CN104224196B - The method of non-invasive measurement blood component concentration - Google Patents
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Abstract
本发明公开了一种无创测量血液成分浓度的方法，所述方法包括：同步采集一段时间内多个不同波长光源下手指指尖处的透射光电容积脉搏波并取对数，得到多波长下的对数光电容积脉搏波；利用时域或频域的直流特征量和交流特征量的提取方法，提取多波长的特征量；根据3σ准则，剔除含有粗大误差的直流特征量和交流特征量，将剔除粗大噪声后的直流特征量和交流特征量的均值作为最终的光电容积脉搏波的特征量；提取一定数量实验对象的光电容积脉搏波特征量样本，同时使用生化分析仪器测量血液成分浓度的真值，建立浓度与光电容积脉搏波特征量的回归模型；提取被测对象的光电容积脉搏波特征量，利用回归模型计算血液成分的浓度。
The invention discloses a method for non-invasively measuring the concentration of blood components. The method comprises: synchronously collecting the transmitted photoplethysmography waves at the fingertips under multiple different wavelength light sources within a period of time and taking the logarithm to obtain the multi-wavelength pulse waves. Logarithmic photoplethysmography; use the time-domain or frequency-domain DC and AC feature extraction methods to extract multi-wavelength feature quantities; according to the 3σ criterion, eliminate the DC feature quantities and AC feature quantities that contain gross errors, and The mean value of the DC feature quantity and the AC feature quantity after removing coarse noise is used as the final feature quantity of the photoplethysmography wave; extract a certain number of samples of the photoplethysmography wave feature quantity of the experimental subjects, and use a biochemical analysis instrument to measure the true concentration of the blood components. value, and establish a regression model of concentration and photoplethysmography feature quantity; extract the photoplethysmography feature quantity of the measured object, and use the regression model to calculate the concentration of blood components.
Description
技术领域technical field
本发明涉及一种无创测量血液成分浓度的方法，尤其涉及一种利用有限个数光源下测得的手指指尖处透射光电容积脉搏波的特征量，建立血液成分浓度与特征量的回归计算模型，来预测血液成分浓度的建模分析方法。The invention relates to a method for non-invasively measuring blood component concentration, in particular to a method for establishing a regression calculation model of blood component concentration and feature quantity by using the characteristic quantity of the transmitted photoplethysmography wave at the fingertip measured under a limited number of light sources , to predict the modeling analysis method of blood component concentration.
背景技术Background technique
目前，已报道的关于无创血液成分检测的研究中涉及到的血液参数包括血糖、血红蛋白及其衍生物、红细胞数、红细胞比容、胆红素、多种蛋白、血液中的酒精含量以及普遍应用的血氧饱和度等，主要集中在血糖和血红蛋白的检测上。各研究小组根据不同血液成分参数的物理和化学特性及在生理组织上的表现，所采用的检测方法不同，主要可以分为两大类：非光学方法和光学方法。非光学方法有反离子电渗透法、热代谢整合法、电导率方法等，其缺点是所使用的电化学传感器、电极片等需要与人体皮肤接触，会引起被测对象的不适感，而且测量时皮肤状况、血流情况、体温等个体差异因素使得测量精度难以提高；光学方法包括：光声光谱法、拉曼光谱法、荧光法、偏振光旋光法、光学相干层析成像法、近红外光谱法等。近红外光谱技术是一种间接测量技术，以朗伯-比尔(Lambert-Beer)定律为基础，利用各种成分光吸收特异性来测量，目前在血糖、血氧、血红蛋白检测上应用较多。根据接收方式的不同，近红外光谱测量主要可以分为漫反射测量和透射测量。随着计算机技术和化学计量学理论的发展，近红外光谱定量分析的灵敏度、准确性和可靠性都有较大提高。近红外光谱法成为目前这些光学方法中最主要的研究方法，部分已进入在体检测实验阶段，取得的进展也是最为显著的。At present, the blood parameters involved in the reported research on non-invasive blood component detection include blood glucose, hemoglobin and its derivatives, red blood cell count, hematocrit, bilirubin, various proteins, alcohol content in blood, and general application Blood oxygen saturation, etc., mainly focus on the detection of blood sugar and hemoglobin. According to the physical and chemical characteristics of different blood component parameters and their performance on physiological tissues, the detection methods adopted by each research group are different, which can be mainly divided into two categories: non-optical methods and optical methods. Non-optical methods include reverse ion electroosmosis method, thermal metabolism integration method, conductivity method, etc. The disadvantage is that the electrochemical sensors and electrodes used need to be in contact with human skin, which will cause discomfort to the measured object, and the measurement Individual differences such as skin conditions, blood flow conditions, and body temperature make it difficult to improve measurement accuracy; optical methods include: photoacoustic spectroscopy, Raman spectroscopy, fluorescence, polarized light rotation, optical coherence tomography, near-infrared spectroscopy, etc. Near-infrared spectroscopy is an indirect measurement technology based on the Lambert-Beer law, using the light absorption specificity of various components to measure, and is currently widely used in the detection of blood sugar, blood oxygen, and hemoglobin. According to different receiving methods, near-infrared spectroscopy can be mainly divided into diffuse reflectance measurement and transmission measurement. With the development of computer technology and chemometric theory, the sensitivity, accuracy and reliability of near-infrared spectroscopy quantitative analysis have been greatly improved. Near-infrared spectroscopy has become the most important research method among these optical methods, and some of them have entered the stage of in vivo detection experiments, and the progress has been the most significant.
