JPH0534978B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] This invention relates to a liver function testing device, and in particular, it injects into the blood a characteristic dye that is selectively taken in and excreted only by the liver, and measures its plasma disappearance rate. The present invention relates to a liver function testing device that measures liver function and stagnation rate and automatically performs measurement processing for testing 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 indocyanine green (hereinafter referred to as ICG) as a specific dye. After ICG is intravenously injected 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 measure the absorbance at a wavelength of 805 nm. measure,
ICG in serum after 5 minutes, 10 minutes, and 15 minutes from the calibration curve (corresponding concentrations V, S, absorbance in ICG) obtained in advance
The concentration is determined, and the plasma elimination rate and stagnation rate are calculated from this concentration change.

In addition, without drawing blood, we irradiate light from the body surface and measure the amount of light reflected from the living body at wavelengths for which ICG has high absorption sensitivity and wavelengths for which ICG has little sensitivity, and this change over time (pigment loss curve) A method for determining the plasma disappearance rate and stagnation rate is proposed in Japanese Patent Publication No. 58649/1982 and Japanese Patent Application Laid-open No. 162934/1982.

However, in the conventional blood sampling method, it is necessary to accurately measure the time of 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 subjects. moreover,
The R _MAX measurement method, which measures the plasma elimination rate by varying the ICG injection volume and measuring the number of times, has recently become popular.
There was a problem that the burden on the subjects became even greater.

In addition, the above-mentioned Japanese Patent Publication No. 60-58649 and
In the method of measurement without blood sampling disclosed in Publication No. 61-162934, when the sensor is actually attached to a living body, blood flow disturbances due to blood vessel compression, shaking of the living body that is the object to be measured, pulsation within the living body, etc. Changes in blood flow within the body (for example, blood flow changes just up and down the arm)
Due to these factors, the output fluctuates, making it impossible to obtain an accurate pigment loss curve. Therefore, the plasma elimination rate and stagnation rate obtained from this curve cannot be said to be accurate.

Therefore, the main purpose of this invention is to eliminate artifacts such as blood flow disturbance, vibration of the living body, pulsation in the living body, and changes in blood flow in the living body when the sensor is attached to the living body, and to enable accurate measurement. An object of the present invention is to provide a functional testing device.

[Means for Solving the Problems] The present invention is a liver function testing device that detects the first and second wavelengths absorbed by a specific pigment that is administered into the blood of living tissue and taken in and excreted by the liver. a light source means for irradiating living tissue with the second light and third and fourth lights having wavelengths that are not absorbed; The first, second, corresponding to light.
a photoelectric conversion means for outputting third and fourth photoelectric conversion signals; a sampling means for sampling the photoelectric conversion output; and a photoelectric conversion means for outputting third and fourth photoelectric conversion signals; , calculate the intensities of the third and fourth photoelectric conversion signals, use the least squares method to calculate a function of a simulation curve for the time change of the calculation results, and calculate the amount of blood in the blood based on the function. comprising a calculation means for calculating a value correlated to the specific dye concentration, the light source means including the first to fourth light sources,
The centers of the first and third light sources are arranged at a predetermined distance d ₁ from the center of the photoelectric conversion means, and the centers of the second and fourth light sources are arranged at a predetermined distance from the center of the photoelectric conversion means. are placed at a distance d ₂ from each other, and the relationship of distance d ₁ <d ₂ is maintained.

[Operation] The liver function testing device according to the present invention irradiates living tissue with first to fourth lights, samples photoelectric conversion signals corresponding to the lights obtained from the living body, and samples the sampled first and second lights. , calculate the intensities of the third and fourth photoelectric conversion signals, and use the least squares method,
A function of a simulation curve of the calculation result over time is calculated, and a value correlated to a specific pigment mode in the blood is calculated based on the function.

[Embodiments of the Invention] FIGS. 2A to 4 are diagrams for explaining the principle of this invention.

