阅读说明：本技术 基于SonoVue的无创经颅超声血压测量装置及方法 (Non-invasive transcranial ultrasonic blood pressure measuring device and method based on SonoVue ) 是由 万明习 乔晓阳 温瑜 于 2020-12-21 设计创作，主要内容包括：本发明公开了一种基于SonoVue的无创经颅超声血压测量装置及方法,包括颅骨仿体仿生模块、血液循环加压系统和测压单元,在颅骨仿体中设置血管仿体,血管仿体与血液循环加压系统连接,在血管仿体中注入SonoVue微泡溶液代替血液运行,并通过血液循环加压系统控制血管仿体的压力,采用任意波形发生器和超声探头对颅骨仿体发射不同的入射声压,同时控制血光仿体的压力,进而获取不同入射声压、血管仿体的声散射信号和血管仿体压力之间的关系,进而根据三者之间的关系确定颅内血压。实现便捷的颅内加压测压,反映颅内血压与射入升压的关系,使SonoVue次谐波幅值与静水压之间的关系呈现最优线性关系,不仅实现准确无创测量颅内血压,还可以研究颅内血压与颅内压的关系。(The invention discloses a non-invasive transcranial ultrasonic blood pressure measuring device and method based on SonoVue, which comprises a skull dummy bionic module, a blood circulation pressurizing system and a pressure measuring unit, wherein a blood vessel dummy is arranged in the skull dummy, the blood vessel dummy is connected with the blood circulation pressurizing system, SonoVue micro-bubble solution is injected into the blood vessel dummy to replace blood to run, the pressure of the blood vessel dummy is controlled by the blood circulation pressurizing system, an arbitrary waveform generator and an ultrasonic probe are adopted to emit different incident sound pressures to the skull dummy, the pressure of the blood vessel dummy is controlled at the same time, and then the relation among the different incident sound pressures, the sound scattering signals of the blood vessel dummy and the pressure of the blood vessel dummy is obtained, and further the intracranial blood pressure is determined according to the relation among the three. The method realizes convenient intracranial pressure measurement, reflects the relation between intracranial blood pressure and injection pressure rise, enables the relation between the SonoVue subharmonic amplitude and the hydrostatic pressure to present an optimal linear relation, not only realizes accurate noninvasive measurement of the intracranial blood pressure, but also can research the relation between the intracranial blood pressure and the intracranial pressure.)

1. A noninvasive transcranial ultrasonic blood pressure measuring device based on SonoVue is characterized by comprising a skull bionic module, a blood circulation pressurizing system and a pressure measuring unit;

the skull bionic module comprises a skull imitation body and a blood vessel imitation body (5) arranged in a skull cavity;

the blood circulation pressurization system comprises a sealed container, a peristaltic pump (20), a blood pressure injection pump and a blood pressure measuring probe;

the sealed container is filled with SonoVue micro-bubbles, one end of the blood vessel imitation body (5) is connected with the sealed container through a peristaltic pump (20), the other end of the blood vessel imitation body (5) is connected with the sealed container through a blood pressure injection pump, and a blood pressure measuring probe is arranged on a pipeline connecting the blood vessel imitation body (5) and the sealed container;

the pressure measuring unit comprises a control unit, an arbitrary waveform generator, an ultrasonic transmitting and receiving unit, an ultrasonic probe and a hydraulic acquisition unit;

the arbitrary waveform generator is connected with the ultrasonic transmitting and receiving unit and the hydraulic acquisition unit, the ultrasonic transmitting and receiving unit is connected with the ultrasonic probe, the ultrasonic probe is used for generating ultrasonic waves to the skull imitation and receiving the sound scattering signals of the blood vessel imitation, the control unit is connected with the output end of the ultrasonic transmitting and receiving unit, the relationship between the subharmonic amplitude of the sound scattering signals and the different pressures of the blood vessel imitation is obtained, and the intracranial blood pressure of a human body is determined according to the relationship between the subharmonic amplitude and the pressure of the blood vessel imitation.

2. A SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 1, characterized in that the vascular phantom (5) is fixed in the cranial cavity by a vascular stent (4).

3. The SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device is characterized in that the skull dummy comprises a left skull half (1) and a right skull half (2), a latex gasket (8) is arranged at the splicing position of cranial cavities of the left skull half (1) and the right skull half, and a stainless steel hose clamp (10) is arranged on the outer side of the left skull half and the right skull.

4. The SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 1, characterized in that a silica gel plug (6) is arranged at the bottom of the skull phantom for opening or sealing the cranial cavity.

5. The SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 4, characterized in that a ventricle phantom (3) is further arranged in the cranial cavity, and the ventricle phantom (3) is connected with a cerebrospinal fluid pressurization system outside the skull phantom and used for measuring intracranial pressure.

6. The SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 5, wherein the cerebrospinal fluid pressurization system outside the craniotomy comprises an intracranial pressure injection pump and an intracranial pressure measuring probe;

the ventricle imitative body (3) is connected with an intracranial pressure injection pump through a pipeline, an intracranial pressure measuring probe is arranged on the pipeline, and the intracranial pressure measuring probe is connected with the control unit.

