Non-invasive Blood Glucose Measurement Research Articles

正弦调制偏振光无创血糖检测的研究

正弦调制偏振光无创血糖检测的研究

Investigation of the specificity of Raman spectroscopy in non-invasive blood glucose measurements

Although several in vivo blood glucose measurement studies have been performed by different research groups using near-infrared (NIR) absorption and Raman spectroscopic techniques, prospective prediction has proven to be a challenging problem. An important issue in this case is the demonstration of causality of glucose concentration to the spectral information, especially as the intrinsic glucose signal is smaller compared with that of the other analytes in the blood-tissue matrix. Furthermore, time-dependent physiological processes make the relation between glucose concentration and spectral data more complex. In this article, chance correlations in Raman spectroscopy-based calibration model for glucose measurements are investigated for both in vitro (physical tissue models) and in vivo (animal model and human subject) cases. Different spurious glucose concentration profiles are assigned to the Raman spectra acquired from physical tissue models, where the glucose concentration is intentionally held constant. Analogous concentration profiles, in addition to the true concentration profile, are also assigned to the datasets acquired from an animal model during a glucose clamping study as well as a human subject during an oral glucose tolerance test. We demonstrate that the spurious concentration profile-based calibration models are unable to provide prospective predictions, in contrast to those based on actual concentration profiles, especially for the physical tissue models. We also show that chance correlations incorporated by the calibration models are significantly less in Raman as compared to NIR absorption spectroscopy, even for the in vivo studies. Finally, our results suggest that the incorporation of chance correlations for in vivo cases can be largely attributed to the uncontrolled physiological sources of variations. Such uncontrolled physiological variations could either be intrinsic to the subject or stem from changes in the measurement conditions.

用于无创血糖检测的调频连续波激光雷达技术理论分析

用于无创血糖检测的调频连续波激光雷达技术理论分析

8I-19 位相シフト法を用いた光センサによる非侵襲血糖値計測システムの試作開発(OS-12 バイオヒート・マストランスファー(2))

8I-19 位相シフト法を用いた光センサによる非侵襲血糖値計測システムの試作開発(OS-12 バイオヒート・マストランスファー(2))

Non-invasive blood glucose measurement by near infrared spectroscopy: Machine drift, time drift and physiological effect

The aim of this paper is to evaluate development of the non-invasive blood glucose measurement of near infrared (NIR) spectroscopy. The results showed that NIR spectroscopy might obtain glucose concentration of up to 200% difference under a same environmental condition with two months apart due to time and machine drifts. These effects can restrict the development of the non-invasive blood glucose measurement. Partial least square (PLS) regression was used, which showed advantage over using simple absorbance for glucose concentration. Non-invasive blood glucose measurement of health subjects (non-diabetics) was also investigated. The results showed that R correlation coefficient of prediction (Rp) was 0.48 and root mean square of prediction (rmsep) was 1.34 mmol/l. The error was mainly due to the physiological effect of different subjects.

Non-invasive blood glucose measurement by near infrared spectroscopy: Machine drift, time drift and physiological effect

The aim of this paper is to evaluate development of the non-invasive blood glucose measurement of near infrared (NIR) spectroscopy. The results showed that NIR spectroscopy might obtain glucose concentration of up to 200% difference under a same environmental condition with two months apart due to time and machine drifts. These effects can restrict the development of the non-invasive blood glucose measurement. Partial least square (PLS) regression was used, which showed advantage over using simple absorbance for glucose concentration. Non-invasive blood glucose measurement of health subjects (non-diabetics) was also investigated. The results showed that R correlation coefficient of prediction (Rp) was 0.48 and root mean square of prediction (rmsep) was 1.34 mmol/l. The error was mainly due to the physiological effect of different subjects.

血糖监测的浮动基准方法中基准点的研究

A problem in terms of the accuracy of noninvasive measurement of blood glucose with near-infrared (NIR) spectroscopy is mainly caused by the weak glucose signal and strong background variations. We report the existence of the radial reference point in a floating-reference method, which is supposed to solve this problem. Based on the analysis of the infinite diffusion theory, the local condition of the reference point is deduced theoretically. Then the experiments using the intralipid solutions are constructed to testify the existence of the reference point. In order to further validate our results, Monte Carlo simulations are performed to calculate the diffused light distribution according to the variation of the glucose concentration in the intralipid solutions. All the reference points existing in three-layer skin model are also listed at the wavelength of 1200-1700 nm.

