Abstract:
Real-time monitoring of tissue ablation is possible by using a vibrating ablation needle coupling lateral shear waves to the tissue. Ultrasonic imaging may characterize the velocity of these shear waves to reveal Young&#39;s modulus of the tissue and, at a discontinuity in Young&#39;s modulus, a boundary of the ablated lesion reflecting an underlying increase in stiffness of ablated tissue. This technique may be coupled with quasi-static elastography-based ablation monitoring techniques for improved measurement.

Description:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
       [0001]    This invention was made with United States government support awarded by the following agencies: 
       NIH CA112192  
       [0002]    The United States government has certain rights in this invention. 
     
    
     CROSS-REFERENCE TO RELATED APPLICATIONS 
     BACKGROUND OF THE INVENTION 
       [0003]    The present invention relates to radiofrequency or microwave ablation and in particular to a method of monitoring tissue ablation concurrent with the ablation process. 
         [0004]    Elastography is an imaging modality that reveals the stiffness properties of tissues, for example, axial strain, lateral strain, Poisson&#39;s Ratio, Young&#39;s Modulus, or other common stiffness measurements. The stiffness measurements may be output as quantitative values or mapped to a gray or color scale to form a picture over a plane or within a volume. 
         [0005]    Generally, stiffness is deduced by monitoring tissue movement under an applied force or deformation. The monitoring may be done by any medical imaging modality including computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonic imaging. Elastography is analogous to a physician&#39;s palpation of tissue in which the physician determines stiffness by pressing the tissue and detecting the amount that the tissue yields under pressure. 
         [0006]    In “dynamic” elastography, a low frequency vibration is applied to the tissue and the velocity of the resulting compression waves is measured, for example, using ultrasonic Doppler detection. In “quasi-static” elastography, two images of the tissue are obtained at different states of compression, typically using the ultrasonic transducer as a compression paddle. Displacement of the tissue between the two images is used to deduce the stiffness of the tissue. 
         [0007]    U.S. Pat. No. 7,166,072, assigned to the same assignee as the present invention and hereby incorporated by reference, describes a novel technique for monitoring a radiofrequency ablation using quasi-static elastography. Radiofrequency or microwave ablation is a process for treating tumors or the like which employs one or more of electrodes inserted percutaneously to the site of a tumor. Ionic heating of the tissue induced by radiofrequency fields in the tissue kills tumor cells and produces a hardened lesion. This lesion, being much stiffer than the surrounding tissue, may be monitored by quasi-static elastography using the ablation electrode as the compression device. Adhesion between the ablated tissue and the electrode allows the source of the compression to be at the site of the tumor (as opposed to external compression to the patient) providing a more accurate characterization of the stress field near the tumor and, accordingly, substantially improved elastographic measurement. As used herein, the term “high-frequency ablation” will be used for ablation using either radiofrequency or microwave frequency electrical energy. 
       SUMMARY OF THE INVENTION 
       [0008]    The present invention provides improved definition of the boundaries of the tumor during ablation, as well as improved quantitative characterization of the tissue by measuring not only axial compression of the tissue but shear wave velocity perpendicular to the deformation axis. A change in velocity of the shear waves characterizes the lateral edges of the ablated volume and provides a direct measurement of Young&#39;s modulus of both the ablation volume and surrounding non-ablated tissue. The technique of monitoring axial compression (per U.S. Pat. No. 7,166,072) and the technique of monitoring shear wave velocity can be combined to obtain a more complete and more accurate picture of the ablation volume during ablation, with the axial compression technique providing axial boundaries and the shear wave technique providing lateral boundaries, for example. 
         [0009]    Specifically then, the present invention may provide an apparatus for monitoring the progress of radiofrequency ablation having an electrode adapted for percutaneous insertion into tissue at a tumor site and a radiofrequency power source communicating with the electrode to ablate tissue at the tumor site. An actuator communicating with the electrode provides vibration of the electrode along a first axis and a tissue imager measures axial displacement of tissue in a volume extending along a second axis perpendicular to the first axis, such displacement characterizing a shear wave directed along the second axis. An electronic computer receives displacement data from the tissue imager and executes a stored program to:
       (a) compute velocity of a shear wave along the second axis;   (b) detect a change in shear wave velocity along the second axis indicating a boundary between ablated and non-ablated tissue along the second axis;   (c) output data indicating a size of an ablation region along the second axis.       
 
