A METHOD AND DEVICE FOR NON-INVASIVE ACOUSTIC TESTING OF ELASTICITY OF SOFT BIOLOGICAL TISSUES

Abstract: The invention provides the noninvasive testing of the elasticity of soft biological tissues for the diagnosing of physiological and pathological state in human and animals, by exciting the tangential oscillatory deformations on the surface of tissue in the frequency range of 0.5 - 30 kHz and by determining the velocity of the excited surface wave propagating along the vector of the initial displacement. The device which provides the application of this method includes a probe with one transmitting and two receiving piezotransducers equipped with contact tips and mounted to the body of the probe by means of the elongated hafts which serve as acoustic delay lines, and the electronic means that forms pulses to excite the transducer, performs the processing of the received acoustic signals, measures the time-of-flight of acoustic pulses from the transmitter to the receiver, converts it into the velocity of sound and displays the value of velocity. The device also has a facility for standardizing the force by which the probe is pressed to a tissue.

Description: The present invention relates to the testing of elastic properties of soft biological tissues. More particularly, the present invention provides an acoustic device and method for noninvasive measurement of the velocity of surface acoustic waves in tissues thus providing the means for estimating the shear elastic properties of tissues for the purposes of medical diagnosis. The viscoelastic properties of biological tissues are directly related to their structural organisation. It was found that bulk elastic properties of tissues are mainly determined by their molecular composition, while shear elasticity is characteristic of higher levels of structure Physiological processes in an organism may result in structural changes in tissues that can be detected by measuring their shear elastic properties. The methods of testing the viscoelastic properties of tissues are essentially based on invasive measurements on isolated samples. Maxwell, for example, employed the torsional vibrations of a sample cut in the form of cylindrical rod fixed at one of the ends (Maxwell B., ASTM Bull, #215, 76, 1956). Shear modulus was determined by measuring the magnitude of force necessary to provide a given deformation at the other end of the rod. The range of working frequencies was 0.001 to 200kHz. For measuring the bulk elastic properties, i.e. the ultrasonic velocity and bulk compressibility of media a great variety of methods using the bulk acoustic waves in a high-frequency range were developed. For example, according to one of those methods (Nole A.W., Mowry S.C. J. Acoust. Soc. Amer., 20, 432, 1948) the speed of sound was evaluated from the measurement of time-of-flight of an acoustic pulse in the sample being tested which is immersed in a liquid between the ultrasonic transducer and reflector. Among the known methods of noninvasive testing of bulk elastic properties of tissues is the method and device for noninvasive monitoring the instantaneous fluctuations in viscoelasticity-related properties of a living tissue (Benjamin Gavish, European Patent EP 0 135 325 A2, U.S. patent #4580574, T. 1065). The device comprises a pair of substantially parallel spaced-apart piezotransducers, one of them being adjustable with respect to the other to enable insertion and clamping of a segment of living tissue therebetween. One transducer is connected to a high frequency generator and the other is attached through an amplifier and demodulator to a signal analyser. The frequency of the ultrasonic resonant oscillations induced in a tissue and their magnitude are characteristic of the viscoelastic properties of the tissue. The said method of testing the tissues makes it possible to detect certain physiological processes and particularly the chnges in the microcirculation of blood. But since the subject of testing are the bulk elastic properties which may vary in tissues by no more than several per cent the accuracy of such a method would not be very high, as compared to the accuracy of the methods using the shear elasticity which may change in some cases by hundreds per cent, depending on the physiological state of a tissue. The method does not imply any means to control the force by which the transducers are pressed to a tissue sample placed in the gap therebetween. But such a pressure affects the properties of the samples and still increases the error of measurement. Besides, because it is often difficult to provide access to the tested tissue from the opposite sides, this technique is not applicable on the most of the body. It is impossible to evaluate by means of this method one of the important characteristics related to the structural organisation of living tissues -- their anisotropy, i.e. the difference in mechanical properties in various directions. The possibilities of testing the shear elastic properties of biological tissues were investigated in the paper (V.A. Passechnik , A.P.Sarvazyan: On the possibility of examination of the muscle contraction models by measuring the viscoelastic properties of the contracting muscle -- Studia Biophysica, Berlin, Band 13, 1969, Heft 2, s 143-150). In this