U.S. patent application number 13/943621 was filed with the patent office on 2013-11-14 for devices and methods for using controlled bubble cloud cavitation in fractionating urinary stones.
The applicant listed for this patent is Charles A. Cain, Thomas W. Davison, J. Brian Fowlkes, Timothy L. Hall, William W. Roberts, Zhen Xu. Invention is credited to Charles A. Cain, Thomas W. Davison, J. Brian Fowlkes, Timothy L. Hall, William W. Roberts, Zhen Xu.
Application Number | 20130303906 13/943621 |
Document ID | / |
Family ID | 43625897 |
Filed Date | 2013-11-14 |
United States Patent
Application |
20130303906 |
Kind Code |
A1 |
Cain; Charles A. ; et
al. |
November 14, 2013 |
Devices and Methods for Using Controlled Bubble Cloud Cavitation in
Fractionating Urinary Stones
Abstract
A medical imaging and therapy device is provided that may
include any of a number of features. One feature of the device is
that it can deliver Lithotripsy therapy to a patient, so as to
fractionate urinary stones. Another feature of the device is that
it can deliver Histotripsy therapy to a patient, so as to erode
urinary stones. In some embodiments, the medical imaging and
therapy device is configured to target and track urinary stones in
the patient during therapy. Methods associated with use of the
medical imaging and therapy device are also covered.
Inventors: |
Cain; Charles A.; (Ann
Arbor, MI) ; Hall; Timothy L.; (Ann Arbor, MI)
; Roberts; William W.; (Saline, MI) ; Xu;
Zhen; (Ann Arbor, MI) ; Fowlkes; J. Brian;
(Ann Arbor, MI) ; Davison; Thomas W.; (Naples,
FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Cain; Charles A.
Hall; Timothy L.
Roberts; William W.
Xu; Zhen
Fowlkes; J. Brian
Davison; Thomas W. |
Ann Arbor
Ann Arbor
Saline
Ann Arbor
Ann Arbor
Naples |
MI
MI
MI
MI
MI
FL |
US
US
US
US
US
US |
|
|
Family ID: |
43625897 |
Appl. No.: |
13/943621 |
Filed: |
July 16, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12868775 |
Aug 26, 2010 |
|
|
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13943621 |
|
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|
|
61237011 |
Aug 26, 2009 |
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Current U.S.
Class: |
600/439 ;
601/2 |
Current CPC
Class: |
A61B 17/2256 20130101;
A61B 2017/00172 20130101; A61B 2090/378 20160201; A61B 2017/22008
20130101; A61B 17/225 20130101; A61B 8/00 20130101; A61N 7/00
20130101 |
Class at
Publication: |
600/439 ;
601/2 |
International
Class: |
A61N 7/00 20060101
A61N007/00; A61B 8/00 20060101 A61B008/00 |
Claims
1. An ultrasound therapy system, comprising: a first ultrasound
therapy transducer configured to deliver to a target ultrasound
pulses having a pulse length of 1 cycle and a pulse repetition
frequency less than or equal to 2 Hz; a second ultrasound therapy
transducer configured to deliver to the target ultrasound pulses
having a pulse length of 3-20 cycles and a pulse repetition
frequency less than or equal to 5 kHz; and a control system
configured to switch between delivering therapy from the first
therapy transducer to delivering therapy from the second therapy
transducer.
2. The system of claim 1 wherein the first ultrasound 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, and a duty cycle less
than 0.1%.
3. The system of claim 1 wherein 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, and a duty cycle of less
than 5%.
4. The system of claim 1 further comprising an imaging system.
5. The system of claim 4 wherein the imaging system comprises a
fluoroscopic imaging system.
6. The system of claim 4 wherein the imaging system comprises an
ultrasound imaging system.
7. The system of claim 4 wherein the imaging system comprises a
combination fluoroscopic and ultrasound imaging system.
8. The system of claim 4 wherein the imaging system is configured
to target and track a urinary stone in a patient.
