ULTRASONIC BONE THERAPY APPARATUS AND METHOD

Abstract: This invention is a method of ultrasonic bone therapy that subjects a bone (10) to an ultrasonic excitation pulse signal of finite duration, supplied to a transducer (14) next to the bone, and involving a sinusoidal signal in the ultrasonic region to approximately 2 Mhz peculiarly modulated by a sinusoidal signal with frequency between 0 Hz and about 25 kHz; the excitation signal is repeated in the range of 1 Hz to 5000 Hz. The exposure time for therapy is chosen to be in the range of 5 minutes to 1 hour, for 1 time to 3 times a day, for a period of days as necessary for healing or for promoting bone growth and ingrowth. An apparatus for implementing the above method for ultrasonic bone therapy is disclosed comprising a transducer (14) having a transmitting and a receiving element, a special waveform signal generator (20), and a computer (16) for performing the necessary operations defining a preferred treatment regime.

Description: ULTBAS01TIC BOKB-THEBAPY APPARATUS AHD METHOD Field of the Invention The invention pertains to apparatus and method for non-invaaively therapeutically treating bone tissue in vivo. Background of the Invention In recent years, various attempts have been made to stimulate bone growth. These approaches have been essentially ad hoc, with no consistent framework within which to identify the most effective stimulation. Kaufman et al., U.S. Pat Ro. 5,309,808 discloses an apparatus and method for therapeutically treating and/or quantitatively evaluating bone tissue in vivo. The Kaufman method includes subjecting bone to an ultrasonic acoustic signal pulse of finite duration, and involving a composite sine-wave signal consisting of plural discrete frequencies. These frequencies are spaced in the ultrasonic region to approximately 2 MHz; the excitation signal is repeated substantially in the range from 1 to 1000 Hz. Duarte, U.S. Pat. No. 4,530,360 discloses an apparatus and a method of using ultrasonic energy for therapeutic treatment of bone tissue in vivo, using a pulsed sine wave at substantially a single frequency within the range from 1.3 to 2.0 MHz, and at a pulse repetition rate of 100 to 1000Hz. McLeod et al., U.S. Pat. Hoe. 5,103,806 and 5,191,880 disclose methods for promoting bone tissue growth and the prevention of oβteopenia, using mechanical loading of the bone tissue. In both patents, the inventors apply a mechanical load to the bone tissue at a relatively low level on the order of between about 10 and about 1000 microstrain, peak to peak, and at a frequency in the range of about 10 to 100 Hertz. Bassett et al., U.S. Patent Ro. 4,928,959 disclose a method and device for providing active exercise treatment for a patient suffering from a bone disorder. A patient is subjected to an impact load in order to stimulate bone growth, with an impact load sensor being used to monitor the treatment strength. The inventors noted that high frequency (up to 100,000 Hz) force components were important for stimulating bone growth. Numerous other patents disclose methods for stimulating bone growth relying on the generation of electromagnetic signals. For example, Ryaby et al., U.S. Patents Hos. 4,105,017 and 4,315,503 describe methods for promoting bone healing in delayed and nonunion bone fractures, using an asymmetric pulsed waveform. In U.S. Patent Ho. 4,993,413, Hc eod et al. disclose a method and apparatus for inducing a current and voltage in living tissue to prevent osteoporosis and to enhance new bone formation. They disclose the use of a symmetrical low frequency and low intensity electromagnetic signal substantially in the range of 1-1000 Hertz. In Liboff et al., U.S. Patent Ho. 5,318,561 (and others), methods are disclosed that incorporate the combined use of a static and time-varying magnetic field to stimulate bone healing and growth. Specific amplitudes and frequencies are disclosed for optimal enhancement of bone growth, based on the theory of "ion-cyclotron resonance". A recent publication by Weinbau et al. provides a comprehensive and theoretically consistent basis to characterize the means by which bone growth occurs. The seminal article "A model for excitation of osteocytes by mechanical loading-induced bone fluid shear stresses," nay be found in the Journal of Biomechanics, Vol. 27, 1994, pp 339-360. In this publication, they propose that it is not strain magnitude but strain rate that is the primary relevant variable responsible for adaptive bone growth and remodeling. The prior art, exemplified by the references that have been briefly discussed, have used primarily ad hoc approaches or empirical findings for determining exogenous stimulations used up to now for the promotion of bone growth and healing. Some have focussed on the generation of specific values of biomechanical strain in the tiasue as the primary modality of action. However, this invention incorporates the realization that fluid flow induced in normal physiological loading is the critically important variable in bone healing, and moreover, includes an efficient means for generating this fluid flow in living tissues. Specifically, this invention includes a means for stimulating fluid flow at relatively high frequencies by taking unique advantage of the nonlinear characteristics of ultrasound propagation in an ionic-fluid-aaturated porous medium such as bone. In addition, this invention incorporates the important features of repetitive stimulation in analogy to that found in normal physiologic loading, and of adaptive feedback control for ensuring that an optimal signal dose arrives at the desired bone tissue site. Summary of the Invention It is an object of this invention to provide an improved method and apparatus for non-invasively therapeutically treating bone tissue in vivo, to promote bone healing and bone growth. Another object is to meet the above object, such that bone healing