IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-24, NO. 5, SEPTEMBER 1977
480
[5] Newhouse, V. L., P. J. Bendick and L. W. Varner, "Analysis of Transit Time Effects on Doppler Flow Measurement," IEEE Trans. Biomed. Eng., Vol. BME-23, pp. 381-387, Sept. 1976. Green, P. S., "Spectral Broadening of Acoustic Reverberation in Doppler-Shift Fluid Flowmeters," Jour. Acoust. Soc. Am., 36, No. 7, pp. 1383-1390, 1964.
3000
[6]
2800 2600 l
2400
--
° -- --
J/
-i
2200
+--
EXPERIF
ENTAL,
60°
8
EXPERIM4ENTAL,8145°
[7]
Newhouse,
V.
"Transit Time Broadening in Ultrasonic Doppler
L.,
Flow Measurement Systems," Internal Report, Purdue University, Nov. 1973.
2000 I 1800
An Inexpensive Modular Pulse Generating System
F 1600 3 1400
JOHN NOLTE AND THEODORE J. TARBY
z
Il
1200
Abstract-A multiple channel pulse generator is described, consisting of a clock module and several identical output modules. Clock frequency can be varied continuously from 0.003 Hz to 100 Hz. Output pulses have continuously variable duration, can be positioned anywhere within the timing cycle, and their amplitude is variable from +5 to -5 V.
1000
800 600
400 200 0_
1
0
2
3
5
4
It is frequently necessary in biological and other experiments to program sequences of events, such as oscilloscope sweeps and various stimuli. The apparatus called for must allow for repetition of the sequence at some selectable frequency, as well as allowing the experimenter to vary the relative positions
6
-RANGE, cm Fig. 3. Doppler bandwidth
f
as a function of
of the events within the
range.
transit time effects. Rough calculations in(dicate that this geometrical broadening will always dominate a for targets in the near field of the transducer. However, ince geometrical idening due to broadening decreases with range and transit time effects is independent of range as long as the )ossible to find beam width remains constant, it may This was conditions where the two effects are compar ffith and Brody probably the case for the experiments in which only transit time effects were consider red [4]. As pointed out above, geometrical broa(dening may be usable as a means of estimating the beltween the ultraa technique for sound beam and the flow direction, measuring flow at right angles to an beam. Whether or not these techniques are in fact il for real time blocity gradients pulsatile blood flow measurements whereve exist and where possibly only 20 ms are available for 1- In any event, spectrum estimation remains to be established the geometrical broadening effects described I ere will have to be taken into account in the design ins intended to measure Doppler bandwidth for the i of factors such as velocity gradient or turbulence. si
broa
be
rable.
of Gri
angle
and
as
L
ultrasound practicl
of
of
data
syste
Good absolute timing
sequence.
accuracy is usually not necessary, since the events, or some
representation
thereof,
chart recorder. We describe here
a
are
displayed
on
an
oscilloscope
simple modular system which
or
offers low
cost and maximum ease of operation. The circuits are based on the widely used type 555 timer. The master frequency control is a single potentiometer by of which the repetition rate can be varied over about five orders of magnitude. No range switches are involved, but the resolution is means
good
throughout
the
entire
range
changes logarithmically with the output channel there are single
since
the
repetition rate
control resistance. For each controls for pulse duration,
amplitude and delay (with respect to the clock pulse). A seven-channel unit is presently used in the senior author's laboratory, controlling two electromechanical shutters, two
electrode
resistance
testers,
current
injection
micropipette
through two
electrodes and a calibration pulse generator. clock output triggers the oscilloscope sweep, and seven events may be positioned at any desired
within the
The
each of the temporal location
sweep.
estimatiol
ACKNOWLEDGMENT
The authors
are grateful to E. S.
Furgason
f
or many helpful
discussions.
REFERENCES Arts, M. G. J. and J. M. J. G. Roevros, "On the Instantaneous Measurement of Blood Flow by Ultrasonic ins", Med. & Biol. XEngng., Vol. IO, pp. 23-24, 1972. 121b lbright, R. J. and J. H. Harris, "Diagnosis Urethral on B Flow [1
Mea
tvarameters Vol.
