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BACKGROUND OF THE INVENTION
This invention relates to a limb blood flowmeter for measuring the blood
flow rate in human limb segments.
For example, in the case of using an artificial kidney, the blood is
dialyzed by a hemodialyzer. In such a case, the measurement of the blood
flow rate is indispensable to the determination of the period time for
hemodialysis, that is, the time for each application of blood of
substantially the whole body to the hemodialyzer. One method that has
usually been employed in conventional hemodialyzers for the measurement of
the blood flow rate is to make transparent a blood flow path between the
hemodialyzer and the human body, form a bubble in the path at a certain
place and measure the time for the passage of the bubble for a
predetermined distance in the path, thereby to measure the blood flow
rate. However, such a method is very troublesome, and the bubble in the
blood entails a danger to the patient and, on top of that, the measurement
obtained is relatively inaccurate.
In view of the abovesaid defects, there is a strong demand for means for
accurately measuring the blood flow rate in the human body by a
non-invasive method. One method for measuring blood flow rate or blood
volume change non-invasively is the venous occlusion method. With this
method, an occluding pressure cuff is wrapped around a limb such as an arm
or leg to occlude the venous return and hence cause an increase in the
tissue volume in the limb by the arterial inflow, and the increased tissue
volume is measured to detect the blood flow rate. Thus the blood flow rate
can be measured non-invasively without taking out a blood vessel for
directly measuring the blood flow rate. This measurement is carried out in
the following manner:- For example, an arm is immersed in water or like
liquid contained in a measuring chamber, and the venous return is stopped,
with the arm and the chamber held liquid-tight therebetween. An increase
in the tissue volume of the arm by the arterial inflow is detected from
the quantity of liquid which is caused to overflow by the arterial inflow,
and then the blood volume flow is measured from the amount of tissue
volume thus increased. However, a change in condition of the human limb
due to the liquid temperature change during the measurement introduces an
error in measurement. Accordingly the liquid temperature must be kept
constant, and its control is complicated and, further, when the arm is
immersed in the liquid for a long period of time, as mentioned above, the
blood flow rate cannot be measured repeatedly and continuously.
A method that has been proposed for measurement of the ventricular stroke
volume by measuring impedance changes based on ventricular systol is
impedance plethysmography. This is set forth, for instance, in Medical
Physics, Vol. II, Year Book 736/743 (1950), J. Nyboer, "Plethysmograph:
Impedance", Aerospace Med. Vol. 37, 1208/1212 (1966), W. G. Kubicek et al,
"Development and Evaluation of an Impedance Cardiac Output System" and so
on. This method is to supply a high-frequency, very small current to a
limb segment and measure the limb blood flow from a change in the
electrical impedance of the limb segment caused by the venous occlusion.
This method enables non-invasive and continuous measurement of the blood
flow, but the impedance variation by a change in the blood volume is
affected by the initial impedance value of the segment to be examined and
does not coincide accurately with the actual change in the volume.
Consequently the impedance variation is measured inclusive of the
electrical characteristics of other tissues than that of the region
desired to be examined, therefore the abovesaid method is defective in
theory and in the accuracy of measurement.
Further, in his thesis submitted to the Faculty of the Graduate School of
the University of Minnesota, 1965, "Cardiac Output Determinations Using
Impedance Plethysmography", R. P. Patterson made a theoretical proposal of
utilizing admittance for measuring the ventricular stroke volume.
An object of this invention is to provide a limb blood flowmeter which
enables non-invasive, continuous and accurate measurement of the limb
blood flow rate.
Another object of this invention is to provide a limb blood flowmeter which
enables accurate measurement of the limb blood flow rate regardless of the
initial admittance value of the limb and without including the electrical
characteristics of other tissues than that of the region to be examined.
Still another object of this invention is to provide a limb blood flowmeter
using the admittance method which is capable of direct measurement of a
change in the blood volume independently of the initial admittance value
of the limb to be examined.