and bone growth may be more efficiently and more effectively stimulated than heretofore. A specific object is to achieve the above objects with an optimal set of ultrasonic signals chosen with respect to the specific nonlinear characteristics of their propagation within the bone tissue and with respect to the emulation of physiological loading. A further specific object is to enable adaptive and on-line evaluation of the optimal dose of an applied exogenous ultrasonic acoustic therapeutic signal. It is a general object of the invention to achieve the foregoing objects with apparatua components that are for the most part commercially available. The invention in its presently preferred form achieves the foregoing objectives by subjecting bone to an ultrasonic acoustic excitation signal pulae of finite duration in the ultrasonic region of approximately 1.1 KHz, supplied to a transducer adapted for acoustic coupling to the skin surface overlying a bone; the excitation signal is repeated in the range of about 1 Hz to about 5000 Hz. The exposure time for therapy is chosen to be in the range of 5 minutes to 1 hour, for 1 to 3 times a day, for a period of days as necessary for complete healing or for promoting bone growth or ingrowth. Before ultrasonic therapy is started, an initial interrogating acoustic ultrasonic pulse is preferably transmitted in order to determine the actual thickness of soft tissue overlying the bone treatment site. (Rote that the thickness may change over time due to tissue swelling, for example.) The bone treatment site may be the zone of fracture, the interface between an implanted device (e.g., hip) and bone, or an intact bone which has reduced bone mass, as for example with osteoporosis. Using the round-trip pulse transmit time between the transducer and the near-bone surface and the nominal attenuation value associated with the soft tissue, the input signal amplitude supplied to the transducer is adjusted to ensure that the spatial-average time-average (SATA) power density (i.e., intensity 1544) r e ACΔln β the near-bone surface is approximately 45 mW/cm 2 . The received signal is also monitored during the actual treatment exposure to ensure that the patient is receiving the prescribed therapy during the prescribed treatment time. With these and other objects and advantages in view, the present invention will be clearly understood from the ensuing detailed description in connection with the drawings. Brief Description of the Drawings FIG. 1 is a diagram diagrammatically showing the interconnections of components of an apparatus of the invention. FIGS. 2, 3 and 4, respectively, illustrate a set of acoustic ultrasonic signals used for stimulation of bone growth and healing for several of the currently preferred embodiments. Detailed Description of the Preferred Embodiments FIG. 1 diagrammatically illustrates selected interconnected components for constructing an apparatus for performing methods associated vlth this invention, namely for non-lnvaslvely therapeutically treating bone tissue in vivo, to stimulate bone growth (ingrowth) and bone healing. These components are, in general, commercially available from different sources and will be identified as the detailed description of their total operation is provided. Referring now to FIG. 1, the bone locale 10, such as a fracture site, an area affected by osteoporosis, or any other part of bone tissue to be treated non-lnvaslvely, is shown surrounded by soft tissue 12. Ultrasonic transducer 14 is placed near bone locale 10, adjacent soft tissue 12. By way of example, transducer 14 can be a rectangular piezoelectric transducer of approximately one by two inches placed on the surface of the skin overlying the fractured bone at approximately the site of fracture. The transducer may have a single piezoelectric element that is adapted for both transmitting and receiving, or one transmitting element and one or more receiving elements (not specifically shown). Such transducers are available from Parallel Designs, Inc., Phoenix, AZ. As shown, transducer 14 is used for signal launching and receiving the launched signals after reflecting back from bone 10 and passing through surrounding soft tissue 12. An ultrasonic couplant (not shown) such as a gel is applied between transducer 14 and the patient's outer skin surrounding the soft tissue 12. Basic operation is governed by a signal processing unit 16, which specifically may be a computer, and more specifically, a personal computer, such as the 66 MHz Pentium available from Gateway 2000, Inc., Horth Sioux City, South Dakota. As its designation suggests, this computer contains a 66 MHz clock-pulse generator, and an Intel 586 (Pentium) processor, vlth provision for keyboard instructions at 18. Computer 16 performs constant on-line monitoring of proper functioning of the apparatus according to the present invention. Specifically, computer 16 ensures providing a prescribed therapy to a patient by responding to and watching the reflected signals to calculate an appropriate treatment dose of ultrasonic exposure. A sinusoidal function-generator at a card 20 is relied upon to generate an excitation signal, which is supplied to launch transducer 14, via power amplifier means 22. The power amplifier is suitably Model Ro. 2401, an RF power amplifier product of EIR, Inc., Rochester, R7. This product provides a 50 dB gain over the range 20 kHz to 10 MHz. The excitation signal produced by the generator at card 20 is a pulsed sine vave signal in the ultrasonic range to about 2 MHz, which is sine wave modulated in the range of 0 to 25 kHz. The generator at card 20 may suitably be a commercially available waveform synthesizer, a product of Qu ech, Inc., Akron, OH, identified by Quatech part Ro. WSB-100. This waveform synthesizer provides generstlon of snalog signals independent of host computer 16, allowing full processor power to be used for other