In this invention, FIGS. 2A, 2B and 3
A sensor section 10 as shown in the figure is used. This sensor section 10 includes a first light source 11 and a second light source 1.
2, a third light source 13, a fourth light source 14, a light receiving element 15, and a preamplifier 16 are integrally arranged on a substrate 17. Light emitting diodes are used as the first to fourth light sources 11 to 14, and photodiodes are used as the light receiving element 15. Light sources 11 and 12 emit light pulses of wavelength λ ₁ that are largely absorbed by specific pigments that are administered into the blood of living tissues and are taken up and excreted only by the liver, and light sources 13 and 14 respectively It emits a light pulse of wavelength λ ₂ that is not absorbed.

Note that the centers of the light sources 11 and 13 are located at the light receiving element 1.
The centers of the light sources 12 and 14 are arranged at a distance of d ₂ from the center of the light receiving element 15, and _{d 1} <
d keeping the relationship between _{the two} . Furthermore, the range of the light sources 11 to 14, the light receiving element 15, and the preamplifier 16 and the space between the light sources 11 to 14 and the light receiving element 15 are provided to prevent light from entering the light receiving element 15 from the outside, and to prevent light from entering the light receiving element 15 from the outside. A light shielding partition wall 18 is provided to prevent direct light from entering the light receiving element 15 from the light receiving element 15 . Detailed tissue propagation in the sensor unit 10 is explained in literature such as "Photon Diffusion Theory" published by Takatani et al., but if this is simplified, it can be considered as follows.

In FIG. 3, light sources 11 and 13 are light receiving elements 1
5, and its reflected light intensity is R _N1 ,
Let it be R _N2 . Furthermore, the light sources 12 and 14 are connected to the light receiving element 1.
It is a light source far away from 5, and its reflected light intensity is
Let them be R _F1 and R _F2 . Now, considering the reflected light intensities R _F1 and R _F2 , it is thought that each reflected light passes through a path as shown in FIG. 3 according to the photon diffusion theory described above. The reflected light intensity R _F1 captures deeper information than the reflected light intensity R _N1 . Therefore, as shown in Fig. 3, the area sampled with the reflected light intensity R _N1 is set as the first layer, and the reflected light intensity R _F1
The area sampled in is the second layer, and the characteristics given to light passing through each layer are α ₁₁ and α ₁₂ . Here, α ₁₁ and α ₁₂ are the wavelengths of the light sources 11 and 12,
It depends on tissue transmission, absorption rate, scattering rate, hemoglobin present in the tissue, etc.

Further, when the amount of incident light at the light sources 11 and 12 is I ₀ , it can be expressed as R _N1 = I ₀ · α ₁₁ R _F1 = I ₀ · α ₁₁ · α ₁₂ (1) It can be seen from the photon diffusion theory. Therefore, R _N1 /R _F1 =I _0・α ₁₁ /I _0・α ₁₁・α ₁₂ = 1/α ₁₂ …
...(2) Therefore, R _N1 /R _F1 can remove the first layer component and detect only the second layer component. Here, for example, as a component of the first layer, the sensor part 10
The distance d ₁ is set to take a capillary layer that is susceptible to blood flow disturbance due to blood vessel compression when the
If the distance d ₂ is selected to set the second layer as a layer that is less susceptible to blood flow disturbance due to blood vessel compression, artifacts caused by blood flow disturbance, which have been a problem in the past, can be removed.

Next, similarly, the reflected light of the light sources 13 and 14 is
Regarding R _N2 and R _F2 , the characteristics of the first and second layers are α ₂₁ ,
If α ₂₂ , R _N2 = I ₀・α ₂₁ R _F2 = I ₀・α ₂₁・α ₂₂ ...(3) Therefore, R _N2 /R _F2 =1/α ₂₂ ...(4) . Therefore, S=ln(R _N1 /R _F1 )/(R _N2 /R _F2 ) =ln・α ₂₂ /α ₁₂ ...(5). That is, S is the second wavelength at wavelengths λ ₁ and λ ₂
This is the difference between the layer characteristics lnα ₂₂ and lnα ₁₂ .

Here, λ ₁ is a wavelength at which the specific dye has high absorbance, and λ ₂ is a wavelength at which the specific dye has approximately 0 absorbance. Therefore, when a specific dye is injected into a living body, _α12
, and S can be detected as a signal of only the specific dye based on S before injection of the specific dye.

