Feasibility study for the non-invasive blood pressure estimation based on ppg morphology: normotensive subject study
© The Author(s) 2017
Received: 6 June 2016
Accepted: 19 December 2016
Published: 10 January 2017
Blood pressure is a critical bio-signal and its importance has been increased with the aged society and the growth of cardiovascular disease population. However, most of hypertensive patients have been suffered the inconvenience in monitoring blood pressure in daily life because the measurement of the blood pressure depends on the cuff-based technique. Nowadays there are many trials to measure blood pressure without cuff, especially, photoplethysmography (PPG) based research is carried out in various ways.
Our research is designed to hypothesis the relationship between vessel wall movement and pressure-flow relationship of PPG and to validate its appropriateness by experimental methods. PPG waveform is simplified by approximate model, and then it is analyzed as the velocity and the acceleration of blood flow using the derivatives of PPG. Finally, we develop pressure index (PI) as an estimation factor of blood pressure by combining of statistically significant segments of photoplethysmographic waveform.
Twenty-five subjects were participated in the experiment. As a result of simulation, correlation coefficients between developed PI and blood pressure were represented with R = 0.818, R = 0.827 and R = 0.615 in systolic blood pressure, pulse pressure and mean arterial pressure, respectively, and both of result showed the meaningful statistically significance (P < 0.05).
Current study can estimate only the relative variation of blood pressure but could not find the absolute pressure value. Moreover, proposed index has the limitation of diastolic pressure tracing. However, the result shows that the proposed PI is statistically significantly correlated with blood pressures, and it suggests that the proposed PI as a promising additional parameter for the cuff less blood pressure monitoring.
KeywordsPhotoplethysmography (PPG) Derivative photoplethysmography Systolic blood pressure Pulse pressure Vessel wall movement
Arterial blood pressure (ABP) is a very important clinical parameter, and numerous attempts have been made for continuous non-invasive measurements of ABP. The term of blood pressure (BP) usually refers to brachial arterial pressure because major vessels are located on the upper left or right arm to take blood away from the heart, moreover brachial pressure measurement has an advantage of non-invasive measurement. BP waveform analysis and synthesis have been investigated from BP and flow analysis, and it is the general consensus that BP waveform is consisted with the combination of the incident wave transmitted directly from the left ventricle to the finger and the reflected wave from the sites of impedance mismatch mainly in lower body [1, 2].
Several observations demonstrate that the amplitude and timing of wave reflections are directly related to the elastic properties of the arterial tree, stiffness index and time delay between the incident and reflected wave peaks are an example to estimate arterial stiffness . The contour of the ascending aortic pressure wave has been classified by analyzing the reflected wave amplitude and temporal characteristics [4–6]. These classifications, however, are in close agreement with the age-related four classes of photoplethysmography (PPG) contour . Moreover, it was demonstrated the age-related trend towards PPG contour triangulation , and showed the similar shape changes compared with the pressure wave. These results imply that PPG contour is dominantly controlled by pressure waveform, and contains cardiovascular information which includes vessel stiffness and BP.
Morphological analysis of PPG has been applied in vascular assessment such as vascular disease [9–11], aging [7, 8, 12, 13], and arterial compliance . Though PPG morphologies have been provided abundant information for cardiovascular analysis, it is difficult to find literatures of BP estimation method performed by PPG morphology characteristic analysis. In most of previous researches, PPG has been used for BP measurement, not as a separated method of its waveform characteristics, but as a tool for the detection of blood volume change related to other devices in specific conditions.
PPG-based non-invasive BP monitoring may be a promising, however, it has not allowed for the clinical application at this time because there still are lacking points for estimation BP from PPG . Most of PPG-based BP estimations were based on surrogate pulse measures of BP, which includes tracking beat-to-beat changes in pressure using the pulse transit time (PTT) [16–20] or pulse arrival time (PAT) [21–23] and PTT or PAT was usually calculated between the ECG-R wave and the foot of the PPG waveform for analysis. In recent research which based on deep belief network restricted Boltzmann machine (DBN-RBM), PPG-based BP estimation shows inadequate performance in BP estimation from intrinsic variability and wide limits of agreement . Another research, which estimates BP by combining PTT and various PPG morphology characteristic such as PTT, time ratio of systole to diastole, area ratio of systole to diastole, time span of PPG cycle and diastolic duration, combined analysis, confirmed that the morphological characteristic could improve the accuracy of BP estimation. However, it also contains clinically significant errors .
