Patent Application
20130303906
All publications, including patents and patent applications, mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.
The present invention generally relates to ultrasound treatment of urinary stones. More specifically, the present invention relates to using a combination of Lithotripsy and Histotripsy to fractionate and erode urinary stones.
Histotripsy and Lithotripsy are non-invasive tissue ablation modalities that focus pulsed ultrasound from outside the body to a target tissue inside the body. Histotripsy mechanically damages tissue through cavitation of microbubbles, and Lithotripsy is typically used to fragment urinary stones with acoustic shockwaves.
Histotripsy is the mechanical disruption via acoustic cavitation of a target tissue volume or tissue embedded inclusion as part of a surgical or other therapeutic procedure. Histotripsy works best when a whole set of acoustic and transducer scan parameters controlling the spatial extent of periodic cavitation events are within a rather narrow range. Small changes in any of the parameters can result in discontinuation of the ongoing process.
Histotripsy requires high peak intensity acoustic pulses which in turn require large surface area focused transducers. These transducers are often very similar to the transducers used for Lithotripsy and often operate in the same frequency range. The primary difference is in how the devices are driven electrically.
As shown by
In comparison, each negative and positive cycle of a Histotripsy pulse grows and collapses the bubbles, and the next cycle repeats the same process. The maximal sizes of bubbles reach approximately tens to hundreds of microns. These micron size bubbles interact with a tissue surface to mechanically damage tissue.
In addition, Histotripsy delivers hundreds to thousands of pulses per second, i.e., 100-1 kHz pulse repetition frequency. Lithotripsy only works well within a narrow range of pulse repetition frequency (usually 0.5-2 Hz, which is the current limit in the United States and in Europe, however higher limits up to 4-5 Hz are contemplated). Studies show that the efficacy and efficiency of Lithotripsy decreases significantly when the pulse repetition frequency is increased to 10-100 Hz. The reduced efficiency is likely due to the increased number of mm size bubbles blocking the shock waves and other energy from reaching the stone.
Prior art treatment of nephrolithiasis (urinary stones) included early generation hydroelectric spark gap Lithotripters, such as the Donier HM3, which targeted a large treatment area, covering a sizeable portion of the kidney. For this reason, treatment success rates were high without the need for precise image guidance, yet substantial damage to the kidney tissue within the large focal volume also occurred. Subsequent Lithotripter development was focused on reducing renal injury by decreasing the focal volume. Some of the current third generation Lithotripters use piezoelectric (PZT) transducers, such as the Richard Wolf Piezolith 3000. The PZT transducer focused ultrasound in a small treatment region. Fluoroscope and ultrasound imaging can be utilized to target the urinary stones prior to and during treatment. By virtue of the smaller focus, the newer generation Lithotripters have reduced collateral tissue damage, but at the expense of success rates. Inaccuracies of targeting and respiratory motion of the kidneys decrease the fraction of pulses that directly impact the targeted stone.
Histotripsy also uses focused PZT transducers but has a different driving system. It uses ultrasound imaging to target the focused ultrasound to the stone and monitor the treatment in real time. The bubble clouds generated by Histotripsy show as a temporally changing hyperechoic zone on ultrasound images. The real-time guidance makes it possible to track the stone movement and adjust the focus position, thus further reducing possible collateral tissue damage. As described earlier, stone fragments produced by lithotripter vary from small granules less than 1.0 mm diameter to macroscopic fragments with diameters significantly greater than 1 mm (as shown in
Shockwave Lithotripsy is favorable in that it is a short (˜30 minute) outpatient procedure that requires only IV sedation in the vast majority of patients. Post-operative pain generally resolves within 1-2 days. Ureteroscopy and percutaneous nephrolithotomy generally require general anesthesia. Although ureteroscopy is an outpatient procedure, patients often suffer with pain and discomfort from a ureteral stent for 4-7 days after treatment. Disadvantages of Lithotripsy include a stone free rate of ˜65% percent 4 weeks after treatment (compared with 90-95% stone free rate in patients having percutaneous and ureteroscopic procedures) and the necessity and occasionally discomfort of passing stone fragments following treatment. Furthermore, urinary stones fragmented using shockwave Lithotripsy can remain up to several mm in size and include sharp or jagged edges that make them difficult and painful to pass through the urinary tract.