         [0013]    It is thus an object of the invention to employ the measurement of shear waves propagated from an ablation electrode to detect the boundary and modulus of an ablation region thereby providing improved guidance to the physician during the ablation process. 
         [0014]    The tissue imager may be an ultrasonic imaging device directing an ultrasonic beam along the first axis. 
         [0015]    It is another object of the invention to provide improved lateral characterization of ablation volume when using an axially directed ultrasonic probe. 
         [0016]    The shear wave velocity may be computed by determining a time of maximum displacement for a variety of points along the second axis and deducing the velocity from the spatial separation of the points divided by differences in the times of maximum displacements for those points. 
         [0017]    It is thus an object of the invention to provide a method of determining shear wave velocity using an imaging system. 
         [0018]    The electronic computer may further use the velocity of the shear wave to compute the modulus of elasticity of the tissue along the second axis and may characterize the ablated or non-ablated tissue using the modulus of elasticity and wherein the output data indicates this characterization of the ablated or non-ablated tissue. 
         [0019]    It is thus an object of the invention to provide an alternative method of measuring tissue elasticity that may be used alone or combined with quasi-static elasticity measurement techniques. 
         [0020]    The electronic computer may output quantitative elasticity measurements of the ablated or non-ablated tissue. 
         [0021]    It is thus an object of the invention to provide a quantitative elasticity measurement that may be used alone or to calibrate or normalize elasticity measurements made by quasi-static techniques. 
         [0022]    The electronic computer may further execute the stored program to measure tissue displacement along the first axis at a first and second time corresponding to different displacements of the electrode by the actuator, and to detect displacement and deduce elasticity along the first axis indicating a boundary between ablated and non-ablated tissue along the first axis. This boundary information may combine the measurement of the boundary between ablated and non-ablated tissue along the second axis to provide output data indicating a multidimensional boundary of an ablated region. 
         [0023]    It is thus an object of the invention to better characterize the boundary of the ablation region. 
         [0024]    The electronic computer may further execute the stored program to deduce modulus of elasticity of the tissue along the second axis from the velocity of the shear wave and export the modulus of elasticity to regions of the tissue defined by the multidimensional boundary. The measured displacements and modulus of elasticity may be combined, for example iteratively, to provide refined tissue elasticity measurements for the regions. 
         [0025]    It is thus an object of the invention to improve quasi-static elasticity measurements. 
         [0026]    The electronic computer may further execute the stored program to measure shifts in sound speed deduced from an apparent changing displacement at a predetermined constant vibrational phase of the electrode to estimate tissue temperature during the ablation procedure. The velocity of the shear wave, used to compute modulus of elasticity of the tissue, may be used to correct this deduced temperature. 
         [0027]    It is thus an object of the invention to provide more accurate absolute temperature information. 
         [0028]    The actuator may provide the vibration through reciprocation of a free mass. 
         [0029]    It is thus an object of the invention to permit a handheld probe that may be easily manipulated by the physician for quasi-static compression and vibrated without attachment to a fixed support for shear wave generation. 
         [0030]    These particular objects and advantages may apply to only some embodiments falling within the claims, and thus do not define the scope of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0031]      FIG. 1  is a simplified block diagram of an RF ablation system for use with the present invention showing: insertion of an ablation probe into a tumor site of an in vivo organ, an ultrasonic imaging system for imaging of the organ and tumor site, and a control system for applying controlled quasi-static compression and shear wave inducing vibration to the tumor site through the RF ablation probe; 
           [0032]      FIG. 2  is a simplified depiction of the tumor of  FIG. 1  showing various modes of tissue vibration including an axial compression wave aligned with a vibration axis of the ablation probe and a shear wave traveling along a lateral axis perpendicular to the vibration axis; 
           [0033]      FIG. 3  is a simplified plot of quasi-static elasticity versus axial distance showing changes in the elasticity demarcating an ablation volume along the vibration axis according to prior art techniques; 
           [0034]      FIG. 4  is a plot of displacement versus time for a set of different laterally separated points, each point associated with a different curve; 
