WO2015059969A1 - 光ファイバ式生体診断用センサシステム及び血管挿入式分布圧力測定装置 - Google Patents
光ファイバ式生体診断用センサシステム及び血管挿入式分布圧力測定装置 Download PDFInfo
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Definitions
- the present invention relates to a medical measurement system, and more particularly, by collecting and analyzing biological information such as blood pressure using a distributed optical fiber sensor system that measures temperature, pressure, and strain distribution using an optical fiber cable.
- the present invention relates to a fiber optic biodiagnostic sensor system that provides biological diagnostic information, and a blood vessel insertion type distributed pressure measuring device that measures blood pressure and the like.
- the coronary flow reserve ratio (FFR) is used as an important diagnostic index.
- PCI percutaneous transluminal coronary angioplasty
- FFR coronary flow reserve ratio
- ischemic heart disease a treatment method for ischemic heart disease, and is accumulated in arterial blood vessels composed of cells containing atheroma, lipids, calcium and various fibrous bonds, and dead bodies of cells. This is a treatment that expands the coronary arteries of the stenotic heart by increasing the blood flow.
- FFR is an index for knowing the degree of blood flow inhibition due to this stenotic lesion, and is an amount expressed as a ratio with respect to the normal value of the blood flow at the distal portion of the lesion.
- FIG. 6A is a schematic diagram showing a stenotic lesion occurring in a blood vessel, and an arrow indicates a blood flow direction.
- FIG. 6B is a model diagram of the pressure change in the blood vessel corresponding to FIG. 6B, the vertical axis indicates the maximum pulsation pressure in the blood vessel, and the horizontal axis indicates the optical fiber length (Lof).
- the optical fiber length is the distance from the start point to the sensor tip position when the predetermined start point of the optical fiber is zero.
- the intravascular pressure (blood pressure) at these positions is the reference pressure P as shown in the figure. Gradually decrease from 0 (corresponding to Pa above). Assuming that the pressure at the stenosis position S1 after the gradual decrease is P 1 and the pressure at the stenosis position S2 is P 2 , P 1 / P 0 and P 2 / P 0 are the coronary blood flow reserve amounts at the respective positions.
- the PCI is applied when this value is 0.75 or less.
- Pa is measured at the tip of a guiding catheter
- Pd is measured by a pressure sensor at the tip of a dedicated catheter called a pressure wire.
- pressure or flow rate measurement in PCI is performed. There is a demand for obtaining a distribution instead of a single value.
- the probe diameter for measurement is better for the coronary artery (thin diameter) and the heart valve membrane to be thinner (for example, 0.4 mm ⁇ or less), and has a suitable rigidity as a probe suitable for measurement, and A device having a mechanism for supporting an optical fiber is required.
- a multifunctional sensor such as the use of a sensor that does not use an electrical sensor is used. It is required to be.
- the conventional technique has the following general usage problems in measuring the pressure in the blood vessel.
- the first point is that the number of measurement points is limited by the number of sensors because the measurement by the sensor is a single point measurement and not a distribution measurement.
- the second point requires measurement by a plurality of sensors as described above.
- the number of measurement points is limited to several, the length of the blood vessel that can be measured without moving the probe is shortened.
- the third point is that it is difficult to measure vascular stenosis having a plurality of lesions because the probe diameter cannot be reduced to a certain extent because a plurality of sensors are required, and the sensor structure is complicated. thing.
- the fourth point is that there is an influence due to variations in sensor sensitivity because a plurality of fibers having different sensitivities are basically used, and there is a variation in sensitivity even though the sensor is temporarily used or disposable. For this reason, all sensors need to be calibrated, which is not suitable for mass production and increases waste. From this point of view, it is considered practically difficult to use a sensor according to the prior art as a sensor for measuring pressure in a blood vessel.
- a measurement method that uses an optical fiber as a sensor, simultaneously separates two or more physical quantities such as pressure and strain of a measured object, and measures its distribution as independent measurement parameters It has been known.
- This measurement method uses a Brillouin or Rayleigh scattering frequency change or phase change (see, for example, Patent Document 3), and utilizes the fact that an optical fiber responds to various physical quantities such as strain, temperature, and pressure as a sensor. Is.
- some optical fibers utilize the property of simultaneously reacting to strain, temperature, and pressure, which will be described in more detail below.
- the present invention proposes a technique for specifying a pressure by measuring strain in an inorganic glass-based optical fiber. In the case of an organic optical fiber, the present invention directly relates to equations (1) and (2). It is also possible to measure the pressure.
- the frequency shift ⁇ R due to Rayleigh scattering and the frequency shift ⁇ B due to Brillouin scattering are simultaneously measured, and in order to further improve the measurement accuracy, Rayleigh scattering is used, An error may be reduced by filtering the Brillouin scattering frequency shift ⁇ B.
- a measurement example of the relationship between each frequency shift and pressure is shown in FIG. In this case, if a TW-COTDR (Tunable Wavelength Coherent Optical Time Domain Reflectometry) method, a BOCDA (Brillouin Optical Correlation Domain Analysis) method, or the like is used as the hybrid measurement method, the distortion accuracy is 0.079 ⁇ and the temperature accuracy is 0.009.
- the optical fiber coating material (protective film, specifically, for example, PFA, that is, tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer)
- the axial effect of volume change is the axis of the optical fiber.
- the coating material has a lower rigidity than glass because it affects the strain in the direction
- the pressure sensitivity can be apparently increased by increasing the thickness by the coating (see FIG. 2).
- the apparent pressure sensitivity is almost equal to the data of 0.25 mm ⁇ , and in fact, the apparent pressure sensitivity does not increase so much.
- the pressure range to be measured is ⁇ 4.0 to 40.0 kPa ( ⁇ 30 to 300 mmHg), heat per 1 ° C.
- the effect is ⁇ 40.0 Pa / ° C.
- the outer diameter of the catheter that can be used is preferably 0.46 mm ⁇ or less (see Patent Document 2).
- the accuracy of the pressure to be measured was compared with the pressure accuracy in the method of measuring pressure, strain and temperature simultaneously by the hybrid measurement method combining Brillouin and Rayleigh scattered light, which is planned to be applied in this application.
- the pressure measurement accuracy cannot be satisfied if the optical fiber as a sensor is in a normal shape.
- the present invention has been made to solve the above-described problems, and simultaneously measures measurement data in which two or more physical quantities such as strain obtained by changing the temperature and pressure of a measured object are mixed using an optical fiber.
