JP3398080B2 - Vascular lesion diagnostic system and diagnostic program storage medium - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention uses ultrasonic waves to
The present invention relates to a vascular lesion diagnostic system and a diagnostic program storage medium for diagnosing lesions of blood vessels such as arteries in the body by non-invasive measurement. (EN) A means for measuring a velocity waveform to accurately detect a local lesion such as atheroma (atheroma) in a blood vessel.

[0002] Myocardial infarction, angina pectoris, cerebral infarction and the like have hitherto been thought to be due to the progression of stenotic lesions of the vascular lumen called atheroma, but are currently used worldwide as hyperlipidemic drugs. It has become clear from the clinical examination of 1. whether the contents of atheroma are easy to break or difficult to break. In fact, the administration of the above-mentioned drugs has a dramatic effect on improving the survival rate and preventing myocardial infarction, although the degree of stenosis of blood vessels is hardly changed. This is believed to be because these agents systematically stabilize the contents of atheroma. For these reasons, a method for investigating the fragility of the contents of atheroma was sought, but it was not possible with conventional methods such as X-ray CT, MRI, and angiography. The present invention makes it possible to diagnose the fragility of the contents of atheroma by remotely measuring the elastic modulus of an arbitrary local blood vessel wall using ultrasonic waves.

[0003]

2. Description of the Related Art One of the reports that has led to the rapid development of medical treatment of arteriosclerosis in recent years is that the stenosis of coronary arteries due to atheroma (atheroma) can be improved by strongly lowering serum lipids. 1990 shown in [Reference 1]
It would be a yearly clinical report. According to subsequent large-scale clinical trials, treatment of strong hypercholesterolemia for about a few years results in reduction of coronary artery stenosis and reduction in incidence of cardiac death. This has had a great impact on the medical field, and the recent increase in the dosage of hyperlipidemia has become one of the causes of the rapid increase in medical expenditure in Japan.

However, changes in arteriosclerotic lesions obtained by this therapeutic method of lowering lipids are subtle on the order of several tens of microns, and it is clinically difficult to accurately grasp changes in vascular lesions. there were.

On the other hand, it is known that this treatment significantly reduces the occurrence of coronary artery disease events such as myocardial infarction and sudden death. This seems to be in conflict with the fact that the improvement in coronary stenosis itself is subtle. However, the recent interpretation is that the occurrence of myocardial infarction or the like is caused by some cause that the lipid-rich atheroma is cracked and the thrombus formation in that part is temporarily caused, rather than the direct coronary artery occlusion caused by atheroma. It is believed that this is due to the narrowing / occlusion of the blood vessel lumen. In other words, the point of lipid-lowering therapy is to stabilize and prevent this atheroma from breaking.

[0006] Therefore, the therapeutic goals for arteriosclerosis at this stage are summarized as follows: 1) selecting the best treatment method while confirming the progress and regression of atheroma that causes stenosis of blood vessels, and 2) rupturing this atheroma. It can be said that it is stabilized so that it does not occur, and 3) with respect to vasospasm that is common in Japanese people, correction of serum lipids is expected to improve abnormal vascular tone (tonus).

As described above, the treatment method based on the recent knowledge of arteriosclerosis has a means for non-invasively repeating arteriosclerosis and atherosclerotic lesions in the local region of the blood vessel and accurately measuring them in micron order. Is essential, and only then can it be clinically effective.
However, as a conventional technique for measuring arteriosclerosis,
1) Angiography examination, MR angiography, which expresses stenosis of blood vessel lumen by image of blood flow, and 2) Method of calculating degree of arteriosclerosis from pulse wave velocity have been reported. As for its characteristics, there has not yet been reported any one that can be measured noninvasively with sufficient accuracy.

On the other hand, there are the following conventional techniques for ultrasonic diagnosis.

Zero- Cross Point Detection Method for RF Signals A method for measuring the vibration of the heart wall and internal tissues from the body surface using ultrasonic waves has been reported. The displacement of the target is measured from the moving time of the zero cross point of the RF (Radio frequency) signal of the reflected wave from the target of the ultrasonic wave. If the clock frequency of the circuit is expressed as f _CLK , a quantization error occurs in the speed estimation depending on its value. Since the displacement waveform is a low-pass filtered version of the velocity waveform, even if the displacement waveform could be measured conventionally and the error was not noticeable,
When converted into a velocity waveform and considered, the measurement error is large. Further, since the displacement waveform contains only components of several to several tens of Hz, it is meaningless to perform frequency spectrum analysis like the velocity waveform.

Tissue Doppler method [Reference 2] can be cited for this technique. This document is an automatic ultrasonic dynamic measurement device that receives a reflected wave of an ultrasonic pulse emitted toward a subject and displays an ultrasonic image based on this reflected wave, and shows the phase of the reflected wave at an arbitrary time point. Phase detecting means for detecting, sample point designating means for defining a sample point at an arbitrary position of the reflected wave, and sample moving means for detecting a phase difference at the sample point of the reflected wave and moving the sample point by a distance corresponding to this phase difference And an ultrasonic dynamic state automatic measuring device provided with a dynamic state measuring and displaying means for automatically measuring the dynamic state of the subject by tracking the movement of the sample point and displaying it on the display.

In this apparatus, the phase difference at the sample point of the reflected wave is detected and the sample point is moved by a distance corresponding to this phase difference, but the interval between the sample points is several hundred mμm.
And the in-vivo wavelength of the ultrasonic wave of 3.5 MHz is about 50.
Since it is 0 μm, it does not make much sense to make the sample points smaller. In any case, since the distance between the sample points is several hundred μm, the roughness of the displacement measurement in this case is in this order, which is very rough.

The displacement waveform obtained by this displacement measurement is obtained by low-pass filtering the velocity waveform. Even if the displacement waveform could be measured conventionally, the measurement error is large when converted into the velocity waveform. Further, since the displacement waveform contains only components of several to several tens of Hz, it is meaningless to perform frequency spectrum analysis like the velocity waveform.

Further, in this apparatus, when measuring the velocity waveform, the reflected waves obtained by transmitting several to ten and several (N) ultrasonic pulses are put together, and the average Doppler shift between them is calculated. Looking for. Therefore, the time resolution of the obtained velocity waveform is poor, and only the velocity waveform sampled at the sampling frequency 1 / N of the pulse transmission frequency PRF can be obtained.