           [0035]      FIG. 5  is a plot of calculated shear wave velocities with respect to lateral distance from the electrode, showing a breakpoint in shear wave velocity demarcating a boundary of the ablated tissue for two different lesions; 
           [0036]      FIG. 6  is a flow chart of a program executed by the control system of  FIG. 1  implementing the present invention; 
           [0037]      FIG. 7  is a representation of an ablation volume showing regions of known modulus of elasticity that may be mapped to the remainder of the volume per the present invention; 
           [0038]      FIG. 8  is a fragmentary flowchart showing additional steps for identifying a vibration frequency dynamically during the ablation process; 
           [0039]      FIG. 9  is a fragmentary flowchart showing use of the modulus of elasticity to refine axial elastographic measurements; and 
           [0040]      FIG. 10  is a simplified diagram of a hand held electrode providing for desired shear wave generating movement. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0041]    Referring now to  FIG. 1 , an RF ablation probe  10  may be inserted percutaneously into a patient  12  to have its tip located at an ablation region  16  within an organ  18  such as the liver. 
         [0042]    Extensible electrode tines  14 , at the tip of the probe  10 , may grip the tissue of the ablation region and provide a greater area of electrical contact to conduct ablative current from a radiofrequency (RF) source  20 . Electrical energy from the RF source  20  is conducted through an insulated shaft of the probe  10  to the conductive tines  14  where ionic heating of the tissue kills tumor tissue. A large-area grounding pad  31  placed on the patient&#39;s skin provides a return path for this current. The tines  14  may include thermocouples for temperature measurements. 
         [0043]    RF ablation probes  10  of this kind having extensible tines and thermocouple sensors are well known in the art and readily available. The RF source  20  may be a Rita Model  30  electrosurgical device manufactured by Rita Medical Systems Inc., Mountain View, Calif., or other similar device. 
         [0044]    RF ablation probes  10  of this kind may also be a single  17 -gauge electrode, with a 2-3 cm long electrically-active region at the tip embedded in tissue. These electrodes offer the option of internally circulating chilled water during the ablation procedure, which prevents the charring of tissue adjacent to the electrically-active region of the electrode. The RF source  20  may also be a Valleylab Cool-tip™ ablation electrode manufactured by Valleylab, Colo., USA., or other similar device. 
         [0045]    During the ablation process, electrical current is conducted from the RF source  20  along line  26  to the ablation probe  10 . The temperature signal is returned along line  24  to be received by the RF source  20  and used to limit the temperature of ablation according to techniques well understood in the art. 
         [0046]    Imaging of the tissue and the tip of the probe  10  may be done using any ultrasonic imaging system, for example, the Siemens Antares Real Time Scanner manufactured by Siemens Incorporated of California. The ultrasonic imaging system in one embodiment includes an ultrasonic transducer  30  and ultrasound processing circuitry  42 . The ultrasonic transducer  30  may be, for example, a linear array transducer approximately forty millimeters wide, operating with dynamic focus over a forty percent bandwidth and producing signals at a center frequency of five megahertz. Generally, 1 D, 1.5 D, and 2 D transducers  30  are suitable for the image generation process. 
         [0047]    During insertion of the probe  10 , the ultrasound transducer  30  is placed against the skin of the patient and moved as needed for accurate visualization of the tip of the probe  10  with respect to the organ  18 . Generally, during the elastographic imaging to be described, the axis  32  of the ultrasound transducer  30  (along which the signals  36  propagate) is aligned as closely as possible to the axis  34  along which the probe  10  is inserted and directed to send the ultrasonic signals  36  into the ablation region  16 . The probe  10  stabilizes the organ  18  and prevents lateral shifting along axis  66 . 
         [0048]    During both insertion of the probe  10  and the ablation process, ultrasonic signal  36  travels into the tissue and is reflected at various tissue structures and boundaries. These echoes are detected by the ultrasound transducer  30  and conducted by cable  40  to the ultrasound processing circuitry  42 . The received signals are digitized at a sampling rate of approximately  50  megahertz and then processed according to techniques well known in the art, to produce an image, for example, a B-mode image, on display terminal  44 . The ultrasonic signal  36  extends generally along a plane incorporating axis  34  and defining an image plane of the B-mode image. 
