Prediction of plasma hemoglobin concentration by near-infrared spectroscopy

The estimation of plasma hemoglobin concentration (Hb) is among one of the daily activities in the practice of clinical anesthesiology. The near-infrared spectroscopy of the brain (rSO(2)) represents a balance between cerebral oxygen delivery and consumption. This study was designed to assess the value of rSO(2) in the prediction of the Hb level while other variables were mathematically controlled. Thirty healthy adult patients undergoing spine surgery, expected to have a moderate degree of intraoperative bleeding, were enrolled in this study. General anesthesia was given and ventilation was mechanically controlled. Measurement of Hb and PaCO(2) were performed at random periods of time. We obtained a total of 97 data combinations for the 30 study patients. The Hb was regressed by independent variables including rSO(2) and PaCO(2). A multilinear regression analysis was performed and the final regression equation was expressed only with statistically significant variables. The measured Hb was tightly regressed with three variables. The final regression equation was Hb=+8.580+0.238.rSO(2)-0.338.PaCO(2)-0.004.anesthetic exposure duration (Tmin) (p=0.000, r(2)=0.809). Near-infrared spectroscopy was shown to be a valuable predictor of plasma Hb in the clinical anesthesiology setting.     

The indirect estimation of hemoglobin concentration in whole blood.

The present conventional methods for determination of Hemoglobin (Hb) concentration in whole blood depend on the direct colorimetric measurement of chemically modified Hb following its release from red cells by lysis. This paper examines an alternative, indirect method which does not require initial red cell lysis, corrects for the falsely elevated Hb due to the lipemic plasma and determines whether elevated WBC count effects a change in the Hb value, without the tedious laboratory manipulations currently required to correct for these artifacts. The method is simple, uncomplicated and is based on the observation of a constant ratio (2.98) between the Mean Corpuscular Volume (MCV) and the Mean Corpuscular Hemoglobin (MCH) indices obtained from standard electronic counters in use in most laboratories. The Hb concentration is calculated by the equation: [formula: see text]. The resultant Hb measurements show an acceptable degree of accuracy and precision when compared with the direct measurements obtained from a Coulter Model S + I, even in the presence of a high WBC or lipid.     

The use of Fourier-transform infrared spectroscopy for the quantitative determination of glucose concentration in whole blood

Fourier-transform infrared transmission spectroscopy has been used for the determination of glucose concentration in whole blood samples from 28 patients. A 4-vector partial least-squares calibration model, using the spectral range 950-1200 cm(-1), yielded a standard-error-of-prediction of 0.59 mM for an independent test set. For blood samples from a single patient, we found that the glucose concentration was proportional to the difference between the values of the second derivative spectrum at 1082 cm(-1) and 1093 cm(-1). This indicates that spectroscopy at these two specific wavenumbers alone could be used to determine the glucose concentration in blood plasma samples from a single patient, with a prediction error of 0.95 mM.     

Changes in hemoglobin concentration in the lateral occipital regions during shape recognition: a near-infrared spectroscopy study

By using near-infrared spectroscopy (NIRS), we measured the changes in the oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb, respectively) concentrations while performing visual tasks. We conducted experiments using two tasks: a shape recognition task and a position recognition task. It was found that the oxy-Hb concentration was substantially higher in the lateral occipital regions during shape recognition than during position recognition. The changes in the oxy-Hb concentration were considered to reflect the activation difference between the two tasks. No difference was observed in the oxy-Hb concentration during the memorization of shape and memorization of position. The deoxy-Hb concentration was different between the two tasks only when different stimuli were used but not when identical stimuli were used. In addition, it was suggested that the deoxy-Hb concentration is more sensitive to activation difference between the hemispheres and the activation at some regions. Measurements of the oxy-Hb and deoxy-Hb concentrations would reflect different aspects of cortical activations. The present results showed that measuring the oxy-Hb and deoxy-Hb concentrations separately can differentiate the activation of the regional cortical functions.     

