JP2004219426A - Method and apparatus for measuring absorbing data of scattering body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To measure a change in the concentration, absolute value or the like of the specific absorbing component in a scattering body having a shape of every kind with high spatial resolution without being affected by the outer shape of the scattering body. <P>SOLUTION: This measuring apparatus is equipped with a light source for emitting pulsed light, a light incident part for allowing the pulsed light to be incident on the scattering body, a light detection part for detecting the light propagated through an object to be measured, a signal detection part for temporally segmenting a part of the light signal obtained in the light detection part and acquiring the measurement signal corresponding to the segmented signal, a first arithmetic part which performs measurement for acquiring respective measuring signals at a plurality of different timings and derives the time integrated values and average the optical path lengths with respect to a plurality of the measuring signals and a second arithmetic part for calculating the change quantity of the concentration of an absorbing component based on a predetermined relation between a plurality of time integrated values, a plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorbing component and the change quantity of the concentration of the absorbing component. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

  The present invention relates to a measuring method and an apparatus, an imaging method and an apparatus, a fluoroscopic method and an apparatus, a tomographic imaging method and an apparatus, or a mammography method and an apparatus capable of obtaining information on absorption inside a scatterer such as a biological tissue. It is. More specifically, the present invention relates to a method and an apparatus for measuring a temporal change in the concentration of a specific absorption component in a specific portion inside a scatterer and a spatial distribution thereof, and a specific absorption component inside a scatterer having variously shaped surfaces. TECHNICAL FIELD The present invention relates to a method and an apparatus for measuring scatterer absorption information capable of non-invasively measuring the concentration distribution of scatterers.

  There are four main methods for measuring or imaging living tissue, which is a scatterer, using light. These methods are (a) those that use baristic photon, and (b) that heterodyne detection of coherent components. (C) those using scattered light, and (d) those using a time-resolved gate.

(a) In the case of using a straight light (baristic photon), a pulse light is incident on a measurement target, and a straight transmission component included in output light is extracted by an ultra-high speed gate. At this time, the flight time of the straight transmitted light is shorter than the scattered light, and is the shortest among the output lights. Therefore, the straight transmitted light can be detected by cutting out the light first coming out of the measurement target by the ultra-high speed gate. This method has an advantage that a high spatial resolution such as X-ray CT can be expected in principle. However, since almost all light is scattered in multiples inside the measurement object, which is a scatterer, there is little or no, if any, linearly transmitted component. As a result, the utilization rate of light at the time of measurement becomes extremely poor. Considering the maximum light incident intensity (about ² mW / mm ² ) that can enter a living body, an extremely long time is required for imaging measurement and the like, which is not practical. In addition, in a large object such as a head or an arm, the signal light becomes extremely weak, and measurement is practically impossible.

  (b) In the method using a coherent component, a coherent high-frequency modulated light is branched and one of the light is incident on a measurement target. Then, the output light and the other high-frequency modulated light interfere with each other, heterodyne detection is performed on a coherent component included in the output light, and the coherent component is used for measurement.

  In other words, in this measurement system, the flight time (or optical path length) and the flight direction of the scattered light change according to the degree of scattering, and the flight direction is changed. Is detected. Therefore, in this case as well, a high spatial resolution is expected in principle, as in the previous example, but the light utilization rate is extremely low, and it is extremely difficult to apply it to measurement or imaging of a living body. Further, it is practically impossible to measure a large object such as a head or an arm.

  (c) For detecting scattered light, continuous (CW) light, pulsed light, or modulated light is incident on the measurement target, and light (output light) scattered and propagated in the measurement target is used. At this time, when pulse light having a pulse width sufficiently short with respect to the time response characteristic of the measurement target is incident, it may be considered that impulse light is incident, and the corresponding output light is represented by an impulse response. Such measurement is called time-resolved measurement (TRS), and measures the time waveform of the impulse response to calculate internal information. The method of inputting continuous (CW) light is called CW measurement, and the method of inputting modulated light is called phase modulation measurement (PMS). The former measures the time integral of the impulse response, and the latter measures the Fourier transform of the impulse response, that is, the system function. From the above, it is understood that in the time-resolved measurement (TRS), a signal including more information than the other two is obtained. The phase modulation measurement (PMS) for sweeping the modulation frequency and the time-resolved measurement (TRS) of the impulse response include almost equivalent information. Although the signal processing method is greatly different between the continuous (CW) measurement and the phase modulation measurement (PMS), the obtained signal contains essentially the same information, so that almost the same information can be measured. In each of these methods, almost all of the output light is used, so that the light utilization rate is improved by orders of magnitude compared to the two examples (a) and (b). However, since the scattered light spreads over almost the entire area of the inside of the measurement object or over a considerably wide area, the above method cannot perform quantitative measurement of a narrow specific site. Further, in imaging and optical CT, spatial resolution is extremely poor, and practical application is difficult.

  On the other hand, (d) those using the time-resolved gate use a part of the impulse response waveform. For example, the photons contained in the first part of the time-resolved output signal (impulse response waveform) are photons that are hardly scattered (photons that did not make a detour), that is, the light incident position (light incident point) and the light detection position It is a photon that has propagated near a straight optical path connecting (light receiving points). Therefore, if a signal from the time-resolved gate is used, it is possible to extract a photon that has propagated near the above-mentioned straight optical path and detected, and it is possible to improve spatial resolution such as imaging. This limit is the ballistic photon mentioned earlier. However, the time-resolved gate method that has been developed or proposed to date cannot quantitatively measure the absorption component inside the scatterer. The reason for this is that no method has been developed to analytically describe the signal obtained by the time-resolved gate method. In other words, there is no known method for analyzing a signal obtained by the time-resolved gate method based on the light diffusion theory and using it for quantification of an absorption component. Even if a method based on the light diffusion theory is developed, the fundamental problem caused by the light diffusion theory is that the diffusion approximation does not hold or the measurement of scatterers with various external shapes The problem remains that is impossible. As described above, the time-resolved gate method can improve the spatial resolution, but has a serious problem that internal information such as absorption components cannot be quantified.

There are many documents on the time-resolved gate method as described above, and typical ones are listed below. However, in each case, there is no discussion or suggestion about quantification of the absorption component as disclosed in the present invention.
AJJoblin, "Method of calculating the image resolution of a near-infrared time-of-flight tissue-imaging system", Appl. Opt. Vol. 35, pp. 752-757 (1996) JCHebden, DJ Hall, M. Firbank and DTDelpy, "Time-resolved opticalimaging of a solid tissue-equivalent phantom", Appl. Opt. Vol. 34, pp. 8038-8047 (1995) G. Mitic, J. Kolzer, J. Otto, E. Plies, G. Solkner and W. Zinth, "Time-gated transillumination of biological tissues and tissue-like phantoms", Appl. Opt. Vol. 33, pp. 6699 -6710 (1994) JCHebden and DTDelpy, "Enhanced time-resolved imaging with a diffusion model of photon transport", Opt. Lett. Vol. 19, pp. 311-313 (1994) JAMoon, R. Mahon, MD Duncan and J. Reintjes, "Resolution limits for imaging through turbid media with diffuse light", Opt. Lett. Vol. 18, pp. 1591-1593 (1993)

  An object of the present invention is to solve the problem that “the quantitative measurement of internal information such as absorption components cannot be performed” while taking advantage of the above-mentioned “high spatial resolution is obtained” of the conventional time gate method. I do. Specifically, the present invention has found a method of describing the behavior of light inside a scatterer having a different shape (basic relational expression), and a method of applying this basic relation to a time-resolved gate method, and utilizes this relation. It is another object of the present invention to provide a method and an apparatus for measuring a change in the concentration or an absolute value of a specific absorption component inside a scatterer of various shapes at a high spatial resolution without being affected by the outer shape of the scatterer. The present invention provides a living body measurement method and apparatus, an imaging method and an apparatus, a fluoroscopic method, and the like, which can significantly improve the measurement accuracy of a specific absorption component of a specific portion and measure their time change and spatial distribution. It is an object to provide a method and an apparatus for measuring absorption information inside a scatterer, such as an apparatus, a tomographic image analysis method and an apparatus, or a mammography method and an apparatus.

