A thorough characterization of the frequency response of various in
vivo blood pressure measurement technologies
Kroehle, J.P. Jr.; Grenwis, J.; Sarazan, R.D
Data Sciences International, (DSI) St. Paul, MN
Introduction
Figure 2 is an actual rat left ventricular pressure signal that has a high heart rate and a high
dP/dtMAX. This time point is where the highest frequency component would exist in an LVP signal.
From the FFT plot (Figure 3) it can be seen that the highest frequency content measured is below
100 H
Hz, as measured.
d
Frequency Response
10
0.1
1
10
The question posed at the beginning of the study was: Do DSI devices
made specifically for the measurement of left ventricular pressure
have the correct characteristics to accurately measure dP/dtMAX and
other endpoints from the species they are intended? The answer is,
yes.
As seen in Figure 10 and Figure 11 below, the Millar sensor and the
HD-S21 implantable transmitter correspond overlay the rat LVP signal
directly at low and high dP/dtMAX values.
For the
F
th Statham
St th
PX23L and
d th
the Ut
Utah
hM
Medical
di l sensor, we concluded
l d d
that these devices are appropriate for measuring systemic arterial
pressures but they would not be recommended for the measurement
of LVP due to their lower frequency response.
5
0
Geddes Handbook of Blood Pressure Measurement (1991) offers a recommendation
that can be used as a starting point for accurately measuring blood pressure. It states
that “for an accurate representation of the blood pressure the frequency response needs
to be six times higher than the highest heart rate in seconds”. If a dog has a 300 BPM
heart rate (5 beats-per-second) then the frequency response should be 30 Hz (5 seconds
* 6). This rule of thumb works reasonably well for a systemic blood pressure signal since
it more closely represents a sine wave but this is not a good rule for the measurement of
LVP due to the more complex morphology of the signal.
100
HD‐S21 (8cm)
Utah Medical disposable, PE50 25 cm
‐5
Statham, PE50 25cm
It is important that the user select the correct device for the goals of
the experiment. Information provided in this report should facilitate
such a well informed decision.
D70
‐10
‐15
‐20
Frequency (Hz)
200
Figure 4: Bode plot of different pressure sensors
Figure 3: FFT of the rat LVP
Control
Figure 5 contains
Fi
t i simulated
i l t d sine
i waves att different
diff
t rates
t collected
ll t d by
b four
f
diff
different
t pressure sensor systems.
t
A can be
As
b seen, there
th
i very little
is
littl change
h
i signal
in
i
l amplitude
lit d as frequency
f
changes.
h
This is true for the external fluid filled type catheter systems as well as the transducer tipped and fully implantable sensors.
LVP (mmH
Hg)
Figure 2: LVP signal of a rat
150
100
50
0
30
DSI HD-S21 Small Animal Telemetry Device with High Frequency Pressure Sensor
dP/dt (mmHg/sec)
The preferred method to determine what is needed to measure LVP is to record a LVP
signal with a high heart rate with a known drug that causes high contractility. The LVP
signal needs to be recorded on a high fidelity system and then perform a Fast Fourier
Transformation (FFT) on the recorded signal. The FFT results allow the user to
determine the highest frequency component of the LVP signal and from that, it can be
determined what the frequency response and sample rate of the system needs to be.
Conclusions/Perspectives
In the Bode plot below (Figure 4), a comparison of sine wave signals measured by the different
pressure sensing systems is plotted across a range of frequencies. The Y axis represents signal
amplitude and the X axis represents frequency in Hz. Traditionally, the frequency response of a
device is defined as the frequency above which the amplitude of the signal is decreased by greater
than 3 decibels (db), which is known as the 3 dB point. The data shown in this plot confirm that the
D70-PCTP large animal transmitter has >70 Hz frequency response and the HD-S21 small animal
transmitter has >100 Hz frequency response. Both devices are more than adequate to measure
dP/dtMAX in the appropriate animal model.