SUMMARY OF THE INVENTION
In accordance with this invention, the venous return in the limb to be
examined is occluded, and the initial admittance value of the limb is
measured and held and is then compared with the subsequent admittance
value of the limb due to the venous occlusion to obtain the difference
.DELTA.Y between them. The blood resistivity .rho., the length L of the
segment to be examined and its volume V.sub.O are respectively set in
setters, and .rho.L.sup.2 .DELTA.Y/V.sub.O is computated, and then the
computation result is recorded on an output device. A series of operations
for the venous occlusion, the holding of the initial admittance and the
drive of the recorder are sequentially carried out under the control of a
controller. Thus the blood flow rate can be obtained from the initial
gradient of a plethysmogram recorded on the recorder to time. In the above
calculation, .rho., L.sup.2 and V.sub.O are constants and thus it is
obvious that the blood volume change is directly proportional to the
difference .DELTA.Y alone.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a schematic diagram of the four electrodes method and the
position of the pneumatic cuff for venous occlusion in a human limb;
FIG. 2 is a block diagram illustrating an embodiment of the limb blood flow
rate of this invention;
FIG. 3 is a block diagram showing an example of a cuff pressure generating
unit utilized in the embodiment of FIG. 2;
FIGS. 4A to 4H are timing signals showing the sequential control of a logic
circuit used in the embodiment of FIG. 2;
FIG. 5 shows plethysmograms obtained in experiments conducted with the
blood flowmeter of this invention;
FIG. 6 shows a graphical representation of human limb blood flow variations
before and after exercise obtained by the blood flowmeter of this
invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In measurement of the limb blood flow, the venous return in the limb to be
examined is occluded, for instance, by a method such as shown in FIG. 1.
In FIG. 1, an occluding pressure cuff 12, usually employed in
sphygmomanometry, is wrapped around the forearm 11 at the side of the
heart, in this case, on the upper arm, and inflated to occlude the venous
return. The occluding pressure is usually lower than the diastolic blood
pressure but higher than the venous pressure and about 40 to 50 mmHg in
the case of a healthy subject. Electrodes 13 and 14 are wound around the
forearm 11 in its longitudinal direction and electrically connected
thereto. An AC signal of 50 KHz, for example, is applied across the
electrodes 13 and 14. On the inside of the electrodes 13 and 14, measuring
electrodes 15 and 16 are similarly wrapped around the forearm 11 to
measure the admittance of the segment between the measuring electrodes 15
and 16. Letting L represent the distance between the measuring electrodes
15 and 16, i.e. the length of the segment to be examined, .rho. represent
the blood resistivity and .DELTA.Y represent the difference between the
admittance between the measuring electrodes 15 and 16 before venous
occlusion and the admittance when the tissue volume of the segment to be
examined has been increased by the arterial inflow after venous occlusion,
an increase .DELTA.V in the limb volume by the arterial inflow is
expressed as follows:
.DELTA.V=.rho.L.sup.2 .DELTA.Y (1)
From this, the blood flow rate F is given as the following time
differentiation of the increase .DELTA.V in the limb volume immediately
after venous occlusion:
F=.rho.L.sup.2 dY/dt (2)
Usually the blood flow rate F is normalized to 100 ml of limb volume.
Accordingly, a volume change .DELTA.V' per unit limb volume is given as
follows:
.DELTA.V'=.rho.L.sup.2 .DELTA.Y/V.sub.O (3)
where V.sub.O is the volume of the limb segment to be examined. The volume
change .DELTA.V' is recorded and the initial gradient of its recorded
curve to time or the differentiated value of the volume change .DELTA.V',
that is, the limb blood flow rate per unit limb volume is measured. The
reason for such measurement of the limb blood flow rate by recording is
that the volume change .DELTA.V' is very slow and hence is difficult to
obtain by differentiation with a calculator circuit.
In the present invention, the volume change .DELTA.V' is measured by the
employment of such a circuit structure as shown in FIG. 2. In FIG. 2,
reference numeral 22 indicates generally an admittance measuring unit, in
which an AC current of 1 mA and 50 KHz, generated from an AC current
generator 23, for example, is applied across the electrodes 13 and 14,
with the common potential point electrically isolated from the AC current
generator 23. To this end, the output from the AC current generator 23 is
applied across the electrodes 13 and 14 via an isolating transformer 24.
The current applying across the electrodes 13 and 14 is maintained
accurately at a constant value of 1 mA, for instance. For this purpose, a
current detecting resistor 25 is connected in series with the secondary
side of the transformer 24 and is connected at both ends to the primary
side of a transformer 26. The secondary side of the transformer 26 is
grounded at one end and connected at the other end to a comparator 27. In
the comparator 27, a voltage detected by the detecting resistor 25 is
compared with a reference voltage from a terminal 28, and the compared
output from the comparator 27 is negatively fed back to the AC current
generator 23 to control it to hold its output current constant.
A signal indicative of the impedance value between the measuring electrodes
15 and 16, that is, a voltage drop based on the abovesaid AC current, is
picked up, with the common potential point isolated from these electrodes.
