近红外无创生化分析中快速高信噪比光谱信号检测技术研究
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摘要
血液中生化成分的含量直接反映了人体的健康状况。目前，临床上常规的检验方法多属于有创或微创，不仅存在交叉感染的隐患，而且需要试剂进行离体分析，很难实现在线实时监测。因此，无创生化检验一直是国内外学者研究的热点之一。近红外光谱分析技术具有无创伤、无试剂、无污染、可实时监测等优点，在无创生化分析领域具有很高的研究价值和广阔的前景。但是由于血液中生化成分的含量较低，且组织背景干扰严重，使得近红外无创生化分析技术至今尚未达到临床应用的水平。
为了消除人体复杂的组织背景干扰，本课题组提出血流容积光谱相减法。利用短时间内不同血流容积下测得的光谱相减，从而得到血液光谱。但是光谱相减法的实现对容积脉搏波信号的采集速度和信噪比要求很高，而现今市面上近红外光谱仪器的性能指标尚未达到要求，因此需要研究快速高信噪比的容积脉搏波采集方法，进而提高仪器的性能。
本文围绕近红外无创生化分析中快速高信噪比光谱信号的采集方法展开研究。主要包括快速高信噪比容积脉搏波信号采集系统的设计和容积脉搏波信号降噪处理的研究。具体研究内容和主要结论如下：
1)针对近红外无创生化采集系统中快速、高信噪比的要求，不同工作方式的InGaAs探测器各有特点。分别针对单元式、多元阵列式和多元分立式铟镓砷探测器设计近红外容积脉搏波采集系统。每套系统包括前置放大电路和数据采集电路两部分。
2)通过对三套近红外容积脉搏波采集系统性能的测试，分析各自的优缺点，研制出符合人体无创生化检测要求的系统。实验测得，单元式容积脉搏波采集系统的信噪比约为28000：1，暗噪声为20左右。虽然单元式采集系统具有较高的信噪比，但只能通过扫描的方式获得光谱，不仅限制了采集速度，而且由于血液的流动性，也很难保证所采集光谱的准确性。多元阵列式容积脉搏波采集系统采用256元铟镓砷探测器G9211，可同时采集256个波长的信号，采集速度快，但实测信噪比平均为7000：1，不能满足无创生化分析的要求。多元分立式容积脉搏波采集系统采用16元铟镓砷探测器G7150，可同时采集16个波长的信号，每秒钟最多采集50幅光谱，信噪比达到13000：1，暗噪声为40左右。综合考虑，16元分立式容积脉搏波采集系统最接近人体无创生化检测的要求。
3)利用16元分立式容积脉搏波采集电路搭建的近红外无创生化检测系统完成临床实验。通过采集不同年龄、不同性别的81名志愿者食指指端容积脉搏波信号，建立定标模型，预测血液中红细胞比容和血红蛋白浓度，预测相关系数分别为0.81和0.73，预测标准差分别为1.82%和14.53g·L-1。
4)深入研究容积脉搏波信号降噪处理的现状，提出一种基于自适应滤波的脉搏波信号降噪处理方法。利用该方法处理临床采集的容积脉搏波信号，结果表明，采用处理后的信号重新建立定标模型，红细胞比容和血红蛋白的预测相关系数分别提升至0.87和0.83，预测标准差分别提升至1.89%和9.16g·L-1。
本文深入研究了近红外无创生化分析中快速高信噪比信号的检测技术，并成功研制出一套快速高信噪比的近红外容积脉搏波采集系统，为实现近红外无创生化检测技术的临床应用奠定了理论和实验基础。
The blood biochemical composition directly reflects the health condition of body.Currently, routine clinical testing methods are almost invasive or minimally invasive.Not only existing the hidden dangers of cross-infection, but also needing reagents forin vitro analysis that is difficult to realize online monitoring. So non-invasivebiochemical monitoring has been one of the hotspots by domestic and foreign scholars.Near-infrared absorption spectroscopy (NIRS) technique is invasive, reagent-free, nopollution and has online monitoring, which has a high research value and broadprospects in the field of non-invasive biochemical analysis. However, near-infrarednon-invasive biochemical analysis technology has not reached level of clinicalbecause of the less biochemical components in blood and serious tissue backgroundinterference.
In order to eliminate human tissue background interferences,“Blood VolumeSpectral Subtraction Method” was proposed. By subtracting two blood spectrameasured in a row within an extremely short time period, effective blood spectra canbe acquired. However, a more quickly speed and higher signal-to-noise ratio (SNR) ofpulse wave signals collecting were needed for “Blood Volume Spectral Subtraction Method”, the performance of near-infrared spectroscopy instruments in the marketcan’t meet those requirements. So it is necessary to research a rapid and high SNRmethod for volume pulse wave acquisition, in order to improve the performance ofinstrument.
