CN106994006A - Bimodal imaging system - Google Patents
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Abstract
一种双模态成像系统,包括:激光光源、光束分光镜、光谱仪、参考臂、显微物镜、一直角边设有声聚焦凹槽的不规则直角三角棱镜、规则直角三角棱镜、水浸式高速扫描振镜和超声探头,其中:激光光源产生光束依次经过设置于激光光源和光束分光镜之间的可变光阑、第一透镜、针孔光阑和第二透镜进入光束分光镜,通过光束分光镜后的一部分光束入射到参考臂,另一部分光束经过光束分光镜入射到显微物镜形成聚焦光束,该聚焦光束射入不规则直角三角棱镜的直角边后由设有声聚焦凹槽的另一直角边射出,本发明系统结构简化,增加系统稳定性,同时降低系统的成本。
A dual-mode imaging system, including: a laser light source, a beam splitter, a spectrometer, a reference arm, a microscope objective lens, an irregular right-angle triangular prism with an acoustic focusing groove on a right-angle side, a regular right-angle triangular prism, and a water-immersed high-speed The scanning galvanometer and the ultrasonic probe, wherein: the light beam generated by the laser light source passes through the variable diaphragm, the first lens, the pinhole diaphragm and the second lens arranged between the laser light source and the beam splitter and enters the beam splitter, and the light beam passes through A part of the beam behind the beam splitter enters the reference arm, and another part of the beam passes through the beam splitter and enters the microscope objective to form a focused beam. Right-angle side injection, the system structure of the present invention is simplified, the stability of the system is increased, and the cost of the system is reduced at the same time.
Description
技术领域technical field
本发明涉及的是一种显微成像领域的技术,具体是一种双模态成像系统。The invention relates to a technique in the field of microscopic imaging, in particular to a dual-mode imaging system.
背景技术Background technique
光学相干显微成像(Optical coherence Microscopy,OCM)原理与光学相干层析成像相似,都是基于入射光子组织后向散射光特性,检测生物组织不同深度层面对入射光子的背向反射或散射强度,从而获得一定深度范围内的组织显微结构信息,进而通过横向扫描获得生物组织的二维或三维结构信息。光分辨光声显微成像(Optical-ResolutionPhotoacoustic Microscopy,OR-PAM)主要是基于生物组织内吸收体对光吸收分布特性,组织因吸收光能而产生超声信号,通过超声换能器探测,从而获取吸收体的形态学和功能参数细微改变及病理状态图像。The principle of optical coherence microscopy (OCM) is similar to that of optical coherence tomography, which is based on the backscattering light characteristics of incident photon tissue, and detects the back reflection or scattering intensity of incident photons at different depths of biological tissue. In this way, the tissue microstructure information within a certain depth range can be obtained, and then the two-dimensional or three-dimensional structural information of biological tissues can be obtained through horizontal scanning. Optical-Resolution Photoacoustic Microscopy (OR-PAM) is mainly based on the distribution characteristics of light absorption by absorbers in biological tissues. The tissue absorbs light energy to generate ultrasonic signals, which are detected by ultrasonic transducers to obtain Subtle changes in the morphological and functional parameters of the absorber and images of pathological states.
OCM成像技术,利用组织散射光子的弱相干干涉信号,检测生物组织内部不同深度组织对入射光子的背向反射或散射强度的变化,能够提供高纵向分辨与高对比结构成像,但是其无法提供血氧饱和度、氧代谢与血氧蛋白含量等重要的微血管重要的功能参数信息。OR-PAM它基于血液中的重要组成成分氧血红蛋白和去氧血红蛋白对不同波段的光吸收系数的差异,可实现有效的特定位置功能成像、以及量化代谢相关的血红蛋白浓度、SO2及总血红蛋白浓度等关键的在临床诊断的生理功能性参数指标测量。OCM imaging technology uses weakly coherent interference signals of tissue scattered photons to detect changes in the back reflection or scattering intensity of incident photons at different depths inside biological tissues. It can provide high longitudinal resolution and high contrast structural imaging, but it cannot provide blood Important functional parameters of microvessels such as oxygen saturation, oxygen metabolism and hemoglobin content. OR-PAM is based on the difference in the light absorption coefficients of oxygenated hemoglobin and deoxygenated hemoglobin in different bands, which are important components in blood, and can realize effective position-specific functional imaging and quantify metabolic-related hemoglobin concentration, SO 2 and total hemoglobin concentration and other key physiological and functional parameters in clinical diagnosis.