Direct measurements of blood glucose concentration in the presence of saccharide interferences using slope and bias orthogonal signal correction and Fourier transform near-infrared spectroscopy

Saccharide interferences such as Dextran, Galactose, etc. have a great potential to interfere with near infrared (NIR) glucose analysis since they have a similar spectroscopic fingerprint and are present physiologically at large relative concentrations. These can lead to grossly inappropriate interpretation of patient glucose levels and resultant treatment in critical care and hospital settings. This study describes a methodology to reduce this effect on glucose analysis using an NIR Fourier transform spectroscopy method combined with a multivariate calibration technique (PLS) using preprocessing by orthogonal signal correction (OSC). A mathematical approach based on the use of a single calibration based bias and slope correction was applied in addition to a standard OSC was investigated. This approach is combined with a factorial interferent calibration design to accommodate for interference effects. We named this approach as a slope and bias OSC (sbOSC). sbOSC differs from OSC in the way it handles the prediction. In sbOSC, statistics on slope and bias obtained from a set of calibration samples are then used as a validation parameter in the prediction set. Healthy human volunteer blood with different glucose (80 to 200 mg/dL) and hematocrit (24 to 48 vol.%) levels containing high expected levels of inteferents have been measured with a transmittance near-infrared Fourier transform spectrometer operates in the broadband spectral range of 1.25-2.5 μm (4000-8000 cm(-1)). The effect of six interferents compounds used in intensive care and operating rooms, namely Dextran, Fructose, Galactose, Maltose, Mannitol, and Xylose, were tested on blood glucose. A maximum interference effect (MIE) parameter was used to rank the significance for the individual interferent type on measurement error relative to the total NIR whole blood glucose measurement error. For comparison, a YSI (Yellow Springs Instrument) laboratory reference glucose analyzer and NIR data were collected at the same time as paired samples. MIE results obtained by sbOSC were compared with several standard spectral preprocessing approaches and show a substantial reduced effect of saccharide interferences. NIR glucose measurement results are substantially improved when comparing standard error of prediction from validation samples; and resulting MIE values are small.     

Total exchange transfusion in rats with hemoglobin solutions: influence of hemoglobin concentration

In most published studies of the oxygen transport capacity of hemoglobin solutions for total or partial replacement transfusions, the hemoglobin concentrations have been in the order of 70 g/l. In this study we tried to identify the hemoglobin concentration that would give the best survival in rats at zero hematocrit. The longest survival time, of more than 4 h, was obtained with a hemoglobin concentration of 125 g/l, despite an oncotic pressure much higher than that of plasma. This observation suggests the use of more highly concentrated solutions of modified or unmodified hemoglobin than are presently recommended, in order to increase their oxygen transport capacity.     

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.     

Comparison of three methods to measure absolute cerebral hemoglobin concentration in neonates by near-infrared spectrophotometry

Three methods by which to determine absolute total cerebral hemoglobin concentration (tHb in micromol/L) by near-infrared spectrophotometry (NIRS) have evolved: (1) tHbo, requiring oxygenation changes and arterial oxygen saturation measurements as a reference using a relative NIRS algorithm, (2) tHbg, using a geometrical multidistance principle and (3) tHbgo, a combination of both. The aim of this study was to compare the three methods quantitatively. Sixteen clinically stable preterm infants with a mean gestational age of 29.6 (range of 25.1-36.4) weeks, birthweight of 1386 (680-2820) g and a postnatal age of 2.5 (0.5-6) days, who needed supplemental oxygen, were enrolled. The mean+/-standard deviation tHbg was 150.2+/-41.8 micromol/L (range of 61.6-228.9 micromol/L), the tHbo was 62.1+/-27.2 micromol/L (26.0-110.8 micromol/L) and the tHbgo was 89.3+/-45.6 micromol/L (26.5-195.9 micromol/L). The correlation coefficient among the three methods were tHbg and tHbgo r=0.736; tHbo and tHbgo r=0.938; tHbg and tHbo r=0.598. A multiple regression with variable selection by Mellow's C(p) showed, that tHbg was correlated to the birthweight, the postnatal age, the heart rate and the pCO2 (r(2)=0.588), tHbo and tHbgo were associated with the hemoglobin concentration in the blood, the mean arterial blood pressure and the pCO2 (r(2)=0.493 and 0.406, respectively). The three methods (tHbg, tHbo, and tHbgo) give systematically different tHb readings and large intersubject variability.     

