微波热致超声波扫描成像系统关键技术研究
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摘要
大量医学统计数据表明各种癌症发生率和死亡率均在逐年增加，然而癌症从确诊到治疗的各种技术发展却并不乐观。一种得到共识的观点是肿瘤或癌的早期发现对治疗效果将存在显著的影响，本文所关注的乳腺肿瘤(癌)的检测也具有这一特点。
微波热致超声波扫描成像(Microwave-Induced Thermo-Acoustic Tomography，MITAT)技术是一种新兴的检测技术，它使用微波脉冲激励组织，组织将吸收的微波能转化为热能，然后生物组织受热不均匀而产生可检测的超声波信号。特别是恶性肿瘤，其介电常数和电导率均远高于周围正常组织，因此，它们可以产生高幅度的微波热致超声波(Microwave-Induced Thermo-Acoustic，MITA)信号。由于微波热致超声扫描成像技术应用微波激励、超声成像，可产生高分辨率和高对比度的成像结果，使它成为一种非常有潜力的生物医学成像技术。
然而，微波热致超声波扫描成像系统也存在许多难点。首先，微波热致超声波涉及多物理场过程，它包括电磁波在非均匀介质中的传播过程、电磁能转换为热能过程、热致膨胀产生机械波(超声波)过程。基于动力学和热扩散、传导方程的微波热致超声波机制解析解的分析，将上述三类物理场有机地结合在了一起，与基于热平衡的状态解析分析相比，这一方法更少地对三物理场所涉及的参数进行近似，能更准确地反映微波热致超声波机制。其次，激励所用的高功率微波脉冲会产生很宽频带的强电磁干扰，这对于微弱的微波热致超声波的检测形成巨大的挑战。如何在减小激励微波功率的前提下，尽量提高热致超声波的信噪比是这一系统的成败关键。为了达到激励微波功率与信噪比的更优化，在对系统的电磁噪声来源进行了研究的基础上，新的具有高电磁兼容能力的超声波检测探头被设计和应用到微波热致超声波扫描系统中。从信号处理的角度，基于小波分析的噪声抑制技术也被应用到对测量的微波热致超声波信号进行处理。另外，为获得辐射微波能在生物组织中尽量均匀的分布和辐射效能，对现有的矩形波导辐射器的优化通过设计低驻波比的圆喇叭天线进行了仿真讨论。最后，非均匀介质(生物组织)中的目标成像也是微波热致超声波扫描成像系统的重点和难点。由于生物组织的非均匀性和成像目标处于微波和超声波的近场，波的衍射和散射不可忽略，一些成像算法，如后向投影算法等无法克服这些因素所产生的多径效应，成像分辨率和对比度均会受到影响；而基于伪谱时域方法(Pseudo-Spectral Time Domain，PSTD)的时间反转镜像(Time Reversal Mirror，TRM)技术在微波热致超声波扫描成像系统中的应用，能充分地利用目标信号通过生物组织的非均匀性带来的多径信息，对目标形成准确的聚集成像。另外，伪谱时域方法作为时间反转镜像技术的计算核的应用可以方便地实现时间反转镜像技术所需的系统格林函数和大尺度生物器官如乳房的快速计算。
本文的研究内容主要包括微波热致超声成像软、硬件系统中的一些关键技术，主要内容概括如下：
1．在讨论了生物组织的微波吸收特点的基础上，基于动力学和热扩散、传导定理推导了生物组织的微波热致超声理论，得到微波能在生物组织中的吸收分布与微波热致超声波源分布等效的结论。
2．从系统的角度讨论了微波热致超声波扫描成像系统的各部分构成，深入讨论了激励微波脉冲源的设计准则、检测子系统的技术细节及电磁兼容考虑。搭建的实验原型机，微波脉冲源中心频率2．45 GHz，脉冲宽度0．5-2．0μs，峰值功率0．8-40kW。
3．对实验数据所反映的超声信号时频域特征进行了研究。对时域微波热致超声波信号的时延误差随样品探头距离增加而减小的现象，通过考虑实际样品的截面积尺寸和样品上不同位置的热声源的叠加过程进行了研究，并对相应的修正方法进行了讨论；由激励源、样品几何尺寸、超声波传感器响应的级联在频域上的关系，讨论了生物组织的几何尺度信息如何在测量信号中通过微波热致超声信号频谱分布反映出来的，同时也揭示了微波热致超声波信号的频率范围特征。
4．研究了基于小波分析的噪声抑制方法在微波热致超声波信号中降噪和多分辨率应用。
5．基于所搭建的微波热致超声成像系统所测得的实验数据，研究了相应的重建算法：反投影成像(Back-Projection，BP)算法和基于PSTD的TRM技术，成像分辨率＜3mm，成像对比度＞25dB。
6．在均匀媒质(变压器油或炼猪油)中的简单目标(单纯高含水量生物组织，如猪肌肉)进行了一维线阵和环阵的微波热致超声波成像实验；对复杂目标(具有皮肤、脂肪和肌肉结构)进行了一维线阵微波热致超声波成像实验。
The accident and the mortality ratio of various cancer is increasing continually reported by a lot of medical literatures in every year, while the technical progress of cancriform detection and therapy is unsatisfactory; A commonsense opinion of cancriform field is that the more early diagnose more surviving, this is also the truth in the breast cancer detection and therapy field. Development a detection instrument about the early breast cancer is the aim of this paper.
