WO1997008994A1 - Bony tissue analyzer and method - Google Patents

Bony tissue analyzer and method Download PDF

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Publication number
WO1997008994A1
WO1997008994A1 PCT/JP1996/002511 JP9602511W WO9708994A1 WO 1997008994 A1 WO1997008994 A1 WO 1997008994A1 JP 9602511 W JP9602511 W JP 9602511W WO 9708994 A1 WO9708994 A1 WO 9708994A1
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Prior art keywords
light
bone tissue
bone
coefficient
transmitted
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PCT/JP1996/002511
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French (fr)
Japanese (ja)
Inventor
Akira Itabashi
Akira Takeuchi
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Akira Itabashi
Akira Takeuchi
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Application filed by Akira Itabashi, Akira Takeuchi filed Critical Akira Itabashi
Priority to AU68896/96A priority Critical patent/AU6889696A/en
Publication of WO1997008994A1 publication Critical patent/WO1997008994A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/45For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4504Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence

Definitions

  • the present invention relates to a bone tissue analysis device and method for examining bone tissue using laser light.
  • a method called the X-ray method that uses a simple X-ray to examine the structural change of the bone and a method that uses two types of X-rays to quantify calcium density in the bone have been used.
  • Bone tissue has also been examined by a method called pQCT using high performance X-ray CT.
  • the results of bone density measurement by the DXA method and the pQCT method have been used as important indicators of bone strength.
  • ultrasonic methods and the like have been studied as analysis methods that reflect not only bone density but also bone quality.
  • Bone tissue has a period of bone formation and resorption called remodeling, and measurement of this period is used, for example, to evaluate the progression rate of osteoporosis.
  • the measurement of the cycle of bone formation and resorption is generally performed by histological examination using biopsy, or by a blood test or urine test. It is performed by measurement.
  • the present invention has been made to solve such a problem, and a laser light source that emits laser light, a light guiding unit that guides the laser light emitted from the laser light source to a bone tissue, and a laser light that has passed through the bone tissue
  • a light receiver that receives light
  • a calculator that calculates the light scattering coefficient and light absorption coefficient of bone tissue from the obtained transmitted light, and the relative relationship between the calculated light scattering coefficient and light absorption coefficient is expressed by the value of each coefficient.
  • the bone tissue analyzer was provided with a classifier for classifying into any of the fourth relative relationships having low values, and a display for displaying the classification result.
  • the third step of determining the light absorption coefficient and the relative relationship between the determined light scattering coefficient and the determined light absorption coefficient are described in the first step where the values of the coefficients are both high.
  • the relative relationship between the obtained light scattering coefficient and light absorption coefficient is classified into the first relative relationship, the amount of bone mineral, which is a light scatterer contained in the bone, is high, and the light absorption in the cavity of the bone is high. It is analyzed that the body contains many blood components. Also, when classified into the second relative relationship, it is analyzed that the bone mineral content is not high, and that the cavity contains a large amount of fat, which is a light scatterer, instead of blood components. In addition, when classified into the third relative relationship, it is analyzed that bone mineral content is low, the cavity is formed large, and a large amount of blood components is contained in the cavity. When classified into the fourth relative relationship, it is analyzed that bone mineral content is low and that the blood cavity and the fat content are little contained in the cavity. BRIEF DESCRIPTION OF THE FIGURES
  • FIG. 1 is a block diagram showing a bone tissue analyzing apparatus according to one embodiment of the present invention
  • FIG. 2 is a time-resolved measurement of each bovine tissue measured using the bone tissue analyzing apparatus according to this embodiment
  • Fig. 3 is a graph showing the measured waveforms.
  • Fig. 3 shows the maximum light intensity and peak time of the time-resolved measured waveform of the human lumbar vertebrae block measured using the bone tissue analyzer according to the present embodiment, and the BMD.
  • FIG. 4 is a graph showing the correlation between the BMD value and the average optical density obtained by irradiating the continuous light to the bovine bone tissue and FIG. FIG.
  • FIG. 5 is a graph showing a time-resolved measurement waveform of the heel of a living human measured using the bone tissue analyzer according to the present embodiment. Schematic diagrams of attenuation due to light absorption and each It is a figure showing a time-resolved waveform of transmitted light.
  • FIG. 1 is a block diagram showing a schematic configuration of the bone tissue analyzer according to the present embodiment.
  • Titanium 'Sapphire' pulsed laser light source 1 has a light intensity of about 400 mW, a beam diameter of 2 mm, a wavelength of 750 to 800 nm, and a half width of 100 fs at a repetition frequency of 76 MHz. Out of the laser beam.
  • This pulsed laser light is guided to the sample 5 by the optical mirrors 2, 3, and 4 constituting the light guiding means.
  • Sample 5 is a specimen 6 such as a bone tissue or the like formed in a block shape of 10 mm square, and is fixed to a box-shaped black acryl senor 8 filled with saline (physiological saline) 7.
  • the pulsed laser light enters from the center of the transparent glass window provided in a part of the black acrylic sensor 8 and is radiated toward the specimen 6.
  • the light transmitted through the sample 6 exits from the transparent glass window provided opposite the entrance window, and is received by the receiver (model name M2816, manufactured by Hamamatsu Photonics) 9 installed immediately after. Is detected.
  • the transmitted light detected by the receiver 9 is integrated 10 times at 2 MHz by an optical oscilloscope (model O ⁇ S—01, manufactured by Hamamatsu Photonics) 10. Then, in this optical oscilloscope 10, based on the integrated output of the light receiver 9, the time that the transmitted light travels from the light incident point of the sample 6 to the light detection point and the intensity of the transmitted light are time-resolved. It is measured.
  • This measurement result is recorded on the optical oscilloscope 10 as a time-resolved measurement waveform.
  • the light emitted from the laser light source 1 and detected by the optical receiver 12 similar to the optical receiver 9 via the optical mirrors 12 and 11 is input to the optical oscilloscope 10 as reference light.
  • the arithmetic unit 13 obtains the light scattering coefficient ⁇ s ′ and the light absorption coefficient ⁇ a of the sample 6 from the obtained time-resolved measurement waveform of the transmitted light.
  • Common methods for evaluating these coefficients include methods that evaluate both coefficients analytically from the light diffusion equation and those that use a computer-based stochastic method called the Monte Carlo method to measure the scattering and absorption of light numerically.
  • the classifier 14 classifies the relative relationship between the light scattering coefficient ⁇ s ′ and the light absorption coefficient / ia obtained by the arithmetic unit 13 into one of the following four relative relationships.
  • the first relative relationship where the value of each coefficient ⁇ s ′ / a is high
  • the second relative relationship where the value of the light scattering coefficient / / s ′ is high and the value of the light absorption coefficient ⁇ a is low
  • the third relative relationship where the value of the coefficient ⁇ s' is low and the value of the light absorption coefficient ⁇ a is high, or each coefficient ⁇ s
  • the display 15 displays the classification result.
  • FIG. 2 is a graph showing the results of time-resolved measurement of each bovine tissue using the above-mentioned bone tissue analyzer.
  • the wavelength of the pulsed laser light was set at 805 nm.
  • the vertical axis of the graph indicates the relative intensity of transmitted light (INTENS ITY), and the unit is the photon amount [COUNTS].
  • the horizontal axis of the graph indicates the elapsed time (T IME) since the pulse laser beam hit the specimen 6, and the unit is [PS:].
  • T IME elapsed time
  • bovine muscle, fat, trabecular bone and cortical bone were each formed into a 10 mm square block.
  • waveform A is a time-resolved measurement waveform of a raw eclipse without light scattering and absorption, and is used as a reference waveform.
  • Waveforms B, C, D, and E are time-resolved measurement waveforms of muscle, fat, cancellous bone, and cortical bone, respectively.
  • the maximum light intensity IM ax entity, IM ax
  • the time-resolved measurement waveform becomes The peak time to reach the peak (peak time, PT) shifts forward, that is, to the left of the graph. If the sample 6 is a tissue with strong light scattering, The peak intensity of the time-resolved measurement waveform shifts backward, that is, to the right of the graph, although the intensity with respect to the intensity also decreases.
  • the maximum light intensity is high, and the peak time is delayed only by about 50 [PS] compared to the peak time of the reference waveform A of the raw food. This is because the muscle has good light transmission and low scattering, even though the muscle contains myoglobin, which has an absorption spectrum in the wavelength region of the irradiated light. Is shown.
  • cancellous bone waveform C the maximum light intensity is high and transmissive, but the scattering is much higher than that of muscle.
  • the peak time of the same waveform is after 100 [PS], and a photon with a long optical path length that has been greatly scattered can be detected near 400 [PS].
  • fat waveform D shows that fat tissue is a strong light scatterer.
  • waveform E of cortical bone shows a stronger light scattering pattern.
  • a 10 mm square block of trabecular bone was formed from the central part of the third lumbar vertebra of the human (human) obtained at the time of the autopsy of three cases. Time-resolved measurement was performed. This human lumbar spine sample was measured before and after ultrasonic cleaning for 40 minutes to consider the effect of hemoglobin (Hb) contained in Sample II.
  • Hb hemoglobin
  • Figure 3 is a graph showing the measurement results.
  • the graph in the same figure (a) shows the correlation between the bone density BMD of the human lumbar vertebra and the maximum light intensity IM aX of the time-resolved measurement waveform.
  • the vertical axis of the graph is BMD [g / cm2], The horizontal axis is I Max [counts].
  • the graph in Fig. 3 (b) is a graph showing the correlation between the bone density BMD of the human lumbar vertebra and the peak time PT of the time-resolved measurement waveform, and the vertical axis of the graph is BMD [g / cm2], horizontal.
  • the axis is PT [ps].
  • the BMD value was measured using a DXA method measuring instrument (model name: DPX-L, manufactured by Luna, USA), and the high resolution mode (High resolution) of small animal software was used. mode). Also, this In each of these graphs, the straight line a obtained from the black circle is the result obtained by measuring the sample before washing, and the straight line b obtained from the white circle is the sample obtained by ultrasonic cleaning. It is a result obtained by measuring later.
  • Plot H1 in each of these graphs is lumbar spine sample data of a 50-year-old man who died of alcoholic liver failure.
  • Plot H2 is sample data from a 54-year-old woman who died of ovarian cancer.
  • Plot H3 is a sample of a lumbar spine sample from a 63-year-old man who died of hepatocyte cancer.
  • the relative relationship between BD and IMaX can also be confirmed by irradiating the sample with continuous light. This has been confirmed by the following experiment.
  • a halogen lamp is used as the light source, and the output of this light source is reduced to about 200 [W] by the dimmer.
