An in vitro tissue model for evaluating the effect ofcarboxyhemoglobin concentration on pulse oximetry

An in vitro tissue model was developed for specific application to noninvasive transmittance pulse oximetry. The model was used to assess the effect of variations in carboxyhemoglobin concentration on noninvasive measurements of arterial hemoglobin oxygen saturation. The predictive nature of this model is important for a better understanding of the limitation of pulse oximetry and for the improved design of pulse oximeters.     

The measurement of oxygen saturation in arterial and venous blood

This article describes about the non-invasive optical measurement techniques to assess oxygen saturation in arterial and venous blood. The pulse oximeters for arterial oxygen saturation measurement use light in two wavelengths, in the red and infrared regions, and calibration is used to account for the difference in optical path-length between them. The accuracy of the commercial pulse oximeters is adequate for monitoring patients during surgical operation, where the clinical information that is needed is the absence of dramatic deterioration in the respiration efficiency. However, the error in pulse oximetry is too high for the clinical assessment of lung function, probably because of the need for calibration in the available technique. The use of two wavelengths in the infrared, instead of one wavelength in the red and one in the infrared region, enables the use of pulse oximetry without calibration. The technique can also be used for determining venous blood saturation, which is important for assessment of the adequacy of tissue blood supply.     

Reflectance pulse oximetry measurements from the retinal fundus

Conventional transmission pulse oximetry is a noninvasive technique for the continuous monitoring of arterial oxygen saturation (SaO₂) from peripheral vascular beds such as the finger tip or earlobe. It is proposed to exploit the unique transparency of the ocular media to make reflectance pulse oximetry measurements on the retinal fundus. This technique potentially offers significant advantages over conventional pulse oximetry, primarily in the ability to monitor cerebral, as opposed to peripheral, oxygen saturation. An in vitro system has been developed to simulate the retinal circulation and ocular optics. This system consists of a flexible cuvette located in a model eye and an extracorporeal blood circuit to simulate arterial blood flow. The system was used to investigate the relationship between SaO₂ and the R/IR ratio in reflectance pulse oximetry. To enable in vivo measurements to be made, a standard haptic contact lens was modified to hold the pulse oximeter probe in front of the pupil. In a preliminary study, the lens was fitted to an awake volunteer and cardiac-synchronous signals were detected by the retinal pulse oximeter     

Simple photon diffusion analysis of the effects of multiplescattering on pulse oximetry

Photon diffusion theory is used to derive analytical expressions that relate the ac-dc intensity ratios measured by transmission-mode and reflectance-mode pulse oximeters to arterial oxygen saturation (SaO2). The effects of multiple scattering are examined by comparing the results of the photon diffusion analysis with those obtained using an analysis based on the Beer-Lambert law which neglects scattering. We show that the difference between the average lengths of the paths travelled by red and infrared photons makes the calibration curve of oximeters sensitive to the total attenuation coefficients of the tissue in the two wavelength bands, as well as to absorption by the pulsating arterial blood. Therefore, the shape of the calibration curve is affected by tissue blood volume, source-detector placement, and other variables that change the wavelength dependence of the attenuation coefficient of the tissue. After evaluating the relationship between SaO2 and the red/IR ac-dc ratio (R) under a variety of physiological conditions, we conclude that, for oximeters utilizing fixed calibration curves based on measurements obtained from normal subjects, errors introduced by interfering variables should be less than a few percent when SaO2 exceeds 70%. Predicted errors at lower oxygen saturation values are substantially greater because R is much more sensitive to interfering variables in this measurement range.     

Pulse oximetry theory and calibration for low saturations

Pulse oximetry is a widely used technique in biomedical optics, but currently available pulse oximeters rely on empirical calibration approaches, which perform poorly at low saturations. We present an exact solution for pulse oximetry and show how this can be used as the basis for the development of a semiempirical calibration approach that may be useful, especially at low saturations and variable probe geometries. This new approach was experimentally tested against traditional empirical calibration techniques on transmission pulse oximetry for monitoring of fetal sheep using a minimally invasive spiral probe. The results open the way for the development of more accurate pulse oximetry.     