Amplitude (dB)
A question exists; what is needed to accurately measure blood pressure or left ventricle
pressure (LVP) to obtain accurate end points such as dP/dtMAX values in animal models?
Th answer depends
The
d
d on severall variables
i bl such
h as ffrequency response off th
the pressure
sensor, frequency response of the associated electronics and sample rate of the digital
acquisition system. All of these variables must be looked at as a system to determine the
best method for measuring the pressure signal of interest.
Determining Frequency Response of Pressure Sensors
To accurately measure end points such as dP/dt, the frequency content of the pressure signal
needs to be known. For this a rat left ventricular pressure signal was measured using a system
with a bandwidth of 1000 Hz to make sure that the highest frequency component could be
measured. The collected pressure signal was then analyzed using an FFT (Fast Fourier
Transformation), which is the common method to determine the highest frequency component in a
signal.
20
HD-S21 Transmitter
mmHg
Since Hale first measured blood pressure by using a water manometer in 1733, there
have been many improvements in the technology used in laboratory animal models.
Throughout history, devices have evolved from mercury manometers to fluid filled
catheter systems using a strain gauge device, followed by implanted solid state
transducers connected via a tether system. Today there are systems that allow a
scientist to measure blood pressure in freely roaming animals by using micro-machined
sensors and telemetry.
10
0
1 Hz (60 beats/min)
2 Hz (120 beats/min)
5 Hz (300 beats/min)
10 Hz (600 beats/min)
20 Hz (1200 beats/min)
-10
-20
-30
30
Materials and Methods
DSI D70-PCTP Large Animal Telemetry Device with High Frequency Pressure Sensor
10000
8000
6000
4000
2000
0
-2000
-4000
-6000
-8000
Time_sec vs LVP_Millar
Time_sec vs LVP_DSI-offest
0.0
In order to determine what is needed to accurately measure blood pressure, left ventricle
pressure and endpoints such dP/dtMAX, we used a pressure generator that simulates the
same conditions as the heart to test pressure sensing systems
systems. The pressure generator
can output different waveforms at different amplitudes and frequencies.
mmHg
20
D70-PCTP Transmitter
0
0.5
1 Hz (60 beats/min)
2 Hz (120 beats/min)
5 Hz (300 beats/min)
10 Hz (600 beats/min)
Figure 10: Millar and HD-S21 signal comparison at low contractility
-30
Statham Pressure Transducer with 25 cm Fluid Filled PE Catheter
30
200
10
0
1 Hz (60 beats/min)
2 Hz (120 beats/min)
5 Hz (300 beats/min)
10 Hz (600 beats/min)
LVP (mmHg)
mmHg
20
A Millar catheter (SPC-330A) was used as the reference since it is well established in
animal research and there are many publications on the performance of this sensor.
Other devices tested included a fluid filled Statham (P23XL) pressure transducer with a
25cm PE50 catheter, a fluid filled disposal Utah Medical (Deltran IV) pressure transducer
with a 25cm PE50 catheter, a DSI HD-S21 small animal transmitter and a DSI D70-PCTP
large animal transmitter.
20 Hz (1200 beats/min)
-10
-20
-30
Millar Catheter-Tipped Pressure Transducer
dP/dt (mmHg/sec)
mmHg
20
Millar catheter
10
0
Dobutamine (60 μg/kg/hr)
150
100
50
0
30
1 Hz (60 beats/min)
2 Hz (120 beats/min)
5 Hz (300 beats/min)
10 Hz (600 beats/min)
20 Hz (1200 beats/min)
-10
-20
-30
Figure 5: Amplitude of different pressure sensors at different rates
10000
8000
6000
4000
2000
0
-2000
-4000
-6000
-8000
Time_sec vs LVP_Millar
Time_sec vs LVP_DSI-offest
0.0
Canine dP/dtMAX Comparison
p
Figure 7 contains the dP/dtMAX values plotted over time during the escalating doses of dobutamine.