  • the continuous diffused light obtained in this way is applied to a bone sample fixed between 2 mm thick white acrylic plates.
  • the light transmitted through the bone sample was received by a computer-type CCD scanner (model name EPS0N6500ART, manufactured by Seiko Epson Corporation), and the obtained image data was analyzed by a computer. That is, the obtained RGB image data was converted to grayscale image data (gray scale) of 256 gradations, and the average optical density was calculated from the converted data.
  • the RGB image obtained by this measurement became brighter as the decalcification proceeded.
  • the relationship between the average optical density (mean density) obtained by analyzing the grayscale image data and the BMD value measured by the DXA method described above is shown in the graph of Fig. 4. .
  • the vertical axis of the graph is the average optical density, and the horizontal axis is BMD [g / cm2].
  • the graph confirms that the average optical density decreases with decreasing BMD, and that the amount of light transmitted through the bone sample increases linearly with decreasing BMD value, and the correlation function R 2 is 0.99. It was as high as 6.
  • the experimental results are consistent with the time-resolved measurement results using pulsed laser light shown in Fig. 3 (a).
  • a titanium channel sapphire (model C4332, manufactured by Hamamatsu Photonics) with more sensitivity was used. Pulsed laser light in the near-infrared region with a wavelength of 754 nm emitted from pulsed laser light source 1 was irradiated from the inside of the heel (about 45 mm thick) of the human. The results shown were obtained. Here, the time-resolved measurement was performed such that the pulsed laser light was integrated 200 times and light irradiation was performed for about 1 minute so that a sufficient signal intensity was obtained.
  • the graph in (a) shows the time-resolved measurement result of the reference light
  • the graph in (b) shows the time-resolved measurement result of the signal light.
  • the horizontal axis is the time [ns] since the light hits the specimen
  • the vertical axis is the number of photon counts representing the light intensity of the transmitted light.
  • the diagonal axis to the right indicates the detection channel of the streak camera.
  • the peak time was delayed by 1500 [ps]. Considering that light travels at a speed of about 0.23 [mm / ps] in the biological tissue ⁇ , the peak position near 150 [ps] in the measured waveform is 4.5 cm thick. This means that the photon scattered 40 [cm] through the heel. The results also revealed that information on such remarkable light scattering of living organisms can be obtained non-invasively.
  • X-rays and light are the same electromagnetic wave, but their properties are different due to their different wavelengths.
  • the photon is absorbed by Ca in the bone tissue.
  • it is necessary to use It is known that remarkable light diffusion occurs due to a change in the refractive index due to a change in the shape of a tissue or bone tissue.
  • both X-rays and light are electromagnetic waves, the absorption attenuation of X-rays in bone tissue and the absorption and scattering attenuation of light in bone tissue have been clarified by the above-mentioned measurement using continuous light. The same tendency was shown.
  • the same attenuation of light is observed whether the target is a dispersive substance or an absorbent substance. Even when measuring with light, it is not possible to distinguish between the power of attenuation of light due to scattering or the attenuation of light due to absorption.
  • This problem can be solved by using photometry based on time-resolved measurement.
  • the specimen is irradiated with ultra-short pulsed light, and changes in the movement process that occur when the incident photons pass through the specimen while being scattered or absorbed, that is, changes in the optical path length, are received.
  • time-resolved measurement can be performed, and the light absorption and scattering characteristics can be accurately evaluated. That is, by measuring how many seconds the photon whose incident time and position are known reaches the light receiver, the optical path length of the scattered photon can be estimated. This makes it possible to distinguish between scattering and absorption factors.
  • Fig. 6 (a) shows the optical path length when light is applied to the specimen (bone tissue) 6 where the light absorber 21 is present
  • Fig. 6 (b) shows the light scatterer 22.
  • the optical path length when the existing specimen (bone tissue) 6 is irradiated with light is shown.
  • the time-resolved measurement waveform is the graph in FIG. (C)
  • the light scatterer 22 is in the sample 6
  • the time-resolved measurement waveform is shown in the graph of (d).
  • the horizontal axis of each graph is time [ps], and the vertical axis is the number of photons.
  • the peak time of the signal waveform 23 is slightly delayed from the peak time of the reference light waveform 24, in the typical light scattering pattern shown in FIG. 11D, the peak time of the signal waveform 25 is the same as that of the reference light waveform. It is significantly behind the peak time of 26.
  • the maximum light intensity of the signal waveform 23 is larger than the maximum light intensity of the signal waveform 25.
  • the parameters obtained by evaluating the waveform measured by light are basically two parameters: equivalent scattering coefficient / s' and absorption coefficient ⁇ a. These coefficients are obtained by the calculator 13 of the bone tissue analyzer shown in FIG. 1 described above, and the state of the bone tissue is classified by the classifier 14 based on the obtained coefficients as described above. It becomes possible to do various state analysis of. For example, the following analysis can be performed by applying the bone tissue analyzer according to the present embodiment to the heel of a living human.
  • the calculated relative values of the light scattering coefficient ⁇ s ′ and the light absorption coefficient / a are classified into the first relative relationship where both the values of the respective coefficients / is ′ and a are high, they are included in the bone.
  • the amount of bone mineral, which is a light scatterer, is high, and the intertrabecular space (cortical bone marrow cavity) is considered to contain a large amount of bone marrow tissue rich in blood components, which are light absorbers. Therefore, the bone tissue classified into the first relative relationship can be analyzed as healthy bone tissue.
  • the bone mineral content is not high, and the intratrabecular space (bone marrow cavity) is not high.
  • the bone marrow tissue which is rich in blood components, is analyzed to have been replaced by fat tissue, which is a light scatterer. Therefore, it can be analyzed that this bone tissue with an increased fat content has undergone bone changes typified by old age, in which the cycle of bone formation and resorption is slow.
  • the bone mineral content is low and the trabecular width is narrow. It is analyzed that the intertrabecular space is large and that the cavity contains a large amount of bone marrow tissue rich in blood components. Therefore, this bone tissue, which is rich in blood components, can be analyzed as having bone changes represented by postmenopausal osteoporosis in women who have a rapid cycle of bone formation and resorption.
  • the evaluation of whether each coefficient value is high or low is based on the average value obtained by statistically processing the coefficient values of normal persons with various foot thicknesses and various skin colors. It is possible to do it.
  • osteoporotic bone lesions change from cortical bone in the diaphysis to trabecular bone such as the lumbar spine, femoral neck, and calcaneus.
  • trabecular bone such as the lumbar spine, femoral neck, and calcaneus.
  • bone mineral density in the trabecular bone decreases, and as a result, the trabecular width narrows and the intertrabecular space
  • the (bone marrow cavity) presents a structural change that increases.
  • osteoporosis is clinically classified as occurring several years after menopause or as occurring in old age.
  • the former is a condition in which bone lesions progress rapidly due to the activation of bone resorption due to the rapid deficiency of female hormones during the earlier period of bone formation and resorption.
  • the pathology is mainly due to a decrease in bone formation, but the disease progresses gradually due to the slow cycle of bone formation and resorption.
  • the two are different in the optimal treatment and the time to start the treatment is also different, so it is very important to distinguish them.
  • a type that has a fast cycle of bone formation and resorption as in postmenopausal osteoporosis In cancellous bone tissue, the intertrabecular space is filled with blood-rich bone marrow tissue. In addition, it is presumed that blood components are replaced by adipose tissue in the bone marrow tissue of the intertrabecular space of the cancellous bone tissue, which has a slow cycle of bone formation and resorption, as represented by old age. Mild changes were also observed in the cortical bone, and in severely advanced osteoporosis, the thickness of the cortical bone decreased, resulting in a decrease in the amount of bone mineral in the cortical bone and the fat in the medullary cavity. Is recognized.
  • the bone tissue shows strong light absorption properties, it can be assumed that the bone is rich in blood components of bone marrow and is a healthy bone tissue with a high BMD. Also, if the absorption characteristics are weak, it is possible that blood is replaced by fat inside the bone marrow, and it is speculated that the increase in scattering in this case is not due to the effect of high BMD but to an increase in fat mass. be able to. In addition, by examining light with a wavelength around 930 [nm], which has the peak of the fat absorption spectrum, it is possible to measure fat more clearly. If the scattering is weak, the BMD is suspected to be low.However, if the trabecular gap is widened due to osteoporosis and contains a lot of blood, the absorption becomes even stronger. .
  • the absorption spectrum of co-gen also exists in a higher wavelength range, so that by using a laser photometering system that can measure in a wider range of wavelengths, , Scattering of bone tissue, It is possible to make a new assessment of bone quality by measuring absorption characteristics and spectroscopic analysis using absorption spectra.
  • time-resolved measurement is also performed on human bone tissue in a living state. Further, when interpreting the time-resolved measurement waveform, the light scattering coefficient and light absorption coefficient of the bone tissue are determined. By classifying these coefficients as described above according to the value of, it became possible to take into account the effects of bone surrounding tissue. It is a very difficult problem to estimate the change in the photon's movement path when light passes through the peri-bone tissue where the skin, adipose tissue, muscular tissue, tendon tissue, etc. are complexly overlapped. In recent years, the effects of the optical path length when transmitting through multiple tissues with different scattering and absorption coefficients have been mathematically studied by various model experiments, but a final solution to this problem has been obtained.
  • the pulse laser system was used to irradiate the pulsed laser beam to the bone tissue, and the light scattering coefficient and the light absorption coefficient in the bone tissue were obtained by the time-resolved measurement method.
  • modulation is applied to the continuous laser light that irradiates the bone tissue, and time information such as how the phase of the modulated light changes by transmitting through the bone tissue is examined.
  • the light scattering coefficient and light absorption coefficient of the bone tissue are determined.
  • the bone tissue ⁇ can be non-invasively analyzed by light. It becomes possible to do.
  • the conventional bone tissue analysis method using X-rays only estimates the structural change of the bone from the distribution and density of calcium in the bone, but according to the present invention, the measured scattering coefficient and It is possible to more specifically evaluate the inside of bone tissue based on the absorption coefficient, and it becomes possible to analyze changes in bone structure with higher precision and accuracy. Therefore, superior analysis can be performed compared to conventional bone tissue analysis methods using ultrasonic methods and indirect conventional analysis methods that measure bone formation and resorption markers using blood and urine tests. It becomes possible to do.
  • since measurement is performed using light there is no need for an exposure protection facility for X-ray exposure, and there is no need to worry about the effects of invasion on the subject.

