JP3878943B2 - Method and apparatus for measuring absorption information of scatterers - Google Patents

Description

  The present invention relates to a measurement method and apparatus, an imaging method and apparatus, a fluoroscopy method and apparatus, a tomographic imaging method and apparatus, or a mammography method and 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 apparatus for measuring the temporal change in the concentration of a specific absorption component in a specific portion inside the scatterer and its spatial distribution, and also the specific absorption component inside the scatterer having variously shaped surfaces. The present invention relates to a method and an apparatus for measuring absorption information of a scatterer capable of noninvasively measuring the concentration distribution of the scatterer.

  There are four main methods for measuring or imaging a biological tissue, which is a scatterer, using light. These include (a) using straight photon, and (b) heterodyne detection of coherent components. And (c) using scattered light, and (d) using a time-resolved gate.

(a) In the case of using straight light (baristic photon), pulsed light is incident on a measurement target, and a straight transmission component contained 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 of the output light. Therefore, the straight transmitted light can be detected by cutting out the light that first emerges from the measurement target with the ultra-high speed gate. This method has an advantage that a high spatial resolution like X-ray CT can be expected in principle. However, since almost all light is scattered in a scatterer within the measurement target, there is little or no trace of linearly transmitted component. As a result, the utilization factor of light during measurement becomes extremely poor, and taking into consideration the maximum light incident intensity (about ² mW / mm ² ) that can enter the living body, an extremely long time is required for imaging measurement and the like, which is not practical. In addition, signal light becomes extremely weak for large objects such as the head and arms, and measurement is impossible in practice.

  (b) In the method using a coherent component, coherent high-frequency modulated light is branched, and one is incident on a measurement target. Then, the output light and the other high-frequency modulated light are caused to interfere with each other, the coherent component contained in the output light is heterodyne detected, and the coherent component is used for measurement.

  In other words, in this measurement system, the scattered light is disturbed by changing the flight time (or optical path length) and flight direction according to the degree of scattering, so that the multiple scattered light does not interfere and almost straightly transmitted light is transmitted. Detected. Therefore, in this case as well, in principle, a high spatial resolution is expected as in the previous example, but the light utilization rate is extremely poor, and it is extremely difficult to put it to practical use for measurement and imaging of living bodies. In addition, it is practically impossible to measure large objects such as the head and arms.

  (c) For detecting scattered light, continuous (CW) light, pulsed light, or modulated light is incident on a measurement object, and light (output light) scattered and propagated in the measurement object is detected and used. At this time, when pulse light having a sufficiently short pulse width with respect to the time response characteristic of the measurement target is incident, it may be considered as impulse light incidence, and the corresponding output light is represented by an impulse response. Such measurement is called time-resolved measurement (TRS), and measures internal information by measuring a time waveform of an impulse response. The method of entering continuous (CW) light is called CW measurement, and the measurement of entering modulated light is called phase modulation measurement (PMS). The former measures the time integral value 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 a signal including more information than the other two is obtained in time-resolved measurement (TRS). In addition, the phase modulation measurement (PMS) for sweeping the modulation frequency and the time-resolved measurement (TRS) of the impulse response contain almost the same information. In continuous (CW) measurement and phase modulation measurement (PMS), the signal processing method is greatly different. However, since the obtained signals contain essentially the same information, almost the same information can be measured. Since both methods use almost all output light, the light utilization rate is improved by an order of magnitude compared to the two examples (a) and (b). However, since the scattered light spreads over almost the entire area inside the measurement target or a fairly wide range, the above-described method cannot quantitatively measure a narrow specific part. Also, imaging and optical CT have extremely poor spatial resolution and are difficult to put into practical use.

  On the other hand, (d) those using the time-resolved gate use a part of the impulse response waveform. For example, the photons included in the first part of the time-resolved output signal (impulse response waveform) are photons that are hardly scattered (photons that have not deviated too much), that is, the light incident position (light incident point) and the light detection position. It is a photon that has propagated near the straight optical path connecting (light receiving points). Therefore, if a signal from the time-resolved gate is used, photons that are detected by propagating near the straight optical path can be extracted, and spatial resolution such as imaging can be improved. This limit is the ballistic photon mentioned earlier. However, the time-resolved gate method developed or proposed to date cannot quantitatively measure the absorption component inside the scatterer. This is because a method for analytically describing a signal obtained by the time-resolved gate method has not been developed. That is, there is no known method for analyzing the signal obtained by the time-resolved gate method based on the light diffusion theory and using it for quantifying the absorption component. Even if a method of analysis based on the light diffusion theory is developed, an essential problem caused by the light diffusion theory, that is, measurement of scatterers with various external shapes when diffusion approximation is not established. The problem remains that is impossible. From the above, the time-resolved gate method can improve the spatial resolution, but has a big 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 any case, there is no discussion or suggestion about the 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, DJHall, 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, MDDuncan and J. Reintjes, "Resolution limits forimaging 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 “quantitative measurement of internal information such as absorption components cannot be performed” while taking advantage of the above-mentioned conventional time gate method that “high spatial resolution can be obtained”. To do. Specifically, the present invention has found a method (basic relational expression) for describing the behavior of light inside scatterers having different shapes, and a method for applying this basic relation to the time-resolved gate method, and uses this relation. It is an object of the present invention to provide a method and apparatus for measuring the concentration change and absolute value of a specific absorption component in various shapes of a scatterer without being affected by the outer shape of the scatterer and with high spatial resolution. And the present invention greatly improves the measurement accuracy related to the specific absorption component of the specific portion, and can measure the temporal change and spatial distribution of the living body measurement method and apparatus, imaging method and apparatus, fluoroscopy method, and It is an object of the present invention to provide a method and apparatus for measuring absorption information inside a scatterer such as an apparatus, a tomographic image analysis method and apparatus, or a mammography method and apparatus.

