U.S. patent application number 14/148637 was filed with the patent office on 2014-05-01 for controlled high efficiency lesion formation using high intensity ultrasound.
This patent application is currently assigned to Kona Medical, Inc.. The applicant listed for this patent is Kona Medical, Inc.. Invention is credited to David M. Perozek, Lee Weng, Jimin Zhang.
Application Number | 20140121568 14/148637 |
Document ID | / |
Family ID | 28456738 |
Filed Date | 2014-05-01 |
United States Patent
Application |
20140121568 |
Kind Code |
A1 |
Weng; Lee ; et al. |
May 1, 2014 |
CONTROLLED HIGH EFFICIENCY LESION FORMATION USING HIGH INTENSITY
ULTRASOUND
Abstract
An ultrasound system used for both imaging and delivery high
intensity ultrasound energy therapy to treatment sites and a method
for treating tumors and other undesired tissue within a patient's
body with an ultrasound device. The ultrasound device has an
ultrasound transducer array disposed on a distal end of an
elongate, relatively thin shaft. In one form of the invention, the
transducer array is disposed within a liquid-filled elastomeric
material that more effectively couples ultrasound energy into the
tumor, that is directly contacted with the device. Using the device
in a continuous wave mode, a necrotic zone of tissue having a
desired size and shape (e.g., a necrotic volume selected to
interrupt a blood supply to a tumor) can be created by controlling
at least one of the f-number, duration, intensity, and direction of
the ultrasound energy administered. This method speeds the therapy
and avoids continuously pausing to enable intervening normal tissue
to cool.
Inventors: |
Weng; Lee; (Bellevue,
WA) ; Perozek; David M.; (Mercer Island, WA) ;
Zhang; Jimin; (Bellevue, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Kona Medical, Inc. |
Menlo Park |
CA |
US |
|
|
Assignee: |
Kona Medical, Inc.
Menlo Park
CA
|
Family ID: |
28456738 |
Appl. No.: |
14/148637 |
Filed: |
January 6, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12247969 |
Oct 8, 2008 |
8622937 |
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14148637 |
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10633726 |
Aug 4, 2003 |
7470241 |
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12247969 |
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09721526 |
Nov 22, 2000 |
6626855 |
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10633726 |
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60167707 |
Nov 26, 1999 |
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Current U.S.
Class: |
601/2 |
Current CPC
Class: |
A61B 8/445 20130101;
A61B 2090/378 20160201; A61N 7/00 20130101; A61B 8/12 20130101;
A61B 2017/4216 20130101; A61N 2007/0052 20130101; A61B 8/4281
20130101; A61N 7/02 20130101; A61B 8/546 20130101; A61N 7/022
20130101 |
Class at
Publication: |
601/2 |
International
Class: |
A61N 7/00 20060101
A61N007/00 |
Claims
1. A method for administering an ultrasonic therapy to a target,
comprising the steps of: (a) providing an ultrasonic transducer
that emits a focused high energy ultrasonic energy when energized;
(b) positioning the ultrasonic transducer to focus it at an imaged
target; (c) directing the ultrasonic transducer toward a desired
focal point within the target; (d) energizing the ultrasonic
transducer so that it emits the focused high energy ultrasonic
energy at the desired focal point, causing heating of a portion of
the target disposed at the desired focal point; (e) creating a
positive feedback process between the ultrasound transducer and the
target; and (f) utilizing an imaging technique to monitor the
degree of tissue injury caused by the heating.
2. The method of claim 1, wherein the heating creates a lesion and
wherein a desired shape and size of the lesion are selected so that
formation of the lesion substantially deprives the target of a
blood supply, causing the ultimate destruction of the target.
3. The method of claim 1, wherein the heating creates a lesion and
wherein a desired shape and size of the lesion are selected to
cause heating of a blood vessel.
4. The method of claim 1, wherein the target is a blood vessel.
5. The ultrasonic system of claim 1, wherein said high intensity
ultrasonic energy is configured to heat tissue between the
transducer and focal point to a temperature of 50.degree. C. or
more.
6. The ultrasonic system of claim 1, wherein the heating creates a
lesion wherein the lesion has a volume of about 4.5 cubic
centimeters.
7. The method of claim 1, wherein the target is a prostate.
8. The method of claim 7, wherein imaging and therapy are
interleaved in time to monitor the ultrasonic therapy.
9. The method of claim 7, further comprising the step of
administering ultrasound contrast prior to administering the
ultrasound therapy.
10. The method of claim 9, further comprising inducing cavitation
to further increase tissue injury.
11. The method of claim 9, further comprising the step of
monitoring the formation of cavitation with the imaging.
12. The method of claim 7, further comprising alternating between
ultrasound therapy and ultrasound imaging to generate a plurality
of ultrasound image frames during treatment.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 12/247,969, filed Oct. 8, 2008, which is a continuation of U.S.
application Ser. No. 10/633,726, filed Aug. 4, 2003, now U.S. Pat.
No. 7,470,241, which is a continuation of U.S. application Ser. No.
09/721,526, filed Nov. 22, 2000, now U.S. Pat. No. 6,626,855, which
claims the benefit of U.S. Provisional Application No. 60/167,707,
filed Nov. 26, 1999.
FIELD OF THE INVENTION
[0002] This invention relates generally to methods and apparatus
for efficiently heating biological tissues with high intensity
ultrasound for therapeutic purposes, and in particular, to
endoscopic devices for applying ultrasound energy to uterine
fibroids and other pathologic tissues that are inside body or organ
cavities, to destroy the tumor or the diseased tissue.
BACKGROUND OF THE INVENTION
[0003] Fibroids are benign tumors in women's uteri. There are
different types of fibroids, including submucosal, which are inside
the uterine cavity; intramural, which are in the uterine wall; and
subserosal, which are outside the uterus. Fibroids may cause
excessive bleeding and pain. For symptomatic fibroids, surgery is
the predominate treatment. Every year in the U.S., there are more
than 200,000 cases of fibroid-caused hysterectomies. To preserve
the uterus, the patient may choose myomectomy, which removes the
fibroids only. There are more than 80,000 abdominal myomectomies
each year in the U.S. These surgical procedures cause significant
trauma to the patients and result in significant costs.
