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Continuous Cuffless Blood Pressure Estimation

Using Pulse Transit Time and
Photoplethysmogram Intensity Ratio

Article in IEEE Transactions on Biomedical Engineering September 2015

DOI: 10.1109/TBME.2015.2480679

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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/TBME.2015.2480679, IEEE Transactions on Biomedical Engineering
Continuous Cuffless Blood Pressure Estimation
Using Pulse Transit Time and
Photoplethysmogram Intensity Ratio
Xiao-Rong Ding, Student Member, IEEE, Yuan-Ting Zhang, Fellow, IEEE, Jing Liu, Wen-Xuan Dai,
Hon Ki Tsang*, Senior Member, IEEE
AbstractPulse transit time (PTT) has attracted much interest
for cuffless blood pressure (BP) measurement. However, its
limited accuracy is one of the main problems preventing its
widespread acceptance. Arterial BP oscillates mainly at high
frequency (HF) because of respiratory activity, and at low
frequency (LF) because of vasomotor tone. Prior studies
suggested that PTT can track BP variation in HF range, but was
inadequate to follow the LF variation, which is probably the main
reason for its unsatisfactory accuracy. This paper presents a new
indicator, the photoplethysmogram intensity ratio (PIR) which
can be affected by changes in the arterial diameter and thus trace
the LF variation of BP. Spectral analysis of BP, PTT, PIR and
respiratory signal confirmed that PTT was related to BP in HF at
the respiratory frequency, while PIR was associated with BP in
LF range. We therefore develop a novel BP estimation algorithm
by using both PTT and PIR. The proposed algorithm was
validated on 27 healthy subjects with continuous Finapres BP as
reference. The results showed that the mean standard deviation
(SD) for the estimated systolic, diastolic and mean BP with the
proposed method against reference were -0.375.21 mmHg,
-0.084.06 mmHg, -0.184.13 mmHg, and mean absolute
difference (MAD) were 4.09 mmHg, 3.18 mmHg, 3.18 mmHg,
respectively. Furthermore, the proposed method outperformed
the two most cited PTT algorithms for about 2 mmHg in SD and
MAD. These results demonstrated that the proposed BP model
using PIR and PTT can estimate continuous BP with improved
accuracy.
Index TermsArterial diameter change, cuffless blood
pressure, photoplethysmogram intensity ratio, pulse transit time,
respiration, vasomotion
This work was supported in part by the Guangdong Innovation Research
Team Fund for Low-cost Healthcare Technologies in China, the External
Cooperation Program of the Chinese Academy of Sciences (Grant GJHZ1212).
Asterisk indicates corresponding author.
Xiao-Rong Ding, Yuan-Ting Zhang, Jing Liu, and Wen-Xuan Dai is with
the Joint Research Centre for Biomedical Engineering, Department of
Electronic Engineering, The Chinese University of Hong Kong, Hong Kong
SAR, China (e-mail: xrding@ee.cuhk.edu.hk; ytzhangapple@icloud.com;
jingliu@ee.cuhk.edu.hk; wxdai@ee.cuhk.edu.hk)
*Hon Ki Tsang is with the Department of Electronic Engineering, The
Chinese University of Hong Kong, Hong Kong SAR, China (e-mail:
hktsang@ee.cuhk.edu.hk).
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I. INTRODUCTION
B LOOD pressure (BP) is an important hemodynamic
parameter varying between systolic BP (SBP) to diastolic
BP (DBP) in each heartbeat. High BP, also known as
hypertension, is one of the major modifiable risk factors
leading to the development of cardiovascular diseases (CVDs)
the number one killer in the world. Hypertension is highly
prevalent but poorly controlled because of the low awareness
and treatment rate [1], which enhances development of CVDs
and results in significant burdens on individuals and society.
BP variability (BPV) has been reported to have prognostic
value for hypertension [2], and thus continuous BP
measurement is crucial for early prevention, detection,
evaluation and treatment of hypertension and related CVDs.
Conventional 24-hour ambulatory BP monitoring can facilitate
monitoring of BPV through measuring BP at regular intervals
with auscultatory or oscillometric approaches. However, it has
limitations including the discontinuous nature and the
discomfort caused by the repeated cuff inflations.
Compared with cuff-based BP techniques, pulse transit time
(PTT) method has received much attention over the recent
decades because of its capability to track BP change, as well as
its advantages as a noninvasive, continuous and most
importantly cuffless tool for BP measurement [3-5]. PTT is the
time taken by the arterial pulse propagating from the heart to a
peripheral site, and can be calculated as the time interval
between the R wave peak of electrocardiogram (ECG) and a
characteristic point of photoplethysmogram (PPG). The
fundamental principle of PTT-based method is based upon the
pulse wave velocity (PWV) recording through the
Moens-Korteweg (M-K) equation:
Eh
PWV (1)
d
which relates PWV with the elastic modulus of vessel wall E,
blood density and arterial dimension properties such as vessel
thickness h and arterial diameter d. PWV is inversely related
with PTT, i.e., PWV=K/PTT, where K is the distance between
heart and certain peripheral site; and E can be exponentially
correlated BP through the following equation [6]:
This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/TBME.2015.2480679, IEEE Transactions on Biomedical Engineering