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Abstract

An apparatus for noninvasively analyzing the interior of a bony tissue with light and a method therefor. The apparatus is equipped with an operator (13), a sorter (14), and a display (15). The operator (13) calculates a light scattering coefficient νs' and a light absorption coefficient νa of a specimen (bony tissue) (6) based on the time-resolved waveform of the obtained transmitted light. The sorter (14) sorts the correlation between the coefficients νs' and νa thus obtained into any one of the first corrections where the values of both νs' and νa are high, the second correlation where the value of νs' is high while that of νa is low, the third correlation where the value of νs' is low while that of νa is high, and the fourth correlation where the values of both νs' and νa are low. The display (15) indicates the result of sorting.

Description

明 細 書 骨組織解析装置および方法 技術分野  Description Bone tissue analyzer and method Technical field
本発明は、 レーザ光を用いて骨組織を調べる骨組織解析装置および方 法に関するものである。 背景技術  The present invention relates to a bone tissue analysis device and method for examining bone tissue using laser light. Background art
従来、 骨の内部を調べるには、 単純 X線によって骨の構造変化を調べ る方法や、 2種の X線を使って骨内カルシウム密度を定量する D X A法 と呼ばれる方法が用いられている。 また、 高性能 X線 C Tによる p Q C T法と呼ばれる方法によっても骨組織が調べられている。 現在、 この D X A法や p Q C T法による骨密度測定の結果が骨強度の重要な指標と し て用いられてきている。 また、 最近では、 骨密度ばかりでなく骨質をも 反映する解析方法と して超音波法などが検討されている。  Conventionally, to examine the inside of a bone, a method called the X-ray method that uses a simple X-ray to examine the structural change of the bone and a method that uses two types of X-rays to quantify calcium density in the bone have been used. Bone tissue has also been examined by a method called pQCT using high performance X-ray CT. At present, the results of bone density measurement by the DXA method and the pQCT method have been used as important indicators of bone strength. Recently, ultrasonic methods and the like have been studied as analysis methods that reflect not only bone density but also bone quality.
また、 骨組織はリモデリ ングと呼ばれる骨の形成と骨の吸収の周期を 持っており、 この周期の測定は例えば骨粗鬆症の進行速度の評価に用い られている。 従来、 この骨の形成と吸収の周期の測定は、 一般的には、 生検による組織検査で行ったり、 あるいは、 血液検査や尿検査によって 得られる骨形成および吸収のマ一力一 (徴候) の測定により行われてい る。  Bone tissue has a period of bone formation and resorption called remodeling, and measurement of this period is used, for example, to evaluate the progression rate of osteoporosis. Conventionally, the measurement of the cycle of bone formation and resorption is generally performed by histological examination using biopsy, or by a blood test or urine test. It is performed by measurement.
しかしながら、 X線を用いた上記従来の全ての骨組織解析手法は、 骨 内カルシウムの分布、 密度から骨の構造変化を推定しているに過ぎない。 また、 X線の被曝に対する防曝施設を設置する必要があり、 さらに、 X 線被曝による被検者に対する侵襲も問題になる。 また、 上記従来の超音波法を用いた骨組織解析手法は、 簡易に解析す ることができ、 骨の物理学的強度 (弾性強度) を測定はしているが、 D X A法により求めた骨塩量 (骨内カルシウム) との相関性の評価に留ま つており、 簡略式骨塩定量器と しての意味合いが強い。 つま り、 この解 析手法では精度良く 、 正確に骨組織内部を解析することは困難である。 また、 骨の形成と吸収の周期に関する骨組織解析手法に関しては、 従 来の生検は観血的であるため、 頻繁に施行することは望めない。 また、 血液検査や尿検査によって骨形成および吸収マーカーを測定する従来の 解析手法は、 骨組織を直接測定していないため、 その評価解析結果は間 接的なものでしかない。 従って、 これら解析手法でもやはり、 精度良く、 正確に骨組織内部を解析することは困難である。 発明の開示 However, all of the above conventional bone tissue analysis methods using X-rays only estimate structural changes in bone from the distribution and density of calcium in bone. In addition, it is necessary to set up an exposure protection facility against X-ray exposure, and invasion of the subject by X-ray exposure is also a problem. In addition, the conventional bone tissue analysis method using the above-mentioned ultrasonic method can easily analyze and measure the physical strength (elastic strength) of the bone, but the bone strength obtained by the DXA method is measured. It only evaluates the correlation with the amount of salt (intraosseous calcium) and has a strong meaning as a simple bone mineral analyzer. That is, it is difficult to accurately and accurately analyze the inside of the bone tissue with this analysis method. In addition, regarding bioanalysis techniques for bone formation and resorption cycles, conventional biopsies are invasive and cannot be performed frequently. In addition, conventional analysis methods that measure bone formation and resorption markers by blood and urine tests do not directly measure bone tissue, and the results of the evaluation analysis are only indirect. Therefore, even with these analysis methods, it is difficult to accurately and accurately analyze the inside of bone tissue. Disclosure of the invention
本発明はこのような課題を解決するためになされたもので、 レーザ光 を出射するレーザ光源と、 このレーザ光源から出射されたレーザ光を骨 組織に導く導光手段と、 骨組織を透過した光を受光する受光器と、 得ら れた透過光から骨組織の光散乱係数および光吸収係数を求める演算器と、 求めた光散乱係数と光吸収係数との相対関係を、 各係数の値が共に高い 第 1 の相対関係, 光散乱係数値が高く光吸収係数値が低い第 2の相対関 係, 光散乱係数値が低く光吸収係数値が高い第 3の相対関係, または各 係数の値が共に低い第 4の相対関係のいずれかに類別する類別器と、 こ の類別結果を表示する表示器とを備え、 骨組織解析装置を構成した。  The present invention has been made to solve such a problem, and a laser light source that emits laser light, a light guiding unit that guides the laser light emitted from the laser light source to a bone tissue, and a laser light that has passed through the bone tissue A light receiver that receives light, a calculator that calculates the light scattering coefficient and light absorption coefficient of bone tissue from the obtained transmitted light, and the relative relationship between the calculated light scattering coefficient and light absorption coefficient is expressed by the value of each coefficient. Are high both, the first relative relationship, the light scattering coefficient value is high, the light absorption coefficient value is low, the second relative relationship, the light scattering coefficient value is low, and the light absorption coefficient value is high. The bone tissue analyzer was provided with a classifier for classifying into any of the fourth relative relationships having low values, and a display for displaying the classification result.
また、 レーザ光源から出射されたレーザ光を骨組織に照射する第 1 の 工程と、 骨組織を透過した光を受光する第 2の工程と、 得られた透過光 から骨組織の光散乱係数および光吸収係数を求める第 3の工程と、 求め た光散乱係数と光吸収係数との相対関係を、 各係数の値が共に高い第 1 の相対関係, 光散乱係数値が高く光吸収係数値が低い第 2の相対関係, 光散乱係数値が低く光吸収係数値が高い第 3の相対関係, または各係数 の値が共に低い第 4の相対関係のいずれかに類別する第 4の工程とを備 え、 骨組織を解析する。 A first step of irradiating the bone tissue with laser light emitted from the laser light source; a second step of receiving light transmitted through the bone tissue; and a light scattering coefficient of the bone tissue based on the obtained transmitted light. The third step of determining the light absorption coefficient and the relative relationship between the determined light scattering coefficient and the determined light absorption coefficient are described in the first step where the values of the coefficients are both high. The second relative relationship where the light scattering coefficient value is high and the light absorption coefficient value is low, the third relative relationship where the light scattering coefficient value is low and the light absorption coefficient value is high, or the fourth relative relationship where the value of each coefficient is low. And a fourth step for classifying the bone tissue into any one of the relative relationships.
求めた光散乱係数および光吸収係数の相対関係が、 第 1の相対関係に 類別された場合には、 骨内に含まれる光散乱体である骨塩量は高く、 骨 の腔内に光吸収体である血液成分が多く含まれているものと解析される。 また、 第 2の相対関係に類別された場合には、 骨塩量は高く なく、 腔内 には血液成分に代わって光散乱体である脂肪分が多く含まれているもの と解析される。 また、 第 3の相対関係に類別された場合には、 骨塩量は 低く、 腔は大きく形成され、 腔内には血液成分が多量に含まれているも のと解析される。 また、 第 4の相対関係に類別された場合には、 骨塩量 は低く、 腔内には血液成分も脂肪分も少ししか含まれていないものと解 析される。 図面の簡単な説明  When the relative relationship between the obtained light scattering coefficient and light absorption coefficient is classified into the first relative relationship, the amount of bone mineral, which is a light scatterer contained in the bone, is high, and the light absorption in the cavity of the bone is high. It is analyzed that the body contains many blood components. Also, when classified into the second relative relationship, it is analyzed that the bone mineral content is not high, and that the cavity contains a large amount of fat, which is a light scatterer, instead of blood components. In addition, when classified into the third relative relationship, it is analyzed that bone mineral content is low, the cavity is formed large, and a large amount of blood components is contained in the cavity. When classified into the fourth relative relationship, it is analyzed that bone mineral content is low and that the blood cavity and the fat content are little contained in the cavity. BRIEF DESCRIPTION OF THE FIGURES
第 1図は、 本発明の一実施例による骨組織解析装置を示すブロック図 であり、 第 2図は、 本実施例による骨組織解析装置を使用して計測され た牛の各組織の時間分解計測波形を示すグラフであり、 第 3図は、 本実 施例による骨組織解析装置を使用して計測されたヒ ト腰椎ブロ ックの時 間分解計測波形の最大光強度およびピーク時間と B M D値との相関関係 を示すグラフであり、 第 4図は、 牛の骨組織に連続光を照射して透過し て得られた平均光学密度と B M D値との相関関係を示すグラフであり、 第 5図は、 本実施例による骨組織解析装置を使用して計測された生きた ままのヒ トの踵部の時間分解計測波形を示すグラフであり、 第 6図は、 光の散乱による減衰および光の吸収による減衰のそれぞれの模式図と各 透過光の時間分解波形を示す図である。 発明を実施するための最良の形態 FIG. 1 is a block diagram showing a bone tissue analyzing apparatus according to one embodiment of the present invention, and FIG. 2 is a time-resolved measurement of each bovine tissue measured using the bone tissue analyzing apparatus according to this embodiment. Fig. 3 is a graph showing the measured waveforms. Fig. 3 shows the maximum light intensity and peak time of the time-resolved measured waveform of the human lumbar vertebrae block measured using the bone tissue analyzer according to the present embodiment, and the BMD. FIG. 4 is a graph showing the correlation between the BMD value and the average optical density obtained by irradiating the continuous light to the bovine bone tissue and FIG. FIG. 5 is a graph showing a time-resolved measurement waveform of the heel of a living human measured using the bone tissue analyzer according to the present embodiment. Schematic diagrams of attenuation due to light absorption and each It is a figure showing a time-resolved waveform of transmitted light. BEST MODE FOR CARRYING OUT THE INVENTION
次に、 本発明の一実施例による骨組織解析装置および方法について説 明する。  Next, a bone tissue analyzing apparatus and method according to an embodiment of the present invention will be described.