  In the first method for measuring absorption information of a scatterer according to the present invention, a first step of generating pulsed light of a predetermined wavelength, and the pulsed light is spot-shaped at a light incident position on the surface of a scatterer that is a measurement object. A second step incident on the surface of the object to be measured, a third step of receiving the light propagating through the measurement object at a light detection position on the surface of the scatterer, and a part of the optical signal obtained in the third step as time. A fourth step of obtaining a measurement signal corresponding to the cut-out signal, and repeating the first to fourth steps at a plurality of different timings, and a plurality of the plurality of the obtained at the plurality of timings. A fifth step of deriving a time integration value and an average optical path length for each of the measurement signals; and the change amounts 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 among the change amount of the absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component, and the concentration change amount of the absorption component, the plurality of timings You may further provide the 7th step which calculates the variation | change_quantity of the density | concentration of the absorption component produced in the meantime.

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

に基づいて導出することとしてもよい。 According to the second method for measuring absorption information of a scatterer of the present invention, a first step of generating pulsed light of a predetermined wavelength, and the pulsed light is incident on the surface of a scatterer that is a measurement object excluding humans. A second step in which the light is incident in a spot shape at a position; a third step in which light propagated inside the measurement object is received at a light detection position on the surface of the scatterer; and the optical signal obtained in the third step. A portion of the image is temporally extracted at a predetermined extraction timing and extraction time, and a fourth step of acquiring a measurement signal corresponding to the extracted signal is fixed, and the distance between the light incident position and the light detection position is fixed. However, the first to fourth steps are repeatedly performed at a plurality of different measurement positions, and time integration values are respectively obtained for the plurality of measurement signals obtained at the plurality of measurement positions. A fifth step of deriving an average optical path length based on the time integration value and the measurement signal for each of the plurality of measurement signals, the plurality of time integration values, the plurality of average optical path lengths, and an absorption coefficient based on a predetermined relationship between the difference, and a sixth step of calculating the difference in absorption coefficient between the plurality of measurement positions, it is how you comprising: a.
Further, in the fifth step, a second time integrated value obtained by multiplying each of the plurality of measurement signals by a time from a predetermined reference time is derived, and the time integrated value and the second time are calculated. The average optical path length may be derived based on the integral value.
In the fifth step, the scattering coefficient is μ _s , the absorption coefficient is μ _a , the speed of light is c, and the impulse response that is a function of the time t corresponding to the optical signal is s (μ _s , t) exp (− μ _a ct), and when the predetermined extraction timing and extraction time are t = [t1, t2] (t1 <t2), the average optical path length L _T (μ _s , μ _a ) is expressed by the following equation:

It is good also as deriving based on.

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

  Further, in the sixth step, based on a predetermined relationship among the plurality of time integral 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, You may calculate the density | concentration difference of the absorption component between several measurement positions.

  According to the third method for measuring absorption information of a scatterer of the present invention, a first step of generating pulsed light having different wavelengths that can be regarded as being equal to or equal to a scattering coefficient with respect to the measurement object, and the pulsed light to be measured A second step of entering the light incident position on the surface of the scatterer that is an object in the form of a spot; a third step of receiving light propagating through 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 cut out in terms of time, and a measurement signal corresponding to the cut out signal is obtained in such a way that the respective time relationships with the pulsed light of different wavelengths are the same. 4 steps, a fifth step for 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 among the difference in absorption coefficient obtained in the sixth step, the absorption coefficient per unit concentration of the absorption component with respect to the pulsed light of the different wavelength, and the concentration of the absorption component, You may further provide the 7th step which calculates the density | concentration of an absorption component.

  Further, in the sixth step, a predetermined value among the plurality of time integration values, the plurality of average optical path lengths, an absorption coefficient per unit concentration of the absorption component with respect to the pulsed light having the different wavelength, and a concentration of the absorption component Based on the relationship, the concentration of the absorption component may be calculated.

  Further, in the third step, light is received at a plurality of light detection positions, and in the fourth step, measurement signals are respectively acquired corresponding to the pulsed light of different wavelengths at the plurality of light detection positions, and the fifth step In the step, a time integration value and an average optical path length are derived for each of the plurality of measurement signals, and in the sixth step, the plurality of time integration values, the plurality of average optical path lengths, and the different wavelengths of the 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.

  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, and the sixth step is performed for each of the plurality of measurement positions by the scanning. It is also possible to further include an eighth step of calculating the concentration of the absorption coefficient obtained in step (1) to calculate a tomographic image of the concentration distribution in the scatterer.

  The apparatus for measuring absorption information of a first scatterer according to the present invention includes a light source that generates pulsed light of a predetermined wavelength, and the pulsed light is incident in a light incident position on the surface of the scatterer that is a measurement object. A light incident part, a light receiving part that receives light propagating inside the measurement object at a light detection position on the surface of the scatterer, and a part of the optical signal obtained by the light receiving part in time, A signal detection unit that acquires a measurement signal corresponding to the cut out signal, and performs measurement to acquire the measurement signal at a plurality of different timings, and each of the plurality of measurement signals obtained at the plurality of timings Based on a predetermined relationship between the first calculation unit for deriving the time integration value and the average optical path length, and the plurality of time integration values, the plurality of average optical path lengths, and the amount of change in the 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 the amount of change in the absorption coefficient obtained by the second calculation unit, the absorption coefficient per unit concentration of the absorption component, and the concentration change amount of the absorption component. Based on the predetermined relationship, the amount of change in the concentration of the absorption component generated during the plurality of timings may be calculated.

  Further, in the second calculation unit, based on a predetermined relationship among the plurality of time integral values, the plurality of average optical path lengths, an absorption coefficient per unit concentration of the absorption component, and a concentration change amount 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.