  In the first method for measuring absorption information of a scatterer according to the present invention, a first step of generating pulsed light having a predetermined wavelength is performed, and the pulsed light is spot-shaped at a light incident position on a surface of the scatterer to be measured. A second step of receiving the light propagating inside the object to be measured at a light detection position on the surface of the scatterer, and transmitting a part of the optical signal obtained in the third step in time. A fourth step of obtaining a measurement signal corresponding to the cut-out signal, and the first to fourth steps are respectively repeated at a plurality of different timings, and a plurality of the plurality of A fifth step of deriving a time integration value and an average optical path length for each of the measurement signals, and a change amount of the plurality of time integration values, the plurality of average optical path lengths, and the absorption coefficient Based on a predetermined relationship between a method characterized by and a sixth step of calculating a change amount of absorption coefficient occurring between said plural timings.

  In this case, based on a predetermined relationship between the variation of the absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component, and the variation in the concentration of the absorption component, the plurality of timings are determined. The method may further include a seventh step of calculating the amount of change in the concentration of the absorption component that has occurred therebetween.

  Further, in the sixth step, based on a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorption component, and the amount of change in the concentration of the absorption component, The amount of change in the concentration of the absorption component generated between the plurality of timings may be calculated.

  In the second method for measuring absorption information of a scatterer according to the present invention, a first step of generating pulsed light having a predetermined wavelength is performed, and the pulsed light is spot-shaped at a light incident position on the surface of the scatterer to be measured. A second step of receiving the light propagating inside the object to be measured at a light detection position on the surface of the scatterer, and transmitting a part of the optical signal obtained in the third step in time. And a fourth step of acquiring a measurement signal corresponding to the clipped signal, and fixing the distance between the light incident position and the light detection position to a plurality of different measurement positions while fixing the distance. Performing a fourth step repeatedly to derive a time integration value and an average optical path length for each of the plurality of measurement signals obtained at the plurality of measurement positions; and Calculating a difference in absorption coefficient between the plurality of measurement positions based on a predetermined relationship between the plurality of measurement positions, a value, a plurality of average optical path lengths, and a difference in absorption coefficient. It is a method.

  In this case, based on a predetermined relationship between the difference in the absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component, and the concentration difference of the absorption component, the plurality of measurement positions The method may further include a seventh step of calculating the difference between the concentrations of the absorption components in the above.

  In the sixth step, based on a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, an absorption coefficient per unit concentration of the absorption component, and a concentration difference of the absorption component, The concentration difference of the absorption component between a plurality of measurement positions may be calculated.

  A third method of measuring absorption information of a scatterer according to the present invention includes a first step of generating pulsed light of a different wavelength that can be regarded as having an equal or equal scattering coefficient with respect to an object to be measured; A second step of making the light incident position on the surface of the scatterer that is an object in a spot shape, and a third step of receiving light that has propagated inside the measurement object at a light detection position on the surface of the scatterer; A part of the optical signal obtained in the third step is temporally cut out, and a measurement signal corresponding to the cut out signal is obtained in such a manner that the respective time relations with respect to the pulse lights of different wavelengths are the same. Four steps, a fifth step of deriving a time integration value and an average optical path length for each of the plurality of measurement signals, the plurality of time integration values, the plurality of average optical path lengths, and Based on a predetermined relationship between the difference between the fine absorption coefficient, a sixth step of calculating the difference in absorption coefficient with respect to the pulsed light of said different wavelengths, a method characterized in that it comprises.

  In this case, based on a predetermined relationship between the difference in the absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component with respect to the pulse light having the different wavelength, and the concentration of the absorption component, The method may further include a seventh step of calculating the concentration of the absorption component.

  In the sixth step, a predetermined value between the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient of the absorption component per unit concentration with respect to the pulse light having the different wavelength, and the concentration of the absorption component is used. The concentration of the absorption component may be calculated based on the relationship.

  Further, in the third step, light is received at a plurality of light detection positions, and in the fourth step, measurement signals are respectively obtained at the plurality of light detection positions in correspondence with the pulse lights having the different wavelengths. Deriving a time integration value and an average optical path length for each of the plurality of measurement signals in the step; and, in the sixth step, the plurality of time integration values, the plurality of average optical path lengths, and the different wavelengths of absorption components. More preferably, the concentration of the absorption component is calculated based on a predetermined relationship between the absorption coefficient per unit concentration for the pulsed light and the concentration of the absorption component.

  In addition, the light incident position in the second step and the light detection position in the third step are scanned along the outer periphery of the scatterer to be measured. It is also possible to further comprise an eighth step of calculating the density of the absorption coefficient obtained in the above, and calculating a tomographic image of the density distribution in the scatterer.

  A first apparatus for measuring absorption information of a scatterer according to the present invention includes a light source that generates pulsed light having a predetermined wavelength, and the pulsed light incident in a spot shape on a light incident position on a surface of a scatterer that is an object to be measured. Light incident portion, and light that has propagated inside the measurement object, a light receiving portion that receives light at a light detection position on the surface of the scatterer, and temporally cuts out a part of an optical signal obtained by the light receiving portion, A signal detection unit that acquires a measurement signal corresponding to the clipped signal, performs measurement to acquire the measurement signal at a plurality of different timings, and performs measurement for each of the plurality of measurement signals obtained at the plurality of timings. A first arithmetic unit for deriving a time integrated value and an average optical path length, and a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, and a variation in an absorption coefficient, A device characterized in that it comprises a second calculator for calculating a change amount of absorption coefficient occurring between the number of timing, the.

  In this case, the second calculation unit further includes a change amount of the absorption coefficient obtained by the second calculation unit, an absorption coefficient per unit concentration of the absorption component, and a change amount of the absorption component concentration. Based on a predetermined relationship, the amount of change in the concentration of the absorption component generated between the plurality of timings may be calculated.

  Further, in the second arithmetic unit, based on a predetermined relationship among the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient of the absorption component per unit concentration, and the amount of change in the concentration of the absorption component. Then, the amount of change in the concentration of the absorption component generated during the plurality of timings may be calculated.

  A second apparatus for measuring absorption information of a scatterer according to the present invention includes a light source that generates pulsed light having a predetermined wavelength, and the pulsed light incident in a spot shape on a light incident position on a surface of a scatterer that is an object to be measured. Light incident portion, and light that has propagated inside the measurement object, a light receiving portion that receives light at a light detection position on the surface of the scatterer, and temporally cuts out a part of an optical signal obtained by the light receiving portion, A signal detection unit that obtains a measurement signal corresponding to the cut-out signal, and a measurement that obtains the measurement signal at a plurality of different measurement positions while fixing a distance between the light incident position and the light detection position. A first calculation unit for deriving a time integrated value and an average optical path length for each of the plurality of measurement signals obtained at the plurality of measurement positions; and the plurality of time integrated values and the plurality of average optical paths. Long, and Based on a predetermined relationship between the difference between the yield coefficients, a device characterized by and a second calculator for calculating the difference in absorption coefficient between the plurality of measurement positions.

  In this case, the second arithmetic unit further includes a predetermined difference between the difference between the absorption coefficients obtained by the second arithmetic unit, the absorption coefficient per unit concentration of the absorption component, and the concentration difference between the absorption components. Based on the relationship, a difference in the concentration of the absorption component between the plurality of measurement positions may be calculated.

  Further, in the second calculation unit, based on a predetermined relationship among the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorption component, and the concentration difference of the absorption component. , The concentration difference of the absorption component between the plurality of measurement positions may be calculated.

  The third apparatus for measuring absorption information of a scatterer according to the present invention includes a light source that generates pulsed light of different wavelengths that can be regarded as having the same or equal scattering coefficient with respect to the object to be measured, and that the pulsed light is measured by the object to be measured. A light incident portion that enters a light incident position on a surface of a certain scatterer in a spot shape, a light receiving portion that receives light propagated inside the measurement target at a light detection position on the surface of the scatterer, and the light receiving portion A signal detection unit that temporally cuts out a part of the optical signal obtained in the above, and obtains a measurement signal corresponding to the cut-out signal, so that the respective time relations to the pulse light of the different wavelengths are the same, A first calculator for deriving a time integrated value and an average optical path length for each of the plurality of measurement signals, and a difference between the plurality of time integrated values, the plurality of average optical path lengths, and the difference between the absorption coefficients; Place Based on the relationship, and a second calculator for calculating the difference in absorption coefficients for the different wavelengths of the pulsed light is a device which is characterized in that it comprises.