In the illustrated embodiment, the above signal is picked up by using a
high input impedance lest the AC current should flow in the signal pick-up
side to introduce an error in the measured value. To perform this, the
measuring electrodes 15 and 16 are respectively connected via coupling
capacitors 29 and 31 to a differential amplifier 32 of high input
impedance, the output from which is supplied to an AC-DC converter 34 via
a common potential point isolating transformer 33. In the converter 34, an
AC signal inputted thereto is smoothed after being subjected to full-wave
rectification to provide a DC current value corresponding to the impedance
between the measuring electrodes 15 and 16. The DC output from the
converter 34 is applied to an analog divider 35 to obtain the reciprocal
of the DC output; in other words, the DC output is converted to the
admittance value between the measuring electrodes 15 and 16. It is also
possible to convert the output from the AC-DC converter 34 by an A-D
converter 36 into a digital signal and supply it via an output terminal 37
to a display (not shown) for providing a display of the impedance between
the measuring electrodes 15 and 16.
The initial value of the admittance measuring unit 22 is retained by a
sampling and holding circuit 38 and an initial admittance V.sub.O is
stored therein. An admittance value having changed with a variation in the
tissue volume of the segment being examined, as a result of venous
occlusion, is provided in the analog divider 35, and this admittance value
and the initial one Y.sub.O are subtracted from each other in a subtractor
39 to obtain a difference .DELTA.Y therebetween, which is supplied as an
input to a calculation circuit 41.
On the other hand, there are provided a setter 42 for setting the blood
resistivity .rho., a setter 43 for setting the length L of the segment to
be examined and a setter 44 for the limb volume V.sub.O of the segment to
be examined. For facilitating the setting of these values, they can be
set, for example, by digital switches, and the set values are converted to
analog signals for input to the calculation circuit 41. The unit of the
blood resistivity .rho. is .OMEGA..multidot.cm, and resistivities of 50 to
199 .OMEGA..multidot.cm can be set at intervals of 1 .OMEGA..multidot.cm,
for instance. The blood resistivity varies with the hematocrit value Hct,
and the following experimental formula can be employed for the correction
of the blood resistivity with respect to the hematocrit value Hct:
.rho.=50.7 exp (0.023 Hct)
The hematocrit value Hct of an ordinary healthy subject is substantially
constant, and the blood resistivity .rho. is about 140
.OMEGA..multidot.cm. The length L between the measuring electrodes 15 and
16 is measured in cm, and the limb volume V.sub.O between these electrodes
is measured in 100 ml.
The set outputs .rho., L and V.sub.O from the abovementioned setters 42
through 44 and the output .DELTA.Y from the subtractor 39 are provided to
the calculation circuit 41 for achieving the calculation of the aforesaid
formula (3). In this case, for example, .rho..multidot.L.sup.2 /V.sub.O is
calculated first and is then multiplied by .DELTA.Y. The output from the
calculation circuit 41 is supplied, for instance, to a heat-pen recorder
45 for recording.
A cuff pressure control unit 46 is provided for controlling the pressure to
the cuff 12 used for occlusion of the venous return. The cuff pressure,
the sampling and holding circuit 38 and the recorder 45 are all controlled
by a control circuit 47. The cuff pressure control unit 46 has a
construction such, for example, as illustrated in FIG. 3. In FIG. 3, since
the control circuit 47 is housed in a casing in close proximity to the
calculator circuit and others, an electrical signal for the cuff pressure
control is converted to a pneumatic signal so as to prevent the cuff
pressure control from generating a large magnetic field which might affect
the operations of the other electric circuits. That is to say, compressed
air from a small compressor 48 is applied via a precision reducing valve
49 to an air tank 51, from which the air pressure is supplied to the cuff
12 via a three-way valve 52 and a throttle 53. In case of controlling the
three-way valve 52 with an electrical signal, an appreciably large
electrical signal is required and generates a large magnetic field, as
referred to above. To avoid this, a converter 54 is provided for
converting an electrical signal to a pneumatic one, and the air pressure
from the compressor 48 is branched to be supplied via a fluidic diode 55
to the air tank 56, from which the air provides a pneumatic control signal
to the three-way valve 52 via a pneumatic relay 57. On the other hand, the
air from the air tank 56 is branched to be supplied via a throttle 58 to a
nozzle 59 and the pneumatic relay 57. A flapper 61 is disposed opposite
the tip of the nozzle 59 and its position is controlled by an
electromagnetic coil 62. Upon energization of the electromagnetic coil 62
to pull the flapper 61 away from the nozzle 59, the three-way valve 52 is
controlled by the output from the pneumatic relay 57 to permit the air
supply from the air tank 51 to the cuff 12. The pressure of the air tank
51 is indicated by a pressure indicator 63.