Modified volume-oscillometric technique [25, 26] and hydrostatic method  is another BP estimation technique based on PPG sensor and two micro-electro mechanical systems (MEMS) accelerometers. Finapres™ (FINger Arterial PRESsure) and Portapres™ technology, which are regarded as a representative PPG-based BP measurement method [28, 29], provides continuous non-invasive BP recording from finger and is widely used, however it substantially measures BP not by PPG waveform but by volume-clamp method. Finger pressure is actually measured by finger cuff, and PPG is used as an auxiliary device to check whether blood volume is changed or not.
Because PPG waveform means the amount of blood in measuring spot and amount of blood is closely related to blood flow, PPG waveform should be influenced by pressure waveform which generates flow. Moreover, many of PPG applications are related to the angiological analysis of blood vessel . From these characteristics of PPG, in this literature, we postulated that PPG could contain BP index and it may be related to blood vessel movements. In investigating blood vessel movement and PPG waveform, first derivative and second derivative PPG was applied to consider of flow-pressure relationship. It was proposed the first derivative-based flow waveform derivation method  and demonstrated derived flow has a very similar shape compared with Doppler flow waveforms . Second derivation PPG, usually referred as the second derivative of the photoplethysmogram waveform (SDPTG) , means the acceleration of blood volume changes, and it means instantaneous power of blood circulation.
The proposed method aims to enhance BP estimation from PPG by using analyzing of PPG morphology and inspection of BP-related features. Our study was designed to (1) analyze first and second derivative PPG waveform and find the meaning of the hemodynamic changes, (2) set up the proper model to extract pressure-related parameters, and (3) assess whether derived indexes can help to identify measured BP with experimental data.
Generally, PPG was measured the reflected or transmitted signal at a minute spot, in other words pressure gradient could be approximated with the derivative of pressure in PPG measurement. Moreover, it has been regarded as the second derivative as acceleration PPG and it implies the rate of change of pressure components in PPG . To validate of derivative characteristics and BP relationship, modeling and evaluation was performed by approximated modeling, derivative analysis and experimental assessment in order.
Vessel wall movement and approximated model
According to blood flow, blood vessel wall moves. It was observed by Doppler method that pulsatile flow, which is generated by heart cycle, directly affect vasoconstriction and vasodilatation . The blood vessel is an elastic tube. Thus, inner volumes and vessel diameter could be varied by pressure gradients. Figure 1c–h represents vessel wall movement and pressure difference of the input (Pi), measurement spot (Pm) and output (Po). The systolic pressure is propagated to vessel in the early-systole period (Fig. 1c), and blood volume increases rapidly because pressure difference is large between Pi and Pm. Blood volume is also increased in the late-systole period (Fig. 1d), however the blood volume change rate is decreased by the diminishing of the pressure gradients. Figure 1e, f shows early-diastole and late-diastole vessel wall movement respectively. In early-diastole, the pressure gradient is increased between Pm and Po, and rapid outflow is occurred. Outflow is diminished by decreasing of the pressure gradient between Pm and Po. Figure 1g, h shows that effect of the reflected wave. Po is increased by reflected wave, and it causes the decrease of output pressure gradients. This change suppresses output flow, thus increasing of blood volume at measurement spot. Pressure gradient inversion causes late-upward peak as the case may be (Fig. 1g). Multiple reflect waves are successively arrived, and Po and blood volume are fluctuated by each wave in late-reflection period (Fig. 1h). In the approximated model, late-reflection period is ignored.