         [0049]    The controller  46 , which may be a computer or logic controller programmed as described below, also receives temperature information via the RF source  20  along cable  50 . This temperature information may also be used to provide control signals to the RF source  20  from the controller  46  to further control the RF ablation as well as to generate and normalize thermographic images as will be described. Controller  46  also provides output lines  53  connected to a motorized carriage  52 , for example, using a motor and a lead screw to provide motion of the probe  10  along its insertion axis  34  in a controlled manner according to signals on output line  53  as will also be described. Other mechanisms for implementing the motorized carriage  52  may be used including those which apply a predetermined compressive force or low frequency oscillation as will be described below. The controller  46  may also communicate with display terminal  44  for displaying images and receiving user input commands. 
         [0050]    According to the invention, the digitized echo signals are further processed either within the ultrasound processing circuitry  42  (for example a computer) to produce an elastographic image  41 , or within controller  46 . In the former case, line  48  communicates signals from the controller  46  to the ultrasound processing circuitry  42  to coordinate generation of the elastographic image; in the latter case line  48  carries the control signals and digitized echo signals from the ultrasound processing circuitry  42  to the controller  46  for processing by the controller  46 . 
         [0051]    Referring now to  FIG. 2 , during a first and optionally only measurement period, the probe  10  is vibrated  60  along the axis  34  of the probe  10 . This vibration produces compression waves  62  traveling axially upward and downward from the ablation region  16  (only downward waves are shown for clarity) and shear waves  64  traveling laterally left and right along a lateral axis  66  substantially perpendicular to a vibration axis parallel to the axis  34  of the probe  10 . As is understood in the art, compression waves  62  involve a dilation and contraction of tissue indicated by arrows  68  along the axis  34  while the shear wave  64  involves a sliding of tissue with respect to neighboring tissue along axis  34  in shear indicated by arrows  70 . Generally both waves  62  and  64  propagate outward during vibration of the probe  10  albeit at different speeds. 
         [0052]    During this measurement period, the shear waves  64  generated by vibration  60  of the probe  10  are captured by rapid imaging of the tissue at a frequency substantially greater than that of the vibration  60  (or by “snapshot” imaging at evolving phases over many cycles of the vibration  60 ) to accurately characterize shear motion of the tissue over time. In the preferred embodiment, the vibration  60  of the probe  10  is in a range of 1 to 1000 Hz and preferably in the 1-50 Hz range with an amplitude of a fraction of a millimeter. As the vibration frequency decreases, the time-to-peak displacement increases, necessitating an increased time-duration for analysis. 
         [0053]    In the present invention, an optional second measurement period may be made in which quasi-static compression is used to provide at least two different states of tissue compression where the tissue is essentially at rest during the compression state. This quasi-static compression may occur at a frequency substantially less than 1 Hz with an amplitude of several millimeters and, in one embodiment, may be done by hand. In the present invention, the compression waves  62  are not employed. 
         [0054]    Referring now to  FIGS. 3 and 6 , the shear wave vibration  60  and the quasi-static compression may be performed at sequential non-overlapping times as indicated by process block  72 . At process block  74 , axial displacement may be determined from the quasi-static compression, and elasticity of different volume elements about the region  16  may be determined. Referring momentarily to  FIG. 2 , as has been described in U.S. Pat. No. 7,166,075 incorporated by reference above, this axial displacement may be used to determine tissue elasticity about the ablation region  16  and, in particular, along the axis  34 . An analysis of elasticity versus axial distance per process block  76  will show a discontinuity  78  demarcating a boundary  81  between the stiffer ablated tissue of ablation region  16  and the softer unablated tissue  80  along each ray line of the ultrasound signal  36 . This approach may be used to define a boundary  81  (shown in  FIG. 5  as will be described below) of the ablation region  16  and is particularly accurate for axial boundaries. 
         [0055]    Referring to  FIGS. 2 and 6 , in addition, the displacement of the shear waves  64 , may be measured, as indicated by process block  82 , and may be used to deduce a shear wave velocity. 
         [0056]    Referring now to  FIG. 4 , this shear wave velocity may be obtained by monitoring series of displacement profiles  84   a - g  taken at each of a set of laterally displaced points along lateral axis  66 . Each displacement profile  84   a - g  measures time-evolving axial displacement at that point. These displacement profiles  84   a - g  are analyzed to find the time to peak displacement (TTP) indicated by points  86   a - g  respectively. 
         [0057]    The TTP data indicates the absolute time of passage of a crest of the shear wave across the different points and thus can be used to deduce shear wave velocity. Generally, the shear wave velocity is related to Young&#39;s modulus by the following equation: 
         [0000]    
       