work the changes in elastic properties of an isolated muscle during contraction were studied. The low frequency acoustic oscillations (450 to 1200 Hz) were excited in a sample by means of a flexural piezotransducer and received at a distance by the like piezotransducer. The tension of muscle was measured in various phases of contraction. The modulus of shear elasticity was evaluated by measuring the amplitude and the phase of received signal. According to the other method of testing the shear elasticity of tissues (R.O.Potts, D.A.Christman, E.M.Buras: The dynamic mechanical properties of human skin in vivo, J. Biomechanics, Vol.16, #6, pp. 365-372, 1983) the shear oscillations in tissue were produced by a "recorder" (a phonograph recording cutterhead) touching the tissue surface with its contact tip (stylus). A phonograph cartrige with a stylus was used as a receiver. Measurements were conducted in the frequency range of 200-1000 Hz. The recorder was excited by the white noise sound generator; the characteristic frequencies were estimated by means of a spectrum analyser. The measured parameters were the velocity of propagation of shear waves and their attenuation. The authors of the cited research came to the conclusion that in the low frequency range investigated by said method, the mechanical waves excited in tissue are of shear character and are localized only in the superficial layer of tissue, i.e. in the skin, and because of that only in this range it is possible to provide the selective measurement of skin elasticity, while at higher frequencies the measurement is more difficult because of the small depth of penetration of surface waves. This conclusion is disputable. Since the velocity of shear waves in soft tissues may be 5 to 50 m/s, the wavelength in the frequency range of about 1kHz should be about 5 to 50 mm. Since the penetration depth of surface waves cannot be much less than a wavelength, the subcutaneous structure elements and in some cases the bone tissue may affect the propagation of the waves of that range, therefore the selectivity of the method as related to measurement in skin seems rather doubtful. The authors of the said method (R.O.Potts et al) do not take into account a peculiarity of surface waves such as the dependence of the velocity and attenuation of a surface wave on the direction of propagation relative to the displacement vector of a tangential oscillation excited by the transmitter on the surface of tissue. Neither was mentioned the anisotropy which is the important feature of shear elasticity in biological tissues (in particular in skin). Further, the US Patent 4,522,071 describes an apparatus for determining stress in a material through the use of ultrasonic shear waves, polarized orthogonally to their direction of propagation. As stated therein, however, this method is essentially insensitive to anisotropies and microstructures in the tested material. It is thus impractical for determining the structure of living tissues, in particular because of the close relationship between this structure and the anisotropy of the tissue. The structure of tissues is subject to certain changes in a wide range of clinical situations. The structural changes are closely related to the change in viscoelastic properties of tissues. The bulk elastic properties are not particularly sensitive to the structure and its anisotropy as compared to the shear properties, so the testing of shear properties will prove to be of greater value for clinical medicine and diagnosis. Therefore, the invention aims at providing a method for noninvasive and highly sensitive testing of shear properties of a tissue along the specified direction. Fig. 1 is an illustration to the principle of the method. Fig. 2 is a cross-sectional view of the probe (a) and the unit for standardizing the force by which the probe is pressed to the tissue (b). Fig. 3 shows the arrangement of the transducers with their contact tips. Fig. 4 is the circuit block diagrams. Fig. 5 is the clock diagram of the basic measurement cycle. The general idea of the method is the following: the transmitting and receiving flexural bimorphous piezotransducers having the contact tips on their ends are brought into mechanical contact with the matter being investigated. Providing an electrical pulse to the transmitter excites a damped tangential oscillation in the matter close to the contact tip of the transmitter, with a frequency in the range of 0.5 to 30 kHz, depending on the construction of the transducer and the properties of the matter. The propagating mechanical oscillation excites an electric signal in the receiver. The velocity of propagation is determined by measuring the time required for a pulse of tangential deformation to travel the distance between the transmitter and the receiver. The velocity and attenuation of a shear wave depends on the angle between the direction of propagation and the vector of displacement of the tangential oscillations excited by the transmitter. The wave propagating along the vector of displacement has the maximum velocity and the minimun attenuation. This is the reason for placing the transmitter and receiver as shown in Fig.1, where 1 and 2 are the transmitting and receiving flexural bimorphous piezotransducers; The vector