JPH04191642A - Method and apparatus for measuring concentration of light-absorbing substance in scattering medium - Google Patents

Abstract

PURPOSE:To detect an absolute value of the concentration of hemoglobin in blood, for instance, in addition to the state of a change in an organism by applying a pulse light to a scattering medium containing a light-absorbing substance. CONSTITUTION:Five kinds of pulse lights selected from a wavelength band of 670nm to 1.33mum are applied to a scattering medium containing oxidation-type hemoglobin, reduction-type hemoglobin, cytochrome and myoglobin, for instance, and the intensity of light for each wavelength is measured. Utilizing that a scattering profile in the case when no light-absorbing substance exists in the scattering medium does not change according to the wavelength, the scattering profile is removed from simultaneous equations of a time-base profile of the intensity of light for each wavelength obtained herein and the scattering profile, and thereby concentration V is obtained. The concentration V is calculated by the equation on the right. In the equation, K denotes a constant of absorption of lights of wavelengths lambda1 and lambda2, C denotes the velocity of light in the scattering medium, f1 denotes the light intensity of the light of the wavelength lambda1 at times t1 and t2, and f2 denotes the light intensity of the light of the wavelength lambda2 at the times t1 and t2.

Description

[Detailed description of the invention] [Industrial application field]

The present invention relates to a method and apparatus for measuring the concentration of a light-absorbing substance in a scattering medium, such as hemoglobin in blood, for measuring the concentration of a light-absorbing substance in a scattering medium.

[Conventional technology]

- Japan - Conventionally, as a non-invasive oxygen metabolism monitor, a method for detecting the concentration of hemoglobin, etc. in blood has been to inject continuous light with a wavelength in the near-infrared region into a living body and transmit it through a part of the living body. There is a method that amplifies the emitted light and correlates the output intensity of each wavelength. Additionally, a pulse oximeter that uses heart pulse waves is used to measure SaO2 in arterial blood. Furthermore, a method has been proposed that takes advantage of the fact that living bodies are strong light scattering media and combines picosecond light pulses with time-resolved measurement of light intensity. The principle is that, as shown in Fig. 14, a picosecond light pulse 2 is introduced into a scattering medium 1 containing a light-absorbing substance, and this picosecond light pulse 2 is spread in time by scattering within the living body. The state is measured by an optical time-resolved measuring device 3 such as a streak camera. This is because when the picosecond light pulse 2 is sufficiently diffused within the scattering medium 1 such as a living body, the temporally measured light intensity pattern decreases exponentially over time, and the degree of this phenomenon decreases exponentially. depends on the concentration of light-absorbing substances in the scattering medium.

[Problem to be solved by the invention]

Since the conventional non-invasive oxygen metabolism monitor is just a monitor, there is a problem in that it measures only the state of changes in the living body and cannot detect the absolute value of, for example, the hemoglobin concentration in the blood. Furthermore, the pulse oximeter is mainly used to check lung function, and if a pulse wave cannot be detected, S
There is a problem that it cannot be used for measuring aO2, etc. In addition, in the measurement method that utilizes the fact that the picosecond pulse of light spreads exponentially due to scattering by living organisms, the intensity pattern of the light obtained is greatly affected by the scattering state of the measurement target, and does not necessarily reflect an exponential phenomenon. This poses a problem in that accurate measurements cannot be stably performed because complex patterns are often observed. The present invention has been made in view of the above conventional problems, and provides a method and apparatus for non-invasively measuring the concentration of a light-absorbing substance in a scattering medium, such as hemoglobin in blood. With the goal. Another object of the present invention is to provide a method and apparatus for measuring the concentration of a light-absorbing substance in a scattering medium even when the exponential scattering of picosecond pulses of light in the scattering medium is unstable. shall be.

[Means to solve the problem]