  In this case, the second arithmetic unit further includes a difference between the absorption coefficients obtained by the second arithmetic unit, an absorption coefficient per unit density of the absorption component with respect to the pulse light having the different wavelength, and a density of the absorption component. And the concentration of the absorption component may be calculated based on a predetermined relationship between

  In the second arithmetic unit, the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient of the absorption component per unit density with respect to the pulse light having the different wavelength, and the concentration of the absorption component The concentration of the absorption component may be calculated based on a predetermined relationship.

  Further, the light receiving unit receives light at a plurality of light detection positions, and the signal detection unit acquires measurement signals corresponding to the pulse lights of different wavelengths at the plurality of light detection positions, respectively. Wherein the first arithmetic unit derives a time integrated value and an average optical path length for each of the plurality of measurement signals, and wherein the second arithmetic unit includes the plurality of time integrated values, Calculating the concentration of the absorption component based on a predetermined relationship between the plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorption component with respect to the pulse light having the different wavelength, and the concentration of the absorption component. Is preferred.

  Further, a light incident position in the light incident section and a light detection position in the light receiving section are scanned along the outer periphery of the scatterer to be measured, and the second calculation is performed on each of a plurality of measurement positions by the scanning. It is also possible to further include a third calculation unit that calculates the concentration of the absorption coefficient obtained by the unit and calculates a tomographic image of the concentration distribution in the scatterer.

  As described above, according to the method and apparatus for measuring the absorption information of a scatterer of the present invention, the concentration change or the absolute concentration of the specific absorption component inside the scatterer having an arbitrary shape composed of a surface that cannot be re-entered, Measurement can be performed with high spatial resolution. Therefore, according to the present invention, it is possible to greatly improve the measurement accuracy of the specific absorption component of the specific portion, and to measure their time change and spatial distribution with high spatial resolution without being affected by the outer shape of the scatterer. It is possible to provide a method and an apparatus for measuring absorption information inside a scatterer, such as a biological measurement method and an apparatus, an imaging method and an apparatus, a fluoroscopic method and an apparatus, a tomographic image analysis method and an apparatus, or a mammography method and apparatus. It becomes possible.

(Principle of the present invention)
First, the principle of the present invention will be described. Here, first, the problems of the generally used light diffusion approximation method will be clarified, and then the principle of the present invention will be described.

  Generally, the behavior of photons inside a scatterer is analyzed by a light diffusion equation based on light diffusion theory (Photon Diffusion Theory). In other words, the behavior of light inside the scatterer is approximated by the light diffusion equation, and when this equation is solved, the relationship between the optical characteristic or optical constant of the measurement target and the output light is obtained, and the absorption information and the like are derived from this relationship. be able to. However, the method based on the light diffusion equation has the following problems.

  That is, when solving the light diffusion equation, it is necessary to set boundary conditions without fail. However, since the boundary condition greatly depends on the shape of the scatterer, it is necessary to set a new boundary condition and solve the light diffusion equation every time the shape of the scatterer changes in order to perform accurate measurement. However, the scatterers that can be set with a certain degree of boundary condition are limited to extremely simple shapes such as an infinite space, a semi-infinite space, an infinitely long cylinder, a slab with an infinitely wide slab, and a sphere. As a result, it is indispensable to use an approximate boundary condition in measurement of a biological tissue or the like whose shape is not simple, which causes a large measurement error. Such problems are discussed, for example, in the recent literature; Albert Cerussiet et al. 1996), pp.24-26.To summarize the above problem, "A measurement method that can be applied unifiedly to scatterers with different shapes has not been developed yet. It is not possible to accurately measure the concentration of specific absorption components inside the body in a unified manner. "

  Therefore, in the following, first, a relational expression that can be uniformly applied to scatterers having different shapes will be disclosed, and then, this relational expression will be applied to the time-resolved gate method, and a method for quantifying an absorption component will be disclosed. In the apparatus and method of the present invention that can improve the spatial resolution and quantify internal information such as absorption components, the spatial resolution can be selected by controlling the gate time and its timing.

When trying to non-invasively measure the inside of a scatterer such as a biological tissue, light is incident on the surface of the scatterer, and the light propagated inside the scatterer is received at another position on the surface to obtain a measurement signal. Then, information such as the concentration of the absorption component contained therein is measured from the measurement signal. At this time, the photons are strongly scattered by the scattering components inside the scatterer, and the optical path is bent zigzag. FIG. 1 shows an example of a photon track when a photon incident at a position P is received at a position Q. The time waveform (impulse response) of the output light when the impulse light is incident on the scatterer at the reference time t = 0 is composed of a plurality of photons having various flight distances (optical path lengths) flying in various zigzag optical paths. You. However, the photons constituting the output light at an arbitrary time t each have a constant flight distance (optical path length) l = ct, where c is the light speed in the medium, and each photon has a bare beam. The Lambert (Beer-Lambert) rule holds. That is, the survival rate of each photon when the absorption coefficient was mu _a becomes exp (-cμ _a t). That is, when an optical pulse composed of a large number of photons enters from the position P and is received at the position Q, many photons that have passed through various optical paths are detected at the time t. amount, i.e. the survival rate is proportional to exp (-cμ _a t). Since the macroscopic refractive index of the living body has a constant value substantially equal to the refractive index of water, the light speed c is regarded as a constant. Hereinafter, the above fact is referred to as the micro-bear Lambert rule.

ここで、ｓ(μ_s,t)は吸収係数がμ_a＝０のときの応答（つまり、散乱のみがあるときの応答）、指数項exp(-μ_act)は吸収係数μ_aによる減衰を表す項である。いずれの関数もｔ＜０のときゼロとなる時間因果関数である。以上ではインパルス光入射を考えたが、媒体の時間応答に対して時間幅が十分短いと見なせるパルス光入射に対して、上記の関係が成立することは明らかである。したがって以下では、時間幅が十分短いと見なせるパルス光入射について考える。 From the above, the impulse response h (t) when the impulse light is incident on the scatterer at t = 0 becomes a function of the scattering coefficient μ _s , the absorption coefficient μ _a , and the time t, and is expressed as follows.

Here, s (μ _s , t) is the response when the absorption coefficient is μ _a = 0 (that is, the response when there is only scattering), and the exponential term exp (-μ _a ct) is the attenuation due to the absorption coefficient μ _a Is a term representing. Both functions are time-causal functions that become zero when t <0. Although impulse light incidence has been considered above, it is clear that the above relationship holds for pulse light incidence whose time width can be considered to be sufficiently short with respect to the time response of the medium. Therefore, in the following, pulsed light incidence whose time width can be considered to be sufficiently short will be considered.

Note that here the above equation does not include variables relating to boundary conditions. This is very different from the solution of the light diffusion equation including variables related to boundary conditions. In the above equation, the boundary condition is reflected on the impulse response h (t) via the function s (μ _s , t). Therefore, the above equation can be widely applied to scatterers having various non-reentrant surface shapes.

のように表される。ここで、ｂは入射光の強度に比例する係数である。出力信号Ｊ(μ_s,μ_a,t)の時間積分は全積分出力信号量Ｉ(μ_s,μ_a)を表わし、ＣＷ計測のときの計測値に対応する。この積分出力信号Ｉ(μ_s,μ_a)は(2.1)式から次のようになる。

At this time, the output signal J (μ _s , μ _a , t) is

Is represented as Here, b is a coefficient proportional to the intensity of the incident light. Output signal _{J (μ s, μ a,} t) of the time integration total integral output signal quantity I (μ _s, μ _a) represents, corresponding to the measured value when the CW measurements. The integral output signal I (μ _s , μ _a ) is as follows from equation (2.1).

Now, as shown in FIG. 2, it is considered that an arbitrary part t = [t ₁ , t ₂ ] (t ₁ <t ₂ ) of the output signal J (μ _s , μ _a , t) is cut out. At this time, the integrated output signal, that is, the measurement signal I _T (μ _s , μ _a ) is represented by the following equation.

