JPH0339265B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION FIELD OF APPLICATION OF THE INVENTION The present invention relates to devices that use ultra-high frequency sonic energy, particularly ultrasound microscopes.

[Prior art]

Ultrasound, which has recently been applied in the medical world as an effective wave to observe the internal structure of the human body, has the property of being able to penetrate optically opaque objects, which is not possible with light or electron beams. The higher the frequency, the more minute objects can be drawn. Furthermore, since the information extracted by ultrasound reflects the mechanical properties of the object, such as its elasticity, density, and viscosity, it is possible to see internal structures that cannot be obtained with light or electron beams.

An ultrasound microscope that takes advantage of the above-mentioned characteristics of ultrasound is being considered by using ultrahigh-frequency sound waves with a sound frequency of IGHz, which corresponds to a sound wavelength of about 1 μm in water (as described by RA Lemon and CF Kweets). A
IEEE entitled Scanning Acoustic Microscope
(References published in Cat.No.73 CH14829SUPP 423-426).

The principle of this ultrasonic microscope is that the sample surface is mechanically divided by an ultrasonic beam narrowed down to about 1 μm.
While performing dimensional scanning, the scattering, reflection, and transmission attenuation caused by the sample are collected and converted into electrical signals, and this electrical signal is transmitted onto a cathode ray tube in synchronization with the mechanical scanning described above. A microscopic image is obtained by displaying the image in two dimensions. The conventional basic configuration will be explained using FIG.

A transducer that generates and detects ultrasonic waves is mainly composed of a piezoelectric thin film 20 and an acoustic lens 40. That is, the acoustic lens 40 (for example, a cylindrical crystal such as sapphire or quartz glass) has one end surface 41 that is an optically polished plane, and the other end surface that has a hemispherical hole with a minute radius of curvature (for example, 0.1 to 1 mm). 42
is formed. If an output electrical signal from the RF pulse oscillator 100 is applied between the upper and lower electrodes of the layered structure consisting of the upper electrode 10, the voltage thin film 20, and the lower electrode 11 provided on the end surface 41 by vapor deposition or the like, the piezoelectricity of the piezoelectric thin film described above is applied. As a result, plane wave RF pulsed ultrasound waves 80 are emitted within the acoustic lens 40 .
This plane ultrasonic wave is focused and focused onto a sample 60 placed at a predetermined focal plane by a positive acoustic spherical lens formed at the interface between the hemispherical hole 42 and a medium 50 (generally pure water is used).

The ultrasonic waves reflected by the sample 60 are collected by the acoustic lens 40, converted into plane ultrasonic waves, propagated within the acoustic lens 40, and finally converted into RF pulse electricity due to the inverse piezoelectric effect of the piezoelectric thin film 20. converted into a signal. This RF pulse electric signal is amplified and detected by the RF receiver 110, and then the video signal (1-10M
Hz) and is used as a luminance signal (Z input) of the cathode ray tube 130.

In this configuration, while the sample 60 affixed on the material stage 70 is subjected to two-dimensional mechanical vibration by the two-dimensional mechanical scanning system 120 in the x-y plane, the video signal is transmitted in synchronization with this scanning. If displayed on the cathode ray tube 130, a microscopic image can be obtained.

By the way, when observing a biological sample such as a biological tissue section using such an apparatus, there is a problem in that a sufficient reflected signal cannot be obtained because the acoustic impedance of the biological sample is very similar to the acoustic impedance of the medium, water. This situation can be solved by selecting a material (for example, a metal material such as glass or stainless steel) whose acoustic impedance is sufficiently larger than the acoustic impedance of the biological sample as the material of the sample stage 70 that supports the material 60 in FIG. This is improved by obtaining a transmitted signal even with this configuration.