The first invention provides a scattering medium containing a light-absorbing substance with different wavelengths λ.
1, A2 pulsed light is incident, and the light intensity f1 (tl), fl (
t2), light intensity f2 of wavelength A2 light at times t1 and t2
(tl), f2 (t2), wavelength λ1, A
2. A light-absorbing substance in a scattering medium characterized in that, where the light absorption constant in the light-absorbing substance and the speed of light in the scattering medium is C, the concentration of the light-absorbing substance is expressed as follows: The above object is achieved by the concentration measuring method described above. Further, in claim 1, the light-absorbing substance is N in the scattering medium.
When different types are included, N+1 types of different wavelengths λ1~
Irradiate the scattering medium with pulsed light of λN+1, measure the light intensity at times t1 and t2 for each wavelength, and calculate the concentration of each light-absorbing substance.
1 to VN may be calculated. Furthermore, in claim 2, the light-absorbing substance is oxyhemoglobin, deoxyhemoglobin, cytochrome aa3, and myoglobin, and the pulsed light is 670 nl to 1.
Five types may be selected from the wavelength range of 33 μI. The second invention provides a scattering medium containing a light-absorbing substance with different wavelengths λ.
1. The process of inputting A2 pulsed light and these λ1, λ
Based on the process of determining the absorbances λ1 and λ2 of the light-absorbing substance in two lights, the process of measuring the optical path length 1 of the light-absorbing substance, and the extinction coefficients ε1 and ε2 of these AI, A2.1 and λ1 and λ2, 8- Then, the concentration V of the light-absorbing substance is V = (AI - A2) / (1 (ε1 - ε2)
The above object is achieved by a method for measuring the concentration of a light-absorbing substance in a scattering medium, which comprises a process of calculating from 1. Further, in claim 4, the optical path length 1 may be determined by determining the time t during which the incident pulsed light travels in the scattering medium, and measuring this time based on the time t. Further, in any one of claims 1 to 5, the pulsed light may be emitted light of a picosecond oscillation laser.
At least two types of wavelengths λ1 are added to the scattering medium containing a light-absorbing substance.
, A2; an optical time-resolved measurement device that time-resolves the light from the scattering medium based on the incident pulsed light to obtain a temporal intensity pattern of each wavelength light; Based on the temporal intensity pattern data of each wavelength light obtained by a time-resolved measurement device, wavelength A1
Light intensity ti (ti), ri at light times t1 and t2
(t2), light intensity f of light with wavelength λ2 at times t1 and t2
2(tln, f2(t2>), wavelength λ1, A2 light absorption constant in the light-absorbing substance, and the speed of light in the scattering medium as C, the concentration V of the light-absorbing substance can be calculated using the following formula. The above object is achieved by an apparatus for measuring the concentration of a light-absorbing substance in a scattering medium, which includes a calculator that calculates the calculation using the % formula %))]. A fourth invention provides a device for measuring the concentration V of the light-absorbing substance from a light-absorbing part by making a laser beam incident on a scattering medium containing a light-absorbing substance, which includes a laser generator that generates two different wavelengths λ1 and A2, and a laser beam that passes through the scattering medium. A photomultiplier tube that measures the intensity of the emitted light, and a time-voltage conversion circuit that detects the time difference from the laser start signal to the rise of the emitted light signal detected by the photomultiplier tube and converts it into a voltage. A pulse counting circuit counts the number of pulses passing through a window of voltage level, and the travel time in the scattering medium is determined from the difference between the voltage at the peak of this pulse counting circuit and the voltage level when it does not pass through the scattering medium. A voltage-distance conversion circuit converts the optical path length to 1, and a change in absorbance is calculated based on the output light intensity for two wavelengths λ1 and A2, and the absorbance is calculated based on data on this change and data from the voltage-distance conversion circuit. The above object is achieved by an apparatus for measuring the concentration of a light-absorbing substance in a scattering medium, which is characterized by comprising a circuit for calculating the concentration of the substance. Further, in claim 8, the pulse counting circuit may change the window voltage by a predetermined amount using a window voltage setting circuit, calculate the travel time from this window voltage, and convert it into an optical path length. Furthermore, in claim 8, the pulse counting circuit may change the sweep timing of the window by a predetermined amount by a CPU, calculate the travel time from this sweep time, and change it to the optical path length.

[Operation and effects of the invention]

First, the basic principles of the first invention and the third invention will be explained. In this invention, when a light pulse is incident on a scattering medium containing a light-absorbing substance, the light intensity of the light pulse that has passed through the scattering medium is , the light intensity (scattering profile) fo(t) when there is no light-absorbing material in the scattering medium, as shown in FIG. 1(A)
Figure 1 (C
), which is expressed by the following equation (1). -εVct f(t) = fO(t) 10...(
1) Here, ε in FIG. 1(B) is the extinction coefficient (varies depending on the wavelength), ■ is the molar concentration of the light-absorbing substance, and C is the speed of light in the scattering medium. Furthermore, in addition to the above, it takes advantage of the fact that the scattering profile does not change depending on the wavelength of the optical pulse, and the absorption profile changes depending on the wavelength. That is, taking advantage of the fact that the scattering profile when there is no light-absorbing material in the scattering medium does not change depending on the wavelength, when there is only one kind of light-absorbing material, pulsed light of two different wavelengths is incident, and the obtained wavelength The concentration of the light-absorbing substance is measured by removing the scattering profile from a simultaneous equation of the temporal profile of light intensity and the expression of the scattering profile. The second and fourth inventions irradiate a scattering medium containing a light-absorbing substance with picosecond oscillation lasers of different wavelengths λ1 and A2, obtain the corresponding absorbances λ1 and λ2, and calculate the difference ΔA=
Determine AI-A2, determine the actual optical path length 1 of the scattering medium by introducing a time measurement method, and further calculate ■=ΔA/1 (ε1-ε2) using an arithmetic circuit to determine the molar concentration V. It is. In these inventions, the concentration of the light-absorbing substance can be accurately measured as an actual value. Furthermore, the amount of data stored is small, and the calculation method and the configuration of the device are simple. Furthermore, the concentration of the light-absorbing substance can be measured even if the input light intensity is not constant. Furthermore, even when multiple types of light-absorbing substances are present in the scattering medium, the concentration of each light-absorbing substance can be accurately measured.