7. The SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 1, wherein the control unit is connected with an ultrasonic probe and an arbitrary waveform generator through an ultrasonic transmitting and receiving unit;

the ultrasonic transmitting and receiving unit comprises a power amplifier, a duplexer, a signal amplifier and a DAQ data acquisition card;

the input end of the power amplifier is connected with the arbitrary waveform generator, the output end of the power amplifier is connected with the duplexer, the duplexer is respectively connected with the ultrasonic probe and the signal amplifier, the output ends of the arbitrary waveform generator and the signal amplifier are respectively connected with the signal input end of the DAQ data acquisition card, and the output end of the DAQ data acquisition card is connected with the control unit.

8. A SonoVue-based noninvasive transcranial ultrasonic blood pressure measuring device according to claim 1, characterized in that the sealed container is provided on a magnetic stirring pump (22).

9. A measuring method of a SonoVue-based noninvasive transcranial ultrasound blood pressure measuring device according to any one of claims 1 to 8, comprising the steps of:

step 1, connecting a skull bionic module, a blood circulation pressurization system and a pressure measuring unit;

step 2, injecting the prepared SonoVue microbubble solution into a blood circulation pressurization system, keeping the pressure of the blood vessel phantom unchanged, adjusting the incident pressure rise of ultrasonic waves through a power amplifier, obtaining sound scattering signals of the blood vessel phantom corresponding to different incident pressure rises, establishing a curve graph of harmonic amplitude and incident sound pressure of infrasound scattering signals, and determining the growth period and the saturation period of the SonoVue according to the curve graph;

step 3, keeping the power constant, performing grouping test by adopting SonoVue solutions with different standing time lengths, gradually increasing the pressure of the blood vessel phantom during each group of test, acquiring the sound scattering signals of the blood vessel phantom of the SonoVue solutions with different standing time lengths under different pressures, establishing a subharmonic amplitude and pressure curve diagram of the blood vessel phantom according to the acquired sound scattering signals and pressure values, and determining the optimal service time for measuring the pressure after the preparation of the SonoVue micro-bubble solution;

step 4, selecting one incident boosting respectively at the growing period, the junction of the growing period and the saturation period of the SonoVue obtained in the step 2 and the saturation period for testing, gradually increasing the pressure of the blood vessel phantom in the testing process, obtaining a subharmonic amplitude and blood pressure relation diagram under three incident sound pressures, and determining the optimal incident sound pressure value suitable for the SonoVue pressure measurement;

step 5, in the optimal using time of the SonoVue micro-bubbles, selecting incident sound pressure at the junction of the growth period and the saturation period of the SonoVue, applying different pressures to the blood vessel phantom, obtaining subharmonic amplitudes of sound scattering signals under different pressures and corresponding blood pressure values collected by a hydraulic unit, and obtaining the relation between the subharmonic amplitudes and the pressures by utilizing linear fitting;

and acquiring subharmonic amplitude of the intracranial blood vessel by adopting incident sound pressure corresponding to the junction of the growth period and the saturation period of the SonoVue, and substituting the subharmonic amplitude into the relation between the subharmonic amplitude and the pressure to obtain the intracranial blood pressure.

10. The measurement method of the SonoVue-based noninvasive transcranial ultrasonic blood pressure measurement device according to claim 9, wherein the optimal use time for manometry after the preparation of the SonoVue microbubble solution in step 3 is within 1 minute after the preparation.

Technical Field

The invention relates to the field of medical instruments, in particular to a non-invasive transcranial ultrasonic blood pressure measuring device and method based on SonoVue.

Background

At present, stroke is a main disease which troubles the health of modern people, and the common cerebral artery and large vessel occlusion brain is the most common and malignant disease. The middle cerebral artery is used as an intermediate link of a closed loop of the brain, the blood pressure of the middle cerebral artery of a person with normal operation is basically equal to the average arterial pressure of the whole body, and when the middle cerebral artery or a common internal carotid artery is narrow or blocked, the blood pressure of the middle cerebral artery is far smaller than the average arterial pressure, which shows that the monitoring of the middle cerebral artery pressure can be used as a screening means of the blockage or the stenosis of the middle cerebral artery, and early warning is provided for preventing cerebral ischemic stroke.

Because the skull is the natural barrier, the measurement of the cerebral artery blood pressure is limited to invasive probe pressure measurement, and the patent is mostly seen in craniotomy operations (such as bypass operations, intracranial external bypass bridges and graft implantation), and the patency and perfusion conditions of the cerebral artery loop are evaluated by monitoring the cerebral artery blood pressure in real time, so that whether the graft placement is failed or whether the cerebral artery closed-loop perfusion condition is suitable for the operation is judged. But the application of the pressure measuring instrument is limited due to the characteristics that the invasive pressure measuring risk is great, and the blood pressure value can be changed by craniotomy and implantation of the probe.

The technical means of measuring pressure by using the enveloped microvesicle is long-standing, the prior related research comparison system is a technology (namely SHAPE method) for measuring pressure by using subharmonic amplitude, and the prior research is applied to measuring pressure of an intracardiac blood vessel and a portal vein of a dog, measuring pressure of a gap between tumor tissues of a mouse and a pig, and measuring pressure of human ventricular pressure and liver portal vein pressure; most of the applied microbubbles are Sonazoid and Definity, wherein Sonazoid is applied most, and then the relation between the harmonic amplitude and the hydrostatic pressure can present a linear relation under a proper condition, so that a foundation is provided for utilizing subharmonic pressure measurement. As the most widely used commercial microvesicles in China, previous experimental researches have tried to measure pressure by using subharmonic signals of SonoVue many times, but the obtained relation between subharmonic amplitude and hydrostatic pressure is nonlinear under most conditions, and no definite method can find a condition which can make the relation present linearity, so that the application of SonoVue in measuring pressure is limited.

