JPH0351177B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] This invention relates to a liver function testing device, and in particular, the present invention relates to a liver function testing device, and in particular, a specific dye that is selectively taken in and excreted only by the liver is injected into the blood to determine the plasma elimination rate and stagnation. The present invention relates to a liver function testing device that automatically performs measurement processing for measuring liver function and diagnosing liver function.

[Prior art] Conventional methods for measuring plasma disappearance rate and stagnation rate include:
A method has been used in which measurement is performed by blood sampling using intocyanin green (hereinafter referred to as ICG) as a specific dye. After intravenously injecting ICG into a subject, blood is collected three times at 5, 10, and 15 minutes after the injection, the blood clot is condensed, the serum is separated, and a spectrophotometer is used to collect blood at a wavelength of 805 nm. Measure the absorbance at
The ICG concentration in the serum after 5, 10, and 15 minutes is calculated from the previously obtained calibration curve (corresponding concentration in ICG vs. absorbance), and the plasma elimination rate and stagnation rate are calculated from this concentration change. .

[Problems to be Solved by the Invention] However, in the conventional blood sampling method, it is necessary to accurately measure the time for blood sampling after injection;
In actual inspections, the measurements were not accurate and the measurement operations were complicated. In addition, blood sampling placed a large mental and physical burden on the subject. moreover,
The R _MAX measurement method, which measures the plasma elimination rate several times by varying the amount of ICG injected, has recently become popular, and blood sampling is required over 10 times, reducing the burden on the test subject. There was a problem with it getting bigger.

Therefore, the main purpose of the present invention is to provide a liver function testing device that can reduce the mental and physical burden on the examinee and can perform liver function testing and diagnosis extremely easily and automatically. It is to be.

[Means for Solving the Problems] The present invention is a liver function testing device for testing liver function, which uses light absorbed by a specific dye that is administered into the blood of living tissues and taken in and excreted by the liver. The first light has a wavelength that absorbs light, and the second light has a wavelength that is not absorbed.
a light source means for irradiating the living tissue with light; and a photoelectric conversion means for outputting first and second photoelectric conversion signals corresponding to the first and second light irradiated onto the living tissue and obtained from the living tissue. , first and second
a sampling means for sampling a photoelectric conversion signal of the sampled first and second photoelectric conversion signals; A simulation curve function is calculated using the least squares method based on the sampling signal and the calculated difference between The elapsed time after injection of the specific dye t
When, based on the calculation formula of y = Ae ^Bt , a coefficient calculation means including a means for calculating constants A and B, and a coefficient of the obtained simulation function, when the plasma disappearance rate is K, When the stagnation rate of the specific dye in a predetermined time T is R% based on a means for determining the plasma disappearance rate of the specific dye including a means for calculating the calculation formula of K=-B and the coefficient of the obtained simulation function. The calculated value of the difference between the first and second photoelectric conversion signals is calculated by a means for calculating the stagnation rate of the specific dye at a predetermined time, including a means for calculating the calculation formula of R%=e ^BT , and a coefficient calculating means. mode switching means for switching between a calibration mode for performing calculation operations and a mode for calculating a value correlated to a specific dye density by means of a coefficient calculation means; So that the level is within a predetermined range,
and setting means for setting the intensities of the first and second lights emitted from the light source means.

[Operation] The liver function testing device according to the present invention irradiates living tissue with first and second lights, samples photoelectric conversion signals corresponding to the light obtained from the living body, and samples the sampled first and second lights. The calculated value of the difference between the photoelectric conversion signals of Compute the function of the curve,
Based on the function, a value correlated to the specific pigment concentration in blood is calculated. When the elapsed time after specific color difference injection is t, based on the calculation formula of y=Ae ^BT ,
Calculate the constants A and B, and based on the coefficients of the simulation function, if the plasma disappearance rate is K, then K
=-B is calculated to determine the plasma disappearance rate of the specific dye. Furthermore, based on the coefficients of the simulation function, when the stagnation rate of the specific dye in a predetermined time T is R%, the calculation formula R%=e ^BT is calculated to find the stagnation rate in a predetermined time. In addition, by switching the mode switching means, there is a calibration mode that performs an operation for calculating the calculated value of the difference between the first and second photoelectric conversion signals, and a calibration mode that performs an operation for calculating the calculated value of the difference between the first and second photoelectric conversion signals, and a calibration mode that performs an operation for calculating the calculated value of the difference between the first and second photoelectric conversion signals, and a calibration mode that performs an operation for calculating the calculated value of the difference between the first and second photoelectric conversion signals. Select a mode for calculating correlated values.

