In vitro
• Total control of confounding variables
– Vasomotion, temperature changes, autoregulation, mean BP
• Most accurate because vessel examined directly
• Best for detailed information about mechanical properties of
vessel material
In vivo (invasive)
• Realistic clinical information
• Limited by technical problems
– Measurement errors, transitory changes in diam. BP etc
In vivo (non-invasive)
• Further technical problems
– Especially pressure
Measurement of blood pressure
• Invasive
– Pressure catheter and transducer
• Non invasive
– Sphygmomanometry
• Auscultation (by ear or automatically by microphone)
• Oscillometry
– Volume clamp
– Tonometry
Advantages/ drawbacks
• Invasive
– Accurate reproduction of central pressure waveforms
– Risk of thrombosis and arrhythmias
• Non-invasive
– Quick, cheap, widely used
– Lack of central pressure measurement
– Requires skilled and experienced operators
Sphygmomanometry
Manometer
(mercury or capsule type)
Pulse detector
(stethoscope or microphone)
www.fmshk.com.hk/sahk/lecture_noninvasive.pp
Sphygmomanometry
• 1896 Blood pressure cuff (Riva Rocci)
• 1905 First report of audible detection of heart
sounds used with cuff (Korotkov)
• 1968 Microphone used for automatic
pressure measurement (Stegall)
Sphygmomanometry
Mercury sphygmomanometer
Capsule manometer
Replacing mercury spymomanometer
Korotkov Sounds
caused by vibration collapse of the arterial wall??
Cuff pressure
Systolic
Diastolic
– Korotkoff IV is a better
indication of diastolic pressure
according to theory
– However Korotkoff V is the
commonly recommended
measuring point except in
pregnant patients because
• It is associated with less interobserver variations
• It is easier to detect by most
observers
www.fmshk.com.hk/sahk/lecture_noninvasive.pp
Errors
• Korotkoff sounds compared to invasive blood pressure
measurement
– Korotkoff IV is on average 8mm Hg above the invasively
measured diastolic blood pressure
– Korotkoff V is on average 2mm Hg above the invasively
measured diastolic blood pressure
Oscillometry
•
•
•
•
Cuff round the arm
Pressurise cuff (> systolic)
Allow pressure to drop slowly to zero
Measure pressure in the cuff during deflation
Oscillometry: set up
Microprocessor
Air pump
Bleed valve
Pressure transducer
Display
Filtered signal
Of cuff pressure
Principle of oscillometry
Variation of cuff pressure as cuff is deflated
Limitations
• Inaccurate / unreliable in shock patients
• Inaccurate / unreliable in patients with
arrhythmias
– The algorithm of measurement assumes a regular
pulse, so the reading is unreliable in patients with
irregular pulse
Advantages
• No skill required
• No subjective errors
Volume clamp
To pump
Infra red emitter
Pressure
Finger
Diameter
Detected
signal
Air
Change cuff
pressure
Air
Artery
Detector
Measure cuff
pressure
Applanation tonometry
Detects pressure of arterial pulsations through the skin
Problem:
•
•
•
•
Aortic and peripheral pressures are different.
The heart doesn’t care what the pressure is in the radial artery.
It only “sees” aortic pressure.
Aortic pressure is difficult (impossible?) to measure noninvasively
• Can we reconstruct the aortic waveform from the radial?
Radial
Aortic
120
Systolic
100
80
Mean
Diastolic
Yes we can. At least in principle
• Record radial waveform with tonometry
• Apply inverse transfer function
• “Reconstruct” aortic waveform
– What is an inverse transfer function?
– How do we reconstruct the waveform?
Fourier analysis
H1
H2
H1 + H2 + H3
H4
2
1
0
-1
-2
90
180
270
360
H1 + H2
H3
H1+H2+H3+H4
Mean
Measured
aortic pressure
radial artery pressure
Pa(t) = pa0
+ pa1Cos(t - a1)
+ pa2Cos(t - a2)
+ pa3Cos(t - a3)
+ ...
Pb(t) = pr0
+ pr1Cos(t - r1)
+ pr2Cos(t - r 2)
+ pr3Cos(t - r 3)
+ ...
For each harmonic (n)
Transfer function phase
= an - rn
Transfer function amplitude = pan / prn
Amplification of the pulse
AA - RA
CA - RA
AA - CA
How to derive the central pressure from
peripheral measurements
• Compare Fourier series of “typical” aortic pressure
waves with Fourier series of the radial pressure
computed from tonometric measurements.
