CN103389273A - Photo-acoustic and optical integrated multi-mode imaging system - Google Patents
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Abstract
Description
技术领域technical field
本发明属于生物医学成像技术领域，尤其涉及一种光声和光学融合的多模态成像系统。The invention belongs to the technical field of biomedical imaging, in particular to a multi-mode imaging system combining photoacoustics and optics.
背景技术Background technique
得益于光学分子探针和成像手段的不断进步，光学分子影像技术在过去十多年中获得了飞速的发展，并因其高灵敏度、高特异性、无电离辐射、成本低廉等特点受到了越来越多的关注。光学分子探针技术使得高特异性的区分正常组织和感兴趣组织(如肿瘤、血管等)成为可能。如何高灵敏度的检测分子探针在生物内的分布情况进而反应生物体生理、病理信息是影像学研究的一个重要问题。由于生物组织对光子具有很强的吸收和散射作用，导致光学成像的深度有限，光学三维重建的空间分辨率比较低。如何进一步提高光学成像的成像深度和三维重建的精度，是光学分子影像亟待解决的问题。为此，光子与物质之间相互作用的两种物理效应——荧光效应和光声效应——被充分挖掘以使得人们能够“看到”和“听到”光与生物组织、分子探针之间的相互作用。荧光效应是指当高能量短波长光子射入某些物质时，物质中的电子吸收能量，从基态跃迁至高能级；由于电子处在高能级时不稳定，就会从高能级跃迁至低能级，从而释放出能量，发出波长较长的荧光光子。与荧光效应中物质以光子辐射的形式释放所吸收的能量不同，在光声效应中，光子照射到物质上的能量，被转化成热能，进而转化为机械振动，以超声波的形式释放吸收的能量。借助荧光效应和光声效应，分别发展起来荧光成像和光声成像这两种广受关注的成像模态。Thanks to the continuous progress of optical molecular probes and imaging methods, optical molecular imaging technology has achieved rapid development in the past ten years, and has been widely recognized for its high sensitivity, high specificity, no ionizing radiation, and low cost. More and more attention. Optical molecular probe technology makes it possible to distinguish normal tissues from interested tissues (such as tumors, blood vessels, etc.) with high specificity. How to detect the distribution of molecular probes in organisms with high sensitivity and reflect the physiological and pathological information of organisms is an important issue in imaging research. Due to the strong absorption and scattering of photons by biological tissues, the depth of optical imaging is limited, and the spatial resolution of optical 3D reconstruction is relatively low. How to further improve the imaging depth of optical imaging and the accuracy of 3D reconstruction is an urgent problem to be solved in optical molecular imaging. To this end, two physical effects of the interaction between photons and matter—the fluorescence effect and the photoacoustic effect—are fully exploited to enable people to "see" and "hear" the interaction between light and biological tissues and molecular probes. Interaction. The fluorescence effect means that when high-energy short-wavelength photons are injected into certain substances, the electrons in the substance absorb energy and transition from the ground state to a high-energy level; because the electrons are unstable when they are at a high-energy level, they will transition from a high-energy level to a low-energy level , thereby releasing energy and emitting fluorescent photons with longer wavelengths. Unlike the fluorescence effect in which the substance releases the absorbed energy in the form of photon radiation, in the photoacoustic effect, the energy of photons irradiated on the substance is converted into thermal energy, which is then converted into mechanical vibration, and the absorbed energy is released in the form of ultrasonic waves. . With the help of fluorescence effect and photoacoustic effect, two imaging modalities, fluorescence imaging and photoacoustic imaging, have been developed respectively.
