U.S. patent application number 14/306433 was filed with the patent office on 2015-01-15 for method of thermal treatment for myolysis and destruction of benign uterine tumors.
This patent application is currently assigned to ACOUSTIC MEDSYSTEMS, INC.. The applicant listed for this patent is ACOUSTIC MEDSYSTEMS, INC., THE REGENTS OF THE UNIVERSITY OF CALIFORNIA. Invention is credited to Everette C. Burdette, Dana L. Deardorff, Chris J. Diederich, Alison F. Jacoby, Will H. Nau.
Application Number | 20150018727 14/306433 |
Document ID | / |
Family ID | 38625786 |
Filed Date | 2015-01-15 |
United States Patent
Application |
20150018727 |
Kind Code |
A1 |
Diederich; Chris J. ; et
al. |
January 15, 2015 |
METHOD OF THERMAL TREATMENT FOR MYOLYSIS AND DESTRUCTION OF BENIGN
UTERINE TUMORS
Abstract
A high-power ultrasound heating applicator for
minimally-invasive thermal treatment of uterine fibroids or myomas.
High-Intensity interstitial ultrasound, applied with
minimally-invasive laparoscopic or hysteroscopic procedures, is
used to effectively treat fibroids within the myometrium in lieu of
major surgery. The applicators are configured with high-power
capabilities and thermal penetration to treat large volumes of
fibroid tissue (>70 cm.sup.3) in short treatment times (3-20
minutes), while maintaining three-dimensional control of energy
delivery to thermally destroy the target volume.
Inventors: |
Diederich; Chris J.;
(Novato, CA) ; Nau; Will H.; (Longmont, CO)
; Jacoby; Alison F.; (San Francisco, CA) ;
Deardorff; Dana L.; (Normal, IL) ; Burdette; Everette
C.; (Champaign, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
ACOUSTIC MEDSYSTEMS, INC. |
Oakland
Champaign |
CA
IL |
US
US |
|
|
Assignee: |
ACOUSTIC MEDSYSTEMS, INC.
Champaign
IL
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Oakland
CA
|
Family ID: |
38625786 |
Appl. No.: |
14/306433 |
Filed: |
June 17, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11738391 |
Apr 20, 2007 |
8790281 |
|
|
14306433 |
|
|
|
|
60793750 |
Apr 20, 2006 |
|
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|
60797421 |
May 3, 2006 |
|
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|
60885845 |
Jan 19, 2007 |
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Current U.S.
Class: |
601/3 |
Current CPC
Class: |
A61N 5/045 20130101;
A61B 17/2202 20130101; A61N 2005/1094 20130101; A61N 2007/0004
20130101; A61N 2007/0078 20130101; A61N 7/02 20130101; A61N 7/022
20130101; A61B 2017/4216 20130101 |
Class at
Publication: |
601/3 |
International
Class: |
A61N 7/02 20060101
A61N007/02 |
Claims
1. An apparatus for treating uterine fibroids, the apparatus
comprising: (a) a catheter having a distal end and a proximal end;
and (b) an ultrasound applicator disposed at the distal end of said
catheter, the ultrasound applicator comprising: one or more
transducers disposed longitudinally along a central axis of the
catheter; the one or more transducers being coupled to a power
source external to said catheter; (c) wherein the ultrasound
applicator is configured to be positioned to a treatment location
at or near a fibroid tissue mass and deliver high-intensity
ultrasound energy sufficient to therapeutically heat said fibroid
tissue mass.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 11/738,391 filed on Apr. 20, 2007, now U.S.
Pat. No. ______, incorporated herein by reference in its entirety,
which claims the benefit of U.S. provisional patent application
Ser. No. 60/885,845 filed on Jan. 19, 2007, incorporated herein by
reference in its entirety, U.S. provisional patent application Ser.