the PTT and the requirement of intermittent calibration to

P
E E0e (2) maintain accuracy. However, to date, few study has addressed
the LF component in cuffless BP estimation. Here we propose a
where E0 is the elastic modulus at zero pressure; is a new indicator, the PPG intensity ratio (PIR) [30], that can
reflect changes in the arterial diameter and thereby the arterial
coefficient depending on particular vessel, and is BP.
vasomotion, and thus allow tracking of BP in the LF range.
Therefore, PTT can be translated into BP with an initial
Furthermore, we develop a novel BP estimation algorithm
calibration under the assumption that h/d keeps constant.
which employs both the PIR and the PTT to improve the
PTT-based BP estimation has been extensively studied ever
estimation accuracy.
since 2000 [7-20], when Chen et al [7] estimated SBP using
pulse arrival time with intermittent calibration, and showed that
II. METHODOLOGY
the estimated SBP was highly correlated with reference SBP
(r=0.970.02). In 2005, Poon et al [9] established a model with A. PTT and PIR
PTT to estimate BP with initial calibration, and achieved an Fig. 1 illustrates the diagram of PTT and PIR calculation,
accuracy of 0.69.8 mmHg and 0.95.6 mmHg for SBP and where PTT is determined as the time interval between the R
DBP, respectively. Recently, Wibmer et al [19] investigated wave peak of ECG and the peak of first derivative of PPG in the
the relationship of PTT and SBP through regression analysis same cardiac cycle, and PIR is the ratio of PPG peak intensity
and found a nonlinear approach was better than linear one. IH to PPG valley intensity IL of one cardiac cycle. Our earlier
Although PTT has been considered a promising surrogate of study shows that PIR can theoretically reflect the arterial
BP and could become the most widely used technique for diameter change d during one cardiac cycle from systole to
noninvasive continuous BP monitoring in the future [4, 5], diastole, and PIR is exponentially linked with d through the
there are still several problems to be solved before its following expression [30]:
widespread application. Frist, some PTT-BP models could only
provide one BP parameter, e.g., exclusively SBP [7, 8, 21, 22], PIR e d (3)
DBP [11], or mean BP (MBP) [18], but SBP, DBP, and MBP
all have clinical significance. Second, a calibration procedure is where is considered to be a constant related to the optical
required to map PTT to BP. However, re-calibration at absorption coefficients in the light path.
intermittent intervals is often necessary for accurate estimation,
potentially owing to the inadequacy of PTT to track BP
variation over a long period. Last and most importantly, the
accuracy of PTT-based BP estimation is unsatisfactory. The
possible reasons are the influences of the vascular or vasomotor
tone and the pre-ejection period (PEP) [3]. Regarding PEP
issue, impedance cardiogram (ICG), phonocardiogram (PCG)
[20], ballistocardiogram (BCG) or two peripheral PPG have
been adopted to eliminate the effect of PEP. Nonetheless,
several studies indicated that PTT with PEP included actually
performs better for BP estimation than that with PEP removed,
which demonstrates the positive effect of PEP on BP estimation
[8, 22, 23]. For the vasomotor tone, previous research has
examined its influence on BP-PTT relationship [24], and
central PPG instead of peripheral PPG was suggested to
alleviate such effect [18]. However, few studies have Fig. 1. Diagram of pulse transit time (PTT) and photoplethysmogram (PPG)
attempted to take this factor into account in the PTT-BP intensity ratio (PIR) calculation, where IH indicates PPG peak intensity, IL the
valley intensity, and 1st dPPG is the first derivative of PPG.
estimation model to improve the accuracy.
BP is dynamic and its rhythmic oscillations can be identified From a physiological perspective, BP is mainly affected by
with the appearance in its spectrum as individual peaks, which four factors: arterial compliance, cardiac output, peripheral
reflect: (1) the oscillations with a frequency typically between resistance, and blood volume [31]. Arterial compliance can be
0.2-0.35 Hz, a frequency similar to that of normal respiratory evaluated by PTT, since PTT is an index of arterial stiffness
activity, defined as high frequency (HF); (2) oscillations with a
[32]. Also, cardiac output can be related to PTT through heart
frequency of approximately 0.1-0.15 Hz, suggesting the
rate. With regard to peripheral resistance and blood volume,
sympathetic modulation of vasomotor tone, defined as low
one of the primary sources is the arterial diameter change which
frequency (LF) [25-27]. According to our prior research work
can be assessed by PIR as described above. Accordingly, PTT
[28, 29], PTT could track BP in HF range, but was inadequate and PIR can capture BP variations indirectly, and be used for
to follow LF variations in BP. This is probably the most BP estimation.
important reason for the inaccuracy of estimated BP with only

0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
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B. Model-based BP Estimation with PTT and PIR