Correlation of functional and resting state connectivity of cerebral oxy-, deoxy-, and total hemoglobin concentration changes measured by near-infrared spectrophotometry

The aim is to study cerebral vascular functional connectivity during motor tasks and resting state using multichannel frequency-domain near-infrared spectrophotometry. Maps of 5.7 × 10.8 cm size displaying changes in cerebral oxyhemoglobin (O(2)Hb), deoxyhemoglobin (HHb), and total hemoglobin (tHb) concentrations were measured in the motor cortex in 12 subjects (mean age of 28.8±12.7 yrs) during resting state and during two palm squeezing tasks with different timing. For each condition, phase plane plots, cross correlation functions, and connectivity indices were generated for O(2)Hb, HHb, and tHb. The amplitude of the concentration changes in O(2)Hb and HHb depends on the age of the subject. We found large regions of connectivity, which were similar for resting state and task conditions. This means the spatial relationships during resting state, when changes in O(2)Hb, HHb, and tHb corresponded to spontaneous oscillations, were correlated to the spatial patterns during the activation tasks, when changes in O(2)Hb, HHb, and tHb concentration were related to the alternation of stimulation and rest. Thus, the vascular functional connectivity was also present during resting state. The findings suggest that the vascular response to functional activation may be a nonlinear synchronization phenomenon and that resting state processes are more important than previously expected.     

Facilitated diffusion of carbon dioxide in whole blood and hemoglobin solutions

The values of effective permeability (Krogh's diffusion coefficient) for carbon dioxide have been measured in horizontal stationary layers of whole blood and hemoglobin solutions in quasi-steady state, with the goal of understanding the specific nature of facilitated diffusion of carbon dioxide occurring in these media. The average partial pressure of carbon dioxide within the layer ranged from 0.74 kPa (5.6 mm Hg) to 15.7 kPa (118 mm Hg). Facilitation effects were significant in hemolysed blood and in hemoglobin solutions at low pCO₂; the facilitation factor was up to 2.3. Facilitation effects were considerably less for intact blood; the facilitation factor of intact blood with hematocrit 45% was 0.3. The presence of the red cell membrane appears to have a negative effect on facilitation of carbon dioxide transport.     

Online monitoring of urea concentration in dialysate with dual-beam Fourier-transform near-infrared spectroscopy

The robustness of a dual-beam, optical null, Fourier-transform near-infrared (FTNIR) spectrometer was investigated by means of online, near-infrared measurements and predictions of urea concentrations in spent dialysate during hemodialysis treatment. Simple multivariate calibration using a few factors based on a small number of prepared samples provided stable and accurate predictions over a period of 1 month. The calibration was robust when faced with adjustment of reference cell intensity and did not require a daily measured reference spectrum. The root-mean-square error of prediction of urea was 0.4 mM based on a two-factor partial least-squares regression model.     

Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range

The optical parameters absorption coefficient, scattering coefficient, and the anisotropy factor of platelets (PLTs) suspended in plasma and cell-free blood plasma are determined by measuring the diffuse reflectance, total and diffuse transmission, and subsequently by inverse Monte Carlo simulation. Furthermore, the optical behavior of PLTs and red blood cells suspended in plasma are compared with those suspended in saline solution. Cell-free plasma shows a higher scattering coefficient and anisotropy factor than expected for Rayleigh scattering by plasma proteins. The scattering coefficient of PLTs increases linearly with the PLT concentration. The existence of physiological concentrations of leukocytes has no measurable influence on the absorption and scattering properties of whole blood. In summary, red blood cells predominate over the other blood components by two to three orders of magnitude with regard to absorption and effective scattering. However, substituting saline solution for plasma leads to a significant increase in the effective scattering coefficient and therefore should be taken into consideration.     

Enhancing effect of cerebral blood volume by mild exercise in healthy young men: a near-infrared spectroscopy study

A mechanism by which exercise improves brain function may be attributed to increase in cerebral blood volume (CBV) with physical activity. However, the exact exercise intensity that influences CBV is still uncertain. To clarify this issue, 10 healthy young male participants were asked to perform a graded cycling exercise to the point of exhaustion while their prefrontal cortex CBVs are being monitored using near-infrared spectroscopy. Overall responsive cerebral oxygenation showed a non-linear pattern with three distinct phases. The CBV-threshold (CBVT), an event where rapid oxygenation takes place, occurred at approximately 42% of the V O2max. The CBVT preceded the lactate threshold (LT), which was at approximately 55% of the V O2max. The V O2max was not predictive of the CBVT in among the subjects. Our results indicate that oxygenation of the prefrontal cortex increases during graded cycling even at exercise intensities below the LT, suggesting the potential role of mild exercise in enhancing CBV.     

