CN101982156B - Blood-pressure noninvasive measuring device based on micro-bubble ultrasound contrast agents and measuring method thereof - Google Patents
Blood-pressure noninvasive measuring device based on micro-bubble ultrasound contrast agents and measuring method thereof Download PDFInfo
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Abstract
本发明公开了一种基于微泡超声造影剂的血压无创测量装置及其测量方法，测量装置包括超声探头、发射模块、接收模块、测压位置选择模块、带通滤波器、频谱分析器、次谐波最优发射频率计算模块和血压计算及显示模块；测量方法包括步骤一：将微泡超声造影剂溶液经静脉注入血液中，并利用诊断超声监视其行踪；步骤二：当造影剂到达测压位置时，采集来自造影剂的声散射信号；步骤三：对采集到的声散射信号进行筛选、频谱分析，得到次谐波最优发射频率；步骤四：根据次谐波最优发射频率与环境压力之间的关系式，得到环境压力；本发明能够提供更加精准的、可重复性和可靠性更高的血压无创测量结果。
The invention discloses a blood pressure non-invasive measuring device and a measuring method based on a microbubble ultrasonic contrast agent. The measuring device includes an ultrasonic probe, a transmitting module, a receiving module, a pressure measurement position selection module, a band-pass filter, a spectrum Harmonic optimal transmission frequency calculation module and blood pressure calculation and display module; the measurement method includes step 1: injecting the microbubble ultrasonic contrast agent solution into the blood through the vein, and using diagnostic ultrasound to monitor its whereabouts; step 2: when the contrast agent reaches the measurement When pressing the position, collect the acoustic scattering signal from the contrast agent; Step 3: Filter and analyze the frequency spectrum of the collected acoustic scattering signal to obtain the optimal emission frequency of the sub-harmonic; Step 4: According to the optimal emission frequency of the sub-harmonic and The relationship between the environmental pressures is used to obtain the environmental pressure; the invention can provide more accurate, repeatable and reliable blood pressure non-invasive measurement results.
Description
Technical field
The present invention relates to a kind of blood pressure non-invasive measurement device and measuring method thereof, belong to the technical field of utilizing the ultrasonic measurement blood pressure based on microcapsular ultrasound contrast agent.
Background technology
Measuring the chambers of the heart and the interior blood pressure of trunk can provide the health status of blood vessel and organ, is that the clinician evaluates and has a heart disease or the effective tool of patient's state of an illness of angiopathy.At present, mainly through measuring blood pressure in the conduit insertion chambers of the heart that will be furnished with pressure transducer.This is a kind of blood pressure measuring method that wound is arranged, and this usually is accompanied by pain, infection even injury of pulmonary artery, endocarditis and hemorrhage.1972, Burton applied to simple and easy bernoulli equation in the ultrasonic Doppler technique, had from then on started the beginning of chambers of the heart internal pressure non-invasive measurement.But Strauss discovers, utilizes this method, and the reliability of measurement result, repeatability are not high.At present, this method only can be used to measure the maximum pressure differential of blood pressure in the chambers of the heart.
The acoustic contrast agent (UCA) that is made up of a large amount of microbubbles (diameter is less than 10 microns) can get into blood circulation through intravenous injection, and gets in the chambers of the heart via the capillary network of pulmonary.Because the compressibility of microvesicle, the change of chambers of the heart internal pressure can cause that the size of microvesicle changes, and then causes the resonant frequency of microvesicle, and acoustic characteristics such as echo amplitude change.Through measuring the change of microvesicle acoustic characteristic, just can obtain the variation of chambers of the heart internal pressure.Therefore microcapsular ultrasound contrast agent can be used as the pressure transducer in the chambers of the heart internal pressure measurement, thereby realizes the non-invasive measurement of blood pressure.