of displacement in both the transducers coincides with the line connecting the contact tips A and B. In the preferred embodiment, the device for measuring the velocity comprises a probe with one transmitting and two receiving piezotransducers, the receiving transducers being placed symmetrically with respect to the transmitter as shown in Figs 2a and 3. Using two receivers instead of single one allows for the differential amplification of the received acoustic signals; this is important because the signal felt by the receiver is small. The three piezotransducers 1, 2, 3 with contact tips 4, 5, 6 are mounted onto the probe as shown in Figs. 3 and 2a by means of acoustic delay lines 7 and 8 in the form of hollow thin-wall metallic shafts. The length of the shafts is great enough to delay the acoustic signal passing from transmitter to receiver through the body of the probe for a time several times greater than the propagation time in the intended media. The transducers 1, 2, 3 are fixed in the shafts 7 and 8 by means of dumping elastic gaskets, all together being placed inside the protective case 12 which serves at the same time as a pressure sensor for standardizing the force by which the probe is pressed to the matter. The case 12 drives the three-state switch (Fig. 2b) comprising the needle contact 13, the spring 14, the immobile tubular contact 15 fixed through insulator plastic gasket in the base 9, the mobile contact plate 16, normally pressed to the contact 15 by the spring 17 and separated from the spring by an insulator plate. The said switch is normally open. During the operation, it may be switched on only in the case where the force compressing the spring 17, i.e. the force by which the probe is pressed to the matter, is great enough to make the needle 13 touch the plate 16 but still is not so great as to break the contact between the plate 16 and the tubular contact 15. According to said hereabove, the lower limit of force is determined by the spring 14 which is adjusted by displacing the base 9 inside the exterior case 10, while the upper limit is adjusted by the spring 17 which is compressed by the screw 18. The admitted range of force may be made almost as small as the hysteresisis of friction inside the contact unit. It must be large enough though, so as to be easily controlled by hand. The case 12 and the transducers are arranged so that in the admitted range of force, the contact tips 4, 5, and 6 occupy a fixed position close to the plane of the working edge of the probe. The said switch enables the operation of the electronic block (See Fig. 4a) comprising the differential input amplifier 19, the clip 20, the bistable(type 74121) 24, the flip-flop 23; the pulse generator 21, delay unit 22, the processing unit 25 and the display unit 26. The pulse generator 21 provides the pulses exciting the flexural deformation in the transmitting piezotransducer; a 30 ms pause between the pulses comprises the elementary measurement cycle (See Fig.5). When all the tips of the probe are brought into a contact with the matter, the two counterphase electric signals induced in the receivers are sensed at the inputs of the differential amplifier 19. At the same time the pulse from the generator 21 via the calibrating delay unit 22 sets the flip-flop 23 which gates the count in the processing unit 25. The output of the amplifier 19 is limited by the clip 20 so as to form the pulses with abrupt edges as shown in Fig.5. The leading edge of the first pulse corresponds to the front of the acoustic wave being first detected by the receiver (event M in Fig.5), and the trailing edge corresponds to the wave's first passing the zero (unexcited) level (event N). Since the front of an acoustic wave is very smooth and difficult to be detected with enough confidence, the event N is used instead to measure the time-of-flight of the acoustic pulse between the transmitter and the receiver. The trailing edge of the pulse U20 associated with that event resets the flip-flop 23 via the bistable 24 thus disabling the count in the processing unit 25. The processing unit 25 performs the averaging of several measurements of time-of-flight of acoustic pulses and converting the average time into velocity of pulses. It consists of a frequency divisor 28 gated through the AND latch 27 by the counter of samples 31, the time/velocity convertor 29, clock generator 30, counter 36, bistables 32 and 35 and NOT element 33. The possible implementation of the convertor unit 29 is shown in Fig. 4c. The frequency divisor 28 together with counter 37 accumulate the total number of clock pulses during several sampling periods; the counter 28 divides that number by the number of samples. The cycle of the counter 31 is twice the number of samples; during the first half of cycle its output is HIGH, thus enabling (via latch 27) the sampling in counters 28 and 37. When the output of 31 goes LOW, the sampling stops with the average value of time being stored in 37. At the same time, the output of the invertor 33 goes HIGH thus enabling the count in the buffer counter 36 for a certain period measured by the timer 34. The counter 36 counts the output of the presettable subtracting counter 38 which runs permanently loading the value from 37 each time its count goes down to