tasks, including calculation of waveform data. Card 20 preferably has the capacity to generate an output signal comprising literally thousands of points in the indicated ultrasonic frequency range. Another card 24 is also shown installed in computer 16, for converting analog signals obtained from the receiving element of transducer 14 into digital format for further processing in computer 16. A known in the art switching element (not shown) can be used for disconnecting transducer 14 from card 20 and connecting it to card 24 which latter card may suitably contain a 100 MHz waveform digitizer, part number STR*8100, a product available from SORIX, of Springfield, VA. A connection 26 (shown by broken lines) connects signal-generator card 20 to A/D card 24, for synchronizing purposes and for the purposes of digitizing the reflected waveform, to enable computer 16 to perform a suitably compensated, continuously operative updating average of the signals received at transducer 14. A conventional reamplifier (not shown) for increasing the level of the reflected waveform before being input to card 24 can be included. In order to obtain an estimate of the thickness of the traversed soft tissue overlying the fracture site and properly adjust the amplitude of the therapeutic ultrasonic signal, an initial interrogating acoustic ultraaonic pulse is preliminarily transmitted by card 20 via transducer 14. An exponentially damped sinusoidal signal at 1.1 MHz, vlth a duration of about 2 μs could be an example of such a pulse. Transducer 14 is then used as a receiver to record the reflected signal from the near bone surface. The arrival time of the reflected signal provides a measure of the round-trip transit time, T, for the acoustic pulse to travel from the transducer through the soft tissue to the bone surface (where it is partially reflected), and back through the soft tissue. The soft-tissue thickness, d § , can then be calculated as v β τ/2 where v 8 is the velocity of ultrasound in soft tissue and is given by v s =1540 ms~ x . Once an estimate of soft tissue thickness is obtained, it may be used for adjusting the input signal amplitude to ultrasonic transducer 14 to ensure that the optimal power intensity impinges on the fractured bone. This is preferably carried out as follows. Through a reflection measurement, an above mentioned estimate of soft tissue thickness, d a [cm], Is acquired. Then, according to, for example, Biomedical Ultrasonics, by P.R.T. Wells, Academic Press, London, 1977, a nominal value for ultrasonic attenuation at 1.1 MHz in soft tissue can be obtained u α, ■ 1 dB/cm. Thus, for a soft tissue thickness given by d s , the total decrease in signal amplitude, Δα in dB at the bone surface is Δα «.*. The following formula may then be used to construct a look-up table which provides the necessary values for the relative amplification, A, applied to the input signal. The signal amplification is calculated from A - lo ^") . For example, the associated input signal amplifications to be used may be calculated for a range of soft tissue thicknesses: It is noted that these signal smplifications are relative to the nominal signal value used for producing the desired power density (intensity I SATA «45mW/cm 2 ), within the near field of the ultrasound transducer in a medium of negligible attenuation, such as water. It should also be noted that for safety considerations, it may not be possible to use arbitrarily large incident pover Intensities (at the skin surface), which may, for example, be needed in ease of excessively thick soft tissue overlying the fractured bone. In these caaes, a maximum pover Intensity vill be specified a priori; anything above this value vill be saturated to this maximum intensity. The therapeutic signal is specifically designed to optimally stimulate the fracture healing process. The optimal signal characteristics, whic are set forth in more detail below, are derived using nonlinear vave-propagation theory and stimulate bone healing and grovth through its direct effect on fluid flow. The reliance on acoustic microstreaming as the primary bio-effective aspect of the endogenous ultrasonic signal has led to a more effective and efficacious treatment for bone repair, in contrast to the prior art, which relies on, for example, the endogenous piezoelectricity of bone (see Duarte, supra), the generation of mechanical strains in the bone tissue (see Baβsett et al., U.S. Patents Hoe. 4,928,959 and 5,046,484, and McLeod et al., supra), or on the induction of electrical currents in bone tissue (see Ryaby et al., U.S. Patent Ro. 4,266,533). For better understanding the fluid flow nature of the ultrasound stimulation of bone growth and repair, it should be taken into consideration that the induction of fluid flow arises out of a complex set of interactions of the externally applied ultrasonic signal with the bone tissue. The interactions can be characterized using a generalized theory of acoustics in porous media that includes the effects of an ionic fluid in the pore spaces, as exists in bone tissue. A summary of this theory given below provides the basis for which the optimal ultrasonic therapeutic signals are derived. Fluid flov is assumed to be the fundamental entity which, when stimulated, vill enhance bone grovth and healing. In what follows, jf is defined to be the displacement vector of the fluid relative to the solid matrix (known also as specific discharge relative to the solid) end ζ»-V*χ is the increment of the fluid content per unit volume of the medium. Here V is the nabla operator, and (•) is the scalar product. Therefore, $£*]t*(d_g/dt)*fi is the Eulerian flux (rnβ -1 ) of fluid crossing a unit Λrβa whose normal unit vector is fi. (This flux is related to the fluid flow In acoustic microβtreaming.) In this case, dξ/dt is the net fluid flux entering the unit volume (i.e., fluid influx). A generalized Darcy equation can be