         
           
             
               
                 
                   
                     v 
                     s 
                   
                   = 
                   
                     
                       E 
                       
                         3 
                          
                         
                             
                         
                          
                         ρ 
                       
                     
                   
                 
               
               
                 
                   ( 
                   1 
                   ) 
                 
               
             
           
         
       
       
         
           
             (a) where: 
             (b) v s  is the shear wave velocity; 
             (c) E is Young&#39;s modulus; 
             (d) and ρ is the material density. 
           
         
       
     
         [0062]    Referring to  FIG. 5 , a plot  90  of time to peak displacement at each point versus lateral location of the point indicates by its slope the inverse of shear wave velocity. The plot  90  will show a breakpoint  92  at the boundary  81  of the ablation region  16  caused by a transition from stiffer to softer tissue and a resulting change in shear wave velocity. Generally, the ablated tissue within the ablation region  16  will be stiffer as a result of processes such as coagulation. 
         [0063]    In addition to defining a boundary  81  of the ablated tissue, the slope of plot  90  will show changes in the absolute stiffness of the ablation region  16  during the ablation process as it evolves, for example, from plot  90 ′ earlier in the ablation process. In this example, plot  90 ′ shows both an earlier boundary  81 ′ and a slightly more elastic ablation region. The ability to extract elasticity data from plots  90  and  90 ′, in addition to the discontinuity data, provides additional insight into the ablation process. 
         [0064]    The detection of the boundary  81  of the ablated tissue operates synergistically with the determination of Young&#39;s modulus for the regions by allowing data of the regions to be combined for a more robust measurement of Young&#39;s modulus in each region. For example, after determination of the boundary  81 , Young&#39;s modulus may be recalculated separately inside and outside the boundary  81  to provide a more accurate measurement of Young&#39;s modulus for these regions. Simulations have suggested that Young&#39;s modulus may be accurately determined for the different regions in this fashion per the following Table I. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE I 
               
               
                   
               
               
                   
                 Measured 
                   
                 Measured 
                 Modulus Ratio 
               
               
                 Actual 
                 Modulus 
                 Actual Modulus 
                 Modulus Of 
                 of Lesion to 
               
               
                 Modulus 
                 Of 
                 Of Surrounding 
                 Surrounding 
                 Surrounding 
               
               
                 Of Lesion 
                 Lesion 
                 Tissue 
                 Tissue 
                 Tissue 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 10 
                 11.317 
                 10 
                 10.523 
                 1:1 
               
               
                 20 
                 26.938 
                 10 
                 10.157 
                 2:1 
               
               
                 50 
                 57.293 
                 10 
                 8.314 
                 5:1 
               
               
                 100 
                 114.19 
                 10 
                 10.523 
                 10:1  
               
               
                   
               
             
          
         
       
     
