14 Current Cardiology Reviews, 2012, 8, 14-25 On the Analysis of Fingertip Photoplethysmogram Signals Mohamed Elgendi* School of Engineering and Information Technology, Charles Darwin University, Australia, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Institute of Media Innovation, Nanyang Technological University, Singapore, Affiliated with Royal Darwin Hospital, Darwin, Australia Abstract: Photoplethysmography (PPG) is used to estimate the skin blood flow using infrared light. Researchers from dif- ferent domains of science have become increasingly interested in PPG because of its advantages as non-invasive, inexpen- sive, and convenient diagnostic tool. Traditionally, it measures the oxygen saturation, blood pressure, cardiac output, and for assessing autonomic functions. Moreover, PPG is a promising technique for early screening of various athero- sclerotic pathologies and could be helpful for regular GP-assessment but a full understanding of the diagnostic value of the different features is still lacking. Recent studies emphasise the potential information embedded in the PPG waveform signal and it deserves further attention for its possible applications beyond pulse oximetry and heart-rate calculation. Therefore, this overview discusses different types of artifact added to PPG signal, characteristic features of PPG wave- form, and existing indexes to evaluate for diagnoses. Keywords: Photoplethysmography, acceleration plethysmogram, second derivative plethysmogram, digital volume pulse, age- ing, artery, autonomic function, blood pressure, cardiovascular, heart rate, pulse wave analysis, vascular disease. INTRODUCTION 10x 10-3 The word plethysmograph is a combination of two an- cient Greek words ‘plethysmos’ which means increase [1, 2] 8 and ‘graph’ which is the word for write [2], and is an instru- 6 ment mainly used to determine and register the variations in 4 blood volume or blood flow in the body which occur with mV 2 each heartbeat. 0 (a) -2 Various types of plethysmograph exist, and each of them measures the changes in blood volume in a different manner -4 with a specific transducer and has certain applications [3]. 8x 10-4 As shown in Table I, the general plethysmograph types are: 7 water [4-8], air, strain gauge, impedance, and photoelectric. 6 5 Photoelectric plethysmography, also known as photo- 4 plethysmography and its acronym in some literature, is mV 3 (PTG/PPG) and when it is called digital volume pulse, the (b) 2 1 acronym is (DVP). In this paper, the abbreviation PPG is 0 going to be used. -1 -2 PPG is easy to set up, convenient, simple and economi- 8x 10-515.9 16 16.1 16.2 16.3 16.4 16.5 16.6 16.7 16.8 cally efficient compared to the other types of plethys- time mograph mentioned in Table I [3]. Moreover, it does not 6 need direct contact with the skin surface, as the other 4 plethysmograph methods. 2 It uses a probe which contains a light source and a detec- (c) mV 0 tor to detect cardio-vascular pulse wave that propagates -2 through the body. -4 The PPG signal reflects the blood movement in the ves- -6 sel, which goes from the heart to the fingertips and toes through the blood vessels in a wave-like motion [32], as Fig. (1). Signal Measurements (a) Original fingertip photoplethys- mogram (b) first derivative wave of photoplethysmogram (c) sec- ond derivative wave of photoplethysmogram. *Address for correspondence to this author at the Institute of Media Innova- tion, Nanyang Technological University, 50 Nany ang Drive, Research shown in Fig. (1a). It is an optical measurement technique Techno Plaza, XFrontiers Block, Level 03-01 Singapore 637553; Tel: +65 8316 0224; E-mail: [email protected] that uses an invisible infrared light sent into the tissue and 1(cid:27)7(cid:24)-(cid:25)(cid:24)(cid:24)(cid:26)/12 $58.00+.00 © 2012 Bentham Science Publishers On the Analysis of Fingertip Photoplethysmogram Signals Current Cardiology Reviews, 2012, Vol. 8, No. 1 15 Table I. Types of Plethysmograph and Its Application Type Transducer Standard Applications (cid:2) Water-filled cuff [4, 5] (cid:2) Measuring penile blood flow [4, 5]. Water (cid:2) Water-filled body [6, 7] (cid:2) Measuring Pulmonary Capillary Blood Flow [6, 7]. (cid:2) Water-filled chamber [8] (cid:2) Measuring maximal blood flow [8]. (cid:2) Evaluation of venous hemodynamics [9, 10]. (cid:2) Measures parameters of global venous function [9] like: • calf venous volume Air Air-filled cuff • venous filling index • ejection fraction • residual volume fraction (cid:2) Assessment of capillary filtration [11]. (cid:2) Assessment of volume changes in venous