used to express the relationship between fluid flux and related quantities In the porous medium by taking into account the contribution of Maxwell's stress tensor in the fluid: η ct β p 3 3w c F 2 (— + )— s -Vp F ■ + c F (V 2 φ F )Vφ F + V(Vφ F .Vφ F ) k 0 f 0 3t 3t 6c 0 In this expression, η (kgm~ 1 a~ 1 ) is the viscosity of the fluid, Oα is the (high frequency) tortuosity of the porous medium, k 0 (m 2 ) is the (low frequency) Darcy permeability, c F and c 0 (F&T 1 ) are the dielectric permittivities of the fluid and vacuum, respectively (c j o»c 0 ), f 0 is the volumetric porosity, and p F (kgm~ s ) is the fluid density. The function φ F (V) is the scalar electric potential in the fluid that results from the perturbation of the endogenous electric potential by the exogenous acoustic exposure (i.e., the ultrasonic signal). The endogenous electric potential arises from several sources, including primarily the interaction of the ionic fluid vith the charged solid matrix surface. It also should be noted that the electric field within the fluid is equal to -Vφ F (VπT 1 ). The pressure in the fluid is denoted by p (RπT 2 ), and is the pressure resulting from the interaction of the exogenous acoustic exposure vith the fluid-filled porous bone structure. After some reasonable simplifying assumptions and using "< >" to denote time average, the previous equation can be used to express the time average Eulerian fluid (streaming) flux ss a function of the time average fluid pressure and electric potential as: ** k 0 k 0 « r c F <4 E > ■ <—> 8 V<p F > + (1 + )V<7φ F -»Vφ F > 3t η η 2 3c 0 This equation demonstrates that the average Eulerian flux of fluid in the porous medium is dependent on the electric field squared, and that the letter's spatial variation can give rise to a non-zero mean (or net) fluid flux irrespective of the time waveform of the perturbation induced by the ultrasound exposure on the electric field -Vφ F . Moreover, the steady component of the fluid flux occurs whether or not the applied mean pressure (i.e., time average) is zero, as may arise for example, with the ultraaonic input. Some of the equations necessary to evaluate all the components of the acoustic field are omitted, as the details are quite cumbersome and do not add additional Insight into the results presented above. It should be noted that the net average fluid flux entering the unit volume ia zero, i.e., 3ξ <—> ■ 0 thus providing an alternating pulsatile fluid influx. It should also be pointed out that the theory presented can also characterize two other sources of nonlinearity In the interaction of the ultrasonic signal vith the bone tiasue. The first is related to convective flov and is one source of the veil-known "radiation pressure" exerted by an acoustic vsve. This phenomenon arises from hydrodynsmical considerations, and in the notation used may be written as dw 3w 4 L = — - — + (4 L .7)w - * E + (4 L -V)ji dt 8t where 4 is the material of Lagrangian fluid (stresming) flux and (H fL -V)w is the convective nonlinearity. Another source of nonlinearity and one which may also be incorporated into the fundamental theory arises due to the constitutive relationship between pressure and density, namely °F ~ PFO B °F ~ Pro P F β P Fo + A[ + —( )-) PFO ^ PFO where p Fo and p Fo are the unperturbed fluid density snd pressure, respectively, and A and B are the well-known nonlinear parameters of the fluid where B/A can typically be as large as 11. This relationship applies to the fluid phase. Analogously, a nonlinear constitutive relationship can also be written for the solid phase of the bone tissue, vhich vill account for additional nonlinearitieβ in the overall solution for fluid flux. Furthemore, the contribution of Maxwell's stress tensor to the solid matrix is another source of nonlinearity. As may be seen readily from the describing equations, both constant and oscillatory fluid flows for promoting bone grovth and repair can be stimulated through appropriate design of the applied acoustic signal that vill be discussed belov in more detail. The above theory clarifies that for obtaining both constant snd oscillatory fluid flovs at rates relevant to therapeutic bone dynamics, the leading term is the square of the applied ultrasonic signal p(t), i.e., p 2 (t). This nonlinearity enables the "in vivo" demodulation of the exogenous ultrasonic waveform, allowing it to have maximal therapeutical effects on bone growth and healing. The signals are specifically designed to be modulated by relatively high frequencies (generally above 500 Hz) in a pulsed excitation mode, which permits the bone tissue to respond maximally during each stimulatory cycle. The foregoing aapects of the nonlinear acoustic theory provide the underlying basis for determining snd thereby inducing fluid flow by the exogenous ultrasonic therapeutic signal. It also should be noted that the received ultrasonic signal is used as a means for providing on-line fault detection, to ensure that the required therapeutic signal is reaching the fracture site during all periods of the treatment prescribed to a patient. General aignal-proceasing/display/atorage software for the signal processing control and operation of computer 16 is not shown but will be understood to be contained on a conventional floppy disk loaded at 28 into computer 16; this software is suitably the MATLAB-386, available from The MathWorks, Inc., Hatick, MA. Further software (not illustrated) includes the signal processing toolbox, also available from MathWorks, aa well as Fortran 5.0, available from Microsoft Corporation, Bothell, WA, and LabView, available from Rational Instruments Corporation, Austin, IX. In the presently preferred embodiments of this invention and vith additional reference to FIGS. 2, 3 and 4, shoving the general outlook of the signals employed, vithout concrete details specifically regarding frequency and pover parameters