US Patent specification US-3640271 discloses a kind of method of utilizing the relation estimation blood pressure between bubble resonant frequency and the ambient pressure on February 8th, 1972.W.M.Fairbank and M.O.Scully; " A new noninvasive techniquefor cardiac pressure measurements:Resonant scattering of ultrasound from bubbles; " IEEE Trans.Biomed.Eng.24; 107-110 (1977) points out because the distribution of sizes of bubble broad has caused the formant of broad, therefore reduces the pressure measurement precision of this method.A.Bouakaz.; P.J.A.Frinking, N.de Jong, N.Bom; " Noninvasivemeasurement of the hydrostatic pressure in a fluid-filled cavity based on the disappearance time ofmicrometer-sized free gas bubbles; " Ultrasound Med.Biol.25, the result of study of 1407-1415 (1999) shows, in the human blood-pressure excursion (0～200mmHg); The side-play amount of the resonant frequency of bubble is less, so the pressure measurement sensitivity of this method is not high.US Patent specification US-6302845B2 discloses a kind of amplitude of microcapsular ultrasound contrast agent subharmonic scattered signal and method of the estimation of the relation between ambient pressure blood pressure utilized October 16 calendar year 2001.F.Forsberg, J.B.Liu, W.T.Shi; J.Furuse, M.Shimizu, B.B.Goldberg; " In vivo pressure estimation usingsubharmonic contrast microbubble signals:proof of concept, " IEEE Transactions on Ultrasonics 52,581-583 (2005) shows in the experimental result of body; Measurement result for a plurality of cardiac cycles is also inconsistent, and its repeatability remains further to be improved.In addition; K.S.Andersen, J.A.Jensen, " Ambient pressure sensitivity of microbubblesinvestigated through a parameter study; " J.Acoust.Soc.Am.126; The result of study of 3350-3358 (2009) shows, between the amplitude of subharmonic and the ambient pressure and not exclusively be linear relation, this can influence the reliability of utilizing the result that linear calibration's method obtains.
Summary of the invention
The objective of the invention is provides a kind of have higher pressure measurement precision and sensitivity in order to overcome the deficiency of existing noinvasive pressure testing method based on microcapsular ultrasound contrast agent, and the result has the blood pressure non-invasive measurement method and system of higher repeatability and reliability.
Blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent of the present invention comprises that ultrasonic probe, transmitter module, receiver module, pressure measurement choice of location module, band filter, frequency spectrum analyser, subharmonic optimum transmission frequency computing module and blood pressure calculate and display module;
Ultrasonic probe links to each other with receiver module with transmitter module respectively, and said receiver module, pressure measurement choice of location module, band filter, frequency spectrum analyser, subharmonic optimum transmission frequency computing module and blood pressure calculate and display module links to each other successively;
Ultrasonic probe comprises transmitting probe and receiving transducer;
Transmitter module comprises signal generator and power amplifier, and signal generator produces pulse signal, and pulse signal encourages the transmitting probe in the ultrasonic probe to produce ultrasound wave behind power amplifier;
Receiver module comprises low noise power amplifier, anti-aliasing low pass filter and A/D converter; The ultrasonic exciting microcapsular ultrasound contrast agent vibration that transmitting probe in the ultrasonic probe produces produces the sound scattering signal; The sound scattering signal is obtained by the receiving transducer in the ultrasonic probe; And respectively via low noise power amplifier to signal amplify, anti-aliasing low pass filter filters out the radio-frequency component in the signal; A/D converter is a digital signal with the signal from analog signal transition, finally collects the sound scattering signal from contrast agent;
Pressure measurement choice of location module is come out the sound scattering signal screening from the pressure measurement position in the sound scattering signal that collects; The sound scattering signal that screens carries out bandpass filtering through band filter, and obtaining frequency is the subharmonic composition that transmitting probe produces frequency of ultrasonic 1/2; Filtered subharmonic input spectrum analyzer obtains the frequency spectrum of subharmonic, inputs to subharmonic optimum transmission frequency computing module;
Subharmonic optimum transmission frequency computing module relatively obtains the maximum subfrequency of amplitude; Then the frequency content in the ultrasound wave of this subfrequency pairing this moment of transmitting probe generation is the subharmonic optimum transmission frequency of this moment, inputs to blood pressure and calculates and display module;
Blood pressure calculates and display module calculates corresponding ambient pressure according to the relational expression between subharmonic optimum transmission frequency and the ambient pressure, and ambient pressure is pressure value; Described relational expression is:
P
amb＝k·f
odf+b
Wherein, P
AmbBe ambient pressure, unit is mmHg, f
OdfBe the subharmonic optimum transmission frequency, unit is MHz, and k is a slope, 50≤k≤200, and b is an intercept ,-1200≤b≤-500.