No. 60/797,421 filed on May 3, 2006, incorporated herein by
reference in its entirety, and U.S. provisional patent application
Ser. No. 60/793,750 filed on Apr. 20, 2006, incorporated herein by
reference in its entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable
INCORPORATION-BY-REFERENCE OF COMPUTER PROGRAM APPENDIX
[0003] Not Applicable
NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION
[0004] A portion of the material in this patent document is subject
to copyright protection under the copyright laws of the United
States and of other countries. The owner of the copyright rights
has no objection to the facsimile reproduction by anyone of the
patent document or the patent disclosure, as it appears in the
United States Patent and Trademark Office publicly available file
or records, but otherwise reserves all copyright rights whatsoever.
The copyright owner does not hereby waive any of its rights to have
this patent document maintained in secrecy, including without
limitation its rights pursuant to 37 C.F.R. .sctn.1.14.
BACKGROUND OF THE INVENTION
[0005] 1. Field of the Invention
[0006] This invention pertains generally to treatment of uterine
fibroids, and more particularly to ultrasound therapy of uterine
fibroids.
[0007] 2. Description of Related Art
[0008] Uterine fibroids, also known as leiomyomas or myomas, are
the most common solid pelvic tumor occurring in women, and are the
reason for nearly 30% of hysterectomies performed in the U.S.
Further, it has been estimated that 25-50% of women of reproductive
age have one or more uterine fibroids, and the incidence is as much
as 9 times higher in black women than in white women. Depending on
the size, number and location of the fibroids, symptoms can be
severe, and often include excessive or persistent menorrhagia,
pelvic pain and cramping, pressure, urinary problems, constipation,
anemia, or infertility. Another concern is the degeneration of
fibroids to malignant leiomyosarcomas, at an incidence rate of
approximately 0.5%.
[0009] FIGS. 1A and 1B are anatomical sketches contrasting a
healthy patient 10 having a normal uterus 22 with a second patient
12 having a uterus showing growth of uterine fibroids in various
regions. Fibroids are nodules of well-differentiated smooth muscle
encased in fibrous tissue that grow in or on the wall of the
uterus, with some reports of myomas demonstrating skeletal muscle
differentiation. Fibroids range in size from approximately 0.5 cm
to greater than 10 cm in diameter, and may grow as submucosal
fibroids 30 just beneath the endometrium 14 (submucous), as
intramural fibroids 36 within the myometrium 16 (intramural), or
subserosal fibroids 28 beneath the serosa. They may also be
pedunculated, and reside either within the uterine cavity 22
(pedunculated submucosal fibroids 34), or outside the uterus 22 in
the pelvic cavity (pedunculated subserosal fibroids 32).
[0010] Treatment options for women considering bearing children are
limited. The most common and permanent treatment for uterine
fibroids is surgical removal of the uterus (hysterectomy),
particularly in women approaching menopause. Although a permanent
solution for fibroids, hysterectomy is a major surgical procedure
associated with significant risk of mortality/morbidity including
fever, wound infection, excessive blood loss, increased risk for
transfusion, and trauma to the bladder and surrounding tissues.
Recent improvements in hysterectomies performed using a vaginal
approach have demonstrated reductions in blood loss, post-op
complications, length of hospital stay, and overall cost. However,
vaginal hysterectomies are not recommended for patients presenting
with a large fibroid uterus.
[0011] For pre-menopausal women wishing to retain their uterus for
reproductive, psychological or hormonal reasons, myomectomy
(surgical removal of fibroids) can be a less invasive alternative
to hysterectomy. The procedure may be performed via open
laparotomy, or via a number of advanced laparoscopic and
hysteroscopic surgical techniques. For women considering
childbearing, preferred surgery is the open myomectomy in order to
preserve the structural integrity of the uterine wall--the ability
to apply multiple layers of suturing is severely limited for
laparoscopic procedures. While complications are similar to those
of hysterectomy, the complication rate is reduced from 25% to as
low as 14.8%, and fertility may be improved, with pregnancy rates
reported as high as 74%. However, the incidence of post-operative
adhesions may be as high as 89%, and the risk of recurring fibroids
requiring additional surgery or hysterectomy is 15-25%.