- two or more physical quantities of the object to be measured can be separated and measured as independent measurement parameters, and multifunctional measurement can be realized with a small number of optical fibers of two or less. It is intended to do.
- An optical fiber biodiagnostic sensor system comprises: Inserted into the blood vessels of the body, An outer layer that is deformed by external pressure and does not allow the measured object to enter the inside, a single-mode optical fiber that is deformed by temperature and strain, and a single-mode optical fiber that is arranged to cover the single-mode optical fiber, and propagates the pressure applied to the outer layer.
- a structure that continuously converts the pressure into strain of the single-mode optical fiber, and a blood vessel insertion type distributed pressure measuring device that measures temperature and pressure distribution at a predetermined location of the measured object, The laser beam is emitted to the single mode optical fiber, the frequency change of the scattered light generated in the single mode optical fiber is continuously detected, and the temperature of the single mode optical fiber obtained from the detected frequency change of the scattered light is detected.
- a measuring device that calculates and calculates a blood pressure at a predetermined position of the single-mode optical fiber from a change and a strain change;
- a memory for storing a calculated value calculated by the measuring machine;
- an analysis / display device for performing a desired analysis or display based on the operation value stored in the memory, It is equipped with.
- the blood vessel insertion type distributed pressure measuring device is inserted into a blood vessel of a living body, and measures the temperature and pressure distribution at a predetermined location of the measured object,
- An outer layer that is deformed by external pressure and does not allow the object to be measured to enter the interior;
- the single mode optical fiber is disposed so as to cover, propagates the pressure applied to the outer layer, continuously converts the pressure distribution into strain of the single mode optical fiber, and a part of the single mode optical fiber. Or a structure that contacts a part of the single-mode optical fiber at a plurality of locations.
- optical fiber biodiagnostic sensor system of the present invention it is possible to separate a plurality of physical quantities to be measured and measure them continuously as independent measurement parameters with high accuracy. Further, even if there are a plurality of measurement sites, it is possible to measure with high accuracy at a time. In addition, there is an effect that multifunctional measurement can be realized with a small number of optical fibers of two or less. In addition, measurement is possible even for blood vessels that are thinner than conventional ones, and there is no need to make holes around the measurement probe. Is possible.
- FIG. 5 is an explanatory diagram of another optical fiber structure material of the optical fiber type biodiagnostic sensor system according to the first to third embodiments of the present invention.
- FIG. 6 is an explanatory diagram of still another optical fiber structure material of the optical fiber type biomedical sensor system according to the first to third embodiments of the present invention. It is a figure which shows an example of the sensor part used for the conventional sensor system for biodiagnosis.
- Embodiment 1 the optical fiber type biodiagnostic sensor system according to the first embodiment of the present invention will be described with reference to FIG.
- the system shown in the first embodiment is a basic system of the sensor system for optical fiber biodiagnosis of the present invention.
- This sensor system is mounted inside a blood vessel insertion type distributed pressure measuring device (hereinafter referred to as “catheter” in the present invention) 1 which is a component of the system inserted into a blood vessel of a living body to be measured.
- the sensor output obtained from the optical fiber that requires the sensor function is stored as data serving as a basis for performing a biological diagnosis, and this data is analyzed and displayed.
- the tip of the catheter 1 is equipped with a jet tip (hereinafter referred to as “J tip”) 2 which is a guide portion for facilitating insertion of the catheter into a blood vessel. Is inclined with respect to the axis of the catheter, and is connected to a metal structure 4 such as SUS at the rear end thereof.
- a spiral wire may be used instead of the rubber outer layer (described in detail later).
- the surface of the catheter 1 has an outer layer 5 made of rubber or a soft skin material that does not adversely affect the human body, and blood to be measured does not pass through the outer layer 5, but the blood pressure passes through the soft outer layer 5. It is transmitted to the structure 4.
- the structure 4 has a function of converting a loaded pressure into an extension in the longitudinal direction, and a single mode optical fiber (hereinafter abbreviated as an SM fiber) 3 having a sensor function inside thereof is added to the longitudinal direction described above. Cause deformation of elongation.
- the catheter 1 is provided with an operation handle 6 for operating a main movement of the catheter at a hand portion.
- the SM fiber 3 is not in direct contact with blood, since the elongation of the structure 4 is proportional to the blood pressure, the axial strain of the SM fiber 3 is proportional to or converted to the pressure of the blood to be measured. Can do.
- a jacket (not shown) for guiding the insertion of the catheter 1 into the living body on the surface of the living body at the insertion portion into the living body is provided on the outer peripheral portion of the catheter 1.
- the temperature of the entire blood vessel is usually not constant, and a measurement method that takes temperature non-uniformity into consideration is required. That is, when measuring pressure, it must also be possible to measure temperature.
- the sensor output detected by the SM fiber 3 passes through the multi-core SM fiber 7 connecting the catheter 1 and the measuring device 8, and the measuring device 8 uses the Brillouin scattering frequency shift ⁇ B and the Rayleigh scattering frequency shift ⁇ R.
- the signal is synchronized with the synchronization signal as necessary) and output to the data memory 9 as distribution data such as the temperature of blood in the blood vessel and the converted blood pressure.
- the data stored in the data memory 9 is analyzed by the analysis / display device 10 to obtain a coronary blood flow reserve ratio (FFR) or the like as diagnostic data as desired data, and the blood pressure distribution at the site to be diagnosed
- FFR coronary blood flow reserve ratio
- the data is output as signal data, and is displayed as a chart on a display or the like provided in the analysis / display device 10 as necessary.
- FIG. 1 A summary of the above measurement procedure is shown in FIG. In this figure, the measurement start time (measurement start time from measuring 8) and t 0, at ⁇ t time interval SM fiber 3, the measurement is repeated. In each measurement, the frequency shift ⁇ R of Rayleigh scattering and the frequency shift ⁇ B of Brillouin scattering, which are sensor outputs, are measured. Next, using these two frequency shifts ⁇ R and ⁇ B and the temperature T 0 and the displacement ⁇ 0 in the reference state previously input to the measuring machine 8 as initial values, the temperature displacement ⁇ T and the strain change A distribution of ⁇ with respect to the measurement position is obtained (see Expressions (3) and (4)).
- a desired blood pressure (pressure) P is obtained using the measuring device 8 as a conversion by a function of the strain ⁇ . Then, the pressure P obtained by the measuring device 8 is output to the data memory 9 and stored. Thereafter, the analysis / display device 10 displays the data analyzed in the data memory 9 as a distribution of the pressure P at time t in a desired display format.