Consequently, patients need several days of hospital stay and
suffer from the prolonged recovery.
[0004] Minimally invasive surgical (MIS) procedures have been
explored to treat uterine fibroid trans-abdominally or
trans-cervically under laparoscopic or hysteroscopic guidance. Many
MIS apparatus have been developed to make the procedure less
difficult. Several prior art devices are described in U.S. Pat. No.
5,304,124; U.S. Pat. No. 5,662,680; and U.S. Pat. No. 5,709,679.
Besides surgically resecting and removing the tumor tissue,
alternative treatments include using different energy forms, such
as laser, radio frequency (RF), and cryo-therapy, to thermally
ablate or necrose the fibroid tissue. Most of these techniques
require the insertion of needles or other types of devices into the
body of the fibroid. The mechanical damage to the fibroid and the
uterus can cause bleeding during the treatment and adhesions after
the treatment. Suturing the damage in the uterus is very difficult
in the laparoscopic MIS procedure. Also, most of these alternative
treatments are time consuming and technically challenging.
[0005] Uterine arterial embolization (UAE) has been investigated as
an alternative treatment for uterine fibroids. In UAE, a catheter
is inserted into the patient's femoral artery. The catheter is then
advanced until its tip reaches the uterine artery. Many small
particles are then injected into the uterine artery to block the
blood flow. Both left and right uterine arteries are treated. Blood
vessels supplying uterine fibroids are typically larger than the
vessels in the normal uterine tissue. With properly sized
particles, the blood vessels feeding the uterine fibroids are
embolized, but not those in the normal uterine tissue. The fibroids
then starve and die due to lack of a blood supply. The uterus
survives, however, on the blood supplied from the ovarian artery
and other collateral circulation. The embolization procedure may
cause severe pain in the first few days after the treatment. Other
disadvantages of UAE may include long X-ray radiation exposure
during the procedure and other long-term potential adverse effects.
The procedure is not recommended if the patient seeks a future
pregnancy.
[0006] Ultrasound is a term that refers to acoustic waves having a
frequency above the high limit of the human audible range (i.e.,
above 20 KHz). Ultrasound waves have the capability of penetrating
into the human body. Based on this property, ultrasound in the
frequency range of 2-20 MHz has been widely used to image internal
human organs for diagnostic purposes. Ultrasound imaging has also
been suggested as a tool for guidance during a resectoscopic
surgery (U.S. Pat. No. 5,957,849).
[0007] When ultrasound energy is absorbed by tissue, it becomes
thermal energy, raising the temperature of the tissue. To avoid
thermal damage to tissue, the power level in diagnostic ultrasound
imaging is kept very low. The typical ultrasound intensity (power
per unit area) used in imaging is less than 0.1 watt per square
centimeter. High intensity focused ultrasound, which can have an
intensity above 1000 watts per square centimeter, can raise the
tissue temperature at the region of the spatial focus to above
60-80 degrees Celsius in a few seconds and can cause tissue
necrosis almost instantaneously.
[0008] High intensity ultrasound has been proposed to treat and
destroy tissues in the liver (G. ter Haar, "Ultrasound Focal Beam
Surgery," Ultrasound in Medicine and Biology, Vol. 21, No. 9, pp.
1089-1100, 1995); in the prostate (N. T. Sanghvi and R. H. Hawes,
"High-intensity Focused Ultrasound," Experimental and
Investigational Endoscopy, Vol. 4, No. 2, pp. 383-395, 1994); and
in other organs. In U.S. Pat. Nos. 5,080,101, 5,080,102, 5,735,796,
5,769,790, and 5,788,636, for example, ultrasound imaging is
combined with a high intensity ultrasound treatment to target the
treatment region and to monitor the treatment process. In U.S. Pat.
Nos. 5,471,988, 5,492,126, 5,666,954, 5,697,897, and 5,873,828,
endoscopic ultrasound devices with both imaging and therapeutic
capabilities are disclosed. These devices all have an elongated
tube or shaft, so that they can be inserted in organ cavities
(e.g., into the rectum) or into the abdominal cavity through a
puncture hole in the abdominal wall to bring the ultrasound imaging
and treatment sources closer to the disease sites. Some of them
have flexible ends, which can be bent to fit the anatomy of a
specific patient.
[0009] The therapeutic ultrasound beam is focused inside tissue to
a small spot of a few millimeters in size. At the focus, tissue
temperature rapidly exceeds a level sufficient to cause tissue
necrosis, thus achieving the desired therapeutic effect. Outside of
the focus, ultrasound energy is less concentrated, tissue
temperature rise remains below the necrosis level during the
typically short exposure times employed. To treat a tissue volume
larger than the focal spot, in the prior art, the ultrasound focus
is deflected mechanically or electronically to scan, or
incrementally expose, the target tissue volume. One disadvantage of
the current high intensity ultrasound therapy is its inefficiency
when treating large tumors or heating a large volume of tissue.
Even though a three-second ultrasound pulse can increase the
temperature of tissue at its focus dramatically, the ultrasound
treatment must typically pause 40-60 seconds between two subsequent
pulses to allow the intermediate tissue between the focus and the
ultrasound transducer to cool sufficiently to avoid thermally
damaging the tissue. The volume of tissue necrosis for each
treatment pulse is very small (.about.0.05 cm.sup.3). For example,
to treat a volume of tissue within a 3 cm diameter sphere, it will
take more than 4 hours, too long to be practical in most clinical
situations. Many symptomatic uterine fibroids are larger than 2-3
cm in diameter, and multiple fibroids are also common. To be
acceptable for clinicians and patients, the ultrasound treatment
time must be significantly reduced.