に基づいて導出することとしてもよい。 According to the second scatterer absorption information measuring apparatus of the present invention, a light source that generates pulsed light of a predetermined wavelength, and the pulsed light is incident on the light incident position on the surface of the scatterer that is the measurement object. A light incident part, a light receiving part for receiving light propagating inside the measurement object at a light detection position on the surface of the scatterer, and a part of an optical signal obtained by the light receiving part in a predetermined manner over time. At a plurality of different measurement positions while fixing a distance between the light incident position and the light detection position, and a signal detection unit that obtains a measurement signal corresponding to the cut out signal at the cutout timing and the cutout time. each performs measurement for acquiring said measurement signal, the deriving a time integration value for each of the plurality of the plurality of the measurement signals obtained at the measurement position, those for each of the plurality of measurement signals A first arithmetic unit for deriving a temporal mean path length based on the time integration value and the measurement signal, said plurality of time-integrated value, said plurality of mean optical path length, and a predetermined between the difference in absorption coefficient A second computing unit that computes an absorption coefficient difference between the plurality of measurement positions based on the relationship.
Further, the first calculation unit derives a second time integrated value obtained by multiplying each of the plurality of measurement signals by a time from a predetermined reference time, and the time integrated value and the second The average optical path length may be derived on the basis of the time integral value.
In addition, the first arithmetic unit has a scattering coefficient as μ _s , an absorption coefficient as μ _a , a light velocity as c, and an impulse response as a function of time t corresponding to the optical signal as s (μ _s , t) exp. (−μ _a ct), when the predetermined cutting timing and cutting time are t = [t1, t2] (t1 <t2), the average optical path length L _T (μ _s , μ _a ) is as follows: Formula of

It is good also as deriving based on.

  In this case, the second calculation unit further includes a predetermined difference between the absorption coefficient difference obtained by the second calculation unit, the absorption coefficient per unit concentration of the absorption component, and the concentration difference of the absorption component. 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 integral 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 the plurality of measurement positions may be calculated.

  A third scatterer absorption information measuring apparatus according to the present invention includes a light source that generates pulsed light having different wavelengths that can be regarded as being equal to or equal to the scattering coefficient of the measurement object, and the pulsed light is measured by the measurement object. A light incident portion that is incident in a spot shape on a light incident position on the surface of a scatterer; a light receiving portion that receives light propagating through the measurement object at a light detection position on the surface of the scatterer; and the light receiving portion. A signal detector that temporally cuts out a part of the optical signal obtained in step (b) and acquires a measurement signal corresponding to the cut-out signal so that each time relationship with respect to the pulsed light of different wavelengths is the same; A first arithmetic unit that derives a time integral value and an average optical path length for each of the plurality of measurement signals, and a difference between the plurality of time integral values, the plurality of average optical path lengths, and an absorption coefficient; 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 calculation unit further includes a difference in absorption coefficient obtained by the second calculation unit, an absorption coefficient per unit concentration for the pulsed light of the different wavelength of the absorption component, and a concentration of the absorption component The concentration of the absorption component may be calculated based on a predetermined relationship between

  Further, in the second arithmetic unit, the plurality of time integration values, the plurality of average optical path lengths, the absorption coefficient per unit concentration for the pulsed light of the different wavelength of the absorption component, and the concentration of the absorption component The concentration of the absorption component may be calculated based on a predetermined relationship.

  Furthermore, the light receiving unit receives light at a plurality of light detection positions, and the signal detection unit acquires measurement signals corresponding to the pulsed light of different wavelengths at the plurality of light detection positions, respectively. The first calculation unit derives a time integration value and an average optical path length for each of the plurality of measurement signals, and the second calculation unit includes the plurality of time integration values, The concentration of the absorption component is calculated based on a predetermined relationship among the plurality of average optical path lengths, the absorption coefficient per unit concentration of the absorption component with respect to the pulsed light having the different wavelength, and the concentration of the absorption component. It is preferable that there is.

  Further, the light incident position in the light incident part and the light detection position in the light receiving part are scanned along the outer periphery of the scatterer that is a measurement target, and the second calculation is performed for each of the 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 absorption information of a scatterer of the present invention, the concentration change or absolute concentration of a specific absorption component inside a scatterer having an arbitrary shape made of a non-re-incident surface, It becomes possible to measure with high spatial resolution. Therefore, according to the present invention, it is possible to greatly improve the measurement accuracy relating to the specific absorption component of the specific portion, and to measure the temporal change and the spatial distribution with high spatial resolution without being affected by the outer shape of the scatterer. It is possible to provide a biological measurement method and apparatus, an imaging method and apparatus, a fluoroscopy method and apparatus, a tomographic image analysis method and apparatus, or a method and apparatus for measuring absorption information inside a scatterer such as 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 are clarified, and then the principle of the present invention is described.

  In general, the behavior of photons inside a scatterer is analyzed by a light diffusion equation based on the Photon Diffusion Theory. In other words, the behavior of light inside the scatterer is approximated by the light diffusion equation, and by solving this equation, the relationship between the optical characteristics of the measurement object or the optical constant and the output light is obtained, and 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, boundary conditions must be set. However, since the boundary condition largely depends on the shape of the scatterer, in order to perform accurate measurement, it is necessary to set a new boundary condition and solve the light diffusion equation every time the shape of the scatterer changes. However, scatterers that can be set accurately to the extent that there are boundary conditions are limited to extremely simple shapes such as an infinite space, a semi-infinite space, an infinite length cylinder, an infinitely wide finite slab, and a sphere. As a result, it is indispensable to use the approximate boundary condition in measurement of a living tissue or the like whose shape is not simple, which causes a large measurement error. Such problems are described, for example, in recent literature; Albert Cerussiet al. "The Frequency Domain Multi-Distance Method in the Presence of Curved Boundaries, in Biomedical Optical Spectroscopy and Diagnostics, 1996, Technical Digest (Optical Society of America, Washington DC, 1996) pp.24-26.The above problems can be summarized as follows: “A measurement method that can be applied uniformly to scatterers with different shapes has not been developed, and scattering with different shapes has not been achieved in the prior art. It is impossible to accurately measure the concentration of the specific absorption component inside the body in a unified manner.