- the time interval ⁇ t is required to have a speed at which blood pulsations can be distinguished, and blood pressure distribution can be obtained at each time interval with reference to 100 times or more per second (in FIG. 15, 250 times per second). Example). Then, a coronary flow reserve ratio (FFR) or the like is obtained using the distribution when the pulsation pressure is maximum.
- FFR coronary flow reserve ratio
- the procedure for determining the coronary blood flow reserve ratio (FFR) will be described in more detail with reference to FIG.
- the measured pressure Pmes (z, t) may include the influence of static strain generated when the catheter 1 is inserted. Therefore, a method for removing the influence of the static strain using the pressure measurement values obtained at the two positions A and B will be described with reference to FIG. In Step 1 of FIG.
- the measurement waveform of ST1 is a model diagram showing changes in left ventricular pressure corresponding to two heart beats.
- step 2 a median value at the position A or the position B is obtained from the measured pressure Pmes (z, t) according to the equation (5) (see the equation (5)), or An average value at the position A or the position B is obtained according to the equation (6) (see the equation (6). The integral symbol ⁇ is used). This value is obtained at all positions to be measured (ST2).
- step 3 abbreviated as ST3
- the median value Pmed (z) or Pav (z) obtained in ST2 is subtracted from the measured value Pmes (z, t), and the pressure value after subtraction is set to P (Z, t) is set (see equations (7) and (8), respectively).
- step 4 the measurement position z is changed to obtain the value of the pressure P (z, t) at each position, and the change in pressure is plotted with z as the horizontal axis (distance). From this change, the FFR is obtained and determined.
- the blood pressure in the blood vessel of the living body to be measured is determined in a predetermined manner, both temporally and spatially, by using frequency shift data by two types of scattered light. Since the measurement can be continuously performed at the position, the physical quantity to be measured can be measured by one measurement only by using one SM fiber 3. Further, in the conventional point measurement sensor, measurement is difficult in the case of a blood vessel having a plurality of vascular stenosis due to the structure of the measurement probe. However, according to the present invention, the blood vessel can be continuously measured. Even when there are a plurality of stenosis, it is possible to cope (see FIG. 6). In FIG.
- FIG. 6 shows a case where there are a plurality of vascular stenosis.
- the present invention is not limited to this. Of course, measurement is possible even when there is only one vascular stenosis. Even in this case, the stenosis position can be obtained from the pressure measurement, which is considered useful as biodiagnosis data.
- FIG. 7 shows a cross-sectional view of the structure of a general sensor portion in this case.
- a J tip 2 made of plastic (for example, vinyl chloride) having an inclined portion is provided at the tip, and an SM fiber 3 is provided at the central axis portion of the sensor portion connected thereto.
- a structure 4 for transmitting external pressure to the outer periphery of the SM fiber 3 and converting the strain into strain of the SM fiber 3 is provided on the outer periphery thereof, and an outer layer 5 made of, for example, rubber is provided on the outer periphery (FIG. 7). (A)).
- a spiral wire layer 16 may be provided on the outer periphery of the outer layer to facilitate insertion of the catheter into the living body (FIG. 7B). Even if the wire layer 16 is attached, the state in which pressure is applied to the outer layer 5 does not change because blood passes between the wires.
- the outer diameter of the SM fiber 3 shown in this figure is about 80 to 250 ⁇ m, and the structure 4 that is a protective layer of the SM fiber disposed on the outer periphery thereof converts the applied pressure into strain, It is composed of SUS, and has a function of proportionally converting the ambient pressure into the amount of elongation in the longitudinal direction that is the axial direction of the SM fiber 3 (which will be described in more detail below).
- the strain of the SM fiber can be made proportional to the pressure.
- the outer diameter as a catheter can be about 0.4 mm or less. For this reason, the specification as a biodiagnosis sensor to which the present invention is scheduled to be applied can be satisfied, and it can be effectively used in the measurement of pressure or flow velocity with PCI. Further, even when the blood vessel of the living body to be measured is a blood vessel having a relatively small outer diameter, pressure (blood pressure) measurement can be performed.
- the structure 4 is integrated as a SM fiber coating.
- the sensitivity received by the SM fiber is increased by changing the pressure received by the coating material.
- the pressure sensitivity can be apparently increased by increasing the thickness by the coating (see FIG. 2).
- the outer diameter of the catheter needs to be about 0.4 mm or less as described above. We cannot expect pressure sensitivity to increase several times or more. It is also effective to construct the SM fiber itself with a plastic material having low rigidity. Therefore, in the following, a description will be given of an appropriate structural material that has a continuous, high-precision, uniform and simple structure and converts distributed pressure into continuous strain.
- FIG. 8A a model is considered in which an opening having a diameter D is formed on the outer peripheral surface of a cylindrical measuring probe in which an SM fiber is disposed on the central axis, and an external pressure acts on the opening.
- the measurement probe simulates a catheter, and the external pressure corresponds to the blood pressure at the opening.
- the structure is an axial object, but in this case, as shown in FIG. 8 (b), two halves arranged at an angle (angle ⁇ ) with respect to the SM fiber, which is displayed only in a half portion, are displayed.
- an elastic bar having the same shape receives external pressure (pressure P) acting on the opening on the outer periphery of the measurement probe at this opening.
- pressure P external pressure
- the structure is disposed at a distance h from the outer periphery of the measurement probe to the SM fiber and a distance (pitch) L between AB in the direction along the SM fiber axis between the two structures.
- the pressure P acting in the vertical direction (corresponding to the blood pressure in this portion) P is separated into two identical rods arranged obliquely at an angle ⁇ with the horizontal axis.
- Tc acts in the horizontal direction (the axial direction of the SM fiber). This axial force Tc causes elongation and strain of the SM fiber, and the strain becomes a measurement target.
- a strain of about 1 ⁇ is necessary, and it is necessary to employ a probe structure (catheter structure) that satisfies this.
- FIG. 9 a frame structure made of a SUS material shown in FIG. 9 is proposed.
- This figure shows a structure 4 that converts the pressure for realizing the above contents into strain of an optical fiber (SM fiber in this case), and the SUS frame 11 is attached to the SM fiber 3 at both end portions (fixed portions) of the pitch L. It is fixed with an adhesive (see C1C1 portion in FIG. 9A, cross section C1C1 in FIG. 9B).
- the SUS frame 11 has a structure bulging outward from the SM fiber axis by the size indicated by h. Note that the upper and lower envelopes of the SUS frame 11 in FIG.
