Viscosity calculation device, viscosity measurement device, viscosity calculation method, and viscosity calculation program

Abstract

This viscosity calculation device comprises: a movement speed calculation unit that applies, to an object body floating in a body fluid within a living body from outside of the living body, force different from hydrodynamic acting force produced by the flow of the body fluid, thereby calculating the movement speed at which the object body moves; and a viscosity calculation unit that calculates the viscosity of the body fluid on the basis of the calculated movement speed.

Description

Viscosity calculation device, viscosity measurement device, viscosity calculation method, and viscosity calculation program

[0001] The present disclosure relates to a viscosity calculation device, a viscosity measurement device, a viscosity calculation method, and a viscosity calculation program.

[0002] It is known that the flow velocity of blood in a blood vessel is measured using ultrasound and the dynamic viscosity coefficient is estimated based on the flow velocity (for example, Patent Document 1 and Non-Patent Document 1).

[0003] Japanese Patent Application Laid-Open No. 2007-175127

[0004] N. Nitta et al. "Ultrasonic Measurement of Fluid Viscosity for Blood Characterization" Japanese Journal of Applied Physics Vol. 44, No. 6B, pp. 4602-4608 (2005)

[0005] However, the method of estimating the viscosity coefficient (viscosity) from the blood flow velocity cannot estimate the viscosity with high spatial resolution and high accuracy.

[0006] An object of the present disclosure is to provide a viscosity calculation device, a viscosity measurement device, a viscosity calculation method, and a viscosity calculation program that are capable of calculating viscosity with high spatial resolution and high accuracy.

[0007] An embodiment of the present disclosure is a viscosity calculation device comprising: a movement speed calculation unit that calculates the movement speed of a subject floating in body fluid within a living organism by applying a force from outside the organism that is different from the hydrodynamic acting force generated by the flow of the body fluid; and a viscosity calculation unit that calculates the viscosity of the body fluid based on the calculated movement speed.

[0008] An embodiment of the present disclosure is a viscosity measurement device including an ultrasound irradiation unit that irradiates the ultrasound contrast agent with the first ultrasound, and the viscosity calculation device.

[0009] An embodiment of the present disclosure is a viscosity calculation method that calculates the movement speed of an object floating in body fluid within a living organism by applying a force from outside the organism that is different from the hydrodynamic acting force generated by the flow of the body fluid, and calculates the viscosity of the body fluid based on the calculated movement speed.

[0010] An embodiment of the present disclosure is a viscosity calculation program that causes a computer to function as a movement speed calculation unit that calculates the movement speed of a subject floating in bodily fluid within a living organism by applying a force from outside the organism that is different from the hydrodynamic acting force generated by the flow of the bodily fluid, and a viscosity calculation unit that calculates the viscosity of the bodily fluid based on the calculated movement speed.

[0011] According to aspects of the present disclosure, viscosity can be calculated with high spatial resolution and high accuracy.

[0012] FIG. 1 is a diagram illustrating the principle of an embodiment. FIG. 2 is a block diagram of a viscosity measurement device according to an embodiment. FIG. 3 is another block diagram of a viscosity measurement device according to an embodiment. FIG. 4 is a functional block diagram of a viscosity calculation device according to an embodiment. FIG. 5 is a flowchart showing processing by a processor according to an embodiment. FIG. 6 is a diagram showing the sound pressure versus time of ultrasound irradiated to a living body by an ultrasound probe. FIG. 7A is a conceptual diagram showing the magnitude of an echo signal versus the frequency of a Doppler signal. FIG. 7B is a conceptual diagram showing the magnitude of an echo signal versus the frequency of a Doppler signal. FIG. 8 is a diagram showing an example of an echo image generated from a contrast echo using the method of FIG. 7B. FIG. 9 is a cross-sectional view showing a system used in an experiment. FIG. 10 is a diagram showing an example of depth Z versus time in an experiment. FIG. 11 is a diagram showing the movement speed v versus viscosity μ in an experiment. Ｚ FIG. 12 shows the relationship between viscosity μ and moving speed v Ｚ FIG. 13 shows the relationship between the viscosity μ and the moving speed v Ｚ 14 is a graph showing coefficients A and B relative to radius Ro in the simulation. FIG. 15 is a graph showing the relationship between the moving velocity v and viscosity μ in the experiment and the simulation. Ｚ16 is a schematic diagram showing an echo image generated by an image generating unit in the embodiment.

[0013] Hereinafter, embodiments for carrying out the present disclosure will be described in detail with reference to the drawings. The following embodiments are examples for embodying the technical ideas of the invention, and the present invention is not limited to the described configurations and numerical values. In each drawing, the same components are given the same reference numerals, and duplicated explanations may be omitted as appropriate. The size, positional relationship, etc. of each component shown in each drawing may be exaggerated to facilitate understanding of the invention.

[0014] (Embodiment) FIG. 1 is a diagram illustrating the principle of an embodiment. The flow direction of body fluid 44 is the X direction, and the direction in which ultrasound 40 is emitted is the Z direction. The Z direction is the depth direction. As shown in FIG. 1, a tube 43 runs through a living body 45. The living body 45 is, for example, a human body. The living body 45 may be a living organism other than a human body. The tube 43 is, for example, a vasculature such as a lymphatic vessel or a blood vessel. A body fluid 44 flows within the tube 43 as indicated by arrows 46. The body fluid 44 is, for example, an intravascular fluid, such as plasma, lymph, or cerebrospinal fluid. The body fluid 44 may also be a body fluid within an organ other than the tube 43. The body fluid 44 may be stationary and not flow. Ultrasound contrast agents 42A to 42C are introduced into the body fluid 44 and float within the body fluid 44. The ultrasound contrast agents 42A to 42C are, for example, microbubbles or nanobubbles, and an example thereof is perfluorobutane microbubbles to which hydrogenated egg yolk phosphatidylserine sodium and refined white sugar have been added.

[0015] Ultrasound contrast agent 42B represents ultrasound contrast agent 42A after a certain time has passed, and ultrasound contrast agent 42C represents ultrasound contrast agent 42B after a certain time has passed. When ultrasound 40 is irradiated from outside living body 45, an acoustic radiation force Ft is applied to ultrasound contrast agent 42A. After a certain time, ultrasound contrast agent 42A moves a distance ΔX1 in the X direction along with the flow of body fluid 44. Due to the acoustic radiation force Ft applied to ultrasound contrast agent 42A, ultrasound contrast agent 42A moves a distance ΔZ1 in the Z direction after a certain time. This causes ultrasound contrast agent 42A to move to the position of ultrasound contrast agent 42B. Similarly, ultrasound contrast agent 42B moves a distance ΔX2 in the X direction due to the flow of body fluid 44, and a distance ΔZ2 in the Z direction due to the acoustic radiation force Ft, thereby moving to the position of ultrasound contrast agent 42C.

[0016] In this embodiment, the moving speeds of the ultrasound contrast agents 42A to 42C in the Z direction are measured. Based on the moving speeds, the viscosity (i.e., viscosity coefficient) of the body fluid 44 is calculated. The moving speeds of the ultrasound contrast agents 42A to 42C are measured using, for example, ultrasound echoes.

[0017] The object whose movement speed is to be measured may be an object other than the ultrasound contrast agents 42A to 42C. The object may be, for example, a cell or cell-derived object such as a white blood cell, red blood cell, platelet, or lymphocyte present in the body fluid 44, or may be an object introduced into the body fluid 44 from the outside.

[0018] (Comparative Example) With reference to Non-Patent Document 1, the following comparative example is considered. In the comparative example, the flow velocity distribution of body fluids in blood vessels is measured using an ultrasonic Doppler method. The viscosity of the body fluid (e.g., dynamic viscosity coefficient) is estimated from the flow velocity distribution. The relationship between the flow velocity distribution and viscosity depends on the diameter and shape of the blood vessel. Therefore, the relationship between the flow velocity distribution and viscosity is determined in advance by actual measurement or simulation.

[0019] In the comparative example, when the vessel is thin, the flow velocity distribution is small and the viscosity cannot be calculated with high accuracy. When the flow velocity is small, it is difficult to distinguish between body fluids and tissues using ultrasound, making it impossible to measure the flow velocity with high accuracy. Furthermore, when the vessel has an unusual shape, for example, when the diameter of the vessel changes or the vessel is tortuous, the viscosity cannot be calculated with high spatial resolution and high accuracy unless a simulation that matches the vessel shape is performed. In the case of vessels that do not contain blood cells, such as lymphatic vessels, the ultrasonic echo is small, making it impossible to measure the flow velocity with high accuracy. Furthermore, since only one viscosity can be calculated for each vessel, the local viscosity within the vessel cannot be calculated with high spatial resolution and high accuracy. Thus, it is difficult to calculate viscosity with high accuracy in the comparative example.

[0020] In a comparative example described in Patent Document 1, ultrasonic waves are emitted from the surface of a living body along the direction of blood flow in a blood vessel, and ultrasonic echoes emitted from the living body via the blood are received. The blood flow velocity distribution is measured from the ultrasonic echoes. The blood viscosity is measured based on the temporal change in the measured flow velocity distribution. However, the ultrasonic echo signals from the blood are weak, making it difficult to distinguish between blood and tissue, resulting in low spatial resolution. It is also difficult to measure blood viscosity with high accuracy.

[0021] (Description of the Embodiment) In the embodiment, a movement speed of a target object floating in a body fluid 44 in a living body 45 is calculated by applying a force from outside the living body 45 separate from the hydrodynamic force generated by the flow of the body fluid 44. The viscosity of the body fluid 44 is calculated based on the calculated movement speed. In this way, the target object is moved using a force applied from outside the living body 45 separate from the flow speed of the body fluid 44, so the viscosity can be calculated with high spatial resolution and high accuracy even when the blood vessels are thin and the flow speed is slow. Furthermore, because the movement speed of the target object is almost independent of the shape of the blood vessels, the viscosity can be calculated with high spatial resolution and high accuracy even when the blood vessels have an unusual shape. Note that the hydrodynamic force generated by the flow of the body fluid 44 is, for example, an inertial force or a viscous force generated by the flow of the body fluid 44. The force separate from the hydrodynamic force applied to the target object is a force applied to the target object other than the inertial force or the viscous force generated by the flow of the body fluid 44, such as an acoustic radiation force Ft applied from outside the living body 45. The force applied to the target object other than the hydrodynamic force may be an electromagnetic force or the like applied from outside the living body 45. The moving speed of the target object may be measured using a method other than ultrasound.

[0022] Using ultrasound contrast agents 42A-42C as the target object, an acoustic radiation force Ft generated by irradiating ultrasound 40 onto the ultrasound contrast agents 42A-42C is used as a force separate from the hydrodynamic force generated by the flow of body fluid 44. This allows for highly accurate viscosity calculation even in cases containing almost no blood cells, such as lymphatic vessels. Furthermore, because the ultrasound echoes are strengthened by the ultrasound contrast agents 42A-42C, viscosity can be calculated with high accuracy and high spatial resolution.

[0023] Specific Example of Embodiment Fig. 2 is a block diagram of a viscosity measuring device according to an embodiment. As shown in Fig. 2, the viscosity measuring device 100 is, for example, an ultrasound imaging device, and includes a main body 10 and an ultrasound probe 11. The ultrasound probe 11 irradiates a living body 45 with ultrasound waves 40 and receives ultrasound echoes 41 reflected from the living body 45. The main body 10 includes a processor 12, a transmission / reception circuit 13, a memory 14, a display device 15, and an input / output device 16. The transmission / reception circuit 13 transmits an electrical signal to the ultrasound probe 11 to irradiate the ultrasound waves 40. The transmission / reception circuit 13 receives an echo signal obtained by converting the ultrasound echo 41 from the ultrasound probe 11 into an electrical signal.

[0024] The processor 12 instructs the transmission / reception circuit 13 on the electrical signals to be transmitted to the ultrasonic probe 11 and acquires echo signals. The memory 14 stores echo images, programs, etc. The display device 15 displays viscosity information, echo images, etc. The input / output device 16 acquires viscosity measurement instructions or programs, etc. from an external device. The input / output device 16 also outputs information related to viscosity or echo images, etc. to the external device.

[0025] Fig. 3 is another block diagram of a viscosity measurement device according to an embodiment. As shown in Fig. 3, a viscosity measurement device 102 includes a computer 20 and an ultrasound imaging device 21. The ultrasound imaging device 21 is, for example, the viscosity measurement device 100 shown in Fig. 2. The computer 20 works in cooperation with software to function as a viscosity calculation device. The computer 20 executes a viscosity calculation program and performs a viscosity calculation method.

[0026] The computer 20 includes a processor 22, a memory 24, a display device 25, an input / output device 26, and an internal bus 23. The processor 22 executes a viscosity calculation program and a viscosity calculation method. The memory 24 stores information, etc., used by the processor 22 when executing the viscosity calculation program and the viscosity calculation method. The memory 24 may also store the viscosity calculation program executed by the processor 22. The display device 25 displays, for example, a viscosity or an echo image. The input / output device 26 inputs information acquired by the processor 22 from the ultrasound imaging device 21 or an external device, and outputs information output by the processor 22 to the ultrasound imaging device 21 or an external device. The external device may be another computer or another program within the same computer. The internal bus 23 connects the processor 22, the memory 24, the display device 25, and the input / output device 26 and transmits information, etc. The viscosity calculation program is stored in, for example, a storage medium 27.

[0027] The processors 12 and 22 are, for example, CPUs (Central Processing Units). The memories 14 and 24 are, for example, optical storage devices, magneto-optical storage devices, or semiconductor storage devices. The display devices 15 and 25 are, for example, liquid crystal displays or organic EL (Electro-Luminescence) displays. The input / output devices 16 and 26 are, for example, external interfaces. The storage medium 27 is, for example, a non-transitory tangible medium, such as an optical storage medium such as a CD-ROM (Compact Disc Read Only Memory) or a DVD (Digital Versatile Disc), a magnetic storage medium, or a semiconductor storage medium.

[0028] FIG. 4 is a functional block diagram of a viscosity calculation device according to an embodiment. As shown in FIG. 4, the viscosity calculation device 30 includes an acquisition unit 31, a movement speed calculation unit 32, a viscosity calculation unit 33, an image generation unit 34, and an output unit 35. The processors 12 and 22 cooperate with a program to function as the acquisition unit 31, the movement speed calculation unit 32, the viscosity calculation unit 33, the image generation unit 34, and the output unit 35. The acquisition unit 31 acquires echo signals. The movement speed calculation unit 32 calculates the movement speeds of the ultrasound contrast agents 42A to 42C based on the acquired echo signals. The viscosity calculation unit 33 calculates the viscosity of the body fluid 44 based on the movement speeds. The image generation unit 34 generates echo image information from the echo signals and viscosity information. The output unit 35 outputs the viscosity information and the echo image information.

[0029] FIG. 5 is a flowchart illustrating the processing of the processors 12 and 22 in this embodiment. As shown in FIG. 5, the acquisition unit 31 acquires echo signals from the transmission / reception circuitry 13 or the ultrasound imaging device 21 (step S10). The image generation unit 34 generates echo image information based on the echo signals (step S11). The movement speed calculation unit 32 extracts ultrasound contrast agents 42A-42C, the movement speed of which is to be calculated, based on the echo image information generated by the image generation unit 34 (step S12). The movement speed calculation unit 32 calculates the movement speeds of the extracted ultrasound contrast agents 42A-42C based on the echo image information (step S13). The viscosity calculation unit 33 calculates the viscosity of the body fluid 44 based on the calculated movement speeds (step S14). The image generation unit 34 superimposes viscosity information on the echo image information (step S15). The output unit 35 outputs the viscosity information and the echo image information (step S16). The process then ends.

[0030] In step S13, the viscosity μ is calculated from the moving speed v using the power law v=Aμ Ｂ Here, A and B are determined in advance and stored in the memory 14 or 24.

[0031] The moving speed calculation unit 32 may calculate the Doppler shift frequencies (ie, moving speeds) of the ultrasonic contrast agents 42A to 42C directly from the echo signals without using the echo image information.

[0032] (Example of imaging an ultrasound contrast agent) Fig. 6 is a diagram showing the sound pressure versus time of ultrasound irradiated by the ultrasound probe 11 to a living body 45. As shown in Fig. 6, the ultrasound probe 11 irradiates a burst wave 48 between pulse waves 47N and 47P. The pulse waves 47N and 47P are ultrasound waves for generating an echo image of the living body 45. The burst wave 48 is ultrasound for applying an acoustic radiation force Ft to the ultrasound contrast agents 42A to 42C.

[0033] The pulse waves 47N and 47P are short pulses. The pulse wave 47N has a negative polarity, and the pulse wave 47P has a positive polarity. The positive or negative polarity indicates whether the ultrasonic vibration starts from the negative side or the positive side, and the pulse waves 47N and 47P have opposite phases. The polarities of the pulse waves 47N and 47P may be the same. The burst wave 48 is an ultrasonic wave with a larger number of cycles than the pulse waves 47N and 47P in order to move the ultrasonic contrast agents 42A to 42C. The pulse waves 47N and 47P are irradiated alternately. The pulse waves 47N and 47P are irradiated at a time different from that when the burst wave 48 is irradiated.

[0034] The sound pressures of the pulse waves 47N and 47P and the burst wave 48 are similar to each other and are not enough to destroy the ultrasound contrast agents 42A to 42C. The pulse wave repetition interval (PRI) is the interval between the pulse waves 47N and 47P. The pulse burst interval (PBI) is the interval between the pulse wave 47N or 47P and the burst wave 48.

[0035] The number of cycles of the pulse waves 47N and 47P is, for example, 1 to 10. The number of cycles of the burst wave 48 is, for example, 10 to 10,000 times the number of cycles of the pulse waves 47N and 47P. Note that one cycle corresponds to one period. The length of the PBI is determined taking into consideration the time from when the pulse waves 47N and 47P are irradiated onto the living body 45 until the ultrasonic echo 41 reflected by the living body 45 is received, as well as the signal processing time. The ultrasonic probe 11 irradiates the living body 45 with ultrasound waves 40, for example, plane waves or diverging waves, which are unfocused waves.

[0036] 7A and 7B are conceptual diagrams showing the magnitude of an echo signal relative to the frequency of a Doppler signal. The horizontal axis represents the frequency f of the Doppler signal, and the vertical axis represents the intensity of the echo signal. The frequency f of the Doppler signal corresponds to the frequency of the Doppler shift in the Z direction, for example. Pass characteristics 52 are the pass characteristics of the filter.

[0037] 7A shows echo signals obtained when pulse waves 47N and 47P are irradiated onto a living body 45 without irradiating a burst wave 48. Tissue echo 51 is an echo signal from the living body 45. Contrast echo 50 is an echo signal from the ultrasound contrast agents 42A to 42C. When the burst wave 48 is not irradiated, the ultrasound contrast agents 42A to 42C hardly move in the Z direction in FIG. 1. Therefore, the frequency f of the tissue echo 51 and the contrast echo 50 is almost zero.

[0038] FIG. 7B shows echo signals obtained when a burst wave 48 and pulse waves 47N and 47P are irradiated onto a living body 45. When the burst wave 48 is irradiated, an acoustic radiation force is applied to the ultrasound contrast agents 42A-42C, causing them to move in the Z direction in FIG. 1 . Therefore, the frequency f of the contrast echo 50 is negative. Meanwhile, the living body 45 does not move even when irradiated with the burst wave 48. Therefore, the frequency f of the tissue echo 51 is approximately zero. A filter having a pass characteristic 52 is provided that passes echo signals with frequencies more negative than the cutoff frequency fcutoff and blocks echo signals with frequencies more positive than the cutoff frequency fcutoff. The cutoff frequency fcutoff is set to a frequency that separates the contrast echo 50 from the tissue echo 51. The contrast echo 50 almost entirely passes through the filter, while the tissue echo 51 is almost entirely blocked. Therefore, an image of the contrast echo 50 can be generated without including the tissue echo 51.

[0039] FIG. 8 is a diagram showing an example of an echo image generated from a contrast echo 50 using the method of FIG. 7B . The image of FIG. 8 is an image acquired using a system simulating a living body, which will be described later. The gel 45A is a material simulating a living body 45. The flow path 43A is a material simulating a tube 43. The glycerin aqueous solution 44A is a material simulating a body fluid 44. As shown in FIG. 8 , the tissue echo signals from the gel 45A, flow path 43A, and glycerin aqueous solution 44A are weak, while the contrast echo from the ultrasound contrast agent 42 is strong. This allows for increased contrast between the ultrasound contrast agent 42 and the gel 45A, flow path 43A, and glycerin aqueous solution 44A.

[0040] (Experiment) An experiment was conducted using a system simulating a living body 45, a tube 43, and a body fluid 44. Figure 9 is a cross-sectional view showing the system used in the experiment. A flow path 43A simulating a tube 43 is provided in a gel 45A simulating a living body 45. A glycerin aqueous solution 44A simulating a body fluid 44 flows in the flow path 43A as indicated by arrows 46. An ultrasound contrast agent 42 is dispersed in the glycerin aqueous solution 44A. A layer of water 49 is provided on the gel 45A. An ultrasound probe 11 is inserted into the water 49.

[0041] The gel 45A uses agarose gel as the phantom matrix, and polyamide particles (ORGASOL (registered trademark) manufactured by Arkema) with a diameter of 10 μm are dispersed in the phantom matrix at a concentration of 5% by mass as acoustic scatterers that scatter ultrasound. The inner diameter of the flow path 43A is 1.5 mm. The flow rates of the glycerin aqueous solution 44A are 0 mL / min (minute) and 1 mL / min. The flow velocities of the glycerin aqueous solution 44A at the center of the flow path 43A are estimated to be 0 mm / s (second) and 51.3 mm / s.

[0042] The ultrasound contrast agent 42 is a microbubble (SONAZOID (registered trademark) manufactured by CE Helfama) in which hydrogenated egg yolk phosphatidylserine sodium and refined sucrose are added to perfluorobutane microbubbles. The number of ultrasound contrast agents 42 per resolution volume in the glycerin aqueous solution 44A is 0.2 particles. The average radius of the ultrasound contrast agents 42 is 1.3 to 1.4 μm.

[0043] The ultrasonic probe 11 is an L11-5v manufactured by Verasonics. For the pulse waves 47N and 47P, the transmission frequency is 5.2 MHz, the sound pressure is 0.23 MPa, the MI (Mechanical Index) is 0.10, the pulse length is 1 cycle, the PRI is 0.44 ms (corresponding to 1 frame), and the number of pulses is 202. For the burst wave 48, the transmission frequency is 7.5 MHz, the sound pressure is 0.16 MPa, the MI is 0.06, the burst length is 350 cycles, and the PBI is 0.22 ms. The pulse length and burst length refer to the number of cycles of the electrical signal supplied to the ultrasonic probe 11, and the number of cycles of the ultrasonic waves may differ from the number of cycles of the electrical signal.

[0044] The viscosity of plasma is 1.3 to 3.3 mPa s. The glycerin concentration of the glycerin aqueous solution that achieves a viscosity in the same range as that of plasma is 10 to 40 w / w%. Therefore, experiments were conducted using glycerin aqueous solution 44A with glycerin concentrations of 0, 5, 10, 20, 30, and 50 w / w% (corresponding to a viscosity of 1 to 6 mPa s).

[0045] Ultrasound contrast agent 42 that satisfies the following conditions was extracted from the echo image. Condition 1: No ultrasound contrast agent 42 is present in the surrounding area. Condition 2: At least 0.1 mm away from the wall of flow path 43A. Condition 3: Present for a certain period of time (20 frames). Condition 4: Movement in the +Z direction (the opposite direction of the ultrasound probe 11). Condition 5: Z is approximately linear with respect to time, and the correlation coefficient is equal to or greater than a certain value. Condition 6: The echo signal is in a stable state.

[0046] Condition 1 is because the moving speed due to acoustic radiation force changes when multiple ultrasound contrast agents 42 are close to each other. Condition 2 is because the moving speed due to acoustic radiation force changes near the wall of the flow path 43A. Conditions 3 and 6 are because the acoustic radiation force is thought to be inconstant for disappearing or unstable ultrasound contrast agents 42. Conditions 4 and 5 are for removing ultrasound contrast agents 42 that move for reasons other than acoustic radiation force.

[0047] FIG. 10 is a diagram showing an example of depth Z versus time in an experiment. A glycerin aqueous solution 44A with a viscosity of 1 mPa·s was flowed at a flow rate of 1 mL / min. Ultrasound contrast agents 42 that satisfy the above conditions 1 to 6 were extracted from the echo image, and the depth in the Z direction versus time for the seven extracted ultrasound contrast agents 42 was plotted. As shown in FIG. 10, the seven ultrasound contrast agents 42 move in the Z direction at a nearly constant moving speed. For glycerin aqueous solutions 44A with different viscosities, the moving speed v of the extracted ultrasound contrast agents 42 was plotted. Ｚ was calculated.

[0048] 11 and 12 show the relationship between viscosity μ and the moving speed v Ｚ 11 and 12 are diagrams showing the flow rates of the glycerin aqueous solution 44A at 0 mL / min and 1 L / min, respectively. The dots at each viscosity are moved at a speed v Ｚ The calculated results are shown below. "-" indicates the average value of dots at each viscosity, and "x" indicates the median value of dots at each viscosity.

[0049] Movement speed v with respect to viscosity μ Ｚ wo v Ｚ = Aμ Ｂ The coefficients A and B were calculated by fitting the viscosity μ to the moving speed v Ｚ The coefficients A and B were calculated using all the data. Ｚ The coefficients A and B were calculated using the following formula.

[0050] As shown in Figure 11, when the flow rate is 0 mL / min, A = 3.65 and B = -1.03 for all data. On average, A = 4.00 and B = -0.98. As shown in Figure 12, when the flow rate is 1 mL / min, A = 3.95 and B = -1.13 for all data. On average, A = 4.18 and B = -0.92. As such, the values ​​of A and B are almost the same regardless of the flow rate.

[0051] (Simulation) A simulation was performed to determine whether A and B calculated in the experiment were valid. For the simulation, Equation 1 was used.

[0052]

[0053] Fｉ is the inertial force acting on the ultrasound contrast agent 42, F ａ is the force due to the added mass effect acting on the ultrasound contrast agent 42, F ｄ is the resistance force acting on the ultrasound contrast agent 42, F ｂ is the buoyancy force acting on the ultrasound contrast agent 42, F ｔｒａｖ is the acoustic radiation force acting on the ultrasound contrast agent 42. R and V are the radius and volume, respectively, of the ultrasound contrast agent 42, ρ is the density of the glycerin aqueous solution 44A, μ is the moving speed of the glycerin aqueous solution 44A, and P ｄｒｉｖｅ is the pressure of the incident ultrasound, u is the translational velocity of the ultrasound contrast agent 42, UR ｅ is the radial Reynolds number, R ｅ is the Reynolds number, F ｂｂ is the history force applied to the ultrasound contrast agent 42, and g is the gravitational acceleration. Since the radius R vibrates, the vibration of the radius R was calculated using the method of P. Marmottant et al., J. Acoust. Soc. Am., 118(6), 3499-3505, 2005.

[0054] Under the same ultrasonic irradiation conditions as in the experiment, the radius Ro of the ultrasonic contrast agent 42 was changed from 0.9 μm to 1.8 μm for each viscosity, and the moving speed v Ｚ Figure 13 shows the relationship between viscosity μ and migration velocity v Ｚ The dots indicate the calculated points, and the curves indicate the v Ｚ = Aμ Ｂ This is a curve fitted to

[0055] 14 is a diagram showing coefficients A and B versus radius Ro in the simulation. As shown in FIG. 14, coefficient A has a peak at radius Ro. This is thought to be related to the resonance frequency of the ultrasound contrast agent 42. As radius Ro increases, coefficient B approaches 0, which is thought to correspond to the viscosity having less of an effect on the movement speed.

[0056] FIG. 15 shows the relationship between viscosity μ and moving velocity v in the experiment and the simulation. Ｚ15 is a diagram showing the results of simulations in which the radius Ro is 1.3 to 1.6 μm, and the results of experiments in which the flow rate is 0 mL / min, including all data and average results, are superimposed. As shown in FIG. 15, the results of the experiments are nearly identical to the results of simulations in which the radius Ro of the ultrasound contrast agent 42 is 1.5 μm.

[0057] When the radius Ro of the ultrasound contrast agent 42 used in the experiment was actually measured, the average radius was 1.45 μm, the standard deviation was 0.33 μm, and the median was 1.41 μm. Thus, the results of the experiment and the simulation are in close agreement.

[0058] In this way, if the relationship between the viscosity of the target body fluid 44 and the movement speed of the ultrasound contrast agent 42 (e.g., coefficients A and B) is determined under the same conditions in an experiment or simulation, the viscosity can be calculated from the movement speed in step S14.

[0059] (Example of Image Generation) FIG. 16 is a schematic diagram showing an echo image generated by the image generation unit in an embodiment. As shown in FIG. 16, the echo image shows a living body 45, a tube 43, and a body fluid 44. Ultrasound contrast agents 42D-42H are shown within the body fluid 44. In step S15 of FIG. 5, the image generation unit 34 can color the images according to the viscosity calculated from the movement speed of the ultrasound contrast agents 42D-42H in the echo image information. For example, the ultrasound contrast agent 42F with a calculated high viscosity is displayed in red, and the ultrasound contrast agents 42D and 42H with a calculated low viscosity are displayed in blue. This allows areas of high and low viscosity of the body fluid to be visually identified.

[0060] 5 , the movement speed calculation unit 32 calculates the movement speed of the object floating in the body fluid 44 in the living body 45 by applying a force to the object. As in step S14, the viscosity calculation unit 33 calculates the viscosity of the body fluid 44 based on the calculated movement speed. This makes it possible to calculate the viscosity of the body fluid 44 in the living body 45 with high spatial resolution and high accuracy.

[0061] The target object is the ultrasound contrast agent 42, and the force that is different from the hydrodynamic force generated by the flow of the body fluid 44 is an acoustic radiation force that is generated by irradiating the ultrasound contrast agent 42 with ultrasound (first ultrasound: for example, burst wave 48 in FIG. 6 ). As a result, even if blood cells or the like are not present in the body fluid 44, the viscosity of the body fluid 44 can be calculated by applying a force to the ultrasound contrast agent 42 from outside the living body 45.

[0062] The ultrasound contrast agent 42 may be microbubbles other than those obtained by adding hydrogenated egg yolk phosphatidylserine sodium and refined sucrose to perfluorobutane microbubbles. The bubbles of the ultrasound contrast agent 42 may be any gas that is chemically stable and insoluble in body fluids, such as air, nitrogen, oxygen, carbon dioxide, perfluoropropane, perfluoropentane, perfluorohexane, or sulfur hexafluoride. The membrane covering the bubbles may be a phospholipid such as DMPC (dimyristoyl phosphatidylserine), DPPC (dipalmitoyl phosphatidylserine), DSPC (distearoyl phosphatidylcholine), DAPC (1,2-distearoyl-sn-glycero-3-phosphocholine), DBPC (1,2-diarachidoyl-sn-glycero-3-phosphocholine), or DLiPC (dilinoleoyl phosphatidylcholine), albumin, or galactose. The diameter of the ultrasound contrast agent 42 is, for example, 100 nm to 10 μm. If the diameter distribution of the ultrasound contrast agent 42 is large, the viscosity calculated from the movement speed will also have a large distribution. Therefore, the standard deviation of the average diameter of the ultrasound contrast agent 42 is preferably 0.5 or less, more preferably 0.3 or less, and even more preferably 0.2 or less.

[0063] Furthermore, the movement speed calculation unit 32 calculates the movement speed based on the ultrasonic echo 41 that is generated when the ultrasonic waves (second ultrasonic waves: pulse waves 47N and 47P in FIG. 6) irradiated to the ultrasonic contrast agent 42 are reflected by the living body 45. This allows the movement speed of the ultrasonic contrast agent 42 to be calculated. Note that, as shown in FIG. 6, it is preferable to use the pulse waves 47N and 47P and the burst wave 48, but the ultrasonic waves for obtaining the ultrasonic echo 41 and the ultrasonic waves for applying a force to the ultrasonic contrast agent 42 may be the same. In other words, the first ultrasonic wave and the second ultrasonic wave may be the same.

[0064] As in step S11, the image generator 34 generates echo image information of the living body 45 and the ultrasound contrast agent 42 based on the ultrasound echoes. This makes it possible to visualize the ultrasound contrast agent 42 as shown in Fig. 8. The image generator 34 may display the echo image on the display devices 15 and 25.

[0065] 10 , the movement speed calculation unit 32 calculates the movement speed based on the trajectory of the ultrasound contrast agent 42 in the echo image information. This allows the movement speed to be calculated for each of the ultrasound contrast agents 42. Therefore, the local viscosity can be calculated. The image generation unit 34 may not display the echo images on the display devices 15 and 25, and the movement speed calculation unit 32 may calculate the movement speed from the echo image information.

[0066] As shown in FIG. 16 , the image generator 34 changes the color of the ultrasound contrast agents 42D-42H in the echo image information based on the viscosity. This makes it possible to visualize the viscosity. Furthermore, the movement speed calculator 32 calculates the movement speed for each of the multiple ultrasound contrast agents 42, and the viscosity calculator 33 calculates the movement speed for each of the multiple ultrasound contrast agents 42. This makes it possible to calculate the viscosity with high spatial resolution. The image generator 34 changes the color for each of the multiple ultrasound contrast agents 42D-42H based on the calculated viscosity. This makes it possible to visualize the viscosity depending on the location of the body fluid 44. In this way, it is possible to evaluate local viscosity.

[0067] The viscosity calculation unit 33 calculates a relationship between a predetermined moving speed v and viscosity μ (for example, a power law v=Aμ Ｂ The viscosity is calculated based on the coefficients A and B of the relational expression. This allows the viscosity calculation unit 33 to calculate the viscosity based on the moving speed.

