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Quantifying tissue mechanical properties using

photoplethysmography
Tony J. Akl,1,* Mark A. Wilson,2,3 M. Nance Ericson,4
and Gerard L. Coté 1
1
Department of Biomedical Engineering, Texas A&M University, 5045 Emerging Technologies Building, 3120
TAMU, College Station, TX 77843-3120, USA
2
Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213 USA
3
VA Pittsburgh Healthcare System, University Dr. C-1w142, Pittsburgh, PA 15240 USA
4
Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN 37831-6006 USA
*
takl@tamu.edu

Abstract: Photoplethysmography (PPG) is a non-invasive optical method


that can be used to detect blood volume changes in the microvascular bed of
tissue. The PPG signal comprises two components; a pulsatile waveform
(AC) attributed to changes in the interrogated blood volume with each
heartbeat, and a slowly varying baseline (DC) combining low frequency
fluctuations mainly due to respiration and sympathetic nervous system
activity. In this report, we investigate the AC pulsatile waveform of the
PPG pulse for ultimate use in extracting information regarding the
biomechanical properties of tissue and vasculature. By analyzing the rise
time of the pulse in the diastole period, we show that PPG is capable of
measuring changes in the Young’s Modulus of tissue mimicking phantoms
with a resolution of 4 KPa in the range of 12 to 61 KPa. In addition, the
shape of the pulse can potentially be used to diagnose vascular
complications by differentiating upstream from downstream complications.
A Windkessel model was used to model changes in the biomechanical
properties of the circulation and to test the proposed concept. The modeling
data confirmed the response seen in vitro and showed the same trends in the
PPG rise and fall times with changes in compliance and vascular resistance.
©2014 Optical Society of America
OCIS codes: (170.3660) Light propagation in tissues; (280.1415) Biological sensing and
sensors.

References and links


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(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2362
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1. Introduction
Photoplethysmography (PPG) is one of the commonly used methods to record the pulse non-
invasively [1]. It can be used to measure changes in optical absorption due to variation in
blood volume in the interrogated tissue. PPG sensors illuminate tissue with various
wavelengths of light and collect the remainder of the light after it travels through tissue.
These sensors can be divided into two categories depending on the probe formation and the
location of light collection. The first approach is transmission which uses a photodetector and
a light source on opposite sides of the tissue to measure optical intensity after light has
propagated through tissue. The second approach is reflectance, in which the light source and
photodetector are placed on the same surface of the tissue to measure the diffuse reflectance
of light. The pulsatile blood flow causes changes in the tissue blood volume. This leads to
variation in optical absorption which modulates the intensity of the collected light. PPG has
been used in various applications ranging from heart rate monitoring [2, 3] to non-invasive
perfusion tracking and imaging [4, 5], but pulse oximetry remains the most common and
widely adapted application of PPG [6, 7].
The aforementioned applications rely on the frequency of the pulse and its amplitude on
various wavelengths to extract the desired physiologic information (hemoglobin oxygen
saturation, perfusion, heart rate, respiratory rate, etc.). However, the waveform of the pulse
has been shown to carry substantial information about the biomechanical state of the
cardiovascular network [8, 9]. For example, the pulse wave velocity can be used for
monitoring blood pressure changes [10]. Similarly, the waveform shape can be employed to
assess arterial stiffening due to aging and cardiovascular problems [8, 9, 11, 12]. These
methods measure the peripheral pulse to assess systemic changes. However, to our
knowledge, there are no PPG based methods to assess local tissue mechanical changes that
are critical in the diagnosis and monitoring of various diseases that affect tissue composition
and blood flow. Current non-invasive methods of measuring mechanical properties are based
mainly on Magnetic Resonance Elastography (MRE) [13] and ultrasound elastography [14]