- FIG. 9 (a) indicate the maximum diameter of the swollen portion, and the outer layer 5 that is the propagation portion of the external pressure of the sensor shown in FIG. 9 (c). It is also a boundary line.
- FIG. 9B the figure on the left side of FIG. 9B
- the SM fiber 3 is bonded to the outer periphery of the SM fiber 3 with an adhesive 12 at a fixed portion (the portion shown by the cross section C1C1).
- the formed SUS frame 11 is concentrically bonded and fixed.
- the SM fiber 3 and the SUS frame 11 are configured so as to be concentrically separated from each other as shown as a typical example in a cross section D1D1 (right side view) in FIG.
- the outer peripheral portion of the SUS frame 11 is covered with an annular outer layer 5 as shown in FIG. A pressure is applied as an external pressure to the SUS frame 11 through the outer layer 5.
- the blood pressure which is an external pressure
- the SUS frame 11 which can also be referred to as the structure 4
- the SUS frame 11 is loaded on the fixed SM fiber, and axial strain occurs in the SM fiber.
- the structure 4 is a structural material that supports the rigidity of the entire catheter, and can be rotated by operating the operation handle 6 by connecting the operation handle 6 and the J tip.
- Embodiment 2 As described above, in the first embodiment, desired data is obtained using the data of the frequency shift due to the reflected and scattered light of the two types of laser light measured with one SM fiber 3. Here, what obtains desired data by using only one type of scattered light will be described with reference to FIGS.
- an SM fiber 13 is further provided as a sensor fiber in addition to the SM fiber 3 shown in the first embodiment.
- the SM fiber 3 receives pressure load and is used as a pressure measurement fiber, while the SM fiber 13 is generally installed so as not to receive pressure load and is used as a temperature measurement fiber.
- the SM fiber 3 is measured with the SM fiber 3 and the SM fiber 13 by utilizing the fact that the sensitivity coefficient related to the frequency shift of Rayleigh scattering is larger than the sensitivity coefficient related to the frequency shift due to Brillouin scattering.
- the measurement by the SM fiber 13 may be performed simultaneously with the measurement of the frequency shift ⁇ R of Rayleigh scattering by the SM fiber 3. Since other components are the same as those in the first embodiment, description thereof is omitted here.
- FIG. 11 is a detailed view showing a structure of a sensor portion of a catheter which is a blood pressure measurement probe equipped with the two SM fibers.
- a SUS frame 11 having a hollow portion as a structure and having a rugby ball-like outer shape is provided around an SM fiber 3 (used for blood pressure measurement or the like) provided in a central axis portion.
- an outer layer 5 that propagates the pressure of blood pressure as an external pressure and protects the SM fiber and the structure is provided on the outer peripheral portion so as to be in contact with the SUS frame at the maximum diameter portion of the SUS frame 11 that is the structure. (See FIGS. 11A and 11B).
- SM fiber 3 In addition to the SM fiber 3, it is free from pressure due to blood pressure as an external pressure, and is not fixed in the SM fiber axial direction and is free. Therefore, an SM fiber that can obtain a Rayleigh scattering frequency shift ⁇ R reflecting only temperature changes. As shown in FIG. 11B, 13 is a position near the outer periphery of the catheter, and is arranged in the gap of the structure 4 so as not to contact the structure 4 and the outer layer 5.
- the optical fiber B detects only the change due to the temperature change ⁇ T among the Rayleigh scattering frequency shift ⁇ R , when this frequency shift is expressed as ⁇ R T , the sensitivity coefficient C 22 of the optical fiber related to the temperature change is used.
- ⁇ T ⁇ R T / C 22
- ⁇ R P C 21 ⁇ + C 22 ⁇ T
- ⁇ ( ⁇ R P ⁇ C 22 ⁇ T) / C 21 .
- the temperature change should be the same as the value measured with the optical fiber B and the value measured with the optical fiber A.
- the SM fiber that is not affected by the pressure is used as a means for measuring the frequency shift due to the temperature change, and a total of two SM fibers are used.
- the same effects as in the first embodiment can be obtained also in the second embodiment.
- the simplified structure of the present invention using a multipoint FBG is considered possible.
- the resolution is limited to the FBG interval, and the measurement distance is also limited.
- the configuration using two SM fibers as the sensor has been described.
- the outer diameter of these two SM fibers is about 80 to 250 ⁇ m as described above, and is arranged on the outer periphery thereof.
- a plurality of optical fiber sensors can be provided in the catheter.
- the outer diameter of a catheter can be about 0.4 mm or less.
- FIG. In this figure, in addition to the two SM fibers 3 and 13, two fibers, for example, an endoscope image fiber 14 and a tomographic image (for example, optical coherence tomography: OCT (Optical Coherence Tomography)) 15 are provided.
- OCT optical Coherence Tomography
- An example in which an optical fiber is installed is shown.
- a projection agent charging tube may be installed. As described above, since a plurality of three or more optical fibers can be installed, multi-functional measurement can be performed.
- Embodiment 3 In actual PCI measurement and the like, there are cases where it is necessary to consider the influence on the blood pressure measurement due to the pulsation of the heart in addition to what has been described so far. In order to cope with such a case, the measurement system shown in the third embodiment is used. Specific examples will be described below with reference to the drawings.
- FIG. 15 An example of the system configuration of the invention according to Embodiment 3 is shown in FIG.
- a pulsation sensing fiber 20 is connected to the measuring machine 8 in addition to the SM fiber 3 shown in the first embodiment.
- the heartbeat signal (see the center curve in FIG. 15) detected by the pulsation sensing fiber 20 is measured by the measuring device 8 in synchronization with the synchronization signal indicated by symbol M in FIG. To be recorded.
- the curve shown at the top is a model diagram showing a change example of the left ventricular pressure measured in synchronization with the synchronization signal, and it can be seen that the curve changes corresponding to the potential of the heartbeat signal.
- FIG. 15 the system shown in FIG.
- data such as pressure (blood pressure) measured by the SM fiber 3 is also measured by the measuring device 8 in synchronization with the synchronization signal indicated by the symbol M in the same manner as the heartbeat signal. Recorded in the memory 9. Therefore, it is possible to compare both heartbeat signal data and pressure (blood pressure) data measured in synchronization with the synchronization signal indicated by symbol M on the same time axis, and by analyzing this, Data such as pressure (blood pressure) in consideration of the influence of pulsation on blood pressure measurement can be obtained.