基于O2-PLS方法的血糖无损检测实验研究

基于O2-PLS方法的血糖无损检测实验研究

Factors Affecting the Accuracy of Non-Invasive Blood Glucose Measurement by Short-Wavelength near Infrared Spectroscopy in the Determination of the Glycaemic Index of Foods

Non-invasive techniques for the analysis of blood glucose are desirable not only for clinical use but also for the determination of the glycaemic index (GI) of foods. Factors that affect the accuracy of non-invasive blood glucose measurements by near infrared (NIR) spectroscopy were identified and examined to establish the optimal conditions for the analysis. Calibration models were obtained by means of partial least squares regression. Several experiments revealed that a good calibration model could be obtained using spectra (700–1100 nm) acquired from the palm of the hand with a large interactance probe fixed to a table provided that spectral acquisition and blood glucose analysis are performed simultaneously. The accuracy of the calibration model developed is clinically acceptable; the coefficient of multiple determination was 0.85 and the standard error of cross-validation was 9.7 mg dL−1. An analysis of a model solution confirmed that NIR spectroscopy in the short-wavelength region 700–1100 nm is capable of measuring glucose concentrations of the order of 0.01% (10 mg dL−1) in blood. The determination of the GI of foods by using the present method will be examined in the near future.

Polarimetry in turbid, birefringent, optically active media: A Monte Carlo study of Mueller matrix decomposition in the backscattering geometry

Determination of the intrinsic polarization properties of a complex turbid medium such as biological tissue in the backscattering geometry (a geometry that is convenient for in situ applications) is complicated due to the confounding influence of scattering, and due to simultaneous occurrence of several polarization effects. We have investigated the polar decomposition approach of Mueller matrices to delineate individual intrinsic polarization parameters (specifically linear retardance δ and optical rotation ψ) of a birefringent, chiral, turbid medium in the backscattering geometry, using Mueller matrices generated with polarization-sensitive Monte Carlo simulations. The results show that near the exact backscattering direction, the interplay of the scattering-induced linear retardance and diattenuation on the intrinsic values for δ and ψ is coupled in a complex interrelated way, due to contribution of the backscattered photons. In contrast, these effects were significantly reduced for detection positions at distances larger than a transport length away from the point of illumination. Simultaneous determination of the intrinsic values for δ and ψ of a birefringent, chiral, turbid medium in the backward detection geometry can thus be accomplished by decomposing the Mueller matrices recorded at distances larger than a transport length away from the point of illumination. Determination of the intrinsic values for these polarization parameters in backscattering geometry could be significant in, for example, for quantification of tissue structural anisotropy and for noninvasive blood glucose measurements of diabetic patients.

Multiparameter techniques for non-invasive measurement of blood glucose

Although painless glycemic control could improve life quality of patients, enabling a better regulation of hyper- and hypoglycaemia episodes, none of the available commercial devices offer enough precision to replace lancet approaches. The aim of this work is to describe the technologies of absorption spectroscopy and bioimpedance applied simultaneously to transcutaneous glycemic measurement. Basic electrical and optic theories were studied systematically and in following experiments glucose characteristics were measured in blood. Light spectroscopy studies were done in MIR ranges (5–40 μm), while complex bioimpedance measurements were scanned from 100 Hz to 30 MHz. Parallel to above parameters, information of epidermis temperature (conductance and IR radiation) was also collected, improving prediction quality. Cutaneous assays showed correlation of 0.43 for impedance and 0.46 for optic spectroscopy alone. The multiparameter analysis allowed the improvement of correlation to 0.57, after data treatment with Partial Least Square and neural networks method in Matlab.

Application of muscle biopotential measurement for sustained, noninvasive blood glucose survey

