Pulse oximetry is one of the most widely used techniques in modern medicine. In pulse oximetry, photoplethysmography (PPG) signals are measured at two different wavelengths and converted into the parameter Gamma, which is used to calculate the oxygen saturation of arterial blood. Although most pulse oximetry sensors are based on transmission geometry, the reflection mode is required for different form factors such as the forehead or wrists. In reflection oximetry, local pressure is applied to the measurement surface. We investigated the relationship between applied pressure and Gamma and found that for the reflection mode, Gamma tends to increase with increasing applied pressure. To explain this, we described the PPG signal in terms of two alternative models: a volumetric model and a Scattering-Driven Model (SDM). We assumed that the application of external pressure results in a decrease in local blood flow. We showed that only SDM correctly qualitatively describes Gamma as a function of the decrease in blood flow. We concluded that both described models coexist and that the relative influence of each depends on the measurement geometry and blood perfusion in the skin.
Pulse oximetry, which is based on photoplethysmography (PPG), has become the standard technique for noninvasive monitoring of arterial oxygen saturation. Pulse oximetry measures arterial blood hemoglobin saturation (SPO2). SPO2 is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin [
The PPG signal is commonly associated with changes in local blood volume. It is assumed that the amount of blood in the illuminated perfused tissue fluctuates at the rate of the heartbeat, as does light transmission or refraction. According to this volumetric model, the periodic changes in blood volume result in changes in the intensity of the measured light. Some studies have questioned the uniqueness of the volumetric model for explaining the origin of the PPG signal. For example, Hocherman and Palti [
In in vitro studies [
Thus, the following question arises: Is it possible to observe the manifestations of RBC aggregation in vivo? Shvartsman and Fine [
Nevertheless, for a pulsating signal in vivo, there is no direct evidence that the aggregation model can be used as at least an additional phenomenon of the PPG if not as an alternative. The aim of this work was to check (a) whether the aggregation model can correctly describe quantitatively the experimentally known Gamma values used in pulse oximetry and (b) whether Gamma is affected by local blood flow.
Diffusion theory for light transmission in tissue is a commonly accepted way to model light propagation in a high-scattering isotropic turbid media such as biological tissue [
The light absorbance of RBCs is a function of oxyhemoglobin and deoxyhemoglobin. Oxygen saturation
The average absorption coefficient is given by the following expression:
The exponential dependence of
The PPG signal is characterized by changes in the intensity of the light after it passes through blood and tissue. The associated pressure waves give rise to periodic changes in the optical properties of the measured blood vessels. However, we are interested in the specific mechanism that causes the changes in the optical properties of the perfused tissue being measured. We considered two different mechanisms that may be responsible for the changes in light intensity as a function of time. One mechanism is called the volumetric model. This is the most accepted model of PPG, whereby during the systolic phase, a pressure wave leads to an increase in blood volume in the tissue. Thus, in equation (
The second, alternative model is known as the scattering-driven model (SDM) whereby the blood pressure wave induces changes in the light-scattering characteristics of blood, most likely through the RBC aggregation-disaggregation mechanism. The changes in RBC aggregation are driven by variations in the shear rate. Formally, we assume that just
To describe the light scattering by RBCs, we used the Mie [
Aggregation of RBCs is approximated by an ellipsoid as the number of RBCs increases.
According to the Mie model, to calculate the scattering cross section, the radius of the sphere,
(a) Scattering coefficient as a function of number of RBCs in the aggregate and (b) reduced scattering as a function of number of RBCs in the aggregate.
In pulse oximetry, the value of SPO2 is determined entirely by Gamma, which is defined as the ratio of the pulsatile (AC) and nonpulsatile (
Next, we called Gamma for the SDM as GammaS and Gamma for the volumetric model as GammaV. The important property of Gamma is that its value is practically unaffected by the local blood volume, blood hematocrit, measurement geometry, and tissue hematocrit. This implies that Gamma has the striking feature of an invariant that depends upon absorption and scattering properties only. Gamma can be converted into SPO2 using an experimentally obtained calibration curve.