[Embodiment of the Invention] FIG. 1 is a schematic block diagram of an embodiment of the invention. First, the configuration of an embodiment of the present invention will be described with reference to FIG. In FIG. 1, the liver function testing apparatus is comprised of a sensor section 20 and a measurement processing section 30. The sensor section 20 is the first
The light source 1 includes a light source 1, a second light source 2, and a light receiving element 4.
The first light source 1 has a wavelength λ at which the specific dye has a large absorbance.
The second light source 2 generates a light pulse of wavelength λ2 having no absorbance. Light receiving element 4
For example, the subject object 3 such as the subject's finger or earlobe
Either the light sources 1 and 2 and the light receiving element 4 can be placed on the same plane to face the light sources 1 and 2 to receive the light pulses transmitted through the object to be inspected, or the light sources 1 and 2 and the light receiving element 4 can be placed on the same plane to receive the light pulses reflected from the object to be inspected. It is mounted to receive light. The light sources 1 and 2 are driven by the measurement processing unit 30 so as to alternately emit light in a pulsed manner.

The measurement processing section 30 includes a CPU 7 as a calculation means. The CPU 7 provides the D/A converter 6 with data for controlling the intensity of light pulses emitted from the light sources 1 and 2. The D/A converter 6 converts the data into an analog signal and supplies it to the analog switch 5. Analog switch 5 includes two switching elements, which are switched by clock signals ASCLK1 and ASCLK2 provided from clock generator 15, respectively, and provide the output of D/A converter 6 to light sources 1 and 2. The output of the light receiving element 4 is given to the amplifier 18 and amplified, and the output is sent to the LOG converter 1.
7 and undergoes logarithmic transformation. The output of this LOG converter 17 is sampled by the A/D converter 16 and output as a digital signal.
This digital signal is passed through I/O port 13.
Given to CPU7. Note that the A/D converter 16
is a clock signal from the clock generator 15.
ADCLK is given. A buzzer 14 is connected to the I/O port 13. This buzzer 14 notifies the timing of injecting the specific dye.

Further, a RAM 8, a ROM 9, a display section 10, a printer 11, and an operation section 12 are connected to the CPU 7. The RAM 8 stores data as shown in FIG. 6, which will be described later, and the ROM 9 stores programs based on flowcharts shown in FIGS. 3 to 5, which will be described later. The display unit 10 displays data as shown in FIGS. 7 to 10, which will be described later. The printer 11 prints out liver function test results.
The operation unit 12 includes an alarm LED 121, a calibration key 122, a start key 123, and a print key 124. Alarm LED121
is used to display a warning when the reliability of the test result is low, the calibration key 122 is used to set the calibration mode, and the start key 123 is used to command the start of the measurement mode. The print key 124 instructs to print out the test results.

FIG. 2 is a timing diagram for detecting the amount of light passing through the object to be measured at wavelengths λ1 and λ2, and FIGS. 3 to 5 are flowcharts for explaining the specific operation of an embodiment of the present invention. In particular, the third
The figure shows the data sample subroutine, FIG. 4 shows the calibration mode, and FIG. 5 shows the measurement mode. Figure 6 shows the RAM shown in Figure 1.
FIGS. 7 to 10 are diagrams showing display examples of the display unit shown in FIG. 1, and FIG. FIG. 12 is a diagram showing an example of a dye disappearance curve, and FIG. 12 is a diagram showing the results of the disappearance curve, plasma disappearance rate K, and 15-minute stagnation rate measured using the present invention.