3 [4]
by Ultrasonic
BME-22,
pp.
of
Backscatter",
IEEE
7'rans.
lamed.
1-91,1975.
CLOCK CIRCUIT
Figure1 is a schematic diagram of the clock circuit, which is simplified from a previously published design (1). If greater wider range of operating frequencies temperature stability are required, the original description should be consulted. The base voltage of Q1 is fixed at 9.1 V by the1N757 zener diode. When the wiper of R3 is at the upper end of its range the emitter voltage of 1Q is Q (shorted to the base of 1), or a
fixed at some value near 9.7 V by the 1N746-ICl feedback loop. Since the emitter-base voltage of 1Q is fixed, a constant collector current flows, charging the 5 pF capacitor. Rotating
Manuscript received August 9, 1976; revised December 2, 1976. This work was supported by Grants EY 01155 (National Eye Blooa Velocity and Angle", Poc. 28th A CEMB, p. 76, Sept. 1975. Institute) and BMS75-17638 (National Science Foundation). The authors are with the Department of Anatomy, University of in UltraGriffith, J. M., and Brody, W. R., "Velocityesolution Re 1975. Colorado Medical School, Denver, CO 80262. sonic Doppler Flowmeters," Proc. 28th ACEMBI p.r- 75,Sept. I --I-
V
L. W., V. L. Newhouse and P. J. Ben4lick, "Application transit Time Effects to the Independent Measurement of
er,
-
--
--
, - -
COMMUNICATIONS
481
SI +
LED
.01
C in pF
Vext
47K
2N3
--L .02
.2 4
The clock module. IC1 and associated circuitry forni a current which charges the 5 juF timing capacitor of IC2, The output clock pulses, of IC2 are buffered by IC3. IC4 substitutes for the positive supply of IC1, allowing for the generation of single clock pulses in response to manual (S3) or external electrical (Vext, >5 V) inputs. R1 trims the maximum clock frequency, R2 the minimum frequency. R,3 is the main frequency control. LED is a resistorcontaining LED designed for 12 V operation.
Fig.
1.
source,
,
R3 lowers the voltage of the noninverting input of ICI and lowers the emitter voltage at Q 1. Sin'e the' base voltage is fixed, the emitter-base voltage is decreased and the collector current decreases. Since the emitter-base voltage of a transistor is related to the logarithm of its collector~current, this part of the circuit acts as a logarithmicolly coptrolled current source charging the 5 gF capacitor. The 5 jiF capacitot charges until the' threshold of IC2 is reaclied, then discharges quickly through the I1002 resistor, resulting in a brief negative pulse at the output of IC2 which, after being buffered by IC3, serves as the clock pulse., When S2 is in the EXT position the current source involving IC . functions only. when there is a positive output from IC4. A negative spike input to IC4 can be prodticed by 5 V or more at Vext or by depressing S3 and IC4'then generates a positive pulse just long enough to produce a, single clock pulse. Leakage currents in the circuit are such thatwhen S2 is in the EXT position, the 5 'MF timing capacitor charges to threshold about every 2minm; If lcnger'intetvals are nfqcssary, a 10 M&Z resistor shunting the timing capacitor will prevent spurious triggering due to leakage currents. In practice, R I is adjusted to produce a maximum, clock frequency of 1 00 Hz,, and R2 is adjusted to produce a minimum frequency of about 0.003 Hz. The entire range can be shifted
toward higher frequencies by using a timing capacitor smaller than 5 pF. The cost of all the electronic components of the clock module in the configuration presented here was less than $25.