thereof, borv member 10 surrounded vith soft tissue 12 is placed next to ultrasound transducer 14. An ultrasound signal is transmitted from transducer 14, passes through soft tissue 12, is partially transmitted into the bony member, and is partially reflected from bone tissue 10 back through soft tissue 12 to be received by the receiving element (not specifically shown) of transducer 14. The transmitted ultrasound signal is generated using a finite-duration sine-wave signal, which is sine-wave modulated. A single cycle of this waveform is described by H-l P(t) -= I p,(t - iT 8 '), (la) i-0 repeating every T seconds (1/T Hz), vhere p β (t) is given by the following equation: K{1 + a βin(2ιrf m t)>sin(2ιrf 0 t), 0 ≤ t ≤ T,, P 8 (t) -{ (lb) 0 otherwise, In equations la and lb, the range of aignal parameter values are 0 ϋ f m i 25 kHz (preferably without the zero value, i.e., in most cases f m ≠ 0), 25 kHz < f 0 ≤ 2 MHz, 0.2 mβ S T ≤ 1.0 s (corresponding to pulse repetition rates of 1 Hz - 5 kHz), 0.1 DI S T, < 1.0 s, 0.1 ms < T a * ≤ 1.0 s (corresponding to a duty cycle, γ * RT S ' T, or effective duty cycle taking into account the integrated "on-time" (the overall pulse durations) within a cycle, γ ■ (T βl + T, 2 + ... + T gR )/T, of 0.0001 ≤ γ < 1), l ≤ H ≤ 10,000. The range of the modulation index, a, is given by 0 ≤ a _S 1000. The constant K is adjusted so that the acoustic ultrasonic vave impinging at the near bone surface has an intensity (IJATA) n t e raB * e °- 2 - 100 mW/cm 2 . In a special case (H«l), where p(t)»p β (t), this waveform is described by p(t) « K {1 + a ain(2ιrf B t)}βin(2*f 0 t), 0<t<T,, repeating every T seconds, for a period of time preferably ranging from 5 minutes to 1 hour. The range of parameters is: 0 ϋ f m ϋ 25 kHz (preferably without the zero value, i.e., in most cases f m ≠ 0); 25 kHz Z f 0 ≤ 2 MHz; 0.2 ma ≤ T ≤ 1 s (corresponding to pulse repetition rates of 1 Hz - 5000 Hz) snd 0.1 ms ≤ T β a 1 s (corresponding to a duty cycle, γ = T B /T, of 0.0001 ϋ γ < 1);. The constant K is adjusted such that an intensity Og TA^ of the acoustic ultrasonic wave impinging at the near bone surface is in the range of 20 - 100 mW/cm 2 . Operating in the pulsed regime takes advantage of the acoustic nonlinearities when high amplitude waves are present. The maximum peak amplitude la K(l+a), and ia constrained not to exceed normal safety levels. Amplitude modulation of the carrier signal at a relatively high frequency is specifically used to generate fluid flux at relatively high rates. For the preferred embodimenta of this invention, the amplitude of the signal, as noted above, is adjusted to provide I SATA of approximately 45 mW/cm 2 at the fracture site. It is noted that dynamic strains induced in the bone tissue are primarily in the ultrasonic spectral region, that is, at the nominal frequency of the applied ultrasonic signal. For the presently preferred embodiment, this frequency is 1.1 MHz, and in all cases is above 25 kHz. Additionally, the strain levels induced in the bone tissue, assuming a characteristic length of 10 centimeters, are extremely small. The peak-to-peak strain value can be reaβonsbly veil approximated from the veil known equation for induced particle displacements associated with an ultrasonic input (see for exsmple Physic*! Principles of Medical Ultrasonics, ed. , CR Hill, Halsted Press, 1986, p. 57) . The particle displacement, D, is given by D - l/(vf) I X /(p 0 c/2) X where I is the ultrssonic pover intensity in the bone tissue, p 0 is the unperturbed bone density, c is the velocity of ultrasound in the bone, and f is the ultrasonic frequency. Using values associated vith bone, and for the preferred ultrasonic signal embodiments, a value of D of about 0.016 microns (at 1.1 MHz) can be obtained, and therefore the induced peak-to-peak strain is found to be less than about 0.2 microstrain. For the purposes of the present invention, the three presently preferred embodiments include ultrasonic signals that are specified as follows: 1. As illustrated in FIG. 2, signal 30 is repeated at a repetition rate of 200 Hz (T ■ 5 ma). A single cycle of the waveform is a 0.5 mβ duration sine wave of carrier frequency 1.1 MHz modulated by a 20 kHz sine wave, followed by 4.5 ms of "off time", with the modulation index, a ■ 0.3. This signal is described by the following equation: K{l+0.3βin(2**20*10 a t)}sin(2*.l.l>10't), 0 ≤ t i 0.5 ms Pχ(t) - { > 0 0.5 ms < t a 5 ms repeating at 200 Hz, and K is adjusted so that I SATA " *' mW/cm 2 . 2. As illustrated in FIG. 3, signal 40 is repeated at a repetition rate of 2000 Hz (T - 0.5 ms). A single cycle'of the waveform is a 0.1 ma duration sine vsve of carrier frequency 1.1 MHz modulated by a 20 kHz sine vave, folloved by 0.4 ma of "off time", vith the modulation index, a - 0.3. This signal is described by the following equation: K{l+0.3sin(2ιr.20.10 2 t)}βin(2*.l.l.lθ't), O S t S 0.1 ms P,(t) - { 0.1 ms < t i 0.5 ms repeating at 2000 Hz, and K is adjusted so that *SATA " A5 "M/e* 2 - 3. Aa illustrated in FIG. 4, signal 50 is repeated at a repetition rate of 1 Hz. A aingle cycle of the waveform consists of 25 repetitions (H * 25) of a 4 ms duration (T s * 4 ms) 1.1 MHz sine wave modulated by a 5 kHz sine wave (f m ■ 5 kHz), each such 4 ms "on time" being followed by 4 ms of signal "off time" (T s ' ■ 8 ms). The entire sequence of 25 sinusoidally modulated sinusoidal pulses, together with their associated 4 ms "off times", lasts for 200 ms, after which time the signal is off for 800 ms. The sequence is then repeated at 1 second intervals (1 Hz), the modulation index being a ■ 0.3. This signal is described by the following equation: 24 P,(t) * ∑ p β (t-i«8 ms), repeating at 1 Hz, i-0 vhere K{l+0.3sin(2ιr'5*10 , t)}sin(2ιr*l.l<lθ't), 0 ≤ t ≤ 4 ms P.