diseases [11]. (cid:2) Identifying limbs with suspected venous incompetence [12]. Fine rubber tube Strain Gauge (cid:2) Evaluation of peripheral circulation in spinal cord injury cases [12]. (filled with mercury) (cid:2) Evaluation of acute and chronic venous insufficiency [13]. (cid:2) Evaluation of peripheral vascular disease [14]. (cid:2) Measurement of deep venous thromboses [15, 16]. (cid:2) Detection of blood flow disorders [17, 18]. Impedance Electrodes (cid:2) Assessment of fat-free mass of the human body [19]. (cid:2) Monitoring of heart and respiratory rates [20]. (cid:2) Monitoring of oxygen saturation [21, 22]. (cid:2) Assessment of blood vessel viscosity [23]. (cid:2) Assessment of venous function [24]. (cid:2) Measuring the ankle pressure [25]. Photoelectric Photo detectors (cid:2) Measuring genital responses [26] (cid:2) Assessment of venous reflux [27]. (cid:2) Measuring cold sensitivity [28, 29]. (cid:2) Measuring blood pressure [30]. (cid:2) Assessment of cardiac output [31]. the amount of the backscattered light corresponds with the the original PPG waves. The first and second derivatives of variation of the blood volume [2]. Hertzman was the first to the PPG signal were developed as methods which allow find a relationship between the intensity of backscattered more accurate recognition of the inflection points and easier light and blood volume in 1938 [33]. The low-cost and sim- interpretation of the original PPG wave. plicity of this optical based technology could offer signifi- The fingertip PPG signal reflects the blood movement in cant benefits to healthcare (e.g. in primary care where non- the vessel, which goes from the centre (heart) to the end invasive, accurate and simple-to-use diagnostic techniques (fingertips) in a wave-like motion as shown in Fig. (1a). are desirable). Further development of PPG could place this methodology among other tools used in the management of It is affected by the heartbeat, the haemodynamics and vascular disease. the physiological condition caused by the change in the properties of an arteriole. The effects can be observed as As shown in Fig. (1a), the wave contour of PPG signal is distortions in the wave profiles. simple and has not been analyzed and investigated because of the difficulty in detecting changes in the phase of the in- Recently, analysing the PPG waveform has attracted in- flections. Therefore , Ozawa [34] introduced the first and the creasing interest especially in circulatory [35] and respiratory second derivative of the PPG signal, as shown in Fig. (1b) [36] monitoring. and Fig. (1c) respectively, to facilitate the interpretation of 16 Current Cardiology Reviews, 2012, Vol. 8, No. 1 Mohamed Elgendi PPG signal with poweline and motion artifacts. The low fre- g n quency artifact can be removed using a high pass filter or PPG Preprocessin Features Extraction Classificatio Diagnosis v dtahsiuceseeu U b mtvoaseeu srvdeasli laibltn.yor e a ttbhidoeei ns atscu aborubirps aemhn acoosevfi c ec mmasuoiegstnnieotda nol bfra yetrsh tiemefm aoscbuttilsboi njneigs c ataor. tsnTisfeuha mcect ysesc dhlc aeapt nooe fbb oaeef sine wave, as shown in Fig. (5). Fig. (2). Common structure for PPG diagnostic system consists of three or four stages: 1) Preprocessing stage to emphasize the de- sired waves. 2) Feature extraction stage to detect the desired waves. 120 3) Calculate an index or a measure using the extracted features for classification and diagnosis. 100 As shown in Fig. (2), any PPG diagnostic structure con- 80 sists of three stages: Pre-processing, features extraction, di- agnosis/ classification. Hz In this paper we discuss features and artifacts in PPG 2Volts/ 60 signals, and role of PPG as a diagnostic tool. 40 I. PRE-PROCESSING IN PPG SIGNALS 20 The quality of the PPG signal depends on the location and the properties of the subject's skin at measurement, in- 0 0 10 20 30 40 50 60 70 80 90 100 cluding the individual skin structure, the blood oxygen satu- Frequency [Hz] ration, blood flow rate, skin temperatures and the measuring environment. Fig. (3). Power Spectrum of the PPG signal. The spectrum illus- These factors generate several types of additive artifact trates peaks at the fundamental frequency of 50 Hz as well as the which may be contained within the PPG signals. This may second harmonic at 100 Hz. affect the extraction of features and hence the overall diag- nosis, especially, when the PPG signal and its derivatives will be assessed in an algorithmic fashion. The main chal- lenges in processing the PPG signals are described as fol- 1 lows: 0.5 1) .Powerline