JP2956777B2 - Biological light measurement method and device therefor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a biological light measurement method, that is, a method for non-invasively measuring a shape or function inside a living body using light of a visible to infrared wavelength. The present invention relates to an apparatus therefor.

[Conventional technology]

In current clinical medicine, it is possible to determine various diseases from morphometric data of internal organs and organs. Recent advances in diagnostic imaging equipment such as ultrasonic diagnostic equipment and X-ray CT equipment have made it possible to detect such morphological abnormalities associated with diseases with considerable accuracy. For this reason, morphological diagnosis is
It has become a very important diagnostic technique. However, abnormalities in metabolic functions precede the morphological abnormalities of the organs accompanying the occurrence of the disease, and when the morphological abnormalities are found, the disease has already progressed and treatment is difficult. Often it is.

Therefore, recent medical research aims at the early diagnosis before morphological abnormalities occur, and the improvement of the cure rate by early treatment, and therefore, there is a strong demand for the development of medical diagnostic devices capable of early diagnosis. Have been. It is necessary for such an early diagnosis device to have a function of grasping changes in metabolic functions prior to morphological changes at an early stage.

By the way, as a medical diagnostic device capable of diagnosing a metabolic function, there is a sample test device for blood, urine and the like. The sample test is a diagnostic device for direct metabolic function because a metabolite collected from a living body is chemically measured. But,
Because the test is performed by collecting a part of the tissue circulating in the body, such as blood and urine, systemic abnormalities can be measured,
It is difficult to determine which part of the body is causing this abnormality by this test.

For this reason, at present, a clinician uses a morphological diagnosis represented by X-rays and a functional diagnosis such as a sample test together in diagnosing a patient, and judges the disease comprehensively based on both information. ing. However, performing such two types of diagnosis increases the time required for the diagnosis and the physical or economic burden on the patient. Further, it is not easy to accurately judge the position and situation of an abnormal organ by integrating image information in morphological diagnosis and information on metabolism such as a specimen test which does not directly correspond to the image information.

By the way, it is well known that light ranging from visible to infrared is wavelength-specifically absorbed by metabolites. For example, cytochrome aa3 important for oxygen metabolism has a specific light absorption band at 830 nm. Specimen testing makes great use of such light absorption. Therefore, by irradiating the living body with light having such characteristics at an appropriate wavelength, a transmission image as in an X-ray imaging apparatus can be obtained, and the distribution of metabolites may be captured as an image. . Thus, it is expected that a new advanced medical diagnostic apparatus (biological light measurement apparatus) having both functional diagnostic ability and morphological diagnostic ability will be obtained. Further, light in this wavelength range causes less damage to a living body and is less invasive, which is also a characteristic of this diagnostic apparatus.

Such a "biological diagnosis method using light" has already been proposed in, for example, Japanese Patent Application Laid-Open Nos. 57-115232 and 60-72542. The former proposes a method of irradiating a living body with light having a relatively long wavelength and measuring a change in function in the living body, and the latter involves replacing an X-ray source in an X-ray CT apparatus with light. This proposes a device for measuring a function distribution on a tomographic plane of a living body.

[Problems to be solved by the invention]

The biggest problem with conventional biophotography is that light emitted through a living body is more strongly affected by dispersion at the body surface and in various parts of the body than light absorption by metabolites to be contrasted. Information about the absorption by the metabolite cannot be extracted. This makes it difficult to obtain a satisfactory metabolite distribution image.

An object of the present invention is to provide a method and an apparatus for examining a living body, which can more accurately extract data on absorption of a specific metabolic substance in an object.

Another object of the present invention is to provide a biological light inspection method and apparatus that can set an accurate time gate according to the shape of an object.

