Yanlu Li1, Patrick Segers, Joris Dirckx, Roel Baets. 1. Photonics Research Group, INTEC-department, Ghent University-IMEC, Sint-Pietersnieuwstraat 41, 9000, Ghent, Belgium ; Center for Nano- and Biophotonics (NB-Photonics), Ghent University, Sint-Pietersnieuwstraat 41, 9000, Ghent, Belgium.
Abstract
Pulse wave velocity (PWV) is an important marker for cardiovascular risk. The Laser Doppler vibrometry has been suggested as a potential technique to measure the local carotid PWV by measuring the transit time of the pulse wave between two locations along the common carotid artery (CCA) from skin surface vibrations. However, the present LDV setups are still bulky and difficult to handle. We present in this paper a more compact LDV system integrated on a CMOS-compatible silicon-on-insulator substrate. In this system, a chip with two homodyne LDVs is utilized to simultaneously measure the pulse wave at two different locations along the CCA. Measurement results show that the dual-LDV chip can successfully conduct the PWV measurement.
Pulse wave velocity (PWV) is an important marker for cardiovascular risk. The Laser Doppler vibrometry has been suggested as a potential technique to measure the local carotid PWV by measuring the transit time of the pulse wave between two locations along the common carotid artery (CCA) from skin surface vibrations. However, the present LDV setups are still bulky and difficult to handle. We present in this paper a more compact LDV system integrated on a CMOS-compatible silicon-on-insulator substrate. In this system, a chip with two homodyne LDVs is utilized to simultaneously measure the pulse wave at two different locations along the CCA. Measurement results show that the dual-LDV chip can successfully conduct the PWV measurement.
Pulse wave velocity (PWV) is an important measure for arterial stiffness, which is highly related
with many cardiovascular diseases. A larger value of PWV indicates a greater arterial stiffness and
thus a higher risk of cardiovascular events, so in clinical practice PWV is used as an important and
independent predictor of cardiovascular mortality [1-4]. In practice, the carotid-femoral
PWV, which describes the average velocity of the arterial pulse propagating from the carotid to the
femoral artery, is usually used. The European Society of Hypertension suggested that a
carotid-femoral PWV of 12 m/s can be considered as the threshold of an estimate of subclinical organ
damage [5], and individuals with a
carotid-femoral PWV higher than this threshold should seek for clinical treatments to prevent
cardiovascular events.Several devices have been introduced to measure the carotid-femoral PWV, the most well known
being the Complior and Sphygmocor system [4].
For the assessment of local arterial PWV, however, there are no widespread commercial devices. It is
only since recent that efforts have been undertaken to measure the propagation of the pulse using
fast ultrasound-based techniques [6, 7]. Additionally, the measurement setup of the carotid-femoral PWV is
usually bulky and sometimes causes discomfort to subjects because they are palpated in the groin. A
new noninvasive method to measure the local PWV of the common carotid arteries (CCAs) using laser
Doppler vibrometry (LDV) technique has been proposed [3, 8]. This method simplifies the measurement
procedures and also overcomes the uneasiness in the conventionally used carotid-femoral PWV
measurement. However, the proposed measurement setup for the CCA PWV measurement is still bulky,
which prevent this technique from being widely used.In this paper, we present a compact device for the CCA PWV measurements, using a photonics
integrated circuit (PIC) consisting of two individual homodyne LDVs [9]. So far, not many LDV PICs have been reported. Compared to the
compact self-mixing technique [10], on-chip
homodyne LDV technique has easy demodulation algorithms. The footprint of this chip is smaller than
5 mm2. This dual-LDV PIC is realized on the silicon photonics platform using CMOS
compatible technologies [11]. Silicon
photonics has become very important in recent years to implement high bandwidth transceivers for
datacommunication applications. With this technology one can integrate passive optical waveguides,
optical filters, optical modulators, optical detectors and optical sources on a silicon-on-insulator
(SOI) wafer and do so with the standard technology portfolio of an advanced CMOS fab. But recently
the same technology has also gained considerable interest for sensing and biosensing applications
[12]. The big strength of silicon photonics
over other optical integration technologies is that one can make use of the very mature toolset in
an existing infrastructure and that there is a direct route to volume manufacturing at low cost.In the following part, the working principle of the proposed dual-LDV system is demonstrated
first. Then we discuss the algorithm for the PWV measurement, especially the cross-correlation
method. The measurement results, including the calibration measurements of the dual-LDV PIC and a
number of in-vivo PWV measurements, are demonstrated afterwards.