Tracker by detecting phase shift of pulse transmission
In the conventional Doppler measurement of blood flow velocity, the distance from the ultrasonic probe to the target reflector is constant, but in the measurement of heart wall vibration, the wall position moves more than 10 mm with the pulsation. , The distance from the ultrasonic probe changes significantly with time. This affected the measurement of heart wall vibration and was a factor of error.

Therefore, the inventors of the present invention, in the prior patent application shown in [Reference 3], send out ultrasonic pulses at regular intervals, detect the phase shift of the pulse reflected from the object, An invention has now been presented for highly accurately tracking the position of an object that fluctuates due to pulsation.

As a result, it is possible to measure minute vibrations in a large amplitude displacement motion associated with a pulsation with an amplitude of 10 mm or more in a frequency band up to several hundreds Hz for approximately 10 consecutive beats with sufficient reproducibility and high accuracy. became. [Reference 1] Brown G, Albers JJ, Fisher LD, Schae
fer SM, Lin JT, Kaplan G, Zhao XQ, Bisson BD, Fitzp
atrick VF, Dodge HT., ”Regression of coronary art
erydisease as a result of intensive lipid-lowering
therapy in men with highlevels of apolipoprotei
n, "BN Engl. J Med., Vol, 323, pp. 1289-1298,19
90. [Reference 2] Japanese Patent Application Laid-Open No. 62-266040 (Applicant: Toshiba Corporation) [Reference 3] Japanese Patent Application Laid-Open No. 10-5226 (Applicant:
Japan Science and Technology Agency)

[0017]

A microvibration occurs in blood vessels due to changes in blood pressure. This minute vibration propagates from the inside to the outside of the blood vessel wall. Therefore, by detecting and analyzing the vibration on the inner surface and the outer surface of the blood vessel wall or each layer constituting the blood vessel wall, it is possible to obtain the temporal change in the thickness of the blood vessel wall and the elastic modulus. In other words, if the easiness / difficulty of local lesions of blood vessels such as atheroma (atheroma) is expressed as instability / stability, it is unstable if the elastic modulus of the blood vessel wall is small, and stable if it is large. I can diagnose. The elastic modulus of such a blood vessel wall is obtained by analyzing the time change of the thickness of the blood vessel wall. That is, since the motion waveform of the microvibration generated inside the blood vessel wall is transmitted to the outside of the blood vessel wall with the amplitude and phase according to the medium characteristics including the elastic modulus of the blood vessel wall, for any local blood vessel wall, the inside If the amplitude and phase of each motion waveform are known by measuring the motion waveforms of minute vibrations on the outside and outside, the elastic modulus of the blood vessel wall at that site can be obtained.

By the way, the blood vessel moves with a large amplitude according to the pulsation of the heart, and the motion of minute vibration caused by the blood flow is superimposed on the large amplitude motion. Moreover, the amplitude of minute vibration is considered to be several tens of microns or less.
Therefore, it is practically impossible to directly measure the motion of minute vibrations by the conventional B-mode or M-mode ultrasonic diagnostic apparatus. Therefore, in the patent application of Reference 3 mentioned above, the present inventors detect the reflected wave signal of the ultrasonic signal radiated toward the blood vessel by the ultrasonic pulse Doppler method and analyze the amplitude and phase of the detected signal. hand,
First, a tracking process is performed to determine the sequential positions of blood vessels that are moving with a large amplitude, and then the movement of minute vibrations is accurately detected based on the determined sequential positions of the large amplitude movements. Made possible

However, when the sequential position of the large amplitude motion of the blood vessel in each pulsation is determined by this tracking process, a phenomenon occurs in which the position fluctuates between successive pulsations due to noise and accumulated error, and it is long. It was not possible to perform stable measurement continuously over time.

The object of the present invention is to continuously measure the physical characteristics of blood vessels such as coronary arteries in the body such as minute changes and fragility associated with the local pulsation of the wall thickness using ultrasonic waves. The object is to provide a vascular lesion diagnostic system that can be accurately measured.

[0021]

According to the present invention, a position generated between consecutive beats is normalized by performing a normalization such that the initial position of each beat in the large amplitude motion of a blood vessel is returned to the original position for each beat. The vascular lesion diagnosis system and the diagnostic program storage medium of the present invention based on the above are intended to be removed as follows. [1] The ultrasonic lesion diagnostic system of the present invention outputs an ultrasonic beam toward a blood vessel in the body, detects an ultrasonic signal reflected from the blood vessel wall, and outputs the detected ultrasonic wave. And a data analysis processing unit that analyzes the characteristics of the blood vessel based on the detected signal.The data analysis processing unit uses the amplitude and phase of the detection signal to determine each instantaneous position of the inner surface and the outer surface of the blood vessel wall. Large amplitude displacement motion analysis means for determining and accurately tracking each large amplitude displacement motion of the inner surface and outer surface of the blood vessel wall based on the heart beat, and the inner surface and outer surface of the blood vessel wall obtained by the large amplitude displacement motion analysis means Based on the sequential position of each large amplitude displacement motion in
Micro-vibration analysis means for obtaining the motion velocity of micro-vibration superposed on large-amplitude displacement motion on the inner and outer surfaces of the blood vessel wall, and micro-vibration motion on the inner and outer surfaces of the blood vessel wall obtained by the micro-vibration analysis means. A wall thickness analyzing means for determining a temporal change of the blood vessel wall thickness based on the difference in velocity, and the large amplitude displacement motion analyzing means is arranged to displace one amplitude pulse of the large amplitude displacement motion for each of the inner surface and the outer surface of the blood vessel wall. The feature is that the analysis is performed under the constraint condition that the sum of is zero. [2] The vascular lesion diagnosis system of the present invention further comprises wall elastic modulus analyzing means for obtaining the elastic modulus of the blood vessel wall based on the temporal change of the blood vessel wall thickness obtained by the wall thickness analyzing means in the above [1]. It is characterized by that. [3] Further, in the vascular lesion diagnosis system of the present invention, in the above-mentioned [2], the wall thickness analyzing unit is elastic for each of a plurality of layers constituting the blood vessel wall due to a difference in motion velocity of microvibrations of the inner surface and the outer surface thereof. The feature is that the rate is obtained. [4] The vascular lesion diagnosis system according to the present invention further provides a tomographic image according to the above [1] to [3], in which the radiation position of the ultrasonic beam is continuously changed to create a tomographic image of a change in blood vessel wall thickness. It is characterized in that it comprises a creating means. [5] The diagnostic program storage medium of the present invention radiates ultrasonic waves toward a blood vessel in the body and detects the ultrasonic signal reflected from the blood vessel wall, and uses the amplitude and phase of the detected signal to detect the blood vessel wall. The inner and outer surfaces of the vessel are determined instantaneously, and the large-amplitude displacement movements of the inner and outer surfaces of the vessel wall based on the heart beat are precisely tracked. A large-amplitude displacement motion analysis function for correcting the sum of displacements of one beat of the motion to be zero, and a sequence of large-amplitude displacement motions on the inner and outer surfaces of the blood vessel wall obtained by the large-amplitude displacement motion analysis function. Based on the position of, the microvibration analysis function for obtaining the motion velocity of the microvibration superimposed on the large amplitude displacement motion on the inner surface and the outer surface of the blood vessel wall, and the inner surface of the blood vessel wall and the inner surface of the blood vessel wall obtained by the microvibration analysis function. Based on the motion velocity of microvibration on the outer surface, the difference is calculated over time, and the wall thickness analysis function that obtains the time change of the blood vessel wall thickness and the time change of the blood vessel wall thickness obtained by the above wall thickness analysis function are used. A program including a wall elastic modulus analysis function for obtaining the elastic modulus of the blood vessel wall is stored in a storage medium.