Arterial BP is a hemodynamic parameter that fluctuates on a
beat-to-beat basis as a result of the dynamic interplay involving
vasomotion, arterial mechanisms and neural regulation [33].
Beat-to-beat BP fluctuations are usually attributed to two
rhythmic events: respiration and vasomotion [34-36]. The
Fig. 2. The two-element Windkessel [39].
respiratory rhythm is a HF spectral component that occurs in
BP variability, and also considered to be a marker of vagal
In a pure Windkessel, the DBP can be theoretically expressed
modulation, whereas the slow oscillation, corresponding to the
in terms of RC using the following equation:
vasomotor waves, is a LF component that is present in BPV,
and is also a marker of sympathetic modulation.
DBP P0 et / RC (8)
Physiological study of BPV showed that both the slow
variability and fast variability can be observed in SBP, while
where P0 is the end-systolic aortic pressure. Since C is constant
the DBP exhibits only on the slow variability [37]. Since SBP
in a relatively short period, DBP mainly varies with R. Noting
is the summation of pulse pressure (PP) and DBP, it is
that the major regulator of peripheral vascular resistance is the
hypothesized that the HF component is mainly dominant in PP. vessel diameter, R will mainly rely on the arterial diameter
Furthermore, PTT and PIR have been investigated to reflect HF change d. As mentioned above in (3), d is related with PIR
and LF component in BPV [30], respectively. It is therefore as follows:
speculated that PP and DBP can be derived from PTT and PIR,
respectively, and consequently the SBP can be estimated 1
e d (9)
accurately. PIR
1) PP Estimation with PTT Based on M-K Equation
And d is inversely related to R. Thus DBP depends on the
In the M-K equation (1), the elastic modulus E is given by reciprocal of PIR:
[38]:
1 (10)
DBP
E

P 2 1 2 RO Ri 2
(4) PIR
RO RO Ri
2 2

Therefore, DBP can be derived with calibrated DBP 0 and PIR0.

where RO is the external radius, RO is the external radius
PIR0
change in response of the pressure change P, and P is the PP DBP DBP0 (11)
in the artery; Ri is the internal radius, and is the Poissons PIR
ratio. PWV is reversely proportional to PTT:
3) SBP Estimation with PP and DBP
1 (5)
PWV SBP is the sum of PP and DBP. Thereupon, beat-to-beat SBP
PTT
can be estimated with the addition of (7) and (11):
Since the artery radius change is quite small compared with
2
elastic modulus change, it is assumed to be constant. According PIR0 PTT0 (12)
SBP DBP0 PP0
to (1) and (4)-(5), P has a relationship with PTT as follows: PIR PTT

1 (6)
PP C. Experiment
PTT 2
To validate the proposed BP estimation using both PTT and
With initial calibrated PP0 and PTT0, PP can be derived in PIR as given by (11) and (12), an experiment was conducted on
terms of measured PTT: 27 healthy adults (14 males) with mean age of 25.62.1 years
(range 21-29 years), who were nonsmokers with no history of
2
PTT0 cardiovascular disease. Reference BP was measured by
PP PP0 (7)
Finapres (Finapres Medical System), a noninvasive continuous
PTT
BP measurement system, with the finger cuff on the left thumb,
and brachial cuff on the left upper arm. ECG and PPG were
2) DBP Estimation with PIR based on Windkessel Model acquired with one-lead ECG electrodes placed on left and right
Two-element Windkessel model, originally proposed by arms, and PPG sensor on left index finger, respectively.
Frank, consists of peripheral resistance R and arterial Synchronous respiratory activity continuously monitored by
compliance C [39], as shown in Fig. 2. recording the chest movement with respiratory monitoring belt
(Vernier Software & Technology). All tests were performed
with subjects in the seated position, and the signals were

0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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recorded at the sampling rate of 1000 Hz for five minutes. All
the subjects gave their informed consent prior to the
experiments, in accordance with the guidelines of the
Institutional Research Ethics Board.
D. Signal Processing and Data Analysis
In order to verify the capability of PTT to track the HF
component of SBP as well as respiratory activity, and PIR to
reflect LF fluctuations of BP, the power spectrum analysis of
SBP, DBP, PP, respiratory signal, PTT and PIR were conducted
in 0-0.5 Hz frequency range based on Lomb-Scargle
periodogram method [40]. Difference mean and standard
deviation (SD), as well as mean absolute difference (MAD)
between estimated BP with the proposed method and reference
BP were used as the evaluation metrics. The agreement
between reference BP and estimated BP with the proposed
method were analyzed according to the Bland-Altman
approach [41], with the agreement limits defined by mean
1.96SD. In addition, the proposed method was compared
with two most cited PTT-based algorithms [7, 9] for cuffless
BP estimation. Statistical significance was estimated using
Students t-test. P<0.05 is regarded as statistically significant.
Furthermore, time series of PP, PTT and respiratory signal
with their corresponding spectrums are presented in Fig. 4. As
can be observed from Fig. 4 (a)-(c), they have a similar
variation pattern with almost the same frequency components
at 0.2-0.3 Hz. Moreover, from the PSD curves, the
respiration-synchronous variation is seen as peaks at the
respiratory frequency of PP spectrum, as well as in PTT. This
indicates that the HF component of PP can be reflected by PTT,
which might be caused by the respiratory activity, as discussed
in the next section.
Example recordings of DBP and PIR and their power spectra
are shown in Fig. 5. The variation of DBP is slower compared
with PP, with its frequency range concentrated at
approximately 0.1 Hz. It can be seen from Fig. 5 (a) and (c) that
the amplitude of DBP is inversely related with that of PIR on
the whole, and they have the similar spectral components. This
is in line with preliminary study about PIR which demonstrated
PIR could potentially evaluate the LF modulation of BP. But it
is worth noting that there is also minor HF component appeared
in PIR spectrum.

