# Patent

## Title
System and method for ultrasound therapy using grating lobes

## Abstract

A system and method for medical treatment of tissue using ultrasound. The system comprises a probe having an array of transducer elements, an ultrasound waveform generator adapted to generate at least one electrical ultrasound signal, and a plurality of phase controls, each coupled to the ultrasound waveform generator and adapted to generate from the electrical ultrasound signal a phase-shifted drive signal that is coupled to an associated transducer element. The drive signal is effective to control grating lobe foci emitted by the array. The method employs the system.

## Background
FIELD OF THE INVENTION
The present invention relates generally to ultrasound, and more particularly, to an apparatus and method for providing medical treatment using high-intensity focused ultrasound.
BACKGROUND OF THE INVENTION
Sound waves that have a frequency greater than approximately 20 kHz are referred to in the art as “ultrasound.” In the medical field, ultrasound waves are useful for both diagnostic and therapeutic applications. Medical diagnostic ultrasound systems are useful for generating images of anatomical structures within a target area of a patient's body. The images are obtained by scanning a target area with waves of ultrasound energy. In therapeutic ultrasound applications, high intensity ultrasound energy is transmitted into a target area to induce changes in state of the target. High-intensity focused ultrasound (“HIFU”) pulses induce changes in tissue state through thermal effects (e.g., induced hyperthermia) and mechanical effects (e.g., induced cavitation).
The use of high intensity focused ultrasound to eliminate tissue or to alter the characteristics of tissue at a target location, volume, region or area within a larger mass, body or area of anatomical tissue presents many advantages, including minimization of trauma and pain for the patient, elimination of the need for a surgical incision, stitches and exposure of internal tissue, avoidance of damage to tissue other than that which is to be treated, altered or removed, lack of a harmful cumulative effect from the ultrasound energy on the surrounding non-target tissue, reduction in treatment costs, elimination of the need in many cases for general anesthesia, reduction of the risk of infection and other complications, avoidance of blood loss, and the ability for high intensity focused ultrasound procedures to be performed in non-hospital sites and/or on an out-patient basis.
In high-intensity focused ultrasound hyperthermia treatments, intensity of ultrasonic waves generated by a highly focused transducer increases from the source to the region of focus where it can reach a very high temperature. The absorption of the ultrasonic energy at the focus induces a sudden temperature rise of tissue, which causes ablation of the target volume of cells in the focal region. Thus, as an example, HIFU hyperthermia treatments can cause necrotization of an internal lesion without damage to the intermediate tissues. The focal region dimensions are referred to as the depth of field, and the distance from the transducer to the center point of the focal region is referred to as the depth of focus. Ultrasound is a promising non-invasive surgical technique because the ultrasonic waves provide effective penetration of intervening tissues, yet with sufficiently low attenuation to deliver energy to a small focal target volume. Currently there is no other known modality that offers noninvasive, deep, localized focusing of non-ionizing radiation for therapeutic purposes. Thus, ultrasonic treatment has a great advantage over electromagnetic and radioactive therapeutic treatment techniques.
The beam emitted by a single ultrasound focused transducer element is generally effective within a fixed region, called the “focal zone.” This focal zone frequently is smaller than the size of the target tissue. Treatment of extensive targets is consequently a problem. A solution to this shortcoming is to utilize a transducer comprising a plurality of individual transducer elements arranged closely together to form an array. These arrays are focused at the desired treatment site through a combination of geometric and electronic focusing. Geometric focusing is determined by the permanent geometry of the array, while electronic focusing involves the use of phase delays and wave interference to achieve constructive interference at the target tissue. Electronic focusing allows movement of the treatment location without the need for mechanical movement of the array.
A particular problem is the use of small ultrasound arrays in relation to certain types of medical treatments, such as HIFU treatment in association with laparoscopic, percutaneous, and interstitial procedures. Individual focused transducer elements are often smaller than the target tissue, requiring movement of the transducer to ablate the tissue. The use of transducer arrays is likewise problematic, since the space available for placement or insertion of the transducer is limited.