Disclosure of Invention

Aiming at the problem that SonoVue in the prior art can not realize pressure measurement, the invention provides a non-invasive transcranial ultrasonic blood pressure measuring device and method based on coated microbubble SonoVue, so that the relation between SonoVue subharmonic amplitude and hydrostatic pressure presents an optimal linear relation, the accurate non-invasive measurement of intracranial blood pressure is realized, and the relation between the intracranial blood pressure and the intracranial pressure can be researched.

The invention is realized by the following technical scheme:

a non-invasive transcranial ultrasonic blood pressure measuring device based on SonoVue comprises a skull bionic module, a blood circulation pressurizing system and a pressure measuring unit;

the skull bionic module comprises a skull imitation body and a blood vessel imitation body arranged in a skull cavity;

the blood circulation pressurization system comprises a sealed container, a peristaltic pump, a blood pressure injection pump and a blood pressure measuring probe;

the blood pressure measuring probe is arranged on a pipeline connecting the blood vessel simulator and the sealed container;

the pressure measuring unit comprises a control unit, an arbitrary waveform generator, an ultrasonic transmitting and receiving unit, an ultrasonic probe and a hydraulic acquisition unit;

the arbitrary waveform generator is connected with the ultrasonic transmitting and receiving unit and the hydraulic acquisition unit, the ultrasonic transmitting and receiving unit is connected with the ultrasonic probe, the ultrasonic probe is used for generating ultrasonic waves to the skull imitation and receiving the sound scattering signals of the blood vessel imitation, the control unit is connected with the output end of the ultrasonic transmitting and receiving unit, the relationship between the subharmonic amplitude of the sound scattering signals and the different pressures of the blood vessel imitation is obtained, and the intracranial blood pressure of a human body is determined according to the relationship between the subharmonic amplitude and the pressure of the blood vessel imitation.

Preferably, the vascular mimics are fixed in the cranial cavity by vascular stents.

Preferably, the skull imitation body comprises a left half skull and a right half skull, a latex gasket is arranged at the splicing position of cranial cavities of the left half skull and the right half skull, and a stainless steel hose clamp is arranged on the outer sides of the left half skull and the right half skull.

Preferably, the bottom of the skull imitation is provided with a silica gel plug for opening or sealing the cranial cavity.

Preferably, a ventricular simulator is further arranged in the cranial cavity and connected with a cerebrospinal fluid pressurization system outside the cranial simulator for measuring intracranial pressure.

Preferably, the cerebrospinal fluid pressurization system outside the skull imitation body comprises an intracranial pressure injection pump and an intracranial pressure measurement probe;

the ventricle imitator is connected with an intracranial pressure injection pump through a pipeline, the intracranial pressure measuring probe is arranged on the pipeline, and the intracranial pressure measuring probe is connected with the control unit.

Preferably, the control unit is connected with the ultrasonic probe and the arbitrary waveform generator through the ultrasonic transmitting and receiving unit;

the ultrasonic transmitting and receiving unit comprises a power amplifier, a duplexer, a signal amplifier and a DAQ data acquisition card;

the input end of the power amplifier is connected with the arbitrary waveform generator, the output end of the power amplifier is connected with the duplexer, the duplexer is respectively connected with the ultrasonic probe and the signal amplifier, the output ends of the arbitrary waveform generator and the signal amplifier are respectively connected with the signal input end of the DAQ data acquisition card, and the output end of the DAQ data acquisition card is connected with the control unit.

Preferably, the sealed container is provided on a magnetic stirring pump.

A measuring method of a non-invasive transcranial ultrasonic blood pressure measuring device based on SonoVue comprises the following steps:

step 1, connecting a skull bionic module, a blood circulation pressurization system and a pressure measuring unit;

step 2, injecting the prepared SonoVue microbubble solution into a blood circulation pressurization system, keeping the pressure of the blood vessel phantom unchanged, adjusting the incident pressure rise of ultrasonic waves through a power amplifier, obtaining sound scattering signals of the blood vessel phantom corresponding to different incident pressure rises, establishing a curve graph of harmonic amplitude and incident sound pressure of infrasound scattering signals, and determining the growth period and the saturation period of the SonoVue according to the curve graph;

step 3, keeping the power constant, performing grouping test by adopting SonoVue solutions with different standing time lengths, gradually increasing the pressure of the blood vessel phantom during each group of test, acquiring the sound scattering signals of the blood vessel phantom of the SonoVue solutions with different standing time lengths under different pressures, establishing a subharmonic amplitude and pressure curve diagram of the blood vessel phantom according to the acquired sound scattering signals and pressure values, and determining the optimal service time for measuring the pressure after the preparation of the SonoVue micro-bubble solution;