2. Description of the dual-LDV PIC
A detailed explanation to the principle of an on-chip single-point homodyne LDV has been given in
[9]. The PIC-based PWV measurement device
proposed in this paper consists of two such homodyne LDVs. The schematic of the on-chip system and
the measurement setup is shown in Fig. 1(a). Despite the
capability of integrating lasers and photo-detectors (PDs) on SOI chips [13, 14], we still use external
laser and PDs in this proof-of-concept setup to solely test the performance of the passive optical
system. The light source and the PDs are connected with the chip via a fiber array (FA), in which 12
single-mode fibers (2 meter long, core/cladding = 9/125 μm) have
one of their ends assembled on a V-groove array with a pitch of 127 μm.
Fig. 1
(a) The schematic of the PWV measurement device using a dual-LDV PIC chip. In the figure
os (in os1 and os2) stands for optical splitter,
hybrid for 90° optical hybrid, PC for polarization
controller, BPD for balanced photo-detectors, Mon for monitor,
TA for transmitting antenna, RA for receiving antenna,
GC for grating coupler. (b) The photo of a real dual-LDV chip with a bonded fiber
array, compared with a two euro coin.
(a) The schematic of the PWV measurement device using a dual-LDV PIC chip. In the figure
os (in os1 and os2) stands for optical splitter,
hybrid for 90° optical hybrid, PC for polarization
controller, BPD for balanced photo-detectors, Mon for monitor,
TA for transmitting antenna, RA for receiving antenna,
GC for grating coupler. (b) The photo of a real dual-LDV chip with a bonded fiber
array, compared with a two euro coin.During the operation, coherent light generated in the external laser is sent to the chip via the
FA. An optimized optical coupling between the fiber and the on-chip grating coupler (GC) is ensured
by a polarization controller (PC). In the 1×4 optical splitter
(os1) light is split into four parts: two parts are sent to the measurement arms of
the two stand-alone LDVs, the third part is split again into two reference signals with another
optical splitter (os2), and the fourth part is directly sent out to a detector
(Mon in Fig. 1(a)) to track the variations
of the light intensity. Two light transmitting antennas (TAs) and two light receiving antennas
(RAs), realized by means of grating couplers, are set in the measurement arms to send light out of
the chip and receive back reflections, respectively. A lens is set in front of the chip to focus the
two light beams from the TAs onto two locations on the neck region of the CCA. The two TAs (or RAs)
have a separation S = 0.98 mm to ensure an adequate large
distance S between the two measurement positions, which can be
calculated as follows where M is the magnification of the optical system,
d and d are the object and image
distances, respectively. The back-scattered signals are collected by the same lens and focused back
to the chip, where they are picked up by the RAs. To ensure that enough reflection is coupled to
their corresponding RAs, the locations of the RAs are set very close the TAs. According to the
Doppler effect, the recaptured reflection signals carry the information of the vibrations in their
time-dependent frequency shifts. They are mixed with the reference signals in the two 90°
optical hybrids [15] (see Fig. 1(a)). From each 90° optical hybrid, four optical signals are
obtained and sent to two external balanced PDs. The footprint of this PIC is smaller than 5
mm2, and most of the space is taken by the FA. A photo of the chip is shown in Fig. 1(b), in which the actual area of the dual-LDV PIC is shown in
the green box.With the help of an analog-to-digital converter (ADC), the generated photocurrents of the
balanced PDs are transformed into digital signals, which are used to recover the instantaneous
velocity of each vibration using a digital “arc-tangent” demodulation method
[9]. After the demodulation, two curves
representing the instantaneous velocities of the vibrations can be obtained. The sampling time of
the ADC t determines the maximal detectable displacement speed of the
neck surface v =
λ0/2t, where
λ0 is the wavelength of the light. In our measurement, the
sampling frequency f = 1/t is
chosen to be 40 kHz, which corresponds to a v of 31 mm/s. Note that the
value v is not related to PWV.Considering the resolution of a measured PWV, it is better to use a large
S value, which is, however, limited by the size of the neck. In
practice, the distance S is normally chosen to be larger than 1 cm,
indicating that the value of |M| is normally larger than 10. In this case, however,
the numerical aperture of the lens on the image side is very small, which results in a strong
reduction in the power of the backscattered light. In order to obtain a stronger reflection, two
pieces of retro-reflective tapes are attached on the sites where the vibrations are measured.