zero, thus providing the pulses with the frequency being the inverse value of the value of time stored in 37. The timer 34 gates those pulses to the counter 36; it is adjustable to provide the means, together with the adjustable delay unit 22, for calibrating the velocity of pulses. The value of velocity accumulated in 36 is displayed by the display unit 26. At the end of sampling/display cycle the output of 31 again goes HIGH thus resetting via bistables 32 and 35 the counters 28, 37, 36 and enabling the sampling via latch 27. According to the present invention the prototype was made to demonstrate the possibilities of the proposed method in different experiments. In Table 1 one can see how the velocity of surface wave may vary over the skin of a human body. The velocity of shear wave, m/s Forehead Cheek Chest Tip of finger Shin 28±5 20±3 21±5 60±10 35±8 Another example is the measurement of the elasticity of human skin before and after the cryomassage. In a group of women chosen by a cosmetologist as having specifically thin skin on their faces the velocity of surface wave measured before the cryomassage was in the range of 20.2 m/s. Immediately after the cryomassage the velocity was in the range of 60 m/s; it returned to the initial value in about 10 minutes. The rate of relaxation of the elasticity of skin after the cryomassage was shown to be specific for the particular type of skin. One more example is the study of shear elasticity of muscle during contraction. In the isolated resting frog muscle, the velocity of propagation of shear wave along the fibres was about 10 m/s. During contraction it reached 35 m/s. The range of variance of shear wave velocity in the same biological tissue often exceeds 100 per cent, while in the case of bulk elastic waves the change is measured by several per cent. It can be seen that the present invention provides the means for testing the tissues, highly sensitive to both the type of tissue and its physiological state, which may be extremely valuable in medical diagnosis, e.g. in diagnosing the skin pathology or in differentiation of normal and pathological tissues while surgical operations. The experiments also showed that some features of the preferred embodiment prove to be advantageous and even necessary. Particularly, it should be mentioned that because of variety of reasons the force by which the probe is pressed to a tissue impacts to the mechanical state of tissue and strongly affects the results of measurement. The proposed feature of limiting the force makes this error nearly constant and allows it to be taken into account during calibration. The other important feature is the use of two receivers instead of single one. Besides the fact that it increases the sensitivity it is used to reduce the error that may occur during the manual application of the probe due to occasional shifts in relative position of the transmitting and the two receiving transducers since, it should be considered, the shafts carrying the transducers serve at the same time as acoustic delay lines and thus they must be essentially flexible. The maximum error occurs when the transmitter shifts towards one of the receivers; in this case, the signal comes to that receiver a little earlier than is expected, and same signal comes to the other receiver as later. The receipt of the signals is detected by their first passing the zero; provided the shift is small, the zero of the sum of the delayed signal and the signal that comes in advance only slightly shifts from the expected zero point. This shift can be roughly estimated in the following way: A sin (ωt+Ψ) = A₁ sin (ωt+ψ) + A₂ sin (ωt-ψ) (4) where: A is the amplitude of the resulting signal; A₁ and A₂ are the amplitudes of the signals in the receivers; Ψ is the phase shift of the resulting signal, which occurs due to non-symmetrical position of receiving contact tips, ±ψ are the phase shifts of summed signals. We can rewrite equation (4) in the following way: In the small range of displacement of the transmitter with respect to the center position between the receivers, the amplitude of the received signal may be considered as a linear function of the distance and, therefore, we can rewrite equation (5) as: where: R o is half the distance between the contact tips of the receiving piezotransducers, ΔR = L-R o is the displacement of the transmitter relative to the contact tips of the receivers. Assuming f = 5 kHz, R o = 3mm, c=40 m sec⁻¹ ΔR = 0,3 mm, where f is the working frequency and c is an average value of the velocity of surface waves in the human skin, taking into consideration the said parameters (6) one can rewrite equation (6) as follows: sin (ωt+Ψ)≈ sin (ωt + Δ R R . ψ) (7) It can be seen that by using two receiving piezotransducers instead of one, the error which occurs due to changes of the distance between contact tips of the transmitting and the receiving piezotransducers, is decreased approximately ( Δ / R R / ) times, i.e., for the parameters given above, the error for double-receiver device is ten times smaller than for one-receiver version of the device. One more advantage of the preferred embodiment is that the probe can be applied to a surface of tissue all over the body, without clamping it between the transducers or fixing in any other way.