が導出される。ここで<t_T>は検出された光子の平均飛行時間、Ｌ_T(μ_s,μ_a)は平均光路長であり、このような考え方は本発明によって初めて開示されるものである。次に、(5)式を積分すると、

が得られる。ここで、右辺第２および第３項は積分定数であり、(4.1)式でμ_a＝０として求められる。当然の結果ではあるが、(6)式は境界条件に関する変数を含んでいない。このことは、境界条件に関する変数を必ず含む光拡散方程式の解とは大きく異なる。前出の(6)式においては、境界条件は測定信号Ｉ_T(μ_s,μ_a)および平均光路長Ｌ_T(μ_s,μ_a)に反映されている。したがって、(6)式は、種々の再入射不可能な表面形状をもつ散乱体に広く適用することができる。 Furthermore, from equations (4.1) and (4.2),

Is derived. Here, <t _T > is the average flight time of the detected photon, L _T (μ _s , μ _a ) is the average optical path length, and such a concept is disclosed for the first time by the present invention. Next, by integrating equation (5),

Is obtained. Here, the second and third terms on the right-hand side are integration constants, which are obtained from equation (4.1) as μ _a = 0. As a matter of course, equation (6) does not include variables related to boundary conditions. This is significantly different from the solution of the light diffusion equation, which always includes variables related to boundary conditions. In the preceding formula (6), boundary conditions measurement signal _{I T (μ s, μ a} ) and mean optical pathlength _{L T (μ s, μ a} ) are reflected in. Therefore, equation (6) can be widely applied to scatterers having various non-reentrant surface shapes.

Here, the following can be understood by considering the trajectories of photons constituting the measurement signal obtained by cutting out a part of the output signal J (μ _s , μ _a , t). If only the first part of the output signal J (μ _s , μ _a , t) is cut out, a photon having a short optical path length is detected as described above, and therefore, in FIG. 3A and FIG. Photons that have propagated in the narrow part indicated by the solid hatch (T ₁ ) are detected, and the spatial resolution is improved. Here, FIG. 3A shows a configuration of the transmission type measurement, and FIG. 3B shows a configuration of the reflection type measurement. When the cutout time T = t ₂ −t ₁ is made longer (T ₁ → T ₂ → T ₃ ), the chain hatching (T ₂ ) and the chain length in FIGS. As shown by the line hatch (T ₃ ), photons that propagate sequentially over a wide portion are detected, so that the amount of light (or the amount of signal) used for measurement increases, but the spatial resolution decreases.

Further, the output signal _{J (μ s, μ a,} t) when cutting out a middle of a portion of, the gradually delayed the clipped timing, a part for measuring, as shown in FIGS. 4 (a) and 4 (b) Can be changed (t ₁ → t ₂ ). Such a measurement can also be realized by a measurement for obtaining a difference between two signals obtained at different time gates. In other words, the fact that a portion after the output signal J (μ _s , μ _a , t) is cut out utilizes more peripheral information. Therefore, in the present invention, by controlling the timing of said cut-out time T = t ₂ -t ₁ and cut, it is possible to select a site to obtain the spatial resolution and information.

  3 (a) and 3 (b) and FIGS. 4 (a) and 4 (b) show the range of the track of a general photon occupying a certain ratio among the photons included in the detection light (output signal). It is shown. Therefore, the photons detected naturally include photons that have propagated outside the illustrated range.

  Hereinafter, a method of calculating information on absorption from a measured value using the above-described formula (6) will be described.

(Measurement of concentration change of absorption component)
Consider a case in which one type of absorbing component is contained in the medium, and the concentration of the absorbing component changes to change the absorption coefficient μ _a from μ _a1 to μ _a2 . In a normal living body or scatterer, it may be considered that the scattering characteristics do not change even if the concentration of the absorbing component changes. This is similar to the case where the ink is put into milk. If before and after the change _s (μ s, t) or scattering coefficient mu _s does not change, the measurement position the mean path length by measuring securing the (pulsed light incident position and photodetection position) L _T (μ _s, μ _a ) is _a function of the absorption coefficient μ _a , and equation (6) holds for the measured values before and after the change. Therefore, the following equation is derived from Equation (6) using μ _a1 and μ _a2 before and after the change.

ただし、μ_xはμ_a1≦μ_x≦μ_a2またはμ_a1≧μ_x≧μ_a2なる適宜の値である。以上から、平均光路長Ｌ_T(μ_s,μ_a)を知ることができれば、変化の前後の測定信号Ｉ_T(μ_s,μ_x)の値から、変化の前後の吸収係数の差μ_a2−μ_a1を算出することができる。 Next, using the average value theorem, the following equation is obtained from the equation (7).

Here, μ _x is an appropriate value that satisfies μ _a1 ≦ μ _x ≦ μ _a2 or μ _a1 ≧ μ _x ≧ μ _a2 . From the above, if the average optical path length L _T (μ _s , μ _a ) can be known, the difference μ _a2 of the absorption coefficient before and after the change from the value of the measurement signal _IT (μ _s , μ _x ) before and after the change. −μ _a1 can be calculated.

と表すことができる。ただし、αは0≦α≦1なる適宜の値をもつ。この場合、Ｌ_T(μ_s,μ_x
)は単調関数であり、通常はμ_a1とμ_a2における値がほぼ等しいから、α＝1/2としてよい。また、それぞれの平均光路長Ｌ_T(μ_s,μ_a1)およびＬ_T(μ_s,μ_a2)は、前出の(5)式に示したように、測定信号の波形の重心（平均タイムディレイ）を演算することによって求めることができる。すなわち、前出の（５）式の第２行に示す式の値を計算する。ここで、ｃは媒質中の光速度であるから、既知あるいは別の方法で知ることができる。また、分子と分母に含まれる項、つまりｓ(μ_s,ｔ)exp(−μ_aｃｔ)＝Ａは前出の（２．１）式に示した出力信号Ｊ(μ_s,μ_a,ｔ)を１／ｂ倍したものである。この係数ｂは積分操作の外に出すことができ、かつ分子と分母の両方に含まれるから消去される。つまり、上記の計算では、Ａを用いても、ｂＡである計測値Ｊ(μ_s,μ_a,ｔ)を用いても、同じ結果が得られる。したがって、分子はｔＪ(μ_s,μ_a,ｔ)を、また分母はＪ(μ_s,μ_a,ｔ)をｔについて、それぞれｔ₁からｔ₂まで積分したものである。これら２つの項、及びそれらの比の計算は、コンピュータを用いて高速に計算することができる。また、上記重心の計算は、上記のように直接（５）式第２行の分子と分母を演算する方法以外に、これと等価な種々の方法がある。いずれの場合にも、この計算結果は平均飛行時間となり、前記ｃを乗じて平均光路長を得る。 Further, in this case, the average optical path length L _T (μ _s , μ _x ) is calculated using the coefficient α.

It can be expressed as. Here, α has an appropriate value of 0 ≦ α ≦ 1. In this case, L _T (μ _s , μ _x
) Is a monotonic function, and since the values at μ _a1 and μ _a2 are generally almost equal, α = 1/2 may be set. The average optical path lengths L _T (μ _s , μ _a1 ) and L _T (μ _s , μ _a2 ) are, as shown in the above equation (5), the center of gravity of the waveform of the measurement signal (average time). Delay). That is, the value of the expression shown in the second row of the expression (5) is calculated. Here, since c is the speed of light in the medium, it can be known by another method or another method. Moreover, terms that are included in the numerator and denominator, that is _{s (μ s, t) exp} (-μ a ct) = A output signal J (mu _s as shown in (2.1) equation supra, mu _a, t) is multiplied by 1 / b. This coefficient b can be taken out of the integration operation and is eliminated because it is included in both the numerator and the denominator. That is, in the above calculation, even with A, a bA measurement _{J (μ s, μ a,} t) be used, the same results are obtained. Thus, molecules tJ the _{(μ s, μ a, t} ), also denominator _{J (μ s, μ a,} t) for the t, is the integral from t ₁ to t _2, respectively. The calculation of these two terms and their ratio can be calculated at high speed using a computer. There are various methods for calculating the center of gravity other than the method of directly calculating the numerator and denominator in the second row of equation (5) as described above. In each case, the result of this calculation is the average flight time, and the above-mentioned c is multiplied to obtain the average optical path length.

To calculate the concentration change ΔV of the absorption component, the following equation derived from the Bear-Lambert rule is used.

が得られる。以上の(11)式によって、散乱体内部の吸収成分の濃度変化ΔＶを計測する方法が明らかとなる。 Here, ε is an absorption coefficient (or extinction coefficient) per unit concentration of the absorption component, and can be measured by a spectrophotometer. Also, the absorption coefficients (or extinction coefficients) of many absorbing substances are published in various documents. Therefore, from equations (8) to (10),

Is obtained. From the above equation (11), a method of measuring the concentration change ΔV of the absorption component inside the scatterer becomes clear.