- a plurality of blood pressure data with an improved S / N ratio can be obtained at a time by wrapping the pulsation sensing fiber 20 around the arm portion, sensing a plurality of pulsations caused by this, and synthesizing data based on this. And the effect of improving accuracy can be obtained.
- the SM fiber 13 shown in the second embodiment is not connected to the measuring machine, but the SM fiber 13 is added to the configuration shown in the second embodiment as the measurement system, that is, the SM fiber 3.
- the blood pressure due to the pulsation of the heart is the same as described in the third embodiment. Data such as pressure (blood pressure) considering the influence on measurement can be obtained.
- the data such as the time distribution of the pulsation peak at a predetermined position and the pulsation reproduction state based on the data obtained by the pulsation sensing fiber 20.
- a synchronization signal level for example, when the system shown in FIG. 14 is used, accuracy of about 4 msec (see FIG. 15)).
- the elastic modulus data at a certain measurement time can be obtained by calculating the pulsation propagation velocity (also referred to as pulse wave velocity) v from the Maines-Corteweg equation (Non-patent Document 3) by the following equation (9).
- the Young's elastic modulus E indicating the hardness of the blood vessel can be derived, which is considered useful as data for diagnosing arteriosclerosis of blood vessels.
- [rho is the density of the blood
- r is the radius of the vessel
- t h a thickness of the blood vessel.
- Example 1 the appropriate configuration of the above-described optical fiber structure material has been described with reference to FIG. 9 (hereinafter referred to as Example 1). It may be as shown in Example 2 or Example 3. It should be noted that the present invention can be freely combined with each other within the scope of the invention, and each embodiment can be appropriately modified or omitted.
- FIG. 16 shows another example of an appropriate configuration of the optical fiber structure material.
- the optical fiber deviates from the central axis of the measurement probe and is disposed in the immediate vicinity of the outer layer 5 near the outer periphery, and is fixed at the mandrel position fixed to the wire (FIG. 16A).
- the outer layer 5 contacts an optical fiber with the load of the pressure which is a blood pressure.
- the load due to the pressure P is transmitted to the optical fiber through the outer layer 5, and as a result, the optical fiber is fixed and bent at the center position between the adjacent mandrels (see the broken line in FIG. 16B).
- the mandrel corresponds to the structure 4 that converts pressure into strain.
- FIG. 16C schematically shows the force relationship, and an axial force indicated by the symbol Tc is generated in the optical fiber.
- FIG. 17 shows still another example of an appropriate configuration of the optical fiber structure material.
- the fixing wire is spirally wound on the cylindrical surface at a pitch Lp, and its outer shape forms a fixing wire outer envelope.
- a driving wire is disposed on the central axis, and the optical fiber can be moved to a desired position.
- blood pressure as external pressure is transmitted to the optical fiber from the position where the fixing wire fixes the optical fiber.
- a structure (fixing wire) that is a protective layer that propagates the pressure of the object to be measured is provided on the outer peripheral portion.