[0010] Large device size is the second disadvantage of the
therapeutic ultrasound apparatus in much of the prior art. Most of
these devices have two separated ultrasound transducers, including
one for imaging and the other for therapy. For effective treatment,
the diameter of the treatment transducer is approximately equal to
the maximum depth, where the f-number (transducer diameter divided
by its focal length) of the transducer is about one (f/1). The
transducer surface area must also be sufficiently large to generate
high ultrasound power. In some prior art endoscopic devices (for
example, in U.S. Pat. Nos. 5,471,988 and 5,873,828), there is a
large orifice in the center of the therapy transducer for
positioning an imaging transducer. This orifice reduces the area of
the treatment transducer and increases its effective f-number. In
this case, the size of the treatment transducer must be increased
to maintain its effectiveness, so that the overall dimensions of
the device are increased. For endoscopic (trans-cervical or
trans-abdominal) uterine fibroid treatments, the maximum acceptable
diameter of an ultrasound device is about 10 mm. It is seen that it
is very difficult to meet this requirement with the large
two-transducer configuration.
[0011] There is another disadvantage of the two-transducer
configuration in which there is an orifice in the center of the
treatment transducer. In endoscopic uterine fibroid treatment, the
ultrasound device is directly brought against the surface of the
fibroid tumor. The tumor surface near the orifice of the transducer
will not be treated unless the transducer is moved away or aside
from its initial position. Oftentimes, the space is very limited,
especially inside the uterus. There may not be sufficient space to
permit the device to move, a limitation that results in incomplete
treatment of the tumor.
[0012] What is needed is a minimally invasive or noninvasive device
for treating uterine fibroids. The device should preferably cause
minimal or no trauma to the patient body so that the patient
requires minimum or no recovery time; it should be easy to use;
and, the treatment should be quickly administered. The device
should preferably not cause blood loss during the treatment
procedure; it should not mechanically damage the treated organ
(e.g. uterus) to avoid the need for complicated organ repair (such
as suturing or extensive cauterization); and, it should not
increase the risk of post-operative adhesions and other
complications. In addition, the device should be capable of
carrying out the following functions: [0013] (1) Ultrasonically
increase the tissue temperature in the uterine fibroid to cause
tumor necrosis. Shrinkage of the necrosed tissue will reduce the
blood supply to the tumor. This occlusion effect will further
reduce the chance of survival for the tumor. [0014] (2)
Significantly reduce the ultrasound treatment time and thereby
improve physician and patient acceptance. A positive feedback
heating process can be provided to efficiently and rapidly raise
the temperature in a large volume of tissue. [0015] (3) Combine the
ultrasound imaging and therapy transducer in one to enable the
dimensions of the apparatus to be more compact so that the device
can be inserted into patient's uterine cavity or permit practical
laparoscopic use (e.g., be inserted trans-abdominally). [0016] (4)
Include a treatment transducer that does not have an orifice in its
center, so that the tumor tissue can be treated thoroughly. [0017]
(5) Provide ultrasound imaging capability for treatment guidance.
The imaging capability should provide real-time assessment of the
anatomy before, during, and after the treatment. Doppler imaging
can be advantageously employed to aid targeting, and the assessment
of treatment. [0018] (6) Use ultrasound to detect and differentiate
the tissue property changes before and after the treatment to make
an assessment of the treatment result possible. [0019] (7) Create
an acoustic absorption barrier inside the treated tissue to prevent
the tissue beyond the desired treatment zone from being thermally
damaged. [0020] (8) Provide a feedback control mechanism to turn
the treatment transducer element off when the transducer is not
properly coupled to the tissue to prevent the device from being
damaged by reflected ultrasound power. [0021] (9) Provide an
effective cooling mechanism to prevent the device from being
thermally damaged. [0022] (10) Use an ultrasound contrast agent
(micro-bubbles) to enhance the treatment effect. [0023] (11)
Provide effective means to acoustically couple an ultrasound source
to targeted tissue structures. [0024] (12) Use elasticity imaging
to assess the state of tissues prior, during, and after ultrasonic
treatment. [0025] (13) Employ cavitation as a therapeutic means to
necrose selected tissues.
[0026] Currently, an endoscopic ultrasound probe is not available
that can provide the above-noted functions. Accordingly, it will be
apparent that both such a device and an effective and efficient
method for treating uterine fibroid tumors and other internal
tissues and diseased tissue masses is needed that overcomes the
problems with prior art apparatus and methods.
SUMMARY OF THE INVENTION
[0027] The present invention is directed to a method and apparatus
for efficiently treating uterine fibroids and other diseases with
high intensity ultrasound, where the apparatus is small enough to
fit in the limited space in a patient organ cavity or a limited
puncture size on an abdominal wall.
[0028] Specifically, an ultrasonic system for destroying undesired
tissue at an internal site within a body of a patient includes a
probe that is sized to be inserted within a body of a patient. An
ultrasonic transducer is mounted proximate a distal end of the
probe and is adapted to couple to a power supply used to
selectively energize the ultrasonic transducer so that it produces
a focused beam of high intensity ultrasonic energy. An ultrasound
transmissive interface is coupled to the distal end of the probe
and is disposed and adapted to conform to a surface of the
undesired tissue. The interface provides a liquid layer that more
efficiently transmits the high intensity ultrasonic energy produced
by the ultrasonic transducer into the undesired tissue. The high
intensity ultrasonic energy increases a temperature of the
undesired tissue sufficiently to cause the tissue to necrose.
[0029] In one form of the invention, the ultrasound transmissive
interface comprises an elastomeric cavity that is adapted to
contain a liquid. The elastomeric cavity is disposed between the
ultrasonic transducer and the surface of the undesired tissue so
that the high intensity ultrasonic energy passes through the liquid
within the elastomeric cavity and into the undesired tissue. The
elastomeric cavity is formed at least in part from a semi-permeable
membrane, so that the liquid from within the elastomeric cavity
weeps onto a surface of undesired tissue to increase the efficiency
with which the high intensity ultrasonic energy is coupled into the
undesired tissue.