Next, with reference to FIGS. 1 to 12, a specific operation of an embodiment of the present invention will be described. First, step SP1 or
The SP8 samples the amount of light having a set of wavelengths λ1 and λ2 after passing through the object to be measured, and stores it in the RAM8. That is, in step SP1 (abbreviated as SP in the diagram), the CPU 7
The data of the drive voltage J _L1 of the first light source 1 stored in the storage area 8f1 of the RAM 8 shown in the figure is read out and applied to the D/A converter 6. The D/A converter 6 converts the voltage data into an analog signal and supplies it to the analog switch 5. The analog switch 5 is supplied with a clock signal ASCLK1 as shown in FIG. 2d from the clock generator 15. At step SP2, the analog switch 5 becomes conductive in response to the clock signal ASCLK1, and supplies the analog voltage V _L1 converted by the D/A converter 6 to the first light source 1.

In response, the first light source 1 emits light of an amount corresponding to the drive voltage V _L1 , and irradiates the object 3 to be measured. The irradiated light is transmitted or reflected by the object to be measured 3 and is received by the light receiving element 4. Light receiving element 4
converts the received light into an electrical signal and supplies it to the amplifier 18. Amplifier 18 amplifies the signal and outputs LOG
It is fed to a converter 17 for logarithmic conversion. The logarithmically converted voltage is applied to the A/D converter 16. A/
The D converter 16 receives a second clock from the clock generator 15.
A clock signal ADCLK as shown in Figure c is provided. Therefore, in step SP3, the A/D converter 16 A/D converts the output of the LOG converter 17 based on the clock signal ADCLK. This A/D conversion output is given to the CPU 7 via the I/O port 13. CPU7 is step SP
4, read the A/D conversion output and store it in RAM8.
8ai storage area.

Next, the CPU 7 reads the data of the drive voltage V _L2 of the second light source 2 shown in FIG. The analog switch 5 is supplied with a clock signal ASCLK2 from the clock generator 15 as shown in FIG. 2e. Therefore, in step SP6, the analog switch 5 becomes conductive based on the clock signal ASCLK2 and applies the drive voltage V _L2 to the second light source 2. In response, the second light source 2 emits light of an amount corresponding to the drive voltage V _L2 , and irradiates the object 3 to be measured.
The irradiated light having a wavelength λ2 is transmitted or reflected by the object to be measured 3, and is received by the light receiving element 4.

The light receiving element 4 photoelectrically converts the received light and supplies it to the amplifier 18. The output of the amplifier 18 is logarithmically converted by the LOG converter 17 and provided to the A/D converter 16 in the same manner as described above. At step SP7, the A/D converter 17 starts A/D conversion based on the clock signal ADCLK from the clock generator 15. This A/D
The converted output is given to the CPU 7 via the I/O port 13. At step SP8, CPU7
Read the A/D conversion output and store it in RAM as P2(1).
8 storage area 8k1.

In step SP9, the CPU 7 determines whether or not the transmitted or reflected light from the first light source 1 and the second light source 2 has been read m times. If the light has not been read, the above-mentioned steps SP1 to SP8 are repeated.
By repeating the operations of these steps SP1 to SP8 m times, m pieces of light amount data of wavelengths λ1 and λ2 are stored in the storage areas 8a1 to 8am.8k1 to 8Km of the RAM 8, respectively.
CPU7 is RAM8's storage area 8a1 or 8am.8K1
After storing the light intensity data for each of the wavelengths λ1 to 8Km, in step SP10, the average of the m times of light intensity of wavelengths λ1 and λ2 is determined as PM1 and PM2, respectively, based on the following calculation formula, and is stored in the storage areas 8b1 and 8b2 of RAM8, respectively. Make me remember.

PM1= _n 〓 ⁱ⁼¹ P(i)/m PM2= _n 〓 ⁱ⁼¹ P2(i)/m After completing the calculation in step SP10 described above, the CPU 7 returns to the original step.
This will be explained in FIG. 4 below.