Interference This artifact could be due to the instrumentation amplifi- V 0 ers, the recording system picking up ambient electromag- m netic signals and other artifact. -0.5 Moreover, high frequency artifact caused by mains power sources interference is induced onto the PPG record- -1 ing probe or cable. This artifact introduces a sinusoidal com- ponent into the recording. In Australia this component is at a frequency of 50Hz. -1.5 0 2 4 6 8 10 12 14 16 18 20 The periodic interference is clearly displayed as a spike Time(s) in Fig. (3) at not only its fundamental frequency of 50 Hz, but also as spikes at 100 Hz and its higher harmonics. Fig. (4). Powerline and motion artifacts in PPG. 2) Motion Artifact 3) Low Amplitude PPG Signal This artifact is may be caused by poor contact to the fin- In general, the PPG waveform is subject to sudden ampli- gertip photo sensor. Variations in temperature and bias in the tude changes due to the automatic gain controller which ad- instrumentation amplifiers can sometimes cause baseline justs the gain of the amplifier automatically based on the drift as well. amplitude of the input signal. This may cause amplitude In our measurements, the body movement was limited saturation in the amplitude of the PPG waveform at a maxi- due to the short time of measurement (20 seconds) and the mum or minimum value, or to rest at some random fixed fixed position of the arm during the fingertip PPG signal value. A low amplitude PPG signal caused by the automatic collection. It is hard to arrange a procedure to measure PPG gain controller is shown in Fig. (6). However, the reduction signal without low frequency artifact, Fig. (4) shows a noisy On the Analysis of Fingertip Photoplethysmogram Signals Current Cardiology Reviews, 2012, Vol. 8, No. 1 17 2 1.5 1.5 1 0.5 1 V m 0 0.5 -0.5 0 -1 -0.5 0 2 4 6 8 10 12 14 16 18 20 Time(s) -1 Fig. (5). Baseline wandering in PPG. 2 4 6 8 10 12 14 16 18 20 Fig. (8). Artifacts in PPG signals. This PPG sample contains differ- ent challenges in analyzing PPG signals: motion artifacts, muscle artifact, arrhythmia, high frequency artifact, and low amplitude. 1 0.5 of PPG amplitude can be directly attributable either to a loss of central blood pressure or to constriction of the arterioles perfusing the skin V 0 m 4) Premature Ventricular Contraction -0.5 The premature ventricular beats (PVCs) interrupt the normal heart rhythm and cause an irregular beat, as shown in -1 Fig. (7). This is often felt as a "missed beat" or a "flip-flop" in the chest. PVCs are often harmless, but when they occur -1.5 very often or repetitively, they can lead to more serious 0 2 4 6 8 10 12 14 16 18 20 Time(s) rhythm disturbances. This type of arrhythmia will affect the main events detection accuracy in PPG signals. Two arrows in Fig. (6). Low Amplitude PPG signals. Generally, the low amplitude Fig. (7) refer to PVC. Sometimes all of the challenges discussed PPG signal is most likely related to the automatic gain controller, could exist at the same time within the PPG signal as shown in but it can be caused due to: bad connectivity between fingertip Fig. (8). probe and the finger, loss of central blood pressure, or constriction The PPG signal is complex and sensitive to artifacts. It of the arterioles. Detecting the heart beats in low amplitude PPG maybe for these reasons the PPG signal has not been widely signals is considered difficult. investigated beyond its use in oximetry [37]. PVC PVC II. PPG FEATURES AND ITS APPLICATIONS 0.4 The photoplethysmogram probe consist of an infrared 0.3 light source (typically a photodiode emitting light at a wave- length of around 900 nm) and a photodetector (phototransis- 0.2 tor) [38]. The light source to illuminate the tissue (e.g. skin), and a photodetector to measure the small variations in V 0.1 light intensity associated with changes in the blood vessels m volume. The increase in blood volume indicates decrease in 0 light intensity and vice versa [35]. Although the morphology of the PPG signal looks similar -0.1 to the arterial pressure pulse, the wave contour is not the -0.2 same. The relationship between the PPG signal and the pres- sure pulse has been quantified by Millasseau et al. [39]. 