Patent Publication Number: US-7217242-B2

Title: Ultrasonic method for visualizing brachytheraphy seeds

Description:
REFERENCE TO RELATED APPLICATIONS 
   This application claims the benefit of U.S. Application Ser. No. 60/363,452, filed Mar. 12, 2002. 

   BACKGROUND OF THE INVENTION 
   The present invention was made in connection with a grant from the National Institute of Health Grant R21 CA88231 
   Permanent interstitial implantation of iodine or palladium radioactive seeds is currently used for the treatment of prostate cancer. In connection with the implantation of such brachytherapy seeds a transrectal ultrasound (TRUS) examination of the prostate is used in the operating room. The TRUS probe is mounted on a fixture that contains a needle guidance template, which rests against the perineum and incorporates detents enabling the probe to be introduced into or withdrawn from the rectum in 5-mm steps. Scans are oriented in a transverse plane perpendicular to the probe axis. The fixture is advanced into the rectum until the seminal vesicles are imaged and scans are performed in planes separated by 5 mm as the probe is withdrawn. During the scans, the prostate is constrained against movement by position-fixing needles. 
   TRUS images are ported through a standard output jack to a laptop computer on which treatment-planning software is run. Such software may, for example, be VariSeed provided by Varian Medical Systems, Inc. (VMSI), Charlottesville, Va. This treatment planning software generates an image of available and optimal needle locations, which are fixed by the template used for needle guidance. The oncologist demarcates the prostate in each scan plane and prescribes a radiation dose for the glad as a whole. The planning software then presents a set of suggested seed positions in each scan plane, which the oncologist can accept or reject based on isodose distributions plotted by the software for whatever seed positions are chosen. 
   The software bases the isodose distributions on seed locations in the 3-D volume spanned by the set of scan planes in the planning set. Immediately after planning is completed, seed-implantation needles are loaded with the radioactive seeds and plastic spacer seeds in a manner that places radioactivity at the specified depths, corresponding to the scan planes, along each needle position. The spacers are not visible in ultrasonic or x-ray computed tomography (CT) images. Loaded needles are then inserted into the prostate via the perineum through the template holes that match the needle positions depicted on the planning-software image. Dosimetric evaluation subsequently is performed using post-implant CT imaging. Traditionally, post-implant CT scans are performed within two weeks of implantation, but in some cases they are performed within 24 hours of implantation. 
   In some cases, the CT scans show that the actual location of implanted seeds differs from their planned locations. Studies by Potters, et al., have shown that 30% of prostate brachytherapy procedures result in a dose to 90% of the prostate that is less than the prescribed dose. [Potters, et al., Int. J. Radiat. Oncol. Biol. Phys., 50:605–614, 2001] Studies by Stock, et al., showed that 32% of under-dosed patients have biochemical failure (as evidenced by a rise in the blood level of prostate-specific antigen (PSA)) within four years, where as only 8% of properly dosed patients have biochemical failure. [Stock, et al, Int. J. Radiat. Oncol. Biol. Phys., 41:101–108, 1998] The conventional B-mode ultrasound images generated at the time of the procedure do not allow adequate visualization of the placed seeds because of clutter, shadowing and the loss of echo signals due to seed angulation. Clutter often increases immediately during the procedure from hemorrhage and edema caused by the trauma of needle insertion. 
   It is an object of the present invention to provide improved imaging of implanted seeds during the implantation process with the result that seed implantation errors can be corrected, for example by implantation of additional seeds during the procedure. 
   SUMMARY OF THE INVENTION 
   In accordance with a first embodiment of the invention there is provided a method for ultrasonically imaging implanted therapeutic seeds in tissue. The method includes determining acoustic reflection properties of the seeds in response to acoustic signals from an ultrasonic probe having selected signal characteristics. The selected signal characteristics may include a scanned beam to create two-dimensional images of the tissue and embedded seeds. The tissue and the seeds are insonated using acoustic signals having the selected signal characteristics and reflected acoustic signals are received from the tissue and the seeds. The reflected acoustic signals are analyzed using a correlation algorithm to generate an image of the tissue and the seeds with image portions corresponding to the seeds enhanced by the correlation algorithm. 