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

When trying to measure the inside of a scatterer such as a living tissue noninvasively, light is incident on the surface of the scatterer, and the light propagated inside the scatterer is received at other positions 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 photon is strongly scattered by the scattering component inside the scatterer, and its 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) that have traveled through various zigzag optical paths. The 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 speed of light in the medium, and Lambert's law holds. That is, the survival rate of each photon when the absorption coefficient was mu _a becomes exp (-cμ _a t). That is, when a light pulse composed of a large number of photons is incident from position P and received at position Q, many photons that have passed through various optical paths are detected at time t. amount, i.e. the survival rate is proportional to exp (-cμ _a t). In the above description, since the macroscopic refractive index of the living body is a constant value substantially equal to the refractive index of water, the light velocity c is regarded as a constant. Hereinafter, the above fact is referred to as a micro bear Lambert law.

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 is 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 exponent term exp (−μ _a ct) is attenuated by the absorption coefficient μ _a Is a term representing Both functions are time-causal functions that are zero when t <0. In the above, the incidence of impulse light is considered, but it is clear that the above relationship is established for the incidence of pulsed light whose time width is considered to be sufficiently short with respect to the time response of the medium. Therefore, in the following, pulsed light incidence that can be regarded as having a sufficiently short time width will be considered.

Note that the above expression does not include variables related 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 in 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-re-incident 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

It is expressed as Here, b is a coefficient proportional to the intensity of incident light. The time integration of the output signal J (μ _s , μ _a , t) represents the total integrated output signal amount I (μ _s , μ _a ) and corresponds to the measured value at the time of CW measurement. The integrated output signal I (μ _s , μ _a ) is as follows from the equation (2.1).

Now, as shown in FIG. 2, let us consider cutting out an arbitrary part t = [t ₁ , t ₂ ] (t ₁ <t ₂ ) of the output signal J (μ _s , μ _a , t). The integrated output signal, that is, the measurement signal I _T (μ _s , μ _a ) at this time is expressed as 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 time of flight of the detected photons, and L _T (μ _s , μ _a ) is the average optical path length. Such a concept is disclosed for the first time by the present invention. Next, integrating equation (5),

Is obtained. Here, the second and third terms on the right side are integral constants, and are obtained as μ _a = 0 in equation (4.1). Naturally, equation (6) does not include variables related to boundary conditions. This is very different from the solution of the light diffusion equation that always includes variables related to boundary conditions. In the above equation (6), the boundary condition is reflected in the measurement signal I _T (μ _s , μ _a ) and the average optical path length L _T (μ _s , μ _a ). Therefore, Equation (6) can be widely applied to scatterers having various surface shapes that cannot be re-incident.

Here, the following can be understood by considering the track 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 FIGS. 3 (a) and 3 (b). A photon propagated through a narrow portion indicated by a solid line hatch (T ₁ ) is detected, and the spatial resolution is improved. Here, FIG. 3A shows a configuration of transmission type measurement, and FIG. 3B shows a configuration of reflection type measurement. Further, when the cutting time T = t ₂ −t ₁ is increased (T ₁ → T ₂ → T ₃ ), the chain diagonal hatch (T ₂ ) and the chain vertical in FIGS. 3 (a) and 3 (b). As shown by the line hatch (T ₃ ), photons that have sequentially propagated through a wide part are detected, so that the amount of light (or signal amount) used for measurement increases, but the spatial resolution decreases.

Further, when a part of the output signal J (μ _s , μ _a , t) is cut out, if the cut-out timing is delayed, a portion to be measured is shown as shown in FIGS. 4 (a) and 4 (b). It can be changed (t ₁ → t ₂ ). Such measurement can also be realized by measuring the difference between two signals obtained at different time gates. In other words, the fact that the information after the output signal J (μ _s , μ _a , t) is cut out is used to include more peripheral information. Therefore, in the present invention, the segmentation time T = t ₂ −t ₁ and the segmentation timing can be controlled to select a region for obtaining spatial resolution and information.

  However, FIGS. 3A and 3B and FIGS. 4A and 4B are general photon track ranges that occupy a certain proportion of the photons contained in the detection light (output signal). Is shown. Accordingly, the detected photons naturally include photons that have propagated outside the illustrated range.

  Hereinafter, a method for calculating information related to absorption from the measured value using the equation (6) will be described.

(Measurement of concentration change of absorption components)
Consider a case in which one type of absorption component is included in the medium, and its concentration 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 exactly the same as when ink is put into milk. If s (μ _s , t) or the scattering coefficient μ _s does not change before and after the change, if the measurement position (pulse light incident position and light detection position) is fixed and measured, the average optical path length L _T (μ _s , μ _a ) is _a function of the absorption coefficient μ _a , and Equation (6) is established for the measured values before and after the change. Therefore, the following equation is derived from the 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 mean value theorem, the following equation is obtained from equation (7).