HIFU treatment using a small focal point, whether generated from a single ultrasound transducer element or a phased array, allows great treatment selectivity. For example, the focal spot can be used to treat particular regions of tissue while sparing critical tissue structures. However, focused transducers are slow when used to treat large volumes of tissue. It is desirable to provide an ultrasound transducer that is capable of providing a small, selective focal spot for treating a specific region of tissue and is also capable of treating large volumes of tissue.
A potential solution is the use of a physically small array having fewer transducer elements, wherein the elements can be electronically controlled to focus or steer the beam. A conventional ultrasound transducer array used for beam forming typically requires small transducer elements having an aperture pitch that is half the wavelength of the ultrasound signal or less. Ultrasound arrays for use in confined spaces preferably have larger transducer elements of two or more wavelengths in aperture pitch for effective ablation. Conventional methods of focusing and beam steering are not compatible with these transducers. When an electronic focus is attempted with such a transducer, large secondary off-axis foci, or “grating lobes” are created. These grating lobes are comparable in amplitude to the primary focus and draw energy from the main focal lobe, reducing the efficacy of the ultrasound beam.
Another potential solution is to use an unfocused ultrasound transducer. An unfocused ultrasound transducer will treat a larger portion of the target tissue. However, the ablation depth may be substantially reduced in relation to a focused ultrasound beam, necessitating more movement of the transducer during the ablation procedure.
Still, scientists and engineers continue to seek improved methods for therapeutic ultrasound medical treatment of tissue. There is a need for a physically small ultrasound array that is capable of treating a relatively large portion of target tissue with a greater ablation depth than is currently available in the art.
SUMMARY OF THE INVENTION
One embodiment of the present invention overcomes the aforementioned limitations of ultrasound transducers by altering the phasing of transducer elements on a transducer array, such as a linear ultrasound array, so that the positions of grating lobes emitted by the array can be changed. A volume of target tissue can be ablated using a sequence of several different insonifications. Each of these insonifications creates multiple grating lobe foci to cover a different subset of the volume. In this manner, ablation of a large target tissue can be accomplished more efficiently than is possible using a single focus without grating lobes.
An embodiment of the present invention is a system for medical treatment of tissue using ultrasound. The system comprises a probe having an array of transducer elements; an ultrasound waveform generator adapted to generate at least one electrical ultrasound signal; and a plurality of phase controls coupled to the ultrasound waveform generator, each phase control adapted to generate from the at least one electrical ultrasound signal a phase-shifted drive signal that is coupled to an associated transducer element. The drive signals are effective to control grating lobe foci emitted by the array.
Another embodiment of the present invention is a system for medical treatment of tissue using ultrasound. The system comprises a probe having an array of transducer elements; an ultrasound waveform generator adapted to generate at least one electrical ultrasound signal; and a plurality of phase controls coupled to the ultrasound waveform generator, each phase control adapted to generate from the at least one electrical ultrasound signal a drive signal that is coupled to an associated transducer element. The phase controls comprise a focusing phase shift portion adapted to produce a first phase shift in the drive signal, and a grating lobe phase shift portion adapted to produce a second phase shift in the drive signal, wherein each drive signal has a composite phase shift that is the mathematical sum of the first and second phase shifts. The drive signals are effective to cause the array to emit acoustic ultrasound signals having a focal point controlled by the first phase shift and grating lobe foci controlled by the second phase shift.
A method of the present invention is for medically treating tissue using ultrasound. The method comprises the steps of providing a probe having an array of transducer elements, generating at least one electrical ultrasound signal, generating from the at least one electrical ultrasound signal a plurality of phase-shifted drive signals, and coupling each phase-shifted drive signal to an associated transducer element. The drive signals are effective to control grating lobe foci emitted by the array.



BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a is a schematic view of the distal portion of an ultrasound treatment probe according to an embodiment of the present invention;
FIG. 2 is a representation of the acoustic pressure amplitude of ultrasound waves emitted by the probe of FIG. 1;
FIG. 3 is another representation of the acoustic pressure amplitude of ultrasound waves emitted by the probe of FIG. 1;
FIG. 4 is a composite representation of the acoustic pressure amplitudes of FIGS. 2 and 3; and
FIG. 5 is a schematic block diagram of a medical ultrasound therapeutic treatment system according to an embodiment of the present invention.



DETAILED DESCRIPTION OF THE INVENTION
Referring now to the Figures, in which like numerals indicate like elements, FIG. 1 is a schematic view of a distal portion of an embodiment of an ultrasound treatment probe 10 that includes a body 12 in the form of a longitudinal shaft having a circumference C. Body 12 has a distal end region 14 which includes a substantially linear ultrasonic transducer array 16 having a plurality of transducer elements 18 that produce acoustic ultrasound signals used to medically treat tissue.
Probe 10 may have various configurations for various uses. For example, probe 10 may be used for laparoscopic, percutaneous and interstitial use for tissue ablation. The particular shape of probe 10 will be dictated by its use and FIG. 1 is merely intended to generally represent the distal end portion of probe 10, which typically is a cylindrical shaft. One skilled in the art will recognize that the present invention is not limited to such a configuration and may be applied to other types of arrays including, without limitation, curved arrays and collections of larger, separate transducer elements on a single probe that are focused, planar, or convex in curvature. A lens or acoustic window (not shown for clarity) may cover the emitting faces of linear transducer array 16.
With continued reference to FIG. 1, to focus a transducer array 16 having a plurality of transducer elements 18, a pitch d, and generating ultrasound at a wavelength λ, the array elements are phased to focus at a focal distance F. The electronic signals applied to each transducer element are separately phase shifted so that the propagating waves emitted by each element combine constructively at the focal point. These phase shifts are equivalent to time delays of the signals applied to the transducer elements. In the XZ plane of FIG. 1, foci of acoustic ultrasound signals will appear at approximate azimuthal positions X given by Equation 1:




  
    
      
        
          Foci
          ⁡
          
            (
            X
            )
          
        
        =
        
          
            F
            ⁢
            
              
            
            ⁢
            λ
            ⁢
            
              
            
            ⁢
            m
          
          d
        
      
    
    
      
        Equation
        ⁢
        
          
        
        ⁢
        1
      
    
  




where m=0, ±1, ±2 . . . .

With the exception of m=0, which is the main lobe or central focus, these maxima are grating lobes and are normally an undesired characteristic of linear transducer arrays. An example illustration of the acoustic amplitude of an ultrasound transducer array 16 exemplifying foci of Equation 1 is shown in FIG. 2. FIG. 2 illustrates the relative spatial positions of the maxima.
An additional phase factor Φ may be expressed by Equation 2:




  
    
      
        Φ
        =
        
          e
          
            
              i2π
              ⁢
              
                
              
              ⁢
              n
            
            N
          
        
      
    
    
      
        Equation
        ⁢
        
          
        
        ⁢
        2
      
    
  




If phase factor Φ is applied to all elements 18 of array 16, where n is an element index, grating lobes will appear at the approximate positions given by Equation 3:





  
    
      
        Foci
        =
        
          
            F
            ⁢
            
              
            
            ⁢
            
              λ
              ⁡
              
                (
                
                  m
                  +
                  
                    1
                    N
                  
                
                )
              
            
          
          d
        
      
    
    
      
        Equation
        ⁢
        
          
        
        ⁢
        3
      
    
  




For example, if N=2 in Equation 2, the phase shift between adjacent elements 18 will be 180°, corresponding to a reversal of polarity between elements. As a result, grating lobes will occur approximate positions defined by Equation 4:




  
    
      
        Foci
        =
        
          
            F
            ⁢
            
              
            
            ⁢
            
              λ
              ⁡
              
                (
                
                  m
                  +
                  
                    1
                    2
                  
                
                )
              
            
          
          d
        
      
    
    
      
        Equation
        ⁢
        
          
        
        ⁢
        4
      
    
  




As can be seen, grating lobes will occur at positions about halfway between lobes generated in accordance with Equation 1. An example illustration of the acoustic field from a group of ultrasound elements 18 focused at the distance Z=F (see FIG. 1) and additionally phased according to Equation 2 with N=2 is shown in FIG. 3.

