(3) microvesicle that the utility model uses, it is cheap, it is easy to use, it is easy to application.
Description of the drawings
Fig. 1 is the structure diagram of photoacoustic microscope described in the utility model.
Specific embodiment
The utility model is further described below in conjunction with attached drawing:
A kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, signal acquisition control System controls drive system and acquires the information of microscopic system, and collected data are stored and analyzed;Driving system System adjusts the position of corresponding assembly, realizes to microscopical adjustment.
The microscopic system includes pulse laser 10, and pulse laser 10 generates short-pulse laser, along short pulse Laser direction of advance is disposed with the first beam expanding lens and combines the 11, first microcobjective 12, fiber coupler 13, single mode optical fiber 14th, collimator 15, the second beam expanding lens combination 16, speculum 17, the second microcobjective 18, beam resolution element 19, acoustic lens 20, water Slot 21 and article carrying platform 22;The beam resolution element 19 is made of right-angle prism and diamond shaped lens, diamond shaped lens or so two Side is both provided with silicon layer 23.
The ultrasonic detector 24, signal amplifier 25, data that the signal acquisition control system includes being sequentially connected in series are adopted Truck 26 and computer 27, ultrasonic detector 24 are arranged on diamond shaped lens, and ultrasonic detector 24 is via ultrasonic coupling agent and beam Resolution element 19 combines, and converts acoustic energy into electric energy, and signal is handled convenient for computer 27;Beam resolution element 19 is by right angle Prism and diamond shaped lens composition, two sides of diamond shaped lens or so are both provided with silicon layer 23, silicone oil have with similar in lens Light refractive index but acoustic impedance difference, therefore can penetrate light beam in silicon layer 23 and reflect acoustic beam, it realizes and swashs pulse The laser that light device occurs is detached with the reflected ultrasonic wave of organism, another side of diamond shaped lens is also equipped with one Layer silicon layer 23, secondary reflection ultrasonic wave are received by ultrasonic detector 24, and ultrasonic detector 24 detects the information of sound wave, sound wave Information pass through signal amplifier 25, data collecting card 26 reach computer 27.
In order to meet different experiment demands, experimenter, which facilitates, is adjusted photoacoustic microscope according to requirement of experiment, The drive system includes the two-dimensional translation platform 29 driven by motor 28, and beam resolution element 19 is put down mounted on two-dimensional translation On platform 29, the signal input part electrical connection computer 27 of motor 28.
For the photoacoustic signal generated using 26 synchronous acquisition of data collecting card per single pulse, the pulse laser 10 are provided with synchronous triggering device 30, and synchronous triggering device 30 is electrically connected data collecting card 26.
In order to be expanded to short-pulse laser, the lens that can more completely be covered on microcobjective are realized Preferable focusing effect reduces the size of focal beam spot, along short-pulse laser direction of advance, first beam expanding lens combination 11 With the second beam expanding lens combination 16 by focal length be the first convex lenses of 20mm with focal length be the second convex lens groups of 30,40 or 60mm into.
Using microvessel density being caused to become before and after photoacoustic microscope Imaging: Monitoring microvesicle explosion described in the utility model The method of change includes the following steps:
1) tumor region is scanned using photoacoustic microscope, obtains the tumor vessel photoacoustic signal before microvesicle explosion;
2) microvesicle is injected into animal body, scans tumor region with ultrasonic generator, make micro- in tumor region Follicular rupture;
3) after microvesicle explosion, tumor region is scanned using photoacoustic microscope, obtains the tumor vessel optoacoustic after microvesicle explosion Signal;
4) data processing is carried out to collected photoacoustic signal, the blood vessel optoacoustic of tumor region is shown before and after comparison microvesicle explosion Micro- image monitors microvesicle explosion in biological tissues with this.
Specific experiment process:
Microbubble solution is prepared, pure microvesicle is taken to add in the physiological saline of corresponding dosage, the microvesicle standard for being configured to 30% concentration is molten Liquid after mouse is anaesthetized, is placed on article carrying platform and continuous narcosis, opto-acoustic microscopic imaging equipment is used before microbubble solution is injected Tumor region is scanned, then in the microbubble solution of 100 microlitres of mouse tail vein injection, emits high-energy ultrasound pair with ultrasonic probe Microbubble solution carries out explosion.It is observed after seven days, photoacoustic imaging is carried out to target area.It is micro- knowable to imaging twice by comparing Steep fragmentation effect of the explosion to tumor region blood vessel.
Finally it should be noted that:Obviously, above-described embodiment is only intended to clearly illustrate the utility model example, And it is not intended to limit the embodiments.For those of ordinary skill in the art, may be used also on the basis of the above description To make other variations or changes in different ways.There is no necessity and possibility to exhaust all the enbodiments.And thus Among changes and variations that derived from are still in the scope of protection of the utility model.