Next, the calibration mode shown in FIG. 4 will be explained. This calibration mode is started when the power of the apparatus is turned on or when the operation of the measurement mode shown in FIG. 5, which will be described later, ends. At step SP21, the CPU 7 causes the display section 7 to display the calibration mode. This display, for example as shown in FIG. 7, indicates that the calibration mode is entered and also instructs the mounting of the sensor section 20. Following this instruction, the measurer attaches the sensor section 20 to the object to be measured 3. Thereafter, the CPU 7 waits at step SP22 until the calibration key 122 is operated. When the calibration key 122 is operated, the CPU 7 proceeds to step SP23 and executes the data sample subroutine shown in FIG. 3 described above.

Then, the average light amount data for wavelengths λ1 and λ2 is
When PM1 and PM2 are stored in the storage areas 8b1 and 8b2 of the RAM 8, the CPU 7 stores the values of PM1 and PM2 as POλ1 and POλ2 in the storage areas 8c1 and 8c2 of the RAM 8, respectively, in step SP24. Then, step SP25 to SP3
2, POλ1 and POλ2 are the light amount data P _MAx stored in the storage areas 8d1 and 8d2 of RAM8.
P _MIN (P _MAX > P _MIN The driving voltage applied to the first and second light sources 1 and 2 is set to between 5
Adjust V _L1 and V _L2 .

Specifically, in step SP25, POλ1 is
If it is larger than P _MAX , proceed to step SP26, set the drive voltage V _L1 to a small value, and execute steps SP23 and SP24 again.
At SP25, it is determined again whether POλ1 is larger than _PMAX . Here, POλ1 from P _MAX
If becomes small, proceed to step SP27 and POλ
It is determined whether 1 is smaller than P _MIN . POλ
If 1 is less than P _MIN , step SP2
At step 8, the value of the drive voltage V _L1 is increased and the process returns to step SP23. By repeating this operation, the drive voltage V _L1 is set so that POλ1 falls between P _MAX and P _MIN .

Next, in SP29 to SP32, similarly to SP25 to SP28, the drive voltage V _L2 is set so that POλ2 falls between P _MAX and P _MIN . In this way, step SP23 or step
Drive voltage V _L1 , V _L2 finally set by SP32
are stored in storage areas 8f1 and 8f2 of RAM8. Then, POλ1 and POλ at these driving voltages V _L1 and V _L2
2 is stored in the storage areas 8c1 and 8c2, and the mode shifts to the measurement mode shown in FIG.

Next, the measurement mode will be explained with reference to FIG. In step SP41, the CPU 7 displays on the display section 10 an instruction to inject a specific dye. Regarding this display, for example, as shown in FIG. 8, a display instructing to inject a specific dye, such as ICG, is performed. Following this display, the measurer makes preparations for injecting the specific dye into the subject. Next, in step SP42, the CPU 7 waits until the start key 123 is turned on. CPU7 is start key 1
When it is determined that 23 has been operated, the step
At SP43, the timing of specific dye injection is displayed, and the buzzer 14 is made to sound an alarm. For example, the display unit 10 has 1
→ 2 → 3 → 4 → 5 are displayed, and when "5" is displayed, the measurer injects the specific dye. Also, for CPU7, the display is “1”, “2”,
When "3" and "4" are displayed, the first sound is generated from the buzzer 14, and when "5" is displayed, the first sound is generated from the buzzer 14.
4 to generate different sounds.

The measurer injects a specific dye when this sound is generated. In step SP44, the CPU 7 sets "0" as the initial value of the timer. Next, in step SP45, the CPU 7 executes the data sample program, which is the subroutine described in FIG. 3 above. And the wavelength λ1,
The average light amount data of λ2 is stored in the storage area 8b1 of RAM8,
8b2 as PM1 and PM2. step
In the SP40, the CPU 7 uses the POλ1,
Using POλ2, a calculation is performed based on the following calculation formula, and dB() is stored in the storage area 8gI of the RAM 8.

dB()=10*[(POλ1−PM1)−(POλ2−
PM2)] This value of dB() is displayed on the display section 10 in step SP47, for example, in the manner shown in FIG. In this Figure 10, the horizontal axis shows the elapsed time after injection of the specific dye, and the vertical axis shows the elapsed time after injection of the specific dye.
It is the value in dB(). Here, if the number of samplings for the disappearance curve of a specific pigment is n, then the uppercase letter is 1.
An integer between n and the measurement time of the vanishing curve.
If Ts, one sampling time is ITM
=Ts/(n-1). Of course, when I=1, it corresponds to the injection of a specific dye. step
At SP48, the CPU 7 waits for this sampling time ITM.