【Example】

Embodiments of the first invention will be described below with reference to the drawings. First, a process of measuring the concentration of a light-absorbing substance when there is only one kind of light-absorbing substance in a scattering medium will be explained. Light scattering depends on the wavelength of the incident light and the substance that causes the scattering. When measuring with two wavelengths, if these two types of wavelength light are incident on the measurement target under equal conditions and observation is performed under equal conditions, it is considered that the influence of the scattering medium on the incident light is equal. Further, the same can be considered even if the scattering medium itself is also a light-absorbing substance. Furthermore, if the wavelengths of incident light of different wavelengths are sufficiently close, it can be considered that the scattering within the scattering medium is approximately equal. Therefore, the scattering profile fo shown in FIG. 1(A)
(t) is common, and light having wavelengths λ1 and λ2 having different extinction coefficients ε1 and ε2 are selected, and the above-mentioned equation (1) is established for each wavelength, as follows. −εIVCt fl(t)=11 ・fo(t)10 ・・・
(2) f2(t)=I2・fo(t)1
0-”~paci... (3) Here, fl(t)
, f2(t) are the observed temporal profiles of wavelengths λ1 and λ2 light, 11, ■2 are the incident light intensities, ε1, ε2
is the light absorption coefficient of the light-absorbing substance at wavelengths λ1 and λ2, ■
represents the concentration of the light-absorbing substance, C represents the speed of light, and t represents time. Note that fl(t) and f2(t) need to be corrected if there is a difference in the profile of the incident light pulse. If the logarithm is taken on both sides of the above equations (2) and (3), the following equation is obtained. log(fl(t)) = 1OQ11 +
log(fo(t) 10(-εI VCt)...
・(2') tag(f2(t) l = Ioa12
+IoQ(fO(t))+(-ε2 VCt
)...(3')(2')-(3') formula is the following (
4) Equation becomes. loa (fl (t) /f2 (t) 1=
100 (11/I21 + (ε2-ε1)vct...
・・・・・・(4) As shown in Figure 2, the above equation (4) is
5 - holds true for , so if we create an equation according to equation (4) for each of t = ti to tn, we get the following. log (fl (tl) /f2 (tl) 1=
to(+i11./I2) + (ε2−εi)v
cttog(fl(tn)/f2(tn))
= log(11/I21 +(ε2−ε1)VC−
tn・・・・・・・・・〈5) In the above equation (5), l0G(II/I2) and the concentration ■ of the light-absorbing substance are unknown quantities, so log (11/
The concentration ■ can be found by simultaneous equations that eliminate I2). For example, when the concentration V is calculated using the equations for times t1 and t2, the following is obtained. loa (fl (tl) /f2 (tl) )-1
0gff1 (t2) /f2 (t2) 1= (ε
2-e 1 ) VC(tl-t2) −(6)
Therefore, 116 − V=[1/IC(ε2−ε1) (tl−t2)
) ]x [10g(fl (tl) /f2
(tl) 1-log (fl (t2) /
f2 (t2) l ] (7). The above is a case where there is one type of light absorbing substance, but the number of light absorbing substances is n
If there are different types, proceed as follows. When measurements are made using N+1 types of wavelength light, the wavelength λ1 ・
・・fl(t) =11fO(t) X10−(ε11v1+ε12V2 +−・・+ε1n
vn) ct wavelength λn...fn(t) = InfO(t)
t )=In+1 fO(t) X 1 0-(En+1.IVI +En”1.2V
2+ −+E, n+1, nvn) ct. fk(t): Observed temporal turn at wavelength k fO(t): Temporal pattern assumed when there is no absorption. Two incident light intensity normalization coefficients at wavelength k. Vk: Concentration of the th light-absorbing substance. ε11j: Absorption coefficient of the third light-absorbing substance at wavelength λi An arbitrary wavelength among wavelengths λ1 to λn+1, for example, wavelength λn+1 is used as a reference. Here, if we take the logarithms of both sides of each equation for wavelengths λ1 to λn+1 and subtract the equation for wavelength λn+1 from the equation for wavelengths λ1 to λn, we get 10(J (fl (t) / fn+1
(t))=1oq(11/In+1
)−((ε1,1−εn+1.1) Vl +...
+ (ε l,n −ε n+1.n ) Vn
) ctloo (fn (t) /
fn+1 (t) 1=log(In
/In+1)−(<ε n, 1 − ε
n+1. ? )−V 1 + ・ ・
・+(ε n, n −ε n+1.n)Vn)ct
...-(s) Yes. . 3. . . 1)/. , 13
02.ノ,...' \ 1 prong V n,,' Rewriting equation (8) using the above, lj' (t) = I-ctεV −-...
...(9) Rewriting the equation at times t1 and t2, I
i' (tl) = I-ct1ε■ ・・・・・・
...(10)F (t2) = 1-ct2ε■
・・・・・・・・・(11) becomes (10)−<11
), F (tl) F (t2) = c(
t2-tl) EV・・・・・・・・・(12) εV= (1/C(t2-tl) IX (F (t
l) -11' (t2) )...(13)V= (
1/ c(t2-tl) 1 Xε (F (tl) -F (t2) )...(
14) Then, the density vector ■ is obtained. Note that if more types of wavelength light are used, V can also be determined using the least power method. In addition, in the above, the extinction coefficient A of the substance to be measured for each wavelength is assumed to be known, but this also applies if the extinction coefficient is not known in advance, for example, by injecting pulsed light into the substance to be measured. The light absorption constant K of the light-absorbing substance may be measured based on the transmitted light of the light-absorbing substance, and this may be used. In this case, it can be replaced with C(ε2−ε1)− in formula (7). Next, an embodiment of an apparatus for measuring the concentration of a self-absorbing substance in a scattering medium according to the third invention will be described with reference to FIG. This embodiment includes a picosecond pulse light source 12 that irradiates a measurement object 10 with picosecond pulse lasers of different wavelengths, and a laser pulse from this picosecond pulse light source 12 that irradiates the measurement object 10 with picosecond pulse lasers of different wavelengths.