FIG. 1 shows the basic configuration of the present invention.

In FIG. 1, 1 is a human body.

Reference numeral 2 is a body surface.

Reference numeral 3 is a blood vessel such as an artery to be measured,
It has a thickness h (t) of the blood vessel wall and a diameter d (t) of the lumen, and vibrates at a motion velocity v (t).

3a is the anterior wall of the blood vessel.

3b is the posterior wall of the blood vessel.

Reference numeral 3c is a lesion such as atheroma occurring in the blood vessel 3.

Reference numeral 4 denotes an ultrasonic probe capable of scanning a certain range by changing the emitting direction of the ultrasonic beam.

An ultrasonic wave measuring unit 5 includes an ultrasonic wave signal generator 6, a quadrature detector 7, a low pass filter 8 and a high speed A / D converter 9. The ultrasonic signal generator 6 generates a transmission signal Vin (t) with an angular frequency ω ₀ at a constant time interval ΔT to drive the ultrasonic probe 4, and the reception signal Vout (Vout () of the reflected wave detected by the ultrasonic probe 4 is generated. t) with quadrature detector 7 at ω ₀
Quadrature detection is performed with the original signal of and the detection signal Vm (t) is obtained by passing through the low pass filter LPF8. Detection signal V
m (t) is further converted into a digital signal format by the high speed A / D converter 9 and output.

Reference numeral 10 is a data analysis processing unit such as a computer, which analyzes the detection signal Vm (t) in digital signal format output from the ultrasonic measurement unit 5 to perform large amplitude displacement, small vibration of the blood vessel 3, The temporal change of the blood vessel wall thickness, the elastic modulus, etc. are obtained, and the processing result is output as a tomographic image or the like.

Reference numeral 11 is a large amplitude displacement motion analysis means,
The amplitude and phase of the detection signal Vm (t) output from the ultrasonic measurement unit 5 are analyzed, and the large amplitude displacement of the inner surface and outer surface of the blood vessel wall or the surface of each layer constituting the blood vessel wall is accompanied by the heartbeat. The locus of movement is determined, that is, tracking is performed. At this time, the displacement motion of the microvibration of each layer of the blood vessel wall stabilizes the image, so that the accumulation of displacement within one beat is set to zero so that it returns to the original position for each beat of the heart. Parsed.

Reference numeral 12 is a microvibration analyzing means, which analyzes the motion velocity of microvibration superposed on the large amplitude displacement motion of the inner surface and outer surface of the blood vessel wall or the surface of each layer based on the fluctuation of the phase.

Reference numeral 13 denotes a wall thickness analyzing means, which obtains a temporal change in thickness of each blood vessel wall or each layer by taking a difference in motion velocity of microvibration between the inner surface and outer surface of the blood vessel wall or the surface of each layer.

Reference numeral 14 is a wall elastic modulus analyzing means, which calculates the elastic modulus of each blood vessel wall or each layer based on the temporal change of the thickness of each blood vessel wall or each layer.

Reference numeral 15 is a tomographic image forming means, which scans a predetermined space by restricting the radiation direction of the ultrasonic beam by the ultrasonic probe 4 to obtain a tomographic image or a three-dimensional image of the thickness and elastic modulus of the blood vessel wall or each layer. An image is created and displayed on 16 display devices.

FIG. 2 exemplifies a spatial scanning method using an ultrasonic probe. 2A shows that the ultrasonic beam is controlled so as to move in parallel to perform scanning.
In FIG. 2B, the ultrasonic beam is controlled so as to swing in a fan shape. By appropriately utilizing these scanning methods, it is possible to scan an arbitrary space including blood vessels.

On the screen of the display device 16 of FIG. 1, an example of a tomographic image obtained by scanning the blood vessel with the ultrasonic beam in this manner is displayed. The hardness (elastic modulus) of the tissue at each site of the blood vessel, which is the result of analysis by the present invention, can be easily identified by the color corresponding to the level.

Next, the basic principle of the blood vessel displacement motion analysis processing according to the present invention will be described in detail. (1) Tracking Method by Phase Shift Detection of Reflected Wave In the present invention, the pulse phase shift of the received ultrasonic pulse with respect to the transmitted ultrasonic pulse is detected to obtain the displacement amount of the object. FIG. 3 shows an outline of the measurement of the minute displacement change waveform of the blood vessel wall according to the present invention.

In FIG. 3, the ultrasonic probe 4 is driven by an ultrasonic pulse having a period of ΔT to emit an ultrasonic beam from the body surface 2 toward the body. The emitted ultrasonic beam is reflected by the blood vessel 3 vibrating at the velocity v (t), and the reflected wave is received by the ultrasonic probe 4. The received ultrasonic wave signal of the reflected wave is amplified in the ultrasonic wave measuring unit 5 and then quadrature detected, and the detected signal is A / D converted at the sampling period Ts, and then a detected waveform y indicating tomographic data is obtained.
It is input to the data analysis processing unit 10 as (x; t).

In the data analysis processing unit 10, the quadrature detection waveform y (x; t) of the reflected wave from the object at time t,
Phase shift Δθ between l orthogonal detection waveform y (x; t + ΔT) of the reflected wave with respect to the pulse transmission wave after ΔT seconds
(T + ΔT / 2) is detected, and the distance that the object has moved in ΔT seconds is calculated. Here, (t + ΔT / 2) indicates an intermediate time between the two times t and t + ΔT, which means that the average value of this section is represented by the value at this intermediate time point.