Section information and physical meaning for each section
Rate of bold volume change
BP is closely related with outward pressure in the vessel, and it is discriminated with propagated pressure in axial direction. Pi, Pm and Po reflect systolic pressure in axial direction, exerted pressure by the walls of blood vessels and diastolic blood pressure (DBP) respectively. Especially, Pm is affected by not only the systolic blood pressure (SBP), but also the pulse pressure (PP) which means the difference of the SBP and DBP. Pi, Pm and Po could be described by derivative method. Period A–D′ in Fig. 1 completely corresponds to derivative section PPi–NPr. From Table 1, NNi section is composed with both the end of systolic effect which related on SBP and the start of the reflected wave effect. This contains the two important points. First, NNi section is composed with both systolic activity (incident wave) and reflected wave, and NNi section is defined by the reflected wave arrival time, which related on angiological parameter such as arterial stiffness and total peripheral resistance, which is closely related to BP change. From the previous study, it is already demonstrated that the reflected wave arrival time is closely related to the vascular characteristics, including pressure-related factors [36–38]. Considering that these characteristics, it is possible to analyze that the NNi section more close to the BP with reflected wave arrival time, especially SBP and PP than any other sections.
PPG was measured by MP150 (Biopac™ Inc., USA) on left index finger by TSD100B, plethysmography transducer. Omron HEM-907 was used for BP measurement. PPG measurement system includes a 0.05 Hz single pole roll-off high pass filters, 10 Hz low pass filter and 60 Hz notch filter for noise reduction. Amplifier specification is as follows; output range: ±10 V, noise voltage: 0.5 µVrms.
Every data was measured in the supine position. Both PPG and BP were measured at the left hand, and BP was measured before and after PPG measurement. After BP measurement cuff was removed to prevent any occlusion of vessel. Before signal acquisition, every subject had 5-min relaxation period in the supine position to allay subject’s excitations. PPG was measured with 5-min length, and BP was measured before and after PPG measurement and averaged. MATLAB 2008b (The MathWorks, Inc., Natick, MA, USA) and SPSS (ver. 12.0, SPSS Inc., IL, USA) was used for signal analysis and statistical analysis respectively.
Sectionization by derivatives
Before sectionization, preprocessing, feature detection and pulse shape extraction were carried out. In preprocessing stage, PPG waveform was filtered using 2nd order Butterworth bandpass filter which passband is 0.5–10 Hz to remove high-frequency noise and low-frequency noise like motion artifact or respiratory movement noise. Then, we used adaptive threshold peak detection method for feature detection . Because those sections are defined within pulse duration and that pulse duration is based on a maximum diastolic point, we detected lower peaks of PPG waveform before dividing sections.
From the analytical results, it was appeared that (1) sectional ratio of NNi is statistically significantly related on BPs such as SBP and PP, but the relationship was not found in other section, (2) proposed PI is statistically significantly correlated with BPs, and it reflects SBP and PP more than other pressures. These results correspond with our hypothesizes respectively: NNi section dominantly reflects SBP and PP, and the combination of incident and reflected wave morphology is affected by BP. NNi length tended to show shorter sectional length by increasing of SBP and PP. From Fig. 1 and Table 1, NNi is defined by ‘decrease blood volume’ and ‘decrease blood volume change velocity’. These mean that the period of NNi is started at the moment that outflow becomes more than inflow and is finished the moment that the outflow velocity is decreased by opposite pressure wave. Here, the moment that the amount of outflow excess inflow could be happened at the maximum systolic pressure and an opposite pressure wave which decreases the outflow velocity could be regarded as a reflected wave. Therefore, it could be postulated that NNi indirectly reflects the time interval between maximum systolic pressure and that the reflected wave becomes effective.
Correlation coefficient between each segment and pressures
In DBP case, suggested method could not show statistically significance results. BP estimation of this paper is based on an approximated model which consists of single incident and reflected wave. Here, incident and reflect wave is naturally generated by the pulsatile activity of heart and peripheral reflection. In other words, there is a little ambiguity in DBP estimation using pulsatile components because pulsatile is more closely related to the systolic activity than diastolic activity. Therefore, in this literature, the correlation value of DBP was not high compared with the correlation value of SBP.
The purpose of this research is for the intermittent use of BP estimation rather than continuous BP monitoring. Therefore, we randomly sampled individual pulses of signal which recorded in resting condition, then compared estimated pressure-related values with average BP of pre- and post-recording. It means that the proposed method is focused on the tendency of BP but it is not validated in analyzing the respiratory variability which is observed in continuous BP monitoring.