[Means for solving the problem]

A feature of the present invention is that, in order to measure the distribution of a specific metabolism-related substance distributed in a living body, the first wavelength within the specific absorption wavelength range of the substance is the first light pulse, and the first light pulse. A second light pulse of a second wavelength in the vicinity of the wavelength is sequentially irradiated, and for each light pulse, the light amount in the gate for a specific time period among the light amounts passing through the living body and detected at a specific light receiving position is determined. Detecting respective integral values, calculating a ratio of a first integral value corresponding to the first light pulse incidence to a second integral value corresponding to the second light pulse incidence, and calculating a distribution of the specific metabolite; In that it is used as data for obtaining As a method of applying the time gate, a high-speed optical shutter is provided at the light receiving position, and the optical shutter is controlled in relation to the generation timing of each optical pulse to guide light to the photodetector only for a specific period. A method and a method of recording the optical detection output corresponding to each optical pulse while sweeping it at a high speed, and obtaining an integral value in a specific time domain of the obtained output waveform (optical time spectrum). There is. The recording of the light detection output waveform in the latter can be realized by a so-called streak camera in which the detection light at the light receiving position is introduced into the photocathode and the electron beam from the photocathode to the anode is swept by an electric field.

More specifically, the measurement using the above two types of light pulses is repeated while changing the light emitting position and the light receiving position within a specific plane, thereby obtaining projection data from a plurality of angles regarding the difference in absorption. Based on the projection data, a tomographic image showing the distribution of the target metabolite in the subject is reconstructed by a computer tomography technique. Reconstruction methods for tomographic images include a convolution method in which convolution integration is performed on each projection data and then backprojection calculation, or a Fourier transform of each projection data, and a filter function in the spatial frequency domain is applied, followed by inverse processing. Various algorithms used in an X-ray CT apparatus, such as a one-dimensional Fourier transform method of performing a Fourier transform, performing a reverse Fourier transform after applying a filter function in a spatial frequency range, and performing a back projection operation using the Fourier transform, can be applied.

[Action]

A light beam from the visible light to the infrared region used in the present invention is different from an X-ray beam in that it is strongly coherently scattered everywhere in a living body. Therefore, even if the transmitted light is detected simply on the optical path of the light beam using the position immediately after the subject as the light receiving position, the scattered light from the subject is mixed in the detected light, so Information on the absorption of the target metabolite is not available. However, certain metabolites, such as cytochromes, have specific peaks in the light absorption spectrum, whereas such peaks do not exist in the light scattering spectra of various parts of the body containing the substance. Therefore, data relating to attenuation of light due to absorption by the metabolite can be extracted from the difference between the two wavelengths of the present invention described above. Further, by introducing a time gate at the time of measurement of each wavelength, light passing through an optical path bypassing refraction and scattering can be excluded, and only a signal transmitted through a linear optical path having a specific width can be extracted. Therefore, according to the present invention, a metabolite distribution image having sufficient resolution for use in diagnosis can be obtained.

〔Example〕

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

FIG. 1 is a configuration diagram of a biological light measurement device showing one embodiment of the present invention. The configuration of this apparatus is similar to an X-ray CT apparatus except for a light source unit and a light detection unit, and has a scanning mechanism similar to that of a third-generation type X-ray CT apparatus. That is, as shown in the figure, the light irradiating unit includes the light source unit 1, the optical system
9, a rotating mirror 8, and the light detecting section includes a light detector 2, an optical shutter 3, and a measuring circuit 6. These light irradiation unit and light detection unit are mounted on a gantry 17 that can be driven to rotate. The projectile 10 is inserted into a central space of the gantry 17. Reference numeral 4 denotes a time control unit for controlling the light source unit 1 and the optical shutter 3. Reference numeral 7 denotes a data collection unit for storing measurement data. Reference numeral 5 denotes a unit for processing the measurement data stored in the data collection unit 7. 2 shows a computer that controls the control unit 4 and the data collection unit 7.

 Next, details of the function of each unit will be described.

The light source unit 1 is composed of a laser light emitting device capable of repeatedly irradiating pulse light having a narrow time width, and is capable of sequentially switching and emitting two types of pulse light having different wavelengths. In addition, the light source unit 1 can repeatedly irradiate the object 10 with pulsed light having a time width of 100 psec or less according to an instruction of the time control unit 4 as described later. As the wavelength of the irradiation laser light, a first wavelength within the specific absorption wavelength range of the biological metabolite to be measured and a second wavelength in the vicinity thereof are alternately selected and used. For example, when measuring reduced hemoglobin in blood, it is the specific absorption wavelength of this substance. 760nm and its vicinity (for example, 800n
Use the wavelength of m).