However, μ _x is an appropriate value such that 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 between the absorption coefficients before and after the change μ _a2 from the value of the measurement signal I _T (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。 Furthermore, 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. However, α has an appropriate value of 0 ≦ α ≦ 1. In this case, L _T (μ _s , μ _x
) Is a monotone function, and since the values in μ _a1 and μ _a2 are generally equal, α = 1/2 may be set. Also, the average optical path lengths L _T (μ _s , μ _a1 ) and L _T (μ _s , μ _a2 ) are expressed by the centroid (average time) of the waveform of the measurement signal as shown in the above equation (5). It can be obtained by calculating (delay). That is, the value of the equation shown in the second row of the above equation (5) is calculated. Here, since c is the speed of light in the medium, it can be known by a known method or another method. A term included in the numerator and denominator, that is, s (μ _s , t) exp (−μ _a ct) = A is an output signal J (μ _s , μ _a , t) is multiplied by 1 / b. This coefficient b can be taken out of the integration operation and is deleted because it is included in both the numerator and denominator. That is, in the above calculation, the same result can be obtained regardless of whether A is used or the measured value J (μ _s , μ _a , t) which is bA. Therefore, the numerator integrates tJ (μ _s , μ _a , t) and the denominator integrates J (μ _s , μ _a , t) with respect to t from t ₁ to t ₂ , respectively. The calculation of these two terms and their ratio can be performed at high speed using a computer. In addition to the method of calculating the numerator and denominator of the second row of the equation (5) directly as described above, there are various equivalent methods for calculating the center of gravity. In either case, the calculation result is the average flight time, and the average optical path length is obtained by multiplying by c.

In order to calculate the concentration change ΔV of the absorption component, the following equation derived from the Bare-Lambert law 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。 However, ε is an absorption coefficient (or extinction coefficient) per unit concentration of the absorption component, and can be measured with a spectrophotometer. In addition, absorption coefficients (or extinction coefficients) of many absorbing materials are published in various documents. Therefore, from the equations (8) to (10),

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

(Application of concentration change measurement of absorption components)
The above method can be applied to measuring temporal changes in the concentrations of plural types of absorption components using pulsed light having different wavelengths while fixing the measurement position. Furthermore, if such a measurement is repeated at a plurality of locations along the outer periphery 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 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 object held so that the thickness is constant, and the measurement value at an arbitrary position is used as a reference value. By doing so, it is also possible to measure the distribution of the difference with respect to the reference value of the concentration of the absorption component inside the scatterer. Such measurement can be applied to optical mammography for diagnosing breast cancer.

  In the above measurement according to the present invention, the spatial resolution is improved by shortening the gate time (cutout time). Further, the part (or part) to be measured can be controlled by changing the gate timing. Specific application examples include fluoroscopic devices, optical CT, and clinical monitors used for surgery and treatment in addition to optical mammography.

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 case where measurement is performed using two types of pulsed light having wavelengths λ ₁ and λ ₂ , that is, a two-wavelength spectroscopic measurement method will be described. Now, the absorption coefficient of the scattering medium containing one absorptive constituent has the time mu _a1 wavelength lambda _1, and a time mu _a2 wavelength lambda _2. The scattering coefficients μ _s1 and μ _s2 of the medium at the wavelengths λ ₁ and λ ₂ are the same or approximately equal. Such a condition is easily realized by selecting a 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 ,

Is established. And from equation (6)

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

Is obtained. However, μ _x is an appropriate value such that μ _a1 ≦ μ _x ≦ μ _a2 or μ _a1 ≧ μ _x ≧ μ _a2 . This equation (14) is equal to the aforementioned equation (7) when b ₁ / b ₂ = 1, that is, when the incident light intensity of the two-wavelength pulse light is equal. The coefficient b ₁ / b ₂ can be set to b ₁ / b ₂ = 1 by adjusting the intensity of the incident pulse light. Further, the b ₁ / b ₂ value can be estimated by actually measuring the intensity of the light source or pulsed light. As described above, the average optical path length L _T (μ _s , μ _x ) and the value of b ₁ / b ₂ , the measurement signal I _T (λ ₁ ) obtained by the measurement using the pulsed light with the wavelengths λ ₁ and λ ₂ , and From the value of I _T (λ ₂ ), the absorption coefficient difference μ _a2 −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 described above.

It can be expressed as. However, α has an appropriate value of 0 ≦ α ≦ 1. In this case, considering that L _T is monotonic function, usually may be as α = 1/2. Each average optical path length L _T (μ _s , μ _a1 ) and L _T (μ _s , μ _a2 ) is the center of gravity (average time delay) of the waveform of the measurement signal as shown in the above equation (5). ) 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,

Thus, 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 with n wavelengths are used, the concentration 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)
When the two-wavelength spectroscopic measurement is performed at two types of detection distances (light incident-light detection position distance), the above-described coefficients b ₁ / b ₂ can be eliminated. That is, the coefficient b ₁ / b ₂ is erased by utilizing the fact that the coefficient b ₁ / b ₂ does not depend on the light incident-light detection position. In this case, the equation (17) is as follows.

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

(Measurement of spatial distribution of absorption component concentration)
It is possible to measure the spatial distribution of the concentration of the absorption component by performing the above-described measurement at multiple locations. In this case, since the measured value of the concentration of the absorption component is measured independently, the detection distance (light incident-light detection position distance) 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 outer shapes that cannot be reincident with high spatial resolution. At this time, the spatial resolution is controlled by the above-described clipping time T = t ₂ −t ₁ and its timing. Specific application examples include optical mammography, fluoroscopy, and optical CT. In these, methods such as light reception at a plurality of locations, scanning of light incident positions and light detection positions, and time-division measurement are used. Further, image reconstruction calculation as seen in CT is performed as necessary. 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.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. However, in the following description, the same elements are denoted by the same reference numerals, and redundant description is omitted.

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 time change of the concentration of the absorption component inside the scatterer 2. In the configuration of the apparatus 1, the concentration change of the absorption component of the scatterer 2 containing one kind of absorption component or the concentration change of the absorbing material composed of a plurality of components is measured. In this configuration, pulse light having a sufficiently narrow time width of a predetermined wavelength λ is incident on a position P (light incident position) on the surface of the scatterer 2, and the scatterer 2 is detected at another position Q (light detection position) on the surface. Receives light that has propagated inside. Then, this measurement is repeated to quantify the change in the concentration of the absorption component in the relatively narrow portion inside the scatterer 2. In this case, if the concentration of the absorption component at the first measurement is taken as a reference value, the change in the concentration of the absorption component can be quantified. The measuring device 1 is integrated and accommodated 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, deoxygenated hemoglobin, oxygenated, and deoxygenated myoglobin are often measured, and the absorption spectrum of these absorption components is shown in FIG. Therefore, light of 600 nm to 1.3 μm is usually used for living body measurement. The pulse width is usually about 20 ps to 200 ps. In addition to the laser diode, a light emitting diode, a pulse laser, or the like can be used as the light source.