• Calculate the amplitude ratio and phase difference for
each harmonic
• Apply this ratio and phase difference to each harmonic
of the measured radial wave and reconstruct aortic
wave that would when transmitted down the arm,
produce the measured radial wave
Question
• How well does the typical transfer function
apply to people of different ages and disease
states
Answer
• Surprisingly well considering the changes
that occur in the arterial system with age and
vascular disease
• However, most believe that more work is
needed to validate the method
Pressure transducers
(for invasive measurement)
Diaphragm manometer
To pressure to be measured,
(via an intra arterial cannula)
Fluid filled chamber
Stiff diaphragm
Measure its movement
electronically
Advantages
• Cheap, disposable
• easy to use
• Accurate mean pressure
Disadvantages
• Clotting in cannula, air
bubbles
• Therefore errors in pulse
pressure
Pressure transducers
(for invasive measurement - 2)
Semi conducting strain gauge
Cannula tip manometer
Diameter may be as small as 0.67 mm
Advantages
• High accuracy
• Especially in very small
vessels
Disadvantages
• No calibration possible when
in position
• Expensive
• Fragile
Pressure: comparison of methods
Method
Sensitivity Invasive Advantages/
disadvantages
Auscultation +
cuff
OK
No
Subjective, limited to arm or
leg. Good in skilled hands
Oscillometry +
cuff
OK
No
As above but less subjective.
No mean pressure.
Catheter
Good
Yes
Only direct way to measure
in central vessels
Volume clamp
Good
No
Limited to peripheral arteries
but can do small ones
Tonometry
V. Good
No
PPG
V. Good
No
Superficial vessels only,
sensitive to movement,
good for carotid. No absolute
P values. Can be calibrated
against cuff methods
Superficial vessels only.
Used as a pulse detector in
conjunction with cuff.
PROMISING
Flow Measurement
• Invasive
– Electromagnetic flow velocimetry
– Ultrasonic transit time
• Non invasive
–
–
–
–
Doppler ultrasound
Ultrasonic transit time
Optical (small superficial vessels only)
MRI
Flow measurement
• 1870 Fick principle described
Flow in a given period of time = Amount of substance injected in that
time/concentration difference before and after point of entry
• 1886 Fick method first used by Grehart &
Quinquardt
• Modern instruments
–
–
–
–
–
Optical
Electromagnetic 1936-1937 Kolin
Ultrasonic transit time 1959
Ultrasonic Doppler 1961
MRI 1990’s (not commercial)
Electrode
Vessel diameter
E = H.d.V
Induced voltage
Mean blood velocity
Magnetic field strength
i.d. 0.5 - 26 mm
Principle of Doppler flow velocimetry
c  fl
c
l
c c+v
l 
'
f
f
'
cf  (c + v ) f
'
cf  cf + vf
'
f - f v

f
c
vf
Df 
c
v
c  f 'l
Flow: comparison of methods
Method
Sensitivity Invasive Advantages/
disadvantages
Dilution
Adequate
No
Cumb ersome, slow,
mean values only
Optical
Good
No
Small superficial vessels only
Doppler
OK
No
Absolute flow values difficult
to measure
Transit time
Good
Yes
None apart from expense and
invasiveness
E.M
OK
Yes
Electrical noise, hard to
calibrate accurately
Diameter Measurement
• Mechanical
• Optical
• Ultrasonic
– Implanted crystals
– Pulse echo
• Cine-angiography
• MRI
Invasive Diameter Measurement
•
•
•
•
•
Ultrasound (external transducers)
IVAS
TV
Mechanical
Cine angiography
Non-invasive diameter measurement
• Pulse echo ultrasound (direct)
• PWV (indirect)
– Diameter wave
– Flow wave
– Pressure wave
Other diameter methods
Springy stainless steel
Differential transformer
TV camera
Ultrasonic crystals
(glued or sutured)
Measure time delay
Artery
Transmitter
Receiver
Principle of pulse echo ultrasound
Measure time delay between transmitted and received pulse
Diameter: comparison of methods
Method
Sensitivity Invasive Advantages/
disadvantages
Mechanical
OK
Yes
Optical
Good
Ultrasound
(crystals)
Very good
Yes (no) Non contact but sensitive to
wall movement. N.I. method
only measures rel. diam.
Yes
Difficult to set up, insensitive
to wall movement
Ultrasound
(echo)
Good
No
Cumb ersome, but insensitive
to wall movement
Sensitive to wall/patient
movement, but only absolute
non invasive method
Elasticity measurement
• Direct
– Stress
• pressure, tension, area, wall thickness
– Strain
• length, diameter
• Indirect
– Pulse wave velocity
• detect pressure, diameter or flow pulse
PWV Methods
• Pressure pulse
– Tonometry
• Flow pulse
– Doppler
• Diameter Pulse
– PPG
Nature of the PPG Signal
• Commonly regarded as a measure of
changes in tissue volume due to arteriolar
and capillary blood flow  time varying
absorption of light or i.r.