[0068] As in step S12, the movement speed calculation unit 32 may extract at least one object from the plurality of objects floating in the body fluid 44 and calculate the movement speed of the at least one object. This makes it possible to avoid calculating viscosity using an object that is not suitable for calculating the movement speed.

[0069] The conditions under which the movement speed calculation unit 32 extracts at least one object from multiple objects are, for example, conditions 1 to 6 described in Figure 10. In particular, it is preferable to extract a target object as at least one object when at least one of the following conditions is satisfied: no other objects exist within a certain distance from the target object; the target object is located at a certain distance or more from the inner wall of the pipe containing the body fluid; and the target object exists for a certain period of time or more. The movement speed calculation unit 32 may extract a target object as at least one object when all of the above three conditions are satisfied.

[0070] The viscosity calculation device 30 in Fig. 4 may be part of the ultrasound imaging device as in Fig. 2, or may be, for example, a computer 20 separate from the ultrasound imaging device 21 as in Fig. 2. The viscosity measurement device includes the viscosity calculation device 30 and an ultrasound irradiation unit such as an ultrasound probe 11. In Fig. 2, the viscosity measurement device is at least part of the ultrasound imaging device. In Fig. 3, the viscosity measurement device 102 includes at least part of the ultrasound imaging device 21 and the computer 20.

[0071] Although the preferred embodiments have been described in detail above, the present invention is not limited to the above-described embodiments, and various modifications and substitutions can be made to the above-described embodiments without departing from the scope of the claims.

[0072] This application claims priority from basic patent application No. 2024-115912, filed with the Japan Patent Office on July 19, 2024, the entire contents of which are incorporated herein by reference.

[0073] REFERENCE SIGNS LIST 10 Main body 11 Ultrasonic probe 12, 22 Processor 13 Transmitting / receiving circuit 14, 24 Memory 15, 25 Display device 16, 26 Input / output device 20 Computer 21 Ultrasonic imaging device 27 Storage medium 30 Viscosity calculation device 31 Acquisition unit 32 Travel speed calculation unit 33 Viscosity calculation unit 34 Image generation unit 35 Output unit 40 Ultrasound 41 Ultrasonic echo 42, 42A, 42B, 42C Ultrasonic contrast agent 43 Tube 44 Body fluid 45 Living body 47N, 47P Pulse wave 48 Burst wave 100, 102 Viscosity measurement device

Claims

1. A viscosity calculation device comprising: a movement speed calculation unit that calculates the movement speed of a target object floating in body fluid within a living organism by applying a force from outside the organism that is different from the hydrodynamic acting force generated by the flow of the body fluid; and a viscosity calculation unit that calculates the viscosity of the body fluid based on the calculated movement speed.

2. The viscosity calculation device according to claim 1, wherein the object is an ultrasound contrast agent, and the other force applied to the object is an acoustic radiation force generated by irradiating the ultrasound contrast agent with a first ultrasound wave.

3. The viscosity calculation device according to claim 2, wherein the movement speed calculation unit calculates the movement speed based on an ultrasonic echo that is generated when a second ultrasonic wave is irradiated onto the ultrasonic contrast agent and reflected by the living body.

4. The viscosity calculation device according to claim 3, further comprising an image generation unit that generates echo image information of the living body and the ultrasound contrast agent within the living body based on the ultrasound echoes.

5. The viscosity calculation device according to claim 4, wherein the movement speed calculation unit calculates the movement speed based on the trajectory of the ultrasound contrast agent in the echo image information.

6. The viscosity calculation device according to claim 4 or 5, wherein the image generation unit changes the color of the ultrasound contrast agent in the echo image information based on the viscosity.

7. A viscosity calculation device according to any one of claims 1 to 5, wherein the movement speed calculation unit extracts at least one object from the plurality of objects floating in the body fluid and calculates the movement speed of the at least one object.

8. The viscosity calculation device according to claim 7, wherein the movement speed calculation unit extracts the target object as the at least one target object when at least one of the following conditions is satisfied: there are no other targets within a certain distance from the target object; the target object is at least a certain distance away from the inner wall of the tube containing the body fluid; and the target object exists for more than a certain period of time.

9. A viscosity calculation device according to any one of claims 1 to 5, wherein the viscosity calculation unit calculates the viscosity based on a predetermined relationship between the moving speed and the viscosity.

10. A viscosity measuring device comprising: an ultrasonic irradiation unit that irradiates the ultrasonic contrast agent with the first ultrasonic wave; and a viscosity calculation device according to any one of claims 2 to 5.

11. A viscosity calculation method comprising: calculating a movement speed of an object floating in body fluid within a living organism by applying a force from outside the organism that is different from a hydrodynamic acting force generated by the flow of the body fluid; and calculating the viscosity of the body fluid based on the calculated movement speed.

12. A viscosity calculation program that causes a computer to function as: a movement speed calculation unit that calculates the movement speed of a target object floating in body fluid within a living organism by applying a force from outside the organism that is different from the hydrodynamic acting force generated by the flow of the body fluid; and a viscosity calculation unit that calculates the viscosity of the body fluid based on the calculated movement speed.

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