As described above, the amount of attenuation due to the transmission of light of two different wavelengths is measured, and the ratio between the measured values obtained by the two is determined, whereby the amount of attenuation due to scattering can be removed from the amount of attenuation. This utilizes the fact that when the wavelength difference between the two wavelengths is sufficiently small, the attenuation due to the scattering between the two wavelengths can be considered to be substantially the same.

When the wavelength difference between the two wavelengths cannot be made sufficiently small, for example, the change in the absorption spectrum of the biological substance to be measured due to the wavelength is small, the difference in the absorption coefficient between the two wavelengths in the vicinity is small, and the difference in the absorption attenuation is small. It may not be possible to obtain large. In the above situation, two types of wavelengths having a large difference in absorption coefficient are selected, and one wavelength between the two wavelengths is selected, and a total of three wavelengths are irradiated and measured.
It is desirable to eliminate the scattering effect by performing an operation between three types of measurement values obtained by measurement at each wavelength.

Also, by measuring the concentration of oxygenated hemoglobin simultaneously with the reduced hemoglobin and calculating the ratio of the two, the so-called oxygen saturation of hemoglobin can be obtained. The oxygen saturation is an amount indicating the supply state of oxygen to the living tissue, and by measuring this, a change in the function of the living body can be accurately detected. In this case, the specific absorption wavelength has a difference in absorption coefficient between both hemoglobins. For example, measurement at a wavelength of 650 nm and measurement at a wavelength of, for example, 805 nm, which show the same absorption coefficient for both hemoglobins, are required. Furthermore, in order to remove the above-mentioned effects of scattering, obtain measurement data using an optical pulse at 650 nm and measurement data using an optical pulse with a wavelength in the vicinity of the data, and take the ratio between the two data. It is necessary to obtain measurement data by a pulse and measurement data by a measurement pulse with an optical pulse having a wavelength in the vicinity of the pulse, and to take a ratio between the two data, so that measurement by an optical pulse with a total of four wavelengths is required.

Note that the wavelength of the laser light used in this embodiment is less scattered in living tissue, and less absorbed by water.
It is desirable to select within the range of 11300 nm.

The optical system 9 has a function of shaping light from the light source unit 1 into a parallel beam having a small cross section. Rotating mirror 8
Rotates under the control of the computer 5, and operates so that the laser beam scans the entire area of the object 10. By these,
The light from the light source unit 1 is shaped into a parallel beam with a small cross section, reflected by the rotating mirror 8 and incident on the object 10.

The time sequence of the above-described irradiation light, the opening and closing of the optical shutter described later, an example of the signal waveform in the light detection unit, etc.
Shown in the figure. As described above, light irradiation is performed at two wavelengths (λ ₁ , λ
₂ ) is alternately switched, and measurement is performed in units of two sets of measurements using pulsed light of these two wavelengths. As shown in FIG. 2, the optical shutter 3 opens at a timing td to be described later from the rise of the irradiation pulse light, and closes with a width of tw. Thus, it is possible to selectively measure only the light that has entered the gate for a set time from the light that has reached the photodetector.

Here, the intensity of the pulse light at each measurement is controlled by the computer 5 so as to be an optimal light irradiation amount. This optimum control is performed so that the total amount of light after passing through the object is substantially uniform in all the photodetector elements. That is, when there is a light beam near the center of the object, the amount of irradiation is increased, and at the periphery of the object, the amount of irradiation is reduced. This control is performed based on the data of the shape of the projecting object measured in advance. Furthermore, it is desirable to repeat the measurement set by the same photodetector element using pulsed light of different wavelengths a plurality of times and to improve the measurement accuracy by averaging.

 Return to the description of the function of each unit.

The photodetector 2 is composed of, for example, a high-sensitivity multi-element photodetector such as a CCD. At the time of measurement of an object, the center of the light beam is set at the position of, for example, the i-th element of the light detection element, and the pulse light of the two wavelengths (λ ₁ , λ ₂ ) is set to 1
Irradiate each time. The i-th optical shutter for each of them is opened, and the photodetector accumulates the light amount during each incident period as a charge amount. Each time the accumulation is completed, the measurement circuit 6
As a result, the charge amount is read out, and data indicating the integral value of the light amount during the period in which the optical shutter is open is sequentially obtained. These are subjected to A / D conversion by the above-mentioned data collection unit 7 and stored as data of a single measurement set of the i-th element. In other words, 2 corresponding to one measurement set of one element
Data are obtained. Further, as described above, a plurality of measurement sets may be performed in response to this one measurement. In this case, data measured by the plurality of measurement sets is averaged to one set. Save as data.