中国发明专利申请CN1550209A，公开了一种无创测量血液成分浓度的方法和装置，通过对被测对象身体部分施加不同的压力，测量不同厚度下的透射近红外光谱，计算得到差值光谱，然后建模分析计算血液成分的浓度，但其测量装置结构复杂，而且外加的压力容易令被测对象产生不适感。Chinese invention patent application CN1550209A discloses a method and device for non-invasively measuring the concentration of blood components. By applying different pressures to the body parts of the measured object, measuring the transmission near-infrared spectra at different thicknesses, calculating the difference spectrum, and then constructing Modular analysis is used to calculate the concentration of blood components, but the structure of the measuring device is complex, and the external pressure is likely to cause discomfort to the measured object.
中国发明专利申请CN101507607A，公开了一种无创测量血液光谱与成分的方法，使用告诉光谱仪连续测量被测体的透射光谱，对各个波长下的脉搏波进行傅里叶变化，取幅值最大的谐波按波长排序，形成光谱，实现无创测量血液成分，该方法仅利用了光电容积脉搏波的交流成分，所含信息量有限，对被测部分的厚度、皮肤色素、水分含量等个体差异的表达能力不足，限制了测量精度的提高。Chinese invention patent application CN101507607A discloses a method for non-invasive measurement of blood spectrum and components, using a high-speed spectrometer to continuously measure the transmission spectrum of the measured object, performing Fourier changes on pulse waves at various wavelengths, and taking the harmonic with the largest amplitude The waves are sorted by wavelength to form a spectrum to realize non-invasive measurement of blood components. This method only uses the AC component of the photoplethysmography wave, and the amount of information contained is limited. Insufficient capacity limits the improvement of measurement accuracy.
发明内容Contents of the invention
本发明提供了一种无创测量血液成分浓度的方法，本发明解决了如何降低人体组织及血液散射对光谱定律分析的影响以及提高血液成分浓度测量精度的问题，详见下文描述：The present invention provides a method for non-invasively measuring the concentration of blood components. The present invention solves the problem of how to reduce the influence of human tissue and blood scattering on spectral law analysis and improve the measurement accuracy of blood component concentration. See the following description for details:
一种无创测量血液成分浓度的方法，所述方法包括以下步骤：A method for non-invasively measuring the concentration of blood components, said method comprising the following steps:
同步采集一段时间内多个不同波长光源下手指指尖处的透射光电容积脉搏波并取对数，得到多波长下的对数光电容积脉搏波；Synchronously collect the transmitted photoplethysmography at the fingertips under multiple light sources of different wavelengths within a period of time and take the logarithm to obtain the logarithmic photoplethysmography at multiple wavelengths;
利用时域或频域的多波长直流特征量和交流特征量的提取方法，提取多波长的特征量；Using the method of extracting multi-wavelength DC feature quantities and AC feature quantities in the time domain or frequency domain to extract multi-wavelength feature quantities;
根据3σ准则，剔除含有粗大误差的直流特征量和交流特征量，将剔除粗大噪声后的直流特征量和交流特征量的均值作为最终的光电容积脉搏波的特征量；According to the 3σ criterion, the DC feature quantity and the AC feature quantity containing gross errors are eliminated, and the average value of the DC feature quantity and the AC feature quantity after the rough noise is removed is used as the final feature quantity of the photoplethysmography wave;
提取一定数量实验对象的光电容积脉搏波特征量样本，同时使用生化分析仪器测量血液成分浓度的真值，建立浓度与光电容积脉搏波特征量的回归模型；Extract the photoplethysmography characteristic quantity samples of a certain number of experimental subjects, measure the true value of the blood component concentration with a biochemical analysis instrument, and establish a regression model between the concentration and the photoplethysmography characteristic quantity;
提取被测对象的光电容积脉搏波特征量，利用回归模型计算血液成分的浓度。The photoplethysmography feature quantity of the measured object is extracted, and the concentration of blood components is calculated by using a regression model.