荧光成像技术在分子影像的发展中占有重要的地位。荧光分子断层成像(fluorescence molecular imaging,FMT)，又被称为荧光扩散光学断层成像(fluorescence diffuse optical tomography,FDOT)，可以实现荧光信号的三维重建。由于荧光光子在生物体内的高散射特性，导致荧光成像的空间分辨率比较低，三维重建也具有很强的病态性。为此，很多研究人员引入其他成像模态来弥补荧光成像技术的不足。将X光CT成像与FMT成像技术融合，可以利用CT成像技术提供的高分辨率生物体解剖结构作为先验信息提高荧光信号的三维重建质量。但是CT成像虽然可以提供高分辨率的结构信息，CT成像时不可避免的存在电离辐射，而且CT成像对软组织的分辨率相对比较低。除了CT成像，磁共振成像(Magnetic ResonanceImaging,MRI)也可用于为光学三维成像提供解剖结构信息。MRI成像不仅可以提供高对比度的软组织分辨率，同时还可以提供生物体的功能代谢信息。但是将光学成像技术和MRI成像相结合，需要产生超高场强的磁场，这导致成像设备的体积比较大，设备成本比较高，从而限制了这种多模态融合方式的发展。需要指出的是，虽然CT和MRI都能提供生物体的解剖结构信息，但是它们都无法直接提供生物体的光学参数信息(生物组织的吸收系数和散射系数)。如何利用其它成像模态获取生物组织的光学特异性信息，从而提高荧光三维断层成像效果是一个值得研究的问题。Fluorescence imaging plays an important role in the development of molecular imaging. Fluorescence molecular tomography (FMT), also known as fluorescence diffuse optical tomography (FDOT), can realize three-dimensional reconstruction of fluorescence signals. Due to the high scattering characteristics of fluorescent photons in living organisms, the spatial resolution of fluorescence imaging is relatively low, and 3D reconstruction is also highly pathological. For this reason, many researchers have introduced other imaging modalities to make up for the shortcomings of fluorescence imaging techniques. The fusion of X-ray CT imaging and FMT imaging technology can use the high-resolution biological anatomical structure provided by CT imaging technology as prior information to improve the quality of three-dimensional reconstruction of fluorescence signals. However, although CT imaging can provide high-resolution structural information, ionizing radiation is unavoidable during CT imaging, and the resolution of CT imaging for soft tissues is relatively low. In addition to CT imaging, magnetic resonance imaging (Magnetic Resonance Imaging, MRI) can also be used to provide anatomical structure information for optical three-dimensional imaging. MRI imaging can not only provide high-contrast soft tissue resolution, but also provide functional and metabolic information of organisms. However, the combination of optical imaging technology and MRI imaging needs to generate a magnetic field with ultra-high field strength, which leads to a relatively large volume of imaging equipment and relatively high equipment cost, which limits the development of this multi-modal fusion method. It should be pointed out that although both CT and MRI can provide the anatomical structure information of the organism, they cannot directly provide the optical parameter information of the organism (absorption coefficient and scattering coefficient of biological tissue). How to use other imaging modalities to obtain the optical specific information of biological tissues, so as to improve the effect of fluorescence three-dimensional tomography is a problem worth studying.
与荧光成像不同，在光声成像中，成像系统检测的是光声效应产生的超声波，通过重建光声效应的初始声压场从而反映出生物组织的光学吸收特性。由于超声波在生物组织传播的散射系数比光子的散射系数小三个数量级左右，因此，可以有效避免荧光成像中荧光光子在生物组织中的散射带来的各种问题。此外，由于超声波的波长比较小，因此可获得高空间分辨率的生物组织结构信息。光声成像结合了光学成像的高对比度特性和超声成像的高空间分辨率特性。将光声成像与荧光成像相结合，可以利用光声成像为荧光三维断层成像提供组织光学特异性信息，从而有效提高荧光三维重建的成像效果。由于声波在生物组织的传播衰减远小于光信号，所以光声成像具有更深的成像深度。结合多光谱光声成像技术，或者采用弧形超声换能器阵列，可以实现小动物全身光声断层成像。荧光和光声成像技术的融合为深度组织的光学成像这一难题提供了一种可行的解决办法。Different from fluorescence imaging, in photoacoustic imaging, the imaging system detects the ultrasonic waves generated by the photoacoustic effect, and reconstructs the initial sound pressure field of the photoacoustic effect to reflect the optical absorption characteristics of biological tissues. Since the scattering coefficient of ultrasonic waves propagating in biological tissues is about three orders of magnitude smaller than that of photons, various problems caused by the scattering of fluorescent photons in biological tissues in fluorescence imaging can be effectively avoided. In addition, because the wavelength of ultrasound is relatively small, high spatial resolution biological tissue structure information can be obtained. Photoacoustic imaging combines the high contrast properties of optical imaging with the high spatial resolution properties of ultrasound imaging. Combining photoacoustic imaging with fluorescence imaging, photoacoustic imaging can be used to provide tissue optical specific information for fluorescence three-dimensional tomographic imaging, thereby effectively improving the imaging effect of fluorescence three-dimensional reconstruction. Since the propagation attenuation of sound waves in biological tissues is much smaller than that of optical signals, photoacoustic imaging has a deeper imaging depth. Combined with multi-spectral photoacoustic imaging technology, or using a curved ultrasonic transducer array, whole-body photoacoustic tomography imaging of small animals can be achieved. The fusion of fluorescence and photoacoustic imaging offers a viable solution to the difficult problem of optical imaging of deep tissues.
发明内容Contents of the invention
本发明目的在于克服现有单一光声成像和单一光学成像模态的不足，反映更全面的解剖结构和生理功能信息。The purpose of the present invention is to overcome the shortcomings of the existing single photoacoustic imaging and single optical imaging modality, and reflect more comprehensive anatomical structure and physiological function information.
为达到上述目的，本发明提供了如下技术方案：一种光声和光学融合多模态成像系统，该系统包括：样品承载模块、光声成像模块、光学成像模块和计算机，其中：In order to achieve the above object, the present invention provides the following technical solution: a photoacoustic and optical fusion multi-modal imaging system, the system includes: a sample carrying module, a photoacoustic imaging module, an optical imaging module and a computer, wherein:
所述样品承载模块用于承载待测生物组织；The sample carrying module is used to carry the biological tissue to be tested;
所述光声成像模块和光学成像模块的光路采用“十字交叉”结构，二者共用所述样品承载模块，作为交叉中心；所述光声成像模块用于对所述待测生物组织进行光声成像，所述光学成像模块用于对所述待测生物组织进行光学成像；The optical path of the photoacoustic imaging module and the optical imaging module adopts a "cross" structure, and the two share the sample carrying module as a cross center; the photoacoustic imaging module is used to perform photoacoustic imaging on the biological tissue to be tested Imaging, the optical imaging module is used for optical imaging of the biological tissue to be measured;
所述计算机与所述样品承载模块、光声成像模块、光学成像模块分别连接，以对所述样品承载模块、光声成像模块、光学成像模块的工作时序进行控制，并对所述光声成像模块和光学成像模块发送的图像数据进行处理。。The computer is respectively connected to the sample carrying module, the photoacoustic imaging module, and the optical imaging module to control the working sequence of the sample carrying module, the photoacoustic imaging module, and the optical imaging module, and to control the photoacoustic imaging module. The image data sent by the module and the optical imaging module are processed. .
本发明与现有技术相比具有如下优点：Compared with the prior art, the present invention has the following advantages:
1、本发明提供的一种融合光声和光学多模态成像系统，可以克服单一模态成像信息的不足，提供更全面的组织结构和功能信息。1. The fusion photoacoustic and optical multimodal imaging system provided by the present invention can overcome the deficiency of single modality imaging information and provide more comprehensive tissue structure and function information.
2、本发明提供的成像系统可以通过建模，达到循环互提升的效果，得到更准确的图像。2. The imaging system provided by the present invention can achieve the effect of circulation and mutual improvement through modeling, and obtain more accurate images.
3、本发明提供的成像系统可以进行小动物全身三维成像。3. The imaging system provided by the present invention can perform whole-body three-dimensional imaging of small animals.
附图说明Description of drawings
图1是依照本发明一实施例的光声和光学融合多模态成像系统的总体结构示意图；FIG. 1 is a schematic diagram of the overall structure of a photoacoustic and optical fusion multimodal imaging system according to an embodiment of the present invention;
图2是依照本发明一实施例的光声成像模块的结构示意图；Fig. 2 is a schematic structural diagram of a photoacoustic imaging module according to an embodiment of the present invention;
图3是依照本发明一实施例的荧光成像模块的结构示意图。Fig. 3 is a schematic structural diagram of a fluorescence imaging module according to an embodiment of the present invention.
具体实施方式Detailed ways
为使本发明的目的、技术方案和优点更加清楚明白，以下结合具体实施例，并参照附图，对本发明进一步详细说明。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with specific embodiments and with reference to the accompanying drawings.
图1是依照本发明一实施例的光声和光学融合多模态成像系统的结构示意图，如图1所示，所述光声和光学融合多模态成像系统包括：样品承载模块、光声成像模块、光学成像模块和计算机，其中：Fig. 1 is a schematic structural diagram of a photoacoustic and optical fusion multimodal imaging system according to an embodiment of the present invention. As shown in Fig. 1, the photoacoustic and optical fusion multimodal imaging system includes: a sample carrying module, a photoacoustic An imaging module, an optical imaging module, and a computer, wherein:
所述样品承载模块用于承载待测生物组织；其包括用于固定所述待测生物组织的固定支架、用于提供所述待测生物组织呼吸环境的呼吸罩、用于带动所述样品承载模块的旋转平移台等部件，使得所述样品承载模块可以进行水平旋转和垂直升降运动，并为待测生物组织提供生命维持环境，带动待测生物组织按照一定的程序移动。在对小动物进行在体成像的时候，小动物不自觉的生理运动会对成像质量造成影响，为了避免这种情况的发生，本发明还设计了专用的小动物固定支架，通过对小动物四肢、头部等位置的固定，最大程度地减小小动物生理运动的幅度，使得小动物在成像过程中保持形态不发生变化，以便与后期的信息融合配准。The sample carrying module is used to carry the biological tissue to be tested; it includes a fixed bracket for fixing the biological tissue to be tested, a breathing mask for providing a breathing environment for the biological tissue to be tested, and a breathing mask for driving the sample carrying The components such as the rotating translation platform of the module enable the sample carrying module to perform horizontal rotation and vertical lifting movement, and provide a life-supporting environment for the biological tissue to be tested, and drive the biological tissue to be tested to move according to a certain program. When performing in vivo imaging on small animals, the unconscious physiological movements of the small animals will affect the imaging quality. In order to avoid this situation, the invention also designs a special small animal fixing bracket. The fixed position of the head minimizes the amplitude of the physiological movement of the small animal, so that the shape of the small animal remains unchanged during the imaging process, so that it can be fused and registered with the later information.
所述光声成像模块和光学成像模块的光路采用“十字交叉”结构，二者共用所述样品承载模块，作为交叉中心；所述光声成像模块用于对所述待测生物组织进行光声成像，所述光学成像模块用于对所述待测生物组织进行光学成像。The optical path of the photoacoustic imaging module and the optical imaging module adopts a "cross" structure, and the two share the sample carrying module as a cross center; the photoacoustic imaging module is used to perform photoacoustic imaging on the biological tissue to be tested Imaging, the optical imaging module is used for optical imaging of the biological tissue to be measured.
所述计算机与所述样品承载模块、光声成像模块、光学成像模块分别连接，以对所述样品承载模块、光声成像模块、光学成像模块的工作时序进行控制，并对所述光声成像模块和光学成像模块发送的图像数据进行处理，所述处理包括光声和荧光图像的重建，以及重建图像的融合配准。The computer is respectively connected to the sample carrying module, the photoacoustic imaging module, and the optical imaging module to control the working sequence of the sample carrying module, the photoacoustic imaging module, and the optical imaging module, and to control the photoacoustic imaging module. The image data sent by the module and the optical imaging module are processed, and the processing includes the reconstruction of photoacoustic and fluorescence images, and the fusion registration of the reconstructed images.
图2是依照本发明一实施例的光声成像模块的结构示意图，如图2所示，所述光声成像模块包括：脉冲激光器、可调谐脉冲激光器、光学装置、超声换能器、数据采集器、机械框架，其中：Fig. 2 is a schematic structural diagram of a photoacoustic imaging module according to an embodiment of the present invention. As shown in Fig. 2, the photoacoustic imaging module includes: a pulsed laser, a tunable pulsed laser, an optical device, an ultrasonic transducer, and a data acquisition Devices, mechanical frames, of which:
所述脉冲激光器用于为后级可调谐脉冲激光器提供泵浦源，在光声成像中，通常使用调Q的掺钕钇铝石榴石激光器(Q-switch Nd:YAG laser)来提供激发源激光脉冲，它是一种纳秒级固体激光器，单脉冲能量可达几百毫焦；The pulsed laser is used to provide a pumping source for the subsequent tunable pulsed laser. In photoacoustic imaging, a Q-switched neodymium-doped yttrium aluminum garnet laser (Q-switch Nd:YAG laser) is usually used to provide the excitation source laser. Pulse, which is a nanosecond-level solid-state laser, with a single pulse energy of up to several hundred millijoules;
所述可调谐脉冲激光器受前级脉冲激光器的驱动，提供波长和能量均可调的脉冲激光输出，以用于多光谱光声成像，在本发明一实施例中，所述波长可调的脉冲激光的可调谐波段为680nm～960nm；The tunable pulse laser is driven by the preceding pulse laser to provide a pulse laser output with adjustable wavelength and energy for multi-spectral photoacoustic imaging. In an embodiment of the present invention, the wavelength-tunable pulse The tunable band of laser is 680nm～960nm;
所述光学装置位于所述可调谐脉冲激光器的后级，其采用两束多模光纤，在耦合了所述可调谐脉冲激光器的脉冲激光输出后，从两个相对的方向照射到放置在样品承载模块上的待测生物组织，以增加成像的深度；The optical device is located at the rear stage of the tunable pulse laser, and it uses two bundles of multimode optical fibers. After coupling the pulse laser output of the tunable pulse laser, it irradiates from two opposite directions to the sample carrier. The biological tissue to be tested on the module to increase the imaging depth;
所述超声换能器位于所述样品承载模块的后方，借助旋转平移台的带动对于所述待测生物组织进行扫描，以实现待测生物组织的三维成像，并在光声成像中将接收到的光声信号转换为电信号。成像深度、信噪比和图像分辨率都是选择超声换能器时需要考虑的问题，超声换能器的一些重要参数包括：灵敏度、中心频率、带宽、探头尺寸、阵元数和形状等。在本发明一实施例中，可以采用128阵元的凹弧形超声换能器，中心频率为5MHz；The ultrasonic transducer is located behind the sample carrying module, and scans the biological tissue to be measured with the help of a rotating translation platform to realize three-dimensional imaging of the biological tissue to be measured, and in photoacoustic imaging, the received The photoacoustic signal is converted into an electrical signal. Imaging depth, signal-to-noise ratio, and image resolution are issues that need to be considered when selecting an ultrasonic transducer. Some important parameters of an ultrasonic transducer include: sensitivity, center frequency, bandwidth, probe size, number of array elements, and shape. In an embodiment of the present invention, a concave arc ultrasonic transducer with 128 array elements can be used, and the center frequency is 5MHz;
所述数据采集器位于所述光声成像模块的末级，其用于将所述超声换能器转换得到的微弱电信号进行放大和量化，并将放大和量化后的电信号数据传输到计算机进行后续的数据处理；在本发明一实施例中，所述数据采集器的采样率为40Msps，量化位数为12位；The data collector is located at the final stage of the photoacoustic imaging module, which is used to amplify and quantify the weak electrical signal converted by the ultrasonic transducer, and transmit the amplified and quantized electrical signal data to the computer Carry out subsequent data processing; In an embodiment of the present invention, the sampling rate of the data collector is 40Msps, and the number of quantization bits is 12;
所述机械框架包括用于盛放耦合液的水箱、用于固定所述超声换能器的连接杆等装置。The mechanical frame includes a water tank for holding coupling fluid, a connecting rod for fixing the ultrasonic transducer and other devices.