(Application of measurement of concentration change of absorption component)
The above method can be applied to measuring the temporal change in the concentration of a plurality of types of absorption components using pulsed light of different wavelengths while the measurement position is fixed. Further, if such a measurement is repeated at a plurality of locations along the outer circumference of the measurement target and a tomographic image reconstruction calculation as seen in X-ray CT, optical CT, or the like is performed, the time of the hemoglobin concentration at a predetermined site can be obtained. It can also be applied to change measurement.

  In addition, the measurement position (light incident position and light detection position) is measured by moving or scanning the measurement target held so that the thickness is constant, and the measurement value at an arbitrary position is set as a reference value. By doing so, it is possible to measure the distribution of the difference of the concentration of the absorption component inside the scatterer from the reference value. Such measurement can be applied to optical mammography for diagnosing breast cancer.

  In the above-described measurement according to the present invention, when the gate time (cutout time) is shortened, the spatial resolution is improved. Further, a part (or a part) to be measured can be controlled by making the gate timing variable. Specific application examples include, in addition to optical mammography, a fluoroscope, optical CT, and a clinical monitor used for surgery and treatment.

が成立する。そして(6)式から

が得られる。すると、(8)式の場合と同様にして、

が得られる。ただし、μ_xはμ_a1≦μ_x≦μ_a2またはμ_a1≧μ_x≧μ_a2なる適宜の値である。この(14)式は、b₁/b₂＝１つまり２波長のパルス光の入射光強度が等しいとき、前出の(7)式に等しくなる。また、係数b₁/b₂は入射パルス光の強度を調整することによってb₁/b₂＝１とすることができる。さらに、光源あるいはパルス光の強度を実測してb₁/b₂の値を推定することもできる。以上により、平均光路長Ｌ_T(μ_s,μ_x)とb₁/b₂の値、および波長λ₁とλ₂のパルス光を用いた計測で得られる測定信号Ｉ_T(λ₁)およびＩ_T(λ₂)の値から、吸収係数の差μ_a2−μ_a1を算出することができる。 (Measurement of concentration of specific absorption component)
Next, a description will be given of a case where measurement is performed using two types of pulsed light having wavelengths of λ ₁ and λ ₂ , that is, a two-wavelength spectroscopic measurement method. Now, it is assumed that the absorption coefficient of a scatterer containing one kind of absorption component is μ _a1 when the wavelength is λ ₁ and μ _a2 when the wavelength is λ ₂ . Then, it is assumed that the scattering coefficients μ _s1 and μ _s2 of the medium at the wavelengths λ ₁ and λ ₂ are the same or substantially equal. Such conditions are easily realized by selecting the wavelength used for measurement. Therefore, when measuring two wavelengths at the same measurement position (pulse light incident position and light detection position), if μ _s1 ≒ μ _s2 = μ _s ,

Holds. And from equation (6)

Is obtained. Then, as in the case of equation (8),

Is obtained. Here, μ _x is an appropriate value that satisfies μ _a1 ≦ μ _x ≦ μ _a2 or μ _a1 ≧ μ _x ≧ μ _a2 . This equation (14) becomes equal to the above equation (7) when b ₁ / b ₂ = 1, that is, when the incident light intensities of the two wavelengths of pulsed light are equal. Further, the coefficient b ₁ / b ₂ can be b ₁ / b ₂ = ₁ by adjusting the intensity of the incident pulse light. It is also possible to actually measure the intensity of the light source or pulsed light to estimate the value of b ₁ / b _2. As described above, the average optical path length L _T (μ _s , μ _x ) and the value of b ₁ / b ₂ , and the measurement signal I _T (λ ₁ ) obtained by measurement using pulsed light of wavelengths λ ₁ and λ ₂ and From the value of I _T (λ ₂ ), the difference μ _a2 −μ _a1 of the absorption coefficient can be calculated.

と表すことができる。ただし、αは0≦α≦1なる適宜の値をもつ。この場合にも、Ｌ_Tが単調関数であることを考慮すると、通常はα＝1/2としてよい。また、それぞれの平均光路長Ｌ_T(μ_s,μ_a1)およびＬ_T(μ_s,μ_a2)は、前出の(5)式に示したように測定信号の波形の重心（平均タイムディレイ）を演算することによって求めることができる。 The average optical path length L _T (μ _s , μ _x ) is calculated using the same coefficient α as above.

It can be expressed as. Here, α has an appropriate value of 0 ≦ α ≦ 1. In this case as well, considering that L _T is a monotonic function, α = 1/2 may normally be set. The average optical path lengths L _T (μ _s , μ _a1 ) and L _T (μ _s , μ _a2 ) are, as shown in the above equation (5), the center of gravity of the waveform of the measurement signal (average time delay). ) Can be calculated.

ただし、ε₁およびε₂の値は前もって分光光度計で測定することができる。したがって、

となり、前出の吸収成分の濃度変化の計測と全く同様にして、吸収成分の絶対濃度Ｖを計測することができる。この場合、２種以上のｎ種の波長のパルス光を使用すれば、(n-1)種類の吸収成分の濃度を計測することができる。 The concentration V of the specific absorption component is calculated from the following equation using absorption coefficients (or extinction coefficients) ε ₁ and ε ₂ per unit concentration of the specific absorption component at wavelengths λ ₁ and λ ₂ .

However, the values of ε ₁ and ε ₂ can be measured in advance with a spectrophotometer. Therefore,

The absolute concentration V of the absorption component can be measured in exactly the same manner as the measurement of the concentration change of the absorption component described above. In this case, if two or more types of pulsed light having n wavelengths are used, the concentrations of (n-1) types of absorption components can be measured.

ただし、Ｉ_T1(λ₁)とＩ_T2(λ₂)およびＬ_T1(μ_s,μ_x1)とＬ_T2(μ_s,μ_x2)は、それぞれ光検出距離１と２で得られる測定信号と平均光路長である。また、μ_x1はμ_a1≦μ_x1≦μ_a2またはμ_a1≧μ_x1≧μ_a2、μ_x2はμ_a1≦μ_x2≦μ_a2またはμ_a1≧μ_x2≧μ_a2なる適宜の値であり、(15)式と同様にして求めることができる。さらに、当然ではあるが、以上に述べた方法は、２つ以上の波長の光を用いる多波長分光計測に拡張することができる。 (2 point 2 wavelength measurement)
Two detection distances - when in (light incidence between the light detection position distance) performing two-wavelength spectroscopic measurement of the can erase coefficients b ₁ / b _2, supra. That is, the coefficient b ₁ / b ₂ light incidence - by utilizing the fact that does not depend on the light detection position, to erase the coefficients b ₁ / b _2. In this case, the above equation (17) becomes as follows.

Here, I _T1 (λ ₁ ) and I _T2 (λ ₂ ) and L _T1 (μ _s , μ _x1 ) and L _T2 (μ _s , μ _x2 ) are the measurement signals obtained at the light detection distances 1 and 2, respectively. Average optical path length. Also, _μx1 is μ _a1 ≦ μ _x1 ≦ μ _a2 or μ _a1 ≧ μ _x1 ≧ μ _a2 , μ _x2 is an appropriate value of μ _a1 ≦ μ _x2 ≦ μ _a2 or μ _a1 ≧ μ _x2 ≧ μ _a2 , It can be obtained in the same manner as in equation (15). Furthermore, it will be appreciated that the above described method can be extended to multi-wavelength spectroscopy using light of two or more wavelengths.

(Measurement of spatial distribution of concentration of absorption component)
By performing the above-described measurement at many places, the spatial distribution of the concentration of the absorption component can be measured. In this case, the measured values of the concentrations of the absorption components are measured independently of each other, so that the detection distances (distance between light incidence and light detection positions) at each measurement position may be different. That is, according to the method of the present invention, it is possible to measure the concentration of the absorption component inside the scatterer having various external shapes that cannot be re-entered with high spatial resolution. At this time, the spatial resolution is controlled by the above-described cutout time T = t ₂ −t ₁ and its timing. Specific applications include optical mammography, fluoroscopy, and optical CT. In these methods, methods such as light reception at a plurality of locations, scanning of a light incident position and a light detection position, and time division measurement are used. Further, if necessary, an image reconstruction operation as seen in CT is performed. As described above, the feature of these measurements is that the concentration distribution of the specific absorption component can be quantitatively measured with high spatial resolution.

  Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. However, in the following description, the same elements will be denoted by the same reference symbols, without redundant description.

Example 1
FIG. 5 shows a first embodiment of the apparatus of the present invention for carrying out the method of the present invention, and shows the configuration of the apparatus 1 for measuring the change over time of the concentration of the absorption component inside the scatterer 2. In the configuration of the device 1, a change in the concentration of the absorption component of the scatterer 2 containing one type of absorption component, or a change in the concentration of an absorption substance including a plurality of components is measured. In this configuration, pulse light of a predetermined wavelength λ having a sufficiently short time width is incident on a position P (light incident position) on the surface of the scatterer 2, and the pulse light of the scatterer 2 is detected at another position Q (light detection position) on the surface. Receives light that has propagated inside. Then, by repeating this measurement, the change in the concentration of the absorption component in a relatively narrow portion inside the scatterer 2 is quantified. In this case, if the concentration of the absorption component at the time of the first measurement is taken as the reference value, the change in the concentration of the absorption component can be quantified. The measuring device 1 is integrated and stored in one housing.

  The light source 10 uses a laser diode or the like, and generates pulsed light having a wavelength λ. In this case, the wavelength is selected according to the scatterer 2 to be measured and the absorption component. In the measurement of a living body, oxygenated and deoxygenated hemoglobin and oxygenated and deoxygenated myoglobin are often measured, and the absorption spectra of these absorption components are shown in FIG. Therefore, light of 600 nm to 1.3 μm is usually used for measurement of a living body. Further, the pulse width is usually set to about 20 ps to 200 ps. As the light source, a light emitting diode, a pulse laser, or the like can be used in addition to the laser diode.

  The pulse light emitted from the light source 10 is incident on the surface of the scatterer 2 to be measured through the light guide 12. The space between the light guide 12 and the scatterer 2 is very small in the embodiment of FIG. However, in practice, the gap may be widened and filled with a liquid material or jelly-like object (hereinafter, referred to as an interface material) having a refractive index and a scattering coefficient substantially equal to those of the scatterer 2. That is, since light propagates through the interface material and enters the measurement target, no problem occurs. When the surface reflection of the scatterer 2 becomes a problem, the influence of the surface reflection can be reduced by appropriately selecting the interface material.

  The light that has propagated inside the scatterer 2 is received by a light guide 13 placed at a position Q (light detection position) at a distance r from the light incident position P. Here, an interface material may be used for the same reason as described above. The photodetector 14 converts the optical signal into an electric signal, amplifies and outputs the electric signal if necessary. As the photodetector 14, in addition to the photomultiplier tube, a phototube, a photodiode, an avalanche photodiode, a PIN photodiode, a streak camera, a streak scope, an optical oscilloscope, or the like can be used. When selecting the photodetector 14, it is only necessary to have a spectral sensitivity characteristic for detecting light of a predetermined wavelength and a required time response speed. When the optical signal is weak, a high-gain photodetector is used. Further, a time-correlated photon counting method for counting photons may be used. It is desirable that a portion other than the light receiving surface of the photodetector be configured to absorb or block light.

  The signal detector 15 cuts out a predetermined time range from the detection signal and outputs a measurement signal. Specifically, a well-known gate circuit is used. At this time, a gate signal for cutting out a predetermined time range is generated in the signal processing unit 11. In this case, the signal processing unit 11 uses a signal synchronized with the pulsed light emitted from the light source 10 as necessary. The spatial resolution can be controlled by making the time width (gate time) of the gate signal variable. In addition, a part to be measured can be selected by changing the timing of the gate signal. For example, if the tip of the detection signal is extracted by a narrow gate, the light that has propagated through the narrow portion 2a inside the scatterer will be measured. Light will be measured. Further, control as shown in FIGS. 3 and 4 is also possible.

  The acquisition of the above measurement signal may be performed by another method, for example, as shown in FIGS. 7 and 8, directly gated by a photodetector. For example, when a photomultiplier tube is used, a gate operation can be performed by applying a pulsed voltage to the photocathode, the first dynode, another dynode, or the anode. Further, a gate operation can be performed by applying a pulse voltage to the avalanche photodiode. The streak camera also has a time gate function. In these cases, the photoelectric conversion and the gate operation are performed by the same device.

First calculation portion 16 calculates the time from the measurement signal integration value I _T and mean optical pathlength L _T (corresponding to the center of gravity of the waveform (mean time delay)). At this time, the (5) for calculating a mean path length L _T according formula. The above measurement is repeatedly executed at different times. Hereinafter, the m-th measurement and the (m + 1) -th measurement will be considered.

The second arithmetic unit 17 uses the two types of time integration values _{IT, m} and _{IT, m + 1} obtained in the m-th measurement and the (m + 1) -th measurement, and Expression (9). The average optical path length L _T (μ _s , μ _x ) obtained from the two types of average optical path lengths L _{T, m} and L _{T, m + 1} is substituted into the above equation (8), and the scatterer 2 Calculate the variation μ _{a (m + 1)} −μ _am (primary information) of the absorption coefficient of the portion, and further calculate the variation (secondary information) of the absorption component by using the above equation (11). Calculate. At this time, the calculation of the average optical path length L _T (μ _s , μ _x ) can be performed with sufficient accuracy by setting α = 1/2 in the above equation (8). These calculation processes are executed at high speed by a microcomputer or the like incorporated in the first and second calculation units.

  The display recording unit 18 has a function of storing the concentration information of the absorption component obtained as described above, and displays or records them.

  In the above, pulse light of one wavelength is used, but pulse light of two or more wavelengths can be actually used. Furthermore, pulsed light can be incident from one light incident position, and propagation light can be detected at two or more light detection positions. These may be detected in parallel or in a time-division manner.

  Means for making light incident on the scatterer 2 include a method using a condensing lens (FIG. 9A), a method using an optical fiber (FIG. 9B), and a pinhole, instead of the light guide 12 shown in FIG. (FIG. 9 (c)), and a method of entering light from inside the body like a gastroscope (FIG. 9 (d)). Also, a thick beam of light may be incident on the scatterer. In this case, it may be considered that a plurality of spot light sources are arranged.

  As means for detecting light diffused and propagated inside the scatterer 2, in addition to the method using the light guide 13 shown in FIG. 5, a method for directly detecting (FIG. 10A) and a method using an optical fiber (FIG. 10) (B)) and a method using a lens (FIG. 10 (c)).

Example 2
In the first embodiment, measurement is performed by scanning along the scatterer 2 while keeping the relative positional relationship between the light incident position P and the light detection position Q of the pulse light constant (fixed), and the light is absorbed at an arbitrary position. Using the concentration of the component as a reference value, the spatial distribution of the difference between the concentration and the reference value can be measured. In this case, similarly to the first embodiment, the spatial distribution of the difference between the concentration of the absorption component and the reference value can be measured using the equations (8) to (11).

  FIG. 11 shows a second embodiment of the device according to the invention for carrying out the method according to the invention, in which the absorption inside the scatterer 2 such as a breast, which is lightly sandwiched with parallel flat surfaces. 1 shows a configuration of an apparatus 1 for measuring a spatial distribution of component concentrations. In FIG. 11, the same reference numerals are used for those having the same functions as those shown in FIG. 5 according to the first embodiment. Pulse light having a predetermined wavelength λ is incident on the surface of the scatterer 2, and the light that has propagated inside the scatterer 2 is received at the position on the opposite surface. At this time, the light incident position and the light detection position of the pulse light are measured by scanning along the scatterer 2 while keeping their relative positional relationship constant. Then, for example, the concentration of the absorption component when the measurement is performed at the first measurement position (the first light incident position and the first light detection position) can be taken as a reference value (that is, a reference value for measuring the amount of change). For example, the spatial distribution of the concentration difference of the absorption component can be measured.