OUTPUT CIRCUIT Figure 2 is a schematic diagram of an output module, many of which can be. connected in parallel to the output of a clock module. The, output of the clock module is a series of brief negative-going pulses from a maintained level of about +11 V, so closing SI causes LED1 to appear to be on constantly, and it serves as a pilot light. IC I and IC2 are wired as monostable multivibrators, The brief negative-going clock pulse triggers IC1, and after an interval determined by R 1, the falling edge of the output'pulse from ICl triggers IC2. 1C2 produces an output pulse whose duration is determined by R2, When S2 is in the PULSE position, the output pulse, buffered by IC3, causes LED2 to turn on for the, duration of the pulse, and is transferred to the gain stage IC4. When S2 is in the DC position, the positive supply is connected to the noninverting input of buffer IC3. Since both the output pulse of IC2 and the positive supply saturate IC3, a
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-24, NO. 5, SEPTEMBER 1977
42
-
AMPLITUDE
DURATION
DELAY 12
+ 12
| out
clock in
C
in pF Fig. 2. The output module. IC1 controls the delay between the clock pulse and the output pulse. IC2 controls the duration of the output pulse, which is buffered by IC3. IC4 controls the pulse amplitude. R1 is the delay control,R2 the durationcontrol,andR4 the amplitude control. R3 and R5 trim the output offset. LED1 and LED2 are resistor-containing LEDs designed for 12 V operation.
signal of the same amplitude reaches IC4 regardless of the position of S2. The gain stage is adapted from a circuit published by Graeme (2). It has been modified to allow the gain to be varied from about I to -1 by rotation of a single control, R4. The input impedance of IC4 in this configuration varies with gain. Since the output characteristics of IC2 vary with load, buffer 1C3 has been inserted. Resistors R3 and R5 allow the output offset to be trimmed. The cost of all the electronic components of each output module was less than $30. ACKNOWLEDGMENT The authors would like to thank Mr. K. C. Rock for scrutinizing the manuscript and Ms. Fay Eldred for drawing the figures. REFERENCES 1. Dobkin, R. C. "Wide range timer". Electronic Eng. Times, 14 January 1974, p. 17. 2. Graeme, J. "A single potentiometer adjusts op-amp's gain over bipolar range". Electronic Des., Vol. 23, p. 68, 1975.
An Algorithm for the Automated Determination of Cardiac Output by the Stewart-Hamilton Method DAVID B. FRANCIS AND KUANG-CHI HU Abstract-An algorithm is described for the digital computer determination of cardiac output by the Stewart-Hamilton method. The algorithm is concerned with the choice of a window over which a negative exponential is fitted to the indicator dilution data to eliminate the effects of recirculated indicator. Trials of the algorithm are reported, and it is found to be suitable for clinical use.
Manuscript received July 12, 1976; revised November 1, 1976. The authors are with the IBM General Systems Division, Rochester,
MN 55901.
The Stewart-Hamilton method is widely used for determination of cardiac output from indicator dilution curves (1, 2). It relies on the property that, in the absence of recirculation of indicator, the washout portion of the curve is a negative exponential. The exponential washout property derives from an idealized single tank model for the central circulation in which complete mixing occurs. Calculation -of cardiac output requires that the area under A the indicator dilution curve be obtained independent of the effects of recirculation. In the Stewart-Hamilton technique, an exponential is fitted to the descending limb of the dilution curve enough below the peak that the curve is approximately exponential, but before the recirculated indicator appears; curve area (which is inversely proportional to cardiac output) is then determined from the actual data up to the exponential and from the exponential thereafter. The exponential is often fitted graphically by plotting the dilution data on semi-log graph paper. Choosing the region for the exponential fit is fairly straightforward when performed manually, but is both difficult and critical when it is desired to automate the StewartHamilton cardiac output calculation. Algorithms for computer determination of Stewart-Hamilton cardiac output have been reported previously (3). The algorithm described here has been validated and is in routine clinical use in an intensive care setting. The algorithm is part of a complete package of computer programs for the acquisition, analysis and display of indicator dilution curves. The package itself is one component of a comprehensive clinical information system developed jointly by the Mayo Clinic and IBM for use in coronary and open-heart-surgical intensive care (4). A sample output from the cardiac output package is shown in Figure 1. Note that the baseline, extrapolated exponential and certain fiducial points are displayed with the indicator dilution curve and that the numerical results are tabulated below. Quantities referred to in this paper have been identified on the computer displayed graph of dye concentration versus time. In addition to Cardiac Output (CO), the program also calculated Cardiac Index (CI-cardiac output normalized for body surface area), Stroke Volume Index (SVI-cardiac output normalized by body surface area and heart rate) and Systemic Resistance (RS-mean arterial pressure divided by car-
480
[5] Newhouse, V. L., P. J. Bendick and L. W. Varner, "Analysis of Transit Time Effects on Doppler Flow Measurement," IEEE Trans. Biomed. Eng., Vol. BME-23, pp. 381-387, Sept. 1976. Green, P. S., "Spectral Broadening of Acoustic Reverberation in Doppler-Shift Fluid Flowmeters," Jour. Acoust. Soc. Am., 36, No. 7, pp. 1383-1390, 1964.
