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

Abstract

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.

Raman Spectroscopy of Blood and Blood Components

“…225,226 It was later shown that this approach was highly sensitive to an individual's peripheral microcirculation 227,228 and the test subject's hemoglobin concentration. 229 Much of the early work on the in vivo analysis of hemoglobin oxygenation for surgical applications was carried out by Torres Filho et al They reported the utility of UV-RRS for the simultaneous identifications of oxyhemoglobin and deoxyhemoglobin in the microvessels of a living rat using a single excitation wavelength (406.5 nm in one study, 230 and 532 nm in another 231 ). When the rat's hemoglobin saturation (as measured by a commercial oximeter) was <1% (deoxygenated) or >98% (oxygenated), a single Raman peak was observed.…”

Noninvasive Glucose Sensing with Raman Spectroscopy

“…In a recent report, 24 the difference spectrum between pressed and unpressed phases was interpreted as the whole blood spectrum. Each spectrum was obtained with excitation power ~31 mW and integration time ~100 seconds.…”

“…17 With the advent of high quantum efficiency CCD detectors and holographic diffractive optical elements, researchers have increasingly employed CCD-based dispersive spectrometers. 3,[18][19][20][21][22][23][24] The advantages of dispersive NIR Raman spectroscopy are that compact solid-state diode lasers can be used for excitation, the imaging spectrograph can be f-number matched with optical fibers for better throughput, and cooled CCD detectors offer shot-noise limited detection.…”

“…Chaiken et al 24,36,37 proposed using Raman spectroscopy to measure glucose in vivo with a technique called "tissue modulation," i.e., continuously press/unpress the measurement site with a mechanical apparatus. The basic principle is that during the "press" phase, blood is expelled from the measuring site and thus the spectrum is considered as nearly devoid of blood.…”

Blood equivalent phantom vs whole human blood, a comparative study

“…Novel optical measurement [1][2][3][4] and imaging [5][6][7][8][9] methods for biomedicine require preclinical optimization and calibration. Such calibration is performed on standardized phantoms -simpli¯ed physical models of tissues.…”