Biopotential, the electric potential generated by living tissues, is affected by changes in extracellular electrolyte and glucose concentrations. We aimed to apply correlation between blood glucose concentrations (BGC) and biopotential of peripheral muscles for noninvasive blood glucose measurement. The study included 58 Wistar rats. In part of them, diabetes was induced by streptozotocin injection. Group 1, comprising 19 normal and 5 diabetic rats, received glucose-challenging protocol (intraperitoneal injection of 1 g/ml glucose). Group 2, 24 normal and 6 diabetic rats, received insulin-challenging protocol (three 30 IU insulin injections with 15-min intervals). Four control rats, group 3, were injected with 2-ml saline. BGC were measured by a standard ACCU-CHEK-Sensor Meter and compared with those estimated by biopotential sensor, further designated as GlucoSat, placed around proximal parts of the tails of the anaesthetized animals. GlucoSat results were calculated using the following biopotential equation: BGC(t) = k1 F1(t) + k2 F2(t) k3 F3(t) + k4, based on an experimental model involving estimation of pH, muscle metabolism, and tissue conductance, where t is time, k1-k4 are coefficients, and F1-F4 are functions. Mean biopotential system measured BGC was 181.7 +/- 4.3 mg/dl, not differing statistically from 187.9 +/- 4.3 mg/dl estimated by ACCU-CHEK. Pearson's correlation coefficient (r(2)) was 0.961 (P < 0.00001), indicating strong, direct correlation between the results. Within the nondiabetic group, r(2) was 0.944 (P < 0.00001), while, within the diabetic group, r(2) was 0.974 (P < 0.00001). No significant, adverse skin reactions were concomitantly observed in any experimental group. Biopotential measurements may be used for continuous, noninvasive estimation of changes in BGC. Further studies are needed to evaluate the applicability of this method to humans.

Mueller matrix decomposition for polarized light assessment of biological tissues

The Mueller matrix represents the transfer function of an optical system in its interactions with polarized light and its elements relate to specific biologically or clinically relevant properties. However, when many optical polarization effects occur simultaneously, the resulting matrix elements represent several "lumped" effects, thus hindering their unique interpretation. Currently, no methods exist to extract these individual properties in turbid media. Here, we present a novel application of a Mueller matrix decomposition methodology that achieves this objective. The methodology is validated theoretically via a novel polarized-light propagation model, and experimentally in tissue simulating phantoms. The potential of the approach is explored for two specific biomedical applications: monitoring of changes in myocardial tissues following regenerative stem cell therapy, through birefringence-induced retardation of the light's linear and circular polarizations, and non-invasive blood glucose measurements through chirality-induced rotation of the light's linear polarization. Results demonstrate potential for both applications.

Finite element analysis of blood flow and heat transfer in an image-based human finger

The human finger is said to be the extension of the brain and can convey the information on mechanical, thermal, and tissue damaging. The quantitative prediction of blood flow rate and heat generation are of great importance for diagnosing blood circulation illness and for the noninvasive measurement of blood glucose. In this study, we developed a coupled thermofluid model to simulate blood flow in large vessels and living tissue. The finite element (FE) model to analyze the blood perfusion and heat transport in the human finger was developed based on the transport theory in porous media. With regard to the blood flow in the large arteries and veins, the systemic blood circulation in the upper limb was modeled based on the one-dimensional flow in an elastic tube. The blood pressure and velocity in each vessel were first computed and the corresponding values for the large vessels in the finger were subsequently transferred to the FE model as the boundary conditions. The realistic geometric model for the human finger was constructed based on the MRI image data. After computing the capillary pressure and blood velocity in the tissue, the temperatures in the large vessels and the tissue of the finger were computed simultaneously by numerically solving the energy equation in porous media. The computed blood flow in tissues is in agreement with the anatomical structure and the measurement. It is believed that this analysis model will have extensive applications in the prediction of peripheral blood flow, temperature variation, and mass transport.

Pulse glucometry: a new approach for noninvasive blood glucose measurement using instantaneous differential near-infrared spectrophotometry

We describe a new optical method for noninvasive blood glucose (BGL) measurement. Optical methods are confounded by basal optical properties of tissues, especially water and other biochemical species, and by the very small glucose signal. We address these problems by using fast spectrophotometric analysis in a finger, deriving 100 transmittance spectra per second, to resolve optical spectra (900 to 1700 nm) of blood volume pulsations throughout the cardiac cycle. Difference spectra are calculated from the pulsatile signals, thereby eliminating the effects of bone, other tissues, and nonpulsatile blood. A partial least squares (PLS) model is used with the measured spectral data to predict BGL levels. Using glucose tolerance tests in 27 healthy volunteers, periodic optical measurements were made simultaneously with collection of blood samples for in vitro glucose analysis. Altogether, 603 paired data sets were obtained in all subjects and two-thirds of the data or of the subjects randomly selected were used for the PLS calibration model and the rest for the prediction. Bland-Altman and error-grid analyses of the predicted and measured BGL levels indicated clinically acceptable accuracy. We conclude that the new method, named pulse glucometry, has adequate performance for safe, noninvasive estimation of BGL.