6 8 10 12 14 16 18 20 The fingertip vasculature (blood vessels) contains an Time(s) abundance of alpha adrenergic receptors which affects the arteries and veins vasoconstriction (narrowing the blood ves- Fig. (7). Premature Ventricular Contraction. It is clear that detec- sels). tion of heart beats in PPG signals will be challenging with the exis- tence of PVCs. 18 Current Cardiology Reviews, 2012, Vol. 8, No. 1 Mohamed Elgendi are the major attractive features to re-investigate the PPG Dicrotic [44]. Moreover, the fast development in semiconductor notch Systolicx P10-e3ak technology has made the PPG probe design even more 10 attractive in terms of size, sensitivity, reliability and 8 reproducibility. This will significantly increase the demand 6 to apply the PPG to a large scale of human health and well- Diastolic Peak 4 being studies. Consequently, a progress in the PPG signal mV 2 processing and pulse wave analysis is expected. 0 Width y x -2 -4 6 4 2 Fig. (9). A typical waveform of the PPG and its characteristic pa- rameters, whereas the amplitude of the systolic peaks is x while y is 0 the amplitude of the diastolic peak. -2 A1 A2 Table II. Different Factors Affecting the Systolic Amplitude -4 [37] Fig. (10). Original fingertip photoplethysmogram. A1 and A2 are the areas under the whole PPG wave separated at the point of in- Systolic flection. Thus, the inflection point area ration can be calculated as Peak Am- Factor Effect the division of A2 by A1. plitude Relative elevation of Decreased blood volume Therefore, this paper will review the PPG signal process- pulsations and decreased ing challenges, features and the existing applications. measurement site venous blood volume Features of the first and second derivative of the PPG Arterial blood pressure will also be discussed. The first and second derivatives of the Decreased blood volume increase due to increased PPG were developed as a method to accurately recognize the pulsations peripheral resistance critical points of the PPG. Decreased blood volume Severe hypovolaemia A. Photoplethysmogram Low pulsations The appearance of the PPG pulse is commonly divided Peripheral vasoconstric- (Local) hypothermia into two phases: the anacrotic phase is the rising edge of the tion pulse, whereas the catacrotic phase is the falling edge of the Sympathetic activation Peripheral vasoconstric- pulse as shown in Fig. (9). The first phase is primarily con- (e.g. stress, cold) tion cerned with systole, and the second phase with diastole and wave reflections from the periphery. A dicrotic notch, shown Vasoconstrictors Peripheral vasoconstric- in Fig. (9), is usually seen in the catacrotic phase of subjects (e.g. Noradrenaline) tion with healthy compliant arteries. A number of features based on the PPG have been described in literature. Arterial blood pressure increase due to increased Increased blood volume 1) Systolic Amplitude: As shown Fig. (9), the systolic ampli- cardiac output pulsations tude (x) is an indicator of the pulsatile changes in blood vol- High ume caused by arterial blood flow around the measurement Most anaesthetics Peripheral vasodilatation site [45, 46]. Systolic amplitude has been related to stroke volume [47]. Dorlas and Nijboer found that systolic ampli- Epidural anaesthesia Peripheral vasodilatation tude is directly proportional to local vascular distensibility over a remarkably wide range of cardiac output [48]. It is Therefore, the peripheral blood flow will be influenced also has been suggested that systolic amplitude is potentially by sympathetic activity as well as temperature variations [40, a more suitable measure than pulse arrival time for estimat- 41]. This can produce significant errors, such as emphasizing ing continuous blood pressure [49]. local effects when relating PPG waveform features to central Table II summarises the several physiological and phar- large artery properties. Penaz [42] developed a technique that macological factors, which influence the systolic amplitude can overcome these PPG problems including the fingertip in PPG signals. cuff occlusions called volume clamping. His technique is used for calibrated and continuous non-invasive measure- 2) Pulse Width: the pulse width in the PPG wave is shown ment of arterial pressure (e.g. using the Finapres device in Fig. (9). Awad et al. [50] used the pulse width as the pulse [43]). width at the half height of the systolic peak. They have sug- gested that the pulse width correlates with the systemic vas- Recently, the desire for a simple, economical, conveni- cular resistance better than the Systolic amplitude. ent, and noninvasive cardiovascular assessment techniques On the Analysis of Fingertip Photoplethysmogram Signals Current Cardiology Reviews, 2012, Vol. 8, No. 1 19 3) Pulse Area: the pulse area is measured as the total area Takazawa et al. [59] defined the augmentation index under the PPG curve. Seitsonen et al. [51] found the PPG (AI) as the ratio of y to x as follows: area response to