CN102488494B - Totally internal reflection type photo-acoustic microscopic imaging system and method - Google Patents
Totally internal reflection type photo-acoustic microscopic imaging system and method Download PDFInfo
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- CN102488494B CN102488494B CN 201110362731 CN201110362731A CN102488494B CN 102488494 B CN102488494 B CN 102488494B CN 201110362731 CN201110362731 CN 201110362731 CN 201110362731 A CN201110362731 A CN 201110362731A CN 102488494 B CN102488494 B CN 102488494B
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Abstract
The invention provides a totally internal reflection type photo-acoustic microscopic imaging system, which comprises a laser device, a focusing lens, a prism, an ultrasonic sensor and an imaging device. Laser transmitted by the laser device successively passes through the focusing lens and the prism to illuminate a boundary of a biological tissue, so that totally internal reflection is realized on the prism and the boundary of the biological tissue, and ultrasonic signals are generated on the biological tissue; and the ultrasonic signals are transmitted to the imaging device via the ultrasonic sensor. The invention further provides a totally internal reflection type photo-acoustic microscopic imaging method. In the totally internal reflection type photo-acoustic microscopic imaging method, totally internal reflection is realized on the boundary of the biological tissue by the aid of light, so that a evanescent wave is generated on the boundary of the biological tissue to stimulate theultrasonic signals, then the ultrasonic sensor detects time domain ultrasonic signals, distribution information of absorbers on the surface of the biological tissue is obtained at one position, and three-dimensional absorber distribution information on the surface of the biological tissue can be obtained by a linear scanning method.
Description
Technical field
The present invention relates to the opto-acoustic microscopic imaging technical field, particularly a kind of total internal reflection type opto-acoustic microscopic imaging system and method.
Background technology
The imaging of high-resolution biological tissue has great importance for fields such as the generation of understanding various physiological process, monitoring of diseases in the organism and development, clinical early diagnosiss, at present common high-resolution imaging pattern has two kinds of optical microphotograph imaging and ultrasonic micro-imagings, technology such as optical microphotograph imaging such as optical coherent chromatographic imaging, the burnt micro-imaging of copolymerization, two-photon micro-imaging, the scattering or the external source fluorescence signal that rely on biological tissue carry out imaging, the acoustic impedance property difference that ultrasonic micro-imaging relies on biological tissue carries out imaging, so contrast is relatively poor.
In recent years, technical research for the imaging of optoacoustic biological tissue constantly has new breakthrough, utilize short-pulse laser to excite absorber such as blood, melanin etc. in the biological tissue to produce ultrasonic signal, thereby the absorber that reconstructs in the biological tissue by the ultrasonic signal that detection is diffused into the biological tissue surface distributes, and these absorbers have often comprised the inner abundant physiological and pathological information of biological tissue, therefore, can obtain reasonable differentiation to biological pathological changes biological tissue and normal biological tissue by photoacoustic imaging.This imaging mode is compared with traditional X ray CT, NMR (Nuclear Magnetic Resonance)-imaging, ultra sonic imaging, is not only Non-ionizing radiation, and is harmless fully to human body, and pathological changes biological tissue is had extraordinary contrast.
The photoacoustic imaging of three-dimensional high definition can be made accurate sign to the information such as distribution of absorber, and therefore significant to the early diagnosis of physiological and pathological, the opto-acoustic microscopic imaging system of high spatial resolution also is developed out gradually.U.S. US 20060184042 discloses the reflective optoacoustic micro imaging system of a kind of details in a play not acted out on stage, but told through dialogues, and system space resolution is decided by the frequency characteristic of ultrasonic probe, can obtain the high-resolution imaging results of micron dimension by using high frequency probe.Document Optical-resolution photoacoustic microscopy in vivo imaging of single capillaries.Optics Letters.33 (9): 929-931 discloses a kind of opto-acoustic microscopic imaging system of optical resolution, cooperates the method for supersonic sounding to realize 5 microns spatial resolution by optical focus.On this basis, document In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA.Optics Letters.35 (24): 4139-4141 discloses the opto-acoustic microscopic imaging system of a kind of sub-wavelength (hundreds of nanometers) resolution.But these systems only improve the lateral resolution of system, and axial resolution still maintains micron dimension, and therefore, this imaging pattern can't be realized three-dimensional high-resolution (nanometer scale) imaging.Document Total internal reflection photoacoustic detection spectroscopy.Proceedings of SPIE, Vol.7899:78993E has introduced a kind of photoacoustic spectrum technology based on total internal reflection, but this technology only limit to biological tissue chemical molecular information analyze, do not relate to imaging.