In some embodiments, a Lithotripsy-Histotripsy system is provided comprising a first therapy transducer configured to deliver Lithotripsy therapy to a target, a second therapy transducer configured to deliver Histotripsy therapy to the target, and a control system configured to switch between delivering Lithotripsy therapy from the first therapy transducer to delivering Histotripsy therapy from the second therapy transducer.
In some embodiments, the first therapy transducer is configured to apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 10-25 MPa, a peak positive pressure of more than 10 MPa, a pulse length of 1 cycle, a duty cycle less than 0.1%, and a pulse repetition frequency of less than 2 Hz.
In other embodiments, the second therapy transducer is configured to apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 8-40 MPa, a peak positive pressure of more than 10 MPa, a pulse length shorter than 50 cycles, a duty cycle of less than 5%, and a pulse repetition frequency of less than 5 KHz.
In some embodiments, the Lithotripsy-Histotripsy system further comprises an imaging system. In some embodiments, the imaging system comprises a fluoroscopic imaging system. In other embodiments, the imaging system comprises an ultrasound imaging system. In additional embodiments, the imaging system comprises a combination fluoroscopic and ultrasound imaging system. The imaging system can be configured to target and track a urinary stone in a patient.
In another embodiment of a Lithotripsy-Histotripsy system, the system comprises a multi-mode therapy transducer configured to deliver Lithotripsy therapy and Histotripsy therapy to a target, and a control system configured to switch between delivering Lithotripsy therapy from the multi-mode therapy transducer to delivering Histotripsy therapy from the multi-mode therapy transducer.
In some embodiments, the multi-mode therapy transducer is configured to apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 10-25 MPa, a peak positive pressure of more than 10 MPa, a pulse length of 1 cycle, a duty cycle less than 0.1%, and a pulse repetition frequency of less than 2 Hz, so as to deliver Lithotripsy therapy to the target.
In other embodiments, the multi-mode therapy transducer is configured to apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 8-40 MPa, a peak positive pressure of more than 10 MPa, a pulse length shorter than 50 cycles, a duty cycle of less than 5%, and a pulse repetition frequency of less than 5 KHz, so as to deliver Histotripsy therapy to the target.
In some embodiments, the Lithotripsy-Histotripsy system further comprises an imaging system. In some embodiments, the imaging system comprises a fluoroscopic imaging system. In other embodiments, the imaging system comprises an ultrasound imaging system. In additional embodiments, the imaging system comprises a combination fluoroscopic and ultrasound imaging system. The imaging system can be configured to target and track a urinary stone in a patient.
A method of treating urinary stones is also provided, comprising applying Histotripsy therapy to generate a bubble cloud, positioning the bubble cloud on a urinary stone, applying Lithotripsy therapy to generate a shock wave to fractionate the urinary stone into macroscopic urinary stone particles, and applying Histotripsy therapy to the macroscopic urinary stone particles to erode the macroscopic urinary stone particles.
In some embodiments, the positioning step further comprises positioning the bubble cloud on a urinary stone under imaging guidance. In other embodiments, the positioning step further comprises positioning the bubble cloud on a urinary stone under ultrasound imaging guidance. In additional steps, the positioning step further comprises positioning the bubble cloud on a urinary stone under fluoroscopic and ultrasound imaging guidance.
In some embodiments, the applying Histotripsy therapy steps comprise applying Histotripsy therapy with a multi-mode transducer. In other embodiments, the applying Lithotripsy therapy step comprises applying Lithotripsy therapy with the multi-mode transducer.