The microwave-induced thermo-acoustic tomography (MITAT) is an innovative technique for tumor's detection, it employees the modulated microwave pulses to irradiate the biologic tissue, there has thermo-deposition due to the electromagnetic energy absorbed by the tissue. Because the different tissue heating originated the electric difference, the detectable ultrasonic signals are generated by this procedure. Especially the malignant tumor with distinct permittivity and electrical conductivity versus the surrounding normal tissue, microwave-induced thermo-acoustic (MITA) signals can be obtained with very high signal-noise-ratio. For the microwave pulses used as the irradiating signals, while the received signals are ultrasound in microwave-induced thermo-acoustic tomography system, high resolve and contrast images can be got. So it has becoming a promising technology in medical imaging field.
However, microwave-induced thermo-acoustic tomography system has very many difficulties. Firstly, the microwave-induced thermo-acoustic is an interdisciplinary field procedure. It includes the electromagnetic wave propagating in heterogeneous medium, the transform from the electromagnetic energy to the thermo-energy and the mechanical wave (ultrasound) generation due the tissue expanding. The analytic studies of the MITA procedure based on dynamics and the function of thermo-diffuse and thermo-conduction combine these three physic field systematically. Compared with situation function with thermo-balance method, the analytic studies based on dynamics have less parameters approximation, and more precision. Meanwhile, the discipline of the microwave energy absorbed by tissue is should studied also. Secondly, there has severe noise with width spectrum due to the powerful irradiating microwave pulses. This is a big challenge to design and realize the receiver subsystem to detect the weak MITA signals. How to improve the signal-noise-ratio of the received thermo-acoustic signals in terms that the irradiating microwave power should be decrease possibly is the keystone of a successful system. In order to balance the power of the irradiating and the receiver signals with optimal signal-noise-ratio, after the study of the noise sources in the MITAT system, an innovative ultrasonic receiver with perfect electromagnetic compatibly and pre-amplifier subsystem are designed and applied to the MITAT system. On the signal processing opinion, the received thermo-acoustic signals is deal with wavelet technique, the noise depressing and wavelet analyses method are very useful for the MITA signals. Meanwhile, in order to obtain uniform microwave energy distribution in biologic tissue and improve the effectiveness of the radiator, a circle horn antenna with low voltage-stand-wave-ratio is simulative studied to replace current rectangle waveguide radiator. Thirdly, it is also difficulty and focus in MITAT system that the imaging algorithm in terms that the biologic tissue is heterogeneous. Due to the heterogeneous and the targets located in the near field of the irradiating, the diffuseness and the multi-path effects can't be neglected. Otherwise, the resolve and contrast of the images generated by some imaging algorithm, such as back-projection, should be of low quality. The superior images can be got by the imaging algorithm of time reversal mirror technique based on pseudo-spectrum time domain method applied to MITAT system. Because that the all the multi-path information can be utilized by this imaging algorithm, and the targets can be refocused at original position correctly. By the way, the characteristics of the TRM noise depressing and statistic stability in terms that the model's parameters have random distribution are studied also. In additional, for the numerical pseudo-spectrum time domain method is employed as the forward core of the time reversal mirror technique, the Green's function required by the TRM can be realized by the numerical model easily and the larger scale biologic organ can be simulated quickly.