(t) - { }, 0 elsewhere and K is adjusted so that IJATA " A5 -^^ ea - 2 ' In order to synthesize the second signal of the presently preferred embodiments, the above-mentioned Quatech card is used in conjunction vith another instrument, suitably a Wavetek Model Ro. 178 Programmable Waveform Synthesizer available from Wavetek, San Diego, California. In this case, the Quatech card outputs the modulating waveform as input to the Wavetek Waveform Synthesizer to smplltude modulate the 1.1 MHz carrier signal. An enlarged class of ultrasonic therapeutic signals includes waveforms, which are frequency modulated in addition to them being amplitude modulated in order to take further advantage of the nonlinear propagation characteristics of bone tissue. In this case, sweeping not only the modulating frequency but alao the carrier frequency contributes both to changing and manipulating so-called hot and cold spots in ultrasonic treating a tissue, snd to bringing energy to a bone at different frequencies. These things considered, the efficiency of treating bone tissues in accordance with the present invention is additionally increased. The waveforms of this class can be described as follows: R-l 1-0 repeating every T seconds, where p,(t)-K{l+a βin[2v(f B +(f a *-f B )t T β )t]βin[2r(f 0 +(f 0 *-f 0 )t T β )t>, (2b) 0 ϋ t i T- vhere all the parameters are contained in the same "I ranges as defined before, f B * and f 0 * define the upper limit values of sweeping for modulating and carrier frequencies, respectively, vith f B ≤f B *<25 kHz and f 0 ≤f 0 *<2 MHz. For the purposes of the present invention, the presently preferred embodiment of this class of algnals Include an ultrasonic vaveform that is specified as follova, vith f 0 *=f 0 «l.l MHZ, f B «500 Hz, and f B *«2000 Hz: 24 P 4 (t) - ∑ p 8 (t-i«8 ms), repeating at 1 Hz, 1-0 vhere K {1 + sin[2ιr(500+(2000-500)t/4ms)t]sin[2ιr«l.l«10 < t]}, 0 ≤ t 54 ms P.Ct) - { >. 0 elsewhere and K is adjusted so that ISATA " 4S mW/cm 2 . From the aforesaid it follows that according to the present invention the following four types of signals could be- employed in its implementation, with the specific parameters discussed in the above: - sine vsve modulated sine vave signals; - svept sine vave modulated sine vave signals; - sine vave modulated svept sine vsve signals; - svept sine vave modulated svept sine vave signals. For the purposes of this invention, a sine vave can be assumed to be used to denote a sinusoidal function at a single frequency or a sinusoidal function vith frequency modulation, i.e., a svept sine vave. It is also appreciated that for most cases the modulating frequency in these signals is not supposed to assume the zero value. Hovever, in some concrete instances it can begin or end at or pass through this value. The main and important advantages of the present invention can be summarized as follows: - the reliance on fluid flow as the primary bio-physical phenomenon related to bone growth, which is affected in a near optimal fashion by the ultrasonic signal; - the use of an analytic model for characterizing ultrasonic wave propagation in a porous medium such as bone, in order to establish the biophysical parameters of interest (i.e., fluid flow), in comparison to the prior art, which used either experimental observations only or ad hoc approaches; - the use of relatively high frequency (preferably greater than 500 Hz and less than 25 kHz) sinusoidal smplltude modulation as a means for directly affecting fluid flow; - the use of a relatively low carrier frequency, allowing greater soft tissue and bone penetration due to significantly decreased signal attenuation; - the use of a repetitive stimulation, emulating physiological loading; the ability to construct the device with components that are largely commercially available; - the use of reflection measurements to estimate actual soft tissue thickness, to thereby adjust the amplitude level (i.e., dose) appropriate for each patient and to provide on-line fault detection. It should be understood that though the apparatus and method in accordance vith the present invention have been described in detail they may be subjected to modifications snd other embodiments incorporating the inventive features. Specifically, the apparatus can be constructed vith the use of snalog components alone, in order to reduce significantly the overall coat and complexity. Accordingly, it is intended that the foregoing disclosure is to be considered as illustrating the principles of the invention as an example of those features and not as a delimiting description, vhich is the purpose of the claims that follow.

Claims: What is claimed is: 1. A method of non-invaβively therapeutically treating a bone tissue in vivo using ultrssonic signals, comprising the steps of: (A) producing a preselected periodic therapeutic sine modulated ultrasonic sine signal; and (B) exposing said bone tissue to said therapeutic ultrasonic signal transmitted through soft tissue overlying said bone tissue; to thereby induce fluid flow in said bone tiasue. 2. The method of non-invasively therapeutically treating a bone tissue in vivo according to claim 1, further comprising the steps of: (C) preselecting a power intensity of said therapeutic signal. 3. The method of non-invasively therapeutically treating a bone tissue in vivo according to claim 2, wherein said atep (C) comprises the substepβ of: transmitting an interrogating acoustic ultrasonic pulse to said bone tissue through said soft tissue overlying said bone tissue; receiving a portion of said interrogating signal reflected from said bone tissue; determining the thickness of said soft tissue using said reflected portion; and adjusting the amplitude of said therapeutic ultrasonic signal as to ensure that spatial-average time-sverage power intensity thereof reaching said bone tiasue corresponds to s predetermined value. 