  The pulsed 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, this gap may be widened to fill a liquid or jelly-like object (hereinafter referred to as 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 object, no problem occurs. Further, when the surface reflection of the scatterer 2 becomes a problem, the influence of the surface reflection or the like can be reduced by appropriately selecting the interface material.

  The light propagating through 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. Again, an interface material may be used for the same reason as described above. The photodetector 14 converts the optical signal into an electrical signal, amplifies it as necessary, and outputs it. 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. In 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 correlation photon counting method for counting photons may be used. It is desirable that a place other than the light receiving surface of the photodetector has a structure that absorbs or blocks light.

  The signal detection unit 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. Spatial resolution can be controlled by varying the time width (gate time) of the gate signal. Further, the part to be measured can be selected by changing the timing of the gate signal. For example, when the leading end portion of the detection signal is extracted with a narrow gate, the light propagated through the narrow portion 2a inside the scatterer is measured, but if the gate time is lengthened, the light propagates through the portion 2b wider than the portion 2a. Light will be measured. Further, control as shown in FIGS. 3 and 4 is possible.

  The above measurement signal may be acquired by another method, for example, as shown in FIGS. 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, other dynodes, or the anode. Further, a gate operation can be performed by applying a pulse voltage in the avalanche photodiode. The streak camera also has a time gate function. In these cases, photoelectric conversion and gate operation are performed by the same device.

The first calculation unit 16 calculates a time integration value I _T and an average optical path length L _T (corresponding to the centroid (average time delay) of the waveform) from the measurement signal. At this time, the (5) for calculating a mean path length L _T according formula. The above measurement is repeated at different times. Hereinafter, the m-th and (m + 1) -th measurements will be considered.

The second calculation unit 17 uses the two types of time integration values I _{T, m} and I _{T, m + 1} obtained by the m-th and (m + 1) -th measurements, and the equation (9). By substituting 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} into the above equation (8), Calculate the amount of change in the absorption coefficient μ _{a (m + 1)} −μ _am (primary information) of the part, and use the above equation (11) to calculate the amount of change in the absorption component (secondary information) Calculate. At this time, the calculation of the average optical path length L _T (μ _s , μ _x ) can be obtained with sufficient accuracy when α = 1/2 in the above equation (8). These arithmetic processes are executed at high speed by a microcomputer or the like incorporated in the first and second arithmetic 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 these.

  In the above, pulsed light having one wavelength is used, but in practice, pulsed light having two or more wavelengths can be used. Furthermore, pulsed light can be incident from one light incident position, and propagating light can be detected at two or more light detection positions. These may be detected in parallel or in time division.

  The means for injecting light into the scatterer 2 is a method using a condensing lens (FIG. 9A), a method using an optical fiber (FIG. 9B), a pinhole instead of the light guide 12 shown in FIG. There are a method of using light (FIG. 9C), a method of entering light from the body like a stomach camera (FIG. 9D), and the like. Further, a thick beam of light may be incident on the scatterer. In this case, it can be considered that a plurality of spot-like light sources are arranged.

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

Example 2
In the first embodiment, the 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 pulsed light constant (fixed), and absorption at an arbitrary position. Using the component concentration as a reference value, the spatial distribution of the difference in concentration with respect to the reference value can be measured. In this case, similarly to the first embodiment, the spatial distribution of the difference with respect to the reference value of the concentration of the absorption component 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, the absorption inside the scatterer 2 like a breast lightly sandwiched so as to have parallel flat surfaces. The structure of the apparatus 1 which measures the spatial distribution of the density | concentration of a component is shown. In FIG. 11, the same symbols 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 receives the light propagated through the scatterer 2 at the position of the opposite surface. At this time, the light incident position and the light detection position of the pulsed light are measured by scanning along the scatterer 2 while keeping their relative positional relationship constant. 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 set to the reference value (that is, the reference value for measuring the change amount). 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 unit 30 for lightly sandwiching the scatterer 2 in parallel. That is, the scatterer 2 such as a breast is stretched slightly flat and measured. The first mechanism unit 30 includes the light incident position (incident part) and the light detection position (light receiving part) of the pulsed light while keeping the relative positional relationship between the light incident position and the light detecting position of the pulsed light constant. A second mechanism 31 for scanning and measuring along the scatterer is provided. Then, a position signal indicating a scanning position is emitted from the second mechanism unit 31 and this position signal is supplied to the display recording unit 18 and used for calculation of spatial distribution and display recording. Further, a wavelength selector 19 is provided after the light source 10 for generating pulsed light so that pulsed light having a desired wavelength can be appropriately selected. Other parts are the same as those of the apparatus of the first embodiment.

  In the apparatus 1 of the second embodiment, the first part of the output light is extracted by the gate signal, but if the gate time is narrowed at that time, the spatial resolution is improved. In the above description, pulsed light having one wavelength is used, but in practice, pulsed light having two or more wavelengths can be used. Furthermore, light can be incident from one light incident position, and propagation light can be detected simultaneously or in time division 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, with reference to pulse light having a wavelength lambda ₁ to [lambda] _n different n types scattering coefficient can be regarded as equal to or equal to, supra (17) against the scatterer 2 (n -1) It is possible to perform imaging of the concentration of species absorbing components. The third embodiment has a configuration 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, but the concentration of the absorption component is measured at each scanning position based on the above equation (17). The relative positional relationship between the incident point) and the light detection position (light receiving point) may change. That is, in the second embodiment, scanning is performed so that the relative position relationship between the light incident position and the light detection position is fixed with the scatterer 2 sandwiched in parallel. However, in the third embodiment, there is no such limitation. The reason for this is as described in the previous section (Measurement of Spatial Distribution of Absorbing Component Concentration).