Blood pressure non-invasive measurement method based on microcapsular ultrasound contrast agent of the present invention comprises following step:
Step 1: microcapsular ultrasound contrast agent solution is injected blood through vein, and utilize diagnostic ultrasound to keep watch on its whereabouts;
Step 2: when contrast agent arrives the pressure measurement position, gather sound scattering signal from contrast agent;
When contrast agent arrives the pressure measurement position; Signal generator produces pulse signal; Pulse signal encourages the transmitting probe in the ultrasonic probe to produce ultrasound wave behind power amplifier; Ultrasonic exciting microcapsular ultrasound contrast agent vibration produces the sound scattering signal, and the sound scattering signal is obtained by the receiving transducer in the ultrasonic probe, the sound scattering signal respectively via low noise power amplifier to signal amplify, anti-aliasing low pass filter filters out the radio-frequency component in the signal; A/D converter is a digital signal with the signal from analog signal transition, finally collects the sound scattering signal from contrast agent;
Step 3: the sound scattering signal to collecting screens, spectrum analysis, obtains the subharmonic optimum transmission frequency;
Sound scattering signal screening from the pressure measurement position in the sound scattering signal that collects is come out, and the sound scattering signal that screens carries out bandpass filtering, and obtaining frequency is the subharmonic composition that transmitting probe produces frequency of ultrasonic 1/2; Filtered subharmonic is carried out spectrum analysis; Obtain the frequency spectrum of subharmonic; The subfrequency that the amplitude that relatively obtains is maximum, then the frequency content in the ultrasound wave that produces of the transmitting probe of this subfrequency institute corresponding this moment is subharmonic optimum transmission frequency at this moment;
Step 4: the relational expression according between subharmonic optimum transmission frequency and the ambient pressure obtains ambient pressure;
Subharmonic optimum transmission frequency substitution subharmonic optimum transmission frequency that step 3 is obtained and the relational expression between the ambient pressure obtain this ambient pressure constantly, and ambient pressure is pressure value, and relational expression is:
P
amb＝k·f
odf+b
Wherein: P
AmbBe ambient pressure, unit is mmHg, f
OdfBe the subharmonic optimum transmission frequency, unit is MHz, and k is a slope, 50≤k≤200, and b is an intercept ,-1200≤b≤-500.
The invention has the advantages that:
(1) pressure measurement precision and sensitivity are higher;
(2) result has higher repeatability and reliability.
Description of drawings
Fig. 1 is the structural representation that the present invention is based on the blood pressure non-invasive measurement device of microcapsular ultrasound contrast agent;
Fig. 2 is a method flow diagram of the present invention;
Fig. 3 is the sub-sine pulse of embodiment of the invention signal generator emission;
Fig. 4 is the frequency diagram of embodiment of the invention sound scattering signal before bandpass filtering;
Fig. 5 is the frequency diagram of embodiment of the invention sound scattering signal behind bandpass filtering;
Fig. 6 is the relation curve of the static balance radius change of embodiment of the invention microvesicle resonant frequency during with microvesicle 0mmHg;
Fig. 7 is the relation curve of the static balance radius change of embodiment of the invention microvesicle resonant frequency shift amount during with microvesicle 0mmHg;
Fig. 8 is the sound scattering cross section of embodiment of the invention SonoVue microvesicle;
Fig. 9 is that the subharmonic optimum transmission frequency is pressed the relation curve that changes under the different acoustic pressures of the embodiment of the invention with environment;
Figure 10 is the relation curve that embodiment of the invention subharmonic optimum transmission frequency side-play amount changes with incident sound pressure;
Figure 11 embodiment of the invention actual result and the comparison diagram of estimating the result.
Among the figure:
1-ultrasonic probe 2-transmitter module 3-receiver module 4-pressure measurement choice of location module
5-band filter 6-frequency spectrum analyser 7-subharmonic optimum transmission frequency computing module 8-blood pressure calculates and display module
The specific embodiment
To combine accompanying drawing and embodiment that the present invention is done further detailed description below.
The present invention is a kind of blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent; As shown in Figure 1, comprise that ultrasonic probe 1, transmitter module 2, receiver module 3, pressure measurement choice of location module 4, band filter 5, frequency spectrum analyser 6, subharmonic optimum transmission frequency computing module 7 and blood pressure calculate and display module 8.
Pressure measurement choice of location module 4 is come out the sound scattering signal screening from the pressure measurement position in the sound scattering signal that collects; Described pressure measurement position sets up on their own; Can be set at one or more; When the transmitting probe of ultrasonic probe 1 and receiving transducer were single array element probe, the pressure measurement position confirmed through the degree of depth of the acoustic beam middle distance detecting head surface of transmitting probe, this degree of depth can multiply by receiving transducer time of reception and transmitting probe time difference launch time by the velocity of sound half calculate; When the transmitting probe of ultrasonic probe 1 and receiving transducer are phased array probe, linear array probe or convex array probe; Confirm apart from the degree of depth of detecting head surface on the relative position of pressure measurement position through scanning line and the place scanning line, this degree of depth multiply by receiving transducer time of reception and transmitting probe time difference launch time by the velocity of sound equally half calculate.The sound scattering signal that screens carries out bandpass filtering through band filter 5, and obtaining frequency is the subharmonic composition that transmitting probe produces frequency of ultrasonic 1/2.Filtered subharmonic input spectrum analyzer 6 obtains the frequency spectrum of subharmonic, and when the ultrasound wave that produces when the transmitting probe in the ultrasonic probe 1 was one group of sine pulse signal, frequency spectrum analyser 6 obtained the frequency spectrum of subharmonic through FFT; When the ultrasound wave of the generation of the transmitting probe in the ultrasonic probe 1 was chirp pulse signal, frequency spectrum analyser 6 obtained the frequency spectrum of subharmonic through Time-Frequency Analysis Method such as short time discrete Fourier transform, Gabor expansion, wavelet transformation, WVD (Wigner-Ville Distribution) or Cohen classes.
