WO1997008994A1 - Appareil et procede d'analyse de tissus osseux - Google Patents

Appareil et procede d'analyse de tissus osseux 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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English (en)
Japanese (ja)
Inventor
Akira Itabashi
Akira Takeuchi
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Akira Itabashi
Akira Takeuchi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4504—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring 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

L'invention porte sur un appareil d'analyse non invasive de l'intérieur de tissus osseux par la lumière et sur le procédé associé. L'appareil comporte un opérateur (13), un trieur (14) et un écran (15). L'opérateur (13) calcule le coefficient de diffusion de lumière νs'et le coefficient d'absorption de lumière νa d'un échantillon du tissu osseux (6) en fonction de la forme d'onde par rapport au temps de la lumière émise reçue. Le trieur (14) trie la corrélation entre les coefficients νs' et νa ainsi obtenus dans l'une quelconque des premières corrections où les valeurs de νs' et de νa sont toutes deux élevées, la deuxième corrélation où la valeur de νs' est élevée et celle de νa est faible, la troisième corrélation où la valeur de νs' est faible et celle de νa est élevée, et la quatrième corrélation où les valeurs de νs' et de νa sont toutes deux faibles. L'écran (15) présente les résultats du tri.
PCT/JP1996/002511 1995-09-07 1996-09-05 Appareil et procede d'analyse de tissus osseux WO1997008994A1 (fr)

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AU68896/96A AU6889696A (en) 1995-09-07 1996-09-05 Bony tissue analyzer and method

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JP7/254463 1995-09-07
JP25446395A JPH0970404A (ja) 1995-09-07 1995-09-07 骨組織解析装置および方法

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JP2006300666A (ja) * 2005-04-19 2006-11-02 Univ Nagoya 農産物の内部品質測定装置
WO2006115207A1 (fr) * 2005-04-22 2006-11-02 Kanazawa University Dispositif de mesure de densite osseuse
JP2007007267A (ja) * 2005-07-01 2007-01-18 Kanazawa Univ 骨密度計測装置
US20090306520A1 (en) 2008-06-02 2009-12-10 Lightlab Imaging, Inc. Quantitative methods for obtaining tissue characteristics from optical coherence tomography images

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63216549A (ja) * 1987-03-05 1988-09-08 帝人株式会社 骨形態評価方法及び装置
JPH06129984A (ja) * 1992-07-20 1994-05-13 Hamamatsu Photonics Kk 散乱吸収体内部の吸収情報計測装置及び方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63216549A (ja) * 1987-03-05 1988-09-08 帝人株式会社 骨形態評価方法及び装置
JPH06129984A (ja) * 1992-07-20 1994-05-13 Hamamatsu Photonics Kk 散乱吸収体内部の吸収情報計測装置及び方法

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