         [0065]    This process of extracting a breakpoint  92  and thus a boundary of the ablated tissue, and in deducing Young&#39;s modulus of the different ablation regions, is represented in  FIG. 6  as process block  94 . 
         [0066]    Referring still to  FIG. 6 , the shear wave deduced boundary  81  and extraction of Young&#39;s modulus from the shear wave may be used alone or may be combined, as indicated by process block  96 , with the data collected in quasi-static compression (per process blocks  74  and  76 ) to provide an improved description of the boundary  81 . Generally this combination may use a weighting of boundaries  81  determined at process blocks  76  and  94  where data from process block  94  is given a greater weight for the lateral boundary along lateral axis  66  and the data from process block  76  is given greater weight for the axial boundary along axis  34 . 
         [0067]    At optional process block  98 , the Young&#39;s modulus data may be used to refine the elasticity measurements as well as the boundaries themselves. Referring to  FIGS. 7 and 9 , following the extraction of Young&#39;s modulus at process block  96 , Young&#39;s modulus will be well characterized in lateral bands  112  to the sides of the ablation region  16  as shown in  FIG. 7 . The data of the bands  112  may be imputed to the remainder of the ablation region  16  within the boundary  81  of ablated tissue of the ablation region  16  and as indicated by process block  114  of  FIG. 9 . 
         [0068]    At process block  116 , elasticity measurements using quasi-static elasticity may then be corrected using this elasticity information from Young&#39;s modulus so as to conform to the measurement approaches. This correction can occur in a number of ways. First, the modulus information may be used to provide a calibration of the elasticity measurements obtained by quasi-static methods by matching the known Young&#39;s modulus data to the elasticity data obtained in the same region. Alternatively, the two elasticity measurements may be averaged together or otherwise combined. In yet another approach, the Young&#39;s modulus data may be used to provide a more accurate model of the stress field implicit in the quasi-static elasticity calculation. 
         [0069]    Referring still to  FIG. 6 , data from the process blocks  94 ,  96 , and/or  98  may be output individually or together in graphical form or as quantitative numeric outputs. 
         [0070]    Referring again to  FIG. 6 , during predetermined intervals in the movement of the electrode at process block  72 , when the electrode is at a “baseline” position and generally static, sound speed measurements of the tissue may be made at process block  102 . Such sound speed measurements may be made by noting apparent tissue displacement from earlier measurements caused by changes in the sound speed through the tissue as described in U.S. Pat. No. 7,166,075 cited above to provide temperature data as indicated by process block  104 . This temperature data may be output, as indicated by process block  106 , as a numeric output associate with the ablated tissue, for example and average or lowest temperature within the boundary  81 , or as an image, for example, a color overlay on top of an image output at process block  100 . This data is presented to provide guidance to the physician undertaking the ablation as to the temperature of the tissue and the progress of the ablation and may be further calibrated by temperature sensors on the probe  10  itself. Knowledge of Young&#39;s modulus from the shear wave measurements permits more accurate temperature measurements using this process. 
         [0071]    Referring now to  FIG. 8 , process block  72 , as described before, may provide for different measurement periods during which the probe  10  is moved in quasi-static compression or shear-wave inducing vibration. The measurement of shear displacement at process block  82  permits a dynamic optimization of the vibration speed through the addition of process block  108 . At process block  108 , the amplitude of the shear wave  66  from process block  82  may be monitored and based on that monitoring a new vibration frequency may be communicated to process block  72  so as to optimize the frequency for the particular tissue type. Process block  108  may affect, for example, a slight perturbation in frequencies to deduce a frequency at which shear waves are best measured. 
         [0072]    Referring now to  FIG. 10 , in one embodiment of the invention the quasi-static movement of the probe can may be provided manually by the physician and the shear wave induced vibrations may be provided by means of a inertial mass  120  attached to a distal end of the probe  10  via an actuator  122 , for example, a solenoid, small motor, or piezoelectric actuator. Activation of the actuator  122  by pulses over lines  53  provides the necessary shear wave inducing movement of the probe  10  and triggers measurement of the peak displacements. Impulse or sinusoidal motions may be readily generated in this manner at a range of desired frequency. A cushioned outer surface  124  may be provided to decouple the vibration from the physician&#39;s hand. 
         [0073]    It is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein, but include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims.