CN106943120A - A kind of photoacoustic microscope and its method for monitoring microvesicle explosion in biological tissues - Google Patents
A kind of photoacoustic microscope and its method for monitoring microvesicle explosion in biological tissues Download PDFInfo
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- CN106943120A CN106943120A CN201710267504.3A CN201710267504A CN106943120A CN 106943120 A CN106943120 A CN 106943120A CN 201710267504 A CN201710267504 A CN 201710267504A CN 106943120 A CN106943120 A CN 106943120A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
- A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/02—Detecting, 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
- A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
- A61B8/0891—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of blood vessels
Abstract
The invention discloses a kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, the invention also discloses the method that microvesicle explosion in biological tissues is monitored using the photoacoustic microscope.Photoacoustic imaging 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, with having deeper penetration depth than traditional optical imaging method；And the processing such as histotomy need not be carried out, with non-invasive, it is possible to achieve long term monitoring, and the opto-acoustic microscopic imaging equipment can realize the imaging of a variety of anatomical locations.
Description
Technical field
The invention belongs to medical science and technical field of medical instruments, and in particular to a kind of photoacoustic microscope and its monitoring microvesicle exist
The method of biological tissue's borehole blasting.
Background technology
For a long time, microvesicle diagnoses contrast medium as a kind of efficient, cheap, good biocompatibility ultrasonic imaging always.
Because microvesicle has higher acoustic scattering characteristic and the nonlinear interaction to incident ultrasound wave, it clinically has many answer
With for example to assessment of coronary artery disease, revascularization, inflammation and tumour formation etc..Generally, these clinics should
With simply by the acoustic impedance of microvesicle carrying out ultrasonic imaging, and it 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 microphotograph imaging side
Method can observe the blood vessel around tumour, but need histotomy, with invasive, be unfavorable for realizing long term monitoring；And it is sharp
Tumor tissues can be carried out with noninvasive imaging with ultrasonic imaging, but its relatively low image resolution ratio can not effectively observe tumour
The change of blood vessels caliber.
The content of the invention
In order to overcome the deficiencies in the prior art, the invention provides a kind of photoacoustic microscope and its monitoring microvesicle in biology
The method for organizing borehole blasting, the characteristics of photoacoustic microscope utilizes opto-acoustic microscopic imaging technology high-contrast and high-resolution,
The blood vessel feature of biological tissue is observed in micron-sized spatial resolution aspect, the purpose of monitoring microvesicle explosion is reached with this；Profit
With the bubble structure of microvesicle, when carrying out explosion treatment to it using high-energy ultrasound, the impulsive force of microvesicle explosion will be to tissue
Zona vascuiosa carrys out certain physics fragmentation effect, it is possible thereby to which this method to be applied to the treatment of monitoring tumor locus.
The technical solution adopted for the present invention to solve the technical problems is：
A kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, signal acquisition control system
Control drive system to gather the information of microscopic system, and the data collected are stored and analyzed；Drive system drives
The position of corresponding assembly, is realized to microscopical adjustment.
Described microscopic system includes pulse laser, and pulse laser produces short-pulse laser, and short-pulse laser is lured
Lead biological tissue and produce optoacoustic effect, i.e., instantaneous expanded by heating sends ultrasonic wave；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 fiber, collimater, the second beam expanding lens, reflection
Mirror, the second microcobjective, beam resolution element, acoustic lens, tank and article carrying platform, the first beam expanding lens combination are sent out pulse laser
The short-pulse laser gone out is expanded, and when making its first microcobjective surface of arrival, can more completely cover the first micro- thing
Lens on mirror, realize preferable focusing effect；First microcobjective is focused to short-pulse laser, reduces focal beam spot
Size, the loss for being passed to fiber coupler into optical fiber is preferably minimized；Single-mode fiber transmission can further reduce loss；
Short-pulse laser goes out after single-mode fiber, and light beam can be in divergent state, is parallel by diverging light collimation by the adjustment of collimater
Light；The combination of second beam expanding lens is expanded to short-pulse laser again, can more completely be covered on the second microcobjective
Lens, realize preferable focusing effect, reduce the size of focal beam spot；Second microcobjective is focused to light beam, makes Jiao
Point is located on acceptor；Acoustic lens is focused to the ultrasonic signal produced by optoacoustic effect so that optical focus is confocal with area for sound,focal
When, reach optimal lateral resolution effect；Tank is easy to acoustical coupling, and bottom of gullet is thin film, by being applied to animal
The couplant on surface can preferably fit animal surface, and the effect of water is also as a kind of couplant, it is ensured that sound wave is by giving birth to
In object energy attenuation will not be caused between acoustic lens because of by air.