When the moving distance is the wavelength λ, the phase shifts by ± 2π, so the phase shift is Δθ (t + ΔT).
The moving distance Δx (t + ΔT / 2) corresponding to / 2) can be calculated by the following equation.

[0043]

[Equation 1]

The formula in the second row is based on the fact that the wavelength λ of the ultrasonic wave in the medium is represented by a value obtained by dividing the sound velocity c by the ultrasonic frequency f ₀ . (2) High-precision detection of phase shift The magnitude of displacement within one beat of the heart wall is several mm to ten and several m.
m, even in the arterial wall, several mm at a large part
is there. However, for example, the thickness change in one beat of the carotid artery wall is only several tens of μm in a healthy person, and the thickness change is smaller in the elderly / arteriosclerosis patient.

For example, ultrasonic frequency f ₀ = 7.5 MH
If z and sound velocity c = 1500 m / s, wavelength λ = 200
μm. Therefore, the moving distance Δx (t + ΔT /
If 2) is 100 μm, the phase difference between the two pulses will be 180 degrees, but in the carotid artery, the maximum thickness change in one beat is several μm, so that one pulse The sum of the phase shifts is 18 degrees or less. If one beat is regarded as one second, thousands of pulses are transmitted and received during that time, and the phase shift per one time is only one thousandth of 18 degrees. Therefore, the phase shift needs to be detected with high accuracy, and two waveforms at time t and time t + ΔT do not change in amplitude and are in phase in order to strengthen against noise when obtaining the phase shift. Under the constraint that only the reflected wave position changes, the least-squares matching of the following equation (2), which will be described later, is performed, and the phase shift Δθ (t + ΔT /
2) is detected. (3) Small displacement of blood vessel wall and measurement of velocity waveform As shown in FIG. 3, a quadrature detection waveform y (x; t) of a reflected wave from an object at time t and a pulse transmission after ΔT seconds are reflected. Regarding the quadrature detection waveform y (x; t + ΔT) of the wave, consider the root mean square value (matching error) of the difference between the two waveforms y (x; t) and y (x; t + ΔT). When the model of the detected waveform (complex waveform) of the reflected wave is considered as in the example of FIG. 4, FIG. 5 shows that the value of the matching error relating to them changes with respect to the deviation Δx (t + ΔT / 2) = δ _x between the waveforms. It shows how to do. In the usual definition of the matching error, both the phase and the amplitude are allowed to change at the time of matching, and therefore, as shown in FIG. 5A, for the true value δ _x = −5 or more, , The minimum value is taken everywhere. Therefore,
During matching, only phase changes are allowed. As a result, as shown in FIG. 5B, only the true value δ _x = −5 takes a unique minimum value. It is also robust against noise in that it reduces the freedom of change between the two waveforms. Hereinafter, FIGS. 4 and 5 will be described in detail.

In FIG. 4, (a) shows the signal y at time t.
(X; t), and (b) shows the next signal y (x; t + ΔT) at time (t + ΔT). The □ mark indicates a real number component, and the X mark indicates an imaginary number component.

Assuming that the object moves by δ _x after ΔT seconds with respect to the detected waveform y (x; t), the amplitude of the detected waveform y (x; t) and y (x + δ _x ; t + ΔT) If the phase does not change and only the phase changes by Δθ (δ _x ), the matching error α (Δθ (δ _x ); δ _x ) when the two waveforms are matched is Given.

[0048]

[Equation 2]

Here, xεR means that a sum is calculated with respect to x in the range of the region R. This matching error α (Δθ
It is necessary to find δ _x that minimizes (δ _x ); δ _x ), but when the waveform y (x; t + ΔT) is moved by δ _x , the power included in the section R of the waveform changes. May end up. Therefore, in order to normalize the power, the right side of Equation 1 (equation (1)) is divided by the average power of the two waveforms of the denominator.

Next, FIG. 5 shows how the matching error value changes with respect to δ _x . (A) in the figure shows a case where both the phase and the amplitude are allowed to change at the time of matching, and the true value δ _x
= For values above -5, the minimum value is taken everywhere. Further, (b) in the figure shows a case where only the change of the phase is allowed at the time of matching, and the true minimum value δ _x = −5 takes the only minimum value.

To obtain Δθ (δ _x ) that minimizes the equation (1) for a certain δ _x , α (Δθ (δ _x );
The [delta] _x), (by placing a zero partial derivatives the formula with _{δ x), α (Δθ (} δ x) Δθ; δ x) best minimizes a [Delta] [theta] ([delta] _x) is, exp {jΔθ ( δ _x )} = exp (j∠C (δ _x )) (2a). Here, C (δ _x ) is given by the following equation.

[0052]

[Equation 3]

∠C (δ _x ) is a complex number C (δ _x )
Represents the phase of. * Represents a complex conjugate.

[0054] The further above operation, each time determined by changing the [delta] _x within a certain range, and the minimum the alignment error [delta] _x in which, to calculate the [Delta] [theta] ([delta] _x) at that time. Using Δθ (δ _x ) obtained as a result, the average velocity v (t + ΔT / 2) in this section ΔT can be calculated by the following equation.

[0055]

[Equation 4]

Where ΔT is the pulse transmission interval, ω _o = 2π
f _o represents the angular frequency of the transmitted ultrasonic wave, and c represents the sound propagation velocity.

Further, by multiplying this velocity value v (t + ΔT / 2) by ΔT, the displacement amount Δx (t + ΔT / 2) of the object at the time ΔT is obtained.

[0058]

[Equation 5]

This displacement amount

[0060]

[Equation 6]

Is the position x (t) of the object at the previous time t.
In addition, the position of the object at the next time can be virtually predicted.

[0062]

[Equation 7]

This is the tracking locus x (t).
When the velocity is 0.001 m / s and ΔT = 160 μs, the displacement width is 0.16 μm, and the spatial resolution is several tens of times more than that of the conventional zero-cross point detection method of about 15 μm. Can be improved. (4) Accurate calculation of phase difference In this way, least-squares matching is performed for the two waveforms under the constraint that “amplitude does not change but only phase and reflected wave position change”, and Phase shift Δθ (t + ΔT
A process for detecting / 2) with high accuracy will be described below.

As shown in FIGS. 3 and 4, the detected waveform y
For (x; t), the target is Δx (t +
Assume that it has moved by ΔT / 2). y (x; t)
In the detected waveform of the received waveform for the i-th transmitted wave, it is a component of a section of width ± Δ centered on the position of the immediately preceding object, and is simply expressed as a complex vector y ′ _i . Similarly, (i +
1) The detection waveform y (x; of the reception waveform for the 1st transmission wave)
In t + ΔT), a component of a section of width ± Δ centered on the position of the immediately preceding object is represented as a complex vector y ′ _{i + 1} .