• When detected in the vicinity of a large
superficial artery, the signal is dominated by
changes in the diameter (volume) of the
artery.
Optical detection of the diameter wave
Upstream
probe
Infra red emitter
Downstream
probe
Detector
SKIN
ARTERY
FLOW
MUSCLE/BONE
Loukogeorgakis, et al. (2002). Physiological Measurement 23: 581-96.
PhotoPlethysmoGraphy (PPG)
for pulse wave velocity measurement.
How does it work?
d
• Infra red probes detect transitory change in conduit artery
volume due to the passage of the pulse wave
• Measure time delay and distance between the probes
• Pulse wave velocity = d/t
• Pulse wave velocity  (compliance)-1/2
t
LED (emitter)
Photo-transistor (detector)
20 mm
20 mm
Validation experiments.
Comparison of PPG with
• Echo Tracking.
– Does PPG method really measure large artery diameter?
• Doppler.
– How well do PPG derived pulse wave transit times
compare to measurements using an established
method?
• Intra-arterial pressure wave.
– Do transcutaneous transit time measurements compare
with intra-arterial ones?
PPG/Echo tracking methods
Probes on the posterior
tibial artery
NIUS ultrasound
probe
PPG
NIUS ultrasound
probe
Probes on the radial artery
PPG
PPG
Relative amplitude
1
PPG
Ultrasound
0.1
0.01
400
Ultrasound
Phase
300
200
100
0
0
2
4
6
Frequency (Hz)
8
10
PPG/Echo Tracking - Conclusions.
• PPG reproduces the diameter wave with
reasonable fidelity, when compared to high
precision echo tracking system.
• Timing of the foot is close
Validation experiments.
Comparison of PPG with
• Echo Tracking.
– Does PPG method really measure diameter?
• Doppler.
– How well do PPG derived pulse wave transit times
compare to measurements using an established
method?
PPG/Doppler methods
Probes on the posterior
tibial artery
Doppler
Doppler
PPG
PPG
ECG
PPG
Probes on the radial artery
Doppler
ECG used as time reference
Comparison of PPG and Doppler transit times
TT PPG [ms]
y = 0.90x + 12.8 r = 0.95
350
300
250
Leg
200
Arm
150
100
100
150
200
250
TT Doppler [ms]
300
350
Comparison of PPG and Doppler.
Difference v mean
Doppler - PPG [ms]
50
+ 2SD
25
Mean difference = 8.6 ms
Leg
0.0
Arm
-25
- 2SD
-50
0
100
200
Average [ms]
300
400
PPG/Doppler - Conclusions.
• PPG transit times agree satisfactorily with Doppler
values recorded at the ‘same’ site.
• The difference plot shows
– the transit time estimated by the Doppler instrument is
consistently greater than that derived from the PPG signals
(mean difference 8.6 ms)
• The discrepancy is due to the Doppler signal processing
Validation experiments.
Comparison of PPG with
• Echo Tracking.
– Does PPG method really measure diameter?
• Doppler.
– How well do PPG derived pulse wave transit times
compare to measurements using an established
method?
• Intra-arterial pressure wave.
– How well do transcutaneous transit time measurements
compare with intra-arterial ones?
Subjects
Measurements on 21 volunteers (8 female, age
range 33 to 78 years, mean 57) after elective
coronary angiography, under the approval of
the regional research ethics committee.
TP1
Pressure
measurement pos. 1
ECG
Femoral arteriotomy
Inguinal ligament
TP1
Pressure
measurement pos. 1
ECG
DTP
DTPPG
TP2
TPPG
Inguinal ligament
PPG measurement
pos.
Pressure
measurement pos. 2
TC
Femoral arteriotomy
= TP2-TP1
= TPPG-TP1
+TC
Comparison of PPG and intra-arterial transit times
PPG transit time [ms]
110
y = 0.68x + 22, r = 0.66, P < 0.005
100
90
80
70
60
50
40
40
50
60
70
80
90
Intra arterial transit time [ms]
100
110
Comparison of PPG and intra-arterial transit times.
Difference v mean
I.A. - PPG [ms]
30
+ 2SD
20
Mean difference = 0.0 ms
10
0.0
-10
-20
- 2SD
-30
40
50
60
70
80
90
Mean transit time [ms]
100
110
Some limitations.
• Non simultaneous measurement of proximal and distal signals
– Ethical constraint of one catheter
• Proximal signal not transcutaneous
– ‘Hybrid’ measurements will avoid this. i.e. aortic signal from Doppler, distal
signal from PPG.