Described signal acquisition control system includes the ultrasonic detector, signal amplifier, data collecting card being sequentially connected in series
And computer, beam resolution element is made up of right-angle prism and diamond shaped lens, and two sides of diamond shaped lens or so are provided with silicone oil
Layer, silicon layer has the light refractive index close from lens but acoustic impedance is different, therefore can penetrate light beam in silicon layer
And acoustic beam is reflected, the effect of optoacoustic separation is reached, 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 is combined, 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 being processed into picture by computer to acoustical signal.
Described drive system is included by motor-driven two-dimensional translation platform, and beam resolution element is arranged on two-dimensional translation
On platform, the position for changing two-dimensional translation platform is driven by motor according to experiment condition, so that different experiment demands are met,
The data of collection are stored and analyzed by computer, pass through image reconstruction by the signal input part electrical connection computer of motor
Algorithm reconstruction image.
Described pulse laser is provided with synchronous triggering device, and synchronous triggering device electrically connects data collecting card, at present
Conventional way is to isolate light beam using a spectroscope, and electric signal is converted to by photodiode, obtains synchronous touch
Hair, the photoacoustic signal that synchronous triggering device of the invention is produced to control data capture card synchronous acquisition per individual pulse.
It is preferred that, the described combination of first beam expanding lens and the combination of the second beam expanding lens by focal length be the convex lens of 20mm first and
Focal length be 30,40 or the convex lens groups of 60mm second into, constitute 1.5,2,3 times of multiplication factor.
A kind of method for monitoring microvesicle explosion in biological tissues, described method is to utilize photoacoustic microscope Imaging: Monitoring
Microvessel density is caused to change before and after microvesicle explosion.
It is preferred that, described method comprises 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, tumor region is scanned with ultrasonic generator, break the microvesicle in tumor region
Split；
3) after microvesicle explosion, tumor region is scanned using photoacoustic microscope, the tumor vessel photoacoustic signal after microvesicle explosion is obtained；
4) data processing is carried out to the photoacoustic signal collected, the blood vessel optoacoustic micrograph of tumor region before and after contrast microvesicle explosion
Picture, microvesicle explosion in biological tissues is monitored with this.
The operation principle of this method is：Tumor tissues metabolism is fast, it is fast to grow, by physiological knowledge, it is known that this
It is primarily due to numerous blood vessels inside tumor region and provides abundant nutritional ingredient.Research shows that injured blood vessel is to suppressing swollen
Growing for knurl has good application prospect, can play the therapeutic effect to tumour.The present invention is caused using microvesicle explosion
Physics fragmentation effect, to tumor vessel cause damage, and pass through opto-acoustic microscopic imaging monitor microvesicle explosion before and after caused by blood
Pipe changes.When pulse laser is beaten in biological tissue, a part of luminous energy is absorbed by extinction material, is converted to by energy deposition
Heat energy, extinction material expanded by heating, and the contract on cooling after laser stops irradiation, generation ultrasound of thus periodically expanding with heat and contract with cold
Ripple, i.e. photoacoustic signal.Because photoacoustic signal reflects the light absorbs distribution of organization internal, therefore it can be rebuild by data processing
Vascular distribution image is obtained, so that the effect to microvesicle blast treatment tumour is estimated.
It is an advantage of the invention that：
(1) the inventive method combines the characteristics of optical imagery high-contrast harmony studies image height resolution ratio, because acoustical signal is passed
Low scattering properties in the tissue is broadcast, with having deeper penetration depth than traditional optical imaging method；
(2) present invention is monitored using photoacoustic technique, without carrying out the processing such as histotomy, with non-invasive, it is possible to achieve
Long term monitoring, and the opto-acoustic microscopic imaging equipment can realize the imaging of a variety of anatomical locations；
(3) microvesicle that the present invention is used, cheap, easy to use, it is easy to application.
Brief description of the drawings
Fig. 1 is the structural representation of photoacoustic microscope of the present invention；
Fig. 2 is that photoacoustic microscope monitors microvesicle blast treatment pre-neoplastic blood vessel opto-acoustic microscopic imaging；
Fig. 3 is tumor vessel opto-acoustic microscopic imaging after photoacoustic microscope monitoring microvesicle blast treatment.
Embodiment
Below in conjunction with accompanying drawing, the present invention is further illustrated：
A kind of photoacoustic microscope, including microscopic system, signal acquisition control system and drive system, signal acquisition control system
Control drive system and the information for gathering microscopic system, and the data collected are stored and analyzed；Drive system is adjusted
The position of corresponding assembly is saved, is realized to microscopical adjustment.
Described microscopic system includes pulse laser 10, and pulse laser 10 produces 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 fiber
14th, collimater 15, the second beam expanding lens combination 16, speculum 17, the second microcobjective 18, beam resolution element 19, acoustic lens 20, water
Groove 21 and article carrying platform 22；Described beam resolution element 19 is made up of right-angle prism and diamond shaped lens, diamond shaped lens or so two
Side is provided with silicon layer 23.
The ultrasonic detector 24, signal amplifier 25, data that described 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 is combined, and converts acoustic energy into electric energy, is easy to computer 27 to handle signal；Beam resolution element 19 is by right angle
Prism and diamond shaped lens are constituted, and two sides of diamond shaped lens or so are provided with silicon layer 23, and silicone oil has close with lens
Light refractive index but acoustic impedance difference, therefore can penetrate light beam in silicon layer 23 and reflect acoustic beam, realization swashs pulse
The laser that light device occurs is separated with the ultrasonic wave that organism reflects, and another side of diamond shaped lens is also equipped with one
Layer silicon layer 23, secondary reflection ultrasonic wave is 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 is convenient to be adjusted according to requirement of experiment to photoacoustic microscope,
Described drive system includes the two-dimensional translation platform 29 driven by motor 28, and beam resolution element 19 is flat installed in two-dimensional translation
On platform 29, the signal input part electrical connection computer 27 of motor 28.
For the photoacoustic signal produced using the synchronous acquisition of data collecting card 26 per individual pulse, described pulse laser
10 are provided with synchronous triggering device 30, the electrical connection data collecting card 26 of synchronous triggering device 30.
In order to be expanded to short-pulse laser, the lens on microcobjective can be more completely covered in, are realized
Preferable focusing effect, reduces the size of focal beam spot, along short-pulse laser direction of advance, described the first beam expanding lens combination 11
With the second beam expanding lens combination 16 by focal length be the convex lens of 20mm first be 30,40 with focal length or the convex lens groups of 60mm second into.
The invention also discloses a kind of method for monitoring microvesicle explosion in biological tissues, described method is utilizes optoacoustic
Microvessel density is caused to change before and after microscope imaging monitoring microvesicle explosion.
Described method comprises 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, tumor region is scanned with ultrasonic generator, break the microvesicle in tumor region
Split；
3) after microvesicle explosion, tumor region is scanned using photoacoustic microscope, the tumor vessel optoacoustic letter after microvesicle explosion is obtained
Number；
4) data processing is carried out to the photoacoustic signal collected, the blood vessel optoacoustic of tumor region is micro- before and after contrast microvesicle explosion
Image, microvesicle explosion in biological tissues is monitored with this.
Specific process of the test：
Microbubble solution is prepared, takes pure microvesicle to add the physiological saline of corresponding dosage, is configured to the microvesicle standard liquid of 30% concentration,
After mouse is anaesthetized, article carrying platform and continuous narcosis are placed on, is swept before injection microbubble solution with opto-acoustic microscopic imaging equipment
Retouch tumor region and obtain Fig. 2, then in the microbubble solution of 100 microlitres of mouse tail vein injection, surpassed with ultrasonic probe transmitting high energy
Sound wave carries out explosion to microbubble solution.Observed after seven days, the optoacoustic after photoacoustic imaging is tested is carried out to target area
Fig. 3.From figure 2 it can be seen that light tone tubular portion is blood vessel, blood vessel relatively enriches；From figure 3, it can be seen that vessel density
Decline, illustrate fragmentation effect of the microvesicle explosion to tumor region blood vessel.
Finally it should be noted that：Obviously, above-described embodiment is only intended to clearly illustrate example of the present invention, and simultaneously
The non-restriction to embodiment.For those of ordinary skill in the field, it can also do on the basis of the above description
Go out other various forms of changes or variation.There is no necessity and possibility to exhaust all the enbodiments.And thus drawn
Among the obvious change or variation that Shen goes out are still in protection scope of the present invention.
Claims (4)
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 gathering microscopic system；It is characterized in that：
Described microscopic system includes pulse laser, and pulse laser produces short-pulse laser, advanced along short-pulse laser
Direction is disposed with the combination of the first beam expanding lens, the first microcobjective, fiber coupler, single-mode fiber, collimater, second expanded
Microscope group conjunction, speculum, the second microcobjective, beam resolution element, acoustic lens, tank and article carrying platform；Described beam resolution element
It is made up of right-angle prism and diamond shaped lens, two sides of diamond shaped lens or so are provided with silicon layer；
Described signal acquisition control system includes ultrasonic detector, signal amplifier, data collecting card and the meter being sequentially connected in series
Calculation machine, ultrasonic detector is 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；
Described drive system is included by motor-driven two-dimensional translation platform, and beam resolution element is arranged on two-dimensional translation platform
On, the signal input part electrical connection computer of motor；
Described pulse laser is provided with synchronous triggering device, synchronous triggering device electrical connection data collecting card.
2. a kind of photoacoustic microscope as claimed in claim 1, it is characterised in that described along short-pulse laser direction of advance
First beam expanding lens is combined and the combination of the second beam expanding lens is the convex lens of 20mm first by focal length and focal length is 30,40 or 60mm second
Convex lens group into.
3. a kind of method for monitoring microvesicle explosion in biological tissues, it is characterised in that described method is micro- using optoacoustic
Microvessel density is caused to change before and after mirror Imaging: Monitoring microvesicle explosion.
4. a kind of method for monitoring microvesicle explosion in biological tissues as claimed in claim 3, it is characterised in that described side
Method comprises 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, tumor region is scanned with ultrasonic generator, break the microvesicle in tumor region
Split；
3) after microvesicle explosion, tumor region is scanned using photoacoustic microscope, the tumor vessel photoacoustic signal after microvesicle explosion is obtained；
4) data processing is carried out to the photoacoustic signal collected, the blood vessel optoacoustic micrograph of tumor region before and after contrast microvesicle explosion
Picture, microvesicle explosion in biological tissues is monitored with this.
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| CN108535196A (en) * | 2018-04-08 | 2018-09-14 | 深圳大学 | A kind of detecting optoacoustic microscopic system and imaging method |
| CN108742528A (en) * | 2018-05-29 | 2018-11-06 | 华南师范大学 | A kind of the fast linear cofocus scanning optoacoustic probe and its imaging method of no water coincidence |
| CN110455719A (en) * | 2019-08-16 | 2019-11-15 | 中国科学技术大学 | Three-dimensional photoacoustic imaging system and method |
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| CN110796603A (en) * | 2019-11-25 | 2020-02-14 | 曲阜师范大学 | High-resolution photoacoustic imaging method for deep tumor neovascularization |
| CN110796603B (en) * | 2019-11-25 | 2023-05-23 | 曲阜师范大学 | High-resolution photoacoustic imaging method for deep tumor neovascular |
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