The frequency spectrum of subharmonic inputs to subharmonic optimum transmission frequency computing module 7; Subharmonic optimum transmission frequency computing module 7 relatively obtains the maximum subfrequency of amplitude, and then the frequency content in the ultrasound wave of this subfrequency pairing this moment of transmitting probe generation is the subharmonic optimum transmission frequency of this moment.
The subharmonic optimum transmission frequency that obtains is inputed to blood pressure to be calculated and display module 8; Subharmonic optimum transmission frequency that blood pressure calculates and display module 8 obtains according to linear regression or linear fit method and the relational expression between the ambient pressure calculate corresponding ambient pressure; Ambient pressure is pressure value, and the drafting pressure-time curve shows.Described relational expression is:
P
amb＝k·f
odf+b
Wherein, P
AmbBe ambient pressure (unit is mmHg), f
OdfBe subharmonic optimum transmission frequency (unit is MHz) that k is a slope, 50≤k≤200, b is an intercept ,-1200≤b≤-500.
Blood pressure non-invasive measurement method based on microcapsular ultrasound contrast agent of the present invention, flow process is as shown in Figure 2, comprises following step:
Step 1: microcapsular ultrasound contrast agent solution is injected blood through vein, and utilize diagnostic ultrasound to keep watch on its whereabouts;
Step 2: when contrast agent arrives the pressure measurement position, gather sound scattering signal from contrast agent;
When contrast agent arrives the pressure measurement position; Signal generator produces pulse signal; Pulse signal encourages the transmitting probe in the ultrasonic probe 1 to produce ultrasound wave behind power amplifier; Ultrasonic exciting microcapsular ultrasound contrast agent vibration produces the sound scattering signal, and the sound scattering signal is obtained by the receiving transducer in the ultrasonic probe 1, the sound scattering signal respectively via low noise power amplifier to signal amplify, anti-aliasing low pass filter filters out the radio-frequency component in the signal; A/D converter is a digital signal with the signal from analog signal transition, finally collects the sound scattering signal from contrast agent.
Described transmitting probe and receiving transducer are with a kind of probe, or are single array element probe or for phased array probe or for linear array probe or be convex array probe.
Step 3: the sound scattering signal to collecting screens, spectrum analysis, obtains the subharmonic optimum transmission frequency;
Sound scattering signal screening from the pressure measurement position in the sound scattering signal that collects is come out, and the sound scattering signal that screens carries out bandpass filtering, and obtaining frequency is the subharmonic composition that transmitting probe produces frequency of ultrasonic 1/2.Filtered subharmonic is carried out spectrum analysis; Obtain the frequency spectrum of subharmonic; The subfrequency that the amplitude that relatively obtains is maximum, then the frequency content in the ultrasound wave that produces of the transmitting probe of this subfrequency institute corresponding this moment is subharmonic optimum transmission frequency at this moment.
Described pressure measurement method for determining position is:
The pressure measurement position sets up on their own, can be set at one or more;
(1) when the transmitting probe of ultrasonic probe 1 and receiving transducer are single array element probe; The pressure measurement position confirms that through the degree of depth of the acoustic beam middle distance detecting head surface of transmitting probe the degree of depth is: the velocity of sound multiply by the half the of receiving transducer time of reception and transmitting probe time difference launch time;
(2) when the transmitting probe of ultrasonic probe 1 and receiving transducer are phased array probe, linear array probe or convex array probe, confirm apart from the degree of depth of detecting head surface on the relative position of pressure measurement position through scanning line and the place scanning line.
The method of said spectrum analysis is:
When the ultrasound wave that 1) produces when the transmitting probe in the ultrasonic probe 1 is one group of sine pulse signal, carry out spectrum analysis, obtain the frequency spectrum of subharmonic through FFT;
When the ultrasound wave that 2) produces when the transmitting probe in the ultrasonic probe 1 is chirp pulse signal; Through Time-Frequency Analysis Method such as short time discrete Fourier transform, Gabor expansion, wavelet transformation, WVD (Wigner-Ville Distribution) or Cohen classes, obtain the frequency spectrum of subharmonic.
Step 4: the relational expression according between subharmonic optimum transmission frequency and the ambient pressure obtains ambient pressure;
Subharmonic optimum transmission frequency substitution subharmonic optimum transmission frequency that step 3 is obtained and the relational expression between the ambient pressure obtain this ambient pressure constantly, and ambient pressure is pressure value, and relational expression is:
P
amb＝k·f
odf+b
Wherein: P
AmbBe ambient pressure (unit is mmHg), f
OdfBe subharmonic optimum transmission frequency (unit is MHz) that k is a slope, 50≤k≤200, b is an intercept ,-1200≤b≤-500.