0, an optical time-resolved measurement device 16 for time-resolved measurement of light, and a light-receiving side that guides the laser pulse transmitted through the measurement object 10 to the optical time-resolved measurement device 16 via a filter 18. An optical fiber 20, a computer 22 that calculates the concentration V of the light-absorbing substance in the measurement target 10 from the measured values of the optical time-resolved measuring device 16, a display 24 that displays the calculation results of this computer 22, and the picosecond pulse light source. 12, and constitutes a concentration measuring device 28 for a scattering medium self-absorbing substance. An incident light pulse monitoring fiber 30 is connected to the incident side optical fiber 14.
A part of the laser pulse passing through the optical time-resolved measuring device 16 is guided through a filter 18 . In this concentration measuring device 28, the picosecond pulse light source 1
2, the multi-wavelength picosecond laser is measured at the same time as the measurement target 1.
It must be input at 0. In this case, a part of the incident light pulse is guided by the incident light pulse monitoring fiber 30 to the optical time-resolved measuring device 16 via the filter 18 and measured simultaneously with the light guided by the light-receiving side optical fiber 20, or the driver 26 The timing of the trigger signal and the picosecond light pulse of each wavelength are matched, or the differences in each wavelength are managed to match the time axes of each wavelength. Further, the plurality of picosecond pulse light sources 12 are turned on alternately in a time-division manner for each wavelength, or the wavelengths to be measured are selected by the filter 18 to obtain a temporal intensity pattern of each wavelength. The computer 22, based on the temporal intensity pattern for each wavelength obtained by the optical time-resolved measuring device 16,
The above equation (14) is calculated, and the results are displayed on the display 24 for each light-absorbing substance. Next, a second embodiment of the third invention shown in FIG. 4 will be described. In this second embodiment, the concentrations of hemoglobin, myoglobin, cytochrome, oxidase, etc. in the blood of a living body are measured, and as a result, the oxygen metabolism in the living body is measured. The bioinstrumentation device 31 according to this second embodiment has a wavelength of 700
A plurality of semiconductor lasers 32 that generate laser pulses of different wavelengths in the near-infrared light region of ~90 On11, and an incident-side optical fiber 36 that guides the laser pulses emitted from the plurality of semiconductor lasers 32 to the living body 34 to be measured. and,
Light intensity time-resolved measuring device 3 consisting of a streak camera, etc.
8, and an output side optical fiber 4 that guides the laser pulse that has passed through the living body 34 to be measured to the light intensity time-resolved measuring device 38.
0, a driver 42 for individually driving the plurality of semiconductor lasers 32, and the light intensity time-resolved measuring device 3.
Based on the temporal intensity pattern for each wavelength obtained in step 8, the above formula (14) is calculated, and each light-absorbing substance moiety, oxidized hemoglobin in blood, deoxyhemoglobin, bioglobin in muscle, bioglobin in cells, is calculated. It is comprised of a computer 44 that calculates the concentration of cytochrome oxidase, etc., and a display 46 that displays the calculation results of this computer 44. The driver 42 includes a pulse generator 42A and a semiconductor laser threshold driver 42B for driving the semiconductor laser 32 based on a pulse signal from the pulse generator 42A. Semiconductor laser driver 42B and the semiconductor laser 32
A delay device 48 is interposed between the semiconductor laser 32 and
It is possible to adjust the variations in each wavelength of the laser pulse from. The pulse signal output from the pulse generator 42A is
The light intensity time-resolved measuring device 38 via the delay device 50
is now entered. In this embodiment, the optical pulse incident on the soil to be measured #34 is oscillated from a semiconductor laser 32, but since this semiconductor laser 32 has very small oscillation jitter, There is no need to monitor the incident light, and by driving the semiconductor laser 32 based on the pulses from the pulse generator 42A, the laser pulse can be applied to the living body 34 to be measured with almost no variation. Moreover, even slight variations can cause the delay device 48 to
It can be adjusted by The light intensity time-resolved measuring device 38 receives the pulse signal from the pulse generator 42A via the delay device 50, and thereby controls the light introduced through the output side optical fiber 40 in synchronization with the semiconductor laser 32. Pulse measurement can be performed. Generally, a living body is a strong light scattering medium, and absorption of light in the near-infrared region is mostly performed by the aforementioned hemoglobin, myoglobin, and cytochrome oxidase. In this example, from the semiconductor laser 32, 700