The aim of this paper is focus on the critical hardware and software research of themicrowave-induced thermo-acoustic tomography system, the contents are:
1. After discussing the character of the microwave energy absorbed by biologic tissue,the mechanism of the microwave-induced thermo-acoustic procedure are analyticstudied based on the dynamics and the function of the thermo-diffuses and thermo-conduction. The important conclusion can be draw that there has an equivalent relationship between the microwave energy absorption distribution and the induced thermo-acoustic sources distribution.
2. The subsystems of the microwave-induced thermo-acoustic tomography system are studied systematically. The design criterions of the irradiating microwave pulses, detection subsystem and electromagnetic compatibility are studied. The technical standards of the MITAT prototype system are: center frequency 2.45 GHz, the width of the pulse 0.5 - 2.0 us and the peak value of the pulse 0.8-40 kW.
3. The measured microwave-induced thermo-acoustic signals are studied in temporal-spectral domain. To explain the phenomenon that the thermo-acoustic signals delay error become larger when the distance of the sample and ultrasonic transducer is small in temporal domain, the model includes that the cross-section scale of the sample and the aperture scale of the ultrasonic transducer, and the synthetic ultrasonic pressure wave generated by the thermo-acoustic sources are considered. The amended thickness information error of the sample based on the model and the synthetic pressure theory can remarkably improve. From the signal processing point of view, the MITAT system is cascaded by each subsystems, the irradiating microwave pulses, sample with geometric information, and the response function of the ultrasonic transducer. According to this viewpoint, the spectral characteristic of the MITA signals are studied to explain how the geometric information of the sample to affect the spectral distribution of the measured signals, meanwhile the bandwidth of a very MITAT system can be evaluated by this analyses.
4. The noise depressing and multi-resolution application of the wavelet technique in an MITAT system are studied.
5. The imaging algorithms are studied base on the measured thermo-acoustic signals from the prototype MITAT system: back-projection algorithm and time reversal mirror technique based on the pseudo-spectral time domain method, the resolution of the image less than 3 mm, and the contrast large than 25 dB.
6. Two-dimension images generated by some simple targets (simplex biologic tissue with high water content, such as pork muscle) immerged in a homogenous medium (mineral oil or porcine oil), the linear and circle scan Patten are used.
Two-dimension images generated by complex targets (a biologic tissue with skin, fat and muscle) are studied also.
微波热致超声波扫描成像(Microwave-Induced Thermo-Acoustic Tomography，MITAT)技术是一种新兴的检测技术，它使用微波脉冲激励组织，组织将吸收的微波能转化为热能，然后生物组织受热不均匀而产生可检测的超声波信号。特别是恶性肿瘤，其介电常数和电导率均远高于周围正常组织，因此，它们可以产生高幅度的微波热致超声波(Microwave-Induced Thermo-Acoustic，MITA)信号。由于微波热致超声扫描成像技术应用微波激励、超声成像，可产生高分辨率和高对比度的成像结果，使它成为一种非常有潜力的生物医学成像技术。