In an embodiment of the present invention, an element-dependent phase factor Φ is applied to the electrical ultrasound signal applied to each transducer element 18, in addition to the phase factor associated with electronic focusing. The element-dependent phase factor Φ causes grating lobe foci to shift in position corresponding to Equation 3. Multiple insonifications using different element-dependent phase factors can cause tissue heating in multiple locations corresponding to the different spatial patterns of grating lobe foci. As a result, heat is deposited in a larger volume of tissue as compared to heating generated with an acoustic ultrasound signal according to Equation 1. The heating of a greater area is represented graphically by FIG. 4, wherein a composite of the insonification patterns of FIGS. 2 and 3 in combination causes tissue heating within a greater region than is possible with the insonifications shown in FIG. 2 or FIG. 3 alone. In one embodiment of the present invention the insonified medium may be tissue to be medically treated.
An example ultrasound treatment system 20 according to an embodiment of the present invention is depicted in FIG. 5. Ultrasound treatment system 20 includes an ultrasound treatment probe 10, a waveform generator 22, and a plurality of phase controls 24.
Ultrasound treatment probe 10 includes a transducer array 16 having a plurality of transducer elements 18. In the example of FIG. 5, transducer array 16 may include two groups of elements, labeled “A” and “B,” arranged in an alternating pattern between adjacent elements.
Waveform generator 22 generates at least one electrical ultrasound signal having a predetermined amplitude, frequency and impedance compatible with transducer elements 18. Waveform generator 22 may have either a plurality of outputs or a single output for the electrical ultrasound signal.
A plurality of phase controls 24 are coupled to waveform generator 22 and are adapted to receive the electrical ultrasound signal. Each phase control 24 generates from the electrical ultrasound signal a drive signal adapted to drive an associated element 18 of array 16. Phase controls 24 each include a focusing phase shift portion 26 that produces a first phase shift in the drive signal, the first phase shift being adapted to drive an associated transducer element 18 such that array 16 emits an electronically focused ultrasound signal.
Each phase control 24 further includes a grating lobe phase shift portion 28. Grating lobe phase shift portion 28 that produces a second phase shift in the drive signal. The second phase shift applies an element-dependent phase factor Φ (see Equations 2 and 3), effective to control the azimuthal position of grating lobes emitted by array 16 in the manner previously discussed. The drive signal that is coupled from each phase control 24 to an associated element 18 thus has a composite phase shift that is the mathematical sum of the first phase shift, adapted to achieve electronic focusing of array 16, and the second phase shift, adapted to control the position of grating lobes produced by the array.
In various embodiments of the present invention, focusing phase shift portion 26 may be used to electronically focus the acoustic signal of array 16 independently of the relative position of the grating lobes. Likewise, grating lobe phase shift portion 28 may be used to vary the relative locations of grating lobes emitted by array 16 independently of the focused acoustic signal. For example, array 16 may be electronically focused at a single location while a plurality of grating lobe foci are produced at one or more predetermined groups of locations, which may be varied periodically and/or sequentially in number and/or location. Similarly, array 16 may also be electronically focused periodically and/or sequentially at variable locations while a plurality of grating lobe foci are produced at one or more predetermined groups of locations, which may also be varied periodically and/or sequentially in number and/or location.
The composite drive signal produced by each phase control 24 is coupled to an associated transducer element 18 by any conventional means including, without limitation, electrical wires and printed circuits. Each transducer element 18 converts the drive signal to a high-intensity acoustic ultrasound signal. In combination, elements 18 of array 16 form a focused acoustic ultrasound signal having grating lobes in accordance with Equations 1-4, as implemented by controlling the phase shifts produced by focusing phase shift portion 26 and grating lobe phase shift portion 28 of phase control 24.
In operation, waveform generator 22 generates at least one electrical ultrasound signal. The electrical ultrasound signal of waveform generator 22 is coupled to phase controls 24, each of which generate a drive signal having a predetermined composite phase shift that is the mathematical sum of a first phase shift directed to electronic focusing of array 16 and a second phase shift that is directed to manipulating the locations of grating lobe foci according to Equation 2. The drive signals from each phase control 24 are coupled to an associated transducer element 18. Each transducer element 18 converts the drive signal to a high-intensity ultrasound acoustic signal having focusing characteristics and grating lobe positions that correspond with the predetermined phase relationships generated by phase shift portions 26, 28 of phase control 24.
Drive signals of phase control 24 may optionally have varying phase-shift patterns to steer grating lobe foci to varying azimuthal positions, such as those illustrated in FIGS. 2 and 3. This is accomplished by periodically or sequentially changing in time the phase shift applied by grating lobe phase shift portions 28 in accordance with multiple element-dependent phase factors Φ (see Equation 2), resulting in a more uniform ultrasound heating pattern. An example is a composite of the patterns of FIGS. 2 and 3, as depicted in FIG. 4. FIG. 2 represents the ultrasonic field when no grating lobe phase shift is employed (N=1). FIG. 3 represents the ultrasonic field for a grating lobe phase shift determined from Equation 2 using N=2, so that group “A” is driven with a grating lobe phase shift of 0 while group “B” is driven with a grating lobe phase shift of π or vice-versa. The composite heating pattern shown in FIG. 4 illustrates that, by applying both grating lobe patterns, a more uniform heating pattern may be achieved by insonifying the medium at spatially interspersed focal locations.