- SM fiber Single mode optical fiber
- 4 structure 5 outer layer
- 6 operation handle 7 multi-core SM fiber
- 8 measuring machine 9 data memory
- 10 analysis / display device 11 SUS frame
- 12 adhesives 14 image fibers
- 16 wire layer 20 Pulsation sensing fiber.
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Abstract
Description
このことを、図6を用いてもう少し詳しく説明する。図6(a)は、血管中に生じた狭窄病変を示す模式図で矢印は血流方向を表す。図6(b)は、図6(a)に対応した血管内の圧力変化のモデル図である。図6(b)において、縦軸は血管内最大脈動圧力を、横軸は光ファイバ長(Lof)を示す。ここで、光ファイバ長とは、光ファイバの所定の始点をゼロとした場合における始点からセンサ先端位置までの距離である。また、病変部Pc1に対応する位置を狭窄位置S1、病変部Pc2に対応する位置を狭窄位置S2とすると、これらの位置で血管内圧力(血圧)はそれぞれ図中に示したように基準圧P0(上記のPaに相当)から漸減する。この漸減後の狭窄位置S1での圧力をP1、狭窄位置S2での圧力をP2とすると、P1/P0、およびP2/P0を、それぞれの位置での冠血流予備量比(FFR)と呼んでいる。そして、この値が0.75以下の場合に、上記PCIが適用される。通常、上記Paはガイディングカテーテルの先端で測定され、Pdはプレッシャーワイヤーと呼ばれる専用のカテーテル先端の圧力センサで測定される。
この場合においては、多箇所の狭窄部などの単一箇所に止まらない症状、あるいはステント(stent)を装着した後の情報としての生理的状況を判断するためには、PCIにおける圧力あるいは流速測定を一点での値ではなく、分布として求めることが要望されている。
また、圧力以外の他の項目を測定可能な多機能化(マルチ測定機能)の仕様を満足するためには、ファイバ本数は3本以上の複数本必要となり、細径の要求を満足させるには障害となっていた(例えば特許文献1参照)。
また、FBGとFBG間のファイバ部分にはセンサ機能がないため、基本的に連続する信号を測定することは困難であった(例えば非特許文献1参照)。
また、複数のセンサを用いれば多点での計測は可能であるが、連続した計測が困難なため取得すべきデータに漏れが生じ、また複数のセンサ間でセンサ感度のばらつきがある。これらにより病状を的確に把握できない恐れがある。
さらに、光ファイバに人工的にFBGを作製したため、光ファイバの本来有するセンシング機能などの機能を利用することができない場合が生じる。
そして、さらに、Δε、ΔTの初期値ε0、T0が与えられれば、上記で求めたΔε、ΔTから、これらの値が、例えば光ファイバの長尺方向の位置に対して連続した値(である分布値)として測定されることから、所定の位置におけるε、Tの値が求まることになる。
また、使用できるカテーテルの外径は、好ましくは0.46mmφ以下とされている(特許文献2参照)。
生体の血管中に挿入され、
外圧により変形し被測定体を内部に侵入させない外層と、温度、及び歪により変形するシングルモード光ファイバと、このシングルモード光ファイバを覆うように配置され、前記外層に負荷される圧力を伝播し、その圧力を前記シングルモード光ファイバの歪に連続的に変換する構造体と、を有して、前記被測定体の所定箇所の温度と圧力の分布を計測する血管挿入式分布圧力測定装置、
レーザー光を前記シングルモード光ファイバへ出射し、該シングルモード光ファイバで発生した散乱光の周波数変化を連続的に検出し、この検出した散乱光の周波数変化から求めた前記シングルモード光ファイバの温度変化、および歪変化から、前記シングルモード光ファイバの所定位置での血圧を演算して求める測定機、
前記測定機で演算した演算値を記憶するメモリ、
並びに
前記メモリに記憶された演算値を基にして、所望の解析あるいは表示を行う解析/表示装置、
を備えたものである。
外圧により変形し被測定体を内部に侵入させない外層と、
温度、及び歪により変形するシングルモード光ファイバと、
このシングルモード光ファイバを覆うように配置され、前記外層に負荷される圧力を伝播し、その圧力分布を前記シングルモード光ファイバの歪に連続的に変換するとともに、前記シングルモード光ファイバの一部に複数箇所で固定されるか、前記シングルモード光ファイバの一部と複数箇所で接する構造体と、を備えたものである。
まず、本発明の実施の形態1である光ファイバ式生体診断用センサシステムについて、図3を用いて説明する。本実施の形態1に示すシステムは、本発明の光ファイバ式生体診断用センサシステムの基本となるシステムである。
本センサシステムは、測定対象とする生体の血管内に挿入された本システムの構成要素である血管挿入式分布圧力測定装置(本発明では、以下これを「カテーテル」と呼ぶ)1の内部に装着された、センサ機能を要する光ファイバから得たセンサ出力を、生体診断を行うための基礎となるデータとして記憶するとともに、このデータを解析し表示するものである。
図において、カテーテル1の先端には、このカテーテルの血管への挿入を容易にするためのガイド部分であるジェーティップ(以下「Jティップ」と記載する)2が装備され、このJティップ2は先端がカテーテルの軸に対して傾斜し、その後端部でSUSなどの金属製の構造体4と接続されている。なお場合によっては、Jティップ2の後端部に繋がるセンサ先端部分の外周に対応する外層部分においては、ゴム製の外層に代わりに、螺旋状のワイヤが用いられる場合もある(後ほど詳しく説明する)。また、カテーテル1の表面はゴム、あるいは人体への悪影響がない柔らかい皮膚材で製造された外層5があり、被測定体である血液は外層5を通過しないが、血液の圧力は柔らかい外層5を通して構造体4に伝わる。構造体4は負荷された圧力を長手方向の伸びに転換する機能を有しており、その内部にあるセンサ機能を有するシングルモード光ファイバ(以下SMファイバと略記する)3に、上述の長手方向の伸びの変形を生じさせる。上記カテーテル1には、手元部分にカテーテルの主要な動きを操作する操作ハンドル6が設けられている。SMファイバ3は直接血液と接触しないが、構造体4の伸びが血液の圧力と比例しているため、SMファイバ3の軸ひずみは、被測定体である血液の圧力と比例、あるいは換算することができる。なお、場合によっては、生体への挿入部分の生体表面においてカテーテル1の生体への挿入をガイドするジャケット(図示せず)が、カテーテル1の外周部に設けられる。
実際には、測定部位や病気の患者では、血管全体の温度は一定でないことが通常であり、温度の不均一性を考慮した測定方法が求められる。すなわち、圧力を測定する際には、温度測定も行うことが可能でなければならない。
そして、このSMファイバ3で検出されたセンサ出力は、カテーテル1と測定機8とを接続する多芯SMファイバ7を通じて、測定機8でブリルアン散乱の周波数シフトΔνB、レイリー散乱の周波数シフトΔνR等の信号として測定されて(必要に応じ同期信号により同期処理されて)、血管中の血液の温度、並びに換算された血圧等の分布データとしてデータメモリ9に出力される。その後、データメモリ9に蓄積されたデータは、解析/表示装置10により解析され、所望のデータである診断用データとして冠血流予備量比(FFR)などが求められ、診断対象部位の血圧分布データが信号データとして出力されるとともに、必要に応じて図表として解析/表示装置10に備えられた表示器等に表示される。
次に、この2つの周波数シフトΔνRとΔνBと、予め初期値として測定機8に入力されていた基準となる状態での温度T0と変位ε0を用いて、温度変位ΔTと歪変化Δεの測定位置に対する分布が求められる(式(3)、式(4)参照)。