[0065] For detection waveform y _'i and y' i _{+ 1,} only the phase without amplitude variation, if those changes by [Delta] [theta] _i, alignment error α when taken alignment between two waveforms
_i is given by the following equation.

[0066]

[Equation 8]

Here, the denominator of the first and second items on the left side
Represents the length (norm) of each vector, and each term is
Included in the waveform as a vector of unit length (unit vector)
The power is normalized. Equation 8 (Equation (7a)) is the minimum
Δθ_iIs α_iIs Δθ _iThe expression that is partially differentiated by
It can be decided by setting. Therefore, the i-th
Phase shift Δθ between the pulse and the (i + 1) th pulse_iFor
And the displacement Δx between them _iIs calculated by the equation 1 (equation (1))
hand,

[0068]

[Equation 9]

Is given by (5) Introducing a constraint to make the accumulated displacement at one beat be zero If the phase shift calculated by two pulse transmissions and receptions is small as described above, it is only one thousandth of 18 degrees. . Therefore, an error is likely to be included in the displacement change waveform and the thickness change waveform obtained by taking the sum of these values several thousand times in one beat, which causes the waveform to be blurred and difficult to see.

For example, as shown in FIG. 6, in the measurement from the R wave of the electrocardiogram to the R wave of the next beat, if the positional relationship between the ultrasonic probe and the measurement site does not change at all, displacement within one beat or The thickness change needs to return to the original value. The displacement of the wall such as the carotid artery is about several mm in one beat, but between the displacement waveform x ₁ (t) on the intima side and the displacement waveform x ₂ (t) on the adventitia side of the wall, There is almost no difference, and the difference between them, that is, the thickness change Δh (t), is only about 10 and several microns at maximum in one beat.

In the carotid artery or the like, a thickness change Δh of several μm
Since it becomes necessary to measure (t), when the above-mentioned accumulated error is mixed, it must be returned to the original position with an accuracy of the order of submicron due to the sum of displacement of one beat and accumulation of thickness change. Therefore, in order to reduce noise, it is necessary to measure such that the accumulated displacement change waveform / thickness change at one beat is always zero. Such a measuring method has not been necessary for the conventional device that does not perform tracking.

For this reason, the present invention introduces a constraint that the cumulative displacement at one beat becomes zero when the displacement motion is analyzed. This means that if the number of pulse transmissions in one beat is F, then i
It is represented by the fact that the displacement x _F up to the F th given by the sum over one beat with respect to the th displacement Δx _i becomes zero.

[0073]

[Equation 10]

Therefore, with this constraint, the equation (2)
Is used, the sum α of the matching errors α _i of the phase shift determination for each of the F pulses is defined by the following equation.

[0075]

[Equation 11]

Here, γ'is a Lagrange undetermined multiplier, and the above constraint is shown in the second item on the right side.

[0077]

[Equation 12]

The value is changed to 2γ again, and

[0079]

[Equation 13]

Is a unit vector

[0081]

[Equation 14]

[0082]

[Equation 15]

Is a unit vector

[0084]

[Equation 16]

By putting the above, it is simply expressed as follows.

[0086]

[Equation 17]

Here, ^* represents the complex conjugate, and ^T represents the transpose of the vector. By minimizing α in this equation with respect to F {Δθ _i } and γ, the optimum phase shift over the entire beat can be determined at one time, and at the same time the displacement waveform is obtained.

In equation 17 (equation (7e))

[0089]

[Equation 18]

Let be a complex constant A _i ,

[0091]

[Formula 19]

Is A ^* _i . However,

[0093]

[Equation 20]

Since each is a unit vector, | A _i
| = 1. Using these, α is

[0095]

[Equation 21]

It is simply expressed as Formula 21 (Formula (7f))
In order to find F {Δθ _i } that minimize
The expressions partially differentiated by Δθ _i and γ are set to zero.

[0097]

[Equation 22]

On both sides of equation 22 (equation (8))

[0099]

[Equation 23]

Multiply by

[0101]

[Equation 24]

By setting X _i as

[0103]

[Equation 25]

A quadratic equation for X _i is obtained. This solution X _i is

[0105]

[Equation 26]

It is obtained as follows. Here, A _i is a complex constant of norm 1 (| A _i | ² = 1),

[0107]

[Equation 27]

Putting it aside,

[0109]

[Equation 28]

Here, although two solutions are obtained, each of them is substituted into the equation 21 (equation (7f)).

[0111]

[Equation 29]

Therefore,

[0113]

[Equation 30]

Is obtained. Using these relationships, α in Equation 21 (equation (7f)) is

[0115]

[Equation 31]

It is represented as follows. Therefore, Equation 28 (equation (1
It can be seen that among the two solutions of 2)), only the upper solution can minimize the matching error.

[0117]

[Equation 32]

Furthermore, the constraint of the equation (9) of the equation 22 is used. If you calculate the exponents of the imaginary numbers on both sides of this equation,

[0119]

[Expression 33]

By substituting the solution of Equation 32 (Equation (16)) into the left side of this equation,

[0121]

[Equation 34]

It becomes: Here, the complex number of the second term on the left side

[0123]

[Equation 35]

Is expressed as Ω, and exp (jΩ)
If you write

[0125]

[Equation 36]

Therefore,

[0127]

[Equation 37]

Holds,

[0129]

[Equation 38]

Is obtained. Where ∠A _i is a complex number A
Indicates the phase angle of _i . From this equation, Equation 16 (Equation (7f))
It is possible to uniquely determine Ω or Lagrange's undetermined multiplier γ in the constrained least squares matching of. If this Ω is used, the following equation 32 (equation (16))

[0131]

[Formula 39]

Is

[0133]

[Formula 40]

It can be determined by. Therefore, equation 9 (equation (7
The displacement Δx _{i in} b)) is

[0135]

[Formula 41]

Is given by Equation (22) of this number 41
Is the instantaneous displacement in one beat {Δx _i }, (i = 1, 2, ...
.., F) means that constrained least-squares matching can be achieved by determining the phase shift such that the sum of them is zero, that is, the bias thereof is zero.

When ΔT is the pulse transmission interval, the average velocity of the object during that period is

[0138]

[Equation 42]

Can be calculated by the following equation (23).