Summary of the invention
Technical problem to be solved by this invention provides a kind of total internal reflection type opto-acoustic microscopic imaging system and method that can realize three-dimensional high-resolution imaging.
For solving the problems of the technologies described above, the invention provides a kind of total internal reflection type opto-acoustic microscopic imaging system and comprise laser instrument, condenser lens, prism, sonac and imaging device; The laser of described laser instrument emission is radiated at the interface of biological tissue successively by described condenser lens, prism, thereby in the interface of described prism and described biological tissue experiences total internal reflection, and at described biological tissue generation ultrasonic signal; Described ultrasonic signal is sent to described imaging device by described sonac.
Further, described total internal reflection type opto-acoustic microscopic imaging system also comprises collimating lens, object lens;
Be disposed with described collimating lens and described object lens between described condenser lens and the described prism.
Further, described total internal reflection type opto-acoustic microscopic imaging system also comprises the two-dimension translational platform that is connected with described imaging device, and described collimating lens, object lens, prism and sonac are arranged on the described two-dimension translational platform.
Further, described sonac is placed on the bottom at the interface of the top margin of described prism or biological tissue.
Further, described total internal reflection type opto-acoustic microscopic imaging system also comprises amplifier and data collecting card; Be disposed with described amplifier and described data collecting card between described sonac and the imaging device.
Further, described prism is the prism that comprises two parallel planes.
The present invention also provides a kind of total internal reflection type opto-acoustic microscopic imaging method may further comprise the steps:
Step 10, be focused into the interface that is mapped to biological tissue by a branch of short-pulse laser, thereby in the interface of biological tissue experiences total internal reflection, produce evanescent wave at the interface of biological tissue, induce the biological tissue surface to produce ultrasonic signal;
Step 20, utilize sonac detecting ultrasonic signal, and collect imaging device;
Step 30, repeating step 10, step 20, thus reconstruct the 3-D view of biological tissue.
Further, described pulse laser wavelength is 300-1000nm.
Total internal reflection type opto-acoustic microscopic imaging system and method provided by the invention, utilize light in the interface of biological tissue experiences total internal reflection, thereby the evanescent wave excitation ultrasound signal that produces at the interface of biological tissue, survey the time domain ultrasonic signal by sonac again, obtain a locational biological tissue surface absorber and distribute, and then obtain the three-dimensional absorber distributed intelligence on biological tissue surface by the method for linear scanning.
Description of drawings
The sketch map of the total internal reflection type opto-acoustic microscopic imaging system that Fig. 1 provides for the embodiment of the invention.
The principle schematic of the total internal reflection type opto-acoustic microscopic imaging system that Fig. 2 provides for the embodiment of the invention;
The principle schematic of the optional total internal reflection type opto-acoustic microscopic imaging system that Fig. 3 provides for the embodiment of the invention.
The specific embodiment
As shown in Figure 1, total internal reflection type opto-acoustic microscopic imaging provided by the invention system, it comprises laser instrument 1, condenser lens 2, optical fiber 3, collimating lens 4-1, object lens 4-2, prism 4-3, sonac 4-4, amplifier 6, data collecting card 7, two-dimension translational platform 8 and imaging device 9 (can be computer).Image reconstruction and process software are housed in the computer, can be used for image reconstruction and post-processed, for example based on the automated image reconstruction process software of the Visual C++6.0 platform development of Microsoft company; The scan control software of translation stage is housed in the computer simultaneously, be used for drives the scanning of translation stage, for example based on the translation stage drive software of the LabVIEW platform development of National Instruments company exploitation.Prism is the prism that comprises two parallel planes, can be shapes such as trapezoidal, prism.Wherein, the laser line focus lens 2 that send of laser instrument 1 are incident to optical fiber 3.The light of optical fiber 3 outputs is through collimating lens 4-1 collimator and extender, object lens 4-2 focuses on, focused beam is incident to the 4-3 of falling the Dove prism, in the interface experiences total internal reflection of the 4-3 of falling the Dove prism with biological tissue 5, at the interface generation evanescent wave of the 4-3 of falling the Dove prism with biological tissue 5, the absorbent body evanescent wave on the surface of biological tissue 5 produces ultrasonic signal simultaneously.Ultrasonic signal transfers to sonac 4-4 through the 4-3 of falling the Dove prism, is converted into the signal of telecommunication, is gathered by data collecting card 7 after amplifier 6 amplifies again, sends into imaging device 9 storages.Collimating lens 4-1, object lens 4-2, the 4-3 of falling the Dove prism and sonac 4-4 are fixed together and form scanheads 4, are placed on the two-dimension translational platform 8.Two-dimension translational platform 8 is electrically connected with imaging device 9, can realize linear scanning under the control of imaging device 9.Operation principle below in conjunction with Fig. 2,3 couples total internal reflection type opto-acoustic microscopic imaging provided by the invention system describes respectively.