本发明提供的技术方案的有益效果是：本方法仅使用有限波长下对数光电容积脉搏波信号的交流量、直流量为新的特征量建立回归模型，定量计算血液成分的浓度。透射光电容积脉搏波的交流量和直流量，均包含了人体组织和血液成分的信息，其中交流量主要反映了脉动的动脉血中光吸收和散射的信息，而直流量中包含了手指厚度、皮肤等组织的吸收和散射、血液的静态吸收和散射的信息，与动态光谱理论仅利用交流量建模分析血液成分相比，引入更多的信息，增加了模型的测量精度；同时，通过研究优选出的有限波长，使用以优选波长为中心波长的发光二极管能够进一步提高系统的信噪比和测量精度，提高模型的定量分析能力。The beneficial effect of the technical solution provided by the present invention is that the method only uses the AC and DC quantities of the logarithmic photoplethysmography signal under limited wavelengths as new feature quantities to establish a regression model and quantitatively calculate the concentration of blood components. The AC volume and DC volume of the transmitted photoplethysmogram both contain information on human tissue and blood components, and the AC volume mainly reflects the light absorption and scattering information in the pulsating arterial blood, while the DC volume includes the finger thickness, Compared with the absorption and scattering of skin and other tissues, and the static absorption and scattering of blood, compared with the dynamic spectrum theory that only uses the exchange volume modeling to analyze blood components, it introduces more information and increases the measurement accuracy of the model; at the same time, through research For the optimized limited wavelength, the use of light-emitting diodes with the optimized wavelength as the center wavelength can further improve the signal-to-noise ratio and measurement accuracy of the system, and improve the quantitative analysis ability of the model.
附图说明Description of drawings
图1为无创测量血液成分浓度方法的流程图Figure 1 is a flow chart of the method for non-invasive measurement of blood component concentrations
具体实施方式detailed description
为使本发明的目的、技术方案和优点更加清楚，下面对本发明实施方式作进一步地详细描述。In order to make the purpose, technical solution and advantages of the present invention clearer, the implementation manners of the present invention will be further described in detail below.
为了解决如何降低人体组织及血液散射对光谱定量分析的影响以及提高血液成分浓度的测量精度的问题，本发明实施例提供一种无创测量血液成分浓度的方法，参见图1，详见下文描述。In order to solve the problem of how to reduce the influence of human tissue and blood scattering on spectral quantitative analysis and improve the measurement accuracy of blood component concentration, an embodiment of the present invention provides a method for non-invasive measurement of blood component concentration, see FIG. 1 , and see the description below for details.
101：同步采集一段时间内多个不同波长光源下手指指尖处的透射光电容积脉搏波并取对数，得到多波长下的对数光电容积脉搏波；101: Synchronously collect the transmitted photoplethysmography at the fingertips under multiple different wavelength light sources within a period of time and take the logarithm to obtain the logarithmic photoplethysmography at multiple wavelengths;
其中，该步骤具体为：Among them, this step is specifically:
多个不同波长的光源是多个中心波长不同的发光二极管光源，波长范围是可见光-近红外波段；Multiple light sources with different wavelengths are multiple light-emitting diode light sources with different central wavelengths, and the wavelength range is visible light-near infrared band;
使用多个发光二极管作为光源时，驱动发光二极管光源的方式可以是分时驱动或者正弦波分频驱动；When multiple light emitting diodes are used as the light source, the way to drive the light emitting diode light source can be time-division driving or sine wave frequency division driving;
光电接收器件可以是光电二极管、光电池等光电器件，但光电接收器件的敏感波长范围满足光源波长的要求，光电接收器件及相关电子线路的响应速度需要满足所选驱动方式的要求；The photoelectric receiving device can be a photodiode, a photoelectric cell and other photoelectric devices, but the sensitive wavelength range of the photoelectric receiving device meets the requirements of the wavelength of the light source, and the response speed of the photoelectric receiving device and related electronic circuits needs to meet the requirements of the selected driving mode;
光源和光电接收器件与被测对象手指指尖的放置方式可以是透射式或者反射式，即测量得到的光电容积脉搏波可以来源于透射光强或者漫反射光强；The placement of the light source, the photoelectric receiving device and the fingertip of the measured object can be transmissive or reflective, that is, the measured photoplethysmogram can be derived from transmitted light intensity or diffuse reflection light intensity;
对采集得到的多个波长下的光电容积脉搏波取对数，得到对数光电容积脉搏波。The logarithm of the collected photoplethysmography waves at multiple wavelengths is taken to obtain logarithmic photoplethysmography waves.