図 1は本実施例による骨組織解析装置の概略構成を示すプロ ック図で ある。  FIG. 1 is a block diagram showing a schematic configuration of the bone tissue analyzer according to the present embodiment.
チタン ' サフアイャ ' パルス レ一ザ光源 1は光強度約 4 0 0 m W , ビ ーム直径 2 m m, 波長 7 5 0〜 8 0 0 n m, 繰り返し周波数 7 6 M H z で半値幅 1 0 0 f s のパルス レ一ザ光を出射する。 このパルス レ一ザ光 は導光手段を構成する光学ミラ一 2, 3, 4によってサンプル 5まで導 かれる。 サンプル 5は 1 0 m m角のブロック状に形成された骨組織等の 検体 6であり、 生食 (生理的食塩水) 7を満たした箱状の黒いアク リル セノレ 8に固定されている。 パルス レ一ザ光は、 この黒いアク リルセノレ 8 の一部に設けられた透明ガラス窓の中央から入射し、 検体 6へ向けて照 射される。 検体 6を透過した光は入射窓に対向して設けられた透明ガラ ス窓から出射し、 直後に設置された受光器 (型名 M 2 8 1 6、 浜松ホ ト 二クス社製) 9で検出される。 受光器 9で検出された透過光は、 光オシ 口スコープ (型名 O〇 S— 0 1、 浜松ホ トニクス社製) 1 0において、 2 M H zで 1 0回積算される。 そして、 この光オシロスコープ 1 0にお いて、 積算された受光器 9の出力に基づき、 検体 6の光入射点から光検 出点に至るまでに透過光が経た時間および透過光の強度が時間分解計測 される。 この計測結果は光オシロスコープ 1 0に時間分解計測波形と し て記録される。 また、 光オシロスコープ 1 0には、 レーザ光源 1から出 射され、 光学ミラ一 2, 1 1を経て受光器 9 と同様な受光器 1 2に検出 された光が、 参照光と して入力されている。 演算器 1 3は、 得られた透過光の時間分解計測波形から検体 6の光散 乱係数 μ s 'および光吸収係数 μ a を求める。 これら係数を評価する一 般的な手法には、 光の拡散方程式から解析的に両係数を評価する手法や、 モンテカルロ法と呼ばれるコンピュータを用いた確率的な手法で、 光の 散乱、 吸収を数値的にシミ ュ レート して評価する手法がある。 類別器 1 4は、 演算器 1 3で求めた光散乱係数 μ s ' と光吸収係数/ i a との相対 関係を、 次の 4つの相対関係のいずれかに類別する。 つまり 、 各係数 μ s ' ' / aの値が共に高い第 1 の相対関係, 光散乱係数/ / s ' の値が高 く光吸収係数 μ a の値が低い第 2の相対関係, 光散乱係数 μ s ' の値が 低く光吸収係数 μ a の値が高い第 3の相対関係, または各係数 μ s Titanium 'Sapphire' pulsed laser light source 1 has a light intensity of about 400 mW, a beam diameter of 2 mm, a wavelength of 750 to 800 nm, and a half width of 100 fs at a repetition frequency of 76 MHz. Out of the laser beam. This pulsed laser light is guided to the sample 5 by the optical mirrors 2, 3, and 4 constituting the light guiding means. Sample 5 is a specimen 6 such as a bone tissue or the like formed in a block shape of 10 mm square, and is fixed to a box-shaped black acryl senor 8 filled with saline (physiological saline) 7. The pulsed laser light enters from the center of the transparent glass window provided in a part of the black acrylic sensor 8 and is radiated toward the specimen 6. The light transmitted through the sample 6 exits from the transparent glass window provided opposite the entrance window, and is received by the receiver (model name M2816, manufactured by Hamamatsu Photonics) 9 installed immediately after. Is detected. The transmitted light detected by the receiver 9 is integrated 10 times at 2 MHz by an optical oscilloscope (model O〇S—01, manufactured by Hamamatsu Photonics) 10. Then, in this optical oscilloscope 10, based on the integrated output of the light receiver 9, the time that the transmitted light travels from the light incident point of the sample 6 to the light detection point and the intensity of the transmitted light are time-resolved. It is measured. This measurement result is recorded on the optical oscilloscope 10 as a time-resolved measurement waveform. In addition, the light emitted from the laser light source 1 and detected by the optical receiver 12 similar to the optical receiver 9 via the optical mirrors 12 and 11 is input to the optical oscilloscope 10 as reference light. ing. The arithmetic unit 13 obtains the light scattering coefficient μ s ′ and the light absorption coefficient μ a of the sample 6 from the obtained time-resolved measurement waveform of the transmitted light. Common methods for evaluating these coefficients include methods that evaluate both coefficients analytically from the light diffusion equation and those that use a computer-based stochastic method called the Monte Carlo method to measure the scattering and absorption of light numerically. There is a method to simulate and evaluate it. The classifier 14 classifies the relative relationship between the light scattering coefficient μ s ′ and the light absorption coefficient / ia obtained by the arithmetic unit 13 into one of the following four relative relationships. In other words, the first relative relationship where the value of each coefficient μ s ′ / a is high, the second relative relationship where the value of the light scattering coefficient / / s ′ is high and the value of the light absorption coefficient μ a is low, The third relative relationship where the value of the coefficient μs' is low and the value of the light absorption coefficient μa is high, or each coefficient μs
H aの値が共に低い第 4の相対関係のいずれかに類別する。 表示器 1 5 はこの類別結果を表示する。  Classify into any of the fourth relative relationships where both values of Ha are low. The display 15 displays the classification result.
図 2は、 上記の骨組織解析装置を用いて牛の各組織を時間分解計測し た結果を示すグラフである。 この計測においてはパルス レーザ光の波長 を 8 0 5 n mと した。 同グラフの縦軸は透過光の相対強度 (INTENS I TY) を示し、 単位は光子量 [ COUNTS] である。 また、 同グラフの横軸はパル ス レーザ光が検体 6 に当たってからの経過時間 (T IME) を示し、 単位は [ P S: である。 検体 6には、 牛の筋肉, 脂肪, 海綿骨および皮質骨の それぞれを 1 0 m m角ブロ ックに形成したものを用いた。 同ダラフにお いて、 波形 Aは光散乱も吸収もない生食の時間分解計測波形であり、 参 照波形と して用いられる。 波形 B, C, Dおよび Eはそれぞれ筋肉, 脂 肪, 海綿骨および皮質骨の時間分解計測波形である。 一般的に、 検体 6 が光学的に吸収が強い組織である場合には、 透過光の減少に伴って最大 光強度 (max imum i nt ens i t y , I M a x ) は低下し、 時間分解計測波形が ピークに達するピーク時間 (peak t ime, P T ) は前方つまり グラフの左 方にシフ トする。 また、 検体 6が光散乱が強い組織である場合には、 相 対強度はやはり低下するが、 時間分解計測波形のピーク時間は後方つま り グラフの右方にシフ 卜する。 FIG. 2 is a graph showing the results of time-resolved measurement of each bovine tissue using the above-mentioned bone tissue analyzer. In this measurement, the wavelength of the pulsed laser light was set at 805 nm. The vertical axis of the graph indicates the relative intensity of transmitted light (INTENS ITY), and the unit is the photon amount [COUNTS]. In addition, the horizontal axis of the graph indicates the elapsed time (T IME) since the pulse laser beam hit the specimen 6, and the unit is [PS:]. For sample 6, bovine muscle, fat, trabecular bone and cortical bone were each formed into a 10 mm square block. In the Dalaf, waveform A is a time-resolved measurement waveform of a raw eclipse without light scattering and absorption, and is used as a reference waveform. Waveforms B, C, D, and E are time-resolved measurement waveforms of muscle, fat, cancellous bone, and cortical bone, respectively. In general, when the specimen 6 is a tissue that has strong optical absorption, the maximum light intensity (IM ax entity, IM ax) decreases as the transmitted light decreases, and the time-resolved measurement waveform becomes The peak time to reach the peak (peak time, PT) shifts forward, that is, to the left of the graph. If the sample 6 is a tissue with strong light scattering, The peak intensity of the time-resolved measurement waveform shifts backward, that is, to the right of the graph, although the intensity with respect to the intensity also decreases.
筋肉の波形 Bでは、 最大光強度は高く 、 ピーク時間は生食の参照波形 Aのピーク時間に比べて 5 0 [ P S ] 位しか遅れていない。 これは、 筋 肉には照射した光の波長領域に吸収スぺク トルを持つミオグロビンが含 まれているにもかかわらず、 筋肉は光の透過性が良く 、 散乱も少ない組 織であることを示している。 また、 海綿骨の波形 Cでは、 最大光強度は 高く透過性はあるが、 筋肉に比べて散乱はかなり多い。 同波形のピーク 時間は 1 0 0 [P S ] 以降になり、 散乱を多く受けた光路長の長いフォ ト ンは 4 0 0 [P S ] 近く に検出することができる。 また、 脂肪の波形 Dからは脂肪組織が強い光散乱体であることが分かる。 また、 皮質骨の 波形 Eではさらに強い光散乱パターンが示されている。  In the waveform B of the muscle, the maximum light intensity is high, and the peak time is delayed only by about 50 [PS] compared to the peak time of the reference waveform A of the raw food. This is because the muscle has good light transmission and low scattering, even though the muscle contains myoglobin, which has an absorption spectrum in the wavelength region of the irradiated light. Is shown. In the case of cancellous bone waveform C, the maximum light intensity is high and transmissive, but the scattering is much higher than that of muscle. The peak time of the same waveform is after 100 [PS], and a photon with a long optical path length that has been greatly scattered can be detected near 400 [PS]. Also, fat waveform D shows that fat tissue is a strong light scatterer. In addition, waveform E of cortical bone shows a stronger light scattering pattern.
また、 上記の骨解析装置を用い、 3例の剖検時に得られたヒ ト (人) の第 3腰椎中央部より海綿骨の 1 0 mm角ブロックを形成し、 これを検 体 6 と して時間分解計測した。 このヒ ト腰椎サンプルについては、 サン プル內に含まれるヘモグロ ビン (H b ) の影響を考慮するため、 4 0分 間の超音波洗浄の前後で測定した。  Using the bone analyzer described above, a 10 mm square block of trabecular bone was formed from the central part of the third lumbar vertebra of the human (human) obtained at the time of the autopsy of three cases. Time-resolved measurement was performed. This human lumbar spine sample was measured before and after ultrasonic cleaning for 40 minutes to consider the effect of hemoglobin (Hb) contained in Sample II.