This paper focuses on the acquisition method for fast and high SNR spectra in thearea of near-infrared noninvasive biochemical analysis. The hardware circuit designof fast and high SNR acquisition system for volume pulse wave signal and the noisereduction processing of volume pulse wave were mainly included in this research. Thedetails and main conclusions of this research were as follows:
1) Based on the requirement of fast and high SNR acquisition system fornear-infrared non-invasive biochemical analysis, detectors with different workingstyles have different characteristics. The near-infrared acquisition systems for volumepulse waves were designed according to each styles of InGaAs detectors of unit type,multi-array type and multiple discrete type. A preamplifier circuit and data acquisitioncircuit were contained of each system.
2) The performances of three near-infrared volume pulse wave acquisitionsystems were tested, and the advantages and disadvantages of three systems wereanalyzed. Then the system which most satisfied the requirements of near-infrarednon-invasive biochemical monitoring was selected. It was proved by relatedexperiments that the SNR of unit style volume pulse wave acquisition system wasabout28000：1, and the dark noise was about20μV. Although the unit style systemhad a higher SNR, the spectrum was obtained only by scanning. Not only theacquisition speed was limited, but also it was very difficult to ensure the accuracy ofspectrum that was due to the blood fluidity.256pixels InGaAs detector G9211wasused in multi-array volume pulse wave acquisition system, which can collect256signals at different wavelength simultaneously with a fast speed. But the average SNRof this system was7000：1, which can’t meet the requirements of non-invasivebiochemical analysis.16pixels InGaAs detector G7150was used in multiple discretevolume pulse wave acquisition system, which can collect16signals at different wavelength simultaneously. About50spectra can be captured per second at most. TheSNR of this system can reach13000：1, and dark noise was about43μV. In summerconsidered, the volume pulse wave acquisition system of16pixels discrete style wasthe best system for near-infrared non-invasive biochemical analysis.
3) Clinical experiment was completed by using the volume pulse waveacquisition system of16pixels discrete style. Eighty-one fingertip absorption curvesof different ages and gentles were collected, and concentrations of hematocrit andhemoglobin were predicted by establishing calibration model. The correlationcoefficients of hematocrit and hemoglobin can reach0.81and0.73relatively, with theRMSEP being1.82%and14.53g·L-1.
4) A noise reduction processing method for pulse wave signal based on adaptivefilter was proposed by researching reduction processing of pulse wave signal noisedeeply. It was shown that the correlation coefficients of hematocrit and hemoglobinwere up to0.87and0.83relatively, with the RMSEP being1.89%and9.16g·L-1byusing the pulse wave signal after processing.
This paper focused on the key problems of monitoring fast and high SNR signalfor near-infrared non-invasive biochemical analysis. And a fast and high SNRacquisition system of near-infrared volume pulse wave was explored. The researchesof this paper provide both theoretical and experimental basis of the clinicalapplication of NIRS non-invasive biochemical monitoring method.
为了消除人体复杂的组织背景干扰，本课题组提出血流容积光谱相减法。利用短时间内不同血流容积下测得的光谱相减，从而得到血液光谱。但是光谱相减法的实现对容积脉搏波信号的采集速度和信噪比要求很高，而现今市面上近红外光谱仪器的性能指标尚未达到要求，因此需要研究快速高信噪比的容积脉搏波采集方法，进而提高仪器的性能。
本文围绕近红外无创生化分析中快速高信噪比光谱信号的采集方法展开研究。主要包括快速高信噪比容积脉搏波信号采集系统的设计和容积脉搏波信号降噪处理的研究。具体研究内容和主要结论如下：
1)针对近红外无创生化采集系统中快速、高信噪比的要求，不同工作方式的InGaAs探测器各有特点。分别针对单元式、多元阵列式和多元分立式铟镓砷探测器设计近红外容积脉搏波采集系统。每套系统包括前置放大电路和数据采集电路两部分。
2)通过对三套近红外容积脉搏波采集系统性能的测试，分析各自的优缺点，研制出符合人体无创生化检测要求的系统。实验测得，单元式容积脉搏波采集系统的信噪比约为28000：1，暗噪声为20左右。虽然单元式采集系统具有较高的信噪比，但只能通过扫描的方式获得光谱，不仅限制了采集速度，而且由于血液的流动性，也很难保证所采集光谱的准确性。多元阵列式容积脉搏波采集系统采用256元铟镓砷探测器G9211，可同时采集256个波长的信号，采集速度快，但实测信噪比平均为7000：1，不能满足无创生化分析的要求。多元分立式容积脉搏波采集系统采用16元铟镓砷探测器G7150，可同时采集16个波长的信号，每秒钟最多采集50幅光谱，信噪比达到13000：1，暗噪声为40左右。综合考虑，16元分立式容积脉搏波采集系统最接近人体无创生化检测的要求。
3)利用16元分立式容积脉搏波采集电路搭建的近红外无创生化检测系统完成临床实验。通过采集不同年龄、不同性别的81名志愿者食指指端容积脉搏波信号，建立定标模型，预测血液中红细胞比容和血红蛋白浓度，预测相关系数分别为0.81和0.73，预测标准差分别为1.82%和14.53g·L-1。
4)深入研究容积脉搏波信号降噪处理的现状，提出一种基于自适应滤波的脉搏波信号降噪处理方法。利用该方法处理临床采集的容积脉搏波信号，结果表明，采用处理后的信号重新建立定标模型，红细胞比容和血红蛋白的预测相关系数分别提升至0.87和0.83，预测标准差分别提升至1.89%和9.16g·L-1。
本文深入研究了近红外无创生化分析中快速高信噪比信号的检测技术，并成功研制出一套快速高信噪比的近红外容积脉搏波采集系统，为实现近红外无创生化检测技术的临床应用奠定了理论和实验基础。
The blood biochemical composition directly reflects the health condition of body.Currently, routine clinical testing methods are almost invasive or minimally invasive.Not only existing the hidden dangers of cross-infection, but also needing reagents forin vitro analysis that is difficult to realize online monitoring. So non-invasivebiochemical monitoring has been one of the hotspots by domestic and foreign scholars.Near-infrared absorption spectroscopy (NIRS) technique is invasive, reagent-free, nopollution and has online monitoring, which has a high research value and broadprospects in the field of non-invasive biochemical analysis. However, near-infrarednon-invasive biochemical analysis technology has not reached level of clinicalbecause of the less biochemical components in blood and serious tissue backgroundinterference.