In one embodiment, the applying Histotripsy therapy steps comprise applying Histotripsy therapy at a first pulse repetition frequency, wherein the applying Lithotripsy therapy step comprises applying Lithotripsy therapy at a second pulse repetition frequency, the method further comprising interleaving Histotripsy therapy and Lithotripsy therapy with virtually no change in the first and second pulse repetition rates.
Another method of treating a target tissue is provided, comprising delivering a first Lithotripsy pulse to the target tissue, delivering a sequence of Histotripsy pulses to the target tissue after the first Lithotripsy pulse, and delivering a second Lithotripsy pulse to the target tissue after the sequence of Histotripsy pulses, wherein the first and second Lithotripsy pulses are separated in time by a pulse repetition frequency. In some embodiments, the target tissue is a urinary stone.
In some embodiments, the method further comprises delivering a sequence of Histotripsy pulses immediately prior to delivering the first Lithotripsy pulse to the target tissue to suppress cavitation. In additional embodiments, the method further comprises delivering a sequence of Histotripsy pulses immediately prior to delivering the second Lithotripsy pulse to the target tissue to suppress cavitation.
In some embodiments, the method further comprises delivering a spatially-varying cavitation suppressing Histotripsy field to allow cavitation to occur within the target tissue while suppressing cavitation outside the target tissue.
In addition to imaging tissue, ultrasound technology is increasingly being used to treat and destroy tissue. In medical applications such as Histotripsy, ultrasound pulses are used to form cavitational microbubbles in tissue to mechanically break down and destroy tissue. In Lithotripsy procedures, ultrasound pulses are used to form acoustic shockwaves that break up urinary stones into smaller fragments. Particular challenges arise in using Lithotripsy to break up urinary stones, including failing to break stones down into sizes small and smooth enough to pass comfortably, as well as visualizing and tracking the stones within the patient. The present invention describes several embodiments of devices and methods for treating urinary stones or other calculi including, but not limited to biliary calculi such as gall stones, particularly through the combination of Histotripsy and Lithotripsy therapy in a single procedure.
Despite the difference between Lithotripsy and Histotripsy, the aperture size, focal characteristics, and piezoelectric materials of the relative transducers are similar in both types of therapy. Thus, a single transducer can be driven in both Histotripsy and Lithotripsy modes. This dual-mode Histotripsy and Lithotripsy system can be configured to treat, fractionate, and dissolve urinary stones in patients suffering from urinary stones.
In some embodiments, a multi-mode Lithotripsy-Histotripsy device is configured to shift virtually instantaneously (electronic speeds) from a Lithotripsy shock wave mode (L-mode) to the Histotripsy “soft” erosion mode (H-mode). The primary advantages of a dual mode Lithotripsy-Histotripsy system are: (1) ability to rapidly fractionate urinary stones into smaller gravel like fragments in L-mode, which can be reduced in size more quickly by H-mode erosion (erosion is effectively a surface phenomena) because of the greatly increased surface area of the Lithotripsy fragments; (2) easy image guidance and initial focal targeting by utilizing the Histotripsy bubble cloud.
Despite the differences between Lithotripsy and Histotripsy, the aperture size, focal characteristics, and piezoelectric materials of the transducers needed for each system are similar. The circuitry and generators required to drive these transducers can be configured to drive a single transducer in both H and L-modes, or alternatively, can be configured to drive separate H-mode and L-mode transducers.
In some embodiments, Histotripsy transducers can apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 8-40 MPa, a peak positive pressure of more than 10 MPa, a pulse length shorter than 50 cycles, a duty cycle between approximately 0.1% and 5% and in some embodiments less than 5%, and a pulse repetition frequency of less than 5 KHz. In other embodiments, Lithotripsy transducers can apply acoustic pulses that operate at a frequency between approximately 50 KHz and 5 MHz, having a pulse intensity with a peak negative pressure of approximately 10-25 MPa, a peak positive pressure of more than 10 MPa, a pulse length of 1 cycle, a duty cycle less than 0.1%, and a pulse repetition frequency of less than 2 Hz.