4. The method of non-invaβively therapeutically treating a bone tissue in vivo sccording to claim 1, wherein βaid sine modulated ultrasonic sine signal is smplltude modulated and includes: a carrier frequency being selected in s range between about 25 kHz and about 2 MHz, a modulating frequency being selected in a range up to about 25 kHz, a modulation index being up to 1000, a pulse width being between about 0.1 ms snd about 1.0 s, a cycle duration being between about 0.2 ms and about 1.0 s, an intensity OSATA^ being in the range of 20 - 100 mW/cm 2 , and a duration of exposure being between about 5 minutes and about 1 hour for 1 to 3 timea a day. 5. The method of non-invasively therapeutically treating a bone tissue in vivo according to claim 4, wherein said sine modulated ultrasonic βine βignal is the amplitude modulated signal having the carrier frequency being 1.1 MHz, the modulating frequency being 20 kHz, the modulation index being 0.3, the pulse width being 0.5 ms, the cycle duration being 5 ms, and the intensity being 45 mW/cm 2 . 6. The method of non-invasively therapeutically treating a bone tiββue in vivo according to claim 4, wherein said sine modulated ultrasonic sine signal is the smplltude modulated βignal having the carrier frequency being 1.1 MHz, the modulating frequency being 20 kHz, the modulstion index being 0.3, the pulse width being 0.1 ms, the cycle duration being 0.5 ms, and the intensity being 45 mW/cm 2 . 7. The method of non-invasively therapeutically treating a bone tiββue in vivo according to claim 1, wherein βaid preβelected periodic therapeutic βine modulated ultraβonic sine βignal iβ the amplitude modulated βignal with a carrier frequency being βelected in a range between about 25 kHz and about 2 MHz, a modulating frequency being βelected in a range up to about 25 kHz, a modulation index being up to 1000, a pulse width being between about 0.1 ma and about 1.0 β, a duration of a pulβe and a pause for one repetition being between about 0.1 ms and about 1.0 β, a number of pulβe repetitions within a cycle being up to 5000, a cycle duration being between about 0.2 ms and about 1.0 β, an intensity being in the range of 20 - 100 mW/cm 2 , and a duration of expoβure being between about 5 minuteβ and about 1 hour for 1 to 3 tlmeβ a day. 8. The method of non-invaβively therapeutically treating a bone tissue in vivo according to claim 7, wherein said preselected periodic therapeutic βine modulated ultrasonic sine signal is the amplitude modulated signal having the carrier frequency being 1.1 HHz, the modulating frequency being 5 kHz, the modulation index being 0.3, the pulβe vidth being between 4 β, the duration of a pulβe and a pauβe for one repetition being 8 mβ, the number of pulβe repetitions within a cycle being 25, the cycle duration being 1 s, end the intensity being 45 mW/cm 2 . 9. The method of non-invasively therapeutically treating a bone tiββue in vivo according to claim 1, wherein βaid preβelected periodic therapeutic βine modulated ultraβonic βine signal is a frequency and amplitude modulated signal with a carrier frequency having a βelected value in the range between about 25 kHz and about 2 MHz, and having a βveep range between the βelected value and about 2 MHz; a modulating frequency having a βelected value in the range up to about 25 kHz, and having a βweep range between the βelected value and about 25 kHz; a modulation index being up to 1000; a pulβe width being between about 0.1 ma and about 1.0 β; a duration of a pulae and a pause for one repetition being between about 0.1 ms and about 1.0 s; a number of pulae repetitionβ within a cycle being up to 5000; a cycle duration being between about 0.2 mβ and about 1.0 β; en intensity being in the range of 20 - 100 mW/cm 2 ; and a duration of exposure being between about 5 minutes and about 1 hour for 1 to 3 timeβ a day. 10. The method of non-invaβively therapeutically treating a bone tiββue in vivo according to claim 9, wherein βaid preβelected periodic therapeutic sine modulated ultrasonic βine βignal iβ the frequency and amplitude modulated βignal with the carrier frequency being 1.1 MHz, the modulating frequency being 500 Hz, βaid modulating frequency having a βveeping range between 500 Hz and 2000 Hz; the modulation index being 1, the pulβe width being between 4 mβ, the duration of a pulβe and a pauβe for one repetition being 8 mβ, the number of pulβe repetitionβ within a cycle being 25, the cycle duration being 1 β, and the intensity being 45 mW/cm 2 . 11. The method of non-invaβively therapeutically treating a bone tiaβue in vivo according to claim 3, wherein βaid thickness of βaid aoft tiββue iβ calculated aβ d 8 - v.τ/2 vhere d 8 is the desired thickness; v 8 is the velocity of ultrasound in soft tiββue; snd τ iβ a round-trip transit time for βaid acouatic pulβe to travel from a βource thereof through the βoft tiββue, to the bone tiββue, and back through the βoft tiββue. 12. The method of non-invaβively therapeutically treating a bone tiββue in vivo according to claim 3, vhereln βaid initial interrogating acouatic ultraβonic pulβe lβ an exponentially damped βinuβoidal βignal at 1.1 MHz, vlth a duration of about 2 μs. 13. A method of non-invaβively therapeutically treating a bone tiββue in vivo ueing ultraβonic βignala, comprising the stepβ of: (A) generating a preβelected periodic therapeutic ultraβonic βignal; (B) βelecting a pover intensity of β aid therapeutic βignal by virtue of (Ba) generating an interrogating ultraβonic pulβe, (Bb) transmitting said interrogating ultraβonic pulβe to βaid bone tiββue through βaid βoft tiββue overlying βaid bone tiββue, (Be) receiving a portion of βaid interrogating pulβe reflected from βaid bone tiββue, (Bd) determining the thickness of βaid βoft tissue using said reflected portion, and (Be) adjuating the amplitude of aaid therapeutic ultraβonic βignal aβ to ensure that a spatial-average time-average power intensity thereof reaching βaid bone tiββue correβpondβ to a predetermined value; and (C) exposing βaid bone tiββue to βaid therapeutic ultraaonic βignal transmitted through βoft tiββue overlying βaid bone tiββue; to thereby induce fluid flow in βaid bone tiaβue. 