  In the second embodiment, there is a first mechanism section 30 for lightly holding the scatterer 2 in parallel. That is, the scatterer 2 such as the breast is stretched slightly flat and measured. The first mechanism 30 includes a light incident position (incident portion) and a light detecting position (light receiving portion) of the pulse light while maintaining a relative positional relationship between the light incident position and the light detecting position of the pulse light. A second mechanism 31 is provided for synchronously scanning and measuring along the scatterer. Then, a position signal indicating the scanning position is issued from the second mechanism unit 31, and the position signal is supplied to the display recording unit 18 and used for calculation of spatial distribution and display recording. A wavelength selector 19 is provided downstream of the light source 10 that generates pulsed light so that pulsed light having a desired wavelength can be selected as appropriate. Other parts are the same as those of the device of the first embodiment.

  In the device 1 of the second embodiment, the first part of the output light is extracted by the gate signal. At that time, if the gate time is shortened, the spatial resolution is improved. In the above description, pulsed light having one wavelength is used, but pulsed light having two or more wavelengths can be used in practice. Further, light can be incident from one light incident position, and propagation light can be detected simultaneously or time-divisionally at two or more light detection positions.

Example 3
FIG. 12 shows a third embodiment of the apparatus of the present invention for carrying out the method of the present invention, and shows the configuration of the apparatus 1 for measuring the concentration distribution of the absorption component inside the scatterer 2. In this case, the scatterer 2 such as a breast is lightly sandwiched. In FIG. 12, the same symbols are used for those having the same functions as those shown in FIG. 5 according to the first embodiment and FIG. 11 according to the second embodiment. In the configuration of the apparatus 1, pulse light of _n different wavelengths λ _{1 to} λ n that can be regarded as having the same or equal scattering coefficient with respect to the scatterer 2 is used, and (n) is obtained by using the above equation (17). -1) Imaging of the concentration of the kind of absorbing component can be performed. The third embodiment has a configuration very similar to that of the second embodiment, but the parameter to be measured is the spatial distribution of the concentration of the absorption component. The measurement position (light incident position and light detection position) is scanned. Since the concentration of the absorption component is measured at each scanning position based on the above equation (17), the light incident position (light The relative positional relationship between the incident point) and the light detection position (light receiving point) may change. That is, in the above-described second embodiment, scanning is performed such that the relative positional relationship between the light incident position and the light detection position is fixed with the scatterer 2 interposed in parallel, but the third embodiment is not limited to this. The reason is as described in the above section (Measurement of spatial distribution of concentration of absorption component).

Light source 10 ₁ to 10 _n uses a laser diode, sequentially generates the pulsed light of different wavelengths of n species. At this time, the oscillation timing of the light sources 10 ₁ to 10 _n is controlled by a signal from the signal processing unit 11. The pulse lights from the light sources 10 ₁ to 10 _n are multiplexed by the multiplexer 20 and are incident on the surface of the scatterer 2 to be measured through the light guide 12.

  The space between the light guide 12 and the scatterer 2 is very small in the embodiment of FIG. However, in practice, the space may be widened as in the first embodiment, and this space may be filled with an interface material having a refractive index and a scattering coefficient substantially equal to those of the scatterer 2. That is, the pulse light propagates through the interface material and enters the measurement target, so that no problem occurs. When the surface reflection of the scatterer 2 becomes a problem, the influence of the surface reflection can be reduced by appropriately selecting the interface material.

  The light that has propagated inside the scatterer 2 is received by a light guide 13 located at a position opposite to the light incident position. Here, an interface material may be used for the same reason as described above. The wavelength of the optical signal from the optical guide 13 is selected by the wavelength selector 21, and the optical signal corresponding to the incident pulse light of each wavelength is guided to the next-stage photodetector 14 via the optical guide 13.

  The scatterer 2 is lightly sandwiched by the first mechanism 30 as in the second embodiment. The first mechanism 30 is provided with a second mechanism 31 for synchronously scanning the light incident position of the pulse light and the light detection position. Then, a position signal indicating the scanning position is issued from the second mechanism unit 31, and the position signal is supplied to the display recording unit 18 and used for spatial distribution calculation and display recording of the result.

  The photodetector 14 converts the optical signal of each wavelength into an electric signal, amplifies the electric signal if necessary, and outputs a detection signal. As the photodetector 14, in addition to the photomultiplier tube, a phototube, a photodiode, an avalanche photodiode, a PIN photodiode, a streak camera, a streak scope, an optical oscilloscope, or the like can be used. When selecting the photodetector 14, it is only necessary to have a spectral sensitivity characteristic for detecting light of a predetermined wavelength and a required time response speed. When the optical signal is weak, a high-gain photodetector is used. Further, a time-correlated photon counting method for counting photons may be used. It is desirable that a portion other than the light receiving surface of the photodetector 14 be configured to absorb or block light.

  The signal detector 15 cuts out a predetermined time range from the detection signal and outputs a measurement signal. A gate signal for cutting out a predetermined time range is generated by the signal processing unit 11. The spatial resolution can be controlled by making the time width (gate time) of the gate signal variable, and the spatial resolution is improved by reducing the gate time. For example, when the tip of the detection signal is extracted by a narrow gate, the light that has propagated through the narrow portion 2a inside the scatterer is measured. If the gate time is lengthened, light that has propagated in a portion wider than the portion 2a is measured, and the spatial resolution is reduced. The above measurement signal may be obtained by another method, for example, a method of directly gating with a photodetector as shown in FIGS. 7 and 8 described above.

First calculation portion 16 calculates the time from the measurement signal integration value I _T and mean optical pathlength L _T (corresponding to the center of gravity of the waveform (mean time delay)). In this case, the mean optical pathlength L _T is calculated according to the equation (5). Second arithmetic unit 17, using the extinction coefficient of the said time of n species obtained by the measurement integration value I _T1 ~I _Tn, the mean path length of the n type L _T1 ~L _Tn and n species, The concentration of the (n-1) absorption components contained in the portion 2a inside the scatterer 2 is calculated. These calculation processes are executed at high speed by a microcomputer or the like incorporated in the first and second calculation units.

  Then, the above-described series of measurements is repeated by changing the measurement position by the second mechanism unit 31, and the concentration of the absorption component at each measurement position (light incident position and light detection position) is calculated. The display recording unit 18 has a function of storing the concentrations of the absorption components obtained as described above, and displays or records them.

  In the above case, the method of sequentially inputting pulsed light of n kinds of wavelengths has been described. However, a method of simultaneously turning on pulsed light of n kinds of wavelengths and coaxially inputting the same may be used. In this case, a method of selecting a wavelength by the wavelength selector 21 provided immediately before the photodetector 14, or a method of splitting the detection light into n and selecting the wavelength, and then detecting the light in parallel by n photodetectors are also available. is there.

  Further, in FIG. 12, the scatterer 2 is sandwiched almost in parallel, but the thickness may actually differ as described above. However, in this case, the second mechanism 31 is configured to scan along the surface of the scatterer 2. Further, in FIG. 12, the light incident position and the light detection position are arranged vertically (up and down on the paper surface). Configuration may be performed.

Example 4
FIG. 13 shows a fourth embodiment of the apparatus of the present invention for carrying out the method of the present invention, and shows the configuration of the apparatus for measuring the concentration distribution of the absorption component in the cross section of the scatterer 2. The light incident position (light incident part) and the light detection position (light receiving part) are scanned along the outer periphery of the scatterer 2. In FIG. 13, the same symbols are used for those having the same functions as those shown in FIG. 5 according to the first embodiment, FIG. 11 according to the second embodiment, and FIG. 12 according to the third embodiment. Using. In the configuration of this apparatus, two types of pulsed light having different wavelengths λ ₁ and λ _{2 that} have the same or equal scattering coefficient are used. Then, the concentration of the specific absorption component at each measurement position (the light incident position and the light detection position) is obtained by using the above equation (17), and the density of the scatterer 2 is determined from the concentration values of the specific absorption component at a plurality of measurement positions. The distribution of the concentration of the specific absorption component in the cross section is obtained. The device of the fourth embodiment has a configuration very similar to that of the third embodiment except for the area around the light incident position and the light detection position, but the measurement result is obtained as a tomographic image.

  The scatterer 2 to be measured is placed in a circular rotation mechanism 32 surrounding the scatterer 2. The gap between the scatterer 2 and the inner wall of the rotation mechanism 32 is filled with an interface material 33 so that the rotation mechanism 32 can rotate while the scatterer 2 is fixed. The rotation mechanism 32 is provided with an optical fiber 12 for light incidence and a light guide 13 for light reception. The rotation mechanism unit 32 emits a position signal indicating a scanning position, and the position signal is supplied to the third calculation unit 22 and used for reconstructing a tomographic image.