[0012] Hormonal therapies such as gonadotrophin releasing hormone
(GnRH) agonists can be used to induce artificial menopause
resulting in a 30-40% decrease in fibroid size, and a 40-50%
reduction in uterine volume. The side effects experienced with
hormonal therapies are similar to symptoms often associated with
menopause (hot flashes, irregular vaginal bleeding, vaginal
dryness, headaches, and depression). However, prolonged use may
result in excessive bone loss, and the fibroids will return to
their pre-treatment volumes within 3 months if treatment is
discontinued. Rather than a long term treatment option, hormonal
therapies are often used prior to myomectomy to reduce the size of
the uterus and the fibroids thus facilitating the surgical
procedure.
[0013] Uterine artery embolization (UAE) is a minimally-invasive
surgical procedure used to treat fibroids by obstructing their
blood supply. A catheter, advanced into the uterine artery under
fluoroscopic guidance, is used to inject polyvinyl alcohol
particles resulting in immediate obstruction of blood flow.
Clinical studies indicate that UAE reduces fibroid volume by
approximately 35-60%, and has been effective in 85% of the
patients. Complications of the procedure include risk of allergic
reaction to medications, infection, contrast-induced renal failure,
uterine perforation, sexual dysfunction, and post-procedure pain
attributed to the ischemic necrosis. Fibroid sloughing requiring
additional surgery occurs in about 10% of the patients.
[0014] Laparoscopic myoma coagulation (myolysis) is a
minimally-invasive procedure in which a laser or a radiofrequency
(RF) needle is used to thermally coagulate and necrose uterine
fibroids and their vascular supply. Both modalities can be used to
thermally coagulate and reduce the size of uterine fibroids by as
much as 40 to 50%. However, a recent clinical study using an RF
needle electrode with extendible secondary electrodes to treat
large fibroids demonstrated the ability to produce a 5 cm diameter
region of necrosis resulting in as much a 77% reduction in fibroid
volume. Yet spatial control of the pattern is very difficult, if
not impossible. An advantage of myolysis performed using a laser
fiber is that treatment can be guided and monitored in real time
with MR thermal monitoring techniques. However, since the
propagation of energy, and hence coagulation of tissue, is limited
to a radial distance of less than 1 cm from the applicator at a
single puncture, high power levels, multiple punctures (sometimes
>50) and longer treatment times are often required to treat
commonly occurring large myomas (5+ cm diameter) using either RF or
laser modality. Techniques using either sequential insertions or
multiple, simultaneously implanted laser fibers around the
circumference of the fibroid have been used to coagulate the outer
boundary, thus destroying the blood supply and shrinking the
fibroid. Although major complications with this technique are rare,
the risk of post-operative adhesions increases with the greater
number of device insertions required to heat larger fibroids.
Control of thermal coagulation with these technologies is
determined by applied power only, with no dynamic angular or
longitudinal spatial control of heating along the length of the
applicator, or radially/angularly from it.
[0015] The feasibility of using cryotherapy for treatment of
fibroids has been investigated. Initial studies demonstrated an
overall reduction in fibroid size of only 10%; recent studies have
shown clinical results similar to those obtained by other
minimally-invasive treatments with mean volume reductions up to
65%. Furthermore, this technology can be used with interventional
MR imaging for visualization and guidance of the cryoneedles, and
monitoring of the freezing procedure. Control of the freezing zone
is problematic. Complications of this technique are similar to
those associated with thermal coagulation methods. The applicator
diameters range 3-5 mm, and are introduced with trocars and
introducer sheaths similar to our proposed procedure.