A laser pulse in the near-infrared light region of ~900 rv is oscillated, and this near-infrared light region detects oxidized and deoxyhemoglobin in the blood, as shown in FIGS. 5(A) and (B). , oxidized and reduced myoglobin in muscles, cytochrome oxidase in cells, etc., and therefore it is ideal for measuring oxygen metabolism in living organisms. The measurement process and the process of calculating by the computer 46 and displaying it on the display 46 are the same as those in the embodiment shown in FIG. 3, so their explanation will be omitted. FIG. 6 shows a measurement example in which a part of an actual living body is irradiated with a semiconductor laser and measured using the embodiment shown in FIG. In the case of Fig. 6 (A), the living body to be measured is the top of the head 3 of the human body.
4A, and the input side optical fiber 36 and the output photometric fiber 40 are placed in the top part 34, and the output port and the input port are arranged directly above the top part, respectively.As shown in FIG. 6(B), 34B, similarly, the input side optical fiber 36 and the output side optical fiber 40 are applied at right angles to the upper arm 34B. Further, as shown in FIG. 6(C), when measuring the heart 34C, the arrangement is such that the laser pulse from the input side optical fiber 36 passes through the heart 34C and enters the output side optical fiber 40. Next, an embodiment of the method and apparatus of the second invention for measuring the concentration of a light-absorbing substance from the optical path length 1 and absorbance will be described. First, the second invention will be considered from a theoretical perspective. Generally, the absorbance A of an opaque substance is expressed by the following formula. A=log(IO/II)=gVl+B-
(15) IO two-person incident light intensity ■1: Outgoing light intensity ε: molar extinction coefficient of light-absorbing substance ■ = molar concentration of light-absorbing substance 1: optical path length B: scattering intensity Absorption measurement of opaque materials excludes the influence of scattered light B For A
Perform two wavelength measurements at 1 and A2. A1 = C1Vl +B - (16) A2
=C2Vl 10B - (17) C1:A
molar extinction coefficient ε2 at A2: molar extinction coefficient at A2 (16) and (17), the following equation is obtained. ΔA=AI-A2=(C1-C2)C1,-,V
=ΔA/1(C1-C2)...(18)(18)
In the equation, the optical path length 1 is longer than the geometric optical path length due to scattering, as shown in FIG. 12, so the absolute concentration V cannot be determined unless the actual optical path length 1 is determined. Here, in order to obtain the actual optical path length 1, if a time meter side method is introduced, it can be obtained from the following equation. l=c-t=CO/n-t=-(19)
C: light source in the sample CO: speed of light in vacuum n: refractive index of the sample t; sample transit time By determining the actual optical path length 1 from this equation (19), the absolute concentration V of the light-absorbing substance is measured. I can do it. Here, as shown in FIG. 12, a picosecond oscillation laser is sent from a laser generator 6I to a sample 62, and after being scattered and absorbed within this sample 62, it is sent to a photomultiplier tube (hereinafter referred to as PMT) 63. shall be. If the thickness of the sample 62 is fixed to L, the travel distance of photons within the sample 62, ΔL (=1), can be determined as follows. From the laser generator 61 to the PMT 6 when there is no sample 62
The running time T1 up to 3 is TI = TO + L/V (20) TO: Running time other than sample (2) - 30 = Running time T2 when there is test f162 is T2 = TO +
(L+ΔL) n/V-(21) This (20), (21
) From the formula, T2-TI = ΔT = (L+ΔL) n/V-L/V,, l=L+ΔL=1/n (L+ΔL)...(
22) Therefore, compared to the time response when there is no sample 62 as shown in Fig. 9, all the signals (photons) that are delayed by ΔT due to the insertion of the sample 62 have traveled a distance of L+ΔL=1, If this ΔT is found, 1 can be found. This ΔT
In order to find this, the problem is how to detect the peak value ytP of the time response when the sample 62 is inserted. FIG. 7 shows an apparatus for detecting peak positions using a single channel analyzer (hereinafter referred to as SCA) that counts pulses of a certain voltage level (window). In this FIG. 7, 61 is a laser generator, and this laser generator 61 is connected to the first and second laser oscillating units 64.
a, 64b and a picosecond laser oscillation unit 6 with wavelengths λ1 and λ2
It consists of 5a-65b. These laser oscillation units 65a, 6
A sample to be measured 62 is set on the output side of the sample 62, and a multi-anode P is connected to the output side of the sample 62 via optical fibers 66a, 66b and interference filters 67a, 67b.
An MT 63 is provided, and its anodes 68a and 68b are respectively connected to time pick-off circuits (hereinafter referred to as TPO) 69.
a, bound to 69b. This TPO69a,