Nonlinear filtering for the estimation of glycated hemoglobin inthe presence of fetal hemoglobin using microcolumn ion-exchangechromatography

An improved method based on nonlinear least-squares to estimate the percentage concentration of glycated hemoglobin levels HbA1ab, HbA1c, HbF, and other Hb variants is presented. If the existing method is enhanced with the improved method, the use of microcolumn ion-exchange chromatography for estimating glycated hemoglobin levels even for patients with elevated fetal hemoglobin (HbF) would provide a more realistic estimate     

Esophageal pulse oximetry utilizing reflectance photoplethysmography

Peripheral perfusion is often poor and barely pulsatile in patients undergoing prolonged major surgery. Hence, the arterial blood oxygen saturation (SpO2) readings from commercial finger pulse oximeters can become unreliable or cease when they are most needed. To overcome this limitation, the esophagus has been investigated as an alternative measurement site, as perfusion may be preferentially preserved centrally. A reflectance esophageal pulse oximeter probe, and a processing system implemented in LabVIEW were developed. The system was evaluated in clinical measurements on 49 cardiothoracic surgery patients. The SpO2 values from the esophagus were in good agreement with arterial blood oxygen saturation (SaO2) values obtained from blood gas analysis and CO-oximetry. The means (+/-SD) of the differences between the esophageal SpO2 and SaO2 results from blood gas analysis and CO-oximetry were 0.02 +/- 0.88% and -0.73 +/- 0.72%, respectively. In five (10.2%) of the patients, the finger pulse oximeter failed for at least 10 min while the esophageal SpO2 readings remained reliable. The results confirm that the esophagus may be used as an alternative monitoring site for pulse oximetry even in patients with compromised peripheral perfusion.     

Pulse oximetry: an improved in vitro model that reduces blood flow-related artifacts

Artifacts may occur in many in vitro models of pulse oximetry due to the optical effects of synchronously oriented and/or deformed erythrocytes. Although these artifacts are most likely negligible in living superficial tissues, they are demonstrated to have considerable influence on the calibration curve obtainable from the in vitro simulation of pulse oximetry in such models, especially at low oxygen saturations. Therefore, we have developed a modified in vitro model which reduces the effect of these artifacts. This is achieved by excluding data obtained during pressure transients and by raising the blood flow velocity. As a result, the model more closely approximates in vivo pulse oximetry, particularly under clinically important conditions of low blood oxygen saturation levels.     

In vivo reflectance of blood and tissue as a function of lightwavelength

Light reflectance from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph and the reflectance pulse oximeter. Incident light on the skin travels into the underlying layers and is in part reflected back to the surface. This paper describes the reflectance of light from in vivo tissue for wavelengths in the range from 420 to 940 nm, based on photon diffusion theory and on experimental results from studies of 17 subjects. The results show a minimum reflectance and a peak sensitivity to the blood pulsations in the wavelength range from 510 to 590 nm. Skin pigmentation is seen to attenuate reflectance rather than altering the character of the modulation spectra. Based on the model introduced in this paper, the dependence of modulation spectra on mean blood fractional volume as well as wavelength is also described theoretically, and corroborated by further experimental data at 570 and 630 nm. At these latter wavelengths, the signal-to-noise ratio was calculated for the blood volume pulsation signal in the presence of physiological noise. The median for calculated ratios of reflectance modulation by blood pulsation and ratios of signal to noise between the two wavelengths were 13.1 and 7.5, respectively, for 93 sites in nine subjects. These results are seen to be consistent with the theory.     

Algorithms for estimating oxygen saturation in biological tissues

A noninvasive technique for estimating the venous-blood oxygenation averaged within one period of a pulse wave is developed, and a method for determining the oxygen utilization in tissues from the difference between oxygenation levels of arterial and venous blood is elaborated. The algorithm for estimating the oxygenation level of venous blood is tested experimentally. The data obtained correlate with the results of alternative experiments described in the literature and reproduced in this study.     

Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

The efficient and specific delivery of nanoparticles (NPs) to brain tumors is crucial for successful glioma treatment. Heparin‐based polymers decorated with two peptides self‐assemble into multi‐functional NPs that specifically target glioma cells. These NPs re‐self‐assemble to a smaller size in blood, which is beneficial for in‐vivo brain drug delivery. The hydrodynamic size of one type of these NPs is 63 ± 11 nm under blood‐mimic conditions (10% fetal bovine serum), but it is 164 ± 16 nm in water. Additionally their zeta potential is more neutral in the blood‐mimic conditions. Transmission electron microscopy reveals the morphology of the spherical NPs. In vitro experiments demonstrate that the NPs exhibit a high cellular uptake and the ability to efficiently discourage proliferation, endothelial‐lined vessels, and vasculogenic mimicry. In vivo studies demonstrate that the NPs can by‐pass the normal blood–brain and blood–(brain tumor) barriers and specifically accumulate in glioma tissues; moreover, they present an excellent anti‐glioma effect in subcutaneous/intracranial glioma‐bearing mice. Their superiority is due to their appropriate size in blood and the synergic effect arising from their targeting of two different receptors. The data suggests that these NPs are ideal for anti‐glioma therapy.     