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2364
which are not suitable for continuous monitoring. Non-invasive measurements of local tissue
mechanical properties can be of great importance to monitoring and diagnosing a wide variety
of conditions such as liver fibrosis, lung fibrosis, wound healing, tissue burns monitoring,
edema, and many others [15–17]. Our research has been primarily focused on the application
of monitoring hepatic tissue and diagnosing vascular complications of liver transplants.
Every year, around 6,000 patients receive a liver transplant in the United States alone
[18]. These patients have the highest graft rejection risk in the first two weeks following the
surgery [19]. During this period, the graft monitoring standard relies on frequent blood tests
for liver enzymes and biopsies [20, 21]. These tests often detect complications in a late stage
increasing the risk on the patient’s life. Our group is working on developing an implantable
optical sensor with telemetry capabilities to monitor transplanted organs and provide
feedback to the medical staff in real-time [22–25]. The system is a three wavelengths PPG
sensor that can measure perfusion and oxygenation changes simultaneously. We believe that,
by using the pulse waveform, we can provide more information to the medical staff to assess
the state of the graft and complement these measurements. For example, an occlusion in a
vein or an artery leads to a decreased level of perfusion. However, an occlusion in the vein
results in an increase downstream resistance to pulsatile flow while an arterial occlusion does
not affect the resistance experienced by the blood in the organ. This can be observed in the
shape of the pulse and can be used to differentiate arterial and venous complications which
are treated differently by the medical care providers.
In addition, after initial diagnosis, liver failure is confirmed by performing a biopsy. Liver
biopsy is an invasive procedure associated with various complications [26, 27] and 40% of
patients undergoing liver biopsies experience pain [28]. Biopsies also suffer from sampling
errors due to tissue heterogeneity [28]. A non-invasive optical system that can measure
mechanical properties can be used to guide biopsies to account for heterogeneity and reduce
the number of needed biopsies. The proposed concept can be applied to a point PPG sensor
[29] or an imaging PPG system [3, 30] to scan the hepatic tissue and create a map of
mechanical properties. In this work, we apply this concept to a point sensor for continuous
graft monitoring.
Specifically in this paper, we present in vitro results showing the ability of using the pulse
waveform to quantify tissue phantom compliance and diagnose vascular complications. The
results are supported by numerical simulations using a Windkessel Model [31, 32].
2. Materials and methods
2.1 Signal processing and instrumentation
A custom bench-top PPG system was used to collect the data. The system was described in
detail by Ericson et al. [25]. In summary, the system uses three time-multiplexed light
emitting diodes (LEDs) emitting light at different wavelengths in the red to near infrared
spectral region (central wavelengths of 735, 805, and 940 nm). The diffuse reflectance is
collected using a single photodetector. The collected signal on each wavelength is filtered and
split into two channels. The first channel provides an amplified version of the AC component
of the PPG while the second channel provides the slowly varying DC component of the PPG
signal. The AC and DC channels are both needed when performing perfusion and
oxygenation measurements. However, in this work, since our interest is focused on the
pulsatile waveform, only the AC channel was used in the processing. Figure 1 shows a
schematic of the collected signal before filtration and separation of the AC and DC
components.

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2365
Fig. 1. Schematic of the PPG signal showing the AC and DC signals.

To understand the reasoning behind the signal processing, we start by a simplified


description of the origin of the pulse. When blood flows into a capillary bed, it encounters an
impedance due to the size and distribution of the vessels, the compliance of the vessels and
surrounding tissue, and many other factors that depend on the mechanical structure of the
tissue and vasculature. In addition, it also encounters a back flow due to a reflected wave
generated at an impedance mismatch point such as the peripheral vessels or the aortic valve.
These properties give the pulse its shape, which is different from the shape of the cardiac
output (blood flow out of the heart).
One method of describing the process is from an electrical circuit perspective. The liver
during the diastole can be thought of as a simple resistive-capacitive (RC) electric circuit
where the resistance is the vascular resistance to the flow and the capacitance is the
compliance of the hepatic circulation. The capacitor discharge describes the emptying of the
hepatic blood content into the main circulation. The current represents the blood flow while
the electric potential (voltage) mimics the blood pressure that controls the blood volume in
the capillary bed. This concept is commonly used in studying biomechanical systems [31, 32].
When the resistance increases the time constant (τ = R*C), which represents the temporal
response of the system, also increases. This increase in resistance is indicative of a
downstream vascular blockage or narrowing. Note that when the narrowing or blockage takes
place upstream from the measurement site, the resistance experienced by the hepatic blood
during diastole is unaffected and the time constant is not expected to change. Similarly, a
capacitance decrease is indicative of a decrease in compliance or rather stiffening of the tissue
that can be due to a variety of conditions such as hepatic edema, which is very common after
transplant, or fibrosis.
To obtain a quantifiable measure of this time constant, we measure the rise time in the
PPG pulse which corresponds to the diastole phase [33]. The rise time was defined as the time
between the foot of the pulse and the peak. To avoid any errors due to noise causing
fluctuations during these periods, we used the time between the point that is 10% larger than
the valley and the point that is 10% lower that the peak as shown in Fig. 2. All measurements
were made using automated software developed in MATLAB (Mathworks, Natick, MA).
Note that the data in Fig. 2 shows the optical intensity corresponding to a simulated pulse.
The optical intensity changes in the opposite direction of the blood pressure and that is why
the pulse looks inverted (an increase in pressure corresponds to an increase in absorption
which leads to a decrease in intensity). This is explained in more detail in previous review
article and book chapter [1, 34].