図 3はこの計測結果を示すグラフである。 同図 ( a ) のグラフはヒ ト 腰椎の骨密度 BMDと時間分解計測波形の最大光強度 I M a X との相関 関係を示すグラフであり、 同グラフの縦軸は BMD [ g /cm2 ] , 横軸 は I Ma x [counts] である。 また、 同図 (b ) のグラフはヒ ト腰椎の 骨密度 BMDと時間分解計測波形のピーク時間 P Tとの相関関係を示す グラフであり、 同グラフの縦軸は BMD [ g /cm2 ] , 横軸は P T [ p S ] である。 ここで、 BMD値の測定は D X A法を用いた測定器 (型名 D PX-L 、 米国ルナ一社製) を使用し、 小動物用ソフ トウェアのハイ . レゾ リ ューシヨ ン . モー ド (High resolution mode) で計測した。 また、 こ れら各グラフにおいて、 黒塗りの丸印から得られる直線 aはサンプルを 洗浄する前に測定して得られた結果であり、 白抜きの丸印から得られる 直線 bはサンプルを超音波洗浄した後に測定して得られた結果である。 また、 これら各グラフにおけるプロッ ト H 1は、 アルコール性の肝不全 で死亡した 5 0才の男性の腰椎サンプルデータである。 また、 プロ ッ ト H 2は、 卵巣がんで死亡した 5 4才の女性の腰椎サンプルデータである。 また、 プロッ ト H 3は、 肝細胞がんで死亡した 6 3才の男性の腰椎サン プルデータである。 Figure 3 is a graph showing the measurement results. The graph in the same figure (a) shows the correlation between the bone density BMD of the human lumbar vertebra and the maximum light intensity IM aX of the time-resolved measurement waveform. The vertical axis of the graph is BMD [g / cm2], The horizontal axis is I Max [counts]. In addition, the graph in Fig. 3 (b) is a graph showing the correlation between the bone density BMD of the human lumbar vertebra and the peak time PT of the time-resolved measurement waveform, and the vertical axis of the graph is BMD [g / cm2], horizontal. The axis is PT [ps]. Here, the BMD value was measured using a DXA method measuring instrument (model name: DPX-L, manufactured by Luna, USA), and the high resolution mode (High resolution) of small animal software was used. mode). Also, this In each of these graphs, the straight line a obtained from the black circle is the result obtained by measuring the sample before washing, and the straight line b obtained from the white circle is the sample obtained by ultrasonic cleaning. It is a result obtained by measuring later. Plot H1 in each of these graphs is lumbar spine sample data of a 50-year-old man who died of alcoholic liver failure. Plot H2 is sample data from a 54-year-old woman who died of ovarian cancer. Plot H3 is a sample of a lumbar spine sample from a 63-year-old man who died of hepatocyte cancer.
同図 ( a ) のグラフから、 B M Dの低いサンプルは光を通し易いこと が分かる。 また、 同図 ( b ) のグラフから、 散乱の増加を示唆する P T の値は B M Dの値が高いほど長くなる傾向が見られた。 また、 このよ う なサンプル計測結果の相対関係は超音波洗浄で H bを除去しても保たれ ていたが、 除去後は図示されるように I M a Xが全体的に増加し、 P T が前方にシフ ト した。  It can be seen from the graph (a) that the sample having a low BMD is easy to transmit light. Also, from the graph of FIG. 11B, the value of PT indicating the increase in scattering tended to increase as the value of BMD increased. In addition, such a relative relationship between the sample measurement results was maintained even when Hb was removed by ultrasonic cleaning, but after removal, IMaX increased as a whole as shown in the figure, and PT increased. Shifted forward.
B Dと I M a X との相対関係はサンプルに連続光を照射することに よっても確認できる。 このことは次の実験によ り確認されている。 つま り、 光源にハロゲンランプを用い、 この光源の出力を調光器によって 2 0 0 [W ] 程度に減光する。 このよ うにして得られる連続拡散光を、 2 m m厚の白色ァク リル板間に固定された骨サンプルに照射する。 骨サン プノレを透過してきた光はコンピュータ一 C C Dスキャナ (型名 EPS0N650 0ART、 セイコーエプソン社製) で受光し、 得られた画像データをコンビ ユータで解析した。 つまり、 得られた R G B画像データを 2 5 6階調の 濃淡画像データ (gray scal e) に変換し、 この変換データから平均光学 密度を算出した。 この実験の測定サンプルには、 牛の大腿骨近位端の海 綿骨部より採った 1 0 m m角の骨ブロ ックを用いた。 そして、 サンプル の透過光量に影響を与える因子をカルシウムによる散乱減衰のみに限定 するため、 このサンプルを p H 7 . 2に調整した 1 5 % E D T A 2 N a 溶液中で徐々に脱灰し、 骨構造を変えずに骨プロック中の C aの結晶体 (ハイ ド口ォキシアパタイ ト) の含量のみを変化させた。 このよ うに脱 灰を開始して 2 日 目, 9 日 目, 1 8 日 目および 3 0 日目における骨サン プル中の B M Dを上記方法によって測定した。 The relative relationship between BD and IMaX can also be confirmed by irradiating the sample with continuous light. This has been confirmed by the following experiment. In other words, a halogen lamp is used as the light source, and the output of this light source is reduced to about 200 [W] by the dimmer. The continuous diffused light obtained in this way is applied to a bone sample fixed between 2 mm thick white acrylic plates. The light transmitted through the bone sample was received by a computer-type CCD scanner (model name EPS0N6500ART, manufactured by Seiko Epson Corporation), and the obtained image data was analyzed by a computer. That is, the obtained RGB image data was converted to grayscale image data (gray scale) of 256 gradations, and the average optical density was calculated from the converted data. As a measurement sample in this experiment, a 10 mm square bone block taken from the trabecular bone of the proximal end of a bovine femur was used. Factors affecting the amount of light transmitted through the sample are limited to the scattering attenuation by calcium. For this purpose, this sample was gradually decalcified in a 15% EDTA 2 Na solution adjusted to pH 7.2, and the crystal of Ca in the bone block (hydraoxyapatite) was maintained without changing the bone structure. G) was changed only. The BMD in the bone samples was measured on the second, ninth, eighteenth, and thirty days after decalcification was started by the above method.
この測定で得られた R G B画像は、 脱灰の進行に伴って明るく見える よ うになった。 また、 濃淡画像データを解析して得られた平均光学密度 ( mean dens i ty) と、 前述の D X A法で測定された B M D値との相対関 係は、 図 4のグラフに示す結果となった。 同グラフの縦軸は平均光学密 度であり、 横軸は B M D [ g / cm2 ] である。 同グラフから、 B M Dの 減少に伴って平均光学密度が低下し、 骨サンプルを透過する光量は B M D値の減少に伴って直線的に增加することが確認され、 相関関数 R 2 は 0 . 9 9 6 という高い値になった。 すなわち、 この実験結果は図 3 ( a ) に示すパルスレ一ザ光を用いた時間分解計測結果と一致している。  The RGB image obtained by this measurement became brighter as the decalcification proceeded. The relationship between the average optical density (mean density) obtained by analyzing the grayscale image data and the BMD value measured by the DXA method described above is shown in the graph of Fig. 4. . The vertical axis of the graph is the average optical density, and the horizontal axis is BMD [g / cm2]. The graph confirms that the average optical density decreases with decreasing BMD, and that the amount of light transmitted through the bone sample increases linearly with decreasing BMD value, and the correlation function R 2 is 0.99. It was as high as 6. In other words, the experimental results are consistent with the time-resolved measurement results using pulsed laser light shown in Fig. 3 (a).
この実験結果より、 光散乱体であるハイ ド口ォキシアパタイ ト含量の みを変化させた場合の透過光量の変化は、 散乱特性の変化、 すなわち散 乱を操り返し、 受光部に到達する前に減衰してしまうフオ ト ンの増減と して評価できることが分かった。 これらのことから光の散乱特性と B M Dには強い相関があることが明らかになり、 光による骨塩量の測定が可 能であることが示唆された。 また、 可視光に比べ組織透過性が良い近赤 外域でのパルスレーザ光による時間分解計測法によって得られる波形を 評価することで、 組織の散乱、 吸収特性を分離して評価することが可能 となり、 さらに、 H bや脂肪などの骨内成分を光学的変化と して測定で きる可能性が示唆された。 また、 これらの結果から、 カルシウムによる X線の吸収減衰と光の散乱減衰は同じ傾向を示すことが明らかになり、 現在主と して X線により測定されている骨塩量が光散乱の測定によって も計量することが可能であることも分かった。 From the experimental results, it can be seen that the change in the amount of transmitted light when only the content of the hydroxyapatite, which is a light scatterer, was changed was due to the change in the scattering characteristics, that is, the scattering was manipulated and attenuated before reaching the light receiving part. It was found that it can be evaluated as an increase or decrease in the number of fonts. These results revealed that there is a strong correlation between light scattering characteristics and BMD, suggesting that bone mineral density can be measured by light. In addition, by evaluating the waveform obtained by the time-resolved measurement method using pulsed laser light in the near infrared region, which has better tissue permeability than visible light, it is possible to separate and evaluate the scattering and absorption characteristics of tissue. Furthermore, it was suggested that intraosseous components such as Hb and fat could be measured as optical changes. These results also show that the absorption attenuation of X-rays and the attenuation of light scattering by calcium show the same tendency, and the amount of bone mineral, which is currently measured mainly by X-rays, is measured by light scattering. By It was also found that it was also possible to weigh.