然而，微波热致超声波扫描成像系统也存在许多难点。首先，微波热致超声波涉及多物理场过程，它包括电磁波在非均匀介质中的传播过程、电磁能转换为热能过程、热致膨胀产生机械波(超声波)过程。基于动力学和热扩散、传导方程的微波热致超声波机制解析解的分析，将上述三类物理场有机地结合在了一起，与基于热平衡的状态解析分析相比，这一方法更少地对三物理场所涉及的参数进行近似，能更准确地反映微波热致超声波机制。其次，激励所用的高功率微波脉冲会产生很宽频带的强电磁干扰，这对于微弱的微波热致超声波的检测形成巨大的挑战。如何在减小激励微波功率的前提下，尽量提高热致超声波的信噪比是这一系统的成败关键。为了达到激励微波功率与信噪比的更优化，在对系统的电磁噪声来源进行了研究的基础上，新的具有高电磁兼容能力的超声波检测探头被设计和应用到微波热致超声波扫描系统中。从信号处理的角度，基于小波分析的噪声抑制技术也被应用到对测量的微波热致超声波信号进行处理。另外，为获得辐射微波能在生物组织中尽量均匀的分布和辐射效能，对现有的矩形波导辐射器的优化通过设计低驻波比的圆喇叭天线进行了仿真讨论。最后，非均匀介质(生物组织)中的目标成像也是微波热致超声波扫描成像系统的重点和难点。由于生物组织的非均匀性和成像目标处于微波和超声波的近场，波的衍射和散射不可忽略，一些成像算法，如后向投影算法等无法克服这些因素所产生的多径效应，成像分辨率和对比度均会受到影响；而基于伪谱时域方法(Pseudo-Spectral Time Domain，PSTD)的时间反转镜像(Time Reversal Mirror，TRM)技术在微波热致超声波扫描成像系统中的应用，能充分地利用目标信号通过生物组织的非均匀性带来的多径信息，对目标形成准确的聚集成像。另外，伪谱时域方法作为时间反转镜像技术的计算核的应用可以方便地实现时间反转镜像技术所需的系统格林函数和大尺度生物器官如乳房的快速计算。
本文的研究内容主要包括微波热致超声成像软、硬件系统中的一些关键技术，主要内容概括如下：
1．在讨论了生物组织的微波吸收特点的基础上，基于动力学和热扩散、传导定理推导了生物组织的微波热致超声理论，得到微波能在生物组织中的吸收分布与微波热致超声波源分布等效的结论。
2．从系统的角度讨论了微波热致超声波扫描成像系统的各部分构成，深入讨论了激励微波脉冲源的设计准则、检测子系统的技术细节及电磁兼容考虑。搭建的实验原型机，微波脉冲源中心频率2．45 GHz，脉冲宽度0．5-2．0μs，峰值功率0．8-40kW。
3．对实验数据所反映的超声信号时频域特征进行了研究。对时域微波热致超声波信号的时延误差随样品探头距离增加而减小的现象，通过考虑实际样品的截面积尺寸和样品上不同位置的热声源的叠加过程进行了研究，并对相应的修正方法进行了讨论；由激励源、样品几何尺寸、超声波传感器响应的级联在频域上的关系，讨论了生物组织的几何尺度信息如何在测量信号中通过微波热致超声信号频谱分布反映出来的，同时也揭示了微波热致超声波信号的频率范围特征。
4．研究了基于小波分析的噪声抑制方法在微波热致超声波信号中降噪和多分辨率应用。
5．基于所搭建的微波热致超声成像系统所测得的实验数据，研究了相应的重建算法：反投影成像(Back-Projection，BP)算法和基于PSTD的TRM技术，成像分辨率＜3mm，成像对比度＞25dB。
6．在均匀媒质(变压器油或炼猪油)中的简单目标(单纯高含水量生物组织，如猪肌肉)进行了一维线阵和环阵的微波热致超声波成像实验；对复杂目标(具有皮肤、脂肪和肌肉结构)进行了一维线阵微波热致超声波成像实验。
The accident and the mortality ratio of various cancer is increasing continually reported by a lot of medical literatures in every year, while the technical progress of cancriform detection and therapy is unsatisfactory; A commonsense opinion of cancriform field is that the more early diagnose more surviving, this is also the truth in the breast cancer detection and therapy field. Development a detection instrument about the early breast cancer is the aim of this paper.
The microwave-induced thermo-acoustic tomography (MITAT) is an innovative technique for tumor's detection, it employees the modulated microwave pulses to irradiate the biologic tissue, there has thermo-deposition due to the electromagnetic energy absorbed by the tissue. Because the different tissue heating originated the electric difference, the detectable ultrasonic signals are generated by this procedure. Especially the malignant tumor with distinct permittivity and electrical conductivity versus the surrounding normal tissue, microwave-induced thermo-acoustic (MITA) signals can be obtained with very high signal-noise-ratio. For the microwave pulses used as the irradiating signals, while the received signals are ultrasound in microwave-induced thermo-acoustic tomography system, high resolve and contrast images can be got. So it has becoming a promising technology in medical imaging field.