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2366
Fig. 2. A PPG waveform obtained by a Windkessel model showing the detected peaks (red
circles) and valleys (red x) using custom automated software developed in MATLAB. The
green symbols show the data points used in calculating the rise time.

2.2 Phantom preparation


The proposed concept was tested in a series of in vitro phantom studies. Polydimethyl-
siloxane (PDMS) phantoms were fabricated with different curing parameters to adjust their
mechanical properties. PDMS was mixed with various optical absorbers (blue food coloring
and black India ink) and scatterers (100 nm and 0.5-1 µm Aluminum Oxide powder) to mimic
the optical properties of hepatic tissue in the 630 – 1,000 nm wavelength range. The recipe
was described in detail in a previous report by our group [35]. The phantoms mimic the
structures of the portal vein (PV), the main blood and nutrients supplier to the liver. The
curing parameters that control the PDMS mechanical properties include the curing
temperature, curing time, and the concentration of the curing agent. A detailed study on the
effects of curing parameters on the Young’s Modulus (YM) of PDMS was reported by Hong
et al. [36]. Note that the addition of the optical scatterers and absorbers changes the
mechanical properties of PDMS.
For the purpose of this study, three different sets of phantoms were fabricated. The curing
time and temperature were 24 hours and 60 °C for all three phantoms while the PDMS to
curing agent volumetric ratio was changed between 30:1, 40:1, and 45:1 v/v which yielded a
Young’s modulus (YM) of 11.7, 15, and 61 KPa respectively. All YM measurements were
obtained from stress-strain curve measurements acquired by an Instron 3345 (Instron, MA,
USA). The calculations were made using an automated program developed in MATLAB.
Note that compliance of a structure is inversely proportional to the incremental modulus
(C∝1/E) and a larger YM indicates a less compliant material [37]. All the reported
measurements are for the PDMS with the optical absorbing and scattering agents included,
which yields a higher YM in comparison to clear PDMS. Figure 3 shows the raw data from
the tensile tests of two of the phantoms.
Similarly, to avoid handling blood, an optical mixture of various optical dyes was used to
mimic the optical properties of oxygenated hemoglobin. The mixture was described in detail
in previous reports [38].

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2367
Fig. 3. Stress-strain curves for the three PDMS phantoms.

2.3 In vitro setup


The phantoms described above were connected to a fluidic circuit to mimic the pulsatile
blood flow. A peristaltic pump controlled via a virtual instrument (VI) designed in LabVIEW
was used to control the pulsatile flow. The phantoms were perfused with the dye mixture and
c-clamps were placed on the tubing on either side of the phantom to occlude flow when
needed. The PPG probe was placed on top of the phantom and held in place with a
mechanical arm. Figure 4 shows a schematic of the system. The insets show the PPG signal
collected from the phantom experiments during a downstream and an upstream occlusion.
Note the change in the waveform when a downstream occlusion is performed. In both cases
the occlusion causes a reduction in flow which leads to a decrease in the pulse amplitude.

Fig. 4. Schematic of the in vitro setup showing the PPG benchtop system, the peristaltic pump,
and the flow circuit used to mimic the portal vein. The insets on the bottom left and bottom
right show PPG waveforms collected during an upstream and a downstream occlusion
respectively.