III. RESULTS
A. Spectral Analysis of BP, Respiratory Signal, PTT and PIR
As can be seen in Fig. 3 (a), slow variability and fast
variability can be observed in a typical continuous BP signal.
Correspondingly, the variations of SBP, DBP and PP are shown
in Fig. 3 (b). Obviously, SBP contained both slow variation and
fast variation, whereas the DBP only showed slow variability,
with PP presented the fast variability. Power spectral density
(PSD) of SBP, DBP, and PP as illustrated in Fig. 2 (c)-(e) can
further describe this, where SBP showed LF variation centered
at around 0.1 Hz, with HF variation dominated between 0.2-0.3
Hz; and the LF spectrum components were more pronounced in
DBP, while PP mainly contained the HF variation. This is
Fig. 4. Time series and corresponding PSD of PP (a-b), PTT (c-d) and
consistent with previous study about BP variation. respiratory signal (e-f) of a representative subject.

Fig. 3. Continuous BP signal (a); beat-to-beat SBP, DBP and PP (b) of a Fig. 5. Typical time series and corresponding PSD of DBP (a-b) and PIR (c-d)
representative subject, with corresponding PSD of SBP (c), DBP (d) and PP (e). of a representative subject.

0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
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B. Performance of Proposed BP Model with PTT and PIR
The estimation results of proposed BP model were compared
with the continuous Finapres BP as the reference with regard to
correlation and agreement. The correlation and the
Bland-Altman plot of the SBP, DBP and MBP estimation for
our proposed method versus Finapres BP are given in Fig. 6.
The Persons correlation coefficient between overall estimated
SBP, DBP, and MBP and that of Finapres is 0.91, 0.88, and
0.89, respectively. For the Bland-Altman plot, the x-axis of the
plots presents the average of the estimation with the proposed
algorithm and the Finapres, while the y-axis shows the
difference between the two methods. The bias (mean) and the
limits of agreement (bias1.96SD) are illustrated in red solid
line and black dash dot lines, respectively. It is observed that
the majority of the points lie within the limit of agreement,
indicating that the estimated BP with the proposed method are
in close agreement with those made by Finapres. The bias for
SBP, DBP, and MBP estimates are -0.37, -0.08 and -0.18
mmHg, respectively.

Fig. 6. Correlation and Bland-Altman plots of SBP (a-b), DBP (c-d), and MBP (e-f) with the reference of Finapres BP.

C. Comparison of Proposed Model against Current PTT And the second PTT algorithm [9] can obtain SBP and DBP
Algorithms based on the following equation set:
To further evaluate the efficiency of the proposed method, 2
PTT0 1 PTT0
SBP0 DBP0
2 (14a)
we compared the proposed method with two of the most cited DBP MBP0 ln
PTT 3 PTT
PTT algorithms in the cuffless BP estimation area [7, 9].
The first PTT algorithm [7] estimates SBP in terms of relative 2
PTT0
PTT change through the following equation: SBP DBP SBP0 DBP0 (14b)
PTT

SBP SBP0
2
PTT PTT0 (13)
Fig. 7 shows a representative example from the subjects of
PTT0
the beat-to-beat Finapres SBP, estimated SBP by proposed

0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
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algorithm with PTT and PIR, compared to those by PTT

algorithms, where SBP_PTT (1) represents the first PTT
algorithm, and SBP_PTT (2) the second PTT algorithm. We
can see that estimated SBP with proposed method tracked
better with Finapres SBP compared with those of PTT methods.
For this dataset with 66 beat-to-beat SBP, the beat by beat
variation can be observed, and the average value measured by
Finapres was 115.194.87 mmHg, and the estimated values by
proposed method, first and second PTT methods were
115.794.82 mmHg, 113.343.65 mmHg, and 120.767.73
mmHg, respectively. The corresponding errors were 0.593.10
mmHg, -1.834.06 mmHg and 5.565.90 mmHg, respectively,
which further reveals that the SBP estimated with our method
shows better correlation with Finapres SBP than the control
PTT algorithms.
Since the first PTT method only contains the algorithm for
SBP estimation, DBP and MBP estimation were only compared
with those of the second PTT method. It can be seen from Fig. 8
that DBP varied slower than SBP, where the average Finapres
value was 73.252.98 mmHg. The estimated DBP with Fig. 8. Estimated beat-to-beat DBP with proposed method (green) and PTT
algorithm (dash blue) with the reference of Finapres DBP (red) (a) and the
proposed method and PTT method were 71.982.03 mmHg estimated errors (b) of one representative subject.
and 79.384.02 mmHg, respectively, with the corresponding
errors -1.272.11 mmHg and 6.135.23 mmHg. Obviously, the
estimation with the PTT method overestimated DBP not only in
terms of the average level but the variability.

Fig. 7. Estimated beat-to-beat SBP with proposed method (green) and PTT
algorithms (solid blue and dash blue) with the reference of Finapres SBP (red)
(a) and the estimated errors (b) of one representative subject.
The variation of MBP is also slow which is similar to that of
DBP, with average value of 87.233.20 mmHg, as depicted in
Fig. 9. The estimated MBP with proposed method and the PTT
method are 85.782.32 mmHg and 93.185.26 mmHg, with
corresponding estimation error of -1.452.27 mmHg and
5.945.37 mmHg, respectively, suggesting that the estimation
with the proposed method correlates better with Finapres MBP
than that of the PTT method.
Fig. 9. Estimated beat-to-beat MBP with proposed method (green) and PTT
algorithm (dash blue) with the reference of Finapres MBP (red) (a) and the
estimated errors (b) of one representative subject.
Furthermore, the overall performance was analyzed in terms
of difference mean, SD and MAD. Difference mean is a
measure of the bias of BP estimates, while difference SD is a
measure of error variability. MAD is a measure of overall
accuracy in estimating BP. The smaller MAD, the better overall
performance. Table I summarizes the values of mean, SD and
MAD for our proposed BP estimation method and the PTT
methods tested on 27 subjects, including 1713 heart beats. It is
observed that the difference mean of our proposed method in
estimating SBP, DBP, and MBP is within -0.37, -0.08, and
-0.18 mmHg of the Finapres, respectively; the difference SD of
the proposed method in estimating SBP, DBP and MBP is