基于光电脉搏波描记方法的多生理参数测量研究

基于单个反射式光电探头,在桡动脉位置测量了脉搏波。利用ATmega16单片机进行660nm和940nm的双波长LED发光控制和数据采集与分析。通过对脉搏波极值的读取实现血氧饱和度和心率的测量;其次,利用时间抽取基2快速傅里叶变换(FFT)对获取的桡动脉信号进行傅里叶变换,实现呼吸频率的测量。测量了10名志愿者的生理参数,并对利用本文设计的系统的测量结果和临床方法记录的结果进行数据的相关性分析,得到血氧饱和度、心率和呼吸频率的相关系数分别为r=0.985、r=0.982和r=0.933。通过相关性分析可以看出,可以利用本文系统进行无创、长时间和多参数的测量。     

NIR‐II Excitable Conjugated Polymer Dots with Bright NIR‐I Emission for Deep In Vivo Two‐Photon Brain Imaging Through Intact Skull

Methods for noninvasive brain imaging are highly desirable to study brain structures in neuroscience. Two‐photon fluorescence microscopy (2PFM) with near‐infrared (NIR) light excitation is a relatively noninvasive approach commonly used to study brain with high spatial resolution and large imaging depth. However, most of the current studies require cranial window implantation or skull‐thinning methods due to attenuation of excitation light. 2PFM through intact mouse skull is challenging due to strong scattering induced by skull bone. Herein, NIR‐II light excitable single‐chain conjugated polymer dots (CPdots) with bright fluorescence in NIR‐I region (peak at ≈725 nm and quantum yield of 20.6 ± 1.0%) are developed for deep in vivo two‐photon fluorescence (2PF) imaging of intact mouse brain. The synthesized CPdots exhibit good biocompatibility, high photostability, and large two‐photon absorption cross section. The CPdots allow 2PF images acquired upon excitation at 800, 1040 and 1200 nm with the highest signal‐to‐background ratio of 208 demonstrated for 1200 nm excitation. Moreover, a 3D reconstruction of the brain blood vessel network is obtained with a large vertical depth of 400 µm through intact skull. This work demonstrates great potential of bright NIR fluorophores for in vivo deep tissue imaging.     

Optical transmission of blood: effect of erythrocyte aggregation

The influence of red blood cell (RBC) aggregation on transparency of blood in the red-near infrared spectral range is investigated. We argue that for relatively thin blood layers the light diffraction on aggregates becomes the dominant phenomenon. The nature of pulsatile changes of blood transparency is explained by pulsations of RBC aggregate size. For another case of over-systolic vessel occlusion the following time evolution of blood transparency strongly depends on light wavelength. This dependence may serve as a basis for an alternative approach to noninvasive blood tests: occlusion spectroscopy. Theoretical results well correspond to both in vivo and in vitro measurements reproducing pulsatile blood flow and long occlusion as well.     

Induced current constraints and capacitance effects in inductivenerve stimulation

A number of studies have reported in vivo and in vitro stimulation of nerves by means of induced currents. We have found that purely inductive stimulation of the frog sciatic nerve and gastrocnemius muscle using unshielded or shielded whole toroids could not be achieved with techniques and EMF intensities and durations consistent with those reported by other investigators. In those instances where stimulation was achieved, our findings suggest that it resulted from capacitive coupling between unshielded toroids and a nerve/grounding electrode. Maximum primary voltages ranged up to 80 V. Corresponding secondary EMF's and pulse durations were as much as 5 V and 100 microseconds, respectively, in different experiments. Stimulating capacitive current densities near the nerve were estimated to be in the range of 100 to 400 mA/cm2, while maximum induced current densities were estimated to be in the range of 10 to 30 mA/cm2 for the same pulse duration.     