次に、所望の血圧(圧力)Pが、歪εの関数による換算として、測定機8を用いて求められる。そして、測定機8で求められた圧力Pはデータメモリ9に出力され記憶される。その後、解析/表示装置10により、データメモリ9で解析されたデータが、所望の表示形式でt時刻の圧力Pの分布として表示される。この場合、時間間隔Δtは血液の脈動を区別できる速さが要求され、1秒間に100回以上を目安として、各時間間隔ごとに血圧分布を得ることができる(図15には、秒速250回の例を示している)。そして、脈動圧力が最大の場合の分布を用いて、冠血流予備量比(FFR)等が求められる。
図4に示すように圧力Pは位置(Lof)と時間tの関数として求められるので、この位置座標をzとおくと、計測された圧力PはP=Pmes(z、t)と表現できる。この計測される圧力Pmes(z、t)には、カテーテル1の挿入時に生じる静ひずみの影響が含まれる可能性がある。そこで、2つの位置Aと位置Bで求めた圧力測定値を用いてこの静ひずみの影響を取り除く方法について図5をもとに説明する。
図5のステップ1(ST1と略記する)において、位置Aで計測された圧力Pmes(z、t)を符号ZAで表し、位置Bで計測された圧力Pmes(z、t)を符号ZBで表わす(ST1で縦軸は圧力、横軸は測定開始後、経過した時間を示す)。ST1の測定波形は心臓の2鼓動分に対応する左心室圧の変化を示すモデル図である。次に、ステップ2(ST2と略記する)では、計測した圧力Pmes(z、t)から、式(5)に従って位置Aあるいは位置Bでの中央値を求める(式(5)参照)か、あるいは式(6)に従って位置Aあるいは位置Bでの平均値を求める(式(6)参照。積分記号∫が用いられている。)。
この値を測定対象となるすべての位置で求める(ST2)。
次に、ステップ3(ST3と略記する)では、計測値Pmes(z、t)から、ST2で得た中央値Pmed(z)またはPav(z)を差し引き、差し引いた後の圧力の値をP(z,t)とおく(それぞれ式(7)、式(8)参照)。この処理により、カテーテル挿入時の静ひずみは除かれる。
最後にステップ4(ST4と略記する)で、測定位置zを変えて各位置での圧力P(z,t)の値を求め、zを横軸(距離)として、圧力の変化をプロットし、この変化から、FFRを求めて判定を行う。
なお、外層の外周には、カテーテルの生体への挿入を容易に行うため、螺旋状のワイヤ層16が設けられる場合もある(図7(b))。ワイヤ層16を取り付けても、血液がワイヤ間を通過するため、外層5に圧力が負荷される状態が変わることはない。
この図に示したSMファイバ3の外径は80~250μm程度であり、その外周に配置されたSMファイバの保護層である構造体4は、負荷された圧力を歪に転換するものであり、SUSで構成され、周囲圧力を比例的にSMファイバ3の軸方向である長手方向の伸び量に変換する機能を有している(以下で、もう少し詳しく説明する)。この機能よってSMファイバの歪を圧力に比例させることができる。また、カテーテルとしての外径は約0.4mm以下とすることができる。このため、本発明が適用を予定している生体診断用のセンサとしての仕様を満たし、PCIでの圧力あるいは流速の測定において有効に活用することが可能となる。また、測定対象となる生体の血管が比較的小さな外径の血管であっても、圧力(血圧)測定が可能となる。
感度を上げる場合には、上述のように、被覆材がガラスより剛性が低いとき、被覆により厚みを増すことで、見掛け上、圧力感度を上げることができる(図2参照)。ただし、本発明が適用を予定しているPCIでの圧力あるいは流速の測定分野では、上記のように、カテーテルとしての外径は約0.4mm以下とする必要があるため、この方法を用いて圧力感度を数倍以上も上げることは期待できない。SMファイバ自体を剛性の低いプラスチック材で構成することも有効である。
そこで、以下では、連続かつ高精度、均一でシンプルな構造を持ち、分布圧力を連続歪に転換する適宜な構造材について説明する。
通常は、軸対象構造であるが、この場合、図8(b)に示すように、1/2の部分だけ表示している、SMファイバに対して斜め(角度θ)に配置された2つの同一形状の弾性棒が、計測用プローブ外周上の開口に作用する外圧(圧力P)を、この開口で受けているとする。つまり、上記構造体は、計測用プローブ外周からSMファイバまでの距離h、2つの構造体間のSMファイバ軸に沿った方向でのAB間の距離(ピッチ)Lで配置されているとする。この場合、図8(c)に示すように、垂直方向に作用する圧力(この部分での血圧に相当)Pが、水平軸と角度θで斜め方向に配置された2つの同一の棒に分離して支持されており、水平方向(SMファイバの軸方向)には、等価的な軸力Tcが作用しているモデルとして考えることができる。この軸力TcはSMファイバの伸びと歪を生じ、その歪が測定対象となる。
また、図9(b)に示したように(図9(b)の左側の図)、SMファイバ3の外周には、固定部分(断面C1C1で示した部分など)において、接着剤12で接着されたSUSフレーム11が同心円状に接着され固定されている。このSMファイバ3とSUSフレーム11は上記固定部分以外では、図9(b)の断面D1D1(右側の図)に典型例として示すように、同心軸状に互いに離れて構成されており、SUSフレーム11は、断面内では互いに120度ずつ離れた円弧形状に構成されるとともに、各円弧形状間は中空となっている。なお、この光ファイバ構造材が実際に使用される場合には、図9(c)に示すように、SUSフレーム11の外周部分は円環状の外層5で覆われており、外圧である血圧による圧力がこの外層5を通じてSUSフレーム11に外圧として負荷される。
なお、構造体4は、カテーテル全体の剛性を支持する構造材とし、それぞれ、操作ハンドル6とJティップを繋いで、操作ハンドル6の操作により、回転することができる。
さらに、上記のSMファイバ先端の測定端にFBGなどの反射装置を持たせて散乱光のダブルエンド測定方式を実施することも可能である。このような構成とすることで、ブリルアン散乱の周波数シフトΔνBの測定分解能を上げることができ、この測定データに基づく演算値の精度を上げることができる。
上述のように、実施の形態1では、1本のSMファイバ3で測定された2種類のレーザー光の反射散乱光による周波数シフトのデータが用いられて所望のデータが得られることになるが、ここでは、使用する散乱光を1種類だけにして所望のデータを得るものについて図10~図13を用いて説明する。
一方、光ファイバAにより計測されるレイリー散乱の周波数シフトをΔνR Pと表すと、ΔνR Pは、圧力を受けていないため、歪変化により影響を受ける要素と、温度変化により影響を受ける要素とを考慮して、式(4)より、ΔνR P=C21Δε+C22ΔTが成立する。よって、Δε=(ΔνR P-C22ΔT)/C21と表される。
被測定体においては、その温度変化は、光ファイバBで測定した値と光ファイバAにより測定した値とは同じであるはずであるから、これを考慮して。光ファイバBで測定したΔTの値を、光ファイバAのΔεを求める式に代入して、Δε=(ΔνR P-ΔνR T)/C21となる(ここでは光ファイバAと光ファイバBにおけるC22の感度特性は同じと仮定している)。ここで、ΔνR PとΔνR Tは光ファイバによって計測されている既知量であるので、これらからΔεが求まり、従って、式(2)を用いることにより、PがΔεの関数として求められる(P=F(Δε))。ここで、図10、図11に示した符号を用いると光ファイバAはSMファイバ3相当であり、光ファイバBはSMファイバ13相当である。
実際のPCI測定等においては、これまで述べてきた以外に、心臓の拍動による血圧測定への影響を考慮する必要がある場合も出てくる。このような場合に対応するために、本実施の形態3に示す測定システムを用いる。具体例について、以下、図を用いて説明する。