The above measurement is performed for all the elements starting from the element at i = 1, and this is set as projection data in one angle direction of CT. Next, like the third generation X-ray CT,
Rotate the gantry 17 around the projectile by a certain angle,
The above measurement is repeated. By performing such rotation scanning of the entire detector system for 360 °, all data as CT can be obtained.

 Next, the function of the optical shutter 3 will be described.

On the front surface (light incident side) of each detector element, an individually controllable optical shutter 3 is arranged corresponding to each element. The optical shutter 3 operates so that light is incident on the detector element for a predetermined gate width. In this embodiment, a CS ₂ car (Ker
r) Use an electro-optical element that can operate at high speed, such as a cell. The time control unit 4 described above, according to an instruction from the computer 5,
Only the optical shutter of the detector element corresponding to the central axis of the irradiation beam is opened at the optimum timing, and the shutters of the other elements are kept closed. The timing of opening and closing the optical shutter is based on the previously measured object shape (particularly,
Set to the optimal time value obtained from (passage thickness).

The opening / closing timing of the optical shutter will be described with reference to FIG. In the Itay 10, when the light beam is in the position indicated by the solid line, of the light reaching the opposing detector, when the minimum value of the time delay from the start of the irradiation of the pulsed light is t _d, t _d is the following formula Is shown.

Here, a distance the rotating mirror surface and the light detector w: distance portion through which light passes to the morphism body c: speed of light in air c _1: speed of light t _p in a subject hurts: a light source In other words, when the time origin is the rising edge of the light pulse from the light pulse to the rotating mirror surface, the signal light should not reach the photodetector before time td, and the light incident before this time is noise. is there. Since t and t _p are determined by the apparatus and are known, the value of t _d can be calculated by obtaining w from the cross-sectional shape of the subject. Thereby, the optical shutter 3 may be opened at a time delayed by t _d from the optical pulse rise of the light source. Between passing through the object morphism body, to repeat a number of times of scattering light, many of the incident light, and reaches the optical shutter 3 later than the time t _d. This delay time differs depending on the width (w) of the area through which light passes. That is, as the light greatly deviates from the center of the light beam, passing distance becomes long, the optical shutter 3, the light that has reached at _{t d <t <t d +} t w becomes time t, and the center axis of the light beam Only light that has passed through the limited area described above. Now, if the time zone of the "open" optical shutter 3 is set to t _d ~t _d + t _w, only the light which has passed through the restricted certain width center axis and the center of the light beam selectively take out be able to. As a result, it is possible to eliminate the influence of scattered light and to limit the light passband except for light that has largely bypassed (refracted), so that it is possible to apply an image reconstruction method using the same CT algorithm as before. Become.

For example, if you give a certain time gate width t _w, light b which is out of the region having a width U shown in Fig. 4, the running time is long, but can not reach the light shutter 3 within the time of the above t _w, light a that passes through the area of the width U is an optical shutter 3 can pass in time of t _w. By setting _{tw in} this manner, the pass band width of light incident on the photodetector 2 can be limited. The passband width U, e.g., in a 10mm may be set above the t _w to a value of few 10p seconds. This means that t _w = U / c ₁ , c ₁ = 3 × 10 ⁸ /1.3 (m / sec) = 2.3 × 10 ⁸ (m
/ sec). As described above, _tw is determined according to the optical path width to be limited, but is set wider than the pulse width of the light pulse to be irradiated in order to obtain a sufficient light detection output. Such a response of several tens of seconds can be realized by the optical shutter using the Kerr cell described above.

As described above, in order to set the time gate by the optical shutter and remove the scattered light and limit the light passage area, as described above, the travel distance of the light passing through the object and the It is necessary to know the speed of light inside the body in advance. In order to realize this, in the living body optical measurement device of the present embodiment, the shape of each object is measured before the original measurement of the object. Hereinafter, an example is shown.