The control circuit 47 in FIG. 2 is constructed to perform the operations
such, for example, as shown in FIG. 4. That is, a main timer incorporated
in the control circuit 47 generates a pulse such as depicted in FIG. 4A
which has a period T.sub.1 and a pulse width W.sub.1. The period T.sub.1
can be selected to be for instance, 10 minutes, 30 minutes, an hour or two
hours, and the pulse width W.sub.1 is selected to be approximately 30
seconds. With the leading edge of the pulse from the main timer, a trigger
pulse shown in FIG. 4B is produced, and when required, a pulse for driving
a buzzer informing the start of measurement to a subject is generated by
the trigger pulse. Further, the trigger pulse is used for driving the
small compressor 48 in FIG. 3 and feeding a recording paper of the
recorder 45 in FIG. 2 and heating its recording pen, as depicted in FIGS.
4D, E and F, respectively. As shown in FIG. 4G, the electromagnetic coil
62 in FIG. 3 is energized after a period T.sub.2 , for instance, 10
seconds, to thereby generate the cuff pressure. The cuff pressure is
maintained for a period T.sub.3, for example, 15 seconds. As illustrated
in FIG. 4H, for a period T.sub.4, commencing for example, about 1.0 second
after the generation of the cuff pressure, the sampling and holding
circuit 38 in FIG. 2 samples and holds the output from the divider 35 to
retain the initial admittance Y.sub.O. For about 15 seconds (a period
T.sub.3) during which the cuff pressure is applied, the output from the
calculator circuit 41 in FIG. 2 is recorded by the recorder 45.
Thereafter, the cuff pressure is removed to return the respective parts of
the device to their initial state. The period T.sub.1 after the abovesaid
trigger pulse, a trigger pulse is generated again to achieve the same
operations as described above. In the recording, before venous occlusion,
the sampling and holding circuit 38 achieves sampling alone and, at this
time, the recording pen of the recorder 45 is held to read "zero" and,
upon venous occlusion, the sampling and holding circuit 38 is switched to
the holding mode of operation to enable recording of only a change in the
volume of the limb segment to be examined. The sampling and holding
circuit 38 is switched by a timer signal between such modes of operation.
The recording by the recorder 45 takes such a form as indicated by 65 to 67
in FIG. 5. The start of each of the curves 65 to 67, that is, the
left-hand end of each curve in FIG. 5, shows the moment of generation of
the trigger pulse. The points indicated by the arrows 68, after the elapse
of time T.sub.2, each show the moment of application of the cuff pressure.
Before the application of the cuff pressure, the recording pen is held to
read null and also immediately after the application of the cuff pressure,
the recording pen is still maintained at the zero point because the
operator output from the calculation circuit undergoes a transient change
the instant of application of the cuff pressure. Then, the output from the
calculation circuit 41 is recorded. In FIG. 5, the arrow 69 indicates the
moment of release of the cuff pressure. The initial gradients of the
recorded curves of the calculation results to the time axis (the
abscissa), that is, the angles of straight lines 71 to 73 along the rising
of the curves 65 to 67 to the lengthwise direction of the recording paper,
represent the limb blood flow rates desired to obtain. The illustrated
examples were obtained in the case where .rho.=142 .OMEGA..multidot.cm,
L=15 cm and V.sub.O =5.25 100 ml and the ambient temperature was changed
in three ways.