Next, assuming that the pulsation in the living body and the change in blood volume in the living body are Δα ₁₁ , Δα ₁₂ , Δα ₂₁ , and Δα ₂₂ , the above-mentioned equations (1) and (3) are as follows: R _N1 = I ₀・α ₁₁・Δα ₁₁ R _F1 = I ₀・α ₁₁・Δα ₁₁・α ₁₂・Δα ₁₂ R _N2 = I ₀・α ₂₁・Δα ₂₁ R _F1 = I ₀・α ₂₁・Δα ₂₁・α ₂₂・Δα ₂₂ ...(6), and S=log(R _N1 /R _F1 )−ln(R _N2 /R _F2 )=(lnα ₂₂ −ln
α ₁₂ )−(lnΔα ₂₂ −lnΔα ₁₂ )……(7).

Here, if the wavelengths of λ ₁ and λ ₂ are chosen to have similar absorption and scattering coefficients of hemoglobin, the second term will be In other words, the influence of blood fluctuations on the information in the second layer is sufficiently small, lnΔα ₂₂ =lnΔα ₁₂ , and can be almost ignored. Therefore, pulsations within the body and changes in blood volume within the body can be ignored.

Next, the rocking of the sensor 10 occurs due to changes in the close contact between the sensor section 10 and the living body. For example, as shown in FIG.
This occurs because the sensor section 10 is displaced in the vertical and horizontal directions. Therefore, the vertical direction is represented by the symbol , and the horizontal direction is represented by the symbols 1 and 2 corresponding to the wavelengths λ ₁ and λ ₂ of the light sources. , the nearby light sources 11 and 13 are represented by the symbol N, and the sensor unit 10
To represent the artifact A of the oscillation, the above-mentioned
Equations (1) and (3) are as follows.

R _N1 = I ₀・α ₁₁・A _N 〓・A ₁ 〓 R _F1 = I ₀・α ₁₁・α ₁₂・A _F 〓・A ₁ 〓 R _N2 ＝I ₀・α ₂₁・A _N 〓・A ₂ 〓 R _F1 = I ₀・α ₂₁・α ₂₂・A _F 〓・A ₂ 〓 ……(8) Therefore, S=ln[(R _N1 /R _F1 )/(R _N2 /R _F2 )] =ln (I ₀・α ₁₁・A _N 〓・A ₁ 〓/I ₀・α ₁₁・α ₁₂・A _F 〓
・A ₁ 〓)／(I ₀・α ₂₁・A _N 〓・A ₂ 〓／I ₀・α ₂₁・α ₂₂・
A _F 〓・A ₂ 〓) =ln(A _N 〓/A _F 〓/α ₁₂ )/(A _N 〓/A _F 〓/α ₂₂ )=
ln(α ₂₂ /α ₁₂ ) (9), and the equation (9) matches the equation (5), which means that the fluctuation of the sensor 10 can be eliminated. Of course, here, all the amounts of incident light from the light sources 11 to 14 are set to _I0 , but this may be any value and is only included in the base of S before injection of the specific dye in equation (5).

FIG. 1 is a schematic block diagram of one embodiment of the present invention. Next, the configuration of an embodiment of the present invention will be described with reference to FIG. In Fig. 1, the liver function testing device is shown in Figs.
It is composed of the sensor section 10 and the measurement processing section 20 described in the figure. As described above, the sensor section 10 has a first light source 11, a second light source 12, and a third light source.
includes a light source 13, a fourth light source 14, and a light receiving element 15. The first light source 11 and the second light source 12 generate a light pulse with a wavelength λ ₁ that has a large absorbance of a specific dye,
The third light source 13 and the fourth light source 14 generate light pulses having a wavelength λ ₂ at which the absorbance of the specific dye is small. The light receiving element 15 is disposed on the same plane as the light sources 11 to 14, and is mounted so as to receive reflected light from the object to be inspected. Note that the light sources 11 to 14 are driven by the measurement processing section 20 so that each of them alternately emits light in a pulsed manner.