2.4 Windkessel model


To study the expected performance of the system theoretically over a wider range of
physiologic conditions, we developed a four element (R, C, L, r) Windkessel model [31]. The
resistive and capacitive elements (R and C) in this model can be explained as mentioned
earlier in the Signal processing and instrumentation section. In summary, the resistance, R,
represents the peripheral/downstream resistance. The capacitive element, C, represents the
compliance of the microvasculature and tissue. In addition, an inductance is added to the
model to account for the inertia of blood flow. Finally, r is the characteristic impedance of the

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2368
circulatory system under investigation and is typically much smaller than R (5-7% of R) [32].
An extensive review of Windkessel models and their relation to physiologic parameters was
reported by Westerhof et al. [32]. The differential equations governing the behavior of this
model were developed by applying circuit theory and solved numerically using software
developed in MATLAB. Figure 5 shows a schematic of the four element Windkessel model.

Fig. 5. Schematic of the four-element Windkessel model used to simulate the arterial pulse.

Note that this model is not meant to be an accurate representation of hepatic circulation
but more of a general model to mimic physiologic signals and highlight the expected changes
in the pulse with various parameters. The blood flow was modeled by Eq. (1) as reported by
Ballal et al. [39]:

 HR HR
 I 0 .sin (π .mod(t , 60 / HR ) . , mod(t , 60 / HR ) ≤
i (t ) =  60.ts 60.ts (1)
 0 , otherwise

where I0 represents the peak blood flow and was set to 500 mL/s. HR is the heart rate in beats
per minute (bpm) and ts is the ratio of the systole time divided by the cardiac cycle time. HR
and ts were set to 70 bpm and 0.4 respectively. “mod” refers to the modulo operation.
As discussed earlier, the modeled pulse (blood pressure and/or volume) mimics the
change in optical absorption. To determine the changes in optical intensity measured by the
PPG sensor, we used the approximation shown in Eq. (2). This approximation can be used
since we are not as interested in the amplitude of the pulse as we are in its waveform. The
blood flow signal and three different pressure waveforms obtained by the Windkessel model
are shown in Fig. 6. These three waveforms were used to mimic data found in the literature to
validate the performance of the model. The shape of the pulses is similar to in vivo data
reported in literature [1, 9].
I ∝ Pmax − P (2)

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2369
Fig. 6. (a) Modeled blood flow. (b) Three pressure waveforms with different mechanical
properties showing the changes in the pulse shape.

3. Results
3.1 In vitro studies
3.1.1 Compliance changes
For the initial studies, two phantoms were developed and used in the testing. The phantoms
have a Young’s modulus of 11.5 and 61 KPa which mimic the change from normal hepatic
tissue to the last stage of fibrosis [40]. The different phantoms were placed in the flow circuit
described above and the benchtop PPG system was used to measure the pulsatile signal.
Figure 7 shows two waveforms measured from the different phantoms.

Fig. 7. Pulse measured from a soft (11.7 KPa) and a stiff (61 KPa) phantom (left and right
respectively)

The rise time was measured from one minute of continuous data for each phantom. This
was repeated three times for each phantom and the average and standard deviation were
calculated accordingly. As depicted in Fig. 8, the rise time decreased with increased Young’s
modulus (decreased compliance). The left panel shows the PPG signal measured from the two
different phantoms and the change in the rise time. Each phantom was placed in the flow
circuit three different times and the average rise time is shown in the bar plot of the right
panel. The error bars correspond to +/− one standard deviation. Note that the rise time is also
affected by the changes in the flow circuit (tubing material, tubing dimensions, pump,
connectors, etc.). The rise time decreased from 305.6 +/− 8.88 ms to 195.3 +/− 10.2 ms for
the 11.7 KPa and 61 KPa phantoms respectively.

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2370
Fig. 8. Changes in the pulse rise time with compliance.

To obtain a more accurate trend of the rise time over the range of interest, a third PDMS
phantom with a YM in between the two original values was prepared and data was recollected
from all three phantoms. The phantom’s YM was 15 KPa as tested by the Instron tensile
tester. Figure 9 shows the data from the three phantoms. Note that the values changed from
the previous experiment since they depend on the flow circuit (i.e. tubing, pumps, etc.) which
was modified between the two experiments.

Fig. 9. Pulse rise time measured from three different PDMS phantoms with YM of 11.7, 15.1,
and 61 KPa.