step 4, selecting one incident boosting respectively at the growing period, the junction of the growing period and the saturation period of the SonoVue obtained in the step 2 and the saturation period for testing, gradually increasing the pressure of the blood vessel phantom in the testing process, obtaining a subharmonic amplitude and blood pressure relation diagram under three incident sound pressures, and determining the optimal incident sound pressure value suitable for the SonoVue pressure measurement;

step 5, in the optimal using time of the SonoVue micro-bubbles, selecting incident sound pressure at the junction of the growth period and the saturation period of the SonoVue, applying different pressures to the blood vessel phantom, obtaining subharmonic amplitudes of sound scattering signals under different pressures and corresponding blood pressure values collected by a hydraulic unit, and obtaining the relation between the subharmonic amplitudes and the pressures by utilizing linear fitting;

and acquiring subharmonic amplitude of the intracranial blood vessel by adopting incident sound pressure corresponding to the junction of the growth period and the saturation period of the SonoVue, and substituting the subharmonic amplitude into the relation between the subharmonic amplitude and the pressure to obtain the intracranial blood pressure.

Preferably, the optimal time of use for manometry after the SonoVue microbubble solution is prepared in step 3 is within 1 minute after preparation.

Compared with the prior art, the invention has the following beneficial technical effects:

the invention provides a non-invasive transcranial ultrasonic blood pressure measuring device based on SonoVue, which comprises a skull bionic module, a blood circulation pressurizing system and a pressure measuring unit, wherein a blood vessel bionic body is arranged in the skull bionic body, the blood vessel bionic body is connected with the blood circulation pressurizing system, SonoVue micro-bubble solution is injected into the blood vessel bionic body to replace blood to run, the pressure of the blood vessel bionic body is controlled through the blood circulation pressurizing system, different incident sound pressures are emitted to the skull bionic body by adopting an arbitrary waveform generator and an ultrasonic probe, the pressure of the blood vessel bionic body is controlled at the same time, the relation between sound scattering signals of the blood vessel bionic body using SonoVue with different standing durations and the pressure of the blood vessel bionic body under different incident sound pressures is further obtained, the optimal conditions of SonoVue pressure measurement are determined, and further intracranial blood pressure monitoring is carried out under the optimal conditions.

Firstly, acquiring acoustic scattering signals of the blood vessel phantom corresponding to different incident boosts, establishing a curve graph of harmonic amplitude and incident sound pressure of the infraacoustic scattering signals, and determining a growth period and a saturation period of the SonoVue; then, acquiring sound scattering signals of the SonoVue solution under different pressures for different standing time lengths, establishing a subharmonic amplitude and pressure curve graph of the blood vessel phantom according to the acquired sound scattering signals and pressure values, and determining the optimal use time of the prepared SonoVue micro-bubble solution for pressure measurement; then obtaining the junction of the growing period and the saturation period of the SonoVue, and respectively selecting one incident boost in the saturation period for testing, obtaining the subharmonic amplitude and the blood pressure relation diagram under three incident sound pressures, and determining the optimal incident sound pressure value suitable for the SonoVue pressure measurement; the method comprises the steps of selecting the junction of the growth period and the saturation period of the SonoVue micro-bubble at the optimal using time of the SonoVue micro-bubble, applying different pressures to a blood vessel phantom to be tested, obtaining subharmonic amplitudes of sound scattering signals under different pressures, obtaining the relation between the subharmonic amplitudes and the pressures, substituting the sound scattering signals of the human skull phantom into the relation to obtain accurate intracranial blood pressure, wherein the conventional micro-bubble subharmonic pressure measurement parameters mainly aim at the Sonaziod and other micro-bubbles and are not suitable for the SonoVue.

Drawings

FIG. 1 is a block diagram showing the structure of a blood pressure measuring device according to the present invention;

FIG. 2 is an internal structural view of the closed skull model of the present invention;

figure 3 is an external structural view of the closed skull model of the invention,

FIG. 4 is a structural view of the blood pressure measuring device of the present invention;

FIG. 5 is a diagram showing the relationship between the SonoVue microbubble subharmonic amplitude and the power amplifier power stage for different standing durations in the embodiment of the present invention;

fig. 6 is a negative peak value of sound pressure at a target blood vessel corresponding to each power gear of the power amplifier according to the embodiment of the present invention;

FIG. 7 is a graph of vascular phantom pressure versus subharmonic amplitude at three incident acoustic pressures using the freshly prepared SonoVue microbubbles according to an embodiment of the present invention;

FIG. 8 is a graph showing the relationship between the subharmonic amplitude of SonoVue microbubbles and the pressure of the blood vessel phantom at different standing time periods under the condition that the negative peak value of incident sound pressure is 346kPa according to the embodiment of the invention.

In the figure: 1-left half skull; 2-right skull; 3-ventricle imitations; 4-a vascular stent; 5-blood vessel imitations; 6-silica gel plug; 7-a glass tube; 8 a latex washer; 9-latex tube; 10-hose clamp; 11-a first hydraulic measurement probe; 12-skull mimetics; 13-a second hydraulic measurement probe; 14-a first switchable double pass; 15-a first syringe pump; 16-a second switchable tee; 17-a third switchable tee; 18-a fourth switchable tee; 19-a second syringe pump; 20-a peristaltic pump; 21-jar; 22-magnetic stirring pump; 23-digital pressure gauge.