69b is sequentially coupled to a pulse height analysis circuit 71, a data analysis circuit 172, and a data display circuit 73 via circuits 70a and 70b that convert time into voltage (hereinafter referred to as TAC). The wave height analysis circuit 71 includes first and second single channel analyzers (hereinafter referred to as SCA) 74a,
74b, first and second counter memories 75a, 75b
, first and second integration circuits 76a and 76b, a peak value detection circuit 77, and an SCA window voltage setting circuit 78. The data analysis circuit 72 includes a division circuit 79, a 10q amplifier 80, a voltage-distance conversion circuit 81, and a molar concentration calculation circuit 8.
Consists of 2. The operation of the circuit configuration as described above will be explained based on the flowchart of FIG. 13. The laser generator 61 is turned on by the 10 o'clock start signal, and the generated picosecond oscillation lasers of λ1 and λ2 are applied to the sample 6.
2. After the laser is scattered and absorbed within this sample 62, it passes through optical fibers 66a and 66b and is sent to interference filters 67a and 67b. After being spectroscopy here, P
Guided to each channel of MT63. At this time, PMT6
The amount of laser light is adjusted so that a single photoelectron is generated on the photocathode No. 3. Further, during measurement, the laser power supplies 64a and 64b are restricted so that the amount of laser light is kept very constant, and a light amount monitor signal is displayed by the data display circuit 73 as necessary. The outputs of the anodes 68a and 68b of the PMT 63 are sent to TPOs 69a and 69b, and the rising edge tl of the signal is detected as shown in FIG. This rise time t1 and the time t of the start signal of the laser power supplies 64a and 64b
Q Which time difference is converted into a directly proportional electrical signal at the TACs 70a and 70b. This electric signal is transmitted to the first and second 5
These first and second 5CAs 74a and 74b, which are sent to the CAs 74a and 74b, count pulses during a window width T at a certain voltage level set by the window voltage setting circuit 78, and count pulses in the first and second counter memories, respectively. 7
Send to 5a and 75b. Then, data Sn at a certain time tn
The peak value detection circuit 77 compares the data S n-1 of the immediately preceding tn-i. If the previous data is 5n-7 and the subsequent data is sn, Sr+-1 until the peak is reached.
The relationship is <Sn. While this relationship is maintained, the calculation returns to the original state and is integrated again. Since the peak P occurs when the previous data S n-1 becomes larger than the subsequent data Sn, the difference between the voltage Vm immediately after this peak P and the window center voltage Vo when there is no sample is measured. 62 is calculated, and this is converted to 1 by the voltage-distance conversion circuit 81 and sent to the molar concentration calculation circuit 82. On the other hand, in the first and second arithmetic circuits 76a and 76b,
Output luminous intensity 111 at λ1 and output luminous intensity 1 at λ2
12 is obtained, which is converted by the division circuit 79 to I 12/I
11 is obtained, and togI 12/I 11 is obtained with log anz 80. That is, the absorbance A1 due to A1 and the absorbance A2 due to A2 are as follows. AI = 100 (IO1/III). A2 = log(IO2/I12) Therefore, ΔA=AI - A2 = 1op(IO1/111) -IoII02/11
2) = too((IOl・I 12) / (r
11・l02)) Here, since the incident light intensity is equal, I
01=I 02, ΔA= IOQ (I 12/I 11)
...(23). The value of this equation 23 is output from the log amplifier 80 and sent to the molar concentration calculation circuit 82. This molar concentration calculation circuit 8
2, in addition to these 1 and ΔA, ε1, which is known in advance,
Equation 18 above is calculated from ε2, and the molar concentration of sample 62 is
is determined as an absolute value. Next, FIG. 10 shows another embodiment of the present invention. That is, in the example shown in FIG.
was used to sequentially change the voltage level (window) by ΔV. In contrast, in FIG. 10, the sweep timing is sequentially changed by Δt. More specifically, the start signal of the laser generator 61 is transmitted to the CPU 8.
3, the sweep device 84 drives the sweep electrode 85 at a time interval of Δt as shown in FIG.
a, 68b. This PMT68a, 68
Since the two wavelengths λ1 and λ2 must be measured simultaneously, two wavelengths of the same performance or two parallel types are used. The outputs of the PMTs 68a and 68b are the first
, to the second integrating circuits 89a and 89b, and the sample 62
The data of λ1 and A2 are integrated and sent to first and second sample-and-hold circuits (hereinafter referred to as SW&) 90a and 90b. The first and second S&Hs 90a and 90b output integrated values sn and S n-1 as described above, and the peak value detection circuit 7
Compare with 7. When Sn > 5n-1, the slope is upward, so a YES signal is output and the sweep continues. sn
When <5n-i, a No signal is output, and time t is converted into distance 1 at time-distance conversion port #r91. At the same time, the No signal from the CPU 83 sends the S&H9 to the divider circuit 79.
Take in data from 0a and 90b and divide. The following process is similar to that shown in FIG. 7 to determine the molar concentration (■).