The measurement processing unit 20 includes a CPU 23 as a calculation means.
including. The CPU 23 provides the D/A converter 22 with data for controlling the intensity of the light pulses emitted from the light sources 11 to 14. The D/A converter 22 converts the data into an analog signal and supplies it to the analog switch 21. The analog switch 21 includes four switching elements, and receives a clock signal from a clock generator 31.
They are switched by ASCLK1, 2, 3 and 4, respectively, and provide the output of the D/A converter 22 to the light sources 11 to 14. The output of the light receiving element 15 is applied to an amplifier 34 via a preamplifier 16, where it is amplified, and then applied to a LOG converter 33, where it is logarithmically converted. The output of this LOG converter 33 is sampled by the A/D converter 32 and output as a digital signal. This digital signal is given to the CPU 23 via the I/O port 29. Note that the A/D converter 32 is supplied with a clock signal ADCLK from the clock generating section 31. A buzzer 30 is connected to the I/O port 29. This buzzer 30 notifies the timing of injecting the specific dye.

Furthermore, the CPU 23 has RAM 24 and ROM 2.
5, a display section 26, a printer 27, and an operation section 28 are connected. The RAM 24 stores data as shown in FIG. 9, which will be described later, and the ROM 25 stores programs based on flowcharts shown in FIGS. 6 to 8, which will be described later. The display section 26 displays data as shown in FIGS. 10 to 13, which will be described later. The printer 27 prints the liver function test results.

The operation unit 28 includes an alarm LED 281, a calibration key 282, a start key 283, and a print key 284. Alarm LED28
1 displays a warning when the reliability of the test result is low, and the calibration key 282
is for setting the calibration mode, the start key 283 is for instructing the start of the measurement mode, and the print key 284 is for instructing to print out the test results.

FIG. 5 is a timing chart for detecting the amount of light passing through the object to be measured at wavelengths λ ₁ and λ ₂ , and FIGS. 6 to 9 are for explaining the specific operation of an embodiment of the present invention. In particular, FIG. 6 shows the data sample subroutine, FIG. 7 shows the calibration mode, and FIG. 8 shows the measurement mode. 9 is a diagram showing data stored in the RAM shown in FIG. 1, FIGS. 10 to 13 are diagrams showing display examples of the display section shown in FIG. 1, and FIG. is a diagram showing an example of a disappearance curve of a specific dye measured by this invention,
FIG. 15 is a diagram showing the results of the elimination curve, plasma elimination rate k, and 15-minute stagnation rate measured using the present invention.

Next, with reference to FIGS. 1 and 5 to 15, a specific operation of an embodiment of the present invention will be described. First, steps SP1 to SP16 shown in FIG. 6 (abbreviated as SP in the figure) are for sampling the light intensity of a set of wavelengths λ ₁ and λ ₂ after passing through the object to be measured, and storing it in the RAM 24. It is. That is, in step SP1, the CPU 23 reads data on the drive voltage V _L1 of the first light source 11 stored in the storage area 8f1 of the RAM 24 shown in FIG. The D/A converter 22 converts the voltage data into an analog signal and supplies it to the analog switch 21. The analog switch 21 is supplied with a clock signal ASCLK1 as shown in FIG. 5g from the clock generator 31. At step SP2, the analog switch 21 becomes conductive in response to the clock signal ASCLK1, and provides the analog voltage V _L1 converted by the D/A converter 22 to the first light source 11.

In response, the first light source 11 emits light of an amount corresponding to the drive voltage V _L1 , and irradiates the object to be measured 50 with the light. The irradiated light is reflected by the object to be measured 50 and received by the light receiving element 15. Light receiving element 1
5 converts the received light into an electrical signal and supplies it to the amplifier 34 via the preamplifier 16. The amplifier 34 amplifies the signal and supplies it to the LOG converter 33 for logarithmic conversion. The logarithmically converted voltage is given to the A/D converter 32. The A/D converter 32 is supplied with a clock signal ADCLK from the clock generator 31 as shown in FIG. 5e. Therefore, in step SP3, the A/D converter 32
Based on the clock signal ADCLK, the LOG converter 3
A/D conversion is performed on the output of step 3. This A/D conversion output is given to the CPU 23 via the I/O port 29. In step SP4, the CPU 23
The conversion output is read and stored in the storage area _8b1 of the RAM 24 as p1.