发明内容Contents of the invention
本发明针对现有技术无法实现大范围高速的活体动物高分辨成像,子成像系统为光学相干层析成像,对微血管成像尤其是在肿瘤发展前期的毛细血管检测中横向分辨存在严重不足,提出一种双模态成像系统。Aiming at the fact that the existing technology cannot realize large-scale high-speed high-resolution imaging of living animals, the sub-imaging system is optical coherence tomography, and there is a serious shortage of lateral resolution in microvascular imaging, especially in capillary detection in the early stage of tumor development. A dual modality imaging system.
本发明是通过以下技术方案实现的:The present invention is achieved through the following technical solutions:
本发明包括:激光光源、光束分光镜、光谱仪、参考臂、显微物镜、一直角边设有声聚焦凹槽的不规则直角三角棱镜、规则直角三角棱镜、水浸式高速扫描振镜和超声探头,其中:不规则直角三角棱镜和规则直角三角棱镜的斜面相粘合,不规则直角三角棱镜和规则直角三角棱镜的两斜面之间设有铝膜层,超声探头与规则直角三角棱镜一直角边贴合且与声聚焦凹槽相对,激光光源产生光束依次经过设置于激光光源和光束分光镜之间的可变光阑、第一透镜、针孔光阑和第二透镜进入光束分光镜,通过光束分光镜后的一部分光束入射到参考臂,另一部分光束经过光束分光镜入射到显微物镜形成聚焦光束,该聚焦光束射入不规则直角三角棱镜的直角边后由设有声聚焦凹槽的另一直角边射出并进入水浸式高速扫描振镜对物体进行扫描,物体表面产生的超声信号经水浸式高速扫描振镜、声聚焦凹槽和规则直角三角棱镜后由超声探头收集,物体表面产生的后向散射光沿原光路返回与参考臂中光束结合产生干涉信号,干涉信号经光束分光镜入射到光谱仪。The invention includes: a laser light source, a beam splitter, a spectrometer, a reference arm, a microscope objective lens, an irregular right-angle triangular prism with an acoustic focus groove on a right-angle side, a regular right-angle triangular prism, a water-immersion high-speed scanning vibrating mirror and an ultrasonic probe , wherein: the slopes of the irregular right-angle triangular prism and the regular right-angle triangular prism are bonded together, an aluminum film layer is arranged between the two slopes of the irregular right-angle triangular prism and the regular right-angle triangular Fitted and opposite to the acoustic focusing groove, the beam generated by the laser light source passes through the variable diaphragm, the first lens, the pinhole diaphragm and the second lens arranged between the laser light source and the beam splitter and enters the beam splitter in sequence, and passes through A part of the beam behind the beam splitter enters the reference arm, and another part of the beam passes through the beam splitter and enters the microscope objective to form a focused beam. The object is scanned from the right-angle side and enters the water-immersed high-speed scanning galvanometer. The ultrasonic signal generated on the surface of the object is collected by the ultrasonic probe after passing through the water-immersed high-speed scanning galvanometer, the acoustic focusing groove and the regular right-angled triangular prism. The generated backscattered light returns along the original optical path and combines with the beam in the reference arm to generate an interference signal, and the interference signal enters the spectrometer through the beam splitter.
所述的第二透镜和光束分光镜之间设有第一反射镜和光电检测器,第一反射镜将第二透镜出射光分束后的一部分射入光电检测器。A first reflector and a photodetector are arranged between the second lens and the beam splitter, and the first reflector injects a part of the beam splitted from the second lens into the photodetector.
所述的参考臂包括依次设置的聚焦透镜、第一光纤耦合器和第二反射镜。The reference arm includes a focusing lens, a first fiber coupler and a second reflecting mirror arranged in sequence.
所述的激光光源发出的光束最大脉冲能量大于20μJ,重复频率大于5KHz,脉冲宽度小于10ns。The maximum pulse energy of the beam emitted by the laser light source is greater than 20μJ, the repetition frequency is greater than 5KHz, and the pulse width is less than 10ns.