图3是依照本发明一实施例的光学成像模块的结构示意图，如图3所示，所述光学成像模块包括：连续波激光器、分光器、聚焦透镜、窄带滤波片和低温制冷CCD相机，其中：Fig. 3 is a schematic structural view of an optical imaging module according to an embodiment of the present invention. As shown in Fig. 3, the optical imaging module includes: a continuous wave laser, a beam splitter, a focusing lens, a narrow-band filter and a cryogenic refrigeration CCD camera, wherein :
所述连续波激光器发射固定波长的连续激光，用于对放置在所述样品承载模块上的待测生物组织内部的荧光物质进行激发；由于每一种荧光物质都有自己的激发光谱和发射光谱，为了能够更加有效地产生激发荧光，通常选择波长在荧光物质激发光谱峰值波长附近的激光器作为激发光源，因此，为了能够进行不同荧光物质的激发实验，往往需要多种波长的连续波激光器；The continuous wave laser emits continuous laser light with a fixed wavelength, which is used to excite the fluorescent substances placed on the sample carrying module inside the biological tissue to be measured; since each fluorescent substance has its own excitation spectrum and emission spectrum , in order to generate excited fluorescence more effectively, a laser with a wavelength near the peak wavelength of the excitation spectrum of the fluorescent substance is usually selected as the excitation light source. Therefore, in order to be able to perform excitation experiments of different fluorescent substances, continuous wave lasers with multiple wavelengths are often required;
分光器位于所述连续波激光器的后级，用于将所述连续波激光器的单束光分为两束，一束照射到后级的聚焦透镜上，另一束通过光纤耦合照射到待测生物组织上。The beam splitter is located at the subsequent stage of the continuous wave laser, and is used to divide the single beam of the continuous wave laser into two beams, one beam is irradiated on the focusing lens of the subsequent stage, and the other beam is irradiated to the test device through optical fiber coupling. on biological tissue.
在现有的FMT重建算法中，都将激发光源看作是皮下一个传输自由程位置的各向同性的点光源，为了能够达到这样的效果，需要将入射到待测生物组织上的激发光聚焦到一个尽量小的点上，而位于所述分光器后级的所述聚焦透镜的作用就是将所述连续波激光器发出的连续激光聚焦在放置在样品承载模块上的待测生物组织上的一个点上；In the existing FMT reconstruction algorithms, the excitation light source is regarded as an isotropic point light source at a subcutaneous transmission free path position. In order to achieve such an effect, it is necessary to focus the excitation light incident on the biological tissue to be measured. to a point as small as possible, and the function of the focusing lens located at the rear stage of the beam splitter is to focus the continuous laser light emitted by the continuous wave laser on one of the biological tissues to be measured placed on the sample carrying module. Point;
所述窄带滤波片位于低温制冷CCD相机镜头的前面，用于过滤所述连续波激光器输出的激发光以及环境中杂散光。The narrow-band filter is located in front of the lens of the cryogenic cooling CCD camera, and is used to filter the excitation light output by the continuous wave laser and stray light in the environment.
所述低温制冷CCD相机位于所述光学成像模块的末级，其用于对待测生物组织被激发的荧光进行信号采集；激发荧光通常是比较微弱的，需要使用低温制冷的CCD相机来进行信号采集，比如可以采用液氮制冷的CCD相机或半导体制冷的CCD相机。The low-temperature cooling CCD camera is located at the final stage of the optical imaging module, and it is used for signal collection of the excited fluorescence of the biological tissue to be tested; the excited fluorescence is usually relatively weak, and a low-temperature cooling CCD camera is required for signal collection , such as a liquid nitrogen cooled CCD camera or a semiconductor cooled CCD camera.
所述系统成像时，先在水箱中利用所述光声成像模块进行光声成像，然后将待成像生物组织提升到水上，利用所述光学成像模块进行荧光成像，然后将光声成像数据和荧光成像数据传输到计算机，对二者的图像进行配准，将相同位置的信息叠加显示。When the system is imaging, first use the photoacoustic imaging module to perform photoacoustic imaging in the water tank, then lift the biological tissue to be imaged above the water, use the optical imaging module to perform fluorescence imaging, and then convert the photoacoustic imaging data and fluorescence The imaging data is transmitted to the computer, the images of the two are registered, and the information of the same position is superimposed and displayed.
以上所述的具体实施例，对本发明的目的、技术方案和有益效果进行了进一步详细说明，所应理解的是，以上所述仅为本发明的具体实施例而已，并不用于限制本发明，凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The specific embodiments described above have further described the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.
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