[0140]

[Equation 43]

The displacement between the i-th pulse and the i + 1-th pulse is

[0142]

[Equation 44]

The position at the time of the i-th pulse transmission can be determined by

[0144]

[Equation 45]

Then, this small displacement

[0146]

[Equation 46]

The virtual position of the object at the time of transmitting the (i + 1) th pulse is added by adding

[0148]

[Equation 47]

Can be predicted.

[0150]

[Equation 48]

This is the tracking locus x (t). (6) Processing for calculating time change of inner diameter and thickness of blood vessel As shown in FIG. 6, the thickness change Δh (t) at the thickness h (t) of the blood vessel wall is the displacement x _ad (t) on the adventitia side. ) And the displacement x _in (t) on the side of the intima (intima) are represented by x _in (t) −x _ad (t). Therefore, the instantaneous displacement change waveforms Δx _ad (t) and Δx _in (t) on the adventitia side and the endocardium side of the blood vessel wall, respectively.
Is calculated and the difference between them is calculated to obtain the thickness change Δh (t) of the blood vessel wall by the following equation.

Δh (t) = x _in (t) −x _ad (t) (25) Similarly, the change Δd (t) in the blood vessel lumen diameter d (t) is defined by the inner wall surface of the anterior wall. X _a (t) = x _in (t) and the displacement x _p (t) of the lumen surface of the posterior wall of the blood vessel. Therefore, the instantaneous displacement change waveforms Δx _a (t) = Δx _in (t) and Δx _{p of the} inner wall surface of the blood vessel and the inner wall surface of the blood vessel
The change Δd (t) in the lumen diameter of the blood vessel can be calculated by the following equation by measuring (t) and calculating the difference therebetween.

Δd (t) = x _p (t) −x _a (t) (26) The thickness change Δh (t) in Eq. (25) is set to 0 during systole when the value at the end of diastole is set to 0. It becomes negative as waves arrive and the vessel lumen bulges and the wall thickness decreases. In addition, the thickness change Δh (t) has an amplitude of about ten and several μm and changes with time. Therefore, it is not possible to measure the thickness change Δh (t) using a B-mode image or an M-mode image in an ultrasonic diagnostic apparatus. It is impossible. (7) Process of calculating elastic modulus E of blood vessel wall Next, the process of calculating the elastic modulus E of the blood vessel wall will be described with reference to FIG. 7.

First, the wall thickness h _d at the time of diastolic blood pressure at the end-diastolic period is measured from the B-mode image or M-mode image of the ultrasonic diagnostic apparatus, and the thickness change Δh (t of the blood vessel wall obtained by the equation (3) is calculated. The incremental strain Δε _r (t) in the radial direction can be calculated by the following equation (27) by the value of the ratio of) to h _d .

[0155]

[Equation 49]

In general, the elastic modulus E (t) is obtained by dividing the strain amount by ε.
Let (t) be the stress and p (t) be the following equation (28).

[0157]

[Equation 50]

The stress p (t) is a force per unit area and corresponds to the intravascular pressure, and the upper arm cuff pressure is used. This is the instantaneous elastic modulus E (t) at time t, but since there is no non-invasive method for measuring the internal pressure, this method uses the method at the time when the blood pressure p _{d at the} end of diastole becomes the minimum and the systole. The average elastic modulus E is calculated by the following equation (29) during the time point at which the blood pressure p _s becomes maximum.

[0159]

[Equation 51]

Here, Δε _max is the maximum value of the strain amount. The elastic modulus E increases as the blood vessel wall becomes harder, and thus serves as an index for evaluating the elastic property of the wall.

Further, since the spatial resolution in the long axis direction of the blood vessel obtained by the main measurement is the beam width in the focal region of the ultrasonic beam, that is, about 2 to 3 mm, it is several mm to ten and several m.
It can be said that it has sufficient spatial resolution to diagnose an early lesion of arteriosclerosis called m. Therefore, the elastic modulus E obtained by this measurement can be expected as an index for early diagnosis of arteriosclerosis. (8) Specific Example of Measurement by the Diagnosis System of the Present Invention FIG. 8 exemplifies the result of measurement of carotid arteries of healthy subjects in their thirties to sixties using the diagnosis system of the present invention.

The graph of FIG. 8A is obtained by
The relationship between the elastic modulus E of (Equation (29)) and age is shown. From this graph, it can be seen that the elastic modulus increases as the age increases, and the blood vessel wall becomes hard. This is in good agreement with clinical results. In addition, the minimum value of the elastic modulus calculated here is about 0.5 MPa, which is a literature value (0.31 ± 0.22 MPa) regarding the elastic modulus of normal tissue of the human carotid artery.
(See [Reference 4]), the result is reasonable.

The graph of FIG. 8 (b) shows the relationship between the stability parameter β and the age. The stiffness parameter β is one of those that have been conventionally proposed as an index for evaluating elastic properties of a blood vessel wall ([Reference 5]).
reference). The stability parameter β is expressed by the following equation.

[0164]

[Equation 52]

Here, p _s , p _d , d _s , and d _d are the systolic blood pressure, the diastolic blood pressure, the maximum value of the artery diameter, and the minimum value of the artery diameter, respectively. This stiffness parameter β is calculated based on the change in blood vessel diameter and the change in internal pressure at that time.
That is, it indicates the extensibility of the blood vessel wall, which is how much the blood vessel wall extends in the circumferential direction when the intravascular pressure changes.
In the graph of FIG. 8B, the change in blood vessel diameter in a normal person in their thirties to sixties is calculated from the above-mentioned formula (4),
The result of calculating the stiffness parameter β from the change in internal pressure at that time is shown. As a result, the stability parameter β also increases with age. Therefore, the stiffness parameter β also shows a tendency similar to the data of the elastic modulus E of FIG. 8A, and this result is considered to be appropriate. However, since this stiffness parameter β is calculated based on the change in blood vessel diameter, it means that the average characteristics of the entire circumference of the blood vessel wall are evaluated, and the vascular lumen is significantly deformed due to atheroma or the like. If this happens, the error will increase. On the other hand, with the proposed elastic modulus E, since the change in the thickness of the arterial wall is directly measured, local evaluation is possible, and it is considered that it can be applied even when the blood vessel wall is deformed.

Further, when calculating the change in the thickness of the arterial wall, the change Δd (t) in the blood vessel diameter was calculated at the same time, and the Poisson's ratio ν was also calculated by the following equation.