With continued reference to FIG. 5, in an alternate embodiment of the present invention, “N” of Equation 3 may be set to 1 (i.e., no grating lobe phase shift) such that array 16 is focused at a single point and additional heating of tissue occurs at the multiple grating lobe foci. In another alternate embodiment of the present invention, “N” of equation 3 may be set to a value of 2, causing grating lobes to occur at positions differing from N=1. In yet another embodiment of the present invention, any sequence of insonifications using transducer 10 may be implemented with differing or varying “N” values or states in any desirable order, sequence or period of time to produce accordingly differing or varying grating lobe patterns implemented in a predetermined sequence, pattern or characteristic to execute a given treatment plan.
One skilled in the art will recognize that the drive signal generated by phase control 24 may be produced in a number of different ways. For example, focusing phase shift portion 26 and grating lobe phase shift portion 28 may be separate components of ultrasound treatment system 20. In addition, each phase control 24 may mathematically derive and generate a single phase shift representing the sum of phase shifts produced by focusing phase shift portion 26 and grating lobe phase shift portion 28. Phase shift control 24 may utilize a conventional computing device, such as a computer or microprocessor, in conjunction with a predetermined set of instructions, such as a computer program, to mathematically derive the summed phase shift value.
Transducer 14 is not limited to a substantially linear array 16. In various other embodiments of the present invention transducer 14 and array 16 may be any combination of phased arrays, a plurality of single-element transducers having a common drive signal, geometrically focused transducers, and convex transducers. In addition, transducer 14 may optionally include an acoustic lens (not shown), which may or may not act to focus or alter the acoustic signals generated by elements 18.
With reference to FIG. 5, alternate embodiments of the present invention are envisioned wherein the focusing phase factor is not needed. Example embodiments include arrangements where focusing is accomplished in some other way including, without limitation, geometrically focused transducers 10. Further, an acoustic lens may optionally be used to focus the ultrasound acoustic signal. In such embodiments focusing phase shift portion 26 may be deleted from phase control 24.
One skilled in the art will recognize that, for situations when the grating lobes are sufficiently separated, that additional insonifications can be made using various phase factors Φ to fill the gaps between grating lobes and thus deposit heat uniformly throughout the volume of tissue to be treated. For example, insonifications where N of Equation 3 equals ±4 may be used in conjunction with N=±2. Grating lobe foci then appear about halfway between all of the foci created using the original insonification of FIG. 2, with no phase factor Φ, and the second insonification with N=±2. Similarly, various other phase factors Φ can be applied separately or in combination to create other insonifications that deposit heat in other desired patterns.
A particular advantage of the present invention is that treatment planning can be optimized using insonifications with manipulated grating lobe foci. In such optimization, planning aspects such as the duration of each insonification, the power level of each insonification, and the order of insonifications can be altered to provide maximal ablation depth. For example, acoustic screening (due to cavitation and/or tissue boiling) can be minimized because proximal tissue regions heating during one insonification can cool during the next insonification that heats different tissue regions. Other advantages include the ability to treat a large tissue volume rapidly while maintaining selectivity with regard to the regions of tissue to be treated. Since multiple foci may be positioned as required for a predetermined treatment plan, critical tissue structures can be spared and target tissue can be efficiently treated.
With reference again to FIG. 1, maximal power may be delivered into the tissue by using the entire length of transducer array 16. However, if greater specificity is desired, the present invention can be used with appropriate sub-apertures (not shown) to limit the extent of tissue ablation. In addition, if a specific tissue structure (such as a major blood vessel) is to be spared, grating lobe foci can be manipulated as disclosed herein to avoid critical structures while ablating surrounding tissue.
As will be recognized by one skilled in the art, embodiments of the present invention are capable of ablating larger volumes of tissue with greater speed than is currently available, using small-diameter ultrasonic probes suitable for interstitial use in soft tissue. In comparison, prior art swept-focus schemes are much slower and less efficient, especially for small-aperture transducers. Planar exposures ablate tissue at greater rates, but do not achieve ablation depths necessary for practical use. Prior art split-focus schemes increase efficiency of ablation, but require much larger probes and this is inappropriate for interstitial use. Embodiments of the present invention overcome both of these disadvantages.
While the present invention has been illustrated by a description of several methods and embodiments, it is not the intention of the applicants to restrict or limit the spirit and scope of the appended claims to such detail. Numerous other variations, changes, and substitutions will occur to those skilled in the art without departing from the scope of the invention. For instance, the ultrasound methods and systems of the invention have application in therapeutic tissue ablation, taking into account the obvious modifications of such methods, systems and components to be compatible with such an ablation system. It will be understood that the foregoing description is provided by way of example, and that other modifications may occur to those skilled in the art without departing from the scope and spirit of the appended claims.