However, microwave-induced thermo-acoustic tomography system has very many difficulties. Firstly, the microwave-induced thermo-acoustic is an interdisciplinary field procedure. It includes the electromagnetic wave propagating in heterogeneous medium, the transform from the electromagnetic energy to the thermo-energy and the mechanical wave (ultrasound) generation due the tissue expanding. The analytic studies of the MITA procedure based on dynamics and the function of thermo-diffuse and thermo-conduction combine these three physic field systematically. Compared with situation function with thermo-balance method, the analytic studies based on dynamics have less parameters approximation, and more precision. Meanwhile, the discipline of the microwave energy absorbed by tissue is should studied also. Secondly, there has severe noise with width spectrum due to the powerful irradiating microwave pulses. This is a big challenge to design and realize the receiver subsystem to detect the weak MITA signals. How to improve the signal-noise-ratio of the received thermo-acoustic signals in terms that the irradiating microwave power should be decrease possibly is the keystone of a successful system. In order to balance the power of the irradiating and the receiver signals with optimal signal-noise-ratio, after the study of the noise sources in the MITAT system, an innovative ultrasonic receiver with perfect electromagnetic compatibly and pre-amplifier subsystem are designed and applied to the MITAT system. On the signal processing opinion, the received thermo-acoustic signals is deal with wavelet technique, the noise depressing and wavelet analyses method are very useful for the MITA signals. Meanwhile, in order to obtain uniform microwave energy distribution in biologic tissue and improve the effectiveness of the radiator, a circle horn antenna with low voltage-stand-wave-ratio is simulative studied to replace current rectangle waveguide radiator. Thirdly, it is also difficulty and focus in MITAT system that the imaging algorithm in terms that the biologic tissue is heterogeneous. Due to the heterogeneous and the targets located in the near field of the irradiating, the diffuseness and the multi-path effects can't be neglected. Otherwise, the resolve and contrast of the images generated by some imaging algorithm, such as back-projection, should be of low quality. The superior images can be got by the imaging algorithm of time reversal mirror technique based on pseudo-spectrum time domain method applied to MITAT system. Because that the all the multi-path information can be utilized by this imaging algorithm, and the targets can be refocused at original position correctly. By the way, the characteristics of the TRM noise depressing and statistic stability in terms that the model's parameters have random distribution are studied also. In additional, for the numerical pseudo-spectrum time domain method is employed as the forward core of the time reversal mirror technique, the Green's function required by the TRM can be realized by the numerical model easily and the larger scale biologic organ can be simulated quickly.
The aim of this paper is focus on the critical hardware and software research of themicrowave-induced thermo-acoustic tomography system, the contents are:
1. After discussing the character of the microwave energy absorbed by biologic tissue,the mechanism of the microwave-induced thermo-acoustic procedure are analyticstudied based on the dynamics and the function of the thermo-diffuses and thermo-conduction. The important conclusion can be draw that there has an equivalent relationship between the microwave energy absorption distribution and the induced thermo-acoustic sources distribution.
2. The subsystems of the microwave-induced thermo-acoustic tomography system are studied systematically. The design criterions of the irradiating microwave pulses, detection subsystem and electromagnetic compatibility are studied. The technical standards of the MITAT prototype system are: center frequency 2.45 GHz, the width of the pulse 0.5 - 2.0 us and the peak value of the pulse 0.8-40 kW.
3. The measured microwave-induced thermo-acoustic signals are studied in temporal-spectral domain. To explain the phenomenon that the thermo-acoustic signals delay error become larger when the distance of the sample and ultrasonic transducer is small in temporal domain, the model includes that the cross-section scale of the sample and the aperture scale of the ultrasonic transducer, and the synthetic ultrasonic pressure wave generated by the thermo-acoustic sources are considered. The amended thickness information error of the sample based on the model and the synthetic pressure theory can remarkably improve. From the signal processing point of view, the MITAT system is cascaded by each subsystems, the irradiating microwave pulses, sample with geometric information, and the response function of the ultrasonic transducer. According to this viewpoint, the spectral characteristic of the MITA signals are studied to explain how the geometric information of the sample to affect the spectral distribution of the measured signals, meanwhile the bandwidth of a very MITAT system can be evaluated by this analyses.
4. The noise depressing and multi-resolution application of the wavelet technique in an MITAT system are studied.
5. The imaging algorithms are studied base on the measured thermo-acoustic signals from the prototype MITAT system: back-projection algorithm and time reversal mirror technique based on the pseudo-spectral time domain method, the resolution of the image less than 3 mm, and the contrast large than 25 dB.
6. Two-dimension images generated by some simple targets (simplex biologic tissue with high water content, such as pork muscle) immerged in a homogenous medium (mineral oil or porcine oil), the linear and circle scan Patten are used.
Two-dimension images generated by complex targets (a biologic tissue with skin, fat and muscle) are studied also.
引文
[1]Surveillance,Epidemiology and End Results(SEER) Program,SEER 9 Registries,Division of Cancer Control and Population Science,National Cancer Institute,US,2007:1973-2004
[2]Ahmedin Jemal,Andrea Thomas.Taylor Murray,and Michael Thun,Cancer Statistics 2002.CA Cancer J Clin,Jan 2002,52:23-47
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