The light sources 10 ₁ to 10 _n use laser diodes or the like, and sequentially generate pulse lights having different n types of wavelengths. 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. Pulse light from the light sources 10 ₁ to 10 _n is multiplexed by the multiplexer 20 and 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, it 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, since the pulsed light propagates through the interface material and enters the measurement object, no problem occurs. Further, when the surface reflection of the scatterer 2 becomes a problem, the influence of the surface reflection or the like can be reduced by appropriately selecting the interface material.

  The light propagating through the scatterer 2 is received by a light guide 13 placed at a position opposite to the light incident position. Again, an interface material may be used for the same reason as described above. The optical signal from the light guide 13 is wavelength-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 through the light guide 13.

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

  The photodetector 14 converts the optical signals of the respective wavelengths into electrical signals, amplifies them as necessary, and outputs detection signals. 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. In 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 correlation photon counting method for counting photons may be used. It is desirable that a place other than the light receiving surface of the photodetector 14 has a structure that absorbs or blocks light.

  The signal detection unit 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 in the signal processing unit 11. Spatial resolution can be controlled by varying the time width (gate time) of the gate signal. If the gate time is narrowed, the spatial resolution is improved. For example, when the leading end portion of the detection signal is extracted with a narrow gate, the light propagated through the narrow portion 2a inside the scatterer is measured. When the gate time is lengthened, the light that has propagated through a portion wider than the portion 2a is measured, and the spatial resolution is lowered. The above measurement signal may be obtained by another method, for example, a method of directly gating with a photodetector as shown in FIGS.

The first calculation unit 16 calculates a time integration value I _T and an average optical path length L _T (corresponding to the centroid (average time delay) of the waveform) from the measurement signal. In this case, the mean optical pathlength L _T is calculated according to the equation (5). The second calculation unit 17 uses the n types of time integration values I _{T1 to} I _Tn obtained by the measurement, the n types of average optical path lengths L _{T1 to} L _Tn, and the n types of extinction coefficients. The concentration of (n-1) types of absorption components contained in the portion 2a inside the scatterer 2 is calculated. These arithmetic processes are executed at high speed by a microcomputer or the like incorporated in the first and second arithmetic units.

  Then, the measurement position is changed by the second mechanism unit 31 and the above series of measurements is repeated, 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 concentration of the absorption component obtained as described above, and displays or records these.

  In the above case, the method of sequentially entering the pulsed light of n types of wavelengths has been described. However, it is also possible to turn on the pulsed light of the n types of wavelengths at the same time and make it incident coaxially. In this case, there is also a method of selecting a wavelength with the wavelength selector 21 provided immediately before the photodetector 14, and a method of detecting in parallel with n photodetectors after branching the detection light into n and selecting the wavelength. is there.

  In FIG. 12, the scatterer 2 is sandwiched almost in parallel. However, as already described, the thickness may actually be different. However, in this case, the second mechanism unit 31 is scanned along the surface of the scatterer 2. Further, in FIG. 12, the light incident position and the light detection position are arranged vertically (in the vertical direction of the paper surface), but image reconstruction such as CT is also performed including data measured by arranging these in an oblique positional relationship. 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 an 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 components 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 can be regarded as being equal or equal in scattering coefficient are used. And the density | concentration of the specific absorption component in each measurement position (light incident position and light detection position) is calculated | required using said (17) Formula, From the density | concentration value of the specific absorption component in a several measurement position, the scattering body 2 is obtained. Obtain the concentration distribution of the specific absorption component in the cross section. The apparatus according to the fourth embodiment has a configuration similar to that of the third embodiment except for the vicinity of 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. An interface material 33 is packed in the gap between the scatterer 2 and the inner wall of the rotation mechanism unit 32 so that the rotation mechanism unit 32 can rotate while the scatterer 2 is fixed. The rotating mechanism 32 is provided with an optical fiber 12 for light incidence and a light guide 13 for light reception. A position signal representing the scanning position is emitted from the rotation mechanism section 32, and this position signal is supplied to the third calculation section 22 and used for reconstruction of 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 timing 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 pulse light sources having different wavelengths may be alternately turned on. Alternatively, two types of pulsed light beams may be simultaneously incident. 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 pulsed light emitted from the wavelength switch 19 is incident on the surface of the interface material 33 that encloses the scatterer 2 to be measured through the optical fiber 12. The interface material 33 has already been described in the first embodiment. The light propagating through the scatterer 2 and the interface material 33 is received by the light guide 13 provided at a position opposite to the light incident position. The optical signal from the light guide 13 is guided to the photodetector 14 at the next stage.

  The photodetector 14 converts the optical signals of the two types of wavelengths into electrical signals, amplifies them as necessary, and outputs detection signals. 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 correlation photon counting method for counting photons may be used. It is desirable that a place other than the light receiving surface of the photodetector 14 has a structure that absorbs or blocks light.

  The signal detection unit 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 in the signal processing unit 11. Spatial resolution can be controlled by varying the time width (gate time) of the gate signal. If the gate time is narrowed, the spatial resolution is improved. The above measurement signal may be obtained by another method, for example, a method of directly gating with a photodetector as shown in FIGS.

The first calculation unit 16 calculates a time integration value I _T and an average optical path length L _T (corresponding to the centroid (average time delay) of the waveform) from the measurement signal. At this time, the average optical path length is calculated according to the equation (5). The second calculation unit 17 uses the two types of time integration values I _T1 and I _T2 obtained by the measurement, the two types of average optical path lengths L _T1 and L _T2 , and two types of extinction coefficients. The concentration of the specific absorption component at the measurement position is calculated.