First, with reference to FIG. 2, we will explain why if the sample is lined with a stage made of such material, a transmitted signal can be obtained despite the reflective structure. In FIG. 2, the upper interface of a biological sample 50 with a certain thickness d is designated as l ₁ and the lower interface is designated as l _2. The lower interface l ₂ is an acoustic reflector with sufficiently large acoustic impedance relative to the biological sample. The sample stage 70 is lined. The ultrasonic beam 170 incident from above the sample is first partially reflected at the interface _l1 , and most of it is transmitted into the sample 60. As mentioned above, the reflected wave at the interface l ₁ is extremely weak in biological samples, and the sound wave propagated through the sample 60 reaches the interface l ₂ while being attenuated by the attenuation rate unique to the _sample . It propagates upward in the sample through the sample, radiates into the water 180 via the interface _l1 , and is received and detected by the probe 40 as a reflected sound wave from the interface _l2 . Here, if a backing material of the above material is used, the reflection at the interface _l2 is almost a complete reflection, and the detected reflection signal with this configuration is a weak reflected wave from the interface _l1 and a weak reflected wave from the interface _l2 . It can be said that the magnitude of the reflected signal is determined by the reflected sound wave from the interface _l2 . It is thought that this reflected signal is subjected to the same disturbance as when it passes through the sample twice.

That is, the structure shown in FIG. 2 has a probe system 21 facing the confocal plane by a mirror surface 200 as shown in FIG.
This is because the sample 230, which is equivalently twice as thick as 0.0.220, is placed between the sample 230 and the sample 230 in the water 240, which is equivalent to a so-called transmission type structure.

In fact, let the thickness of the biological sample be d, the attenuation rate be αs,
Letting the acoustic impedances of the biological sample, water, and lining material be Z _S , Z _W , and Z _B , respectively, the effective reflectance γ is given by the following equation (1): γ = (Z _W − Z _S ) ( Z _S + Z _B ) + (Z _W + Z _S ) (Z _S − Z _B ) e ^-j
〓/(Z _W + Z _S ) (Z _S + Z _B ) + (Z _W − Z _S ) (Z _S − Z _B ) e ^-j
〓(1) Here, θ=2(k−j〓 _s ) k is the wave number Furthermore, under the mirror-backed condition where Z _B ≫ Z _S and Z _B ≫ Z _W , γ=Z _S −Z _W ／Z _S +Z _W +4Z _S Z _W / (Z _S +Z _W ) ² e ^-2 〓 ^Sd /1
+Z _S −Z _W /Z _S +Z _W e ^-2 〓 ^Sd (2). The first term on the right side is the reflected signal from interface _l1 , and the second term is the reflected signal from interface _l2 .

In particular, such as biological samples, Z _S Z _W , Z _S = Z _W +△
Under the condition that Z, △Z/Z _W ≪1, equation (2) becomes γ=△Z/2Z _W +e ^-2 〓 ^sd (3).

Therefore, the reflected signal from a biological sample lined with a material that can be considered a perfect reflector is equivalent to the transmitted signal from a biological sample conventionally lined with a soft material such as Mylar.

Now, with such a configuration, discrimination between the reflected sound waves from the interface _l1 and the reflected sound waves from the interface _l2 is based on time discrimination. However, as the thickness of the sample becomes thinner or the width of the transmitted and received ultrasonic pulses becomes wider, these two signals overlap, making it extremely difficult to distinguish between the two signals. As can be seen from equation (3), the sound waves reflected from the interface _l1 reflect the two-dimensional distribution of the acoustic impedance of the sample, and the sound waves reflected from the interface _l2 reflect the two-dimensional distribution of the attenuation rate of the sample. If it is possible to distinguish between the two, it will be possible to independently determine the two parameters that determine the mechanical properties of biological samples, acoustic impedance and attenuation rate, and it will also be possible to add measurement functions to ultrasonic waves. Become.

[Purpose of the invention]

The present invention has been made in view of the above points, and provides means for separating and extracting the two reflected waves in the above configuration.

[Summary of the invention]

The present invention focuses on the frequency dependence of the two reflected waves, and solves the above problem by using a difference value between detected reflected signals at a plurality of different frequencies.

In other words, the reflected wave from interface _l1 is determined only by the acoustic impedance of the sample, and moreover, the reflected wave from interface l1 is determined only by the acoustic impedance of the sample, and
The velocity dispersion is also small in the frequency range used by the ultrasonic microscope, so it can be considered constant regardless of the frequency. On the other hand, the reflected wave from the interface _l2 is determined by the attenuation rate αs of the sample, and as is well known, exhibits significant frequency dependence. The amount γ of reflected sound waves at a certain frequency f is expressed by the following equation (4).