[0030] In another form of the present invention, the ultrasound
transmissive interface comprises a cap made of an elastomeric
material, which is disposed to surround the ultrasonic transducer.
The cap is adapted to seal against the undesired tissue and to
contain a liquid that increases an efficiency with which the high
intensity ultrasonic energy is coupled into the undesired tissue.
In addition, the cap preferably includes a rim having a double lip
seal formed around a perimeter. A passage in the cap is adapted to
couple the double lip seal to a vacuum line so that the rim of the
cap is held against a surface of the undesirable tissue, sealing
the liquid inside of the cap.
[0031] Another aspect of the present invention is directed to a
method for administering an ultrasonic therapy to destroy at least
a portion of an undesired tissue mass. The method includes the
steps of providing an ultrasonic transducer that emits a focused
high energy ultrasonic energy when energized, and positioning the
ultrasonic transducer proximate the undesired tissue mass. The
ultrasonic transducer is directed toward a desired focal point
within the undesired tissue mass. Then, the ultrasonic transducer
is energized so that it emits the focused high energy ultrasonic
energy at the desired focal point, causing necrosis of a portion of
the undesired tissue mass disposed at the desired focal point. At
least one of an f-number, an intensity, a time, and a direction of
the high intensity ultrasonic energy emitted into the undesired
tissue mass is controlled to achieve a desired shape and size of a
necrotic zone of undesired tissue, destroyed as a result of being
heated by the high intensity ultrasonic energy. The necrotic zone
substantially blocks the high intensity ultrasonic energy from
penetrating beyond the necrotic zone. The desired shape and size of
the necrotic zone are preferably selected and formed so as to cause
substantially of the undesired tissue mass to ultimately be
destroyed.
[0032] The step of controlling preferably includes the step of
repositioning the ultrasonic transducer to direct the high
intensity ultrasonic energy at a different portion of the undesired
tissue mass, to achieve the desired shape and size of the necrotic
zone. In one application of the method, the desired shape and size
of the necrotic zone are selected so that formation of the necrotic
zone substantially deprives the undesired tissue mass of a blood
supply, causing the ultimate destruction of the undesired tissue
mass. In another application of the method, the desired shape and
size of the necrotic zone are selected to control bleeding at a
treatment site.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0033] The foregoing aspects and many of the attendant advantages
of this invention will become more readily appreciated as the same
becomes better understood by reference to the following detailed
description, when taken in conjunction with the accompanying
drawings, wherein:
[0034] FIG. 1 is a block diagram of the positive feedback mechanism
of the improved tissue heating process;
[0035] FIGS. 2A-2D illustrate different thermal lesion shapes;
[0036] FIG. 3A is a cross-sectional view of a portion of a
patient's body, illustrating application of an endoscopic device in
accord with the present invention, which can both acquire
ultrasound images and generate high intensity therapeutic
ultrasound at its distal end;
[0037] FIGS. 3B and 3C are side elevational views of a portion of
the device shown in FIG. 3A, illustrating an imaging field and a
treatment field of the device;
[0038] FIGS. 4A and 4B are schematic diagrams of different
treatment beam forming techniques used to control the lesion
geometry and illustrating spatial lesion formation;
[0039] FIGS. 5A and 5B are schematic diagrams of different
treatment beam forming techniques used to control the lesion
geometry and illustrating spatial-temporal lesion formation;
[0040] FIG. 6 is a schematic diagram of the trans-cervical
ultrasound device with an articulated end;
[0041] FIGS. 7A and 7B are schematic diagrams showing transcervical
hemostasis treatment performed in combination with resectoscopic
removal of submucosal fibroids;
[0042] FIGS. 8A and 8B are schematic diagrams respectively showing
the trans-cervical and the trans-abdominal ultrasound device
treating intramural fibroids from inside and from outside of the
uterus;
[0043] FIGS. 9A and 9B are schematic diagrams respectively showing
laparoscopic occlusion treatment of subserosal fibroids, and a
wedge of necrosed tissue produced thereby;
[0044] FIG. 10 is a block diagram of the trans-cervical ultrasound
device connected with its control unit, display, and fluid
management unit;
[0045] FIG. 11 is a side elevational view of the ultrasound device
and a cross-sectional view of a liquid-filled vacuum cap that
provides coupling between the fibroid tumor and the ultrasound
transducer;
[0046] FIG. 12 is a system block diagram of the control electronics
in the control unit; and
[0047] FIG. 13 is an isometric view of a portion of an ultrasound
device that includes a structure to maintain a gap between the
tissue being treated and an ultrasound transducer array, to convey
a coolant liquid.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0048] In the following description of the present invention, its
application in treating uterine fibroid tumors is discuss in some
detail. However, it should be emphasized that the device and
methods described herein may also be used to apply ultrasound
therapy treatment to other organ systems, lesions, and disease
states. The therapy delivered may be thermal ablation, where a
temperature rise is established to a level at which tissues are no
longer viable; mechanical ablation, where cavitation is employed as
the primary ablative means; or may achieve hemostasis wherein
bleeding or blood flow in intact organs is arrested. Such
applications of the present invention may be accomplished in open,
invasive surgery, by way of established minimally invasive
techniques (for example, by way of body entry through one or more
small incisions or punctures), or in some cases, noninvasively,
through the skin surface or through the linings of body cavities
such as the rectum, vagina, or esophagus. Ablative treatment with
the present invention may be applied to a wide range of benign or
cancerous lesions of the liver, kidney, pancreas, spleen, prostate,
breast, bowel, rectum or similar organ systems, wherein the device
described herein may be placed in close proximity to the disease
location. Also, acoustic hemostasis treatment may be employed to
deprive a disease lesion of its blood supply or used to facilitate
surgical procedures by arresting bleeding or blood flow.
[0049] Many tumors, such as uterine fibroids, locate superficially
inside or outside the organ. During hysteroscopic or laparoscopic
surgeries, surgeons can easily reach the surfaces of those tumors
with an intra-cervical or intra-abdominal instrument. For an
ultrasound transducer at the tip of the intra-cavity instrument
touching the tumor directly, there will be little or no
intermediate tissue that needs to be spared and cooled, so that
pauses in the treatment for this purpose may become
unnecessary.