102：利用时域或频域的多波长直流特征量和交流特征量的提取方法，提取多波长的特征量；102: Using the time-domain or frequency-domain multi-wavelength DC and AC feature extraction methods to extract multi-wavelength feature quantities;
该步骤具体包括时域和频域的多波长直流特征量和交流特征量的提取方法，详见步骤1021-1022：This step specifically includes the extraction method of multi-wavelength DC feature quantities and AC feature quantities in the time domain and frequency domain, see steps 1021-1022 for details:
1021：时域的直流特征量和交流特征量提取方法是，在时域中，将对数光电容积脉搏波按照脉搏周期进行划分区段，提取出每个脉搏周期中对数光电容积脉搏波的峰值和谷值，将峰值或者峰值和谷值的平均值作为光电容积脉搏波的直流特征量，将峰值和谷值的差值作为光电容积脉搏波的交流特征量；1021: The DC and AC feature extraction methods in the time domain are: in the time domain, the logarithmic photoplethysmography is divided into sections according to the pulse cycle, and the logarithmic photoplethysmography in each pulse cycle is extracted The peak value and the valley value, the peak value or the average value of the peak value and the valley value are used as the DC characteristic quantity of the photoplethysmography wave, and the difference between the peak value and the valley value is used as the AC characteristic quantity of the photoplethysmography wave;
1022：频域的直流特征量和交流特征量提取方法是，在频域中，取一定时间内连续采集的对数光电容积脉搏波，采用动态光谱的频域提取法，对对数光电容积脉搏波做傅里叶变换，将对数脉搏波频谱中的直流分量作为光电容积脉搏波的直流特征量，将频谱中的基波分量(幅值最大的谐波)作为光电容积脉搏波的交流特征量。1022: The DC and AC feature extraction method in the frequency domain is to take the logarithmic photoplethysmogram collected continuously within a certain period of time in the frequency domain, and use the frequency domain extraction method of dynamic spectrum to logarithmic photoplethysmography Wave Fourier transform, the DC component in the logarithmic pulse wave spectrum is used as the DC characteristic quantity of the photoplethysmography wave, and the fundamental wave component (the harmonic with the largest amplitude) in the spectrum is used as the AC characteristic of the photoplethysmography wave quantity.
103：根据3σ准则，在提取出的所有直流特征量和交流特征量中剔除含有粗大误差的直流特征量和交流特征量，将剔除粗大噪声后的直流特征量和交流特征量的均值作为最终的光电容积脉搏波的特征量；103: According to the 3σ criterion, remove the DC and AC features that contain coarse errors from all the extracted DC and AC features, and take the mean value of the DC and AC features after removing coarse noise as the final The characteristic quantity of photoplethysmography;
测量过程中，某个时刻的光电容积脉搏波信号如果包含运动伪迹或含有较大噪声，会影响该段提取光电容积脉搏波特征量的准确性。若每个实验对象的同种特征量(直流特征量或者交流特征量)组成的合集中的某个元素与合集的平均值之差大于等于3σ，则认为该元素误差较大并剔除，若小于3σ则保留。During the measurement process, if the photoplethysmography signal at a certain moment contains motion artifacts or contains large noise, it will affect the accuracy of extracting the photoplethysmography feature quantity in this segment. If the difference between an element in the collection composed of the same characteristic quantity (DC characteristic quantity or AC characteristic quantity) of each experimental object and the average value of the collection is greater than or equal to 3σ, the error of the element is considered to be large and eliminated, if it is less than 3σ is reserved.