Role of Light Scatterng in Whole Blood Oximetry

We investigated the role of light scattering in whole blood oximetry by transmission spectrophotometry. To delineate the role of scattering and absorbance in the measurement of oxyhemoglobin saturation, we applied Twersky's theory of radiation scattering and measured the apparent optical density of whole blood and hemoglobin solutions. The optical density versus hematocrit relationship predicted by Twersky's theory was found to give a good fit to the data obtained at 660, 813, 880, and 940 nm. A semi-empirical variation of Twersky's equation and photon diffusion equations were also compared to the data, and Twersky's original equation was found to give the best fit. Therefore, Twersky's equation was employed throughout the rest of the data analysis. Total scattering effects were shown to be wavelength and oxygenation dependent. Moreover, the relationship between total scattering effects and percent O2 saturation was approximately linear, and it had a greater slope (at 660 nm) than absorbance versus O2 saturation. Thus, scattering effects in the red-infrared range do not detract from the linearity of whole blood oximeters. By contrast, scattering effects increase the sensitivity of oximeters by contributing linearly to the total O. D. change that occurs with altered oxygenation.     

System for the Measurement of Velocity of Microscopic Particles in Liquids

A system for the measurement of velocity of particles suspended in liquids was developed, based on the on-line computation of the time to maximum cross correlation between the optical signatures made by particles, as their image traverses two adjacent photo-detectors aligned in the direction of flow. Cross correlation computation is performed with a commercially available computer, and the time to maximum cross correlation is detected by digital pulse circuitry. The system is particularly suited for measurements of blood flow in vivo and in vitro. Frequency response is linear to 1 Hz where the phase lag is 30°.     

A Weak Signal Extraction Method for Human Blood Glucose Noninvasive Measurement using Near Infrared Spectroscopy

Background interference from optical absorption of matrix components, low spectral selectivity and low spectral sensitivity are the main interference factors for human blood glucose noninvasive measurement using near infrared (NIR) spectroscopy. In order to extract the weak glucose concentration information, a modified uninformative variable elimination (mUVE) method combined with successive projections algorithm (SPA) named as mUVE-SPA, is proposed. mUVE is used to eliminate matrix background and high-frequency noise by wavelet multi-resolution technology. SPA is followed to select variables with minimum colinearity by projection algorithm in a vector space. The proposed method was applied in two NIR spectra data sets (plasma samples experiment in vitro and human blood glucose noninvasive measurement experiment in vivo) respectively. The performance and adaptability of the proposed strategy were discussed. The results indicate that the proposed hybrid method can give an alternative path to extract weak glucose information and yield more parsimonious models with higher precision.     

基于小波分析的光电脉搏波奇异性处理

高精度的光电脉搏波信号,对于动态光谱法血液成分无创检测非常重要。要获得高精度的脉搏波信号,首先就要对信号中的噪声奇异点进行定位和修正。本文选择Marr小波,针对信号中的单个脉冲噪声和窄带脉冲噪声。研究了基于小波分析的光电脉搏波奇异性处理。利用脉搏波信号极大值线的周期性,在每个周期段内,首先利用单个脉冲噪声与有用信号截然不同的李氏指数特性,对单个脉冲噪声进行了处理。然后利用窄带脉冲的小波系数极大值线的特点对常规小波方法难以处理的窄带脉冲噪声进行分析定位。鉴于模极大值重构算法比较复杂,本文利用线性插值法对被定位的噪声奇异点进行了修正。仿真实验表明,利用小波分析和线性插值相结合的方法可以完成对光电脉搏波信号的奇异性处理,提高了脉搏波信号的幅值检测精度。     

Wavelength selection for low-saturation pulse oximetry

Conventional pulse oximeters are accurate at high oxygen saturation under a variety of physiological conditions but show worsening accuracy at lower saturation (below 70%). Numerical modeling suggests that sensors fabricated with 735 and 890 nm emitters should read more accurately at low saturation under a variety of conditions than sensors made with conventionally used 660 and 900 nm band emitters. Recent animal testing confirms this expectation. It is postulated that the most repeatable and stable accuracy of the pulse oximeter occurs when the fractional change in photon path lengths due to perturbations in the tissue (relative to the conditions present during system calibration) is equivalent at the two wavelengths. Additionally, the penetration depth (and/or breadth) of the probing light needs to be well matched at the two wavelengths in order to minimize the effects of tissue heterogeneity. At high saturation these conditions are optimally met with 660 and 900 nm band emitters, while at low saturation 735 and 890 nm provide better performance