Next, the CPU _{23 reads the data of the drive voltage V L2 of} the second light source 12 shown in FIG. .
The analog switch 21 receives a clock signal ASCLK2 from the clock generator 31 as shown in FIG. 5h.
is given. Therefore, the analog switch 21 outputs the clock signal at step SP6.
It becomes conductive based on ASCLK2 and applies the drive voltage V _L2 to the second light source 12. Accordingly, the second light source 12
emits light of an amount corresponding to the drive voltage V _L2 , and irradiates the object to be measured 50 with it. The irradiated light of wavelength λ ₁ is reflected by the object to be measured 50 and received by the light receiving element 15 .

The light receiving element 15 photoelectrically converts the received light and supplies it to the amplifier 34 via the preamplifier 16. The output of the amplifier 34 is as explained above,
Logarithmically converted by LOG converter 33, A/D
Converter 32 is provided. At step SP7, the A/D converter 32 starts A/D conversion based on the clock signal ADCLK from the clock generator 31. This A/D conversion output is an I/O
It is given to the CPU 23 via the port 29.
At step SP8, the CPU 23 reads the A/D conversion output and stores it in the storage area _8b2 of the RAM 24 as P2.

Next, the CPU _{23 reads the data of the drive voltage V L3 of} the third light source 13 shown in FIG. The analog switch 21 is supplied with a clock signal ASCLK3 from the clock generator 31 as shown in FIG. 5i. Therefore, the analog switch 21 receives the clock signal at step SP10.
It becomes conductive based on ASCLK3 and applies the driving voltage V _L3 to the third light source 13. Accordingly, the third light source 13
generates light with an amount of light corresponding to the drive voltage V _L3 , and irradiates the object to be measured 50 with it. The irradiated light of wavelength λ ₂ is reflected by the object to be measured 50 and received by the light receiving element 15 .

The light receiving element 15 photoelectrically converts the received light,
It is applied to the amplifier 34 via the preamplifier 16. The output of the amplifier 34 is as explained above,
Logarithmically converted by LOG converter 33, A/D
Converter 32 is provided. At step SP11, the A/D converter 32 starts A/D conversion based on the clock signal ADCLK from the clock generator 31. This A/D conversion output is an I/O
It is given to the CPU 23 via the port 29.
At step SP12, the CPU 23 reads the A/D conversion output and stores it in the storage area _8f3 of the RAM 24 as P3.

Next, the CPU _{23 reads the data of the driving voltage V L4 of} the fourth light source 14 shown in FIG. .
The analog switch 21 receives a clock signal ASCLK4 from the clock generator 31 as shown in FIG.
is given. Therefore, the analog switch 21 receives the clock signal at step SP14.
It becomes conductive based on ASCLK4 and applies the driving voltage V _L4 to the fourth light source 14. Accordingly, the fourth light source 14
emits light of an amount corresponding to the drive voltage V _L4 , and irradiates the object to be measured 50 with it. The irradiated light of wavelength λ ₂ is reflected by the object to be measured 50 and received by the light receiving element 15 .

The light receiving element 15 photoelectrically converts the received light and supplies it to the amplifier 34 via the preamplifier 16. The output of the amplifier 34 is logarithmically converted by the LOG converter 23 in the same manner as described above.
The signal is applied to the A/D converter 32. Step SP15
, the A/D converter 32 is connected to the clock generator 3.
Based on the clock signal ADCLK from 1, A/
Start D conversion. This A/D conversion output is given to the CPU 23 via the I/D port 29. In step SP16, the CPU 23
The conversion output is read and stored in the storage area _8b4 of the RAM 24 as P4.

After completing the calculation at step SP16, the CPU 24 returns to the original step.
This will be explained in FIG. 7 below.

Next, the calibration mode shown in FIG. 7 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. 8, which will be described later, ends. At step SP21, the CPU 23 causes the display section 26 to display the calibration mode. This display, for example as shown in FIG. 10, indicates that the calibration mode is entered and also instructs the mounting of the sensor section 10. Following this instruction, the measurer
is attached to the object to be measured 50. After that, CPU23
waits at step SP22 until the calibration key 282 is operated. When the calibration key 282 is operated, the CPU 2
Step 3 proceeds to step SP23 and executes the data sample subroutine shown in FIG. 6 described above.