[Brief explanation of the drawing]

Fig. 1 is a line section showing the principle of the first invention of the method for measuring the concentration of a light-absorbing substance in a scattering medium, Fig. 2 is a line diagram for explaining the same principle, and Fig. 3 is a line section showing the principle of the method for measuring the concentration of a light-absorbing substance in a scattering medium according to the third invention. FIG. 4 is a block diagram showing the first embodiment of the device for measuring the concentration of a light-absorbing substance, FIG. 4 is a block diagram showing the second embodiment of the same, and FIG. 6 is an explanatory diagram showing the measurement method when measuring each part of a living body according to the second embodiment of FIG. 4, and FIG. 7 is a measurement of light absorbing substance concentration according to the fourth invention. A block diagram showing an embodiment of the device, FIG. 8 is a diagram showing the voltage-time relationship, FIG. 9 is a diagram showing the time response, and FIG. 10 is a diagram showing the voltage-time relationship.
The figure is a block diagram of another embodiment of the fourth invention, FIG. 11 is an explanatory diagram of sweep time, FIG. 12 is a block diagram for explaining optical path length 1, FIG. 13 is a 70-chart, and FIG. 14 is an explanatory diagram of the sweep time. FIG. 2 is a block diagram showing the process of inputting picosecond pulsed light into a scattering medium containing a light-absorbing substance and the measurement results of the emitted light. 10...Measurement object, 12...Picosecond pulse light source, 14.36...Incidence side optical fiber, 16.38...
- Optical time-resolved measuring device, 20.40... Output photometric fiber, 22.46... Computer, 24.44... Display, 26.42... Driver, 28... Concentration measuring device, 31 ... Biological measurement device, 32 ... Semiconductor laser, 34 ... Living body to be measured, 61 ... Laser generator, 62 ... Absorbing substance (sample), 63 ... PMT, 66a, 66b. ...Optical fiber, 67a, 67b...Interference filter, 69a, 69b -TPO1 70a, 70b-TAC. 71... Wave height analysis, 72... Data analysis device, 73... Data display circuit, 74a, 74b-8CA, 77... Peak value detection circuit, 78... Window setting circuit, 79... Division circuit, 80... Log amplifier, 81... Voltage-distance conversion circuit, 82... Molar concentration calculation circuit, 83... CPU, 84... Sweep device, 86... Slit, 87 ... Fluorescent material, 88a, 88b, PMT, 91... Time-distance conversion circuit.