## Claims

1. A method for medical treatment of tissue using ultrasound, comprising the steps of:
providing a probe having an array of transducer elements;
generating at least one electrical ultrasound signal;
generating from the at least one electrical ultrasound signal a plurality of phase-shifted drive signals;
coupling each phase-shifted drive signal to an associated transducer element, effective to control grating-lobe foci emitted by the array without changing array steering direction relative to the probe and without changing array focusing relative to the probe;
electronically focusing the array at a single location;
producing a plurality of grating-lobe foci only at a first predetermined group of locations for a first period of time for medical treatment of tissue with the array electronically focused at the single location; and
producing a plurality of grating-lobe foci only at a second predetermined group of locations for a second period of time for medical treatment of tissue with the array electronically focused at the single location, wherein the locations of the second predetermined group of locations are different from the locations of the first predetermined group of locations, and wherein the second period of time occurs later and separate from the first period of time.

2. The method of claim 1, further comprising the step of selecting a transducer that includes at least one of a substantially linear array, a phased array, a curved array, a geometrically focused transducer, a plurality of single-element transducers having a common drive signal, and a convex transducer.

3. The method of claim 2, further comprising the step of adding an acoustic lens to the transducer.

4. The method of claim 1, further comprising the steps of:
forming a plurality of groups of elements;
coupling drive signals that are substantially alike in phase shift to transducer elements within each group; and
substantially differing the phase shifts of drive signals between groups of elements.

5. The method of claim 1, further comprising the step of periodically varying the phase shifts of the drive signals.

6. The method of claim 5, further comprising the step of periodically varying the phase shifts of the drive signals between a plurality of predetermined states.