Then, data P1, P2, P3, and P4 are measured m times, and the average light amount data is stored in storage areas 8l ₁ , 8l ₂ , 8l ₃ , 8l ₄ of PM1, PM2, PM3,
Save as PM4. CPU23 is a step
At SP24, the values of PM1 to PM4 are stored as PO1 to PO4 in the storage areas _8c1 to _8c4 of the RAM 24, respectively. and,
Execute steps SP25 to SP32, and PO1 to PO4 obtain the light amount data P _MAX and P _MIN (P _MAX > P _MIN ) stored in the storage areas 8d ₁ and 8d ₂ of the RAM 24.
The drive voltage V _L1 to be applied to the first to fourth light sources 11 to 14 is set between
Adjust V _L4 .

More specifically, in step SP25, PO1
If it is larger than P _MAX , proceed to step SP26, set the drive voltage V _L1 to a small value, execute steps SP23 and SP24 again, and in step SP25, it is again determined whether PO1 is larger than P _MAX . be done. Here, if PO1 is not smaller than P _MAX ,
Proceeding to step SP27, it is determined whether PO1 is smaller than _PMIN . If PO1 is smaller than _PMIN , the value of drive voltage V _L1 is increased in step SP28 and the process returns to step SP23. By repeating this operation, the drive voltage V _L1 is set so that P ₀ λ ₁ falls between P _MAX and P _MIN .

Next, in steps S29 to SP40, PO2, PO3, and PO4 are
Drive voltage V _L2 , so that it falls between P _MAX and P _MIN
V _L3 and V _L4 are set sequentially. In this way,
The drive voltages V _L1 to V _L4 finally set in steps SP23 to SP32 are applied to the memory area 8 of the RAM 24.
It is stored in each of f ₁ to 8f ₄ . and,
PO1 to PO4 of this driving voltage V _L1 to V _L4
are stored in the storage areas _8c1 to _8c4 , 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 23 displays on the display section 26 an instruction to inject a specific dye. For this display, for example, as shown in FIG.
A display instructing to inject ICG is displayed. Following this display, the measurer makes preparations for injecting the specific dye into the subject. Next, the CPU
23 is the start key 2 at step SP42.
Wait until 83 is turned on. When the CPU 23 determines that the start key 283 has been operated, it displays the specific dye injection timing and causes the buzzer 30 to sound an alarm. This is, for example, the 12th
As shown in the figure, the order is displayed as 1 → 2 → 3 → 4 → 5, and when "5" is displayed, the measurer
A specific dye is injected. Further, the CPU 23 causes the buzzer 3 to generate a first sound when the display is "1", "2", "3", or "4", and causes the buzzer 30 to generate a different sound when "5" is displayed. generate.

The measurer injects a specific dye when this sound is generated. In step 44, the CPU 23
Set “0” as the initial value of the timer. next,
At step SP45, the CPU 23
Execute the data sample program, which is the subroutine explained in the figure. Then, they are stored in storage areas 8b ₁ to 8b ₄ of the RAM 24 as P1 to P4, respectively. In step SP46,
The CPU 23 uses PO1 to PO4 respectively stored in the storage areas _8c1 to _8c4 of the RAM 24 in the calibration mode explained in FIG. 7 above, and performs calculations based on the following calculation formula,
dB() is stored in the storage area _8g1 of the RAM 24.

dB()=10*[(P1-P2)-(P3-P4)] The value of this dB() is calculated as follows at step SP47.
For example, in the manner shown in FIG.
will be displayed. In Figure 13, the horizontal axis shows the elapsed time after injection of the specific dye, and the vertical axis shows dB ()
is the value of Here, if the number of samplings of the disappearance curve of a specific dye is n, I is an integer from 1 to n, and if the measurement time of the disappearance curve is T _s , then 1
The sampling time is ITM= _Ts /(n-1)
It is. Of course, when n=1, it coincides with the injection of the specific dye. At step SP48, the CPU
23 waits during this sampling time ITM.