Considering the source side of the lens, the aperture of the lens D should be large
enough to collect both light beams from the chip to avoid additional loss, indicating that
D > D = S
+ 2d tan(θ/2), where
θ ≃ 11° is the divergence angle of the output light (see
Fig. 1(a)) and D is the total
size of the two beams when they reach lens. In this setup, a lens (C280TME-C from Thorlabs) with a
focal length f = 18.4 mm and aperture D = 5.5 mm
is used, and its position is adjusted with the help of a translation stage. The separation
S is around 1.5 cm, which leads to d
= 300 mm and D = 4.8 mm (being smaller than
D).Since optical frequency shifters are not used in homodyne LDVs (see [16]), homodyne LDVs have a relatively low production cost compared to
heterodyne. Hence homodyne LDVs are used in this device. However, homodyne LDVs also have drawbacks,
e.g. they may not work well for vibrations smaller than half a wavelength. But this problem is not
critical in the PWV measurement and can be alleviated by stabilizing the laser source and using a
temperature controller. In addition, the wave pulse is usually very strong and thus weaker
vibrations can usually be ignored.
3. Algorithms for retrieving PWV
The PWV is usually retrieved by measuring the transit time of the pulse wave between the two
measurement locations, denoted as Δt. The value of PWV can be obtained from
Δt and S using the following formula
The accuracy of the PWV measurement thus depends on the accuracy of the
retrieved transit time Δt. The maximal detectable PWV value
PWV is ultimately limited by the sampling frequency
t of ADC, and their relation can be written as
PWV =
S/t. Providing
f = 40 kHz and S = 1.5 cm,
a PWV of 600 m/s can be obtained. However, due to the inaccuracy in the
algorithm for retrieving Δt and deviations in the measurements, the
PWV is determined by the transit-time error
t in the measurement rather than t. The
value t depends on many factors, including shape changes between the
two pulses, errors in the LDV outputs due to the weak useful reflection and the existence of on-chip
spurious reflections, and limitations in the algorithms used for retrieving
Δt. In [3], a
cross-correlation algorithm is used to retrieve the PWV, in which the transit time between the two
measurement locations (Δt) is obtained from the cross-correlation of the
two measured velocity curves. The accuracy of this method depends on the shape changes between the
measured velocity curves of the two vibrations. These shape changes are partly caused by propagation
dispersion of the pulse wave and reflection at sites with impedance mismatch [6], and partly caused by errors of homodyne LDVs when light
reflection is not strong enough. Hermeling et al. proposed to use the transit time
of the systolic foot of the pressure waveform [6], in which the deviation also depends on the shape variation and the accuracy of
the LDV system. However, this algorithm is more complex than the cross-correlation method in many
cases.
4. Measurement results
The LDV PICs are fabricated via ePIXfab [17]. A calibration measurement was firstly done on two separate earphones, on which
two pulses were generated by two voltage signals with the same shape but a relative preset time
delay Δt. The input light with a wavelength of 1550 nm has a power of 6 dBm
and linewidth of 150 kHz. Light at this wavelength has the minimal loss in both optical fibers and
SOI devices. These challenging test conditions correspond to a pulse wave velocity of up to 150 m/s,
which is well beyond the values that can be expected in vivo. In Fig. 2(a), the velocity curves of the two pulses with a preset delay
Δt = 0.8 ms is shown. It can be seen that a time delay of 0.8 ms is
retrieved from the leading edge delay of two pulses, while the delay derived from the
cross-correlation method is around 0.85 ms (see Fig. 2(b)).
The retrieved results of these two methods have been compared using a series of measurements (see
Fig. 2(c)). The measured root-mean-square deviations of the
leading-edge and cross-correlation algorithms are 0.13 ms and 0.08 ms, respectively. The
cross-correlation method is less sensitive to noise and spurious reflections in this situation.
Besides, their influences are also strongly reduced by filtering. Therefore, the estimated deviation
is mainly caused by the shape difference between the two pulses.
Fig. 2
Calibration measurement results of two pulses generated on two separate earphones. The two pulses
are with similar shapes but are generated at different times. (a) The measured two pulses with a
delay of 0.8 ms. (b) The cross correlation of the two velocity curves, which shows a time delay of
0.85 ms. (c) The recovered delay time for different method, where
x-corr means cross-correlation method.