skin incision to differ between movers and y non-movers. AI = (2) x Peak to Peak interval As shown Fig. (9), y is the height of the late systolic peak and x is the early systolic peak in the pulse. Padilla et al [60] used the RI as a reflection index as follows: y RI = x (3) T Pulse interval x 10-3 10 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 Fig. (11). Two consecutive PPG waves. Wang et al. [52] have divided the pulse area into two areas at the dicrotic notch. They found that the ratio of the two areas, see Fig. (10), can be used as an indicator of total peripheral resistance. This ratio is called the inflection point area ratio (IPA) and is defined as A2 IPA= (1) A1 Fig. (12). Typical waveform of the PPG and its (cid:1)T feature. 4) Peak to Peak Interval: The distance between two conse- cutive systolic peaks will be referred to as Peak-Peak inter- Rubins et al. [61] used the reflection index as in equation val, as shown in Fig. (11). 3 and introduced an alternative augmentation index as fol- lows The R-R interval in the ECG signal correlates closely with the Peak-Peak interval APG signal as both represent a x(cid:1)y completed heart cycle. The Peak-Peak interval has been used AI = (4) x to detect the heart in PPG signals [53-56]. 7) Large Artery Stiffness Index: The systolic component of 5) Pulse Interval: The distance between the beginning and the waveform arises mainly from a forward-going pressure the end of the PPG waveform, as shown in Fig. (11). The wave transmitted along a direct path from the left ventricle to Pulse interval is usually used instead of the Pulse interval the finger. The diastolic component arises mainly from pres- when the diastolic peaks are more clear and easier to detect sure waves transmitted along the aorta to small arteries in the compared to the systolic peak. lower body, from where they are then reflected back along Poon et al. [57] suggested that ratio of Pulse interval to the aorta as a reflected wave which then travels to the finger. its systolic amplitude could provide an understanding of the The upper limb provides a common conduit for both the di- properties of a person's cardiovascular system. In 2008, Lu et rectly transmitted pressure wave and the reflected wave and, al. [58] compared the HRV using the Pulse interval in PPG therefore, has little influence on their relative timing. As signals with the HRV using R-R intervals in ECG signals. shown in Fig. (12), the time delay between the systolic and Their results demonstrated that HRV in PPG and ECG sig- diastolic peaks (or, in the absence of a second peak, the point nals are highly correlated. They strongly suggested that PPG of inflection) is related to the transit time of pressure waves signals could be used as an alternative measurement of HRV. from the root of the subclavian artery to the apparent site of reflection and back to the subclavian artery. This path length 6) Augmentation Index: The augmentation pressure (AG) is can be assumed to be proportional to subject height (h). the measure of the contribution that the wave reflection makes to the systolic arterial pressure, and it is obtained by Therefore, Millasseau et al [62] formulated an index of measuring the reflected wave coming from the periphery to the contour of the PPG (SI ) that relates to large artery stiff- the centre. Reduced compliance of the elastic arteries causes ness. an earlier return of the ‘reflected wave’, which arrives in h systole rather than in diastole, causing a disproportionate rise SI = (5) (cid:1)T in systolic pressure and an increase in pulse pressure, with a They have examined the timing of discrete components consequent increase in left ventricular after load and a de- of the PPG to formulate an index of the contour of the PPG crease in diastolic blood pressure and impaired coronary perfusion. 20 Current Cardiology Reviews, 2012, Vol. 8, No. 1 Mohamed Elgendi T B. First Derivative Photoplethysmogram The first derivative is hardly used in literature and its main features are: Age:60yrs 1) Diastolic point definition: Millasseau et al [62] defined the diastolic point as the point at which the first derivative of T 147ms the waveform is closest to zero, shown in Fig. (14). SI 12.2m/s Systolic Peak x 10-3 Age:45yrs 10 Dicrotic T 270ms 8 Notch SI 6.8m/s 6 4 mV 2 Age:29yrs (a) 0 T 1346ms -2 SI 5.4m/s -84x 10-5 Diastolic 6 a Fig. (13). Typical PPG waveforms show the parameters changes 6 Peak with age [62]. 4 10x 10-3 (b) 2 e 8 mV 0 c d 6 -2 4 -4 mV 2 -6 b (a) 0 -2 Fig. (15). Signal Measurements (a) Original fingertip photop- -48x 10-4 lethysmogram (b) second derivative wave of photoplethysmogram. 