3000
[6]
2800 2600 l
2400
--
° -- --
J/
-i
2200
+--
EXPERIF
ENTAL,
60°
8
EXPERIM4ENTAL,8145°
[7]
Newhouse,
V.
"Transit Time Broadening in Ultrasonic Doppler
L.,
Flow Measurement Systems," Internal Report, Purdue University, Nov. 1973.
2000 I 1800
An Inexpensive Modular Pulse Generating System
F 1600 3 1400
JOHN NOLTE AND THEODORE J. TARBY
z
Il
1200
Abstract-A multiple channel pulse generator is described, consisting of a clock module and several identical output modules. Clock frequency can be varied continuously from 0.003 Hz to 100 Hz. Output pulses have continuously variable duration, can be positioned anywhere within the timing cycle, and their amplitude is variable from +5 to -5 V.
1000
800 600
400 200 0_
1
0
2
3
5
4
It is frequently necessary in biological and other experiments to program sequences of events, such as oscilloscope sweeps and various stimuli. The apparatus called for must allow for repetition of the sequence at some selectable frequency, as well as allowing the experimenter to vary the relative positions
6
-RANGE, cm Fig. 3. Doppler bandwidth
f
as a function of
of the events within the
range.
transit time effects. Rough calculations in(dicate that this geometrical broadening will always dominate a for targets in the near field of the transducer. However, ince geometrical idening due to broadening decreases with range and transit time effects is independent of range as long as the )ossible to find beam width remains constant, it may This was conditions where the two effects are compar ffith and Brody probably the case for the experiments in which only transit time effects were consider red [4]. As pointed out above, geometrical broa(dening may be usable as a means of estimating the beltween the ultraa technique for sound beam and the flow direction, measuring flow at right angles to an beam. Whether or not these techniques are in fact il for real time blocity gradients pulsatile blood flow measurements whereve exist and where possibly only 20 ms are available for 1- In any event, spectrum estimation remains to be established the geometrical broadening effects described I ere will have to be taken into account in the design ins intended to measure Doppler bandwidth for the i of factors such as velocity gradient or turbulence. si
broa
be
rable.
of Gri
angle
and
as
L
ultrasound practicl
of
of
data
syste
Good absolute timing
sequence.
accuracy is usually not necessary, since the events, or some
representation
thereof,
chart recorder. We describe here
a
are
displayed
on
an
oscilloscope
simple modular system which
or
offers low
cost and maximum ease of operation. The circuits are based on the widely used type 555 timer. The master frequency control is a single potentiometer by of which the repetition rate can be varied over about five orders of magnitude. No range switches are involved, but the resolution is means
good
throughout
the
entire
range
changes logarithmically with the output channel there are single
since
the
repetition rate
control resistance. For each controls for pulse duration,
amplitude and delay (with respect to the clock pulse). A seven-channel unit is presently used in the senior author's laboratory, controlling two electromechanical shutters, two
electrode
resistance
testers,
current
injection
micropipette
through two
electrodes and a calibration pulse generator. clock output triggers the oscilloscope sweep, and seven events may be positioned at any desired
within the
The
each of the temporal location
sweep.
estimatiol
ACKNOWLEDGMENT
The authors
are grateful to E. S.
Furgason
f
or many helpful
discussions.
REFERENCES Arts, M. G. J. and J. M. J. G. Roevros, "On the Instantaneous Measurement of Blood Flow by Ultrasonic ins", Med. & Biol. XEngng., Vol. IO, pp. 23-24, 1972. 121b lbright, R. J. and J. H. Harris, "Diagnosis Urethral on B Flow [1
Mea
tvarameters Vol.