Calibration measurement results of two pulses generated on two separate earphones. The two pulses
are with similar shapes but are generated at different times. (a) The measured two pulses with a
delay of 0.8 ms. (b) The cross correlation of the two velocity curves, which shows a time delay of
0.85 ms. (c) The recovered delay time for different method, where
x-corr means cross-correlation method.Then the device was used to measure the CCA PWV in vivo. The person under test
was a healthy male volunteer aged 26 years. During the test, the volunteer was sitting in an upright
position in front of the device, with two retro-reflective tapes attached to two locations along the
CCA (see Fig. 3). The separation of the two locations was
between 1.5 cm and 1.7 cm. The two light beams were adjusted to be focused on the two
retro-reflective tapes, respectively. The demodulated velocity results for a representative
measurement are shown in Fig. 4(a), and the cross-correlation
of the velocities is obtained and shown in Fig. 4(b). It is
seen that the transit time of the pulse is around 3.3±0.1 ms, and this corresponds to a PWV
between 4.85±0.45 m/s. The displacement and acceleration signals are also shown in Fig. 5(a) and Fig. 5(b). If
a proper filter is applied, the cross-correlation method can also work well with the acceleration
signal, but not with the displacement signal, which has a strong low-frequency variation. Another
byproduct of the LDV system is the heart rate of the subject. In this measurement, the average heart
rate of the subject is around 78 bpm, which is calculated according to the time delay between two
adjacent pulses.
Fig. 3
Schematic of the CCA PWV measurement using on-chip dual-LDV system.
Fig. 4
(a) The velocity curves of the two pulses. (b) The cross-correlation of the two measured pulses.
A time delay Δt = 3.3 ms is obtained using the correlation
method.
Fig. 5
(a) The displacements of the two pulses. (b) The accelerations of the two pulses.
Schematic of the CCA PWV measurement using on-chip dual-LDV system.(a) The velocity curves of the two pulses. (b) The cross-correlation of the two measured pulses.
A time delay Δt = 3.3 ms is obtained using the correlation
method.(a) The displacements of the two pulses. (b) The accelerations of the two pulses.
5. Conclusion
In this paper, the proof-of-concept of a miniaturized PWV measurement device utilizing dual-LDV
photonic integrated circuit is demonstrated with initial experimental results. The cross-correlation
method is used to derive the PWV, and the time delay error was found to be 0.1 ms. When the
separation between the two measurement spots is only 1.5 cm apart from each other, the measurable
range of this device can cover all possible values of the CCA PWV. In future work, efforts should be
made to integrate lasers and photo-detectors on the same photonic integrated circuits. A PIC with
more than two LDVs is also interesting for future study since it can be used to obtain more
information of the pulses at different locations.
Authors: Giuseppe Mancia; Guy De Backer; Anna Dominiczak; Renata Cifkova; Robert Fagard; Giuseppe Germano; Guido Grassi; Anthony M Heagerty; Sverre E Kjeldsen; Stephane Laurent; Krzysztof Narkiewicz; Luis Ruilope; Andrzej Rynkiewicz; Roland E Schmieder; Harry A J Struijker Boudier; Alberto Zanchetti; Alec Vahanian; John Camm; Raffaele De Caterina; Veronica Dean; Kenneth Dickstein; Gerasimos Filippatos; Christian Funck-Brentano; Irene Hellemans; Steen Dalby Kristensen; Keith McGregor; Udo Sechtem; Sigmund Silber; Michal Tendera; Petr Widimsky; Jose Luis Zamorano; Sverre E Kjeldsen; Serap Erdine; Krzysztof Narkiewicz; Wolfgang Kiowski; Enrico Agabiti-Rosei; Ettore Ambrosioni; Renata Cifkova; Anna Dominiczak; Robert Fagard; Anthony M Heagerty; Stephane Laurent; Lars H Lindholm; Giuseppe Mancia; Athanasios Manolis; Peter M Nilsson; Josep Redon; Roland E Schmieder; Harry A J Struijker-Boudier; Margus Viigimaa; Gerasimos Filippatos; Stamatis Adamopoulos; Enrico Agabiti-Rosei; Ettore Ambrosioni; Vicente Bertomeu; Denis Clement; Serap Erdine; Csaba Farsang; Dan Gaita; Wolfgang Kiowski; Gregory Lip; Jean-Michel Mallion; Athanasios J Manolis; Peter M Nilsson; Eoin O'Brien; Piotr Ponikowski; Josep Redon; Frank Ruschitzka; Juan Tamargo; Pieter van Zwieten; Margus Viigimaa; Bernard Waeber; Bryan Williams; Jose Luis Zamorano Journal: Eur Heart J Date: 2007-06-11 Impact factor: 29.983
Authors: Viviana Mancini; Aslak W Bergersen; Jan Vierendeels; Patrick Segers; Kristian Valen-Sendstad Journal: Cardiovasc Eng Technol Date: 2019-04-01 Impact factor: 2.495