– Current hardware and software will allow this.
• Effect of errors in distance between measurement sites not
investigated
– Careful comparison between I.A. and external distance measurements
required.
PPG/Intra-arterial - Conclusions.
• Reasonable correlation between intra-arterial and PPG
transit times and pulse wave velocities.
• Mean difference between the two methods close to zero
• Transcutaneous estimation of pulse wave transit time
provides an acceptable estimate of its intra-arterial value.
– Errors in distance measurement must be carefully considered
Summary of validation results.
Comparison of PPG with
• Echo Tracking.
– Does PPG faithfully measure large artery diameter
changes and pulse wave timing?
•
Yes!
Doppler.
– How well do PPG derived pulse wave transit times compare to
measurements using an established method?
Reasonably
•
Intra-arterial pressure wave.
– Do transcutaneous transit time measurements compare with intra-arterial ones?
Reasonably
Examples of current usage
• Paediatric PWV studies
– Kawasaki disease
– Twin to twin transfusion syndrome
– Children of diabetic mothers
– Zambian schoolchildren of known birthweight and
nutritional status
Conclusions
• PPG measurements of PWV in superficial
arteries compare well with other methods
• Although we don’t yet know quite what we’re
measuring
– Capillary and/or large artery volume changes?
– More work needed
Assessment of endothelial function
• Endothelial function
– The ability of the vascular endothelium to release vasodilators in
response to reduced mean shear stress
• Nitric oxide
• PGI2
• EDHF
• Endothelial function is a reliable indicator of vascular “health”
– Continuous production of nitric oxide maintains a low basal level of
vascular tone and peripheral resistance
– If NO production is impaired:
• Coronary arteries  angina
• Peripheral arteries  mean BP increases
• Peripheral endo function closely mirrors that in coronary artery
Assessment of endothelial function
Impaired endothelial function has prognostic
and diagnostic value
• a strong predictor of cardiovascular morbidity and
mortality
• associated with a wide range of CV pathology
–
–
–
–
Angina
Type II diabetes
Smoking
Essential hypertension
How to assess
endothelial function
• Direct
– Measure diameter of muscular artery in response to
change in shear stress (flow)
• Normally induced by reactive hypersaemia after a period of
downstream occlusion
• B mode or echo tracking ultrasound (+ doppler)
– Expensive
– Highly skilled operators needed
– Not in routine clinical use
• Indirect
–
–
–
–
Venous occlusion plethysmography
Peripheral artery tonometry
Distal temperature changes
Change in arterial compliance
Principle
• Relaxation of vascular smooth muscle 
reduction in arterial stiffness
• Reduced stiffness  reduced pulsewave
velocity
Protocol
Experiment A
Effect of exercise on brachio-radial PWV
•
•
•
•
Base line PWV measurement
5 minutes biceps curl
PWV measurements at 1, 2, 5 and 10 minutes
47 healthy volunteers
Experiment B
Effect of ischaemia on brachio-radial PWV
•
•
•
•
Base line PWV measurement
3 minutes forearm artery occlusion (BP cuff)
PWV measurements at 0.5, 1, 2 and 5 minutes
36 healthy volunteers
Results
Exercise test
Mean pulse wave velocity change relative to baseline
0.3
0.2
0.1
0
0
1
2
3
4
5
6
7
-0.1
-0.2
-0.3
Time after exercise [minutes]
8
9
10
11
Results
Mean pulse wave velocity change relative to baseline
Forearm ischaemia
0.4
0.3
0.2
0.1
0
1
2
3
4
-0.1
-0.2
-0.3
-0.4
Time after cuff deflation [minutes]
5
6
Conclusions
• PPG is a reliable, repeatable low cost and
robust alternative to the range of methods
available for measuring PWV
• It is ideal for paediatric studies
• Changes in PWV may be a simple, low cost
method for assesing endothelial function.
– Very preliminary study
Flow-mediated changes in pulse wave
velocity: a new clinical measure of
endothelial function.
Naka KK. Tweddel AC. Doshi SN. Goodfellow J. Henderson AH.
European Heart Journal. 27:302-9, 2006 Feb.
Leg
Arm
Hyperaemia increased
brachial artery diameter by
8% at this time.
GTN had similar effect
Hyperaemia had negligible
effect on brachial artery
diameter.
GTN reduced diameter by
similar amount to controls
Mandrel: diameter 4-10 mm
Centralising lid
Sleeve: i.d 4 - 12.5 mm
o.d 18 mm
Artery
Outer Container
Ejection screw
Frozen A rtery
Reaming T runnion