Draw the time dependent curve of blood pressure then.
Embodiment:
It is the microcapsular ultrasound contrast agent that lipid film wraps up free bubble that present embodiment adopts microbubble contrast agent, is specially the SonoVue that Italian Bracco produces.Its coated fertilizer is a phospholipid, and inner filling gas is SF6, microvesicle particle size range 1～10 μ m, and mean diameter 2.5 μ m, wherein 90% microvesicle particle diameter is less than 8 μ m, and the particle diameter of 60% microvesicle is less than 2 μ m.80% energy is provided by the microvesicle of particle diameter in 3～9 mu m ranges in the echo-signal, the tranmitting frequency below 7MHz, and the influence of the following microvesicle of 2 μ m can be ignored.(1～10MHz), SonoVue has obtained clinical practice preferably in common medical ultrasonic frequency range.
The transmitted pulse signal that signal generator adopts is the sine pulse in a series of 32 cycles, and the acoustic pressure scope is 100KPa～900KPa, and frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz, a sub-sine pulse wherein is as shown in Figure 3, and incident sound pressure is respectively 150KPa, 300KPa and 380KPa, frequency range is 6.0MHz～12.0MHz, frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz, step-length 0.01MHz.Pulse signal encourages the transmitting probe in the ultrasonic probe 1 to produce ultrasound wave behind power amplifier; The vibration of ultrasonic exciting microbubble contrast agent produces the sound scattering signal;
The sound scattering signal is through receiver module 3, and said band filter is three rank Butterworth band filter groups.In the band filter group mid frequency of each subfilter bandwidth be respectively signal generator each sub-sine pulse tranmitting frequency of sine pulse signal 1/2, bandwidth is 0.4MHz.Be one to one between each sub-sine pulse in each subfilter and the transmitted pulse signal in the bank of filters.The ultrasonic exciting microcapsular ultrasound contrast agent vibration that transmitting probe in the ultrasonic probe 1 produces produces the sound scattering signal; The sound scattering signal is through three rank Butterworth band filter group filtering; The frequency spectrum of the sound scattering signal before and after the filtering is respectively like Fig. 4, and is shown in Figure 5.Before the filtering, can find out from Fig. 4 that the sound scattering signal outside second harmonic and the triple-frequency harmonics, also has tangible subharmonic and ultraharmonics composition except first-harmonic, after filtering, from Fig. 5, only can observe the subharmonic composition.
Perhaps, the transmitted pulse signal that signal generator adopts is a linear FM signal, and the acoustic pressure scope is 100KPa～900KPa, and frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz, the passband initial frequency of said band filter is min (f
1/ 2, f
2/ 2) be max (f, by frequency
1/ 2, f
2/ 2); The signal of said frequency spectrum analyser after to band-pass filter carries out the time frequency analysis short time discrete Fourier transform, when incident sound pressure is respectively 150KPa, and 300KPa and 380KPa, frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz.Then the sound scattering signal of microbubble contrast agent is min (f through a passband initial frequency
1/ 2, f
2/ 2) be max (f, by frequency
1/ 2, f
2/ 2) wave filter.
As shown in Figure 6, the static balance radius that microbubble contrast agent produces microvesicle is more little, and resonant frequency is high more.When the static balance radius of microvesicle during less than 2 microns, the resonant frequency of microvesicle increases fast.Result of calculation according to matched curve has, R
eDuring=2 μ m, f
0=2.63MHz; R
eDuring=1 μ m, f
0=3.61MHz; R
eDuring=0.5 μ m, f
0=4.97MHz, wherein R
eBe the static balance radius of microvesicle, f
0Resonant frequency for microvesicle.This result shows, utilizes the bigger microvesicle pressure measurement of particle diameter, for example R
e=2.5 μ m, if the bandwidth of wideband pulse is 1.5MHz～3.5MHz, R almost then
eThe microvesicle of＞1 μ m all can produce resonance, and therefore the microvesicle in this frequency domain resonance has the distribution of sizes of broad, so the formant of broad can occur.If select R
eThe microvesicle of=0.8 μ m carries out pressure measurement; If transmitted bandwidth is 3.5MHz～5.5MHz; The radius of the microvesicle that then can resonate in this frequency range is between 0.4 μ m～1.0 μ m; The microvesicle of this frequency domain internal resonance has narrower distribution of sizes, and uniform particle diameter is so can exist narrower formant.Therefore, utilize the less microvesicle of particle diameter (diameter range of microvesicle is between 0.5 μ m～3 μ m) pressure measurement can effectively solve the problem that formant that the microvesicle distribution of sizes brought is widened, improved the accuracy of detection of formant, thereby improved the pressure measurement precision.