[0167]

[Equation 53]

Here, Δd _m , d _d , Δh _m , and h _d are the maximum value of arterial diameter change, the arterial diameter at the end of diastole, the maximum value of arterial wall thickness change, and the arterial wall thickness at the end of diastole, respectively. is there. The graph in (c) of FIG. 8 shows the results of calculating the Poisson's ratio ν for the same normal subjects in their thirties to sixties.
As is clear from the graph, the Poisson's ratio tended to decrease with age. Since the Poisson's ratio becomes smaller as the wall becomes harder, this tendency is considered to be appropriate. The Poisson's ratio of the carotid artery is smaller than the Poisson's ratio of the abdominal aorta, but this tendency has been confirmed in the rat and is considered to be caused by the difference in the composition of the arterial wall. However, since this Poisson's ratio also includes the term of the change in blood vessel diameter, local evaluation may be difficult when evaluating the deformed arterial wall.

[Reference 4] RTLee, AJ Grodzinsky,
EHFrank, et al: ”Structure-dependent dynamicme
chanical benavior of fibrous caps from human ather
oacleresic plaque?, "Circulation vol.83, pp.1764-177
0, 1991. [Reference 5] F. Hansen, P. Mengell, B. Smesson, et a.
l: ”Diameter and compliance in the human common ca
rotid artery-variation with age and sex, "Ultrasou
nd inMedicine and Biology, vol.21, 1995; 1-9. In Fig. 9, the local elastic modulus of the carotid artery was measured in a group of subjects (risk factor group) having some risk factors for arteriosclerosis tendency. The results are shown. FIG. 9A shows the distribution of the carotid artery elastic modulus E with respect to the value of the risk rate of arteriosclerosis of each subject in the risk factor group of 46 persons, and there is a significant correlation between the two. I understand. FIG. 9B shows the distribution of the carotid artery elastic modulus E by age for 46 risk factor groups in which no remarkable thickening of the blood vessel wall is observed and 10 healthy groups for control. From the examination, it can be seen that there is a significant difference between the risk factor group and the healthy group. As described above, even if no abnormality is found in the blood vessel wall thickness by the conventional diagnostic method, the system of the present invention can detect the abnormality.

Further, according to the system of the present invention, as shown in Table 1, it is easy to measure the local elastic modulus of each layer of the blood vessel wall, so that the presence of an atheroma (atheroma) in the blood vessel wall. And its position, hardness and size can be detected, enabling accurate diagnosis.

Table 1: Elastic modulus at each depth from the luminal surface of atheroma Depth from the lumen (mm) Elastic modulus (MPa) 0.00-0.75 3.47 ← Inside 0.75-1.50 0.51 1.50-2.25 0.61 2.25- 3.00 0.32 3.00−3.75 0.37 3.75−4.50 1.39 ← Outside (9) Example configuration of vascular lesion diagnosis system FIG. 10 shows an example of a suitable hardware configuration that can realize the vascular lesion diagnosis system according to the present invention. In FIG. 10, 21 is an ultrasonic diagnostic system, 22 is a frequency converter, 23 is an RF signal generator, 24 is a probe selector, 2
5 is a frame identification signal generator, 26 is B / M-mode
Selector, 27 is a sample position generator, 28 is a trackball, 29 is an amplifier, 30 is a quadrature detector, and 31 is B-m.
ode image display device, 32 is an ultrasonic probe for arterial wall, 33 is an ultrasonic probe for heart wall, 34 is a sampling signal generator, 35 is an oscilloscope, 36 is a real-time system, 37 and 38 are signal processors DS.
P, 39 is a workstation EWS, 40 is an A / D converter / digital I / O, 41 is a D / A converter,
M-mode image display device, 43 is a keyboard, 4
Reference numeral 4 is a hard disk device HDD.

The system shown in the figure is roughly divided into: an ultrasonic diagnostic system 21 for scanning a blood vessel by ultrasonic waves to obtain a tomographic signal containing information on microvibration of the blood vessel; It is composed of two real-time systems 36 which detect characteristics such as a local change in elastic modulus of the wall and display them as an image. Ultrasonic diagnostic system 21
Is basically the same as the mechanism of a conventional ultrasonic diagnostic system. The real-time system 36 is the main part of the present invention, and the tomographic signal acquired by the ultrasonic diagnostic system 21 is analyzed in real time to determine the hardness of the tissue in the blood vessel wall from the difference in local microvibration displacement of the blood vessel. The distribution is obtained, and the color image showing the distribution is displayed in B / M-mode, ECG, P
It is displayed at the same time as an image such as CG to facilitate diagnosis of a lesion.

In the ultrasonic diagnostic system 21, the frequency converter 22 generates a frame trigger and a 10 MHz clock from a 40 MHz main clock.
The RF signal generator 23 is driven by the frame trigger,
A burst-shaped ultrasonic signal is generated. The generated ultrasonic signal is output to the ultrasonic probe 32 or 33 selected by the probe selector 24. The ultrasonic probe 32 or 33 emits an ultrasonic beam toward the body of the subject and receives the reflected wave. The received ultrasonic signal is amplified by the amplifier 29 and then quadrature detected by the quadrature detector 30 to generate an in-phase signal and a quadrature signal. The in-phase signal and the quadrature signal are output to the real-time system 36 in an analog signal format. Further, the frame identification signal generator 25 generates a frame identification signal according to the mode selected by the B / M-mode selector 26, and outputs the frame identification signal to the real-time system 36.

From the sample position generator 27, a sample position signal which defines the sample take-out timing position set according to the operation of the trackball 28 is generated and supplied to the sampling signal generator 34 together with the clock of 10 MHz. Sampling signal generator 34
Generates a sampling clock of 1 MHz at an intermediate timing position defined by the sample position signal within the period T ₀ , and the A / D of the real-time system 36 is
Supply to the converter digital I / O 40.

In the real-time system 36, A
/ D converter digital I / O 40 and DSP 37 perform input signal processing, and DSP 38 and D / A converter 41
Performs output signal processing. DSP37,38 and EWS39
Are connected by VME-bus, and EWS39
Thus, the data analysis processing of the present invention for obtaining the large amplitude displacement motion of the blood vessel, the minute vibration, the time change of the blood vessel wall thickness, the elastic modulus, and the like is performed. The program for executing these data analysis processes is stored in the HDD 44 or the main memory, but is installed by a removable storage medium such as a CD-ROM or MO or downloaded from a file device on the network. be able to.

The B-mode image and the M-mode image are displayed on the display devices 31 and 42, respectively, and the blood vessel wall hardness distribution image and the like are displayed as color images using the oscilloscope 35.