Imaging system 306 can provide real-time imaging guidance of the patient while during L-mode and H-mode therapy. In the embodiment of
Control system 308 can include all the necessary drive electronics and signal generators necessary to drive therapy transducers 302 and 304 in both L-mode and H-mode. For example, the drive electronics and signal generators of control system 308 should be configured to drive therapy transducers 302 and/or 304 according to the parameters set forth in Table 1 above for both H-mode and L-mode transducers. The control system 308 can including a switching mechanism configured to instantaneously switch operation of the system between an L-mode and an H-mode, or to allow for simultaneous operation in H and L-modes. Control system 308 can further include a CPU or computer configured to set treatment parameters, receive and process imaging information, and direct L-mode and H-mode therapy according to a surgical plan. The therapy transducer drive electronics may be configured to generate both types of pulses as a pulse sequence in addition to Histotripsy pulses that optimize Lithotripsy pulses by suppressing and enhancing cavitation. One therapy transducer may have the capability of focusing outside of the target are to suppress cavitation and thereby provide active protection of tissues outside of the target area. This technique is more fully described in U.S. patent application Ser. No. 12/121,001, filed May 15, 2008, now U.S. Pat. No. 8,057,408, titled “Pulsed Cavitational Ultrasound Therapy.”
Methods of using a Lithotripsy-Histotripsy system, such as the system described herein, will now be discussed. The choice of modality for treating patients with nephrolithiasis depends upon stone size, stone location, anatomic factors, patient factors, and patient preference. In general, for stones in the ureter or kidney having a size less than 2 cm in greatest dimension, shockwave Lithotripsy and ureteroscopy are first-line treatment options. For stones in the kidney (particularly those that reside in the lower pole of the kidney), percutaneous nephrolithotomy, albeit much more invasive of a procedure, can also be an appropriate option. Shockwave lithotripsy was the primary modality for managing these stones; however, advances in ureteroscopic instrumentation and technology have placed ureteroscopy on equal footing with shockwave lithotripsy, such that this has become the preferred first-line therapy at many academic medical centers.
The primary advantage of Histotripsy therapy over Lithotripsy therapy is the uniformly microscopic size of the reduced stone particles compared to Lithotripsy. For some stones which do not break down via L-mode therapy into sufficiently small fragments to be passed through the urinary tract, this may be critical. Some situations might be best approached primarily in the L-mode (harder stones in places where fragments are easily passed) and some situations might be best approached primarily in the H-mode (softer more easily eroded stones). Some may require a combination of each system with optimal application to be determined by clinical and laboratory experience with such a system. Additionally, visualization of Lithotripsy procedures is typically challenging and requires large and expensive imaging equipment, such as a fluoroscopic C-Arm. However, cavitational bubble clouds formed with a Histotripsy H-mode pulse can be easily viewed in real time under ultrasound imaging. Thus, it can be possible to visualize and target a urinary stone or by placing an H-mode bubble cloud on the stone, then focusing an L-mode shockwave towards the position of the bubble cloud to fragment the stone.
Thus, referring back to
Next, the Lithotripsy-Histotripsy system can be switched to an L-mode with a switching mechanism (e.g., switching mechanism 418 of
Thus, L-mode and H-modes of operation can be alternated so as to break down urinary stones into macroscopic particles (with L-mode pulses) and subsequently erode the macroscopic particles into a fine powder (with H-mode pulses). Histotripsy and Lithotripsy are naturally complementary as Lithotripsy shockwaves are efficient at causing initial coarse subdivision of targeted stones which greatly increases surface area and rate for subsequent Histotripsy erosion. Since the actual position of the original urinary stone can be tracked by image analysis (e.g., visual tracking of the stone itself or speckle tracking), the Lithotripsy-Histotripsy system can allow for movement of the kidney and can continually reposition the focus onto the tracked target volume. Visualization of the Histotripsy bubble cloud at the target position can confirm proper targeting.