Influence of contact state on NIR diffuse reflectance spectroscopy in vivo

In the practice of non-invasive blood glucose measurement by near-infrared (NIR) diffuse reflectance spectroscopy, an optical probe usually directly contacts skin in order to eliminate specular reflection. In this paper, the influence of contact state on the diffuse reflectance in vivo and the variation trend of diffuse reflectance with contact time under the same contact pressure, are investigated at wavelengths ranging from 1100 to 1700 nm. The result shows that the diffuse reflectance decreases with increasing contact pressure under the contact state. At a certain applied pressure, the diffuse reflectance fluctuates significantly at the beginning of contact, and the fluctuation becomes stable with elapsing contacting time. It is our aim in this paper to find out the optimal contact state and optimal measuring time, in order to reduce the influence of contact pressure on diffuse reflectance measurements. It is found from our experiments that, for in vivo measurement, the optimal contact state appears when the skin is pressed to about 0.5 mm by the probe, where the probe contacts the palm entirely, and that the optimal measuring time is at the 30th second since the probe contacting with the measuring site. Putting the above conclusions into practice, the repeatability of spectra is improved greatly.

Evaluation of Time-Course Changes of Gingival Crevicular Fluid Glucose Levels in Diabetics

A minute volume such as a few hundred nano-litres of gingival crevicular fluid (GCF) will evaporate within one minute at room temperature after collection. In order to investigate the feasibility of a method for noninvasive blood glucose measurement using this fluid, a fabricated GCF-collecting device, and the time-course changes of blood and GCF glucose levels in diabetics were evaluated. As a result of improvement in the GCF-collecting device such that the color of a filter paper changed from white to black upon collection of the sample, the completion of the collecting procedure could be visually confirmed. Using this device, we succeeded in collecting 200 nl of GCF within 30 s, despite the fact that GCF is usually secreted at a rate between 2 and 3 microl per tooth per hour. This method could be applicable for collecting small volume of other biological fluids. The time-course changes of blood and GCF glucose levels in ten type 2 diabetic subjects were examined, the correlation coefficient, R, between both glucose levels was 0.878. The result proved to be similar to that for normal healthy subjects in a previous study. A significant time difference between the two glucose levels was not observed. In diabetes period of 4.8 +/- 1.7 years, the influence of the disease on the GCF glucose level was minimal. Furthermore, from the ROC curve analysis, both sensitivity and specificity showed favorable results. It was suggested that the measurement of GCF glucose levels was a promising screening method for diabetics.

Development of Noninvasive Blood Glucose Sensor Using the Infrared Spectroscopy

Recently, diabetics have been steadily increasing, because change of diet, lack of exercise, increase an alcoholic intake, and increase a stress. It is a very serious problem for us. About 23.6 millions of people in Japan approach the danger of diabetes. Therefore, it is necessary to get insulin injection. And they have to measure blood glucose again and again a day. So, they are burden too heavy.This paper describes a new noninvasive measurement of blood glucose based on optical sensing. This uses Fourier transform infrared spectroscopy of attenuated total reflection. Non-invasive measurement was carried out by using 3 methods. And standard error of prediction is about ±20mg/dl by 3 method. This paper also describes practical application of this method.

Advances in Photoacoustic Noninvasive Glucose Testing

We report here on in vitro and in vivo experiments that are intended to explore the feasibility of photoacoustic spectroscopy as a tool for the noninvasive measurement of blood glucose. The in vivo results from oral glucose tests on eight subjects showed good correlation with clinical measurements but indicated that physiological factors and person-to-person variability are important. In vitro measurements showed that the sensitivity of the glucose measurement is unaffected by the presence of common blood analytes but that there can be substantial shifts in baseline values. The results indicate the need for spectroscopic data to develop algorithms for the detection of glucose in the presence of other analytes.

Phantom glucose calibration models from simulated noninvasive human near-infrared spectra.

The validity of published reports claiming to have successfully measured in vivo blood glucose from noninvasive near-infrared spectra collected in a time-dependent manner is challenged on the basis of results obtained from a phantom glucose spectral data set. An in vitro model is used to simulate noninvasive human near-IR spectra. The phantom glucose data set is created by purposely omitting glucose in these modeled samples. Glucose values are then assigned to successive phantom glucose spectra, and multivariate calibration models are generated for glucose based on partial-least squares regression. As expected, calibration models are incapable of predicting glucose values when the glucose assignments are made randomly. Apparently functional models are obtained, however, when glucose assignments are made in a nonrandom, time-dependent manner. Prediction errors from these nonrandom models are essentially identical to those published by other as evidence of successful noninvasive blood glucose measurements. Chance temporal correlations between assigned glucose concentrations and some uncontrolled experimental parameter are responsible for this apparent model functionality.