0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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within 5.21, 4.06, and 4.13 mmHg of the Finapres, respectively; pulmonary vascular and aortic pressure, thereby leading to the
and the MAD of the proposed method in estimating SBP, DBP cyclic variation in BP. Several researchers have found that the
and MBP is within 4.09, 3.18, and 3.18 mmHg of the Finapres, modulation of this HF component for SBP spectrum was
respectively. Comparing with the PTT methods, it is evident linearly related to the respiratory sinus arrhythmia (RSA),
that our proposed method in estimating SBP, DBP and MAP indicating that respiratory fluctuations in BP was attributable to
achieves smaller difference mean, SD, as well as MAD, and the RSA [43]. Moreover, Drinnan et al [44] quantified the
difference is significant, indicating a better accuracy. relation between heart rate and PTT through paced respiration,
and found that there was a strong relationship between PTT and
TABLE I heart rate interval. Johansson et al [45] confirmed that PTT
ACCURACY, PRECISION, AND AGREEMENT BETWEEN FINAPRES BP AND varied in pace with respiration and detected the respiration rate
ESTIMATED BP WITH PTT, AND THAT WITH PTT AND PIR
reliably from PTT. The result of present study about the
PTT PTT
Proposed coupled frequency between PTT and respiratory signal further
Method (1) Method (2)
Method
[7] [9] verified this. Besides, PTT has been used as a measure of
SBP 0.19 -0.11 -0.37 respiratory effort [46], because PTT is inversely proportional
Mean DBP
(mmHg)
N/A 0.19 -0.08 to BP, and BP falls with inspiration with the rise in PTT. This
MBP N/A 0.09 -0.18 can also be observed from time series of PP, PTT and
SBP 6.21 7.31 5.21* respiratory signal as depicted in Fig. 4. With these
SD DBP N/A 6.03 4.06
considerations, we thus reasoned that PTT could reflect the
(mmHg) effect of respiration activity on BP, and can be used to estimate
MBP N/A 6.25 4.13
the HF component of BP variation, particularly PP.
SBP 4.94 5.76 4.09*
MAD On the other hand, the LF component of BP is associated
DBP N/A 4.80 3.18
(mmHg) with vasomotion waves that result from an oscillation of the
MBP N/A 4.96 3.18 sympathetic vasomotor tone. Except for the respiratory
*Statistically significant at the level 0.05 compared with PTT method (1); synchronous oscillations in BP, the vasomotor tone is also an
statistically significant at the level 0.05 compared with PTT method (2).
essential determinant of BP. A number of investigators
evidenced that the oscillations of vasomotor tone is caused by
IV. DISCUSSION
local changes in smooth muscle constriction and dilation
In the present study, we proposed a new indicator, the PIR through the modulation of the sympathetic nervous activity
that can reflect the arterial diameter change, to trace the LF [35, 36]. Though the underlying mechanism has remained
variation of BP, and established a novel BP model with the elusive, the fluctuations in vasomotor tone are considered to
combination of PIR and PTT. We found that the beat-to-beat relate to the local adjustment of peripheral resistance to regulate
BP contained both the HF and LF variation components, where the blood flow thus to meet the local metabolic demand. The
the HF component was dominant in PP and similar to that of adjustment of the peripheral resistance is mainly determined by
PTT as well as respiratory signal, while the LF range was the arterial diameter change, which is the result of the variations
primarily in DBP and was also coupled with the PIR. The PTT in the tension exerted by the smooth muscle in the vessel walls
and PIR were therefore adopted to estimated PP and DBP, [47]. In other words, the arterial diameter change might be the
respectively, and SBP can be obtained accordingly. The
primary factor that affects the vasomotor tone. PIR is related to
preliminary results on 20 healthy subjects demonstrated the
the arterial diameter change, and thus is hypothesized to reflect
feasibility of using both PTT and PIR to enhance the accuracy
the vasomotor tone and further the LF oscillations in BP. The
of PTT-based BP estimation.
spectrum of PIR and BP in this study could explain the
A. Effect of Respiration and Vasomotor Tone on BP hypothesis, which is also consistent with earlier reported
It has been long recognized that arterial BP fluctuates on a results. Our previous study analyzed the relationship between
beat-to-beat basis, and the application of spectral techniques to PIR and BP under the influence of autonomic nervous
continuous BP has revealed the presence of spontaneous activities, such as deep breathing, Valsalva maneuver, and
fluctuations including the oscillations at the HF range similar to sustained handgrip, and showed that increase level of BP was
respiratory frequency, and vasomotion waves in the LF range associated with a shift of PIR spectral power toward the LF
slower than the respiratory frequency [35, 36]. Power spectral component, suggesting the capability of PIR to evaluate the
analysis of SBP in this study was consistent with this, i.e., SBP modulation of sympathetic nervous activity on BP [30]. In
spectrum contained both the HF peak at around 0.25 Hz, which addition, Nitzan et al [48] used a similar indicator, the relative
was coupled with the respiratory frequency, and the LF peaks amplitude variability of PPG signal, to evaluate autonomic
focused at approximately 0.1 Hz. nervous system, and claimed that the variation of PPG baseline
Previous investigations demonstrated that the HF component and amplitude were mainly concentrated in the LF range,
oscillation in BP is related to the respiratory activity [42]. The implying the influence of the sympathetic nervous activity.
underlying mechanisms of the fluctuation of BP with B. PTT Methods for BP Estimation
respiration is probably due to the intrathoracic pressure change
PTT has been extensively studied for continuous BP
with breathing which has a mechanical effect on venous return,