First, an object is placed at the center of the apparatus. Next, with the optical shutters 3 on the front of the photodetector 2 all being in the open state, a CT-like optical scan and a detector scan are performed to detect a plurality of projections indicating the external shape of the subject. That is, the laser beam is scanned within a certain angle by changing the angle of the mirror 8, and each element of the photodetector 2 successively detects the presence or absence of light attenuation by the subject. As a result, projection data represented by binary values “0” and “1” is obtained. The above measurement is repeated at a plurality of angles while rotating the gantry 17. On the other hand, the data collection unit 7 superimposes a sector shape for each projection from each light source (mirror) position at each angle on the two-dimensional memory indicating the slice plane by AND logic. As a result, data indicating the cross-sectional shape of the subject is left on the memory. From the cross-sectional shape of the subject thus obtained, the distance through which the light beam passes through the subject is obtained. This is determined by simple geometric calculations. Note that the speed of light inside the object is almost the same as that of the living body as the object.
Since it is composed of 70% water, it can be approximated by the speed of light in water. This speed c ₁ is, as described above, c ₁ = c / 1.
3 (1.3 is the refractive index of water).

And the object to be painful passing distance of the light beam obtained by the above procedure, the speed c ₁ of the light, determining an optimum time gate settings td using equation (1) above. The cross-sectional shape of the projectile is represented by X
If it is determined in advance using a radiographic apparatus, it is possible to set a more precise gate time in consideration of the difference in the speed of light due to the tissue in the living body.

Hereinafter, the main points of the measuring operation by the measuring device of the present embodiment configured as described above will be described with reference to FIG.

First, preliminary measurement of the object shape by light or X-ray is performed (step 11). Based on the result, various settings such as the intensity of the measuring pulse light, the number of repetitions (set), and the setting of the photodetector time gate are performed (step 12). After the completion of the various settings, optical measurement of the object is actually performed (step 13). Using the data signal obtained by this measurement, arithmetic processing is performed by a computer to obtain projection data (step 14), and further, image reconstruction for output to a display device (not shown) is performed (step 15). )

In the data processing described above, first, the two wavelengths (λ ₁ ,
λ ₂ ), the signals X _i1 and X _i2 (i is the number of the photodetector) obtained with the pulsed light, Indicates attenuation due to absorption of light passing through the band-shaped region defined by the time gate. This is because, for light having a small wavelength difference (actually, several tens of nm), the scattering in the scatterer is almost the same, so that the attenuation due to the scattering for the light of each wavelength of λ ₁ and λ ₂ is This is because the effect is the same, and only the effect due to the difference in the number of absorption systems appears as the difference in output. By performing such measurement for all the detector elements, so-called projection data in the third generation X-ray CT is obtained. Here, by repeating the above measurement while rotating the detector and the light source integrally, a whole projection image can be obtained, and further, if a CT algorithm is used, a distribution image of the absorbing substance can be obtained.

According to the above-described embodiment, it is possible to realize a biological light measurement method and an apparatus therefor that can remove an influence of scattered light in a subject and use light to image a structure inside a living body.

FIG. 6 and FIG. 7 show the configuration of a photodetector of another embodiment,
The function is shown. If a device capable of analyzing and recording a temporal change in light quantity (hereinafter referred to as an optical time spectrum) in picosecond units is used in the light detection unit, the above-described time gate function can be performed without using an optical shutter. In this embodiment, the array 21 of the light receiving windows arranged in an arch shape in FIG. 6 corresponds to one element of the optical shutter 3 and the photodetector 2 of the apparatus in FIG. An optical fiber 22 is connected to these light receiving windows. The other end of the optical fiber 22 is a streak camera 26
Are arranged at regular intervals in the X direction near the photocathode. Each time the light pulse is sequentially irradiated as described above, light reaches each light receiving window, and this light is input to each position of the photocathode 23, respectively. As a result, the transmitted light received at each light receiving window is converted into an electron beam each time the light pulse is irradiated, and the plurality of electron beams fly toward the anode 25.
A high-frequency deflection voltage is applied to the polarizing electrode 24 of the streak camera 26, so that each electron beam is swept at high speed in the Y direction. That is, the time variation of the amount of received light as shown in FIG. 7A is converted into a distribution of the number of electrons reaching the anode 25 in the Y direction. The anode 25 is coated with a phosphor for storing electron beam intensity as emission intensity for a predetermined time. Therefore, the anode 25 per one light pulse irradiation
In FIG. 7, a two-dimensional light intensity distribution indicating an optical time spectrum at each light receiving window as shown in FIG. 7B is stored for a short time.
This light intensity distribution is photographed by, for example, a TV camera and recorded in the memory of the data collection unit 6 in FIG. Of the recorded data, if rendered only data corresponding to the hatched portion in FIG. 7 (a), to realize the time gate time width T _w.