9. An ultrasound therapy system, comprising: a multi-mode therapy
transducer configured to deliver acoustic pulses to a target in a
first mode in which the pulses have a pulse length of 1 cycle and a
pulse repetition frequency less than or equal to 2 Hz and in a
second mode in which the pulses have a pulse length of 3-20 cycles
and a pulse repetition frequency less than or equal to 5 kHz; and a
control system configured to switch between delivering therapy from
the multi-mode therapy transducer in the first mode to delivering
therapy from the multi-mode therapy transducer in the second
mode.
10. The system of claim 9 wherein in the first mode the multi-mode
therapy transducer is configured to apply to the target 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, and a duty cycle less than 0.1%.
11. The system of claim 9 wherein 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, and a duty cycle of less
than 5%.
12. The system of claim 9 further comprising an imaging system.
13. The system of claim 12 wherein the imaging system comprises a
fluoroscopic imaging system.
14. The system of claim 12 wherein the imaging system comprises an
ultrasound imaging system.
15. The system of claim 12 wherein the imaging system comprises a
combination fluoroscopic and ultrasound imaging system.
16. The system of claim 12 wherein the imaging system is configured
to target and track a urinary stone in a patient.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] 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.
INCORPORATION BY REFERENCE
[0002] 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.
FIELD OF THE INVENTION
[0003] 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.
BACKGROUND OF THE INVENTION
[0004] 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.
[0005] 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.
[0006] 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.
[0007] As shown by FIGS. 1A-1B, Histotripsy pulses comprise
(usually) small number of cycles of a sinusoidal driving voltage
whereas Lithotripsy is (most usually) driven by a single high
voltage pulse with the transducer responding at its natural
frequencies. Even though the Lithotripsy pulse is only one cycle,
its negative pressure phase length is equal to or greater than the
entire length of the Histotripsy pulse, lasting tens of
microseconds. This negative pressure phase allows generation and
continual growth of the bubbles, resulting in bubbles of sizes up
to 1 mm. The Lithotripsy pulses use the mechanical stress produced
by a shockwave and these 1 mm bubbles to fracture the stones into
smaller pieces.
[0008] 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.
[0009] 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.
[0010] 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.
[0011] 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 FIG. 2A), while Histotripsy erodes
stones into fine particles smaller than 100 .mu.m (as shown in FIG.
2B). Table 1 lists the Histotripsy and Lithotripsy parameters for
comparison.
TABLE-US-00001 TABLE 1 Histotripsy and Lithotripsy Parameters
Parameters Histotripsy Lithotripsy Energy Source Short ultrasound
pulses Short ultrasound pulses Image Guidance Ultrasound
Fluoroscopy, Ultrasound Peak negative ~8-40 MPa ~10-25 MPa pressure
Peak positive ~30-200 MPa ~50-200 MPa pressure Pulse Length 3-20
cycles 1 cycle Duty Cycle .ltoreq.5% .ltoreq.0.1% Pulse Repetition
.ltoreq.5 kHz .ltoreq.2 Hz Frequency
[0012] Shockwave Lithotripsy is favorable in that it is a short
(.about.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 .about.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.
SUMMARY OF THE INVENTION
[0013] 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.
[0014] 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.
[0015] 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.
[0016] 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.
[0017] 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.
[0018] 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.
[0019] 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.
[0020] 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.
[0021] 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.
[0022] 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.
[0023] 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.
[0024] 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.
[0025] 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.
[0026] 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.
[0027] 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIGS. 1A and 1B illustrate a typical Histotripsy pulse and
Lithotripsy pulse, respectively.
[0029] FIG. 2A illustrates a urinary stone eroded by Histotripsy
therapy.
[0030] FIG. 2B illustrates a urinary stone fractionated by
Lithotripsy therapy.
[0031] FIG. 3 illustrates one embodiment of a
Lithotripsy-Histotripsy system.
[0032] FIG. 4 illustrates a schematic view of a
Lithotripsy-Histotripsy system.
[0033] FIG. 5 illustrates a pulse sequence of Lithotripsy therapy
interleaved with Histotripsy therapy.
DETAILED DESCRIPTION OF THE INVENTION
[0034] 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.
[0035] 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.
[0036] 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.
[0037] 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.