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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
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estimation without a cuff. Despite of its theoretical feasibility,
the PTT-based BP measurement method hasnt been widely
applied clinically because of several existed problems;
particularly the accuracy issue remains the overarching
challenge facing researchers. Prior studies have reported that
PTT mainly presents the HF component variation of BP, but is
inadequate to follow the LF variation [28, 29], which we
hypothesize to be the utmost reason leading to the
unsatisfactory accuracy of most current PTT-based BP
measurement approaches.
Continuous BP could be accurately tracked if the
noninvasive physiological parameters used for cuffless BP
estimation can not only follow the HF respiratory influence on
BP, but also its LF oscillation due to the sympathetic
modulation of vasomotor tone. McCarthy et al [17] examined
two popular PTT-BP algorithms, which are also used in this
study as contrast methods, and found that neither these two
algorithms could provide reliable BP estimations over a long
period. The reason for Chens method with acceptable accuracy
with intermittent calibration is probably due to the combination
of LF variation of cuff-based BP with HF variation of PTT.
Without the intermittent calibration, the estimation accuracy of
SBP was reported to deteriorate from 0.641.55 mmHg to
-3.4229.22 mmHg within 10 min. As for Poons method, the
accuracy remained relatively stable, from 1.7910.50 mmHg to
1.249.74 mmHg within 10 min. The larger SD after the initial
calibration was potentially attributed to the HF variation of PTT
for DBP estimation, as can be seen in Fig. 9 (a). However, DBP
varies mainly in LF range, as shown in Fig. 5 (b). As a result,
the accuracy of SBP estimation was decreased, because SBP
was derived from DBP and PP. Besides, most of PTT-based
approaches estimated BP with PTT through linear or nonlinear
regression method, mostly for SBP estimation, rather than
theoretical model based on physiological significance. And
DBP has been reported to correlate less with PTT than SBP,
which is probably a consequence of the smaller range of
variations in DBP as found in those studies [10, 12, 16, 19].
Investigation by Liu et al [24] about the relationship
between PTT and BP during exercise and recovery revealed the
influence of the vascular smooth muscle tone on BP-PTT
relationship, suggesting that the vascular tone should be
considered into PTT-based BP estimation. Nevertheless, few
studies have attempted to take account this factor into the
PTT-based BP model to enhance the accuracy. The strengths of
this study, compared with previous studies of PTT-based
cuffless BP methods, are the introduction of a novel indicator to
evaluate the LF variation of BP, and its combination with PTT
to estimate BP to achieve more accurate estimations. With the
LF and HF of BP evaluated by PIR and PTT, continuous BP is
supposed to be predicted accurately without frequent
calibration. Moreover, despite of SBP, estimations of DBP and
MBP have also been achieved with acceptable accuracy.
C. Limitations
There are some limitations in this study. One concern is that
we validated our proposed method with Finapres monitor as the
reference, while the gold standard for continuous BP
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measurement should be the invasive intra-arterial method.
Second, the beat-to-beat estimation with the proposed method
and PTT methods were only within a short period of time. The
estimation with long-term period should be further validated.
Third, though the effects of breathing pattern on the respiratory
component of SBP spectrum have already been analyzed in
previous study [49], the pattern on PTT should be further
investigated. Furthermore, the utilization of PIR to assess the
vasomotor tone on BP should be further validated with more
experiments. Finally, the proposed method was tested on 20
healthy subjects, where the sample size is not large enough and
subjects with CVDs were not included.
V. CONCLUSION AND FUTURE WORK
In summary, we have presented a new model for BP
estimation using PTT and PIR, and validated the model
experimentally. We obtained more accurate results for the
cuffless BP estimation by using both PTT and the new
indicator, the PIR. By means of one-point calibration, the
beat-to-beat SBP, DBP and MBP can be calculated. We found
that PIR can indicate the LF variation of BP, whereas PTT
reflects the HF fluctuations of BP. In addition, a novel BP
model was established with the combination of PIR and PTT,
which outperformed the compared PTT-based methods in
terms of accuracy on 27 subjects. Most notably, this is the first
study to our knowledge to consider the use of PIR to estimate
the influence of vasomotor tone on BP. Our results provide