   In a preferred arrangement of the first embodiment, acoustic reflection properties are determined by isolating at least one of the seeds in an acoustically transparent medium and acquiring reference reflected radio-frequency (RF) echo signals from the seeds in response to acoustic signals from the same ultrasonic probe at same settings. The analyzing may be done by performing a two-dimensional correlation analysis of two-dimensional RF echo signals of scans of embedded seeds in the prostate with the two-dimensional reference RF echo signals. The analysis may use a normalized or an unnormalized correlation function. 
   In accordance with a second embodiment of the invention there is provided a method for ultrasonically imaging implanted brachytherapy seeds in tissue. First, the tissue is insonated in a two dimensional scanning mode using acoustic signals from an ultrasonic probe having selected signal characteristics and reflected acoustic signals are received from the tissue and the seeds. Second, the tissue containing the seeds then is mechanically deformed and the tissue and the seeds are insonated again using the same acoustic signals having the selected signal characteristics following the mechanical deformation, and reflected acoustic signals again are received from the tissue and the seeds. Correlation analysis is applied on the first and second reflected acoustic signals on a window-by-window basis and, a display of a correlation map of the first and second reflected signals is generated and displayed. The seeds typically exhibit a higher correlation value than the tissue, especially if the deformation is large. 
   In a preferred arrangement of the practice of the second embodiment reflected signals are received by acquiring RF signals for the first and second reflected acoustic signals after high strains are applied that are sufficient to decorrelate signals from tissue that is not mechanically stiff compared to rigid metallic seeds while retaining the correlation of signals from mechanically much stiffer seeds. Either a one-dimensional or a two-dimensional correlation analysis (using either unnormalized or normalized correlation function) of the acquired RF signals (or its envelope) may be performed. 
   In accordance with a third embodiment of the invention there is provided a method for ultrasonically imaging implanted therapeutic seeds in tissue. The method includes determnining at least one mechanical resonance frequency for the seeds. The implanted seeds are stimulated with a first acoustic signal having a frequency corresponding to its resonance frequency to cause the seeds to vibrate at the resonance frequency. The tissue and the seeds are imaged using second acoustic signals and a Doppler method is used to sense the vibratory motion of the seeds. The second acoustic signals have a frequency higher than the resonance frequency. 
   In accordance with a preferred practice of the third embodiment the mechanical resonance frequency is determined by embedding a sample seed of the seed type of interest in an appropriate medium that is mechanically equivalent to a prostate gland, and placing the embedded seed in the overlapping fields of two transducers. A first transducer is driven with signals having various frequencies and the response of the second transducer is observed to determine signal peaks indicating resonance. 
   The stimulating may comprise insonating the tissue along a first axis and the imaging may comprise insonating the tissue along a second axis, which may be different from or the same as the first axis. Alternately, an array can be arranged with a central, high-frequency linear-array or mechanical-scanning portion which images the seed—or the gland that contains the seed—and two larger, unfocussed elements on either side or an element that surrounds the scanning array that provides the resonance-stimulating ultrasound. In this case, the two axes would be the same. 
   For a better understanding of the present invention, together with other and further objects, reference is made to the following description, taken in conjunction with the accompanying drawings, and its scope will be pointed out in the appended claims. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a drawing illustrating an arrangement that can be used to practice a first embodiment of the invention. 
       FIG. 2  is a cross-sectional view of a typical brachytherapy implant seed containing radioactive palladium. 
       FIG. 3  is a drawing illustrating the acquisition of reflective characteristic data for a brachytherapy seed in connection with practice of the embodiment of  FIG. 1 . 
       FIG. 4  illustrates the practice of a second embodiment of the invention. 
       FIG. 5  illustrates the practice of a third embodiment of the invention. 
       FIG. 6  illustrates a method for determining resonance frequency of brachytherapy seeds in connection with practice of the third embodiment of the invention. 
   

   DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION 
   A first embodiment of the method of the present invention will be described with reference to  FIGS. 1 through 3 . As used herein, the term therapeutic seeds includes brachytherapy seeds, which are well known, and other seeds of similar dimension which may be used for delivering a therapeutic agent to a localized region. Shown in  FIG. 2  is a typical palladium seed  18  currently used in connection with brachytherapy of the prostate. The seed includes a thin cylindrical shell  26  of titanium, having overall dimensions of 4.5-mm length and 0.8-mm diameter. Different types of radioactive palladium and iodine seeds have different amounts of interior space and solid material. The illustrative palladium seed has graphite plugs  30 ,  32  at each end of the interior space  28 , that is coated with radioactive palladium. The seed also contains a central lead plug  34 , which is provided to enhance visibility on post-implantation CT scans. Iodine seeds come in a wide variety of configurations, but all seeds have the same external cylindrical dimensions. Ultrasonic reflections from the seed  18  are specular, and tilting the seed axis away from perpendicular to the beam markedly reduces the amount of reflected energy returned to the transducer. The curvature of the seed causes it to be imaged as a fine-wire profile of the incident beam. The seed has indented cup ends, as shown in  FIG. 2 , which typically trap air, which may confound the ultrasonic properties of the seeds. 
   Referring to  FIG. 3 , there is shown an arrangement for obtaining an ultrasound echo “signature” of a brachytherapy seed  18 . A transrectal ultrasonic probe  10 , having a radiation aperture  14  is immersed in water  46  contained in a vessel  44 . A brachytherapy seed  18 , or a non-radioactive replica thereof, is placed within an acoustically transparent medium  50  immersed in water  46 . An absorbent medium  48  supports transparent medium  50 . RF echoes from seed  18  are digitally acquired in two dimensions by scanning the beam in the acoustically transparent medium using the same signal characteristics, such as settings of power, time-gain control, fixed gain, and so forth, that are used for brachytherapy procedures. This procedure acquires an acoustic signature for the brachytherapy seed  18  for use in subsequent procedures. 
   Referring to  FIG. 1  there is shown an arrangement useful for practice of a first embodiment of the method of the present invention. A transrectal probe  10  having an aperature  14  is inserted in the rectal canal  12  of a patient in an arrangement to insonate prostate  16  in which brachytherapy seeds  18  have been placed using an insertion device  20 . RF data from the transrectal ultrasound device  10  is acquired by a computer  22  having a display  24 . During a seed implantation procedure digital RF echo signal data from transrectal ultrasound probe  10  are acquired in two dimensions by the computer by scanning the beam used to image the seed bearing prostate  16 . Computer  22  performs a two-dimensional correlation analyses between reference signature signals from an isolated seed and the signals from the entire prostate scan plane and thereafter displays correlation maps on display  24 . Correlations can be performed using RF or envelope-detected signals, and the results can be computed as either normalized or unnormalized correlation coefficients. Depending on the processing option, the displayed correlation maps show either localized bright spots or a distinctive pattern at the apparent location of implanted seeds. 
   A suitable normalized correlation function is as follows: 
   
     
       
         
           
             
               