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

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

  The display recording unit 18 has a function of storing the concentration distribution of the absorption component obtained as described above, and displays or records these as a tomographic image. Note that a technique or hardware well known as CT can be used to reconstruct the tomographic image.

  In the above embodiment, the relative positional relationship between the light incident position of the pulsed light and the light detection position is made constant. However, the relative positional relationship may be made 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. Furthermore, the relative positional relationship between the light incident position and the light detection position of the above-described pulsed light can be variably controlled in three dimensions to obtain a CT that performs three-dimensional analysis.

It is a schematic diagram which shows the track of the photon which propagated the inside of the scatterer. It is a wave form diagram for demonstrating the measurement signal (signal cut out) concerning this invention. (A) And (b) is a schematic diagram which shows the relationship between the cutting time and the part (part in a scatterer) measured, respectively. (A) And (b) is a schematic diagram which respectively shows the relationship between a cutting-out timing and the measured part (part in a scatterer). 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. It is a schematic diagram which shows the other method for obtaining a measurement signal. It is a wave form diagram which shows the relationship between the output light at the time of the method shown in FIG. 7, a gate signal, and a measurement signal. (A)-(d) is the schematic which shows the light-injection method to a scatterer, respectively. (A)-(c) is the schematic which shows the light-receiving method, respectively. It is a structure schematic of the apparatus of 2nd Example concerning this invention. It is a block schematic diagram of the apparatus of 3rd Example concerning this invention. It is a block schematic diagram of the apparatus of 4th Example concerning this invention.

Explanation of symbols

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

Claims (10)

A first step of generating pulsed light of a predetermined wavelength;
A second step in which the pulsed light is incident in a spot shape on a light incident position on the surface of a scatterer that is a measurement object excluding a human ;
A third step of receiving the light propagated inside the measurement object at a light detection position on the surface of the scatterer;
A fourth step in which a part of the optical signal obtained in the third step is temporally cut out at a predetermined cut-out timing and cut-out time, and a measurement signal corresponding to the cut-out signal is acquired;
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 a plurality of the measurements obtained at the plurality of measurement positions are performed. A fifth step of deriving a time integral value for each of the signals and deriving a temporal average optical path length based on the time integral value and the measurement signal for each of the plurality of measurement 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 integral values, the plurality of average optical path lengths, and the difference in absorption coefficient;
Measurement method of absorption information of that scattering bodies be characterized in that it comprises a.
  In the fifth step, a second time integrated value obtained by multiplying each of the plurality of measurement signals by a time from a predetermined reference time is derived, and the time integrated value and the second time integrated value are derived. The method of measuring absorption information of a scatterer according to claim 1, wherein the average optical path length is derived based on:   In the fifth step, the scattering coefficient is μ _s , Μ _a , The speed of light c, and the impulse response as a function of time t corresponding to the optical signal s (μ _s , T) exp (−μ _a ct), when the predetermined cut-out timing and cut-out time are t = [t1, t2] (t1 <t2), respectively, the average optical path length L _T (Μ _s , Μ _a )

3. The method for measuring absorption information of a scatterer according to claim 2, wherein the absorption information is derived based on the scatterer. Based on a predetermined relationship among the difference in 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 The method for measuring absorption information of a scatterer according to any one of claims 1 to 3 , further comprising a seventh step of calculating a difference in concentration of the scatterer. In the sixth step, based on a predetermined relationship among the plurality of time integral 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 method for measuring absorption information of a scatterer according to any one of claims 1 to 3 , wherein a concentration difference of absorption components between measurement positions is calculated. A light source that generates pulsed light of a predetermined wavelength;
A light incident portion that incidents the pulsed light in a spot shape on a light incident position on the surface of a scatterer that is a measurement object;
A light receiving unit that receives light propagating through the measurement object at a light detection position on the surface of the scatterer; and
A signal detection unit that obtains a measurement signal corresponding to the cut out signal by cutting out a part of the optical signal obtained by the light receiving unit temporally at a predetermined cutout timing and cutout time ;
The measurement is performed by acquiring the measurement signals at a plurality of different measurement positions while fixing the distance between the light incident position and the light detection position, and a plurality of the measurement signals obtained at the plurality of measurement positions are measured. A first calculation unit that derives a time integral value for each of the plurality of measurement signals, and derives a temporal average optical path length based on the time integration value and the measurement signal for each of the plurality of measurement signals ;
A second computing unit that computes an absorption coefficient difference between the plurality of measurement positions based on a predetermined relationship among the plurality of time integration values, the plurality of average optical path lengths, and the difference in absorption coefficient; When,
An apparatus for measuring absorption information of a scatterer, comprising:   The first calculation unit derives a second time integrated value obtained by multiplying each of the plurality of measurement signals by a time from a predetermined reference time, and calculates the time integrated value and the second time. The apparatus for measuring absorption information of a scatterer according to claim 6, wherein the average optical path length is derived based on an integral value.   The first arithmetic unit calculates a scattering coefficient by μ. _s , Μ _a , The speed of light c, and the impulse response as a function of time t corresponding to the optical signal s (μ _s , T) exp (−μ _a ct), when the predetermined cut-out timing and cut-out time are t = [t1, t2] (t1 <t2), respectively, the average optical path length L _T (Μ _s , Μ _a )

The scatterer absorption information measuring apparatus according to claim 7, wherein the scatterer absorption information is derived on the basis of The second calculation unit is further based on a predetermined relationship among the difference in absorption coefficient obtained by the second calculation unit, the absorption coefficient per unit concentration of the absorption component, and the concentration difference of the absorption component. The apparatus for measuring absorption information of a scatterer according to any one of claims 6 to 8 , wherein a difference in concentration of an absorption component between the plurality of measurement positions is calculated. In the second calculation unit, based on a predetermined relationship among the plurality of time integral 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 any one of claims 6 to 8 , wherein a concentration difference of an absorption component between a plurality of measurement positions is calculated.

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