3.1.2 Diagnosing vascular complications


For each of the phantoms, after collecting baseline data for 30 – 60 s, flow was occluded
using a c-clamp either upstream or downstream from the phantom. For the first occlusion, the
clamp was tightened until a visual decrease in pulse amplitude was observed. The same
number of turns on the c-clamp was used for every occlusion afterwards. During both
upstream and downstream occlusions, the amplitude of the PPG signal decreased indicating a
decrease in the pulsatile flow. However, in the case of downstream occlusions, an increase in
the PPG rise time was recorded which is due to the increase in the resistance. This was not
observed during upstream occlusions. Figure 10 shows examples of a downstream and an
upstream occlusion. In both cases, the rise time in the recovery period, after the occlusion was
released, was the same as the baseline value.

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2371
Fig. 10. Example of a downstream (left column) and an upstream occlusion (right column). In
both cases, the amplitude of the pulse (top line) decreases indicating a drop in flow level. The
rise time (bottom line) increased only in the case of downstream occlusions.

This experiment was repeated three times for each type of occlusion. The bar graphs in
Fig. 11 show the average and standard deviation of all runs for the 11.7 and 61 KPa
phantoms.

Fig. 11. Bar plot of the rise time during upstream (USO) and downstream (DSO) occlusions
for the 11.7 and 61 KPa phantoms. The error bars correspond to +/− one standard deviation.

3.2 Modeling results


To test the proposed concept over a wider range of parameters that cover the full physiologic
range, we used the Windkessel model described earlier. The compliance was changed
between 0.35 and 3.25 cm3/mmHg which correspond to Young’s moduli of 73.2 to 7.9 KPa
respectively. This conversion was made by assuming that the vessel is expanding only in the

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2372
radial direction and using the equations for elastic modulus and compliance as reported by
Gosling et al. [41]. Note that the relationship between compliance and Young’s modulus is
not linear. The compliance is proportional to the inverse of the modulus (C∝1/E). Similar to
the in vitro data, the rise time increased for higher compliance levels while the fall time
decreased (Fig. 12).

Fig. 12. Changes in the rise time and fall time of the PPG pulse for different simulated
compliance values using the Windkessel model. The green region indicates the range for
normal tissue while the red correspond to fibrotic tissue at different stages. The right panel
shows the data after conversion of the compliance values to YM.

Because the rise time depends on parameters other than the compliance such as the
resistance in the flow circuit, we scaled our in vitro results to fit the model. Specifically, the
data from the lowest YM (11.7 KPa) was scaled to the rise time curve obtained by the
Windkessel model and the same scaling factor was used for the other two phantoms. This
scaling does not affect the trend of the data and helps compare the trend from the theory to
that of the in vitro data. The dots in the right panel of Fig. 12 show the scaled data from the in
vitro studies (data from Fig. 9).
To mimic vascular occlusions, we modeled the case of increased resistance. The normal
physiologic range of systemic vascular resistance is typically in the range of 11.25 to 18
mmHg.min/L (1,170 +/− 270 dynes-sec/cm5) [42]. We modeled resistance changes between
8.3 and 27.3 mmHg.min/L which covers the normal range and the elevated resistance range
as shown in Fig. 13.

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2373
Fig. 13. Changes in the pulse rise and fall time for different levels of vascular resistance. The
green region indicates the normal range while the red corresponds to increased vascular
resistance that can be caused by downstream vascular complications.