3 [4]
by Ultrasonic
BME-22,
pp.
of
Backscatter",
IEEE
7'rans.
lamed.
1-91,1975.
CLOCK CIRCUIT
Figure1 is a schematic diagram of the clock circuit, which is simplified from a previously published design (1). If greater wider range of operating frequencies temperature stability are required, the original description should be consulted. The base voltage of Q1 is fixed at 9.1 V by the1N757 zener diode. When the wiper of R3 is at the upper end of its range the emitter voltage of 1Q is Q (shorted to the base of 1), or a
fixed at some value near 9.7 V by the 1N746-ICl feedback loop. Since the emitter-base voltage of 1Q is fixed, a constant collector current flows, charging the 5 pF capacitor. Rotating
Manuscript received August 9, 1976; revised December 2, 1976. This work was supported by Grants EY 01155 (National Eye Blooa Velocity and Angle", Poc. 28th A CEMB, p. 76, Sept. 1975. Institute) and BMS75-17638 (National Science Foundation). The authors are with the Department of Anatomy, University of in UltraGriffith, J. M., and Brody, W. R., "Velocityesolution Re 1975. Colorado Medical School, Denver, CO 80262. sonic Doppler Flowmeters," Proc. 28th ACEMBI p.r- 75,Sept. I --I-
V
L. W., V. L. Newhouse and P. J. Ben4lick, "Application transit Time Effects to the Independent Measurement of
er,
-
--
--
, - -
COMMUNICATIONS
481
SI +
LED
.01
C in pF
Vext
47K
2N3
--L .02
.2 4
The clock module. IC1 and associated circuitry forni a current which charges the 5 juF timing capacitor of IC2, The output clock pulses, of IC2 are buffered by IC3. IC4 substitutes for the positive supply of IC1, allowing for the generation of single clock pulses in response to manual (S3) or external electrical (Vext, >5 V) inputs. R1 trims the maximum clock frequency, R2 the minimum frequency. R,3 is the main frequency control. LED is a resistorcontaining LED designed for 12 V operation.
Fig.
1.
source,
,
R3 lowers the voltage of the noninverting input of ICI and lowers the emitter voltage at Q 1. Sin'e the' base voltage is fixed, the emitter-base voltage is decreased and the collector current decreases. Since the emitter-base voltage of a transistor is related to the logarithm of its collector~current, this part of the circuit acts as a logarithmicolly coptrolled current source charging the 5 gF capacitor. The 5 jiF capacitot charges until the' threshold of IC2 is reaclied, then discharges quickly through the I1002 resistor, resulting in a brief negative pulse at the output of IC2 which, after being buffered by IC3, serves as the clock pulse., When S2 is in the EXT position the current source involving IC . functions only. when there is a positive output from IC4. A negative spike input to IC4 can be prodticed by 5 V or more at Vext or by depressing S3 and IC4'then generates a positive pulse just long enough to produce a, single clock pulse. Leakage currents in the circuit are such thatwhen S2 is in the EXT position, the 5 'MF timing capacitor charges to threshold about every 2minm; If lcnger'intetvals are nfqcssary, a 10 M&Z resistor shunting the timing capacitor will prevent spurious triggering due to leakage currents. In practice, R I is adjusted to produce a maximum, clock frequency of 1 00 Hz,, and R2 is adjusted to produce a minimum frequency of about 0.003 Hz. The entire range can be shifted
toward higher frequencies by using a timing capacitor smaller than 5 pF. The cost of all the electronic components of the clock module in the configuration presented here was less than $25.