As shown in Figure 7, when environment is pressed in when changing between 0mmHg～200mmHg, the microvesicle that particle diameter is more little, the side-play amount of resonant frequency is big more.According to the result of calculation of matched curve, during 0mmHg, R
eThe microvesicle of=2 μ m, during 200mmHg, the static balance radius is reduced to R
e=1.86 μ m, resonant frequency shift amount Δ f=0.4MHz.During 0mmHg, R
eThe microvesicle of=0.8 μ m, during 200mmHg, the static balance radius is reduced to R
e=0.74 μ m, resonant frequency shift amount Δ f=0.77MHz.Therefore, in identical ambient pressure variations scope, the less microvesicle (diameter range of microvesicle is between 0.5 μ m～3 μ m) of particle diameter has higher resonant frequency shift amount, thereby can obtain higher pressure measurement sensitivity.
Fig. 8 for respectively according to Gorce at document J.M.Gorce, M.Arditi, M.Schneider; " Influence for BubbleSize Distribution on the Echogenicity of Ultrasound Contrast Agents:A Study of SonoVue; " Investigate Radiology 35,661-671 (2000) and Tu are at document Juan Tu, Jingfeng Guan; Yuanyuan Qiu; Thomas J.Matula, " Estimaing the shell parameters of SonoVue microbubbles using lightscattering, " J.Acoust.Soc.Am.126; The peplos parameter of the SonoVue microvesicle of announcing among the 2954-2962 (2007), diameter is the scattering section of the SonoVue microvesicle of 2 μ m under the 0mmHg of calculating.Under the incident sound pressure below the 10KPa, the scattering section that the film parameter that obtains from the acoustic attenuation spectrometry is calculated almost can't see formant by Gorce; Under the incident sound pressure of 150KPa, then there is tangible formant in the scattering section that the film parameter that the radius-time graph that vibrates from microvesicle records is calculated by Tu.Therefore, when utilizing the microvesicle pressure measurement about radius 1 μ m, under higher sound pressure level (＞150KPa) can produce significant formant, thus the accuracy of detection of formant improved, and then reached higher pressure measurement precision.
P.M.Shankar, P.D.Krishna, V.L.Newhouse; " Subharmonic backscattering from ultrasoundcontrast agents, " J.Acoust.Soc.Am.106,2104-2110 (1999); James Chomas, Paul Dayton, Donovan May; With Katherine Ferrara, " Nondestructive Subharmonic Imaging, " IEEE transactionson ultrasonics ferroelectrics and frequency control 49; The incident frequency that doubles resonant frequency is adopted in discovering of 883-892 (2002), can depress more in a low voice, when microvesicle does not destroy; Produce stronger rd harmonic signal, therefore exist the optimum transmission frequency that produces rd harmonic signal.According to linear theory, do by the computing formula of microvesicle resonant frequency
R wherein
0Be the static balance radius of microvesicle, ρ
LBe fluid density, κ is the polytropic index of gas in the bubble, P
0Be ambient pressure, G
sBe the modulus of shearing of microvesicle peplos, d
SeThickness for microvesicle peplos.By this Shi Kede, during 0mmHg, R
eThe resonant frequency of the microvesicle of=0.8 μ m is 4.31MHz, and then the subharmonic optimum transmission frequency is 8.62MHz; During 200mmHg, the static balance radius is reduced to R
e=0.74 μ m, resonant frequency are 5.12MHz, and then the subharmonic optimum transmission frequency is 10.24MHz.Can find out that thus the variable quantity of subharmonic optimum transmission frequency is the twice of corresponding variation of resonant frequency amount, i.e. 2 Δ f=1.62MHz.Therefore, the pressure measurement sensitivity of the pressure measurement remolding sensitivity resonant frequency shift method of subharmonic optimum transmission frequency deflection method is higher.In theory, under identical condition, the former is the latter's a twice.
As shown in Figure 9, respectively at 150KPa, 300KPa, when having obtained 0mmHg under the incident sound pressure of 380KPa, R
eThe subharmonic optimum transmission frequency of the SonoVue microvesicle of=0.8 μ m is with the curve of ambient pressure variations, and the ambient pressure step-length is 5mmHg.Have fabulous linear dependence between subharmonic optimum transmission frequency and the ambient pressure, its linearly dependent coefficient is respectively 0.9967,0.9968,0.9987, and relational expression between the two is respectively P
Amb=136.21f
Odf-1096, P
Amb=117.16.f
Odf-863.48, P
Amb=96.54f
Odf-639.05.Optimum transmission frequency increases along with the increase of ambient pressure, and this is the compressibility owing to microvesicle, and when ambient pressure raise, the static balance radius of microvesicle reduced accordingly, thereby causes due to the resonant frequency rising.In addition, when ambient pressure was constant, optimum transmission frequency reduced along with the increase of incident sound pressure.2 times of linear resonance frequencies that calculate are higher than the subharmonic optimum transmission frequency that calculates under other three acoustic pressures.This explanation subharmonic optimum transmission frequency depends on incident sound pressure.