ここで、ρは血液の密度、rは血管の半径、thは血管の肉厚である。この場合においては、実施の形態1の測定フローチャート中に示した表示例のように、2つの異なった時間帯でのデータを比較して、血管の動脈硬化の時間的変化のデータも得ることができるので、従来より有用なデータとなることが期待できる。
図16は光ファイバ構造材の適宜の構成の別の例である。光ファイバは、測定用プローブの中心軸から外れ、外周寄りの外層5のごく近傍に配置され、ワイヤに固定されたマンドレル位置で固定される(図16(a))。そして、血圧である圧力の負荷により、外層5は光ファイバに接触する。この場合、圧力Pによる負荷は外層5を介して光ファイバに伝わり、この結果、光ファイバは固定され、隣接するマンドレル間の中央位置で撓む(図16(b)の破線を参照)。この場合、マンドレルは圧力を歪に転換する構造体4に相当する。力関係をモデル的に図16(c)に示すが、光ファイバには記号Tcで示す軸力が発生することになる。
図17は光ファイバ構造材の適宜の構成のさらに別の例である。実線で示した光ファイバは、全部で3本あり、軸断面図に示すように互いに120度方向に1本ずつ配置されている(図17(b)参照)。また、これら光ファイバは、固定用ワイヤにより軸方向に記号G1で示した位置に固定されている(図17(b)の左側の断面G1G1参照)。なお、断面H1H1位置では、光ファイバは拘束されず自由になっている(図17(b)の右側の図参照)。上記固定用ワイヤは円筒面上にピッチLpで螺旋状に巻回され、その外形は固定用ワイヤ外形包絡線を形成している。また、中心軸には駆動用ワイヤが配置され、所望の位置に光ファイバを移動させることができる。この例では、上記固定用ワイヤが光ファイバを固定している位置から外圧である血圧が光ファイバに伝わることになる。なお、被測定体の圧力を伝播する保護層たる構造体(固定用ワイヤ)は外周部に設けられている。
3、13 シングルモード光ファイバ(SMファイバ)、4 構造体、
5 外層、6 操作ハンドル、7 多芯SMファイバ、8 測定機、
9 データメモリ、10 解析/表示装置、11 SUSフレーム、
12 接着剤、14 イメージファイバ、
15 断層画像計測用ファイバ(OCTファイバ)、16 ワイヤ層、
20 脈動感知ファイバ。
Claims (10)
- 生体の血管中に挿入され、
外圧により変形し被測定体を内部に侵入させない外層と、温度、及び歪により変形するシングルモード光ファイバと、このシングルモード光ファイバを覆うように配置され、前記外層に負荷される圧力を伝播し、その圧力を前記シングルモード光ファイバの歪に連続的に変換する構造体と、を有して、前記被測定体の所定箇所の温度と圧力の分布を計測する血管挿入式分布圧力測定装置、
レーザー光を前記シングルモード光ファイバへ出射し、該シングルモード光ファイバで発生した散乱光の周波数変化を連続的に検出し、この検出した散乱光の周波数変化から求めた前記シングルモード光ファイバの温度変化、および歪変化から、前記シングルモード光ファイバの所定位置での血圧を演算して求める測定機、
前記測定機で演算した演算値を記憶するメモリ、
並びに
前記メモリに記憶された演算値を基にして、所望の解析あるいは表示を行う解析/表示装置、
を備えた光ファイバ式生体診断用センサシステム。 - 前記測定機は、レイリー散乱光の周波数変化とブリルアン散乱光の周波数変化を検出することを特徴とする請求項1に記載の光ファイバ式生体診断用センサシステム。
- 前記血管挿入式分布圧力測定装置は、少なくとも2本のシングルモード光ファイバを備え、そのうちの1本は温度変化による歪を生じ、圧力を受圧しない構成とされたシングルモード光ファイバであり、かつ前記測定機は、レイリー散乱光の周波数変化を検出することを特徴とする請求項1に記載の光ファイバ式生体診断用センサシステム。
- 前記シングルモード光ファイバは、終端に反射装置を持つことを特徴とする請求項2に記載の光ファイバ式生体診断用センサシステム。
- 腕部に巻き付け、心拍を感知する脈動感知ファイバを備え、この脈動感知ファイバにより心拍を測定するとともに、この測定された信号と同期して前記散乱光の周波数変化を検出するタイミングを制御することを特徴とする請求項1~4のいずれか1項に記載の光ファイバ式生体診断用センサシステム。
- 生体の血管中に挿入され、被測定体の所定箇所の温度と圧力の分布を計測するものであって、
外圧により変形し被測定体を内部に侵入させない外層と、
温度、及び歪により変形するシングルモード光ファイバと、
このシングルモード光ファイバを覆うように配置され、前記外層に負荷される圧力を伝播し、その圧力分布を前記シングルモード光ファイバの歪に連続的に変換するとともに、前記シングルモード光ファイバの一部に複数箇所で固定されるか、前記シングルモード光ファイバの一部と複数箇所で接する構造体と、を備えたことを特徴とする血管挿入式分布圧力測定装置。 - 前記構造体は、中空部分を有し、中心軸部で前記シングルモード光ファイバに固定され、外周部で前記外層と接することを特徴とする請求項6に記載の血管挿入式分布圧力測定装置。
- 前記構造体は、ワイヤ軸に固定された複数の円板状のマンドレルであって、前記シングルモード光ファイバが前記マンドレルの外周部に複数箇所で固定され、前記外層からの圧力負荷により前記シングルモード光ファイバが隣接する前記マンドレル間で内周方向へ撓むことを特徴とする請求項6に記載の血管挿入式分布圧力測定装置。
- 前記構造体は、3重の螺旋状に巻回され、軸断面内で前記3重の螺旋が互いに中心角が120度離れた外周位置に配置され、軸方向にはワイヤ外形包絡線位置で前記シングルモード光ファイバの外周に固定される固定用ワイヤを有することを特徴とする請求項6に記載の血管挿入式分布圧力測定装置。
- 前記シングルモード光ファイバの代わりに多点FBGを用いて多点測定を行うことを特徴とする請求項6に記載の血管挿入式分布圧力測定装置。
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JP (1) | JP6190467B2 (ja) |
CN (1) | CN105683730B (ja) |
WO (1) | WO2015059969A1 (ja) |
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WO2020129277A1 (ja) * | 2018-12-20 | 2020-06-25 | 日本電信電話株式会社 | 光センサプローブおよび該光センサプローブを用いた血液流量、血液粘度および血管弾性率の測定方法 |
JPWO2020129277A1 (ja) * | 2018-12-20 | 2021-10-21 | 日本電信電話株式会社 | 光センサプローブおよび該光センサプローブを用いた血液流量、血液粘度および血管弾性率の測定方法 |
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CN115177229A (zh) * | 2022-08-17 | 2022-10-14 | 合肥中纳医学仪器有限公司 | 一种基于光纤传感器的中心静脉压测量方法及系统 |
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EP3062078B1 (en) | 2019-07-03 |
EP3062078A1 (en) | 2016-08-31 |
US20160220131A1 (en) | 2016-08-04 |
EP3062078A4 (en) | 2017-07-05 |
US10028667B2 (en) | 2018-07-24 |
JPWO2015059969A1 (ja) | 2017-03-09 |
JP6190467B2 (ja) | 2017-08-30 |
CN105683730B (zh) | 2019-01-11 |
CN105683730A (zh) | 2016-06-15 |
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