evidence for BP variations in both the LF and the HF range
where PTT can mainly reflect HF component, and indicates
that LF component of BP should be considered to improve the
estimation accuracy. Although the pilot study offers a potential
method for estimating cuffless BP with better accuracy, it
should be further validated with larger sample following with
corresponding standard requirement, for example, the IEEE
1708 standard for wearable cuffless BP measuring devices.
With better accuracy, we expect this method to provide insight
for cuffless BP estimation technique. Moreover, through
continuous monitoring BP in an unobtrusive way with an
acceptable accuracy permits better prevention and management
of hypertension, thus reducing the global burden generated by
CVDs.
ACKNOWLEDGMENT
The authors would like to thank the student volunteers from
Dept. of Electronic Engineering, The Chinese University of
Hong Kong for their participation in the experiment, and Dr. W.
Karlen from Mobile Health Systems Laboratory, ETH Zurich
for kindly helping to revise this manuscript.
REFERENCES
[1] C. K. Chow, et al., "Prevalence, awareness, treatment, and control of
hypertension in rural and urban communities in high-, middle-, and
low-income countries," JAMA, vol. 310, pp. 959-968, 2013.
[2] G. Parati, et al., "Assessment and management of blood-pressure
variability," Nat. Rev. Cardiol., vol. 10, pp. 143-155, 2013.
[3] D. Buxi, et al., "A survey on signals and systems in ambulatory blood
pressure monitoring using pulse transit time," Physiol. Meas., vol. 36,
pp. R1-R26, 2015.
This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/TBME.2015.2480679, IEEE Transactions on Biomedical Engineering
[4] Y. L. Zheng, et al., "Unobtrusive sensing and wearable devices for
health informatics," IEEE Trans. Biomed. Eng., vol. 61, pp. 1538 - 1554,
2014.
[5] L. Peter, et al., "A review of methods for non-invasive and continuous
blood pressure monitoring: Pulse transit time method is promising?,"
IRBM, vol. 35, pp. 271-282, 2014.
[6] D. J. Hughes, et al., "Measurements of Young's modulus of elasticity of
the canine aorta with ultrasound," Ultrason. Imaging., vol. 1, pp.
356-367, 1979.
[7] M. W. Chen, et al., "Continuous estimation of systolic blood pressure
using the pulse arrival time and intermittent calibration," Med. Biol. Eng.
Comput., vol. 38, pp. 569-574, 2000.
[8] J. Muehlsteff, et al., "Cuffless estimation of systolic blood pressure for
short effort bicycle tests: the prominent role of the pre-ejection period,"
in Proc. 27th Annu. Int. Conf. IEEE Eng. Med. Biol. Soc., Shanghai,
China, 2005, pp. 5088-5092.
[9] C. C. Y. Poon and Y. T. Zhang, "Cuff-less and noninvasive
measurements of arterial blood pressure by pulse transit time," in Proc.
27th Annu. Int. Conf. IEEE Eng. Med. Biol. Soc., Shanghai, China, 2006,
pp. 5877-5880.
[10] J. S. Kim, et al., "Effect of confounding factors on blood pressure
estimation using pulse arrival time," Physiol. Meas., vol. 29, p. 615,
2008.
[11] Y. Chen, et al., "Continuous and noninvasive blood pressure
measurement: a novel modeling methodology of the relationship
between blood pressure and pulse wave velocity," Ann. Biomed. Eng.,
vol. 37, pp. 2222-2233, 2009.
[12] M. Y. M. Wong, et al., "An evaluation of the cuffless blood pressure
estimation based on pulse transit time technique: a half year study on
normotensive subjects," Cardiovasc. Eng., vol. 9, pp. 32-38, 2009.
[13] M. Mas, et al., "Feasibility of cuff-free measurement of systolic and
diastolic arterial blood pressure," J. Electrocardiol., vol. 44, pp.
201-207, 2011.
[14] H. Gesche, et al., "Continuous blood pressure measurement by using the
pulse transit time: comparison to a cuff-based method," Eur. J. Appl.
Physiol., vol. 112, pp. 309-315, 2012.
[15] M. Forouzanfar, et al., "Coefficient-free blood pressure estimation based
on pulse transit time-cuff pressure dependence," IEEE Trans. Biomed.
Eng., vol. 60, pp. 1814-1824, 2013.
[16] A. Hennig and A. Patzak, "Continuous blood pressure measurement
using pulse transit time," Somnologie, vol. 17, pp. 104-110, 2013.
[17] B. McCarthy, et al., "An examination of calibration intervals required
for accurately tracking blood pressure using pulse transit time
algorithms," J. Hum. Hypertens., vol. 27, pp. 744-750, 2013.
[18] J. Sola, et al., "Noninvasive and nonocclusive blood pressure estimation
via a chest sensor," IEEE Trans. Biomed. Eng., vol. 60, pp. 3505-3513,
2013.
[19] T. Wibmer, et al., "Pulse transit time and blood pressure during
cardiopulmonary exercise tests," Physiol. Res., vol. 63, pp. 287-296,
2014.
[20] V. Chandrasekaran, et al., "Cuffless differential blood pressure
estimation using smart phones," IEEE Trans. Biomed. Eng., vol. 60, pp.
1080-1089, Apr 2013.
[21] J. H. Shin, et al., "Non-constrained monitoring of systolic blood pressure
on a weighing scale," Physiol. Meas., vol. 30, p. 679, 2009.