The blood flow rate is measured in the manner described above. FIG. 6 shows
examples of measurement of blood flow variations after exercise in an
examinee, the curve 74 indicating the case of the forearm being examined
and the curve 75 the case of the calf being examined. The examinee had
some exercise for five minutes, as indicated by 76 in FIG. 6. It will be
seen from FIG. 6 that the blood flow rate markedly increases immediately
after exercise but naturally decreases to return to the state at rest
before the exercise as time passes. As referred to previously, this blood
flowmeter is capable of automatically monitoring the blood flow rate at
regular time intervals T.sub.1, but it is also possible to achieve the
measurement by generating the trigger pulse at a desired moment. For the
calibration of such recording, it is arranged that the output .DELTA.V'
from the computation circuit 41 becomes 0.25 ml/100 ml, for example, when
.rho.=111 .OMEGA..multidot.cm, L=15 cm and V.sub.O =999 ml and .DELTA.Y
(=0.1 mm ) is applied to the computation circuit 41. This is in the case
where the recording sensitivity is 0.25 m/100 m/FS, and the sensitivity of
the recorder 45 is adjusted so that the recorder reaches its full scale
under the abovesaid conditions. For such calibration, a calibration box is
incorporated in the blood flowmeter, which box sets resistance values, for
instance, 0 to 200.OMEGA. at intervals of 10.OMEGA. and is capable of
changing each resistance value by 0.1.OMEGA. and 1.OMEGA.. Various values
of .DELTA.Y are produced with the calibration box and applied as the
reference values of .DELTA.Y to the computation circuit 41 for the
abovesaid calibration. By picking up the AC components in the output from
the divider 35 or the subtractor 39, arterial ripples are measured. For
example, in FIG. 2, the output from the analog divider 38 is branched by a
capacitor 81, and only the AC components are picked up. The AC components
are shaped by a wave-form shaping circuit 82 into shaped pulses, which are
counted by a counter 83 for unit time. The count value of the counter 83
is indicative of the heart rate. Such simultaneous measurement of the
heart rate with the blood flow rate enables an analysis of their
relationship to each other.
On top of that, the blood flowmeter of this invention can be employed for
sphygmomanometry. In the measurement of the blood flow rate the cuff
pressure is selected, for instance, about 50 mmHg to occlude the venous
return alone, but in the measurement of blood pressure the cuff pressure
is further raised to occlude the arterial inflow as well as the venous
return. Upon occlusion of the arterial inflow, the cuff pressure is
gradually reduced, and the generation of the arterial inflow is detected
in the form of generation of a ripple, for instance, by means of a monitor
84 connected to the input side of the waveform shaping circuit 82, and
then the systolic blood pressure is measured from the cuff pressure at
which the arterial inflow is permitted. The cuff pressure is further
lowered, and restoration of the arterial inflow to its steady state is
detected from the amplitude of the ripple having become constant in the
monitor 82, and then the diastolic blood pressure is measured from the
cuff pressure at that time. It is also possible that the cuff pressure at
which the ripple disappears as a result of raising the cuff pressure is
used as the systolic blood pressure.
The blood flow rate is obtained by recording with the recorder but may also
be obtained in the following manner: For instance, in FIG. 2, the output
level of the calculation circuit 41 is sampled by a circuit 85 under an
instruction from the control circuit 47 T.sub.5 seconds after the
application of the cuff pressure, and the sampled output is multiplied by
60/T.sub.5 in a circuit 86 to be converted into the blood flow rate per
minute, thereafter being displayed in a digital or analog form on a
display 87.
As has been described in the foregoing, it is possible with the limb blood
flowmeter to measure the limb blood flow non-invasively and successively.
On top of that, since the measured output bears no relationship to the
initial admittance, as expressed by the formula (3), the measured value
excludes the electrical characteristics of tissues outside of the object
to be examined, and hence is accurate. Further, the blood flowmeter of
this invention can be easily used without any danger to examinees and is
also convenient for measuring the limb blod flow rates of many persons. As
described previously with regard to FIG. 2, an AC signal is applied to the
limb to be examined, but since the measuring device and the common
potential are isolated by the transformers 24, 26 and 33 from each other,
there is no possibility of the limb receiving an electrical shock. The
measuring electrodes 15 and 16 are connected via capacitors to the input
side of a differential amplifier, so that a circuit of high input
impedance can be connected to the electrodes 15 and 16. For example, in
the case of connecting the isolating transformer 33 directly between the
electrodes 15 and 16, even if a high input impedance transformer is
employed, its input impedance becomes appreciably low to introduce an
error in measurement, but the abovesaid embodiment is free from such a
defect and ensures highly accurate measurement.
The current applying across the electrodes 13 and 14 is detected by the
resistor 25 and controlled by the detected output to remain constant, and
this also assures measurement of high accuracy. For instance, even if the
AC signal generator 23 itself is so constructed as to provide a constant
current output, a constant AC current cannot always be produced due to a
change in the contact resistance between the electrodes 13 and 14 and the
limb 11 being examined, but the circuit structure shown in FIG. 2 ensures
to accurately provide a constant current. While the foregoing has
described the blood flowmeter of this invention in connection with the
case where the impedance components are measured and then the admittance
is obtained by way of division, it is also possible to design the blood
flowmeter to directly measure the admittance. In such a case, a method of
voltage clamp is available to the limb to be examined in place of the
method of current clamp.
It will be apparent that many modifications and variations may be affected
without departing from the scope of the novel concepts of this invention.
* * * * *
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