Therefore, in this embodiment, measurement by the above-mentioned streak camera and recording of the optical time spectrum obtained by the above-mentioned streak camera are performed for each repeated irradiation of the light pulse of the two wavelengths described in the previous embodiment. The integrated value of the data within the gate for a predetermined time of the spectrum of the light receiving window at the position is obtained. This is repeated every time the beam angle is changed to obtain projection data as in the previous embodiment. The procedure of image reconstruction is the same as in the previous embodiment.

Note that the above embodiment is shown as an example, and any change in the constituent requirements or change in the measurement method described in describing the function of each part may be an effective embodiment of the present invention. However, it goes without saying that the present invention should not be limited to these. For example, in the above embodiment, the effect of scattered light can be further reduced by providing a polarizing filter in front of the photodetector and using polarized light as a light source.

〔The invention's effect〕

As described above, according to the present invention, by providing a time gate or the like in the photodetector unit, the time gate or the like scatters in the living body and the flight distance becomes longer, and the arrival time at the photodetector unit becomes a predetermined time. By cutting off the light delayed from the time and removing the influence on the measurement signal, it is possible to image the structure inside the living body using the light, the biological light measurement method and the influence of the scattered light are removed. This has a remarkable effect that the device can be realized.

[Brief description of the drawings]

FIG. 1 is a block diagram of a biological light measuring device showing one embodiment of the present invention, FIG. 2 is a diagram showing a time relationship of each signal in a measuring operation according to the present invention, and FIG. 3 is a method of setting a time gate. FIG. 4, FIG. 4 is a diagram showing the scattered light removing effect of the time gate, FIG. 5 is a diagram for explaining the essential points of the measuring operation by the measuring device of the embodiment, and FIG. FIG. 7 is a waveform diagram showing the operation of FIG. 1: light source section, 2: photodetector, 3: optical shutter, 4: time control section,
5: computer, 6: measurement circuit, 7: data collection unit, 8: rotating mirror, 9: optical system, 10: object.

Continued on the front page (72) Inventor Yoshitoshi Ito 1-280 Higashi Koikebo, Kokubunji-shi, Tokyo Inside the Central Research Laboratory, Hitachi, Ltd. JP-A-1-209342 (JP, A) JP-A-49-17192 (JP, A) JP-A-63-168439 (JP, U) (58) Fields investigated (Int. Cl. ⁶ , DB name) G01N 21 / 00-21/01 G01N 21/17-21/61 JOIS

Claims (4)

(57) [Claims] 1. Irradiating a living body with light having a wavelength from visible to infrared wavelengths, measuring light emitted from the living body by the light irradiation,
In the living body light measurement method for imaging the distribution of substances or functions in the living body, the influence of the light scattering inside the living body is measured in advance from the shape of the living body, and passed through a time gate set based on the measurement. A biological light measurement method characterized by measuring light. 2. An X-ray CT apparatus or an NMR CT
The biological light measurement method according to claim 1, wherein the measurement is performed using an apparatus. 3. A means for irradiating a living body with light of a visible to infrared wavelength, a means for measuring light emitted from the living body by the light irradiation, and imaging a distribution of a substance or a function in the living body. In the living body optical measurement device having imaging means, the influence of the scattering of the light inside the living body is measured in advance from the shape of the living body, and the light passing through the time gate means set based on the measurement is measured. Characteristic biological light measurement device. 4. An X-ray CT apparatus or an NMR CT
The biological optical measurement device according to claim 3, wherein the measurement is performed by an apparatus.