In order to eliminate human tissue background interferences,“Blood VolumeSpectral Subtraction Method” was proposed. By subtracting two blood spectrameasured in a row within an extremely short time period, effective blood spectra canbe acquired. However, a more quickly speed and higher signal-to-noise ratio (SNR) ofpulse wave signals collecting were needed for “Blood Volume Spectral Subtraction Method”, the performance of near-infrared spectroscopy instruments in the marketcan’t meet those requirements. So it is necessary to research a rapid and high SNRmethod for volume pulse wave acquisition, in order to improve the performance ofinstrument.
This paper focuses on the acquisition method for fast and high SNR spectra in thearea of near-infrared noninvasive biochemical analysis. The hardware circuit designof fast and high SNR acquisition system for volume pulse wave signal and the noisereduction processing of volume pulse wave were mainly included in this research. Thedetails and main conclusions of this research were as follows:
1) Based on the requirement of fast and high SNR acquisition system fornear-infrared non-invasive biochemical analysis, detectors with different workingstyles have different characteristics. The near-infrared acquisition systems for volumepulse waves were designed according to each styles of InGaAs detectors of unit type,multi-array type and multiple discrete type. A preamplifier circuit and data acquisitioncircuit were contained of each system.
2) The performances of three near-infrared volume pulse wave acquisitionsystems were tested, and the advantages and disadvantages of three systems wereanalyzed. Then the system which most satisfied the requirements of near-infrarednon-invasive biochemical monitoring was selected. It was proved by relatedexperiments that the SNR of unit style volume pulse wave acquisition system wasabout28000：1, and the dark noise was about20μV. Although the unit style systemhad a higher SNR, the spectrum was obtained only by scanning. Not only theacquisition speed was limited, but also it was very difficult to ensure the accuracy ofspectrum that was due to the blood fluidity.256pixels InGaAs detector G9211wasused in multi-array volume pulse wave acquisition system, which can collect256signals at different wavelength simultaneously with a fast speed. But the average SNRof this system was7000：1, which can’t meet the requirements of non-invasivebiochemical analysis.16pixels InGaAs detector G7150was used in multiple discretevolume pulse wave acquisition system, which can collect16signals at different wavelength simultaneously. About50spectra can be captured per second at most. TheSNR of this system can reach13000：1, and dark noise was about43μV. In summerconsidered, the volume pulse wave acquisition system of16pixels discrete style wasthe best system for near-infrared non-invasive biochemical analysis.
3) Clinical experiment was completed by using the volume pulse waveacquisition system of16pixels discrete style. Eighty-one fingertip absorption curvesof different ages and gentles were collected, and concentrations of hematocrit andhemoglobin were predicted by establishing calibration model. The correlationcoefficients of hematocrit and hemoglobin can reach0.81and0.73relatively, with theRMSEP being1.82%and14.53g·L-1.
4) A noise reduction processing method for pulse wave signal based on adaptivefilter was proposed by researching reduction processing of pulse wave signal noisedeeply. It was shown that the correlation coefficients of hematocrit and hemoglobinwere up to0.87and0.83relatively, with the RMSEP being1.89%and9.16g·L-1byusing the pulse wave signal after processing.
This paper focused on the key problems of monitoring fast and high SNR signalfor near-infrared non-invasive biochemical analysis. And a fast and high SNRacquisition system of near-infrared volume pulse wave was explored. The researchesof this paper provide both theoretical and experimental basis of the clinicalapplication of NIRS non-invasive biochemical monitoring method.
引文
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