[0016] In some, the above thermal techniques (e.g. cryotherapy or
high-temperature thermal ablation) have at least one of the
following limitations: inability to spatially control the
distribution of energy output to conform to the fibroid volume,
inadequate single treatment volumes requiring multiple device
insertions (increases risk of adhesions), long procedural times, or
limited use due to proximity of critical tissue structures (e.g.,
bladder, bowel). These limitations may reduce their effectiveness
and overall applicability to consistently and safely treat
symptomatic fibroids.
[0017] High-intensity externally-focused ultrasound (HIFU) is a
another, non-invasive method used to generate well-localized
thermal damage deep within the body, while possibly avoiding damage
to the overlaying or surrounding tissues. Although this technique
is non-invasive and capable of precise coagulation of tissue, long
treatment times (>2 hours) are required to treat small tissue
volumes (12 cm.sup.3), access to fibroids located in proximity to
bowel or bladder is limited, and lack of adequate acoustic window
and pre-focal heating limits this technology to accessible small
fibroids. Significant reported complications include thermal damage
or burns in deep tissue, bowel, and superficial tissue layers,
including the skin beneath the acoustic interface.
[0018] There is a substantial clinical need for a
minimally-invasive alternative to traditional open surgical
approaches with the promise of less morbidity and recovery time,
faster procedure time, and lower cost. Interstitial ultrasound has
potential to provide a superior minimally-invasive heating
technique for the laparoscopic treatment of uterine fibroids with
the promise of more precise and thorough targeting, accessibility
to a larger number of fibroids, faster procedure times, and
repeatable performance acceptable to the gynecological surgeon.
BRIEF SUMMARY OF THE INVENTION
[0019] The present invention may be used to treat fibroids,
including ones considered too large for existing heating
technologies, by using ultrasound energy to heat or ablate the
fibroid or a portion of the fibroid. The ultrasound system and
methods of the present invention allow directional control and deep
penetration of energy patterns for directed thermal arterial
occlusion/coagulation. With the system of the present invention,
large fibroids can be treated by targeting a smaller portion of the
tumor with the feeding vasculature, thus reducing the treatment
time and improving chances for complete regression. In addition,
this requires less of a volume be thermally fixed or destroyed,
which may remain in the body for some time and in some circles
considered clinically undesirable.
[0020] The present invention is directed to a high-power
intracavitary and interstitial ultrasound heating applicators for
minimally-invasive thermal ablation of uterine fibroids or myomas.
High-Intensity intracavitary and interstitial ultrasound, applied
with minimally-invasive laparoscopic or hysteroscopic procedures,
is used to effectively treat fibroids within the myometrium in lieu
of major surgery, providing a better alternative treatment for
women wishing to bear children. The applicators of the present
invention are configured with high-power capabilities and thermal
penetration to treat large volumes of fibroid tissue (>70
cm.sup.3) in short treatment times (3-20 minutes), while
maintaining three-dimensional control of energy delivery to
thermally destroy the target volume. Directional or selective
heating may be used as a means of preserving surrounding healthy
tissue, for example to avoid bladder, bowel or other sensitive
organs.
[0021] An aspect of the invention is an apparatus for treating
uterine fibroids, having a catheter with a distal end and a
proximal end and an ultrasound applicator disposed at the distal
end of the catheter. The applicator has one or more transducers
disposed longitudinally along a central axis of the catheter,
wherein the one or more transducers are coupled to a power source
external to the catheter. In particular, the ultrasound applicator
is configured to be positioned to a treatment location at or near a
fibroid tissue mass and deliver high-intensity ultrasound energy
sufficient to heat and destroy the fibroid tissue mass. The
delivered energy is sufficient to ablate or necrose the fibroid
tissue.
[0022] In a preferred embodiment, the applicator is configured such
that sufficient energy is applied to treat the fibroid tissue
within a period ranging between approximately 3 to 20 minutes, and
preferably 5 to 15 minutes.
[0023] The applicator ideally comprises an array of two to five
transducers, and more preferably three to four transducers. In one
embodiment, the transducers are tubular and disposed adjacent each
other over a support element in a linear array.