6 7 Systolic 6 Peak Diastolic Peak 2) (cid:1)T calculation: (cid:1)T is the peak-to-peak time which is 5 related to the time taken for the pressure wave to propagate 4 from the heart to periphery and back. The time between the (b) mV 3 systolic and diastolic peaks is (cid:1)T. The definition of (cid:1)T de- 2 pends on the PPG waveform as its contour varies with sub- 1 jects. When there is a second peak as in Fig. (14a), (cid:1)T is 0 defined as time between the two maxima. -1 In other words, (cid:1)T is the time between the two positive -2 CT T to negative zero-crossings of the derivative as in Fig. (14b). However, in some PPG waveforms, there is no clear second Fig. (14). Signal Measurements (a) Original fingertip photop- peak. In this case, (cid:1)T is defined as the time between the lethysmogram (b) first derivative wave of photoplethysmogram peak of the waveform and the inflection point on the down slope of the waveform which is a local maximum of the first derivative. expected to relate to large artery stiffnessSI . As shown in 3) Crest time (CT) calculation: Crest time is the time from Fig. (13), the time delay between the systolic and diastolic the foot of the PPG waveform to its peak; see Fig. (14b). peaks decreases with age as a consequence of increased large artery stiffness and increased pulse wave velocity of pressure Alty et al [63] proved that the crest time is a useful fea- waves in the aorta and large arteries. Therefore, Millasseau ture for cardiovascular disease classification. They developed et al. [62] proved that the SI increases with age. a method to classify subjects into high and low pulse wave velocity (equivalent to high and low cardio vascular disease In order to facilitate the interpretation of the original PPG risk) using features extracted from the PPG. They found that waves, Ozawa differentiated the PPG signals to be able to peak-to-peak time ((cid:1)T), crest time (CT), and stiffness index analyse the PPG wave contour [59]. (SI =h/ (cid:1)T) were the best features for accurate classifica- On the Analysis of Fingertip Photoplethysmogram Signals Current Cardiology Reviews, 2012, Vol. 8, No. 1 21 tion of cardiovascular disease using the first derivative of the tribute to the discrimination of the high-risk subjects for car- PPG. They used sets of these features for classification. diovascular heart disease Using a support vector machine based classifier they achieve Baek et al [71] confirmed that the b/a ratio increases with a classification result of 87.5%. age. C. Second Derivative Photoplethysmogram • Ratio c/a Takazawa et al. [59] demonstrated that the c/a ratio re- The second derivative is more commonly used than the flects decreased arterial stiffness, hence the c/a ratio de- first derivative. In literature, the second derivative of photop- creases with age. The c/a index was also used by (cid:4)imek et al lethysmogram is also called the acceleration plethysmogram (2005) [69] who found that the c/a index distinguishes sub- because it is an indicator of the acceleration of the blood in jects with essential hypertension from healthy controls. Baek the finger. Three abbreviations are commonly used for the et al [71] found that the c/a ratio decreases with age just as second derivative: SDPTG (Second Derivative of the Phot- the b/a ratio, described above. hophleThysmoGram), SDDVP (Second Derivative of Digital Volume Pulse) and APG (Acceleration PlethysmoGram). • Ratio d/a In 1998, Takazawa et al. [59] demonstrated that the d/a As shown in Fig. (15), The waveform of the APG in- ratio reflects decreased arterial stiffness, hence the d/a ratio cludes four systolic waves and one diastolic wave, namely a- decreases with age. Moreover, they found the -d/a ratio is a wave (early systolic positive wave), b-wave (early systolic useful index for the evaluation of vasoactive agents, as well negative wave), c-wave (late systolic reincreasing wave), d- as an index of left ventricular afterload. Baek et al [71] con- wave (late systolic redecreasing wave) and e-wave (early firmed that the d/a ratios decreases with age. diastolic positive wave). The e-wave represents the dicrotic notch as shown in Fig. (15). Its location corresponds to the • Ratio e/a closure of the aortic valve and subsequent retrograde blood Takazawa et al. [59] demonstrated that an increase of the flow, and can be used to monitor cardiac function [64, 65]. e/a ratio reflects decreased arterial stiffness, and that the e/a ratio decreases with age. Baek et al [71] confirmed that the In literature, the second derivative