Shown in figure 10, when ambient pressure when 0mmHg increases to 200mmHg, when incident sound pressure changes in the scope of 100KPa～900KPa, be the position of 380KPa at incident sound pressure, exist the maximum (2.07MHz) of subharmonic optimum transmission frequency side-play amount.On the acoustic pressure section of 100KPa～280KPa, subharmonic optimum transmission frequency side-play amount almost remains unchanged; On the acoustic pressure section of 280KPa～380KPa, subharmonic optimum transmission frequency side-play amount increases along with the increase of acoustic pressure; On the acoustic pressure section of 380KPa～740KPa, subharmonic optimum transmission frequency side-play amount reduces along with the increase of acoustic pressure; On the acoustic pressure section greater than 740KPa, subharmonic optimum transmission frequency side-play amount almost no longer changes.Therefore, the size through preferred incident sound pressure can make subharmonic optimum transmission frequency side-play amount reach maximum, thereby improves pressure measurement sensitivity.
Figure 11 is for when incident sound pressure is 380KPa, based on the estimation result of the present invention to the left ventricle blood pressure.The result shows the deviation of estimation blood pressure and actual blood pressure in 5mmHg, and has obtained very consistent result for three cardiac cycles.This has shown that blood pressure noinvasive estimation result of the present invention has higher precision, and higher repeatability and reliability.
Claims (7)
1. based on the blood pressure non-invasive measurement device of microcapsular ultrasound contrast agent; It is characterized in that, comprise that ultrasonic probe, transmitter module, receiver module, pressure measurement choice of location module, band filter, frequency spectrum analyser, subharmonic optimum transmission frequency computing module and blood pressure calculate and display module;
Ultrasonic probe comprises transmitting probe and receiving transducer;
Transmitter module comprises signal generator and power amplifier, and signal generator produces pulse signal, and pulse signal encourages the transmitting probe in the ultrasonic probe to produce ultrasound wave behind power amplifier;
Receiver module comprises low noise power amplifier, anti-aliasing low pass filter and A/D converter; The ultrasonic exciting microcapsular ultrasound contrast agent vibration that transmitting probe in the ultrasonic probe produces produces the sound scattering signal; The sound scattering signal is obtained by the receiving transducer in the ultrasonic probe; And respectively via low noise power amplifier to signal amplify, anti-aliasing low pass filter filters out the radio-frequency component in the signal; A/D converter is a digital signal with the signal from analog signal transition, finally collects the sound scattering signal from contrast agent;
Pressure measurement choice of location module is come out the sound scattering signal screening from the pressure measurement position in the sound scattering signal that collects; The sound scattering signal that screens carries out bandpass filtering through band filter, and obtaining frequency is the subharmonic that transmitting probe produces frequency of ultrasonic 1/2; Filtered subharmonic input spectrum analyzer obtains the frequency spectrum of subharmonic, and the frequency spectrum of subharmonic inputs to subharmonic optimum transmission frequency computing module;
Subharmonic optimum transmission frequency computing module relatively obtains the maximum subfrequency of amplitude; Then the frequency content in the ultrasound wave of subfrequency pairing this moment of the transmitting probe generation of amplitude maximum is the subharmonic optimum transmission frequency of this moment, and the subharmonic optimum transmission frequency inputs to blood pressure and calculates and display module;
Blood pressure calculates and display module calculates corresponding ambient pressure according to the relational expression between subharmonic optimum transmission frequency and the ambient pressure, and ambient pressure is pressure value; Described relational expression is:
P
amb＝k·f
odf+b
Wherein, P
AmbBe ambient pressure, unit is mmHg, f
OdfBe the subharmonic optimum transmission frequency, unit is MHz, and k is a slope, 50≤k≤200, and b is an intercept ,-1200≤b≤-500.
2. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1; It is characterized in that; Said microcapsular ultrasound contrast agent is the microcapsular ultrasound contrast agent that lipid film wraps up free bubble, and the diameter range that is used to measure the microvesicle of blood pressure in the said microcapsular ultrasound contrast agent is 0.5 μ m～3 μ m.
3. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1; It is characterized in that; Transmitting probe and receiving transducer all adopt with a kind of probe, or are single array element probe or for phased array probe or for linear array probe or be convex array probe.
4. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1; It is characterized in that; Described pressure measurement position sets up on their own; Be one or more, when the transmitting probe of ultrasonic probe and receiving transducer were single array element probe, the pressure measurement position was confirmed through the degree of depth of the acoustic beam middle distance detecting head surface of transmitting probe; When the transmitting probe of ultrasonic probe and receiving transducer are phased array probe, linear array probe or convex array probe, confirm apart from the degree of depth of detecting head surface on the relative position of pressure measurement position through scanning line and the place scanning line; The described degree of depth is that the velocity of sound multiply by the half the of receiving transducer time of reception and transmitting probe time difference launch time.
5. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1 is characterized in that the pulse signal of described signal generator is one group of sine pulse signal, and the acoustic pressure scope is 100KPa～900KPa, and frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz;
Said band filter is the band filter group, and the mid frequency of each subfilter bandwidth is respectively 1/2 of each sub-sine pulse tranmitting frequency of sine pulse signal that signal generator produces in the band filter group; Corresponding one by one between each sub-sine pulse in the sine pulse signal that each subfilter and signal generator produce in the said band filter group;
Said frequency spectrum analyser carries out FFT respectively to the signal behind band filter neutron filter filtering.
6. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1 is characterized in that, the pulse signal that described signal generator produces is a linear FM signal, and the acoustic pressure scope is 100KPa～900KPa, and frequency is from f
1=6.0MHz increases to f
2=12.0MHz is perhaps from f
1=12.0MHz is decreased to f
2=6.0MHz;
The passband initial frequency of said band filter is min (f
1/ 2, f
2/ 2) be max (f, by frequency
1/ 2, f
2/ 2);
The signal of said frequency spectrum analyser after to band-pass filter carries out time frequency analysis.
7. the blood pressure non-invasive measurement device based on microcapsular ultrasound contrast agent according to claim 1 is characterized in that, said blood pressure calculates and display module is also drawn pressure-time curve.
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| DK2702578T3 (en) * | 2011-04-25 | 2016-11-14 | Endotronix Inc | Wireless sensor reader. |
| CN102488532A (en) * | 2011-12-12 | 2012-06-13 | 南京大学 | Peripheral static pressure measurement method based on micro-vesicle super-harmonic response |
| CN103267800B (en) * | 2013-05-03 | 2015-08-05 | 西安交通大学 | The ultrasonic fast imaging of cavitation microvesicle high s/n ratio and dynamic dimension distribution estimation method |
| CN103445808B (en) * | 2013-09-12 | 2016-06-15 | 深圳先进技术研究院 | Large artery trunks noinvasive continuous blood pressure measurer |
| CN107561157B (en) * | 2016-06-30 | 2023-08-04 | 重庆医科大学 | Water quality detector and method thereof |
| TWI731339B (en) * | 2018-06-11 | 2021-06-21 | 當代漢雲企業有限公司 | Device and method for pulse diagnosis measurement |
| CN112641467B (en) * | 2020-12-21 | 2022-03-01 | 西安交通大学 | Non-invasive transcranial ultrasonic blood pressure measuring device and method based on SonoVue |
| CN113331868B (en) * | 2021-04-29 | 2023-06-27 | 西安交通大学 | Method for measuring intracranial vascular blood flow reserve parameters by utilizing ultrasonic microbubbles |
| WO2022241650A1 (en) * | 2021-05-18 | 2022-11-24 | 中国科学院深圳先进技术研究院 | Contrast-enhanced ultrasound technology-based signal processing system and method, and terminal device |
| CN113343784A (en) * | 2021-05-18 | 2021-09-03 | 中国科学院深圳先进技术研究院 | Signal processing system and method based on ultrasonic contrast imaging technology and terminal equipment |
| WO2023092329A1 (en) * | 2021-11-24 | 2023-06-01 | 中国科学院深圳先进技术研究院 | Blood pressure measurement system and method based on single array-element ultrasonic pulse echo |
| CN114287967B (en) * | 2021-11-24 | 2023-12-29 | 中国科学院深圳先进技术研究院 | Blood pressure measurement system and method based on single-array element ultrasonic pulse echo |
| CN116026919A (en) * | 2022-11-23 | 2023-04-28 | 中国科学院深圳先进技术研究院 | Method, device, equipment and storage medium for measuring acoustic characteristics of contrast agent microbubbles |
| CN116098652B (en) * | 2023-04-12 | 2023-07-11 | 中国医学科学院北京协和医院 | Ultrasonic contrast blood pressure measuring device and method based on subharmonic resonance frequency |
| CN117064442B (en) * | 2023-10-10 | 2024-03-29 | 中国医学科学院北京协和医院 | Arterial pressure waveform measuring method and device based on ultrasonic radiography |
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