As shown in Figure 2, the operation principle of total internal reflection type opto-acoustic microscopic imaging provided by the invention system is: the pulse laser that laser instrument 1 sends line focus lens 2, collimating lens 4-1 and object lens 4-2 successively is incident to the 4-3 of falling the Dove prism inside that is placed on biological tissue 5 surfaces, and in the base of the 4-3 of falling Dove prism experiences total internal reflection; Interface in biological tissue 5 in the time of total internal reflection produces evanescent wave, the absorber 5-1 on the surface of biological tissue 5 absorbs evanescent wave and produces ultrasonic signal, ultrasonic signal transfers to sonac 4-4 along the 4-3 of falling the Dove prism, the signal that sonac 4-4 receives is sent into imaging device 9 by data collecting card 7 after amplifier 6 amplifies, under the drive of two-dimension translational platform 8, scan whole biological tissue surface again, thereby obtain the three-dimensional absorber distributed image of biological tissue.
As shown in Figure 2, the operation principle of total internal reflection type opto-acoustic microscopic imaging provided by the invention system is: the pulse laser that laser instrument 1 sends line focus lens 2, collimating lens 4-1 and object lens 4-2 successively is incident to the 4-3 of falling the Dove prism inside that is placed on biological tissue 5 surfaces, and in the base of the 4-3 of falling Dove prism experiences total internal reflection; Interface in biological tissue in the time of total internal reflection produces evanescent wave, the absorber 5-1 on the surface of biological tissue 5 absorbs evanescent wave and produces ultrasonic signal, ultrasonic signal transfers to the sonac 4-4 of the bottom that is placed on biological tissue 5 along biological tissue 5, the signal that sonac 4-4 receives is sent into imaging device 9 by data collecting card 7 after amplifier 6 amplifies, under the drive of two-dimension translational platform 8, scan whole biological tissue surface again, thereby obtain the three-dimensional absorber distributed image of biological tissue 5.
Select for use each member to connect to form this device, wherein: the Nd:YAG laser instrument that laser instrument 1 selects for use Spectra-Physics to produce, the short-pulse laser of output 532nm can the complex dye laser output wavelength be the short-pulse laser of 600-1000nm also; Sonac 4-4 selects the V2022 contact ultrasonic probe of U.S. Olympus Corp production for use, has the mid frequency of 75MHz, can obtain higher spatial resolution; The SR445A that amplifier 6 selects for use U.S. Stamford instrument institute to produce, bandwidth be direct current to 350MHz, can realize maximum 625 amplification; The ATS9350 that data collecting card 7 selects for use Canadian Alazartech company to produce, the maximum sampling rate 500MSPS of the dual pathways; Imaging device 9 adopts Pentium 3 microcomputers; The ANT95-50-ULTRA that two-dimension translational platform 8 selects for use U.S. aerotech company to produce, precision and repetitive positioning accuracy are nanometer scale, are fit to high resolution scanning.
The embodiment of the invention also provides a kind of total internal reflection type opto-acoustic microscopic imaging method may further comprise the steps:
Step 10, be focused into the interface that is mapped to biological tissue by a branch of short-pulse laser, thereby in the interface of biological tissue experiences total internal reflection, produce evanescent wave at the interface of biological tissue, induce the biological tissue surface to produce ultrasonic signal.Pulse laser wavelength is 300-1000nm.