所述的超声探头的中心频率大于30MHz,-6dB带宽大于50%,灵敏度大于-220dB,延迟线为4.25μs。The center frequency of the ultrasonic probe is greater than 30MHz, the -6dB bandwidth is greater than 50%, the sensitivity is greater than -220dB, and the delay line is 4.25μs.
所述的规则直角三角棱镜和不规则直角三角棱镜的直角都边大于15mm,斜边都大于21.2mm。Both the right angle sides of the regular right-angle triangular prism and the irregular right-angle triangular prism are larger than 15 mm, and the hypotenuses are larger than 21.2 mm.
所述的声聚焦凹槽的直径为9mm,曲率半径大于7.07mm,中心深度大于2.2mm。The diameter of the acoustic focusing groove is 9mm, the radius of curvature is greater than 7.07mm, and the center depth is greater than 2.2mm.
所述的水浸式高速扫描振镜的工作频率快轴大于25KHz,慢轴大于2KHz,其镜面直径大于1mm,振动周期大于10-11s。The working frequency of the water-immersed high-speed scanning galvanometer has a fast axis greater than 25KHz, a slow axis greater than 2KHz, a mirror diameter greater than 1 mm, and a vibration period greater than 10 -11 s.
技术效果technical effect
与现有技术相比,本发明系统结构简化,增加系统稳定性,同时降低系统的成本,对于系统的产品化和用户的使用操作都十分有利,有效的降低了声波透射过程中的衰减,系统更加集成化,光与声达到了共轴的目的,大大提高了系统的探测的信噪比和灵敏度,且将光与声的传输、扫描与传输结合在一个系统内。Compared with the prior art, the system structure of the present invention is simplified, the system stability is increased, and the cost of the system is reduced at the same time. More integrated, light and sound achieve the purpose of coaxiality, which greatly improves the signal-to-noise ratio and sensitivity of the system's detection, and combines the transmission, scanning and transmission of light and sound in one system.
附图说明Description of drawings
图1为本发明结构示意图;Fig. 1 is a structural representation of the present invention;
图2为成像对比图;Figure 2 is an imaging comparison chart;
图中:(a)为普通装置成像;(b)为本发明成像;Among the figure: (a) is the common device imaging; (b) is the imaging of the present invention;
图中:1激光光源、2可变光阑、3第一透镜、4针孔光阑、5第二透镜、6第一反射镜、7光电检测器、8光束分光镜、9聚焦透镜、10第一光纤耦合器、11第二反射镜、12大孔径显微物镜、13不规则直角三角棱镜、14规则直角三角棱镜、15铝膜层、16水浸式高速扫描振镜、17声聚焦凹槽、18超声信号、19水槽、20超声探头、21信号放大器、22控制采集电脑、23光谱仪、24第二光纤耦合器、25聚焦物镜。In the figure: 1 laser light source, 2 iris diaphragm, 3 first lens, 4 pinhole diaphragm, 5 second lens, 6 first reflector, 7 photoelectric detector, 8 beam splitter, 9 focusing lens, 10 The first optical fiber coupler, 11 the second mirror, 12 large-aperture microscope objective lens, 13 irregular right-angle triangular prism, 14 regular right-angle triangular prism, 15 aluminum film layer, 16 water immersion high-speed scanning vibrating mirror, 17 acoustic focusing concave Tank, 18 ultrasonic signal, 19 water tank, 20 ultrasonic probe, 21 signal amplifier, 22 control acquisition computer, 23 spectrometer, 24 second fiber coupler, 25 focusing objective lens.