γ=a+b(f) (4) Here, a is a constant independent of frequency f and corresponds to the first term of equation (3), and b(f) is a function of frequency f and corresponds to the second term of equation (3). This corresponds to Therefore, if a microscopic image of a biological sample is captured and stored at two frequencies f ₁ and f ₂ and a screen of the difference is displayed, this image corresponds to the frequency difference of the two-dimensional distribution of the attenuation rate of the sample. , the image reflecting the two-dimensional distribution of acoustic impedance will be erased.

Such a difference is calculated for a large number of frequencies (f ₀ < f ₁
<f ₂ <...<f _o ), you may take the difference between adjacent ones, or you may take the difference always with f ₀ as the reference.

The present inventors performed the above-mentioned differential operation on four types of frequencies: 300, 400, 500, and 600 MHz, and obtained good results.

[Embodiments of the invention]

For the purpose of explanation, embodiments will be described below with reference to the drawings in the case of two different frequencies.

FIGS. 4 and 5 are diagrams showing the configuration of an embodiment of the present invention. FIG. 6 is a waveform diagram for explaining these operations. First, the first RF continuous oscillator 50
The analog switch 510 converts the RF continuous wave signal (e.g. 500MHz) generated at
100 ns) into an RF pulse signal (Fig. 6a), and sends it to the transducer 53 via the directional coupler 520.
Apply to 0. The reflected echo signal from the sample 540 is amplified by the RF amplifier 560 via the directional coupler 520 again (FIG. 6b). Here, A
indicates a launch signal, B indicates an echo from the interface between the lens and the water medium, and C indicates a reflected echo from the sample. The output of the RF amplifier is processed by a diode detector 565 to convert the video signal (e.g.
10MHz) (Fig. 6c), and is sampled by a sampling circuit 570 such as a sample-and-hold circuit, and this sampled output is converted into a digital value by an AD converter 580, and then first sent to a first latch circuit 585. Multiply. Next, using the RF continuous wave signal generated by the second RF continuous wave oscillator 505 (frequency 400MHz),
A sampling circuit 570 detects the reflected signal in the same manner as above.
After sampling and AD conversion, the second latch circuit 59
Accumulate to 5. The outputs of the latch circuits 585 and 595 are subtracted by a subtracter 600, and the difference output is
It is converted into an analog signal by the DA converter 610 and used as the Z input signal of the cathode ray tube.
FIG. 5 shows an embodiment of the synchronization control circuit 550 in _FIG . Pulse width TD
is converted into a pulse train (FIG. 6d), and this is used as the control 1 signal to the analog switch 51.
It is used to turn 0 ON and OFF. Further, the output of the pulse oscillator 551 is delayed by a variable delay device 553, and then converted into a pulse train with a pulse width ts by a one shot 554 (control 2 signal in FIG. 6e),
It is used as a tight gate signal for the sampling circuit mentioned above.

In such a structure, if the detection of reflected ultrasound waves at 500 MHz and the reflected ultrasound waves at 600 MHz are repeated alternately, and the difference value of the detection output is used as pixel information, the reflected ultrasound signal, which is the object of the present invention, can be obtained. An output corresponding to an attenuation factor that depends on the frequency difference is obtained.

〔Effect of the invention〕

As described above, according to the present invention, it is possible to provide means for eliminating the frequency-independent contribution of acoustic impedance from the ultrasonic reflected signal and determining the difference value of only the attenuation factor-dependent component.

[Brief explanation of the drawing]

FIG. 1 is a diagram showing the schematic configuration of a conventional ultrasound microscope, FIGS. 2 and 3 are diagrams explaining the principle of the present invention, and FIGS. 4 and 5 are diagrams showing the configuration of an embodiment of the present invention. The block diagram shown in FIG. 6 is an explanatory diagram of its operating waveforms.

Claims (1)

[Claims] 1 An ultrasonic device comprising a transducer for transmitting and receiving a focused ultrasonic beam, a sample whose lower surface is in contact with a reflector, and means for mechanically scanning the sample two-dimensionally within the focal region of the beam. In a sonic microscope, ultrasonic beams of different frequencies are emitted to the same point on a sample, and the received reflected echoes are compared to obtain a difference value. An ultrasonic microscope characterized by comprising means for displaying brightness at a position on the screen.