This study has other important limitations, however, mostly stemming from its small subject size. PPG morphology could be affected by not only BP, but also aging , vessel stiffness [41, 42], cardiovascular diseases and other hemodynamic properties. Moreover, it could be varied by vasoactive drugs or endothelial function [3, 43]. Especially, factor which closely related to the arterial stiffness needs to be investigated sophisticatedly because it could effect on the wave reflection; therefore, much larger sample set including a wide range of age and BP would be needed in the future research. In Allen’s review, we can find the various factors in changing PPG morphology . In this literature, we only focused on the macroscopic morphology of PPG waveform based on reflected wave analysis. Reflected wave naturally includes the angiological characteristics like vessel stiffness, and this approach may have a meaning as a simple approach to BP. However, this approach not yet provide a sophisticated estimation for the separated analysis of various subject’s physiological characteristics. For example, subjects who have the cardiovascular diseases and receive vasoactive drugs were excluded in this paper. Therefore, proposed method may not be adaptable to cardiac and vascular patients, and it should be solved by detailed and specified parameter centered experiment such as patient group test pharmacological test.
Also, the morphology of PPG waveform could vary due to other physiological factors, such as spring clip pressure, cardiac output, airway pressure, venous pressures and fluid responsiveness. Changes of photoplethysmographic morphology could be interpreted in terms of earlier arrival of a pressure wave reflected from the peripheral circulation [7, 12]. Therefore, it should be studied about the interaction between reflected wave and variation factors for practical application using the proposed index in the future works.
Results from the present study highlight the PPG morphological analysis based on pressure-flow relationship and correlation analysis between BP and derived parameter. It is appeared that proposed estimation index is statistically significantly correlated (P < 0.05) with SBP (R = 0.826), PP (R = 0.852) and MAP (R = 0.601). This is a novel study to analyze between PPG morphology and BP without any other assistive devices, and it may be applied to further researches based on PPG and BP analysis. Unfortunately, current study could not explain clearly to the DBP and which pressure component would most suitably be estimated using the technique. Moreover, this study has some insufficiency to use in practice, which is stemmed from a limited subject group. However, we expect that this study could be an effective way of BP estimation by additional angiological and pharmacological experiment. Currently, cuff less BP measurement technique, PTT-based measurement technique, has been well studied however; it requires multi-devices which are ECG and PPG. Moreover, PTT-based BP estimation has a limitation for SBP and DBP estimation because it could provide only a variable, PTT. Thus, if an additional parameter like our proposed parameter adapted to an existing method PTT, BP estimation would be enhanced. Also, our further study would make a possible to estimate BP with only PPG. We strongly believe that our proposed study could provide potential techniques for the more accuracy BP estimation and the more efficiency for BP measurement.
arterial blood pressure
diastolic blood pressure
mean arterial pressure
micro-electro mechanical systems
pulse arrival time
pulse transmit time
systolic blood pressure
second derivative of the photoplethysmogram waveform
HS designed the framework of research and investigation of BP by morphological analysis of PPG. And, he wrote the manuscript. SDM contributed to verifying of proposed research method and participated in study and coordination. Both authors read and approved the final manuscript.
This research was supported from the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the ITRC (Information Technology Research Center) support program, which has Grant No. IITP-2016-H8601-16-1009 supervised by the IITP (Institute for Information and communications Technology Promotion). This work was supported by the Soonchunhyang University Research Fund (No. 20130599).
Both authors declare that they have no competing interests.
Availability of data and supporting materials
Supporting materials: MP150 (Biopac™ Inc., USA) was used for measuring PPG, Omron HEM-907 was used for measuring BP, MATLAB2008b (The MathWorks, Inc., Natick, MA, USA), SPSS (ver.12.0, SPSS Inc., IL, USA) was used for signal analysis and statistical analysis respectively, and data will not be shared.
Ethics approval and consent to participate
Before the experiment, written informed consent was obtained from each participant. Our study followed the guidelines of the Institutional Review Board fo Wonju Christian Hospital, Yonsei University Wonju College of Medicine.
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