Then, after this waiting time, CPU7
In step SP49, it is determined whether I is greater than n. If I is larger than n, proceed to step SP50, but if it is smaller,
Returning again to step SP45, repeated sampling is performed. Here, the data dB() stored in the storage areas 8g1 to 8gn of the RAM 8 draws a disappearance curve of a specific dye as shown in FIG. 11, for example.
In SP50, the previous data is used as the baseline, subtracted from each dB(), and the storage area is
Store in 8g1 or 8gn.

Next, in step SP51, the CPU 7 selects the time T1 to T2 (O<T1<T2<Ts) from among the dB() data stored in the storage areas 8g1 to 8gn.
For data between dB()=Ae ^Bt I=Ts/(n-1) (min), constants A and B are determined using the least squares method using a simulation curve.

Next, in step SP52, the CPU 7 calculates K and R by calculating the plasma disappearance rate K=-B and the 15-minute stagnation rate R%=e ^B×15 . Then, the obtained K and R are stored in the storage areas 8j1 and 8j2 of the RAM 8, respectively. At this time, the CPU 7 calculates the correlation coefficient r using the least squares method, and calculates the calculated correlation coefficient r.
Store it in the storage area 8j3 of RAM8. Also,
At this time, the CPU 7 causes the buzzer 14 to generate an end buzzer sound.

Furthermore, the CPU 7 displays the value of K and the value of R% on the display section 10 in the manner shown in FIG. 10, for example. Next, in step SP53, the CPU 7 determines whether the correlation coefficient r is smaller than, for example, 0.95. This is to check the degree of correlation, since the closer the correlation coefficient r is to -1, the better the correlation. However, the value -0.95 is a value between 0 and -1 and is provisional; of course, the closer it is to -1, the more reliable the device will be. Here, if the correlation coefficient r is greater than, for example, -0.95, it is determined that the reliability is low, and the alarm 121 is turned on in step SP54, and the process proceeds to step SP55. However, step SP53
If the correlation coefficient r is smaller than, for example, −0.95 and the measurement is reliable, an alarm
Step SP5 without lighting LED121
Proceed to step 5. Then, in step SP55, the CPU 7 determines whether the print key 124 is operated or not, and if it is operated, the printer 11
The value of K and the value of R% are printed. In addition, if necessary, 8g1 RAM8 storage area
The specific dye loss curve of dB'() stored in dB' to 8gn is also printed, and the mode shifts to the calibration mode shown in FIG. 4 described above. Also, step
In SP55, when it is determined that the print key 124 is not operated, the process also shifts to the calibration mode.

Next, FIG. 12 shows experimental results measured by the liver function testing apparatus shown in FIG. 1. The experimental results shown in Figure 12 are based on a 43-year-old male liver cirrhosis patient (weight:
The sensor unit 20 was attached to the fingertips of the left hand of a human (48 kg), and an aqueous solution containing 20 mg of ICG (0.5 mg per 1 kg of body weight) was intravenously injected into the right antecubital vein. Figure 12 shows the changes over time in the absorbance differences A830 to A925 when a light emitting diode with a wavelength λ1 = 830 nm is used as the first light source 1, and a light emitting diode with a wavelength λ2 = 925 nm is used as the second light source 2. It shows. This ICG
As shown in Figure 12, the calculated value of K was 0.041 and the value of R% was 54% based on the disappearance curve, and at the same time, the value of K measured by the conventional blood sampling method was 0.043, R%.
= 52%, so we were able to almost agree.

Note that the present invention can be extended to an apparatus for measuring R _MAX , which is calculated by determining the value of k for various ICG doses, using the value of k obtained by the present invention.