[0050] According to conventional wisdom, the pre-focal heating is
considered to be a negative effect and needs to be minimized. In
the case of intra-cavity treatment of uterine fibroids, however,
this pre-focal heating can provide significant enhancement to the
efficiency of tissue heating when the ultrasound transducer can be
disposed in close contact with the tumor surface. A positive
feedback mechanism of tissue heating (illustrated in FIG. 1) is
preferably used to improve the efficiency of the treatment provided
by the present invention. The positive feedback indicated by a
block 2 of FIG. 1 enhances acoustic absorption. The acoustic energy
is converted to heat, as noted in a block 4, resulting in a greater
temperature rise in the tissue, as indicated in a block 6. Tissue
acoustic absorption increases significantly when its temperature
rises above 50.degree. C. Referencing FIG. 2A, a small f-number,
high intensity ultrasound transducer 10, running in continuous-wave
(CW) mode, raises the temperature in tissue 12 at its focus to
70-90.degree. C. in less than two seconds and forms a small lesion
14. This isolated thermal lesion serves two purposes. First, it is
the initial seed to start the positive feedback heating process;
and, secondly, its high acoustic absorption blocks ultrasound
energy from penetrating beyond the focal depth to cause undesirable
damage to normal tissue. In an experimental study, it was observed
that after the lesion started at the focus, it first grew along the
central axis of the transducer and towards the transducer to form
an elongate lesion. Then, the end of the elongate lesion closer to
transducer began growing laterally wider. Eventually, the lesion
became a wedge shape 16 (FIG. 2B). The tissue layer near the
surface, adjacent to transducer 10, was the last portion to
necrose.
[0051] In an experimental study, a wedge-shaped lesion of tissue
necrosis was generated with this mechanism by running the
ultrasound power continuously, while keeping the transducer
position fixed. The volume of the thermal lesion was about 4.5
cm.sup.3, and the treatment time was approximately two minutes. The
average treatment rate was about 2.25 cm.sup.3/min, which was 45
times faster than provided by a conventional pulse-pause treatment
strategy.
[0052] Using the present invention, the size and the shape of the
large thermal lesion can be readily controlled. To form a thin
elongate lesion column 20 in the tissue (FIG. 2C), a circular
transducer 18 with a relatively large f-number (.about.2) is used
to treat the tissue over a relatively short time. To create a
conical shaped lesion, a circular transducer with a small f-number
(.about.1) is used to treat the tissue for a relatively long time.
To form a thin, wedge-shaped lesion, i.e., shaped like a slice of
pie (FIG. 28), a cylindrical or truncated circular transducer is
used to treat the tissue over a relatively long time. A generally
rectangular lesion plane 21 (FIG. 2D) can be generated by forming a
row of tightly spaced lesion columns 22, 24, and 26. Each column is
formed from a fixed transducer position in a short time. The
transducer may then be quickly shifted laterally to generate the
next adjacent column, moving from position "A" to "B" to "C" as
shown in FIG. 2D. Thermal diffusion in the tissue fuses the columns
together to form rectangular lesion plane 21. It is also possible
to create a large lesion in the tissue without damaging the organ
surface. One approach is to cool the tissue surface with
circulating water or saline. The other approach is to use an
attenuation measurement technique described below, to monitor
lesion progress (growth) and control power, accordingly.
[0053] The basic concept and configuration of a high intensity
ultrasound device 29 in accord with the present invention are shown
in FIGS. 3A and 3B. The device has a thin, elongate shaft 28 that
can be inserted through the cervix into the uterine cavity, or, as
shown in FIG. 3A, through a laparoscopic opening 34 in the
abdominal wall and into the abdominal cavity. A distal end 30 of
the shaft contains a concave-shaped ultrasound transducer array 36
(FIG. 3B) and may be formed into different curves to fit different
anatomies of individual patients. The distal end that is thus
formed can be permanently fixed or articulated by turning a control
knob 32 on a handle 33 of the device. Transducer array 36 in FIG.
3B is operable for both ultrasound imaging and treatment. To form
an ultrasound image, the transducer array generates ultrasound
pulses and receives echoes from the imaged anatomy in a
cross-sectional area 40. The two-dimensional (2D) ultrasound image
displays the cross-sectional view of the anatomy. The image can be
updated rapidly in real-time with a frame rate of, for example,
10-30 frames per second. Physicians can then view this real-time
image to locate the tumor or other tissue that needs to be treated
or spared from treatment. When the treatment area is identified in
the image, the transducer array is employed to generate high
intensity ultrasound focused in a treatment area 38. After the
tissue in the treatment area has been necrosed, the distal end of
the ultrasound device is moved to a new location to sequentially
treat another part of the tumor tissue. The imaging and the
treatment are interleaved in time so that the treatment process and
the progress of the treatment may be monitored.
[0054] Doppler flow imaging (spectral Doppler or power mode
Doppler) may be utilized to assist targeting and to monitor
treatment effects and to determine the endpoint of the therapy.
Imaging blood flow is particularly useful when a blood flow
occlusion strategy is being utilized, since the cessation of blood
flow can be directly monitored. Doppler imaging facilitates
localization of the vascularity typically surrounding uterine
fibroid tumors or other tumor masses.
[0055] There are many possible combinations of the imaging and
treatment capabilities. Imaging and therapy may be one-, two-, or
three-dimensional in various combinations; scan geometries may be
fixed or selectable; and imaging and therapy may proceed either
simultaneously or sequentially in time. A preferred embodiment of
the ultrasound intra-cavity device discussed herein has the
capability to carryout 2D real-time imaging and the capability to
produce tissue necrosis in a substantially 2D slice (thickness of
this slice is nominally less than one centimeter). Including the
lesion-control techniques discussed above, there are many ways to
control treatment geometry with this device. Different spatial beam
patterns can be generated from by the ultrasound transducer array
included on the device to form a specific lesion shape, or
potentially, to reduce treatment time. Multiple sequential
exposures of different spatial beam patterns can also be used to
control the treatment dosage at different locations to form lesion
shapes that cannot be generated by fixed beam patterns.