Claims (2)

1. a kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, signal acquisition control system System control drive system and the information for acquiring microscopic system;It is characterized in that:
The microscopic system includes pulse laser, and pulse laser generates short-pulse laser, advances along short-pulse laser Direction is disposed with the combination of the first beam expanding lens, the first microcobjective, fiber coupler, single mode optical fiber, collimator, second expands Microscope group conjunction, speculum, the second microcobjective, beam resolution element, acoustic lens, sink and article carrying platform;The beam resolution element It is made of right-angle prism and diamond shaped lens, two sides of diamond shaped lens or so are both provided with silicon layer;
The signal acquisition control system includes the ultrasonic detector, signal amplifier, data collecting card and the meter that are sequentially connected in series Calculation machine, ultrasonic detector are arranged on diamond shaped lens, and ultrasonic detector detects the information of sound wave, and the information of sound wave is put by signal Computer is reached after big device, data collecting card;
The drive system is included through motor-driven two-dimensional translation platform, and beam resolution element is mounted on two-dimensional translation platform On, the signal input part electrical connection computer of motor;
The pulse laser is provided with synchronous triggering device, synchronous triggering device electrical connection data collecting card.
2. a kind of photoacoustic microscope as described in claim 1, which is characterized in that described along short-pulse laser direction of advance First beam expanding lens combines and the combination of the second beam expanding lens is the first convex lenses of 20mm by focal length and focal length is 30,40 or 60mm second Convex lens group into.
CN201720425684.9U 2017-04-21 2017-04-21 A kind of photoacoustic microscope Active CN207532377U (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106943120A (en) * 2017-04-21 2017-07-14 厦门大学 A kind of photoacoustic microscope and its method for monitoring microvesicle explosion in biological tissues
CN110146450A (en) * 2019-06-05 2019-08-20 南京大学 A kind of photoacoustic ultrasound dual-mode microscopic imaging device
NL2025628A (en) * 2019-07-30 2020-07-10 Univ Harbin Medical Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance
US11002708B2 (en) * 2015-01-07 2021-05-11 Olympus Corporation Photoacoustic microscope objective lens unit and photoacoustic microscope including the same
CN113576415A (en) * 2021-08-04 2021-11-02 广东光声医疗科技有限公司 Four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11002708B2 (en) * 2015-01-07 2021-05-11 Olympus Corporation Photoacoustic microscope objective lens unit and photoacoustic microscope including the same
CN106943120A (en) * 2017-04-21 2017-07-14 厦门大学 A kind of photoacoustic microscope and its method for monitoring microvesicle explosion in biological tissues
CN110146450A (en) * 2019-06-05 2019-08-20 南京大学 A kind of photoacoustic ultrasound dual-mode microscopic imaging device
NL2025628A (en) * 2019-07-30 2020-07-10 Univ Harbin Medical Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance
CN113576415A (en) * 2021-08-04 2021-11-02 广东光声医疗科技有限公司 Four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system

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