In some method embodiments, urinary stones can be treated solely with Histotripsy H-mode pulses. Thus, Histotripsy acoustic sequences can be applied directly to the stones to cause erosion of the stones, producing extremely fine debris particles less than 100 μm in diameter which can be passed painlessly by the patient and eliminate the risk of steinstrasse (multiple obstructing fragments within the ureter). Still referring to
Alternative embodiments of methods of treating urinary stones can include multi-frequency systems for additional optimization, e.g., L-mode at higher frequencies (probably about 1 MHz) to fragment the stone and H-mode at lower frequencies (about 500 Khz) to cover the whole stone area and to make sure the increased stone surface area is usable for enhanced surface-based erosion. Referring now to
This L-mode and H-mode interleaving technique can be used to treat urinary stones. Thus, referring back to
Next, the Lithotripsy-Histotripsy system can generate an L-mode pulse to deliver a shock wave to the urinary stone to macroscopically fractionate the stone. Since L-mode pulses typically have a PRF≦2 Hz (but possibly ≦5 Hz), the time between subsequent L-mode pulses can be used to apply H-mode pulses, which typically have a PRF≦5 kHz. Thus, the method of treatment can comprise delivering an L-mode pulse to a urinary stone to fractionate the stone, instantaneously switching to an H-mode of operation to deliver a series of H-mode pulses to the urinary stone, and instantaneously switching back to an L-mode to deliver another Lithotripsy shockwave to the stone(s). As described above, verification of the stone position can be achieved by switching to H-mode and visualizing the H-mode bubble cloud under imaging guidance.
Histotripsy can be used to enhance shockwave (Lithotripsy) fragmentation of stones through control of the cavitation environment. Histotripsy can be used to control the cavitation environment to enhance and suppress cavitation at appropriate times. For example, Histotripsy can be used to suppress cavitation to improve efficacy at higher Lithotripsy shockwave rates. Additionally, Histotripsy can be used to suppress cavitation in healthy tissue to facilitate a higher Lithotripsy shockwave rate. High repetition rate Lithotripsy (>2 Hz) is currently limited by the persistence of microbubbles created during the process (cavitation) which interfere with subsequent shockwaves. Simple suppression of cavitation does not improve overall comminution because some cavitation is necessary for complete fragmentation. Time-varying Histotripsy sequences applied immediately before the arrival of a Lithotripsy shockwave to suppress cavitation, followed by enhancement sequences during the tensile portion of the Lithotripter wave (acting as a pump) can maximize both methods of comminution. This technique can greatly increase the efficiency of shockwaves as well as the rate which can be used allowing more complete comminution of even difficult urinary stones.
Cavitation suppressing Histotripsy acoustic sequences can be used to reduce collateral tissue injury during high dose and high rate shockwave application. Studies have shown increased risk of injury when high shockwave rates or high shockwave doses are attempted limiting the thoroughness and effectiveness of a treatment. A spatially-varying cavitation suppressing Histotripsy field can allow cavitation to occur within a target zone while suppressing cavitation outside the target zone. This technique can be used to eliminate collateral injury from shockwaves while permitting necessary cavitation on the stone surface when large shockwave doses and higher rates are used for more complete comminution. Thus, a method of treating tissue can comprise delivering Lithotripsy therapy to a target tissue to treat the target tissue, and delivering spatially-varying Histotripsy therapy to allow cavitation to occur within the target tissue while suppressing cavitation outside the target tissue.
As for additional details pertinent to the present invention, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “and,” “said,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.
This application is a continuation of pending U.S. patent application Ser. No. 12/868,775, filed Aug. 26, 2010, which application claims the benefit under 35 U.S.C. 119 of U.S. Provisional Patent Application No. 61/237,011, filed Aug. 26, 2009, titled “Devices and Methods for Using Controlled Bubble Cloud Cavitation in Fractionating Kidney Stones”. These applications are herein incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61237011 | Aug 2009 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12868775 | Aug 2010 | US |
| Child | 13943621 | US |