of photoplethys- e/a ratios decreases with age. mogram (SDPTG) has been called acceleration plethys- mogram (APG) or second derivative of digital volume pulse • Ratio (b-c-d-e)/a (SDDVP). In this paper, the abbreviation APG is going to be Takazawa et al. [59] found that the (b-c-d-e)/a in- used. dex, increases with age and may be useful for evaluation of The height of each wave was measured from the base- vascular aging and for screening of arteriosclerotic disease. line, with the values above the baseline being positive and Kimura et al. [72] calculated the vascular age as those under it negative. The ratios of the height of the each 45.5(b-c-d-e)/a + 65.9 years old. wave to that of the a-wave (b/a, c/a, d/a and e/a) are usually • Ratio (b-e)/a used for wave analyses [66]. Baek et al [71] suggested the (b-e)/a ratio as the APG The second derivative of the finger PPG waveform is aging index instead of (b-c-d-e)/a , when the c and d used to stabilize the baseline and enable the individual fea- waves are missing. tures to be visualized and detected easily. The APG main features are: • Ratio b/a Takazawa et al. [59] demonstrated that the b/a ratio re- flects increased arterial stiffness, hence the b/a ratio in- creases with age. Imanaga et al. [67] provided a direct evi- dence that magnitude of b/a of the APG is related to the dis- tensibility of the peripheral artery, and suggest that the mag- nitude of b/a is a useful non-invasive index of atherosclero- sis and altered arterial distensibility. Aiba et al. [68] suggested the parameter -b/a in the expo- sure group dose dependently decreased with increases in length of working career (duration of exposure to lead) and blood lead concentration (Pb-B). The parameter -b/a signifi- cantly decreased in subjects with working careers of 5 years or more and in subjects whose Pb-B was 40(cid:2)g/100 ml or more. While (cid:4)imek et al. [69] found that the b/a index Fig. (16). APG waveforms and types of photoplethysmogram [73]. discriminates independently between subjects with essential There are different types of APG waveforms. The first APG wave- hypertension and healthy controls. form A (far left) refers to good circulation, whereas the amplitude Otsuka et al. [70] found that the b/a, is positively corre- of b wave is lower than c wave. The last APG waveform G (far lated to the Framingham risk score. Framingham risk score right) refers to distinctively bad circulation, whereas the amplitude has been used to estimate individual risk of cardiovascular of c wave is lower than b wave. heart disease. Their results suggest that b/a index might con- 22 Current Cardiology Reviews, 2012, Vol. 8, No. 1 Mohamed Elgendi Table III. APG Wave Form Types [73] measure method and the size of neighbourhood space in chaos attractor to diagnose stress using the APG. Beat Type Description III. DISCUSSION A Good circulation Photoplethysmography has the advantage of being a low B Good circulation but deteriorating cost, simple and portable technology which can be used in primary health care and remote clinics. This review has de- C Poor circulation scribed a number of features of the photoplethysmogram and their potential applications. Two indices based on the origi- D-G Distinctively bad circulation nal photoplethysmogram (PPG) signal have been described: the augmentation index and large artery stiffness index. Fea- • Ratio (b-c-d)/a tures based on the first derivative of the photoplethysmo- Ushiroyama et al. [74] reported that patients with a sen- gram are: the diastolic point, the peak to peak time ((cid:1)T), and sation of coldness showed an improvement of the APG index the crest time. The first derivative of the PPG can also be (b-c-d)/a upon treatment with a herbal supplement. used to calculate the augmentation index and the large artery stiffness index more accurately. • Ratio (c+d-b)/a Sano et al. [75] proposed a more comprehensive aging Most indices are based on the second derivative of the index (c+d-b)/a . It increases with age. finger photoplethysmogram (APG) which seems to provide more information than the first derivative of PPG. The in- Sano et al. distinguished seven main categories of APG dices calculated from the APG waveforms are reported to signals depending on the waveforms as shown in Fig. (16). correlate closely with the distensibility of the carotid artery • a-a interval [67], age [59], the blood pressure [84], the estimated risk of The R-R interval in the ECG signal correlates closely coronary heart disease [70], and the presence of atheroscle- with the a-a interval in APG signal as both represent