104：按上述步骤101-103，提取一定数量实验对象的光电容积脉搏波特征量样本，同时使用生化分析仪器测量血液成分浓度的真值，使用某种建模方法，建立浓度与光电容积脉搏波特征量的回归模型；104: According to the above steps 101-103, extract a certain number of samples of photoplethysmographic characteristics of the experimental subjects, and use a biochemical analysis instrument to measure the true value of the concentration of blood components, and use a certain modeling method to establish the concentration and photoplethysmogram Regression model of feature quantity;
该步骤具体包括步骤1041-1043，详见下文描述：This step specifically includes steps 1041-1043, see the description below for details:
1041：对每个实验对象进行多波长光电脉搏波的采集，同时采集实验对象的血液，进行生化分析，记录血液成分浓度的真值；1041: Collect multi-wavelength photoelectric pulse waves for each test subject, collect the blood of the test subjects at the same time, conduct biochemical analysis, and record the true value of the concentration of blood components;
1042：提取每个实验对象的多波长光电容积脉搏波的特征量；1042: Extracting the characteristic quantities of the multi-wavelength photoplethysmography of each experimental subject;
1043：将每个实验对象的多波长光电容积脉搏波的特征量及其高次项作为自变量，生化分析结果中得到的血液成分浓度的真值作为因变量，使用合理的建模方法，比如偏最小二乘建模、神经网络建模等建模方法，建立因变量与自变量的对应关系，即浓度真值与光电容积脉搏波特征量的回归模型。1043: The characteristic quantity of multi-wavelength photoplethysmography and its high-order items of each experimental subject are used as independent variables, and the true value of the blood component concentration obtained from the biochemical analysis results is used as a dependent variable, using a reasonable modeling method, such as Modeling methods such as partial least squares modeling and neural network modeling establish the corresponding relationship between the dependent variable and the independent variable, that is, the regression model of the true value of the concentration and the characteristic quantity of the photoplethysmogram.
以特征量为自变量为例，通过建模方法得到的回归模型如公式(1)所示：Taking the feature quantity as the independent variable as an example, the regression model obtained by the modeling method is shown in formula (1):
公式(1)中，c表示某种血液成分的浓度，表示的是N个波长下提取的对数光电容积脉搏波的直流特征量d和交流特征量a，f表示回归模型函数；In formula (1), c represents the concentration of a certain blood component, Represents the DC characteristic quantity d and the AC characteristic quantity a of the logarithmic photoplethysmogram extracted under N wavelengths, and f represents the regression model function;
本方法要求被测实验对象的手指厚度、肤色、年龄等个体差异分布要尽可能范围广泛，这样才能使模型充分包含各种个体差异，增加使用模型计算血液成分浓度的准确性；This method requires that the distribution of individual differences such as finger thickness, skin color, and age of the test subject should be as wide as possible, so that the model can fully include various individual differences and increase the accuracy of using the model to calculate the concentration of blood components;
被测实验对象的血液成分浓度分布范围应该符合医学统计要求，才能满足人体生理参数测量的要求，增加模型计算血液成分浓度的准确性。The distribution range of the blood component concentration of the tested subject should meet the requirements of medical statistics in order to meet the requirements of the measurement of human physiological parameters and increase the accuracy of the model to calculate the concentration of blood components.
105：在测量时，按照上述步骤101-103，提取被测对象的光电容积脉搏波特征量，利用步骤104中的回归模型计算血液成分的浓度。105: During measurement, according to the above steps 101-103, extract the photoplethysmography characteristic value of the measured object, and use the regression model in step 104 to calculate the concentration of blood components.
本发明实施例中应用到的对数运算、傅里叶变换、偏最小二乘建模，神经网络建模、3σ判定准则均为数据处理方法中的公知技术，为本领域工程技术人员所公知。The logarithmic operation, Fourier transform, partial least squares modeling, neural network modeling, and 3σ judgment criterion applied in the embodiment of the present invention are all well-known technologies in data processing methods, and are well known to those skilled in the art .
综上所述，本发明实施例提供了一种无创测量血液成分浓度的方法，仅使用有限数量波长下对数光电容积脉搏波信号的交流量、直流量为新的特征量及其高次项进行建模，引入了光散射的信息，测量精度与传统方法相比进一步得到了提高，一定程度上补偿了散射带来的非线性影响。To sum up, the embodiment of the present invention provides a method for non-invasively measuring the concentration of blood components, using only the AC volume and DC volume of the logarithmic photoplethysmography signal under a limited number of wavelengths as new characteristic quantities and their high-order items Modeling is carried out, and the information of light scattering is introduced. Compared with the traditional method, the measurement accuracy is further improved, and the nonlinear effect caused by scattering is compensated to a certain extent.
本领域技术人员可以理解附图只是一个优选实施例的示意图，上述本发明实施例序号仅仅为了描述，不代表实施例的优劣。Those skilled in the art can understand that the accompanying drawing is only a schematic diagram of a preferred embodiment, and the serial numbers of the above-mentioned embodiments of the present invention are for description only, and do not represent the advantages and disadvantages of the embodiments.
以上所述仅为本发明的较佳实施例，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The above descriptions are only preferred 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 in the protection of the present invention. within range.
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