[0056] As shown in FIG. 6, a trans-cervical ultrasound device 68 is
adapted to treat submucosal fibroids. The device is inserted into a
patient's uterine cavity through the vagina and the cervical canal.
The uterine cavity is distended with sterile water or saline under
50-80 mm Hg pressure delivered through internal channels inside a
shaft 70 of the device and connected to couplings 78 and 76. The
water provides working space for manipulation of the device, and
the water thus infused also serves as a transducer coupling and
cooling medium.
[0057] The fibroid is visualized by ultrasound imaging using
trans-cervical ultrasound device 68. As a function of the tumor
size and shape, the physician selects the appropriate treatment
geometry and turns the therapeutic ultrasound power on to necrose a
slice volume of the tumor tissue in front of the transducer. The
entire tumor is then treated typically piece by piece. During the
treatment, the transducer (not separately shown) at a distal end 72
of the device does not have to directly contact the tumor
surface--the water in the uterus is a good acoustic coupling and
transmission medium. After the tumor is completely treated, the
physician removes the device and drains the water from the
patient's uterus. The procedure is finished without any surgical
invasion to the tissue.
[0058] There are two possible approaches for providing treatment of
a submucosal fibroid tumor 94 with trans-cervical ultrasound device
68. The physician can treat the whole tumor directly with the
ultrasound device, as shown in FIG. 7A, or treat only a remaining
tumor base 96, as shown in FIG. 7B, after a portion of the tumor is
removed by using a resectoscope. In FIG. 7A the transducer in
distal end 72 is placed adjacent to tumor 94 inside a water-filled
uterine cavity 90. For the latter approach, the ultrasound device
works not only as an ablation tool, but also as a hemostasis tool
to seal off the open, bleeding vessels around and inside the
exposed tumor base.
[0059] A similar technique may be used to treat intramural fibroids
as illustrated in FIGS. 8A and 8B. If a tumor 93 is closer to the
inside of the uterus (FIG. 8A), a trans-cervical ultrasound device
is the choice for the treatment. Otherwise, a trans-abdominal
device may be used (FIG. 8B). Some intramural fibroids 96 are
imbedded inside normal uterine tissue, e.g., in a uterine wall 92.
The physician may want only to necrose the tumor but not the
uterine wall that covers the tumor. In this case, the physician can
use the lesion geometry control techniques described above to heat
only the tumor inside the uterine wall without thermally damaging
the surrounding tissue.
[0060] Subserosal fibroids are disposed substantially outside of
the uterus. When these are symptomatic, they may be larger than
submucosal and intramural fibroids. However, the trans-abdominal
ultrasound device according to the present invention can also be
used to treat them. If the physician uses the same treatment
technique as described above to thermally necrose the entire tumor,
it will take longer time, because they are relatively large. An
alternative approach is shown in FIGS. 9A and 9B, where only the
tumor base is treated by a series of sectors, or pie-shaped
applications 100, 102 (FIG. 9B) that are circumferentially disposed
around the base of a tumor 98. After the entire tumor base is
heated sector by sector, the tumor tissue in the base shrinks. The
tissue shrinkage occludes blood vessels in the base and achieves
effective tumor starvation as oxygen and nutrient supplies are
interrupted. Without a blood supply, the tumor will die. The
necrosed tumor will then shrink in volume, so that the pressure
symptoms experienced by the patient due to the growth of the tumor
will be relieved.
[0061] A system 104 that supports operation of trans-cervical
ultrasound device 68 is shown in FIG. 10. The system consists
includes one or more ultrasound applicators 126, an optional
optical hysteroscope (not separately shown), which is inside the
applicator, and its associated camera 112, a treatment control unit
110, a TV monitor 122, and a fluid management system that includes
a fluid management system pump 120, tubing 116, and a waste
collection container 114. The hysteroscope, camera, monitor, and
fluid management system are typically available in a well-equipped
gynecology operating room. The optional hysteroscope may be useful
for visually locating the tumor. Control unit 110 provides
electronic signals and power to the ultrasound transducer for both
imaging and therapy. The ultrasonic image and the optical image
from the camera attached to the hysteroscope are combined in the
control unit and are preferably displayed on the monitor in a
"picture-in-a-picture" format 124. Alternatively, either one of the
images may be displayed alone. Fluid management system pump 120
controls the saline or water pressure and the flow rate into the
uterus.
[0062] Different configurations of the trans-cervical ultrasound
device shown in FIG. 6 have specific advantages. They all have two
irrigation channels for fluid in and out, one electrical cable to
connect to the control unit, and one utility channel for the
hysteroscope. The difference is in their tip configuration. In FIG.
6, the distal end of the applicator can bend to different angles 80
about a pivot 74, to accommodate different approaches to the
treatment zone. A knob 77 at the device handle controls the tip
articulation, providing an adjustable head angle over a range of up
to 90 degrees. Alternatively, the distal end of the device may be
fixed, and several applicators of different fixed tip angles can be
provided for different treatments.
[0063] The ultrasound transducer in the end of the trans-cervical
applicator may have a limited usable lifetime. The tip of the
device may be a reposable (disposable, with a limited number of
times of reuse). A used tip can thus be removed, and a new tip
attached. The reposable portion may include shaft 70, so that the
connection port will be in the handle, which stays outside the
patient and is not immersed in fluid.