[0038] FIG. 3 illustrates a combination Lithotripsy-Histotripsy
system 300, comprising therapy transducer 302, therapy transducer
304, imaging system 306, control system 308, display 310, and
patient support 312. In one embodiment, therapy transducer 302 can
be a Lithotripsy transducer configured to operate in an L-mode to
deliver Lithotripsy therapy to a target, and therapy transducer 304
can be a Histotripsy transducer configured to operate in an H-mode
to deliver Histotripsy therapy to a target. In another embodiment,
a combination Lithotripsy-Histotripsy system may include only a
single transducer, such as therapy transducer 302, the transducer
being configured to deliver both Lithotripsy therapy and
Histotripsy therapy, without requiring a second therapy transducer
304. Therapy transducers 302 and 304 may have a single focus with
mechanical or electromechanical steering of the respective
Lithotripsy-Histotripsy focus. Alternatively, the therapy
transducers may comprise a phased array to provide electrical
steering of the focal point. Histotripsy transducers can be
fabricated from piezo-electric ceramic materials that are pulsed
with high voltage electric signals at ultrasonic frequencies.
Lithotripsy transducers can be fabricated from piezo-electric
ceramic materials or they may be magneto-resistive magnetic
transducers or spark gap transducers, for example.
[0039] 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.
[0040] Imaging system 306 can provide real-time imaging guidance of
the patient while during L-mode and H-mode therapy. In the
embodiment of FIG. 3, imaging system 306 comprises an ultrasound
and fluoroscopic C-Arm imaging system. However, due to the size and
cost of C-arm imaging solutions, in other embodiments the imaging
system can comprise a high-resolution ultrasound imaging system. If
an ultrasound imaging system is used, it can be separate from
therapy transducers 302 and 304. Alternatively in some embodiments,
the ultrasound imaging system can be disposed on or within the
therapy transducers 302 and 304. Real-time imaging from imaging
system 306 can be displayed on display 310, which can comprise and
electronic display or a graphical user interface (GUI). In some
embodiments, the display can visualize treatment from both the
therapy transducers 302 and 304 at the same time, thus having the
capability to overlap or fuse the fluoroscopic and ultrasonic
images to optimize image planning and therapy tracking. Therapy
transducers 302 and 304 and imaging system 306 can be packaged
together as a single unit, as shown in FIG. 3, to facilitate
imaging and treatment of a patient lying on patient support
312.
[0041] 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."
[0042] FIG. 4 is a schematic drawing showing additional details of
the system of FIG. 3. Lithotripsy-Histotripsy system 400 of FIG. 4
can include therapy transducer 402, imaging system 406, optional
ultrasound imaging probe 407, H-mode driving system 414, L-mode
driving system 416, and switching mechanism 418, which can be a
physical or electronic control switch. In FIG. 4, therapy
transducer 402 can represent either therapy transducers 302 and 304
of FIG. 3, or alternatively, can represent a single therapy
transducer capable of both H and L-mode pulses. The
Lithotripsy-Histotripsy system 400 of FIG. 4 allows virtually
instantaneous switching between H-mode driving system 414 and the
L-mode driving system 416 with electronic control switch 418 to
allow an infinite range of possibilities for time division
multiplexing of the H-mode and L-mode pulses.
[0043] 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.
[0044] 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.
[0045] Thus, referring back to FIGS. 3-4, one method of treating
urinary stones with a Lithotripsy-Histotripsy system (e.g.,
Lithotripsy-Histotripsy system 300/400 of FIG. 3/4) may include
positioning a patient on a patient support (e.g., patient support
312 of FIG. 3) and imaging the patient with an imaging system
(e.g., imaging system 306 of FIG. 3). The imaging system can be,
for example, an ultrasound imaging system or a fluoroscopic imaging
system. The method can include targeting a urinary stone or urinary
stones within the patient with the imaging system. Next, the method
can include focusing an H-mode therapy transducer (e.g., therapy
transducer 304 of FIG. 3) on the urinary stone and generating a
bubble cloud onto the stone under the ultrasound image guidance.
The Histotripsy bubble cloud can be visualized as a greatly
enhanced backscatter region on a visual display (e.g., display 310
of FIG. 3).