また、 図 1 に示す光オシ口スコープに代えてより感度の優れた 6 0 0 チャンネルのス ト リ一クカメラ (型名 C 4 3 3 2、 浜松ホ トニクス社製) を用い、 チタンサフアイァパルス レーザ光源 1 より出射された波長 7 5 4 n mの近赤外領域におけるパルス レ一ザ光をヒ 卜の踵部 (約 4 5 mm 厚) の内側よ り照射したところ、 図 5のグラフに示す結果が得られた。 ここで、 時間分解計測は、 このパルス レーザ光を 2 0 0回積算して約 1 分間の光照射と し、 十分な信号強度が得られるように行った。 同図 ( a ) のグラフは参照光の時間分解計測結果, 同図 (b ) のグラフは信号光の 時間分解計測結果を示す。 これら各グラフにおいて、 横軸は検体に光が あたってからの時間 [ n s ] であり、 縦軸は透過光の光強度を表す光子 のカウント数である。 また、 右斜めの軸はス トリークカメラの検出チヤ ンネルを示している。 同図 ( a ) に示すグラフから、 生食の参照光はピ ーク時間が約 4 0 0 [ p s ] 付近に認められる。 また、 同図 ( b ) に示 すグラフから、 約 4 5 [mm] 厚の踵部を透過した初期のフオ ト ンは、 生食の参照波形に比べて 5 0 0 [ p s ] ほど遅れて現れ、 そのピーク時 間は 1 5 0 0 [ p s ] 遅れていた。 生体組織內で光は約 0. 2 3 [mm / p s ] のスピー ドで進むことから考えると、 測定波形における 1 5 0 0 [ p s ] 付近のピーク位置は、 4. 5 [ c m] 厚の踵部をフオ トンは 4 0 [ c m] も散乱しながら通過したことを意味する。 また、 この結果 から、 このよ うな生体の著しい光散乱の情報を非侵襲的に得られること が明らかになった。 Instead of the optical oscilloscope shown in Fig. 1, a titanium channel sapphire (model C4332, manufactured by Hamamatsu Photonics) with more sensitivity was used. Pulsed laser light in the near-infrared region with a wavelength of 754 nm emitted from pulsed laser light source 1 was irradiated from the inside of the heel (about 45 mm thick) of the human. The results shown were obtained. Here, the time-resolved measurement was performed such that the pulsed laser light was integrated 200 times and light irradiation was performed for about 1 minute so that a sufficient signal intensity was obtained. The graph in (a) shows the time-resolved measurement result of the reference light, and the graph in (b) shows the time-resolved measurement result of the signal light. In each of these graphs, the horizontal axis is the time [ns] since the light hits the specimen, and the vertical axis is the number of photon counts representing the light intensity of the transmitted light. The diagonal axis to the right indicates the detection channel of the streak camera. From the graph shown in ( a ) of the same figure, the reference light of the raw edible is observed at a peak time of about 400 [ps]. Also, from the graph shown in the same figure (b), the initial photon that passed through the heel of about 45 [mm] thickness appeared about 500 [ps] later than the reference waveform of saline. However, the peak time was delayed by 1500 [ps]. Considering that light travels at a speed of about 0.23 [mm / ps] in the biological tissue 內, the peak position near 150 [ps] in the measured waveform is 4.5 cm thick. This means that the photon scattered 40 [cm] through the heel. The results also revealed that information on such remarkable light scattering of living organisms can be obtained non-invasively.
X線と光は同じ電磁波であるが、 波長が違う ことによりその性質は異 なる。 X線の波長域 (数 n m) の電磁波で骨組織を測定する場合は、 フ オ トンは骨組織中の C aにより吸収されてしまう。 また、 光の波長域の 電磁波で骨組織を測定する場合には、 骨組織中のハイ ドロォキ ィ トおよび骨組織の形態変化などに伴う屈折率の変化により、 著しい光 拡散が起こることが知られている。 このよ うに X線と光は共に電磁波で ありながら、 骨組織中における X線の吸収減衰と骨組織中の光の吸収、 散乱減衰とは、 前述の連続光を用いた計測で明らかになつたように同じ 傾向を示した。 従って、 光によって骨組織中を解析する場合、 対象が散 乱物質であろう と吸収物質であろう と同様な光の減衰が見られるため、 光吸収体および光散乱体が混在する物質を連続光で測定しても、 散乱に よる光の減衰なの力 、 あるいは吸収による光の減衰なのかを区別するこ とはできない。 X-rays and light are the same electromagnetic wave, but their properties are different due to their different wavelengths. When bone tissue is measured using electromagnetic waves in the X-ray wavelength range (several nm), the photon is absorbed by Ca in the bone tissue. Also, when measuring bone tissue with electromagnetic waves in the wavelength range of light, it is necessary to use It is known that remarkable light diffusion occurs due to a change in the refractive index due to a change in the shape of a tissue or bone tissue. Thus, while both X-rays and light are electromagnetic waves, the absorption attenuation of X-rays in bone tissue and the absorption and scattering attenuation of light in bone tissue have been clarified by the above-mentioned measurement using continuous light. The same tendency was shown. Therefore, when analyzing bone tissue using light, the same attenuation of light is observed whether the target is a dispersive substance or an absorbent substance. Even when measuring with light, it is not possible to distinguish between the power of attenuation of light due to scattering or the attenuation of light due to absorption.
この問題は時間分解計測法に基づく測光法を用いることにより解決す ることが可能である。 すなわち、 超短時間パルス光を検体に照射し、 入 射したフォ トンが散乱や吸収を受けながら検体内を透過していく際に生 じる運動行程の変化、 つまり光路長変化を、 受光したフオ トンを時間軸 にプロッ トすることによって時間分解計測し、 光吸収、 散乱特性を正確 に評価することが出来る。 すなわち、 入射した時間と位置とが分かって いるフォ トンが、 何秒後にいくっ受光器まで到達したかを測定すること により、 散乱を受けたフォ 卜ンの光路長を推測することができ、 散乱と 吸収の要素を鑑別することが可能になる。  This problem can be solved by using photometry based on time-resolved measurement. In other words, the specimen is irradiated with ultra-short pulsed light, and changes in the movement process that occur when the incident photons pass through the specimen while being scattered or absorbed, that is, changes in the optical path length, are received. By plotting the photons on the time axis, time-resolved measurement can be performed, and the light absorption and scattering characteristics can be accurately evaluated. That is, by measuring how many seconds the photon whose incident time and position are known reaches the light receiver, the optical path length of the scattered photon can be estimated. This makes it possible to distinguish between scattering and absorption factors.
図 6 ( a ) には光吸収体 2 1が存在する検体 (骨組織) 6に光が照射 された場合における光路長が示されており、 同図 ( b ) には光散乱体 2 2が存在する検体 (骨組織) 6に光が照射された場合における光路長が 示されている。 光吸収体 2 1が検体 6内に存在する同図 ( a ) に示す場 合には時間分解計測波形は同図 ( c ) のグラフ、 光散乱体 2 2が検体 6 内に存在する同図 ( b ) に示す場合には時間分解計測波形は同図 ( d ) のグラフに示される。 これら各グラフの横軸は時間 [ p S ] 、 縦軸は光 子のカウン ト数である。 同図 ( c ) に示す典型的な光吸収パターンでは、 信号波形 2 3のピーク時間は参照光波形 2 4のピーク時間から僅かしか 遅れていないが、 同図 ( d ) に示す典型的な光散乱パターンでは、 信号 波形 2 5のピーク時間は参照光波形 2 6のピーク時間から大きく遅れて いる。 また、 信号波形 2 3の最大光強度は信号波形 2 5の最大光強度よ り も大きい。 Fig. 6 (a) shows the optical path length when light is applied to the specimen (bone tissue) 6 where the light absorber 21 is present, and Fig. 6 (b) shows the light scatterer 22. The optical path length when the existing specimen (bone tissue) 6 is irradiated with light is shown. When the light absorber 21 is present in the sample 6 as shown in (a), the time-resolved measurement waveform is the graph in FIG. (C), and the light scatterer 22 is in the sample 6 In the case of (b), the time-resolved measurement waveform is shown in the graph of (d). The horizontal axis of each graph is time [ps], and the vertical axis is the number of photons. In the typical light absorption pattern shown in Fig. (C), Although the peak time of the signal waveform 23 is slightly delayed from the peak time of the reference light waveform 24, in the typical light scattering pattern shown in FIG. 11D, the peak time of the signal waveform 25 is the same as that of the reference light waveform. It is significantly behind the peak time of 26. The maximum light intensity of the signal waveform 23 is larger than the maximum light intensity of the signal waveform 25.
光による測定波形を評価して得られるパラメータは、 基本的には等価 散乱係数/ s ' 、 吸収係数 μ aの 2つである。 これら各係数を前述した 図 1 に示す骨組織解析装置の演算器 1 3で求め、 求めた各係数に基づい て骨組織の状態を類別器 1 4で前述のよ うに類別することにより、 骨組 織の多彩な状態分析をすることが可能になる。 例えば、 本実施例による 骨組織解析装置を、 生きたままのヒ 卜の踵部に適用することにより、 以 下の分析をすることが出来る。  The parameters obtained by evaluating the waveform measured by light are basically two parameters: equivalent scattering coefficient / s' and absorption coefficient μa. These coefficients are obtained by the calculator 13 of the bone tissue analyzer shown in FIG. 1 described above, and the state of the bone tissue is classified by the classifier 14 based on the obtained coefficients as described above. It becomes possible to do various state analysis of. For example, the following analysis can be performed by applying the bone tissue analyzer according to the present embodiment to the heel of a living human.
すなわち、 求めた光散乱係数 μ s ' および光吸収係数/ a の相対関係 力 各係数 /i s ' , a の値が共に高い第 1 の相対関係に類別された場 合には、 骨内に含まれる光散乱体である骨塩量は高く、 骨梁間腔 (皮質 骨では骨髄腔) 内には光吸収体である血液成分に富んだ骨髄組織が多く 含まれているものと解析される。 従って、 この第 1の相対関係に類別さ れる骨組織は健康な骨組織であると分析することができる。  That is, if the calculated relative values of the light scattering coefficient μ s ′ and the light absorption coefficient / a are classified into the first relative relationship where both the values of the respective coefficients / is ′ and a are high, they are included in the bone. The amount of bone mineral, which is a light scatterer, is high, and the intertrabecular space (cortical bone marrow cavity) is considered to contain a large amount of bone marrow tissue rich in blood components, which are light absorbers. Therefore, the bone tissue classified into the first relative relationship can be analyzed as healthy bone tissue.
また、 光散乱係数 /X s ' の値が高く光吸収係数 μ aの値が低い第 2の 相対関係に類別された場合には、 骨塩量は高く なく、 骨梁間腔 (骨髄腔) 内の血液成分に富んだ骨髄組織は、 光散乱体である脂肪組織に置き換え られているものと解析される。 従って、 脂肪含量が増加しているこの骨 組織には、 骨形成、 吸収の周期が遅い老年期に代表される骨変化が起き ているものと分析することができる。  In addition, when the value of the light scattering coefficient / X s' is high and the value of the light absorption coefficient μa is low, the bone mineral content is not high, and the intratrabecular space (bone marrow cavity) is not high. The bone marrow tissue, which is rich in blood components, is analyzed to have been replaced by fat tissue, which is a light scatterer. Therefore, it can be analyzed that this bone tissue with an increased fat content has undergone bone changes typified by old age, in which the cycle of bone formation and resorption is slow.