Clearance, distribution volume, and dialyzer mass area transport coefficient of glucose in whole blood

The extracorporeal transport of glucose was studied to determine the dialyzer mass transfer coefficient K(0)A for glucose in whole blood under conditions of glucose delivery and glucose removal. Glucose was removed from blood or delivered to blood using glucose-free dialysate or dialysate with a glucose concentration of 200 mg/dl (11.1 mmol/L). FX8 dialyzers (Fresenius Medical Care, Bad Homburg, Germany) were studied at constant dialysate flow Q(d) (500 ml/min) and variable blood flows Q(b) (200, 300, and 400 ml/min) under countercurrent flow conditions in a series of laboratory bench studies. Glucose clearance K(d) and glucose distribution volume flow rate Q(e) were determined from glucose mass balance. In 32 studies done with bovine blood at different hematocrit levels glucose was calculated to distribute in plasma water and to be excluded from red cell water when passing the FX8 dialyzer. The dialyzer mass transfer area coefficient K(0)A for glucose computed from Q(e), Q(d), and K(d) was 301.6 ± 45.2 ml/min and not different between modes of glucose delivery or glucose removal but lower than expected from the diffusivity of glucose estimated for aqueous solutions.     

Preliminary evaluation of optical glucose sensing in red cell concentrations using near-infrared diffuse-reflectance spectroscopy

Bacterial contamination of blood products is one of the most frequent infectious complications of transfusion. Since glucose levels in blood supplies decrease as bacteria proliferate, it should be possible to detect the presence of bacterial contamination by measuring the glucose concentrations in the blood components. Hence this study is aimed to serve as a preliminary study for the nondestructive measurement of glucose level in transfusion blood. The glucose concentrations in red blood cell (RBC) samples were predicted using near-infrared diffuse-reflectance spectroscopy in the 1350 to 1850 nm wavelength region. Furthermore, the effects of donor, hematocrit level, and temperature variations among the RBC samples were observed. Results showed that the prediction performance of a dataset which contained samples that differed in all three parameters had a standard error of 29.3 mg/dL. Multiplicative scatter correction (MSC) preprocessing method was also found to be effective in minimizing the variations in scattering patterns created by various sample properties. The results suggest that the diffuse-reflectance spectroscopy may provide another avenue for the detection of bacterial contamination in red cell concentrations (RCC) products.     

Error in noninvasive spectrophotometric measurement of blood hemoglobin concentration under conditions of blood loss

This paper discusses a current misinterpretation between different parameters of hemoglobin concentration measurement and its amplification under conditions of blood loss. The paper details the distinction between microcirculatory hematocrit and the hematocrit of the macrocirculation to analyze clinical use of real-time patient hemoglobin concentration measurement by noninvasive point-of-care devices such as the Rainbow Pulse CO-Oximetry™ (Masimo Corp., Irvine, CA). The hemoglobin concentration or hematocrit values have clinical significance such as for diagnosing anemia or as indicators to when a blood transfusion is needed. The device infers hemoglobin concentration from spectrophotometry of the fingertip and therefore the measured absorption is due to hemoglobin present in capillaries as well as in larger vessels, and the device accordingly reports the hemoglobin concentration as ‘total hemoglobin’ in a proprietary SpHb parameter. SpHb and macro hemoglobin concentration are different parameters. However, the numerical resemblance of SpHb values to values of macro hemoglobin concentrations, combined with the widely used unspecified term “Hb” in the medical setting, suggests that SpHb values are often interpreted by the clinician as macro hematocrit values.The claim of this paper is that under conditions of blood loss the portion of the SpHb total hemoglobin measure that is contributed from microcirculation increases, due to the decrease of macro hematocrit while microcirculatory hematocrit remains constant when above a critical value. The device is calibrated from phlembotomy drawn blood (from a vein in the arm), which is the gold standard in blood collection, and hence this changing contribution of microcirculatory hemoglobin to the SpHb value would distort the gap between macro hemoglobin and total hemoglobin, SpHb. The hypothesis is that if clinicians indeed interpret the SpHb values as macro hemoglobin values then there is an unreported discrepancy between SpHb to macro hemoglobin concentrations during blood loss due to the increasing effect of microcirculatory hemoglobin measurement on the mixed parameter, SpHb.