After this waiting time has elapsed, the CPU 23 determines whether or not i is greater than n in step SP49. If i is larger than n, the process proceeds to step SP50, but if it is smaller, the process returns to step SP45 and repeats sampling.
Here, the data dB(I) stored in the storage areas 8g ₁ to 8g _o of the RAM 24 is, for example, the first
Draw a disappearance curve for a specific pigment as shown in Figure 4.
This rising point is detected, and in step SP50, each
Subtract from dB(I) and re-storage area 8g ₁ to 8
memorize in g _o . Of course, in order to improve measurement accuracy, P1 to P4 in step SP45 may be the average value of m times. Also, in Figure 1,
The output of the light receiving element 15 is given to the LOG converter 33, but without providing this LOG converter 33,
The output of the amplifier 34 is directly given to the CPU 23 via the A/D converter 32 and the I/O port 29,
The CPU 23 reads the value of V _PD shown in Figure 5 and logs it.
It may also be converted.

Next, in step SP51, the CPU 23 selects the time _T1 to _T2 (0<T1<T2<
For the data between dB(I)=Ae ^Bt I= _Ts /(n _- 1)(min), use the least squares method to find the constants A and B. .

Next, in step SP52, the CPU 23 calculates K and R by calculating the plasma disappearance rate K=-B and the T minute stagnation rate R%=e ^Bt . Then, the obtained K and R are stored in the storage areas 8j ₁ and 8j ₂ of the RAM 24, respectively. At this time, the CPU 23 calculates the correlation coefficient r using the least squares method, and calculates the calculated correlation coefficient r.
is stored in the storage area _8j3 of the RAM 24. Also,
At this time, the CPU 23 causes the buzzer 14 to generate an end buzzer sound.

Furthermore, the CPU 23 causes the display unit 26 to display the value of K and the value of R% in a manner as shown in FIG. 13, for example. Next, in step SP53, the CPU 23 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, and of course the closer it is to -1, the more reliable the device will be.

Here, if the correlation coefficient r is larger than, for example, 0.95, it is assumed that the reliability is low and the step is
At SP54, the alarm LED 281 is turned on and the process proceeds to step SP55. However, in step SP53, if the correlation coefficient r is smaller than -0.95,
If the measurement is reliable, alarm LED2
Proceed to step SP55 without turning on 81.
Then, in step SP55, the CPU 23 determines whether the print key 284 is operated or not, and if it is operated, the printer 27 prints the print key 284.
The value of and the value of R% are printed.

Furthermore, if necessary, the specific dye loss curve in dB'(I) stored in the memory areas 8g ₁ to 8g _o of the RAM 24 can also be printed, and the calibration mode shown in FIG. Move. Also,
In step SP55, when it is determined that the print key 284 is not operated, the process also shifts to the calibration mode.

Next, FIG. 15 shows the experimental results of measurement using the liver function testing apparatus shown in FIG. 1. The experimental results shown in FIG. 15 were obtained by attaching the sensor unit 10 to the fingertips of the left hand of a 43-year-old male liver cirrhosis patient (weight 48 kg).
An aqueous solution containing 24 mg of ICG (1 body weight) from the right antecubital vein.
0.5mg/kg) was administered intravenously. FIG. 15 shows the wavelength λ ₁ =
The third light source 1 uses an 830nm light emitting diode.
3 shows changes over time in absorbance differences A830 to A925 when light emitting diodes with a wavelength λ ₂ =925 nm are used as the third and fourth light sources 14. This ICG
As shown in Figure 15, the calculated value of k from the disappearance curve is 0.041, and the value of R% is 54%, and at the same time, the value of k measured by the conventional blood sampling method is 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 and second light having wavelengths that are absorbed by a specific pigment and third and fourth light having wavelengths that are not absorbed; The photoelectric conversion signal corresponding to each light obtained from the living tissue is sampled, and a value that correlates to the concentration of a specific pigment in the blood is calculated based on the magnitude of the sampling output, making it easy to attach the sensor to the living body. It is possible to calculate a value that correlates to a specific dye concentration by removing artifacts such as blood flow disturbances and body vibrations and pulsations. 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 the drawing]