また、 光散乱係数 μ s ' の値が低く光吸収係数 μ a の値が高い第 3の 相対関係に類別された場合には、 骨塩量は低く、 それに伴い骨梁幅は細 く なり、 骨梁間腔は大きく形成され、 腔内には血液成分に富んだ骨髄組 織が多量に含まれているものと解析される。 従って、 血液成分に富んだ この骨組織には、 骨形成、 吸収の周期が早い女性の閉経後骨粗鬆症に代 表される骨変化が起きているものと分析することができる。 When the light scattering coefficient μ s ′ is low and the light absorption coefficient μ a is high, the bone mineral content is low and the trabecular width is narrow. It is analyzed that the intertrabecular space is large and that the cavity contains a large amount of bone marrow tissue rich in blood components. Therefore, this bone tissue, which is rich in blood components, can be analyzed as having bone changes represented by postmenopausal osteoporosis in women who have a rapid cycle of bone formation and resorption.
また、 各係数 μ s ', aの値が共に低い第 4の相対関係に類別され た場合には、 骨塩量は低く、 骨梁間腔 (骨髄腔) 内には血液成分も脂肪 分も少ししか含まれていないものと解析される。 従って、 この類別は、 骨自体が細い (小さい) 力、、 萎縮しているなどの、 病態的には分類困難 であるが、 上記第 2の相対関係に類別された型の憎悪した型と見ること ができる。 骨組織には老年期に多いと思われる骨変化が起きているもの と分析することができる。  In addition, when the values of the coefficients μ s ′ and a are both low, the bone mineral content is low, and the blood component and fat content in the intertrabecular space (bone marrow cavity) are small. Is analyzed to be included. Therefore, this classification is difficult to classify pathologically, such as thin (small) bones and atrophied bones, but it is regarded as a hated type of the type classified in the second relative relationship above. be able to. Bone tissue can be analyzed to have bone changes that are likely to be common in old age.
ここで、 各係数値が高いか低いかの評価は、 色々な足の厚さ、 色々な 皮膚の色をした正常人の各係数値を統計的に処理して得られた平均値に 基づいて行う ことが考えられる。  Here, the evaluation of whether each coefficient value is high or low is based on the average value obtained by statistically processing the coefficient values of normal persons with various foot thicknesses and various skin colors. It is possible to do it.
骨粗鬆症の骨病変は、 初期には、 骨幹部の皮質骨より、 腰椎、 大腿骨 頸部、 踵骨に代表されるような海綿骨に変化が大きい。 骨粗鬆症罹患に より海綿骨部の骨塩量は減り、 それに伴い骨梁幅は細くなり、 骨梁間腔 Initially, osteoporotic bone lesions change from cortical bone in the diaphysis to trabecular bone such as the lumbar spine, femoral neck, and calcaneus. With osteoporosis, bone mineral density in the trabecular bone decreases, and as a result, the trabecular width narrows and the intertrabecular space
(骨髄腔) は大きく なるという構造変化を呈する。 また、 骨粗鬆症は、 女性の場合、 臨床的に閉経後数年に起こるものと、 老年期に起こるもの とに分類される。 このうちの前者は、 前述の骨の形成と吸収の周期が早 い時期に、 女性ホルモンの急激な欠乏による骨吸収の活性化により急激 に骨病変が進行する病態である。 また、 後者は、 骨の形成の低下が病態 の主因になるが、 骨形成と吸収の周期が遅いため、 病変は徐々に進行す る。 当然、 これら両者は最適な治療法も異なり、 治療開始の時期も異な るため、 両者の鑑別は非常に重要である。 The (bone marrow cavity) presents a structural change that increases. In women, osteoporosis is clinically classified as occurring several years after menopause or as occurring in old age. The former is a condition in which bone lesions progress rapidly due to the activation of bone resorption due to the rapid deficiency of female hormones during the earlier period of bone formation and resorption. In the latter, the pathology is mainly due to a decrease in bone formation, but the disease progresses gradually due to the slow cycle of bone formation and resorption. Naturally, the two are different in the optimal treatment and the time to start the treatment is also different, so it is very important to distinguish them.
閉経後骨粗鬆症におけるような骨の形成と吸収の周期が早いタイプの 海綿骨組織では、 骨梁間腔は血液成分に富んだ骨髄組織が満たされてい る。 また、 老年期に代表される骨の形成と吸収の周期が遅い海綿骨組織 の骨梁間腔の骨髄組織は、 血液成分が脂肪組織に置き換わっていること が推測される。 また、 皮質骨部においても軽度の変化は認められ、 骨粗 鬆症の重度の進行例では、 皮質骨の厚さが減少し、 それに伴う皮質骨の 骨塩量の低下や、 骨髄腔の脂肪化などが認められる。 A type that has a fast cycle of bone formation and resorption as in postmenopausal osteoporosis In cancellous bone tissue, the intertrabecular space is filled with blood-rich bone marrow tissue. In addition, it is presumed that blood components are replaced by adipose tissue in the bone marrow tissue of the intertrabecular space of the cancellous bone tissue, which has a slow cycle of bone formation and resorption, as represented by old age. Mild changes were also observed in the cortical bone, and in severely advanced osteoporosis, the thickness of the cortical bone decreased, resulting in a decrease in the amount of bone mineral in the cortical bone and the fat in the medullary cavity. Is recognized.
—方、 光は X線や超音波と異なり、 骨内カルシウムに対しては強い散 乱特性を示し、 近赤外域の光は骨髄腔 (海綿骨では骨梁間腔) 内の H b に対しては吸収特性を示す。 また、 光は脂肪組織に対しては主に散乱特 性を示す。 従って、 測定結果で散乱が非常に強かった場合には、 骨組織 は、 カルシウムの含量が多く、 骨内部構造が複雑か、 もしく は脂肪の含 有量が多いかの 2通りの評価が考えられる。 これら評価の鑑別は、 H b による吸収特性を上記のよ うに評価することによって行える。 もし、 骨 組織が強い光吸収特性を示せば、 骨内部には骨髄の血液成分が豊富に含 まれ、 B M Dの高い健康な骨組織であることが推測できる。 また、 吸収 特性が弱ければ、 骨髄内部で血液が脂肪に置き換えられている可能性が 考えられ、 この場合の散乱の増加は高い B M Dの影響ではなく、 脂肪量 の増加によるものであると推測することができる。 さらに、 脂肪の吸収 スぺク トルのピークがある 9 3 0 [ n m ] 付近の波長光での検討を加え れば、 より明確に脂肪分を計測することが可能である。 また、 散乱が弱 い場合は B M Dが低いことが疑われるが、 骨粗鬆症などで骨梁間隙が広 くなり、 そこに血液が多く含まれているなどの状態であれば、 さらに吸 収は強くなる。  On the other hand, light is different from X-rays and ultrasound, and has a strong scattering property for intraosseous calcium, and near-infrared light is directed to Hb in the bone marrow cavity (intertrabecular space in cancellous bone). Indicates absorption characteristics. In addition, light mainly exhibits scattering characteristics with respect to adipose tissue. Therefore, if the scattering is very strong in the measurement results, two types of evaluation can be considered as to whether the bone tissue has a high calcium content, a complicated internal structure of the bone, or a high fat content. Can be Discrimination of these evaluations can be performed by evaluating the absorption characteristics of Hb as described above. If the bone tissue shows strong light absorption properties, it can be assumed that the bone is rich in blood components of bone marrow and is a healthy bone tissue with a high BMD. Also, if the absorption characteristics are weak, it is possible that blood is replaced by fat inside the bone marrow, and it is speculated that the increase in scattering in this case is not due to the effect of high BMD but to an increase in fat mass. be able to. In addition, by examining light with a wavelength around 930 [nm], which has the peak of the fat absorption spectrum, it is possible to measure fat more clearly. If the scattering is weak, the BMD is suspected to be low.However, if the trabecular gap is widened due to osteoporosis and contains a lot of blood, the absorption becomes even stronger. .
本実施例で今回使用した装置では測定しなかったが、 コ 7一ゲンの吸 収スペク トルもさらに高い波長域に存在するため、 より広範囲な波長域 で測定可能なレーザ測光システムを用いることにより、 骨組織の散乱、 吸収特性の測定と、 吸収スぺク トルを利用した分光分析法により、 骨質 の新しい評価をすることが可能である。 Although the measurement was not performed by the apparatus used in this example in this example, the absorption spectrum of co-gen also exists in a higher wavelength range, so that by using a laser photometering system that can measure in a wider range of wavelengths, , Scattering of bone tissue, It is possible to make a new assessment of bone quality by measuring absorption characteristics and spectroscopic analysis using absorption spectra.
本実施例により生きたままのヒ トの骨組織についても時間分解計測す ることが明らかになり、 さらに、 その時間分解計測波形の解釈をする際 に、 骨組織の光散乱係数および光吸収係数の値に応じてこれら係数を前 述のように類別することにより、 骨の周辺組織の影響を考慮することも 可能になった。 皮膚、 脂肪組織、 筋組織、 腱組織などが複雑に重なり合 つている骨周辺組織を光が透過する際におけるフォ トンの運動行程の変 化を推測するのは非常に難しい問題である。 近年、 散乱、 吸収係数の異 なる複数の組織を透過する際の光路長の影響については、 様々なモデル 実験による数学的検討がなされているが、 この問題についての最終的な 解決は得られていない。 また、 骨組織を光学的に検討した報告は少なく、 僅かに連続光を用いた豚の頭蓋骨薄切片での基礎光学特性の検討がある だけである。 本実施例のよ うな観点から骨組織を解析した例は今まで世 界になく、 本報告が最初のものと思われる。 このよ うな本実施例による 骨組織解析装置および方法により、 骨組織を分析することにより、 骨粗 鬆症罹患に伴う上述した骨変化は精度良く、 正確に解析することが可能 である。  This example demonstrates that time-resolved measurement is also performed on human bone tissue in a living state. Further, when interpreting the time-resolved measurement waveform, the light scattering coefficient and light absorption coefficient of the bone tissue are determined. By classifying these coefficients as described above according to the value of, it became possible to take into account the effects of bone surrounding tissue. It is a very difficult problem to estimate the change in the photon's movement path when light passes through the peri-bone tissue where the skin, adipose tissue, muscular tissue, tendon tissue, etc. are complexly overlapped. In recent years, the effects of the optical path length when transmitting through multiple tissues with different scattering and absorption coefficients have been mathematically studied by various model experiments, but a final solution to this problem has been obtained. Absent. There have been few reports of optical studies of bone tissue, and there is only a study of the basic optical properties of thin slices of pig skull using continuous light. There has been no example in the world of analyzing bone tissue from the viewpoint as in this example, and this report seems to be the first one. By analyzing the bone tissue using the bone tissue analysis apparatus and method according to the present embodiment, the above-described bone change accompanying osteoporosis can be analyzed with high accuracy.