具体实施方式detailed description
如图1所示,本实施例包括:激光光源1、光束分光镜8、光谱仪23、参考臂、大孔径显微物镜12、一直角边设有声聚焦凹槽17的不规则直角三角棱镜13、规则直角三角棱镜14、水浸式高速扫描振镜16和超声探头20,其中:不规则直角三角棱镜13和规则直角三角棱镜14的斜面相粘合,不规则直角三角棱镜13和规则直角三角棱镜14的两斜面之间设有铝膜层15,超声探头20与规则直角三角棱镜14一直角边贴合且与声聚焦凹槽17相对,激光光源1产生光束依次经过设置于激光光源1和光束分光镜8之间的可变光阑2、第一透镜3、针孔光阑4和第二透镜5进入光束分光镜8,通过光束分光镜8后的一部分光束入射到参考臂,另一部分光束依次经过光束分光镜8入射到大孔径显微物镜12形成聚焦光束,该聚焦光束射入不规则直角三角棱镜13的直角边后由设有声聚焦凹槽17的另一直角边射出并进入水浸式高速扫描振镜16对物体进行扫描,物体表面产生的超声信号18经水浸式高速扫描振镜16、声聚焦凹槽17和规则直角三角棱镜14后由超声探头20收集,物体表面产生的后向散射光沿原光路返回与参考臂中光束结合产生干涉信号,干涉信号经光束分光镜8入射到光谱仪23。As shown in Figure 1, the present embodiment comprises: a laser light source 1, a beam splitter 8, a spectrometer 23, a reference arm, a large-aperture microscopic objective lens 12, an irregular right-angled triangular prism 13 that is provided with an acoustic focusing groove 17 on a right-angled side, Regular right-angle triangular prism 14, water immersion type high-speed scanning vibrating mirror 16 and ultrasonic probe 20, wherein: irregular right-angle triangular prism 13 and the slope of regular right-angle triangular prism 14 are bonded, irregular right-angle triangular prism 13 and regular right-angle triangular prism An aluminum film layer 15 is arranged between the two slopes of 14, and the ultrasonic probe 20 is attached to the right-angle side of the regular right-angled triangular prism 14 and is opposite to the acoustic focusing groove 17. The variable diaphragm 2, the first lens 3, the pinhole diaphragm 4 and the second lens 5 between the beam splitters 8 enter the beam splitter 8, and a part of the beam passing through the beam splitter 8 enters the reference arm, and the other part of the beam Sequentially pass through the beam splitter 8 and enter the large-aperture microscopic objective lens 12 to form a focused beam. The high-speed scanning galvanometer 16 scans the object, and the ultrasonic signal 18 generated on the object surface is collected by the ultrasonic probe 20 after passing through the water-immersion high-speed scanning galvanometer 16, the acoustic focusing groove 17 and the regular right-angle triangular prism 14, and the ultrasonic signal generated on the surface of the object The backscattered light returns along the original optical path and combines with the light beam in the reference arm to generate an interference signal, and the interference signal enters the spectrometer 23 through the beam splitter 8 .
所述的第二透镜5和光束分光镜8之间设有第一反射镜6和光电检测器7,第一反射镜6将第二透镜5出射光分束后的一部分进入光电检测器7。参考臂包括依次设置的聚焦透镜9、第一光纤耦合器10和第二反射镜11。光束分光镜8和光谱仪23之间依次设有聚焦物镜25和第二光纤耦合器24。A first reflector 6 and a photodetector 7 are arranged between the second lens 5 and the beam splitter 8 , and the first reflector 6 splits a part of the light emitted by the second lens 5 into the photodetector 7 . The reference arm includes a focusing lens 9 , a first fiber coupler 10 and a second mirror 11 arranged in sequence. A focusing objective lens 25 and a second fiber coupler 24 are sequentially arranged between the beam splitter 8 and the spectrometer 23 .
所述的水浸式高速扫描振镜16、规则直角三角棱镜14、不规则直角三角棱镜13和超声探头20都沉浸于水槽19中。The water-immersed high-speed scanning galvanometer 16 , the regular right-angle triangular prism 14 , the irregular right-angle triangular prism 13 and the ultrasonic probe 20 are all immersed in the water tank 19 .