[Effects of the Invention] As described above, according to the present invention, living tissue is irradiated with first light having a wavelength that is absorbed by a specific pigment and second light having a wavelength that is not absorbed, and the first light obtained from the living body is The photoelectric conversion signal corresponding to the first and second light is sampled, the calculated value of the difference between the first and second photoelectric conversion signals is calculated, and the sampling signal output is calculated for a predetermined period of time from the injection of the specific dye. Based on the calculated value of the calculated difference, a function of the simulation curve is calculated, and a value that correlates to the specific pigment concentration in the blood is calculated based on the function, so that it is easy to attach the sensor to a living body. It is possible to calculate a value correlated to a specific dye concentration by removing artifacts such as blood flow disturbances at the time, rocking and pulsation of the living body by living body calibration. This enables accurate time management of the disappearance curve of a specific dye, and accurate data can be obtained. Furthermore, it becomes possible to more accurately represent the plasma disappearance rate, stagnation rate, etc. from a large number of disappearance curve data, rather than from several samples obtained by conventional blood sampling methods, and the reliability of the data is improved.

[Brief explanation of drawings]

FIG. 1 is a schematic block diagram of one embodiment of the present invention. FIG. 2 is a timing diagram for detecting the amount of light passing through the object to be measured at wavelengths λ1 and λ2. 3 to 5 are flowcharts for explaining the specific operation of an embodiment of the present invention, in particular, FIG. 3 shows a data sample subroutine, and FIG. 4 shows a calibration mode. shows,
FIG. 5 shows the measurement mode. FIG. 6 is a diagram showing data stored in the RAM shown in FIG. 1.
7 to 10 are diagrams showing display examples of the display section shown in FIG. 1. FIG. 11 is a diagram showing an example of a disappearance curve of a specific dye measured by the present invention. FIG. 12 is a diagram showing the results of the elimination curve, plasma elimination rate, and 15-minute stagnation rate measured using the present invention. In the figure, 1 is a first light source, 2 is a second light source, 3 is an object to be measured, 4 is a light receiving element, 5 is an analog switch, 6 is a D/A converter, 7 is a CPU,
8 is RAM, 9 is ROM, 10 is a display unit, 11 is a printer, 12 is an operation unit, 13 is an I/O port,
14 is a buzzer, 16 is an A/D converter, 17 is
LOG converter, 18 is amplifier, 121 is alarm
LED, 122 is calibration key, 12
3 indicates a start key, and 124 indicates a print key.

Claims (1)

[Scope of Claims] 1. A liver function testing device for testing liver function, which comprises: light source means for irradiating the biological tissue with light and second light having a wavelength that is not absorbed; photoelectric conversion means for outputting first and second photoelectric conversion signals, sampling means for sampling the first and second photoelectric conversion outputs from the photoelectric conversion means; A calculated value of the difference between the first and second photoelectric conversion signals is calculated, and a minimum A simulation curve function is calculated using the square method, and based on the function, a value correlated to the specific dye concentration in the blood is calculated, and when the elapsed time after the specific dye injection is t, , y=Ae ^Bt , a coefficient calculation means including a means for calculating constants A and B, and a plasma elimination rate K based on the coefficient of the simulation function determined by the coefficient calculation means. means for calculating the plasma disappearance rate of the specific dye by calculating the arithmetic expression K=-B; When the stagnation rate at time T is R%, means for calculating the formula R%=e ^BT to obtain the stagnation rate of the specific dye for the predetermined time T; 1st and 2nd
a mode for switching between a calibration mode for calculating a calculated value of the difference between the photoelectric conversion signals and a mode for calculating a value correlated to the specific dye density by the coefficient calculation means; a switching means, and a setting means for setting the intensities of the first and second lights emitted from the light source means so that the levels of the first and second photoelectric conversion signals are within a predetermined range. A liver function testing device equipped with 2. The liver function testing device according to claim 1, further comprising means for outputting the plasma elimination rate determined by the means for determining the plasma elimination rate. 3. The liver function testing apparatus according to claim 1, further comprising means for outputting the stagnation rate determined by the means for determining the stagnation rate at the predetermined time T.