なお、 上記実施例の説明においては、 パルス レーザシステムを用い、 骨組織にパルスレーザ光を照射して時間分解計測法によつて骨組織内の 光散乱係数および光吸収係数を求めた。 しかし、 骨組織に連続レーザ光 を照射するフユ一ズモジュレーション法を採用してこれら各係数を求め るようにしてもよレ、。 この場合には、 骨組織に照射する連続レーザ光に 変調が加えられ、 骨組織を透過することによってこの変調光の位相がど のように変化するかといった時間情報が調べられることによ り、 骨組織 の光散乱係数および光吸収係数が求められる。 連続レーザ光を光源とす るシステムは、 光源の冷却方法, 安定性や整備法などの点において、 パ ルス レーザ光を光源とするシステムに比較して扱いが簡易であり、 しか も、 低価格に得られる。 従って、 このような光源を用いて装置を構成す れば、 より簡易に骨組織を解析することが可能になる。 産業上の利用可能性 In the description of the above embodiment, the pulse laser system was used to irradiate the pulsed laser beam to the bone tissue, and the light scattering coefficient and the light absorption coefficient in the bone tissue were obtained by the time-resolved measurement method. However, it is also possible to employ a fuse modulation method in which bone tissue is irradiated with continuous laser light to obtain each of these coefficients. In this case, modulation is applied to the continuous laser light that irradiates the bone tissue, and time information such as how the phase of the modulated light changes by transmitting through the bone tissue is examined. The light scattering coefficient and light absorption coefficient of the bone tissue are determined. Use continuous laser light as the light source This system is simpler to handle than a system using a pulse laser beam in terms of cooling, stability and maintenance of the light source, and can be obtained at a low price. Therefore, if the device is configured using such a light source, it becomes possible to analyze the bone tissue more easily. Industrial applicability
以上説明したよ うに本発明によれば、 透過光から得られた骨組織中の 光散乱係数および光吸収係数の相対関係を類別することによ り、 骨組織 內部を光によって非侵襲的に解析することが可能になる。 このため、 X 線を用いた従来の骨組織解析手法は、 骨内カルシウムの分布、 密度から 骨の構造変化を推定しているに過ぎなかったが、 本発明によれば、 計測 した散乱係数および吸収係数に基づいてより具体的に骨組織内部を評価 でき、 より精度良く正確に骨構造変化を解析することが可能になる。 従 つて、 従来の超音波法による骨組織解析手法や、 血液検査や尿検査によ つて骨形成および吸収マ一カーを測定する間接的な従来の解析手法と比 較しても優れた解析をすることが可能になる。 また、 光を用いて計測す るため、 X線の被曝に対する防曝施設は不要になり、 しかも、 被検者に 対する侵襲の影響を心配する必要もない。  As described above, according to the present invention, by analyzing the relative relationship between the light scattering coefficient and the light absorption coefficient in the bone tissue obtained from the transmitted light, the bone tissue 內 can be non-invasively analyzed by light. It becomes possible to do. For this reason, the conventional bone tissue analysis method using X-rays only estimates the structural change of the bone from the distribution and density of calcium in the bone, but according to the present invention, the measured scattering coefficient and It is possible to more specifically evaluate the inside of bone tissue based on the absorption coefficient, and it becomes possible to analyze changes in bone structure with higher precision and accuracy. Therefore, superior analysis can be performed compared to conventional bone tissue analysis methods using ultrasonic methods and indirect conventional analysis methods that measure bone formation and resorption markers using blood and urine tests. It becomes possible to do. In addition, since measurement is performed using light, there is no need for an exposure protection facility for X-ray exposure, and there is no need to worry about the effects of invasion on the subject.

Claims

求 の 範 囲 Range of request
1 . レーザ光を出射するレーザ光源と、 この レーザ光源から出射された レーザ光を骨組織に導く導光手段と、 骨組織を透過した光を受光する受 光器と、 得られた透過光から骨組織の光散乱係数および光吸収係数を求 める演算器と、 求めた光散乱係数と光吸収係数との相対関係を各係数の 値が共に高い第 1 の相対関係, 光散乱係数値が高く光吸収係数値が低い 第 2の相対関係, 光散乱係数値が低く光吸収係数値が高い第 3の相対関 係, または各係数の値が共に低い第 4の相対関係のいずれかに類別する 類別器と、 この類別結果を表示する表示器とを備えて構成されたことを 特徴とする骨組織解析装置。 1. A laser light source that emits laser light, a light guide that guides the laser light emitted from the laser light source to bone tissue, a light receiver that receives light transmitted through the bone tissue, and the obtained transmitted light. A calculator for calculating the light scattering coefficient and the light absorption coefficient of the bone tissue, and the first relation, where the values of the coefficients are both high, and the light scattering coefficient value Classified as either a second relative relationship with a high light absorption coefficient value and a low relative value, a third relative relationship with a low light scattering coefficient value and a high light absorption coefficient value, or a fourth relative relationship with both low coefficient values A bone tissue analyzer, comprising: a classifier; and a display for displaying the classification result.
2 . 前記レーザ光源はパルス レーザ光を出射し、 前記演算器は骨組織の 光入射点から光検出点に至るまでに透過光が経た時間および透過光の強 度の時間分解計測結果に基づいて前記光散乱係数および光吸収係数を求 めることを特徵とする請求の範囲第 1項記載の骨組織解析装置。  2. The laser light source emits a pulsed laser beam, and the arithmetic unit calculates the time required for the transmitted light to travel from the light incident point to the light detection point of the bone tissue and the time-resolved measurement result of the transmitted light intensity. 2. The bone tissue analyzer according to claim 1, wherein the light scattering coefficient and the light absorption coefficient are obtained.
3 . 前記レーザ光源は連続レーザ光を変調して出射し、 前記演算器は骨 組織を透過したこの連続レーザ光の変調光の位相変化に基づいて前記光 散乱係数および光吸収係数を求めることを特徴とする請求の範囲第 1項 記載の骨組織解析装置。  3. The laser light source modulates and emits continuous laser light, and the calculator determines that the light scattering coefficient and the light absorption coefficient are based on the phase change of the modulated light of the continuous laser light transmitted through the bone tissue. The bone tissue analysis device according to claim 1, wherein
4 . 前記各係数値の高いか低いかの評価は、 正常人の前記各係数値の平 均値に基づいて行う ことを特徴とする請求の範囲第 1項記載の骨組織解 析装置。  4. The bone tissue analyzer according to claim 1, wherein the evaluation of whether each of the coefficient values is high or low is performed based on an average value of each of the coefficient values of a normal person.
5 . レーザ光源から出射されたレーザ光を骨組織に照射する第 1 の工程 と、 骨組織を透過した光を受光する第 2 の工程と、 得られた透過光から 骨組織の光散乱係数および光吸収係数を求める第 3の工程と、 求めた光 散乱係数と光吸収係数との相対関係を、 各係数の値が共に高い第 1の相 対関係, 光散乱係数値が高く光吸収係数値が低い第 2の相対関係, 光散 乱係数値が低く光吸収係数値が高い第 3の相対関係, または各係数の値 が共に低い第 4の相対関係のいずれかに類別する第 4の工程とを備えた ことを特徴とする骨組織解析方法。 5. The first step of irradiating the bone tissue with the laser light emitted from the laser light source, the second step of receiving the light transmitted through the bone tissue, and the light scattering coefficient of the bone tissue from the obtained transmitted light. The third step of obtaining the light absorption coefficient and the relative relationship between the obtained light scattering coefficient and the light absorption coefficient are described by the first phase in which the values of each coefficient are both high. Pair relation, second relative relation with high light scattering coefficient value and low light absorption coefficient value, third relative relation with low light scattering coefficient value and high light absorption coefficient value, or fourth relation with low coefficient values And a fourth step of categorizing the bone tissue into any one of the relative relationships described above.
6 . 前記第 1 の行程における前記レ一ザ光源はパルス レーザ光を出射し、 前記第 3の行程における前記光散乱係数および光吸収係数を求める演算 は骨組織の光入射点から光検出点に至るまでに透過光が経た時間および 透過光の強度の時間分解計測結果に基づいて行う ことを特徴とする請求 の範囲第 5項記載の骨組織解析方法。  6. The laser light source in the first step emits a pulsed laser beam, and the calculation of the light scattering coefficient and the light absorption coefficient in the third step is performed from the light incident point of the bone tissue to the light detection point. 6. The bone tissue analysis method according to claim 5, wherein the method is performed based on a time elapsed through the transmitted light and a time-resolved measurement result of the intensity of the transmitted light.
7 . 前記第 1 の行程における前記レーザ光源は連続レーザ光を変調して 出射し、 前記第 3の行程における前記光散乱係数および光吸収係数を求 める演算は骨組織を透過した前記連続レーザ光の変調光の位相変化に基 づいて行う ことを特徴とする請求の範囲第 5項記載の骨組織解析方法。 7. The laser light source in the first step modulates and emits a continuous laser beam, and the calculation of the light scattering coefficient and the light absorption coefficient in the third step is performed by calculating the continuous laser light transmitted through a bone tissue. 6. The bone tissue analysis method according to claim 5, wherein the method is performed based on a phase change of the modulated light.
8 . 前記第 4の行程における前記各係数値の高いか低いかの評価は、 正 常人の前記各係数値の平均値に基づいて行う ことを特徴とする請求の範 囲第 5項記載の骨組織解析方法。 8. The bone according to claim 5, wherein the evaluation of whether each of the coefficient values is high or low in the fourth step is performed based on an average value of each of the coefficient values of a normal person. Tissue analysis method.
PCT/JP1996/002511 1995-09-07 1996-09-05 Bony tissue analyzer and method WO1997008994A1 (en)

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JPS63216549A (en) * 1987-03-05 1988-09-08 帝人株式会社 Bone form evaluating method and apparatus
JPH06129984A (en) * 1992-07-20 1994-05-13 Hamamatsu Photonics Kk Method and device for absorption information measurement within scatterer-absorber

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Publication number Priority date Publication date Assignee Title
JPS63216549A (en) * 1987-03-05 1988-09-08 帝人株式会社 Bone form evaluating method and apparatus
JPH06129984A (en) * 1992-07-20 1994-05-13 Hamamatsu Photonics Kk Method and device for absorption information measurement within scatterer-absorber

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