14. The method of non-invaβively therapeutically treating a bone tiββue In vivo according to claim 13, wherein aaid preβelected periodic therapeutic ultraβonic βignal iβ amplitude modulated and haβ a carrier frequency being between about 25 kHz and about 2 MHz, a modulating frequency being up to about 25 kHz, a modulation index being up to 1000, a effective duty cycle being between about 0.0001 and about 1, an intensity being in the range of 20 - 100 mW/cm 2 , and a duration of exposure being between sbout 5 minutes and about 1 hour for 1 to 3 times a day. 15. The method of non-invaβively therapeutically treating a bone tiββue in vivo according to claim 14, wherein βaid amplitude modulated βignal haβ the carrier frequency of 1.1 MHz, the modulating frequency of 20 kHz, the modulation index of 0.3, the pulβe width of 0.5 mβ, the cycle duration of 5 ms, and the intensity of 45 mW/cm 2 . 16. The method of non-invasively therapeutically treating a bone tisβue in vivo according to claim 14, wherein βaid amplitude modulated βignal haβ the carrier frequency of 1.1 MHz, the modulating frequency of 20 kHz, the modulation index of 0.3, the pulae width of 0.1 mβ, the cycle duration of 0.5 mβ, and the intensity of 45 mW/cm 2 . 17. The method of non-invasively therapeutically treating a bone tisβue in vivo according to claim 14, wherein βaid amplitude modulated βignal has: a pulse vldth of between about 0.1 mβ and about 1.0 β , a duration of a pulβe and a pauβe for one repetition of between about 0.1 ma and about 1.0 β, a number of pulβe repetitionβ within a cycle of up to 5000, and a cycle duration of between about 0.2 mβ and about 1.0 β. 18. The method of non-invaaively therapeutically treating a bone tiββυe in vivo according to claim 17, wherein βaid amplitude modulated βignal haβ the carrier frequency of 1.1 MHz, the modulating frequency of 5 kHz, the modulation index of 0.3, the pulβe width of 4 mβ, the duration of a pulβe and a pauβe for one repetition of 8 ms, the number of pulse repetitions within a cycle of 25, the cycle duration of 1 β, and the intensity of 45 mW/cm 2 . 19. The method of non-invasively therapeutically treating a bone tiββue in vivo according to claim 13, wherein βaid preβelected periodic therapeutic ultraβonic βignal iβ a frequency and amplitude modulated βignal vith a carrier frequency having a βelected value in the range betveen about 25 kHz and about 2 MHz, and having a βveep range betveen the selected value and about 2 MHz; a modulating frequency having a aelected value in the range up to about 25 kHz, and having a βveep range betveen the selected value and about 25 kHz; a modulation index being up to 1000, a pulβe vidth being betveen about 0.1 mβ and about 1.0 a, a duration of a pulβe and a pauβe for one repetition being between about 0.1 mβ and about 1.0 β, a number of pulae repetitionβ within a cycle being up to 5000, a cycle duration being between about 0.2 ms and about 1.0 s, an intensity being in the range of 20 - 100 mW/cm 2 , and a duration of exposure being between about 5 minutes and about 1 hour for 1 to 3 times a day. 20. The method of non-invaaively therapeutically treating a bone tissue in vivo according to claim 19, wherein βaid frequency and amplitude modulated βignal has the carrier frequency of 1.1 MHz, the modulating frequency of 500 Hz, βaid modulating frequency βweeping range of between 500 Hz and 2000 Hz; the modulation index of 1, the pulβe width of between 4 mβ, the duration of a pulse and a pause for one repetition of 8 ms, the number of pulse repetitions within a cycle of 25, the cycle duration of 1 s, and the intensity of 45 mW/cm 2 . 21. The method of non-invaaively therapeutically treating a bone tiββue in vivo according to claim 13, wherein βaid thickneββ of βaid βoft tiββue iβ calculated aβ d β - v,τ/2 where d 8 iβ the deβired thickneββ; v 8 iβ the velocity of ultraaound in βoft tiββue; and τ ia a round-trip tranβit time for βaid acouatic pulβe to travel from a source thereof through the soft tisβue, to the bone tiββue, snd back through the soft tisβue. 22. The method of non-invaβively therapeutically treating a bone tiaβue In vivo according to claim 13, wherein aaid initial interrogating acouatic ultraaonic pul β e i β an exponentially damped βinuβoidal βignal at 1.1 MHz, with a duration of about 2 μβ. 23. An apparatus for non-invaaively therapeutically treating bone tiββue in vivo eompriβing: a waveform βy theβizer for producing an initial interrogating acouatic ultraβonic βignal to determine the thickneββ of a βoft tiββue overlying said bone tisβue, and an excitation βignal to be applied to βaid bone tiββue, βaid excitation βignal being a finite duration βine wave carrier βignal with a frequency βelected in the ultraaonic region to approximately 1.1 MHz, modulated by a modulating aine βignal with a frequency βelected between about 0 Hz and about 25 kHz, βaid excitation βignal being repeated βubβtantially in the range 1 to 5000 Hz; an ultrasonic tranβducer having a transmitting element being connected to βaid waveform βyntheβizer and adapted for acouatic coupling to nearby akin and for conveying βaid interrogating and βaid excitation aignala along an aβcertained path to βaid bone tiββue, a receiving element for receiving e reflected portion of said interrogating βignal reflected from βaid bone tiββue; and a computer coupled to βaid tranβducer end βaid receiving element, for adjusting said excitation βignal reβponβive to βaid received reflected βignal.

Inventors: CHIABRERA ALLESSANDRO E, KAUFMAN JONATHAN J, CHIABRERA, ALLESSANDRO, E., KAUFMAN, JONATHAN, J.
Applicants: CHIABRERA ALLESSANDRO E, KAUFMAN JONATHAN J, ORTHOLOGIC CORP, CHIABRERA, ALLESSANDRO, E., KAUFMAN, JONATHAN, J., ORTHOLOGIC CORPORATION
Application year: 1995
Main classification: A61N1
IPC codes: A61B17, A61F2, A61H23, A61N1, A61N7