[0064] Trans-abdominal ultrasound device 29 shown in FIGS. 3A and
3B has a long shaft 28 that can be inserted into the patient's
abdominal cavity through laparoscopic surgery cannula 34, which is
disposed in a puncture hole on the abdominal wall. Under visual
guidance of a laparoscope, distal end 30 of the device is brought
in close contact with the uterine fibroid. As in the trans-cervical
device, ultrasound array transducer 36 is preferably mounted at
distal end 30 of the device for imaging and therapy. Guided by the
ultrasound image, the physician uses the device to necrose the
fibroid tissue. The distal end of the device is preferably
articulated at a flexible shaft segment 31, as shown in FIG. 3C,
with one or two knobs 32 (depending upon whether one or two axes of
articulation are provided) that are disposed on handle 33 of the
device. This flexible shaft segment permits treatment zone 38 to
point in different directions to accommodate different tumor
positions. The ultrasound transducer may be disposed in a cover
case balloon 41 or other cover at the tip of the device (FIG.
3C).
[0065] Cover case balloon 41 is elastomeric and conforms to an
outer surface of a tumor, providing more efficient acoustical
coupling between the transducer and the treatment area; the
curvature of the tumor contour will, in general, be different from
the curvature of the ultrasound transducer. Moreover, during a
conventional laparoscopic procedure, the patient's abdomen is
inflated with CO.sub.2 gas to create a large working space. A gas
gap between the transducer and the tumor, however, would block the
ultrasound transmission. Instead of penetrating into the tumor, the
ultrasound beam would be reflected back to the transducer. The
therapeutic effect would thus be diminished and the transducer
might be damaged by the reflected ultrasound energy.
[0066] It thus is important to maintain good acoustic coupling
between the treatment tissue and the ultrasound transducer while
provide the ultrasound therapy. Water, saline, and most water-based
solutions and gels are excellent coupling media. In diagnostic
ultrasound imaging, water-based coupling gel is widely used.
However, gel may have limitations in trans-abdominal ultrasound
therapy for treating uterine fibroids. Unlike skin, the fibroid is
much less compressible. It is also more difficult to apply manual
pressure during a laparoscopic procedure to conform the fibroid to
the surface contour of the transducer. Gel may be used to fill the
remaining gaps, but gas bubbles trapped in the gel are difficult to
squeeze out.
[0067] In this preferred embodiment of the present invention,
water-filled cover case balloon 41 (FIG. 3C) is fabricated of thin
elastic material and is placed between the transducer and the
fibroid to ensure effective coupling of the ultrasonic energy into
the tumor mass. Under a small manual pressure, the balloon is
conformed to both the transducer surface and the fibroid surface.
If the transducer is inside the balloon, only the fibroid surface
needs to be wetted with sterile saline to keep a good coupling to
the balloon surface. Alternatively, cover case balloon 41 may be
fabricated of a semi-permeable membrane material that enables
liquid to weep from inside the balloon. The "weeping" of the fluid
from the balloon thus can keep the fibroid surface wet during the
treatment. When the internal pressure is higher than the pressure
in the abdominal cavity, the sterile saline or water inside the
semi-permeable balloon readily weeps through the semi-permeable
membrane to create a fluid interface-layer that maintains
continuous effective coupling.
[0068] Alternatively, as shown in FIG. 11, a vacuum cap 138 made of
soft rubber, plastic, or other elastomeric material, may also be
applied at the distal end of the device to provide the acoustic
coupling as shown in cross section at FIG. 11. The cap surrounds
ultrasound transducer array 36 and is open at its front, opposite
the array. The front opening of the cap is large enough to permit
the ultrasound beam to pass without obstruction. Around the open
end of the cap, a rim 131 has a double lip 130. The double lip is
soft and elastomeric and can conform to the shape of a tumor
surface 136. A vacuum port 134 is provided in fluid communication
with the double lip, and a vacuum source coupled to this port
provides a negative pressure within the double lip that holds the
cap tightly on the tumor. Sterile water is then provided through a
port 132 that communicates with an interior of the cap to provide
the acoustic coupling between the transducer and the tumor. The cap
works as a wall to block gas from getting into the cap. In case
there are any minor leaks, the leaking gas and water are removed
immediately at the double lip.
[0069] To protect the ultrasound transducer against accidental
damage caused by the reflected ultrasound power when there are
large gas bubbles or gaps between the transducer and the tumor, or
when the device is lifted from the tumor while the high intensity
ultrasound output is still on, the present invention preferably
uses the ultrasound imaging capability to detect the existence of
gas. When a gas gap exists, it causes a strong reflection detected
when ultrasound imaging. The reflection may also bounce back and
forth between the transducer and the gas gap, resulting in a
reverberation (multiple reflections). The strong reflection or
reverberation appear(s) as very bright echoes in a large portion of
the image. When observing this unique echo image, the medical
practitioner may adjust the position or the coupling of the
ultrasound device to eliminate the trapped gas. As an alternative,
an automatic gas detection technique may be used to avoid the
reflection damage. By using the unique characteristics of the gas
in the reflected echo signal, the system may detect its existence
during the imaging process. When the strong echo is detected, the
system may automatically turn off the high intensity ultrasound
output to the area where there are gas gaps. This automatic power
shut down process is accomplished almost instantaneously, so that
thermal damage to the transducer array is avoided.
[0070] During therapy application, the ultrasound transducer
generate heat internally. This heat can possibly cause damage or
reduce the service life of the transducer array. Moreover, if the
transducer array touches the tumor tissue directly, the high
temperature of the transducer array can prematurely, or
inadvertently, necrose the tissue surface. The high acoustic
absorption of the necrosed tissue at the surface would also prevent
the ultrasound beam from penetrating deep into the tumor, so that
the deep tumor tissue might not be properly treated. It is
therefore very important to keep the temperature of the transducer
array and at the tissue interface relatively low during the
treatment.