[22] M. Y. M. Wong, et al., "The effects of pre-ejection period on
post-exercise systolic blood pressure estimation using the pulse arrival
time technique," Eur. J. Appl. Physiol., vol. 111, pp. 135-144, 2011.
[23] C. Douniama, et al., "Blood pressure tracking capabilities of pulse transit
times in different arterial segments: a clinical evaluation," in Comput.
Cardiol., 2009, pp. 201-204.
[24] Q. Liu, et al., "Attenuation of systolic blood pressure and pulse transit
time hysteresis during exercise and recovery in cardiovascular patients,"
IEEE Trans. Biomed. Eng., vol. 61, pp. 346 - 352, 2013.
[25] A. Malliani, et al., "Physiology and Clinical Implications of Variability
of Cardiovascular Parameters with Focus on Heart Hate and
Blood-Pressure," Am. J. Cardiol., vol. 73, pp. C3-C9, Apr 7 1994.
[26] A. Malliani, et al., "Cardiovascular Neural Regulation Explored in the
Frequency-Domain," Circ., vol. 84, pp. 482-492, Aug 1991.
[27] G. Parati, et al., "Spectral analysis of blood pressure and heart rate
variability in evaluating cardiovascular regulation a critical appraisal,"
Hypertension, vol. 25, pp. 1276-1286, Jun 1995.
[28] H. T. Ma and Y. T. Zhang, "Spectral analysis of pulse transit time
variability and its coherence with other cardiovascular variabilities," in
0018-9294 (c) 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
View publication stats http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
Proc. 28th Annu. Int. Conf. IEEE Eng. Med. Biol. Soc., New York, USA,
2006, pp. 3958-3961.
[29] Q. Liu, et al., "Time-frequency analysis of variabilities of heart rate,
systolic blood pressure and pulse transit time before and after exercise
using the recursive autoregressive model," Biomed. Signal. Proces., vol.
6, pp. 364-369, Oct 2011.
[30] X. R. Ding and Y. T. Zhang, "Photoplethysmogram intensity ratio: a
potential indicator for improving the accuracy of PTT-based cuffless
blood pressure estimation," To be published in Proc. 37th Annu. Int.
Conf. IEEE Eng. Med. Biol. Soc., Milan, Italy, 2015.
[31] Factors that affect blood pressure. Available:
http://www.edises.it/file/minicd/germ002/misc/assignmentfiles/cardiov
ascular/Fact_Aff_Blood_Pressure.pdf
[32] Y. L. Zhang, et al., "Radial pulse transit time is an index of arterial
stiffness," Hypertens. Res., vol. 34, pp. 884-887, 2011.
[33] G. Mancia, "Short-and long-term blood pressure variability present and
future," Hypertension, vol. 60, pp. 512-517, 2012.
[34] J. M. Karemaker and J. Strackee, "Hemodynamic fluctuations and
baroreflex sensitivity in humans: a beat-to-beat model," Am. J. Physiol.
Heart. Circ. Physiol., vol. 253, pp. H680-H689, 1987.
[35] A. Malliani, et al., "Cardiovascular neural regulation explored in the
frequency domain," Circ., vol. 84, pp. 482-492, 1991.
[36] M. Pagani, et al., "Low and high frequency components of blood
pressure variability," Ann. N. Y. Acad. Sci., vol. 783, pp. 10-23, 1996.
[37] R. W. de Boer, "Beat-to-beat blood-pressure fluctuations and heart-rate
variability in man: physiological relationships, analysis techniques and a
simple model," Ph.D. Dissertation, Department of Physiology,
University of Amsterdam, Amsterdam, Netherland, 1985.
[38] D. H. Bergel, "The dynamic elastic properties of the arterial wall," J.
Physiol., vol. 156, pp. 458-469, 1961.
[39] N. Westerhof, et al., "The arterial windkessel," Med. Biol. Eng. Comput.,
vol. 47, pp. 131-141, 2009.
[40] T. Ruf, "The Lomb-Scargle periodogram in biological rhythm research:
analysis of incomplete and unequally spaced time-series," Biol. Rhythm.
Res., vol. 30, pp. 178-201, 1999.
[41] J. M. Bland and D. Altman, "Statistical methods for assessing agreement
between two methods of clinical measurement," Lancet, vol. 327, pp.
307-310, 1986.
[42] A. C. Dornhorst, et al., "Respiratory variations in blood pressure," Circ.,
vol. 6, pp. 553-558, 1952.
[43] J. A. Taylor and D. L. Eckberg, "Fundamental relations between
short-term RR interval and arterial pressure oscillations in humans,"
Circ., vol. 93, pp. 1527-1532, Apr 15 1996.
[44] M. J. Drinnan, et al., "Relation between heart rate and pulse transit time
during paced respiration," Physiol. Meas., vol. 22, pp. 425-432, Aug
2001.
[45] A. Johansson, et al., "Pulse wave transit time for monitoring respiration
rate," Med. Biol. Eng. Comput., vol. 44, pp. 471-478, 2006.
[46] O. Contal, et al., "Pulse transit time as a measure of respiratory effort
under noninvasive ventilation," Eur. Respir. J., vol. 41, pp. 346-353, Feb
2013.
[47] L. H. Peterson, "Regulation of blood vessels," Circ., vol. 21, pp.
749-759, 1960.
[48] M. Nitzan, et al., "The variability of the photoplethysmographic signal-a
potential method for the evaluation of the autonomic nervous system,"
Physiol. Meas., vol. 19, p. 93, 1998.
[49] D. Laude, et al., "Spectral-Analysis of Systolic Blood-Pressure and
Heart-Rate Oscillations Related to Respiration," Clin. Exp. Pharmacol.
Physiol., vol. 22, pp. 352-357, May 1995.