Detailed Description

The present invention will now be described in further detail with reference to the attached drawings, which are illustrative, but not limiting, of the present invention.

Referring to fig. 1-4, the non-invasive transcranial ultrasonic blood pressure measuring device based on SonoVue comprises a skull bionic module and a pressure measuring device.

The skull bionic module comprises a skull bionic body 12, a ventricle bionic body 3, a blood vessel bracket 4 and a blood vessel bionic body 5.

The skull cavity in the skull imitation is a sealed cavity, the blood vessel support 4 is pasted on the inner wall of the skull cavity, the two ends of the blood vessel imitation 5 are sleeved on the support through thin latex tubes, the two ends of the blood vessel imitation 5 are connected with the glass tubes 7 through pipelines, the bottom of the skull imitation is provided with the silica gel plugs 6 for opening or sealing the skull cavity, the lower ends of the glass tubes 7 penetrate through the silica gel plugs 6 and extend out to the outside of the skull imitation, the ventricle imitation 3 is arranged above the occipital macropore of the skull imitation, the ventricle imitation 3 is connected with the other glass tube, and the lower end of the glass tube penetrates through the silica gel plugs 6 and extends out to the outside of the skull imitation.

The skull imitation comprises a left skull 1 and a right skull 2, a latex gasket 8 is arranged at the splicing position of the cranial cavity of the left skull 1 and the right skull, a stainless steel hose clamp 10 is arranged on the outer sides of the left skull 1 and the right skull and used for closing the left skull and the right skull, and when the skull imitation is used, the hose clamp is adjusted to tightly press the latex gaskets adhered to the junction of the two skull imitation bodies so that the cranial cavity of the skull imitation body is in a closed state.

The blood vessel imitation is a thin latex tube which is customized by opening the die and has sound attenuation coefficient similar to that of human artery, can bear high pressure of 160mmHg, and is convenient to be taken out and sleeved on any blood vessel support.

The blood vessel support 4 is made of organic glass and can be fixed at any position in the skull imitation body to simulate different blood vessels, for example, the blood vessel support can be fixed at the occipital bone to simulate the posterior cerebral artery.

The ventricle imitator 3 is a hollow latex ball, pressure is injected through a glass tube connected with the hollow latex ball to simulate and measure intracranial pressure, and the latex ball can bear 140mmHg high pressure.

The skull imitation is formed by establishing a 3D model based on CT data of real human skull, arranging a round hole for installing a silica gel plug 6 at the position of a big hole of an occipital bone of the 3D model, dividing the 3D model into a left half and a right half, and then printing the two halves by PLA materials in a 3D mode, forming a skull cavity in the skull imitation, and enabling the skull imitation to bear high intracranial pressure.

The pressure measuring device comprises a blood circulation pressurizing system, a cerebrospinal fluid pressurizing system and a pressure measuring unit.

The blood circulation pressurization system comprises a sealable wide-mouth bottle 21, a magnetic stirring pump 22, a peristaltic pump 20, a second syringe pump 19 and a first hydraulic pressure measurement probe 11.

Wherein, sealed wide-necked bottle 21 sets up on magnetism agitator pump 22, wide-necked bottle 21 connects the glass pipe at the imitative body both ends of blood vessel through two root canals respectively, connect peristaltic pump 20 on one of them pipeline, but set up third switch tee bend 17 on the pipeline between peristaltic pump 20 and the imitative body of blood vessel, but first hydraulic pressure measuring probe 11 is connected to third switch tee bend 17, but first hydraulic pressure measuring probe 11 is used for measuring the pressure that the imitative body of blood vessel, but be provided with fourth switch tee bend 18 on another pipeline, but fourth switch tee bend 18 is connected with second syringe pump 19.

A liquid inlet and a liquid outlet are arranged at the upper part of the wide-mouth bottle 21, one end of the liquid outlet is connected with a peristaltic pump 20 through a pipeline, one end of the liquid inlet is connected with a second injection pump 19 through a pipeline, the other end of the liquid inlet is connected with a long glass tube, the other end of the liquid outlet is connected with a short glass tube, and the long glass tube and the short glass tube are both positioned inside the wide-mouth bottle 21, and the height of the lower end of the short glass tube is higher than that of the lower end of the long glass tube, so that a circulation path simulating intracranial blood flow is formed, the contrast medium is filled in the pipeline and the blood vessel phantom, the SonoVue micro-bubble enters the wide-mouth bottle 21 through the long glass tube, in getting into peristaltic pump and blood vessel imitative through short glass tube, because the length of long glass tube is longer, can directly flow in the bottom of wide-necked bottle 21 with the SonoVue microbubble, avoid it directly to flow out through short glass tube, consequently ensure that the microbubble solution that gets into the peristaltic pump stirs completely.

Cerebrospinal fluid pressurization system includes first syringe pump 15 and second hydraulic pressure measuring probe 13, and first syringe pump 15 is connected with the one end of pipeline through first switch bi-pass 14, and the glass union coupling that the other end and the imitative body 3 of ventricles of brain of pipeline are connected is provided with switch tee bend 16 of second on this pipeline, but switch tee bend 16 of second is connected with second hydraulic pressure measuring probe 13, and second hydraulic pressure measuring probe 13 is used for measuring intracranial pressure, also is cranial cavity pressure.