a com- rotic disorders [85]. Some of the photoplethysmogram in- pleted heart cycle. In 2007, Taniguchi et al. [76] used the a-a dices have been calculated with different formulas. For exam- interval instead of the R-R interval to evaluate the surgeon's ple the aging index can be calculated as stress. In 2010, Elgendi et al. calculated the heart rate and (b-c-d-e)/a, (b-e)/a or (c+d-b)/a. A number of indices heart rate variability from the APG signals [77-80]. are reported to indicate vascular stiffness; the b/a index in- creases with increasing arterial stiffness while the c/a, d/a • APG waveform and e/a indices decrease. At this stage it is unclear which of The shape of the APG waveform has been categorized these indices is most informative. Sometimes the same fea- into seven types, A to G as shown in Fig. (16). The shape of ture is used as a measure of different but potentially related the APG waveform can be described as in Table III. Type A physiological variables. The b/a ratio has been used as an is often observed in healthy young people indicating good indicator of arterial stiffness, hypertension, vascular aging circulation. While, Type D-G is often observed in patients and risk of cardiovascular disease. with cerebrovascular disease, ischemic heart disease, breast tumour and uterine diseases. The changes from D to G re- Most research relating to the APG has been done in Ja- flect the disease development. pan. In addition to cardiovascular risk factors, the APG has also been described as a potential diagnostic tool for other Nousou et al. [69] developed a diagnostic system using disorders, varying from a sensation of coldness [74] and APG and Self-Organizing Maps (SOM). They needed to stress experienced by surgeons [76] to exposure to lead [70], adjust the original APG signal in order to be classified cor- pneumonia, intracerebral haemorrhage and acute poisoning rectly by the SOM. The b and the d wave had to be shifted [82]. This has its origins in Eastern medicine where the pulse along the time axis. They used a similar classification as is considered a very important diagnostic variable. Self or- Sano et al. [75] as shown in Fig. (16). ganising maps and chaos theory have been applied to find a • Section of the APG waveform measure of the disease state or the general state of health Tokutaka et al. [81] also developed a diagnostic tool to [69], [81], [82]. describe the general state of health. They used the first sec- Currently a full understanding of the diagnostic value of tion of the APG signal after the a peak in combination with the different features of the PPG signal is still lacking and self organising maps. Their approach was similar to Nousou more research is needed. et al.[69]. • Chaos Attractor IV. CONCLUSION Iokibe et al. [82] used the APG of healthy subjects and of This review discussed the photoplethysmography tech- patients with a different diseases, varying from a common nology and demonstrated their potential diagnostic applica- cold to pneumonia, intracerebral hemorrhage and acute poi- tions. soning. Their aim was to find an indicator for the seriousness of the disease, the disease state. They applied chaos theory to A common structure of any PPG diagnostic system con- the APG signals. sists of three stages preprocessing, feature extraction, and diagnosis. The main focus of this review was the preprocess- Fujimoto et al. [83] proposed a criterion which combines ing and feature extraction stages. two evaluations based on chaos theory; the trajectory parallel On the Analysis of Fingertip Photoplethysmogram Signals Current Cardiology Reviews, 2012, Vol. 8, No. 1 23 In the preprocessing stage, different artifact sources af- [8] Horwitz D, Patel D. Maximal hand blood flow in hypertensive and fecting the PPG signal are described. The sources of artifact normal subjects. Am J Cardiol 1985; 55(4): 418-22. [9] Criado E, Farber M, Marston W, Daniel P, Burnham C, Keagy B. can be the power line interface, motion artifacts, low ampli- The role of air plethysmography in the diagnosis of chronic venous tude, and the existence of arrhythmia. insufficiency. J Vasc Surg 1998; 27(4): 660-70. In the feature extraction stage, the characteristics of the [10] Weingarten M, Czeredarczuk M, Scovell S, Branas C, Mignogna G, Wolferth C. A correlation of air plethysmography and color- PPG waveform and its derivatives have been clarified. Fea- flow-assisted duplex scanning in the quantification of chronic tures of the PPG signal have been discussed. These features venous insufficiency. 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