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   In connection with obtaining good correlation results using RF data it was found to be helpful to provide jitter correction. In connection with using unnormalized correlation values, a depth dependent compensation was applied to the data using an empirical value of 0.5 dB per MHz-cm for the attenuation coefficient. Unnormalized correlation analysis using envelope detected RF signals also depicted the seeds as bright areas which was similar to results from RF correlation analyses. Normalized correlation analyses using the echo signal envelope produces sharp bright spots surrounded by distinctive pattern where implanted seeds are present. 
   Referring to  FIG. 4  there is shown a second embodiment of the method of the present invention. In connection with the second embodiment a transrectal probe  10  is likewise used for providing a display of the prostate  16  and implanted seeds  18  during an implantation procedure. In the method illustrated in  FIG. 4  a reference measurement is made using transrectal ultrasound probe  10  to obtain data representing acoustic reflections from prostate  16  and implanted seed  18 . Thereafter mechanical stress is applied to the tissue, compressing prostate  16  and the measurement of echo signals is repeated. One method for applying mechanical stress is to displace the probe toward the prostate. Another technique, illustrated in  FIG. 4 , is to fill a balloon  36  surrounding probe  10  with fluid to compress the surrounding tissue. In a preferred embodiment, three or more measurements may be made of the acoustic reflections from prostate  16  and implanted seeds  18  using varying amounts of applied mechanical stress. 
   The second embodiment is based on cross-correlation analyses of echo signals from tissue before and after a high-strain deformation. In typical implementations of elastography applied to tissue, compression and deformation must be small in order to prevent decorrelation. In contrast, because the brachytherapy seeds are extremely stiff compared to tissue, they do not measurably distort upon compression, and large deformations beneficially decorrelate tissue signals, while retaining the correlation in signals from undeformed implanted seeds. At excessive strains, seeds may undergo complex motion, including out of plane motion and rotation, which can reduce correlation. The transducer axis is approximately perpendicular to the long axis of the seed. At least one RF frame is acquired before compression and one or more RF frames are acquired after each compression step. A one or two-dimensional correlation analysis between pre and post-deformation RF echo signals or their envelope signals may be applied to quantify seed displacement and to evaluate echo signal shape changes during displacement. The resultant correlation maps can then be displayed with an envelope detected scan image for comparison. The soft tissue surrounding the seed implant will decorrelate thus displaying the seeds as regions with a high correlation coefficient value. 
   Referring to  FIGS. 5 and 6  there is shown a third embodiment of the method of the present invention. The third embodiment is based on determining the resonance characteristics of the implanted seeds with respect to acoustic signals. The resonance vibration of excited seeds can be detected and imaged using Doppler ultrasound. 
   Referring to  FIG. 6  there is shown an experimental determination of the natural resonance frequencies of palladium seeds with a resonance ultrasound spectroscopy apparatus. In this apparatus a small seed-simulating sample  18  is embedded in suitable material  58  having mechanical properties equivalent to prostate tissue and placed in the overlapping fields of a lower frequency resonance stimulating piezo electric transducers  60  and a higher frequency imaging transducer  62 . By sweeping frequency of signals applied to the resonance stimulating transducer and detecting the frequencies at which Doppler components reach maxima in the signal received by the higher frequency transducer, it is possible to determine mechanical resonance frequencies of the sample  18 . 
   In the apparatus indicated in  FIG. 6 , sample  18  was placed within a section  56  of simulated tissue, such as animal liver tissue and mounted on an ultrasound absorbing rubber block  54  placed at the bottom of a vessel  52 . Water  58  is placed in the vessel sufficient to cover the radiating portions of transducers  60  and  62 . When simulated seed  18  is excited with ultrasound signals at a resonance frequency, strong Doppler signals were detected through the receiving transducer. Standard simulated seeds have shown a resonance at about 1 MHz. This frequency is far below the range of conventional diagnostic ultrasound scanners used for prostate imaging. The resonant frequency of the seeds can also be determined with a Resonant Ultrasound Spectroscopy apparatus. 
     FIG. 5  illustrates a procedure for imaging a prostate  16  and implanted seeds  18  in a patient. Images are acquired by transrectal ultrasound unit  10  and supplied to computer  22  having display  24 , after seeds  18  have been implanted in prostate  16  using insertion device  20 . During the imaging process a transmitter  40  provides a signal to low frequency transducer  38 , such as an airbacked therapeutic transducer, which insonifies prostate  16  with acoustic signals at a resonance frequency of seeds  18 . The signals from transducer  38  cause seeds  18  to mechanically resonate, which should be easily detected using color/power Doppler detection of the output of transrectal ultrasound device  10 . It is believed that the insonification angle of the low frequency resonant acoustic signals provided to prostate  16  should be at an angle, for example 45 degrees, away from the resonance-stimulating transducer axis. It has been experimentally determined that a relatively low intensity of the ultrasound provided by transducer  38 , for example an intensity of about 13.5 mW per square cm., provides adequate resonant excitation of seeds  18  to enable a Doppler detection to occur which effectively enhances the imaging of the seeds on display  24 . 
   While there have been described what are believed to be the preferred embodiments of the invention, those skilled in the art will recognize that other and further changes and modifications may be made thereto without departing from the spirit of the invention, and is intended to claim all such changes and modifications as fall within the true scope of the invention.