The pipelines are all latex tubes 9.

As shown in fig. 1, the pressure measuring device includes a control unit, an arbitrary waveform generator, an ultrasonic probe, an ultrasonic transmitting and receiving unit, and a hydraulic pressure collecting unit.

The control unit is connected with the output end of the ultrasonic transmitting and receiving unit, the input end of the ultrasonic transmitting and receiving unit is respectively connected with the ultrasonic probe and the arbitrary waveform generator, the ultrasonic probe is used for being abutted against the position of a temporal window of a skull imitation, the input end of the hydraulic acquisition unit is connected with the second hydraulic measurement probe 13 and the first hydraulic measurement probe 11, and the output end of the hydraulic acquisition unit is connected with the arbitrary waveform generator.

The ultrasonic transmitting and receiving unit comprises a power amplifier, a duplexer, a signal amplifier and a DAQ data acquisition card.

The input end of the power amplifier is connected with the arbitrary waveform generator, the output end of the power amplifier is connected with the duplexer, the duplexer is respectively connected with the ultrasonic probe and the signal amplifier, the output ends of the arbitrary waveform generator and the signal amplifier are respectively connected with the signal input end of the DAQ data acquisition card, and the output end of the DAQ data acquisition card is connected with the control unit.

The DAQ data acquisition card is used for synchronously uploading a pressure value of the blood vessel phantom acquired by the first hydraulic measurement probe 11 to the DAQ data acquisition card through triggering of the arbitrary waveform generator by the hydraulic acquisition unit, and the DAQ data acquisition card sends the pressure value, incident sound pressure of the ultrasonic wave and the sound scattering signal of the blood vessel phantom to the control unit.

The ultrasonic transmitting and receiving unit is used for transmitting ultrasonic waves and synchronously receiving acoustic scattering signals corresponding to the ultrasonic waves.

The second hydraulic pressure measuring probe 13 and the first hydraulic pressure measuring probe 11 form a hydraulic pressure measuring unit, the measured pressure of the blood vessel phantom and the measured pressure of the brain ventricle phantom are triggered by an arbitrary waveform generator through a digital pressure gauge 23, are synchronously uploaded to a DAQ data acquisition card and then are sent to a control unit, and the control unit is connected with a display.

The control unit screens out acoustic scattering signals in the vascular phantom in the acquired acoustic scattering signals, extracts subharmonic amplitudes of the acoustic scattering signals, obtains frequency spectrums after carrying out fast Fourier transform (Matlab), and takes the average value of the amplitudes in a 0.4MHz bandwidth with 2.5MHz as the center as the subharmonic amplitude.

And then, performing linear fitting on the subharmonic amplitude and the pressure of the blood vessel phantom to obtain a relational expression between the subharmonic amplitude and the blood pressure, and calculating according to the relational expression between the subharmonic amplitude and the blood pressure to obtain the corresponding blood pressure.

The model of the arbitrary waveform generator is KEYSIGHT, 33500B, and the emitted acoustic pulse signal is a sinusoidal signal.

The power amplifier is of the type RPR4000, RITEC Inc., Warwick, US, with a transmission frequency of 5MHz, a sub-harmonic component frequency of 2.5MHz, a pulse length of 12cycles, and a pulse repetition frequency of 25 Hz. .

The duplexer is model number RDX-2, RITEC inc, Warwick, US.

The signal amplifier is model No. BR640, RITEC inc, Warwick, US.

The ultrasonic probe is a single-array-element non-focusing probe with the model number of V382, Panamerics, Waltham, MA, USA, the central frequency of 3.5MHz, the bandwidth of-6 dB 2.25MHz-4.83 MHz.

The hydraulic acquisition unit is a digital pressure gauge.

The following is a detailed description of the measurement method of the non-invasive transcranial ultrasound blood pressure measurement device based on the coated microbubble SonoVue provided by the present invention, where it is to be noted here that, when intracranial blood pressure measurement is performed, the ventricular phantom does not participate in measurement, and may be connected or not connected, and when intracranial blood pressure measurement is performed, whether the cranial cavity is in a sealed environment or not may be performed, and the method specifically includes the following steps:

step 1, preparation of a bionic model before experiment.

The SonoVue is prepared into suspension according to the instruction, 0.8mL of the suspension is pumped and then is injected with 400mL of normal saline, the mixture is uniformly mixed to obtain a microbubble solution, 370mL of the microbubble solution is injected into a wide-mouth bottle, and the rest 30mL of the microbubble solution is injected into a second injection pump 19 for regulating the pressure of the blood vessel phantom.

The peristaltic pump is opened to adjust the flow rate to 60rpm, so that the micro-bubble solution slowly flows into the blood vessel phantom until the micro-bubble solution fills the pipeline of the whole blood circulation pressurization system, the bottle cap of the wide-mouth bottle is screwed down after air in the pipeline is emptied, the wide-mouth bottle is in a sealed state, and the fourth switchable tee joint 18 is opened.

The whole preparation process did not exceed 3 minutes, and the SonoVue suspension was always placed in the original bottle, ready to use only when the test started.