  The light source 10 uses a laser diode or the like to generate two types of pulsed light having different wavelengths, and the wavelength switch 19 alternately switches and passes the two types of pulsed light. The oscillation of the light source 10 and the switching timing of the wavelength switch 19 are controlled by a signal from the signal processing unit 11. At this time, two types of pulsed light sources having different wavelengths may be alternately turned on. Alternatively, a method of simultaneously inputting two types of pulsed light may be adopted. In this case, the wavelength selector 19 is omitted, and a wavelength selector is provided in front of the photodetector 14 described later to select a wavelength to be used for measurement. .

  The pulse light emitted from the wavelength switch 19 is incident on the surface of the interface member 33 surrounding the scatterer 2 to be measured through the optical fiber 12. The interface member 33 has been described in the first embodiment. The light that has propagated inside the scatterer 2 and the interface member 33 is received by a light guide 13 provided at a position opposite to the light incident position. The optical signal from the light guide 13 is guided to a photodetector 14 at the next stage.

  The photodetector 14 converts the optical signals of the two wavelengths into an electric signal, amplifies the electric signal if necessary, and outputs a detection signal. As the photodetector 14, in addition to the photomultiplier tube, a phototube, a photodiode, an avalanche photodiode, a PIN photodiode, a streak camera, a streak scope, an optical oscilloscope, or the like can be used. When the optical signal is weak, a high-gain photodetector is used. Further, a time-correlated photon counting method for counting photons may be used. It is desirable that a portion other than the light receiving surface of the photodetector 14 be configured to absorb or block light.

  The signal detector 15 cuts out a predetermined time range from the detection signal and outputs a measurement signal. A gate signal for cutting out a predetermined time range is generated by the signal processing unit 11. The spatial resolution can be controlled by making the time width (gate time) of the gate signal variable, and the spatial resolution is improved by reducing the gate time. The acquisition of the measurement signal described above may be performed by another method, for example, a method of directly gating with a photodetector as shown in FIGS. 7 and 8 described above.

First calculation portion 16 calculates the time from the measurement signal integration value I _T and mean optical pathlength L _T (corresponding to the center of gravity of the waveform (mean time delay)). At this time, the average optical path length is calculated according to the above equation (5). The second arithmetic unit 17 uses the two types of time integrated values _IT1 and _IT2 obtained by the above measurement, the two types of average optical path lengths _LT1 and _LT2 , and the two types of extinction coefficients. , The concentration of the specific absorption component at the measurement position is calculated.

  These calculation processes are executed at high speed by a microcomputer or the like incorporated in the first and second calculation units.

  Next, the rotation mechanism 32 is rotated by an appropriate angle to change the measurement position (the light incident position and the light detection position), and the above series of measurements is repeated, and the concentration of the absorption component at each measurement position is repeated. Is calculated. The third calculation unit 22 calculates the concentration distribution (tomographic image) of the absorption component in the cross section from the concentration values of the absorption component at a plurality of measurement positions obtained in this manner.

  The display recording unit 18 has a function of storing the concentration distribution of the absorption components obtained as described above, and displays or records these as tomographic images. For reconstruction of the tomographic image, a method and hardware well known as CT can be used.

  In the above embodiment, the relative positional relationship between the light incident position of the pulsed light and the light detection position is fixed, but the relative positional relationship may be variable. In this case, the sampling density for the scatterer is improved and the number of measurement data is increased, so that the spatial resolution of the tomographic image is improved. Further, the relative positional relationship between the light incident position and the light detection position of the pulse light can be variably controlled in three dimensions to provide a CT for performing three-dimensional analysis.

It is a schematic diagram which shows the track of the photon which propagated inside the scatterer. FIG. 4 is a waveform chart for explaining a measurement signal (cut-out signal) according to the present invention. (A) and (b) are each a schematic diagram showing a relationship between a cutout time and a measured part (a part in a scatterer). (A) and (b) are each a schematic diagram showing a relationship between a cutout timing and a measured part (a part in a scatterer). BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic configuration diagram of an apparatus according to a first embodiment of the present invention. It is a graph which shows the absorption spectrum of hemoglobin and myoglobin. FIG. 9 is a schematic diagram showing another method for obtaining a measurement signal. FIG. 8 is a waveform chart showing a relationship among output light, a gate signal, and a measurement signal in the case of the method shown in FIG. 7. (A)-(d) is a schematic diagram which shows the light-incidence method to a scatterer, respectively. (A)-(c) are each a schematic diagram showing a light receiving method. FIG. 6 is a schematic diagram of the configuration of an apparatus according to a second embodiment of the present invention. FIG. 7 is a schematic diagram of the configuration of an apparatus according to a third embodiment of the present invention. FIG. 11 is a schematic diagram of the configuration of a device according to a fourth embodiment of the present invention.

Explanation of reference numerals

  DESCRIPTION OF SYMBOLS 1 ... Absorption information measuring device, 2 ... Scatterer, 2a ... First part inside a scatterer, 2b ... Second part inside a scatterer, 10, 101 ... 10n ... Light source, 11 ... Signal processing part, 12, DESCRIPTION OF SYMBOLS 13 ... Light guide, 14 ... Photodetector, 15 ... Signal detection part, 16 ... First calculation part, 17 ... Second calculation part, 18 ... Display recording part, 19 ... Wavelength switch, 20 ... , 21: wavelength selector, 22: third operation unit, 30: first mechanism unit, 31: second mechanism unit, 32: rotation mechanism unit, 33: interface material.

Claims (6)

A first step of generating pulsed light of a predetermined wavelength;
A second step of irradiating the pulsed light in a spot shape at a light incident position on a surface of a scatterer that is a measurement target;
A third step of receiving light that has propagated inside the measurement object at a light detection position on the surface of the scatterer;
A fourth step of temporally cutting out a part of the optical signal obtained in the third step and obtaining a measurement signal corresponding to the cut out signal;
The first to fourth steps are repeated at a plurality of different measurement positions while fixing the distance between the light incident position and the light detection position, and the plurality of measurements obtained at the plurality of measurement positions are performed. A fifth step of deriving a time integral and an average optical path length for each of the signals;
A sixth step of calculating a difference in absorption coefficient between the plurality of measurement positions based on a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, and a difference in absorption coefficient;
A method for measuring absorption information of a scatterer, comprising:   Based on a predetermined relationship between the difference in the absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component, and the concentration difference of the absorption component, the absorption component between the plurality of measurement positions is determined. The method for measuring absorption information of a scatterer according to claim 1, further comprising a seventh step of calculating a difference in density of the scatterers.   In the sixth step, the plurality of time integrated values, the plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorption component, and the plurality of the plurality of The method for measuring absorption information of a scatterer according to claim 1, wherein a concentration difference of the absorption component between the measurement positions is calculated. A light source for generating pulsed light of a predetermined wavelength,
A light incident portion that impinges the pulsed light in a spot shape at a light incident position on the surface of a scatterer that is an object to be measured,
A light receiving unit that receives light that has propagated inside the measurement target at a light detection position on the surface of the scatterer,
A signal detection unit that temporally cuts out a part of the optical signal obtained by the light receiving unit and obtains a measurement signal corresponding to the cut out signal,
Perform the measurement to obtain the measurement signal at each of a plurality of different measurement positions while fixing the distance between the light incident position and the light detection position, of the plurality of measurement signals obtained at the plurality of measurement positions A first calculation unit for deriving a time integration value and an average optical path length for each of the first and second calculation units;
A second calculating unit configured to calculate a difference in absorption coefficient between the plurality of measurement positions based on a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, and a difference in absorption coefficient. When,
An apparatus for measuring absorption information of a scatterer, comprising:   The second arithmetic unit further includes a predetermined relationship between the difference between the absorption coefficients obtained by the second arithmetic unit, the absorption coefficient per unit concentration of the absorption component, and the concentration difference between the absorption components. The apparatus according to claim 4, wherein a difference in the concentration of the absorption component between the plurality of measurement positions is calculated. In the second calculation unit, based on a predetermined relationship between the plurality of time integrated values, the plurality of average optical path lengths, an absorption coefficient per unit concentration of the absorption component, and a concentration difference of the absorption component, The apparatus for measuring absorption information of a scatterer according to claim 4, wherein a concentration difference of an absorption component between a plurality of measurement positions is calculated.

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