From the anesthetized rat study, Figure 8 contains the dP/dtMAX values from LVP for both a Millar
pressure sensor and an HD-S21 transmitter. dP/dtMAX was increased to approximately 14,000
mmHg/Sec by administering increasing doses of dobutamine. The Millar compared with the HDS21 and shows a very good correlation between the two signals with an R2 value of 0.9463.
Figure 9 contains the dP/dtMAX values plotted over time during the escalating doses of dobutamine.
Figure 1: DSI HD-S21 small animal transmitter and D70-PCTP large animal transmitter
5sec Averages dP/dtMAX
9000
5sec Averages dP/dtMAX
5sec Averages dP/dtMAX
18000
16000
8000
16000
8000
14000
7000
14000
7000
12000
6000
mmHg/S
5000
4000
5000
4000
I1+dP/dt
D70
I6+dP/dt
Millar
12000
10000
+dP/dt
6000
Millar
y = 0.9725x + 227.03
R² = 0.9463
5sec Averages +dP/dtMAX
18000
9000
HD‐S21
All devices were simultaneously connected to the pressure generator and different signals
were applied. Signals were measured with a Ponemah acquisition system sampling at
2000 Hz with no filters.
y = 1.0374x ‐ 418.21
R² = 0.9893
8000
10000
8000
Series1
Millar
Series2
HD‐S21
3000
3000
6000
6000
2000
2000
4000
1000
2000
0
2000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
0
0
D70
0
2000
4000
6000
8000
10000
12000
14000
16000
0
Millar
Figure 6: Millar compared to D70-PCTP dP/dtMAX values
Figure 7: Millar compared to D70-PCTP dP/dtMAX values over time
Figure 8: Millar compared HD-S21 dP/dtMAX values
1.0
1.5
Time (seconds)
Figure 11: Millar and HD-S21 signal comparison at high contractility
References
• R.D. Sarazan. Validation of a Digital Data Acquisition and Analysis
System in a Cardiovascular in a Toxicology Laboratory. Toxicology
Methods Vol.4 No. 4 pp 274-291, 1994
• Main B.W., C.A. Strnat, R. D. Sarazan. Addition of left ventricular
pressure telemetry in dogs and monkeys is a powerful tool in safety
pharmacology. Safety Pharmacology Society, Annual Meeting.
Noordwijk, The Netherlands. September 2003
• Jason Segreti, Andrew Lisowski, James Polakowski, Eric Blomme,
Bryan Cox, Andrew King. Simultaneous measurement of arterial and
left ventricular pressure in conscious rats by telemetry. Safety
Pharmacology Society, Annual Meeting poster 101, September 2010.
• Angela Jenkins, Dusty Sarazan. Validation of a Digital Data Acquisition
and Analysis System. Safety Pharmacology Society, Annual Meeting,
September 2006.
4000
1000
0.5
Millar
DSI
Rat dP/dtMAX Comparison
p
From the anesthetized canine study, Figure 6 contains the dP/dtMAX values from LVP for both a
Millar pressure sensor and a D70-PCTP transmitter. dP/dtMAX was increased to approximately
8000 mmHg/Sec by administering increasing doses of dobutamine. The Millar compared to the
D70-PCTP and shows a very good correlation between the two signals with an R2 value of 0.9893.
In each study a Millar catheter tipped transducer was used to compare and correlate data
to the transmitters.
1.5
20 Hz (1200 beats/min)
-20
Statham
After the frequency response of the devices was determined, two animal studies were
performed. First an anesthetized rat with an HD-S21 implanted was administered doses
of dobutamine to create high values of dP/dtMAX. A second study was done with an
anesthetized canine with a D70-PCTP implanted that was administered doses of
dobutamine to create high values of dP/dtMAX.
1.0
Time (seconds)
Millar
DSI
10
-10
Figure 9: Millar compared to HD-S21 dP/dtMAX values over time
• Geddes, L.A. “Handbook of Blood Pressure Measurement” Clifton: The
Humana Press, 1991.