[0071] A plurality of techniques can be employed to cool the
transducer array. The simplest approach is to immerse the
transducer in water, maintain a gap between the transducer surface
and the tumor, and then ensure that the water flows through the gap
during the treatment. Two water channels preferably disposed inside
the device casing to circulate the cooling fluid may optionally be
used for this purpose. The ultrasound transducer array is disposed
in one of the channels. Alternatively, both the transducer and the
tumor may be immersed in water. In the trans-cervical approach, the
uterine cavity is conveniently filled with water. In certain
trans-abdominal situations, it may be possible to fill a portion of
the abdominal cavity with water. And, in some non-invasive
situations it is possible to construct a water dam, sealed at its
periphery to the organ surface, creating a water pool in which the
applicator may be positioned. As shown in FIG. 13, a thin-wire
fence 162 or frame attached to distal end 72 maintains a gap
between transducer array 36 and the first interface of patient
tissue (e.g., the tumor's outside surface). A variety of such
useful standoff structures may be employed, as best suited for the
geometric requirements of the application and specific applicator
designs. During treatment, a water jet from a port 160 introduces
water, or saline, into the gap. Circulation of conditioned water
through one or more such ports may be used to control water
temperature, pressure, chemical composition, gas content, or
volume. Alternatively, the transducer array may be cooled by using
a thermal-conductive, acoustic-matching layer (e.g., aluminum)
bonded to the piezoelectric ceramic of the ultrasound transducer
array. This thermal-conductive layer removes the heat from the
transducer ceramic. The heat is removed by water flowing in
attached lines or by heat sinks that are connected to the
thermal-conductive layer.
[0072] To simplify the device design and to reduce the size of the
endoscopic instrument, one ultrasound transducer array is used for
both imaging and therapy. A concave transducer array provides a
good compromise to simplify the design for both functions. Natural
focusing of the concave geometry simplifies the ultrasound beam
forming, where there is no (or less) phase delay needed, and
cross-talk among array elements is less of a problem. Because of
the minimum phase delay required, larger element pitch size can be
used. Large pitch size reduces the number of elements in the array
and the number of electronic signal channels required. It also
helps to reduce the cost of the transducer and the cost of the
control unit. Treatment area 38 is geometrically inside imaging
area 40 of the array (see FIG. 3B). The entire treatment area is
under the ultrasound imaging monitoring--there is no blind spot in
the treatment area.
[0073] FIG. 12 is a simplified block diagram of the electronic
control system according to the invention. The specific applicator
device connected to the control system is recognized electronically
by a system controller 206, which reads applicator data from a
memory device, an ID tag 172. Such data include specific functional
and calibration information. A switch matrix 176 connects a concave
transducer array 170 to the therapeutic circuitry or to the imaging
circuitry. During imaging, an imaging transmitter 186 generates
pulse sequences to drive the ultrasound transducer array through a
transmit-receive switching matrix 190. The imaging receiver
amplifies and processes the echo signals captured by the transducer
array. During the therapy phase, switch matrix 176 connects the
transducer array to the therapeutic transmitter chain to form and
steer a high intensity ultrasound beam within the tissue being
treated. To monitor the treatment process, the transducer array may
be periodically switch back to the imaging circuitry to form frames
of ultrasound images during the treatment.
[0074] System controller 206 provides overall control and
synchronization of the multiplicity of functions executed by the
system including an operator interface control panel 208, a foot
switch 200 that is used for initiating and arresting therapy, and a
timing logic 194, employed for establishing appropriate phasing of
the therapeutic phased array transmit chain. This chain comprises a
primary oscillator 182, a phase locked loop 184, a multi-channel
power amplifier 180 and matching networks 178. Additionally, timing
logic 194 provides data to the imaging chain that includes the
receive amplifiers and time-gain compensation circuits 188, a
quadrature detection circuit 196, an analog-to-digital conversion
circuit 192, an Intensity (B) mode processing circuit 198, an
attenuation processing circuit 204, a Doppler flow processing
circuit 212, and a scan conversion circuit 202. Images of the
target tissue are converted to a format compatible with
standardized operating room video display in image merging circuits
210 and mixed with other video sources (e.g., hysteroscopic optical
imaging), and user interface graphics, and processed in graphic
overlay 216; which is included in a video processor module 214, for
display.
[0075] Thermally necrosed tissue has a much higher acoustic
attenuation (>1.0 dB/cm/MHz) than the untreated tissue (0.4-0.7
dB/cm/MHz). This property may be used to monitor or visualize the
treatment area. One technique to measure the tissue attenuation
change is to measure the frequency spectral change in the echo
signal. High frequency components in the frequency band are
attenuated more than the low frequency components. By subtracting
the spectrum before the treatment from the spectrum after the
treatment, the attenuation change can be measured. If the
subtracted spectrum is near zero, it indicates that the tissue
where the echo is acquired has not been treated. If the result of
spectrum subtraction has a significant slope, it means the tissue
attenuation has changed, indicating that this area has been
necrosed.
[0076] Alternatively, or in combination with this attenuation
imaging, elasticity imaging may be employed to assess tissue state
before, during, or after ultrasonic treatment. Elasticity imaging,
the principles of which are well known in the art, provides a
visualization of physical and mechanical tissue properties.
Necrosed tissues are stiffer and demonstrate elasticity changes.
Treatment endpoints may be manually or automatically controlled
(under operator control) by use of elasticity imaging
parameters.
[0077] As an alternative method of therapy that may reduce the
treatment time even further, the patient may be given an injection
of ultrasound contrast agent, which is a solution of encapsulated
air-containing micro-bubbles that are sufficiently small to
circulate safely in the blood and blood vessels. When the bubbles
are flowing through the fibroid, they will be hit by the high
intensity therapeutic ultrasound. The bubbles enhance the
ultrasound heating process at the treatment area and make the
treatment more efficient.
[0078] As a further alternative method of therapy, cavitation may
be utilized as a mechanism for speeding effective treatment.
Ultrasound with high acoustic pressure and lower frequency
increases the likelihood of stimulating the onset of cavitation.
The presence of contrast media or bubbles also encourages
cavitation. Cavitation can aggressively disrupt tissue and increase
energy transfer for an enhanced heating effect.
[0079] Although the present invention has been described in
connection with the preferred form of practicing it, those of
ordinary skill in the art will understand that many modifications
can be made thereto within the scope of the claims that follow.
Accordingly, it is not intended that the scope of the invention in
any way be limited by the above description, but instead be
determined entirely by reference to the claims that follow.
* * * * *