[0177]

According to the present invention, a fast vibration component up to several hundreds Hz can be measured with high precision at an amplitude of vascular motion of several microns, so that the thickness change and strain of the blood vessel wall can be measured on the order of several microns. To enable. As a result, it has become possible to quantitatively measure the elastic properties of the arterial wall and atheroma lesions with high accuracy, which was previously impossible, and to display the spatial distribution of the images in real time. Regression,
Accurate diagnosis and treatment can be performed by clinically repeatedly evaluating the rupture property and stability of plaque in a short time.

[Brief description of drawings]

FIG. 1 is a basic configuration diagram of the present invention.

FIG. 2 is an explanatory diagram of a spatial scanning method using an ultrasonic probe.

FIG. 3 is an explanatory diagram of a minute displacement change waveform measurement process of a blood vessel wall.

FIG. 4 is an explanatory diagram of a (complex waveform) model of a detection waveform of a reflected wave.

FIG. 5 is an explanatory diagram of a change in matching error when only a change in phase is allowed.

FIG. 6 is an explanatory diagram of the necessity of a constraint that the cumulative displacement in one beat becomes zero.

FIG. 7 is an explanatory diagram of a method of calculating the elastic modulus of a blood vessel wall.

FIG. 8 is a graph showing measurement results of carotid arteries of healthy persons in their thirties to sixties.

FIG. 9 is a graph showing distributions of a healthy group and a risk factor group regarding a local elastic modulus of a carotid artery.

FIG. 10 is a configuration diagram of an embodiment of a vascular lesion diagnosis system.

[Explanation of symbols]

1: Human body 2: Body surface 3: Blood vessel 3a: front wall of blood vessel 3b: posterior wall of blood vessel 3c: Lesion 4: Ultrasonic probe 5: Ultrasonic measuring unit 6: Ultrasonic signal generator 7: Quadrature detector 8: Low pass filter 9: High-speed A / D converter 10: Data analysis processing unit 11: Large amplitude displacement motion analysis means 12: Micro vibration analysis means 13: Wall thickness analysis means 14: Wall elastic modulus analysis means 15: tomographic image creating means

Continuation of the front page (56) Reference JP-A-55-143133 (JP, A) JP-A-62-266040 (JP, A) JP-A-9-313485 (JP, A) JP-A-9-313486 (JP , A) JP-A-10-5226 (JP, A) JP-A-11-128277 (JP, A) Hiroshi Kanai, Michie Sato, Yoshiro Koiwa, Noriyoshirau sew punishment sect. relations, IEEE TRANSACTIONS ON ULTRASO NICS, FERROELECTRICS, AND FREQUENCY CONTROL, September 1996, vol. 43, no. 5, pp791-810 Hiroshi Kanai, Mid eyuki Hasegawa, Nor iyoshi Chubachi, Yo shiro Koiwa, Motona o Tanaka, Noninvasi ve Evaluation of L ocal Myocardial Th ickening and Its C olor-Coded Imagin g, IEEE TRANSACTION S ON ULTRASONICS, F ERROELECTRICS , AND FREQUENCY CONTROL, July 1997, vol. 44, no. 4, p752-768 (58) Fields investigated (Int.Cl. ⁷ , DB name) A61B 8/00

Claims (5)

(57) [Claims] 1. An ultrasonic measurement unit that emits an ultrasonic beam toward a blood vessel in a body, detects an ultrasonic signal reflected from a blood vessel wall, and outputs the detected wave, and a blood vessel of the blood vessel based on the output detected signal. The data analysis processing unit for analyzing characteristics determines each instantaneous position of the inner surface and the outer surface of the blood vessel wall by using the amplitude and phase of the detection signal, and based on the heart beat. Large-amplitude displacement motion analysis means for precisely tracking the large-amplitude displacement motions of the inner surface and the outer surface of the blood vessel wall, and the large-amplitude displacement motions of the inner surface and the outer surface of the blood vessel wall obtained by the large-amplitude displacement motion analysis means. The microvibration analysis means for obtaining the motion velocity of the microvibration superposed on the large-amplitude displacement motion on the inner surface and the outer surface of the blood vessel wall based on the sequential positions, and the microvibration analysis means. Wall thickness analysis means for determining a temporal change of the blood vessel wall thickness based on a difference in motion velocity of minute vibrations on the inner surface and the outer surface of the blood vessel wall, wherein the large amplitude displacement motion analysis means is provided for each of the inner surface and the outer surface of the blood vessel wall. A system for diagnosing vascular lesions, characterized in that a large amplitude displacement motion is analyzed under the constraint condition that the sum of displacements at one beat becomes zero. 2. The vascular lesion according to claim 1, further comprising wall elastic modulus analyzing means for obtaining an elastic modulus of the blood vessel wall based on a temporal change in the blood vessel wall thickness obtained by the wall thickness analyzing means. Diagnostic system. 3. The wall thickness analyzing means according to claim 2, wherein each of a plurality of layers forming a blood vessel wall obtains an elastic modulus by a difference in motion velocity of microvibrations on the inner surface and the outer surface thereof. Vascular lesion diagnosis system. 4. The tomographic image creating device according to claim 1, further comprising a tomographic image creating unit that creates a tomographic image of a change in blood vessel wall thickness by continuously changing the radiation position of the ultrasonic beam. Vascular lesion diagnosis system. 5. An instantaneous wave of an inner surface and an outer surface of a blood vessel wall by using an amplitude and a phase of a detection signal obtained by radiating an ultrasonic wave toward a blood vessel in a body and detecting an ultrasonic wave signal reflected from the blood vessel wall. Of the large-amplitude displacement motions of the inner and outer surfaces of the blood vessel wall based on the heart beats, and the displacement of each large-amplitude motion of the inner and outer surfaces of the blood vessel wall is accurately tracked. A large-amplitude displacement motion analysis function that corrects the sum to be zero, and based on the sequential positions of each large-amplitude displacement motion on the inner surface and the outer surface of the blood vessel wall obtained by the large-amplitude displacement motion analysis function, A microvibration analysis function for obtaining the motion velocity of a microvibration superimposed on a large-amplitude displacement motion on the inner and outer surfaces of the wall, and a motion of the microvibration on the inner and outer surfaces of the blood vessel wall obtained by the microvibration analysis function. Based on the velocity, the difference is taken and integrated over time, and the wall thickness analysis function for obtaining the time change of the blood vessel wall thickness, and the elasticity of the blood vessel wall based on the time change of the blood vessel wall thickness obtained by the above wall thickness analysis function A diagnostic program storage medium storing a program including a wall elastic modulus analysis function for obtaining a modulus.