OUTPUT CIRCUIT Figure 2 is a schematic diagram of an output module, many of which can be. connected in parallel to the output of a clock module. The, output of the clock module is a series of brief negative-going pulses from a maintained level of about +11 V, so closing SI causes LED1 to appear to be on constantly, and it serves as a pilot light. IC I and IC2 are wired as monostable multivibrators, The brief negative-going clock pulse triggers IC1, and after an interval determined by R 1, the falling edge of the output'pulse from ICl triggers IC2. 1C2 produces an output pulse whose duration is determined by R2, When S2 is in the PULSE position, the output pulse, buffered by IC3, causes LED2 to turn on for the, duration of the pulse, and is transferred to the gain stage IC4. When S2 is in the DC position, the positive supply is connected to the noninverting input of buffer IC3. Since both the output pulse of IC2 and the positive supply saturate IC3, a
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-24, NO. 5, SEPTEMBER 1977
42
-
AMPLITUDE
DURATION
DELAY 12
+ 12
| out
clock in
C
in pF Fig. 2. The output module. IC1 controls the delay between the clock pulse and the output pulse. IC2 controls the duration of the output pulse, which is buffered by IC3. IC4 controls the pulse amplitude. R1 is the delay control,R2 the durationcontrol,andR4 the amplitude control. R3 and R5 trim the output offset. LED1 and LED2 are resistor-containing LEDs designed for 12 V operation.
signal of the same amplitude reaches IC4 regardless of the position of S2. The gain stage is adapted from a circuit published by Graeme (2). It has been modified to allow the gain to be varied from about I to -1 by rotation of a single control, R4. The input impedance of IC4 in this configuration varies with gain. Since the output characteristics of IC2 vary with load, buffer 1C3 has been inserted. Resistors R3 and R5 allow the output offset to be trimmed. The cost of all the electronic components of each output module was less than $30. ACKNOWLEDGMENT The authors would like to thank Mr. K. C. Rock for scrutinizing the manuscript and Ms. Fay Eldred for drawing the figures. REFERENCES 1. Dobkin, R. C. "Wide range timer". Electronic Eng. Times, 14 January 1974, p. 17. 2. Graeme, J. "A single potentiometer adjusts op-amp's gain over bipolar range". Electronic Des., Vol. 23, p. 68, 1975.
An Algorithm for the Automated Determination of Cardiac Output by the Stewart-Hamilton Method DAVID B. FRANCIS AND KUANG-CHI HU Abstract-An algorithm is described for the digital computer determination of cardiac output by the Stewart-Hamilton method. The algorithm is concerned with the choice of a window over which a negative exponential is fitted to the indicator dilution data to eliminate the effects of recirculated indicator. Trials of the algorithm are reported, and it is found to be suitable for clinical use.
Manuscript received July 12, 1976; revised November 1, 1976. The authors are with the IBM General Systems Division, Rochester,
MN 55901.
The Stewart-Hamilton method is widely used for determination of cardiac output from indicator dilution curves (1, 2). It relies on the property that, in the absence of recirculation of indicator, the washout portion of the curve is a negative exponential. The exponential washout property derives from an idealized single tank model for the central circulation in which complete mixing occurs. Calculation -of cardiac output requires that the area under A the indicator dilution curve be obtained independent of the effects of recirculation. In the Stewart-Hamilton technique, an exponential is fitted to the descending limb of the dilution curve enough below the peak that the curve is approximately exponential, but before the recirculated indicator appears; curve area (which is inversely proportional to cardiac output) is then determined from the actual data up to the exponential and from the exponential thereafter. The exponential is often fitted graphically by plotting the dilution data on semi-log graph paper. Choosing the region for the exponential fit is fairly straightforward when performed manually, but is both difficult and critical when it is desired to automate the StewartHamilton cardiac output calculation. Algorithms for computer determination of Stewart-Hamilton cardiac output have been reported previously (3). The algorithm described here has been validated and is in routine clinical use in an intensive care setting. The algorithm is part of a complete package of computer programs for the acquisition, analysis and display of indicator dilution curves. The package itself is one component of a comprehensive clinical information system developed jointly by the Mayo Clinic and IBM for use in coronary and open-heart-surgical intensive care (4). A sample output from the cardiac output package is shown in Figure 1. Note that the baseline, extrapolated exponential and certain fiducial points are displayed with the indicator dilution curve and that the numerical results are tabulated below. Quantities referred to in this paper have been identified on the computer displayed graph of dye concentration versus time. In addition to Cardiac Output (CO), the program also calculated Cardiac Index (CI-cardiac output normalized for body surface area), Stroke Volume Index (SVI-cardiac output normalized by body surface area and heart rate) and Systemic Resistance (RS-mean arterial pressure divided by car-