And 2, setting test parameters, adjusting the power of a power amplifier to control the incident boosting of the ultrasonic waves under the condition that other parameters are not changed, testing once when the power is adjusted, obtaining the acoustic scattering signals of the blood vessel imitations corresponding to n powers, establishing a curve graph of subharmonic amplitude and incident sound pressure according to all the transmitting powers and the acoustic scattering signals of the blood vessel imitations corresponding to the transmitting powers, and determining the growth period and the saturation period of the SonoVue according to the curve graph.

The specific process is as follows: the pressure of the blood vessel phantom is kept constant at 20mmHg, the power gear of the power amplifier is increased from 1 to 24, the power amplifier can be adjusted in a mode of increasing gear by gear, or can be adjusted as an increasing step by every two or more gears, namely 3 gears, 6 gears, 9 gears … and the like, and the adjusted power is used for testing once when the power is adjusted.

Acquiring 50 pulse signals at each power gear, acquiring 3 times, totally 150 pulse signals, simultaneously acquiring acoustic scattering signals corresponding to the interior of the vascular phantom, performing fast Fourier transform on the acquired acoustic scattering signals through Matlab to obtain a frequency spectrum, extracting an average value of amplitudes within a 0.4MHz bandwidth with 2.5MHz as a center as a subharmonic amplitude, establishing a curve graph according to the obtained subharmonic amplitude and the incident boost of the corresponding pulse signals, determining the growth period and the saturation period of the SonoVue, and selecting the optimal emission sound pressure according to the incident sound pressure values corresponding to the growth period and the saturation period of the SonoVue to provide an alternative range for the step 4.

Note that the entire experimental procedure was approximately 3 minutes without microbubble replenishment.

Fig. 5 is a graph showing the relationship between the subharmonic amplitude and the incident sound pressure, and fig. 6 is a graph showing the corresponding transcranial and transcranial negative pressure peak values of the power gear of the power amplifier, and the results show that: the negative peak value of incident sound pressure at the vascular phantom is the growth period of subharmonic when 100-346 kPa, the subharmonic enters the saturation period after 346kPa, namely, the region of subharmonic amplitude increasing along with the increase of the incident sound pressure is the growth period, and the region of harmonic amplitude keeping stable along with the increase of the incident sound pressure is the saturation period; the standing time has no influence on the relationship between the subharmonic amplitude of the SonoVue and the incident sound pressure.

Step 3, setting test parameters, keeping the power constant, performing grouping test by adopting SonoVue suspension liquid with different standing time lengths, gradually increasing the pressure of the blood vessel simulator during each group of test, acquiring the acoustic scattering signals of the blood vessel simulator of the SonoVue suspension liquid under different pressures during each group of test, further acquiring the acoustic scattering signals of the blood vessel simulator of the SonoVue suspension liquid under different pressures during different standing time lengths, establishing a subharmonic amplitude and pressure curve graph of the blood vessel simulator according to the acquired acoustic scattering signals and pressure values, and determining the optimal service time for pressure measurement after the SonoVue microbubble suspension liquid is prepared.

Specifically, a SonoVue suspension is prepared, the suspension is injected into a blood vessel phantom according to the method in the step 1, the power position 12 of a power amplifier is selected, the blood pressure is increased from 30mmHg to 160mmHg, 50 pulse signals are collected at each blood pressure for three times, the whole experiment process is about 3 minutes without supplementing microbubbles in the whole process, a blood circulation pressurization system is emptied after each group of experiments are finished, the SonoVue is extracted, the time from the current time to the preparation of the SonoVue is recorded, the collection process in the step 3 is repeated until one bottle of SonoVue is used up, and the acoustic scattering signals of the blood vessel phantom of 5 groups of SonoVue suspensions at different standing time lengths under different pressures can be obtained.

And then extracting subharmonic amplitude values in the blood vessel simulator in the same manner as in the step 2, obtaining five subharmonic amplitude values and pressure relation graphs under different standing time lengths, determining the optimal use time suitable for Sonovue pressure measurement, setting the time in which the harmonic amplitude values and the pressure in the relation graphs are in linear relation as Sonovue micro-bubble as the optimal use time, and setting the optimal use time for pressure measurement after the Sonovue micro-bubble solution is prepared as the time within 1 minute after the preparation.

As shown in fig. 7, only the subharmonic amplitude of the Sonovue microbubble just prepared and the blood pressure value of the blood vessel show good linear relationship in the whole pressure section, and as the standing time of the Sonovue increases, the range of the linear relationship between the subharmonic amplitude and the pressure is smaller and smaller, and the reduction amplitude in the linear relationship is smaller and smaller, so when using Sonovue manometry, the freshness of the Sonovue microbubble needs to be noticed besides the sound pressure, and only the Sonovue microbubble just prepared has the maximum manometry range and sensitivity.

Step 4, selecting the optimal transmitting sound pressure

And (3) respectively selecting one incident sound pressure at the boundary of the growth period, the saturation period of the growth period and the saturation period of the SonoVue obtained in the step (2) for testing, gradually increasing the pressure of the blood vessel phantom in the testing process, obtaining the subharmonic amplitude and blood pressure relation diagram under three incident sound pressures, and determining the optimal incident sound pressure value suitable for the SonoVue pressure measurement.