FIG. 1 is a schematic block diagram of one embodiment of the present invention. Figures 2A, 2B, 3 and 4
The figure is a diagram for explaining the principle of the invention.
FIG. 5 is a timing diagram for detecting the amount of light reflected from the object to be measured at wavelengths λ ₁ and λ ₂ . 6 to 8 are flowcharts for explaining specific operations of an embodiment of the present invention, in particular, FIG. 6 shows a data sample subroutine, and FIG. 7 shows a calibration mode. , and FIG. 8 shows the measurement mode. FIG. 9 is a diagram showing data stored in the RAM shown in FIG. 1. FIGS. 10 to 13 are diagrams showing display examples of the display unit shown in FIG. 1. FIG. 14 is a diagram showing an example of a disappearance curve of a specific dye measured according to the present invention. 1st
FIG. 5 is a diagram showing the results of the disappearance curve, plasma disappearance rate, and 15-minute stagnation rate measured using the present invention. In the figure, 10 is a sensor section, 11 is a first light source, 12 is a second light source, 13 is a third light source, 14
is a fourth light source, 15 is a light receiving element, 16 is a preamplifier, 20 is a measurement processing unit, 21 is an analog switch, 22 is a D/A converter, 23 is a CPU, 2
4 is RAM, 25 is ROM, 26 is display section, 27
is a printer, 28 is an operation unit, 29 is an I/O port, 30 is a buzzer, 31 is a clock generator, 32
is the A/D converter, 33 is the LOG converter, 34 is the amplifier, 281 is the alarm LED, 282 is the calibration key, 283 is the start key, 28
4 indicates a print key.

Claims (1)

[Scope of Claims] 1. A liver function testing device for testing liver function, which comprises: a light source means for irradiating the biological tissue with a second light and third and fourth lights having wavelengths that are not absorbed; Second,
1st, 2nd, and 3rd lights corresponding to the 3rd and 4th lights.
and a photoelectric conversion means for outputting a fourth photoelectric conversion signal, the first, second and third signals from the photoelectric conversion means
and a fourth sampling means for sampling the photoelectric conversion output, and calculating the intensity of the sampling signal of the sampling means during a predetermined time from the injection of the specific dye, and calculating the intensity using the least squares method. Calculating means for calculating a function of a simulation curve in the time change of the result, and calculating a value correlated to the specific pigment concentration in the blood based on the function, and the light source means 2, 3, and 4 light sources respectively, the centers of the first and third light sources are located at a predetermined distance from the center of the photoelectric conversion means. The centers of the second and _fourth light sources are located a predetermined distance d ₂ from the center of the photoelectric conversion means, and the distance is A liver function testing device characterized in that a relationship of d ₁ < d ₂ is maintained. 2. The liver function testing device according to claim 1, wherein the calculation means includes means for determining the plasma disappearance rate of the specific dye based on the calculated coefficients of the simulation function. 3. The liver function testing device according to claim 2, wherein the calculating means includes means for outputting the plasma elimination rate determined by the means for determining the plasma elimination rate. 4. The liver function testing device according to claim 1, wherein the calculation means includes means for determining the stagnation rate of the specific dye in the predetermined time based on the coefficients of the determined simulation function. 5. The liver function testing apparatus according to claim 4, further comprising means for outputting the stagnation rate determined by the means for determining the stagnation rate. 6 The calculation means calculates the intensities of the first, second, third and fourth lights reflected from the living tissue as P ₁ ,
When P ₂ , P ₃ and P ₄ are assumed, the key as set forth in claim 1 includes means for obtaining y=10×[logP ₁ /P ₂ −logP ₃ /P ₄ ] as the calculated value y. Functional testing equipment. 7. The calculation means includes means for calculating constants A and B based on the calculation formula y=Ae _Bt , where t is the elapsed time after the injection of the specific dye. Liver function testing device. 8. The liver function testing device according to claim 3, wherein the means for determining the plasma disappearance rate includes means for calculating an arithmetic expression: K=-B, where K is the plasma disappearance rate. 9 The means for determining the stagnation rate includes means for calculating an equation of R%=e _BT , where the stagnation rate for the predetermined time T is R%. Functional testing equipment. 10 Furthermore, the first, second, third and fourth
a calibration mode for setting the intensities of the first, second, third and fourth lights irradiated from the light source means so that the level of the photoelectric conversion signal of the light source is within a predetermined range; 2. The liver function testing apparatus according to claim 1, further comprising mode selection means for selecting a measurement mode in which said calculation means performs an operation for calculating a value correlated to said specific dye concentration.