4. Discussion
The mechanical properties of tissue can be significant for a number of medical applications.
In particular for our work, mechanical properties are of great importance to the success of
transplant surgeries [43] and are indicators of hepatic health [44–46]. In this paper, we
showed the ability of using the waveform of the PPG signal to monitor changes in compliance
and diagnose vascular complications that are the second most common cause of graft failure
after primary graft non function [47, 48]. The proposed concept can be used in sensing
systems for continuous graft monitoring or point interrogation, and potentially in imaging
systems (i.e. iPPG) for rapid assessment of tissue mechanical properties.
The sensitivity to compliance changes in the physiologic range was shown theoretically
through modeling and confirmed in vitro using PDMS based phantoms. The YM of hepatic
tissue for healthy individuals has been shown in previous reports to be around 5.5 KPa (Stage
F0-1) [40]. This value is higher for vessels, for example the portal vein YM was reported by
Wang et al. to be 32.04 +/− 5.65 KPa for a pressure of 75 mmHg [45]. Tissue compliance has
been reported to decrease 3 to 10 times with the development of fibrosis [40, 44, 49] which
results in a similar increase in its YM. For our in vitro studies, phantoms were developed with
YM of 11.7, 15 and 61 KPa and the analysis of the PPG rise time showed a significant
decrease with the increase of the YM. In addition, to test the expected changes over a wider
range of mechanical properties, the concept was applied to signals generated from a
Windkessel model. YM levels in the range of 7 to 73 KPa were tested and the results are
similar to the in vitro experiments. Note that the absolute values of the rise time are different
since these values depend on various other factors that were not accounted for in vitro such as
the blood flow pattern, downstream resistance of the pipes or vessels, and viscosity of the
fluid. If this system is used in vivo, all these systemic variables can be accounted for by a
second PPG measurement on a different site in the body (i.e. peripheral PPG on the fingers or
ear lobe). The model shows that the PPG rise time is most sensitive to changes in the
compliance below 15 KPa which coincides with the range of mechanical properties of healthy
individuals and early stages of fibrosis which is the most critical range for monitoring. By
fitting the in vitro data to a calibration model similar to the one obtained from the Windkessel
simulations, we found that our PPG system has a standard error of 4 KPa.
The results show that the proposed concept is also able to discriminate downstream
vascular complications from upstream complications. Downstream vascular complication (i.e.
stenosis) can result in an increased vascular resistance which leads to an increase in the PPG

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2374
rise time. This is opposite to the stiffening of the tissue that results in a decrease in the rise
time. Simulation data show the same trends in the rise time of the pulse confirming the
proposed approach. The error bars from the data collected in these experiments are very small
suggesting that the system can resolve minute changes in downstream resistance. However,
the method used to increase the downstream resistance (c-clamps) in our in vitro studies is not
quantitative and thus we did not attempt to quantify the resolution of the system. Note that the
periodic variation seen during data collection is due to the pressure buildup in the flow circuit
which results in increased resistance leading to backflow and an increase in the rise time. This
was thoroughly discussed and quantified in a previous report by our group describing the
PDMS phantoms’ performance [38]. Part of the error seen during the occlusion periods (Fig.
11) is due to the variation in the pressure induced by the c-clamp between the different
occlusion periods.
In addition to the changes in the PPG pulse rise time, the fall time of the pulse changes in
the opposite direction. This was seen in the phantom experiments and the Windkessel
modeling. In this work, we elected to use the rise time because it is more sensitive and
showed a larger response to compliance and resistance changes. This trend is the same in the
modeling and in vitro data.
The data integration time used in this work is roughly 60 seconds. However, as seen in
Fig. 10, the rise time measurement is very stable and the only variation is due to the back flow
that mimics the respiratory effect seen in vivo.
5. Conclusion
In this manuscript, we analyzed a PPG waveform collected in vitro using new PDMS based
phantoms that mimic tissue elasticity, and used a simplified Windkessel model to examine a
broader physiologic range. The modeling results are in agreement with the data collected in
vitro. The system used in this research showed a resolution to YM changes of 4 KPa. The
modeling and in vitro results show that the PPG signal has strong potential for ultimate use in
non-invasive monitoring of tissue mechanical properties due to the sensitivity of the pulse
shape to changes in compliance and vascular resistance. In particular, the approach has the
potential of staging liver fibrosis that changes the YM from 5.5 KPa (F0-1) up to 48 KPa
(F4). In addition, the concept can potentially be applied to monitor changes in downstream
resistance which can be used to detect and diagnose vascular complications.
Acknowledgments
This research was funded by a bioengineering research partnership (BRP) grant from NIH,
(#5R01-GM077150).

#207897 - $15.00 USD Received 1 Apr 2014; revised 23 May 2014; accepted 16 Jun 2014; published 19 Jun 2014
(C) 2014 OSA 1 July 2014 | Vol. 5, No. 7 | DOI:10.1364/BOE.5.002362 | BIOMEDICAL OPTICS EXPRESS 2375

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