[0046] Next, the Lithotripsy-Histotripsy system can be switched to
an L-mode with a switching mechanism (e.g., switching mechanism 418
of FIG. 4) to deliver a shock wave or shock waves to the urinary
stone to macroscopically fractionate the stone. Verification of the
focal position and its relationship to the urinary stone can be
achieved by switching back to H-mode and visualizing the H-mode
bubble cloud under imaging guidance. Furthermore, the H-mode bubble
cloud can continue to erode the macroscopic urinary stone particles
due to the increased surface area of multiple fractionated stone
particles compared to the original urinary stone. The Histotripsy
therapy can function to smooth (by erosion) the Lithotripsy
fragments so as to facilitate passage of these fragments by
removing sharp corners, edges, or elongated dimensions which can
hinder passage of fragments through the ureter.
[0047] 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.
[0048] 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
.mu.m 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 FIGS. 3-4, another method of
treating urinary stones with a Lithotripsy-Histotripsy system
(e.g., Lithotripsy-Histotripsy system 300/400 of FIG. 3/4) may
include positioning a patient on a patient support (e.g., patient
support 312 of FIG. 3) and imaging the patient with an imaging
system (e.g., imaging system 306 of FIG. 3). The method can further
comprise targeting a urinary stone or urinary stones within the
patient with the imaging system. Next, the method can include
focusing an H-mode therapy transducer (e.g., therapy transducer 304
of FIG. 3) on the urinary stone and generating a bubble cloud onto
the stone under the ultrasound image guidance. The Histotripsy
bubble cloud can be visualized as a greatly enhanced backscatter
region on a visual display (e.g., display 310 of FIG. 3). The
method can further comprise applying Histotripsy therapy to the
urinary stone to erode the stone into fine particles having a size
less than 100 .mu.m in diameter.
[0049] 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 FIG. 5, since L-mode pulses 520 typically
have a maximum pulse repetition frequency (PRF) about 2 Hz (2
pulses per second), and L-mode pulses are generally less than 100
micro-seconds long, most of the time during L-mode therapy is
available for H-mode pulses 522. In some embodiments, L-mode pulses
can have a maximum PRF of about 5 Hz. Since the H-mode PRF can be 1
kHz or larger, the H-mode pulses 522 and L-mode pulses 520 can
progress together appropriately interleaved in time with little
decrease in PRF for either, as shown in FIG. 5. Thus during urinary
stone treatment, L-mode pulses can fracture a large urinary stone
into fragments to increase the stone surface area for the H-mode,
which can then progress virtually undiminished in PRF by temporal
sharing with the L-mode. It should be noted that the H-mode can
trap fragments within its focal field. This may allow trapping of
L-mode fragments until the H-mode pulses erode all fragments to
very small particles that then escape the trapping field.
[0050] This L-mode and H-mode interleaving technique can be used to
treat urinary stones. Thus, referring back to FIGS. 3-5, one method
of treating urinary stones with a Lithotripsy-Histotripsy system
(e.g., Lithotripsy-Histotripsy system 300/400 of FIG. 3/4) may
include positioning a patient on a patient support (e.g., patient
support 312 of FIG. 3) and imaging the patient with an imaging
system (e.g., imaging system 306 of FIG. 3). The imaging system can
be, for example, an ultrasound imaging system or a fluoroscopic
imaging system. The method can include targeting a urinary stone or
urinary stones within the patient with the imaging system. Next,
the method can include focusing an H-mode therapy transducer (e.g.,
therapy transducer 304 of FIG. 3) on the urinary stone and
generating a bubble cloud onto the stone under the ultrasound image
guidance. The Histotripsy bubble cloud can be visualized under
ultrasound image guidance as a greatly enhanced backscatter region
on a visual display (e.g., display 310 of FIG. 3). Since the bubble
cloud cannot be imaged under solely fluoroscopic imaging, if no
ultrasound imaging is used then the stones can be targeted by
positioning the geometric focus of the therapy transducer (e.g.,
the expected location of the bubble cloud) on the targeted urinary
stone.
[0051] 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.ltoreq.2 Hz (but possibly .ltoreq.5 Hz), the
time between subsequent L-mode pulses can be used to apply H-mode
pulses, which typically have a PRF.ltoreq.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.
[0052] 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.
[0053] 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.
[0054] 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.
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