Step 20, utilize sonac detecting ultrasonic signal, and collect imaging device.
Step 30, repeating step 10, step 20, thus reconstruct the 3-D view of biological tissue.
Above method step can be realized by total internal reflection type opto-acoustic microscopic imaging system shown in Figure 1.
Total internal reflection type opto-acoustic microscopic imaging system and method provided by the invention has following beneficial effect:
(1) the present invention utilizes photoacoustic signal to carry out the three-dimensional imaging of biological tissue, is not only Non-ionizing radiation, and the information that comprises is more than simple ultrasonic signal, can realize the biological function imaging.
(2) the present invention utilizes the signal of evanescent wave detection of biological tissue surface, can obtain high axial resolution, thereby realize high-resolution imaging at three dimension scale.
(3) the present invention utilizes ultrasonic signal to rebuild biological tissue's internal information, can obtain the system of different resolution by simple replacing sonac, need not system structure is changed, and simple to operate, adaptability is strong.
(4) the present invention is simple in structure, and it is cheap to fake, and is easy to realize having bigger marketing prospect.
It should be noted last that, the above specific embodiment is only unrestricted in order to technical scheme of the present invention to be described, although with reference to example the present invention is had been described in detail, those of ordinary skill in the art is to be understood that, can make amendment or be equal to replacement technical scheme of the present invention, and not breaking away from the spirit and scope of technical solution of the present invention, it all should be encompassed in the middle of the claim scope of the present invention.
Claims (1)
1. a total internal reflection type opto-acoustic microscopic imaging system is characterized in that, comprising:
Laser instrument, condenser lens, prism, sonac, imaging device, collimating lens, object lens, the two-dimension translational platform, amplifier and the data collecting card that are connected with described imaging device;
The laser of described laser instrument emission is radiated at the interface of biological tissue successively by described condenser lens, prism, thereby in the interface of described prism and described biological tissue experiences total internal reflection, and at described biological tissue generation ultrasonic signal;
Described ultrasonic signal is sent to described imaging device by described sonac;
Be disposed with described collimating lens and described object lens between described condenser lens and the described prism; Described collimating lens, object lens, prism and sonac are arranged on the described two-dimension translational platform;
Described sonac is placed on the bottom at the interface of the top margin of described prism or biological tissue;
Be disposed with described amplifier and described data collecting card between described sonac and the imaging device;
Described prism is the prism that comprises two parallel planes;
It is trapezoidal or prismatic that the shape of described prism is down.
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| CN104188625B (en) * | 2014-08-20 | 2016-03-16 | 上海交通大学 | A kind of multi-modal micro imaging system |
| JP6553210B2 (en) * | 2015-01-15 | 2019-07-31 | ハーリング、ロドニー | Diffuse acoustic confocal imaging device |
| CN106236145B (en) * | 2016-09-07 | 2019-02-22 | 北京大学 | A kind of supersonic sounding and opto-acoustic imaging devices and its method based on total reflection |
| CN107692975B (en) * | 2017-10-26 | 2020-08-28 | 电子科技大学 | Three-dimensional photoacoustic tomography device and method |
| CN109745626A (en) * | 2017-11-02 | 2019-05-14 | 钱浙滨 | A kind of method and device inside laser beam irradiation human body |
| CN109276229B (en) * | 2018-08-15 | 2022-04-15 | 华中科技大学苏州脑空间信息研究院 | Rapid focusing system and method for photoacoustic microscopic imaging |
| CN111449629B (en) * | 2020-04-28 | 2023-04-25 | 北京信息科技大学 | Optical coherence elastography method and device |
| CN113100928B (en) * | 2021-03-25 | 2023-03-24 | 苏州芙迈蕾医疗科技有限公司 | Multi-wavelength picosecond laser beauty instrument based on photoacoustic imaging guidance and control method thereof |
| CN116499975B (en) * | 2023-06-29 | 2023-09-22 | 之江实验室 | Prism device for optical surface wave sensor and design and installation method thereof |
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| CN101918811A (en) * | 2007-10-25 | 2010-12-15 | 圣路易斯华盛顿大学 | Confocal photoacoustic microscopy with optical lateral resolution |
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