Specifically, according to the result obtained in step 2, selecting one incident sound pressure at the growth phase, the boundary of the saturation phase in the growth phase and the saturation phase of SonoVue, using the SonoVue microbubble just prepared, increasing the blood pressure from 30mmHg to 160mmHg, collecting 50 pulse signals at each blood pressure for three times, extracting the sub-harmonic amplitude in the blood vessel in the same manner as in step 2, obtaining the relationship diagram of the sub-harmonic amplitude and the blood pressure under 3 incident sound pressures, and determining the optimal incident sound pressure value suitable for the SonoVue pressure measurement.

As shown in fig. 7: when the negative peak value of the sound pressure at the blood vessel phantom is 238kPa, the subharmonic amplitude shows a significant descending trend only after the pressure value of the blood vessel phantom is more than 60 mmHg; when the negative peak value of the sound pressure at the position of the blood vessel phantom is 346kPa, the subharmonic amplitude is in the range of 30-160 mmHg of the blood pressure value, the linear relation of the pressure value is good, and the corresponding pressure measuring sensitivity is 0.25 dB/mmHg; when the negative peak value of the sound pressure at the blood vessel phantom is 454kPa, the subharmonic amplitude is in the range of the blood pressure value of 30 to 160mmHg, although the linear relation of the pressure value is good, the manometric sensitivity is only 0.10 dB/mmHg. Therefore, for SonoVue microbubbles, the optimal manometric sound pressure value is at the boundary between the growth phase and the saturation phase of the subharmonics.

Therefore, when SonoVue is used to measure intracranial blood pressure, the optimal incident sound pressure should be the sound pressure corresponding to the boundary between the anagen phase and the saturation phase. Previous studies on SHAPE selected the point at which the growth rate was greatest during the growth phase for optimal incident sound pressure, which was suitable for Sonazoid, Definity, but not for SonoVue. This is why current studies using SonoVue for sub-harmonic amplitude manometry do not yield ideal results.

And 5, measuring the pressure according to the optimal pressure measuring conditions obtained in the step.

And (3) using the just-prepared SonoVue micro-bubbles, selecting incident sound pressure at the junction of the growth phase and the saturation phase of the SonoVue, applying different pressures to the blood vessel phantom, obtaining subharmonic amplitudes of sound scattering signals under different pressures, and obtaining the relation between the subharmonic amplitudes and the pressures by utilizing linear fitting.

When measuring intracranial blood pressure of a human body, applying incident sound pressure corresponding to the junction of the SonoVue growth period and the saturation period on a temporal window to obtain the subharmonic amplitude of an intracranial blood vessel, and substituting the subharmonic amplitude into the relation between the subharmonic amplitude and the pressure to obtain the intracranial blood pressure.

The method for researching the relation between the intracranial blood pressure and the intracranial pressure by using the non-invasive transcranial ultrasonic blood pressure measuring device based on the coated microbubble SonoVue provided by the invention is explained in detail below.

The blood vessel simulator and the ventricle simulator 3 are installed in the skull simulator, water is filled in the ventricle simulator 3, the two halves of the skull simulator are closed through the hose clamp, water is filled in the cranial cavity, the bottom of the skull simulator is sealed by the silica gel plug 6 to seal the cranial cavity, the blood vessel simulator is connected with the blood circulation pressurization system, the ventricle simulator 3 is connected with the cerebrospinal fluid pressurization system, water is filled in the first injection pump 15, and the first switchable double-way 14 and the second switchable double-way 16 are opened to pressurize and measure the pressure in the ventricle simulator 3.

Injecting water into the ventricle imitative body 3 through the first injection pump 15 to change the intracranial pressure, enabling the second injection pump 19 to be fixed, collecting the intracranial pressure through the second hydraulic measurement probe 13, simultaneously obtaining the pressure of the blood vessel imitative body, and monitoring the influence of the change of the intracranial pressure on the pressure of the blood vessel imitative body; the microbubble solution is injected into the vascular loop through the second injection pump 19 to change the pressure of the vascular phantom, the first injection pump 15 is fixed to simultaneously acquire the pressure of the vascular phantom and the intracranial pressure, and the influence of the change of the pressure of the vascular phantom on the intracranial pressure is monitored.

The effect of vessel occlusion and stenosis on intracranial pressure and intracranial blood pressure can also be studied by implanting an embolus into a vascular mimic or by clamping the vessel.

Because the measurement of the intracranial pressure is widely applied clinically, the measurement is an important physiological parameter for judging the state of the whole cranial cavity, but the physiological phenomenon influencing the intracranial pressure is various and complex, the research on the relationship between the intracranial blood pressure and the intracranial pressure can help us to better utilize the physiological index of the intracranial pressure, and the intracranial vascular state is reversely deduced according to some fluctuation characteristics of the physiological index; the method can also help us to find out an application scene that intracranial blood pressure monitoring is different from intracranial pressure monitoring.

Aiming at the fact that no device for measuring intracranial vascular blood pressure by using microbubble subharmonic exists at present, the invention provides the practical operation specification and the optimal sound pressure parameter when the SonoVue subharmonic amplitude is used for measuring the pressure, and provides technical support for avoiding the nonlinearity.

The above-mentioned contents are only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited thereby, and any modification made on the basis of the technical idea of the present invention falls within the protection scope of the claims of the present invention.