To derive an explicit expression for Gamma, we used equations (
Using equation (
For the SDM model,
To calculate Gamma, we chose commonly used wavelengths of 660 and 940 nm and SPO2 = 100%, which approximately corresponds to the normal level of oxygenation of arterial blood. Figures
Gamma dependence on RBC aggregation length for (a) SDM and (b) volumetric model.
The goal of our study was to examine experimentally the behavior of Gamma for two types of measurement geometry: reflection and transmission. The idea was to create conditions under which the average length of RBC aggregates could be increased by changing the local blood flow. A decrease in blood flow velocity should lead to a shift in dynamic equilibrium upon which the average length of the aggregates should increase. We reduced the blood flow velocity by applying pressure. In this way, we investigated the dependence of Gamma on the level of local pressure for several form factors: fingertip (transmission and reflection), wrist, and forehead.
For pulse oximetry, we used a standard optical system that consisted of two LEDs at 660 and 940 nm and a photodetector (PD) with an amplifier. The digitized signal was stored in a computer for further processing and analysis. Inflatable silicone cushions were used to create local pressure (Figure
Measurement setup for reflection and transmission.
The pressure level in the cushions was set using a pressure controller, which was managed by software on the computer. The difference between the pressure in the cushion and the pressure applied to the skin was taken into account [
(a) Curved surface of the tissue (finger). (b) Flat surface of the tissue (forehead).
Figure
Gamma as a function of applied pressure at different locations for reflection geometry. Squares: fingertip; triangles: forehead; circles: wrist. Filled and open symbols indicate the two sets of measurements taken at the different locations.
Figure
Gamma as a function of applied pressure on the finger for transmission (dashed lines) and reflection (solid line) geometry. Right ordinate axis is the applied pressure, and the green line is the pressure as a function of time (in torr).
We analyzed different possible causes of the dependence of Gamma on the pressure applied. For reflection geometry, one can speculate that applied pressure may induce the so-called crosstalk effect. In other words, the external pressure applied to the tissue “squeezes” the blood out of the capillaries of the dermis, which leads to direct leakage of the specular component of light from the LED to the detector. To test this assumption, we made the following assessment: assume that the increase in the baseline of the PPG signal (DC component) as the pressure increases is entirely due to crosstalk. In this case, the effect of crosstalk on the Gamma value should be maximal. To obtain the measured Gamma value caused by the alleged crosstalk, we substituted the experimentally measured change in the DC for the red
These changes are due to the applied pressure. We found that the measured changes in Gamma were significantly greater than those estimated by equation (
We explained our experimental results for reflection geometry by assuming that the applied pressure results in a decrease in blood flow velocity and shear rate in the arteriole vessels. Following this process, the dynamic balance between the formation and the destruction of aggregates shifts toward longer aggregates. According to the prediction of the SDM, Gamma should increase, as was observed in our experiments.
However, a similar effect is not observed in transmission geometry. This is explained by the significant connection between vessel diameter and shear rate forces. Relatively large arteries with diameters between 150 and 242
It should be noted that the Gamma values were calculated completely based on the basic properties of red blood cells, including their size and aggregability. It is noted in the literature that the readings of pulse oximeters for sickle-shaped anemia patients, in which both the form of red blood cells and the ability to aggregate are distorted, give systematic deviations [
In summary, we showed the dependence of Gamma on the pressure applied to blood vessels in pulse oximetry. The experimental result was explained by applying a model in which the pulsatile changes in the intensity of the reflected light result from the variations in the average size of RBC aggregates. The average aggregate size at each instant of time depends on the size of the vessel and the speed of blood flow. Both volumetric and aggregation models of the PPG signal yield similar Gamma values for small aggregates. With increasing aggregate length, the behavior of Gamma differs between the two models. Therefore, we assumed that the two underlying mechanisms of the PPG signal are superimposed. The relative contribution of each of these mechanisms may depend on the form factor, measurement geometry, and blood flow conditions.
The raw PPG data used in this study are available from the corresponding author upon request.
The authors have no relevant financial interests in the manuscript and no other potential conflicts of interest.