Claims (10)

[Claims] (1) Different wavelengths λ1 and λ are used in the scattering medium containing the light absorbing substance.
In the time response function of the light from the scattering medium based on the input pulsed light, the light intensities f1(t1) and f1(t2) of the wavelength λ1 light at times t1 and t2, and the light intensities f1(t1) and f1(t2) of the wavelength λ2 light are Light intensity f2(t1), f at time t1, t2
2(t2), and the concentration V of the light-absorbing substance is calculated by the following formula, V=1/KC, where C is the speed of light in the scattering medium and the constant of absorption in the light-absorbing substance for wavelengths λ1 and λ2 light.・1/(t1-t2) × [log{f1(t1)/f2(t1)}-log{
f1(t2)/f2(t2)}] A method for measuring the concentration of a light-absorbing substance in a scattering medium. (2) In claim 1, when the scattering medium contains N types of light-absorbing substances, N+1 types of different wavelengths λ1
A method of irradiating a scattering medium with pulsed light of ~λN+1, measuring the light intensity at time t1 and t2 for each wavelength, and calculating the concentration V1 to VN of each light absorbing substance. Concentration measurement method. (3) In claim 2, the light-absorbing substance is oxyhemoglobin, deoxyhemoglobin, cytochrome aa3, and myoglobin, and the pulsed light is 670 nm to 1.3 nm.
A method for measuring the concentration of a light-absorbing substance in a scattering medium, characterized in that five types are selected from a wavelength range of 3 μm. (4) Different wavelengths λ1, λ
2, a process of determining the absorbances A1 and A2 of the light-absorbing substance in these λ1 and λ2 lights, a process of measuring the optical path length l of the light-absorbing substance, and a process of determining the optical path length l of the light-absorbing substance;
Extinction coefficients ε1, ε at 1, A2, l and λ1, λ2
2, a method for measuring the concentration of a light-absorbing substance in a scattering medium comprises the step of calculating the concentration V of the light-absorbing substance from V=(A1-A2)/{l(ε1-ε2)}. (5) In claim 4, the optical path length l is determined by determining a time t for the incident pulsed light to travel through the scattering medium, and is measured based on the absorption of light within the scattering medium. Method for measuring concentration of substances. (6) A method for measuring the concentration of a light-absorbing substance in a scattering medium according to any one of claims 1 to 5, wherein the pulsed light is emitted light from a picosecond oscillation laser. (7) A pulsed light source that injects pulsed light of at least two wavelengths λ1 and λ2 into a scattering medium containing a light-absorbing substance, and time-resolved measurement of the light from the scattering medium based on the input pulsed light, so that each wavelength Based on the optical time-resolved measuring device that obtains the temporal intensity pattern of light, and the data of the temporal intensity pattern of each wavelength light obtained by this optical time-resolved measuring device, the optical intensity of the wavelength λ1 light at times t1 and t2 is calculated. f1(t1), f
1 (t2), the light intensities f2 (t1) and f2 (t2) at times t1 and t2 of light with wavelength λ2 are measured, and the light intensities f2 (t1) and f2 (t2) of light with wavelength λ2 are
When the light absorption constant K in the light absorbing substance and the speed of light in the scattering medium are C, the concentration V of the light absorbing substance can be calculated using the following formula: V=1/KC・1/(t1−t2) X[log{ f1(t1)/f2(t1)}-log{
f1(t2)/f2(t2)}];
A device for measuring the concentration of a light-absorbing substance in a scattering medium, comprising: (8) A device that measures the concentration V of the light-absorbing substance from the light-absorbing part by inputting a laser beam into a scattering medium containing a light-absorbing substance, which includes a laser generator that generates two different wavelengths λ1 and λ2, and an emitted light that has passed through the scattering medium. A photomultiplier tube that measures the intensity;
A time-voltage conversion circuit that detects the time difference between the laser start signal and the rise of the emitted light signal detected by the photomultiplier tube and converts it into voltage, and counts the number of pulses that pass through a set voltage level window. a voltage-distance conversion circuit that calculates the traveling time in the scattering medium from the difference between the peak voltage of the pulse counting circuit and the voltage level when not passing through the scattering medium, and converts it into an optical path length l; , a circuit that calculates a change in absorbance based on the respective output light intensities for two wavelengths λ1 and λ2, and calculates the concentration of the light-absorbing substance based on data on this change and data from the voltage distance conversion circuit. A device for measuring the concentration of a light-absorbing substance in a scattering medium, characterized in that: (9) In claim 8, the pulse counting circuit is characterized in that the window voltage setting circuit changes the window voltage by a predetermined amount, calculates the traveling time from this window voltage, and converts it into an optical path length. A device for measuring the concentration of light-absorbing substances in a scattering medium. (10) The scattering medium according to claim 8, wherein the pulse counting circuit changes the sweep timing of the window by a predetermined amount by a CPU, calculates the travel time from this sweep time, and converts it into an optical path length. Concentration measuring device for internally absorbing substances.