所述的激光光源1发出的光束最大脉冲能量大于20μJ,重复频率大于5KHz,脉冲宽度小于10ns,可提供波长为500~980nm宽谱波段。超声探头20的中心频率大于30MHz,-6dB带宽大于50%,灵敏度大于-220dB,延迟线为4.25μs。规则直角三角棱镜14和不规则直角三角棱镜13的直角都边大于15mm,斜边都大于21.2mm。声聚焦凹槽17的直径为9mm,曲率半径大于7.07mm,中心深度大于2.2mm。水浸式高速扫描振镜16的工作频率快轴大于25KHz,慢轴大于2KHz,其镜面直径大于1mm,振动周期大于10-11s,可获得80°的光学扫角。The maximum pulse energy of the beam emitted by the laser light source 1 is greater than 20μJ, the repetition frequency is greater than 5KHz, the pulse width is less than 10ns, and it can provide a wide spectrum band with a wavelength of 500-980nm. The center frequency of the ultrasonic probe 20 is greater than 30MHz, the -6dB bandwidth is greater than 50%, the sensitivity is greater than -220dB, and the delay line is 4.25μs. Both the right angles of the regular right-angled triangular prism 14 and the irregular right-angled triangular prism 13 are greater than 15 mm, and the hypotenuses are greater than 21.2 mm. The diameter of the acoustic focusing groove 17 is 9mm, the radius of curvature is greater than 7.07mm, and the center depth is greater than 2.2mm. The working frequency of the water-immersed high-speed scanning galvanometer 16 has a fast axis greater than 25KHz and a slow axis greater than 2KHz. Its mirror diameter is greater than 1mm, and its vibration period is greater than 10 -11 s. It can obtain an optical sweep angle of 80°.
所述的超声探头20收集的超声信号经信号放大器21传输到控制采集电脑22,光谱仪23采集的干涉信号也传输到控制采集电脑22,在控制采集电脑22中重建二维和三维双模态显微结构功能图像。The ultrasonic signal collected by the ultrasonic probe 20 is transmitted to the control acquisition computer 22 through the signal amplifier 21, and the interference signal collected by the spectrometer 23 is also transmitted to the control acquisition computer 22, and the two-dimensional and three-dimensional dual-mode display is reconstructed in the control acquisition computer 22. Microstructure-function image.
如图2所示,本装置可实现快速的活体浅表层疾病微血管新生成像,成像比普通装置成像更为清晰,大大推信进了该技术在预临床转化应用进程。水作为声信号传输介质在光声系统都存在,故本设计中声信号理论上只经石英玻璃与铝膜二次界面传输即到探头界面,根据声信号入射和折射角,铝膜和石英玻璃的声阻抗,声波在此设计中的透射率为97.5%,经过二次后传输后仍可获得95%的探测效率,灵敏度提高了约12.3%。As shown in Figure 2, this device can realize rapid microvascular imaging of superficial diseases in vivo, and the imaging is clearer than that of ordinary devices, which greatly promotes the application process of this technology in pre-clinical transformation. Water as the acoustic signal transmission medium exists in the photoacoustic system, so in this design, the acoustic signal theoretically only transmits through the secondary interface between the quartz glass and the aluminum film to the probe interface. According to the incident and refraction angles of the acoustic signal, the aluminum film and the quartz glass Acoustic impedance, the transmittance of the sound wave in this design is 97.5%, after the second transmission, the detection efficiency of 95% can still be obtained, and the sensitivity is increased by about 12.3%.
与现有技术相比,本装置系统结构简化,增加系统稳定性,同时降低系统的成本,对于系统的产品化和用户的使用操作都十分有利,有效的降低了声波透射过程中的衰减,系统更加集成化,光与声达到了共轴同心的目的,大大提高了系统的探测的信噪比和灵敏度,且将光与声的传输、扫描与传输集成在一个系统内。Compared with the existing technology, the system structure of this device is simplified, the system stability is increased, and the cost of the system is reduced at the same time, which is very beneficial to the productization of the system and the user's use and operation, and effectively reduces the attenuation in the process of sound wave transmission. More integrated, the light and sound achieve the purpose of coaxial concentricity, which greatly improves the signal-to-noise ratio and sensitivity of the system's detection, and integrates the transmission, scanning and transmission of light and sound in one system.
上述具体实施可由本领域技术人员在不背离本装置原理和宗旨的前提下以不同的方式对其进行局部调整,本装置的保护范围以权利要求书为准且不由上述具体实施所限,在其范围内的各个实现方案均受本装置之约束。The above specific implementation can be locally adjusted in different ways by those skilled in the art without departing from the principle and purpose of the device. The protection scope of the device is subject to the claims and is not limited by the above specific implementation. Each implementation within the scope is bound by this device.
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