Claims: A method for noninvasive acoustic testing of the elasticity of soft biological tissues by transmitting and receiving surface acoustic waves, comprising the steps of : applying to the tissue surface a probe consisting of spaced apart transmitting and receiving flexural piezotransducers (1, 2, 3) positioned so that their tips (4, 5, 6) lie in a line, said tips (4, 5, 6) being pressed against said tissue with a chosen range of force; providing an electrical pulse to the transmitter transducer (1) to cause flexural oscillation in the said transmitter transducer (1) and to excite a damped oscillation in the said tissue tangential to the tissue surface such that the vector of displacement of the oscillations in the tissue surface coincides with the direction of propagation of said oscillations and with the line connecting said contact tips (4, 5, 6); detecting at and by the receiver (2, 3) the oscillations which occur in the direction of the induced deformation; determining the time elapsed between the sending and receipt of the acoustic pulse travelling across the surface of the tissue; converting the value of the elapsed time into the velocity of said surface wave, this being indicative of the elasticity of the measured tissue in the direction of wave propagation. The method as claimed in claim 1, wherein said determination of the time between the sending and receipt of the acoustic pulse starts at the moment where the tangential displacement of the tissue in contact with the transmitter first returns to its unexcited level and stops at the moment where the signal induced in the receiver first returns to zero. Device for noninvasive acoustic testing of the elasticity of soft biological tissues by transmitting and receiving surface acoustic waves, comprising a probe with : one transmitting and two receiving flexural bimorphous piezotransducers (1 and 2, 3) equipped with contact tips (4 and 5, 6) and mounted, by means of elongated shafts (7, 8) serving as acoustic delay lines, to the body of the probe so that the vectors of displacement of flexural oscillation in the transmitting and the two receiving transducers (1, 2, 3) coincide with the line connecting said contact tips (4, 5, 6); and with a unit for limiting the range of force with which the piezotransducers (1, 2, 3) are pressed against the tissue being tested; and further comprising circuit means connected to said transducers (1, 2, 3) and said force limiting unit, including means (21) to provide an electrical pulse to transmitting piezotransducer (1) to induce a damped oscillation in the tissue, tangential to the tissue surface such that the vector of displacement of the oscillations and the direction of propagation of said oscillations coincide with the line connecting said contact tips (4, 5, 6), means (25) to determine the time taken by acoustic pulses to pass through the tissue from transmitter (1) to the receivers (2, 3) and to convert it to a pulse velocity, and display means (28) to display the value of velocity which is indicative of the elasticity of said tissue in the direction of wave propagation. A device according to claim 3, where the contact tips of the receiving transducers are rigidly bound to each other. The device as claimed in claim 3, wherein the said force limiting unit includes a hollow case (12) enclosing the transducers (1 - 3), said case (12) also forming part of the probe and having an opening through which the transducers (1 - 3) access the tissue surface; a spring (14) supporting case (12) at opposite end to said opening, said spring being attached to a base (9) which is adjustably secured within an exterior case (10) which forms the main body of the probe; a three state electric switch operated by the case (12); a mobile needle contact (13) attached to the case (12) at the same end as the spring (14); an immobile contact (15) fixed through the base (9); a second mobile contact (16) held in contact with the immobile contact (15) by means of an adjustable spring (17), such that, when the force with which the probe transducers are applied to the tissue is within the admitted range, the spring (14) between base (9) and case (12) is compressed enough to-put mobile needle contact (13) in contact with the second mobile contact (16), if the force exceeds its upper limit, further compression of the spring (14) and compression of the adjustable spring (17) occurs such that the circuit between second mobile contact (16) and immobile contact (15) breaks; however if the force is beyond the lower limit the spring (14) supporting the case (12) is not compressed enough to allow the mobile contact needle (13) attached to the case (12) to reach the second mobile contact (16); thus in the described switch, the short circuit indicates that the force acting is within the admitted range.

Inventors: PONOMARJEV, VIKTOR, POPOVIC, GORAN, SARVAZYAN, ARMEN, VEXLER, AKIVO, VUCELIC, DUSAN
Applicants: INSTITUTE OF BIOLOGICAL PHYSICS OF THE USSR ACADEMY OF SCIENCE, INSTITUTE OF GENERAL AND PHYSICAL CHEMISTRY
Application year: 1988
Main classification: G01N29
IPC codes: G01N29, A61B9, A61B5, A61B8