[0024] In another embodiment, the transducers are configured to
provide directional energy distribution of the ultrasound energy in
a first direction associated with the fibroid while shielding
ultrasound energy in a second direction. The transducers may be
configured to emit ultrasound energy in a substantially 360.degree.
pattern radially from the axis of the catheter, or emit a radial
pattern less than 360.degree., e.g. 180.degree., 120.degree., or
90.degree., etc. In addition, the transducers may be sectored and
individually wired to each emit a portion of a 360.degree. radial
pattern. Additionally, the transducers may be each arcuate and emit
focused energy as a line focus in a specific direction pointing
into the fibroid, which may be selected by rotating the
transducer.
[0025] The ultrasound transducers may be disposed within the
catheter, (e.g. emit through the catheter walls, or be disposed
adjacent to the distal end of the catheter.
[0026] The catheter may also be configured to provide fluid cooling
to the ultrasound elements. In one embodiment, the applicator
further comprises a balloon emanating at the distal end of the
catheter, wherein the balloon configured to surround the one or
more transducers to circulate the cooling fluid around the one or
more transducers. The catheter may also comprise a multi-lumen
catheter with a first lumen configured to deliver fluid to the
applicator, and a second lumen configured to transport fluid out of
the applicator.
[0027] The device may also comprise a retractable sheath configured
to surround the applicator during delivery to the treatment
site.
[0028] In another embodiment, the device includes a temperature
probe disposed at the distal end of the catheter, wherein the
temperature probe is configured to acquire temperature readings at
one or more locations of tissue in vicinity to the applicator.
[0029] In yet another embodiment, the catheter comprises a bendable
portion proximal to the applicator such that the applicator may be
oriented at an angle with respect to the catheter proximal to the
bendable portion, wherein the bendable portion comprises a material
configured to retain the angle as the applicator is delivered to
the treatment site.
[0030] The applicator may be configured to be delivered via
laparoscopic access, hysteroscopic access, or both.
[0031] Another aspect of the invention is a method of treating a
uterine fibroid. The method includes the steps of positioning an
ultrasound transducer at a treatment location at or near a fibroid
tissue mass, and administering power to the transducer to deliver
high-intensity ultrasound energy to the fibroid tissue mass
sufficient to heat and destroy the fibroid tissue mass, e.g. via
ablating or necrosing the fibroid tissue.
[0032] Prior to delivery of the ultrasound energy, the power,
treatment time, and frequency of the ultrasound energy may be
determined based on the fibroid tissue anatomy, and input into a
computer controlling the energy transmitted from the
transducer.
[0033] In one embodiment, the ultrasound energy is delivery to only
a portion of the fibroid tissue, ideally the portion comprising
feeding vasculature.
[0034] In another embodiment, a thermal sensor may be deployed to
obtain temperature feedback of tissue at or near the applicator.
Also, the method may include determining the extent of arterial
occlusion by applying one or more of the following diagnostic
techniques: such as fluoroscopic, Doppler ultrasound, MRI, or CT
imaging.
[0035] The energy may be delivered from the applicator in an array
of transducers. In some embodiments, the transducers are
individually operable to independently or concurrently deliver
ultrasound energy.
[0036] In one embodiment, the applicator is delivered to a
substantially central location within the fibroid tissue, and is
controlled to emit ultrasound energy in a substantially 360.degree.
pattern radially from an axis of the catheter.
[0037] Alternatively, the applicator is delivered to a location
substantially adjacent the fibroid tissue, and controlled to emit
ultrasound energy in a radial pattern less than 360.degree., e.g. a
radial pattern of approximately 180.degree. or less.
[0038] In another embodiment, the method may include delivering a
cooling fluid to the applicator through the catheter during
delivery of ultrasound energy.
[0039] Another aspect of the invention is an apparatus for treating
uterine fibroids, having a catheter with a distal end and a
proximal end, and an ultrasound applicator disposed at the distal
end of the catheter. One or more tubular or arcuate transducers are
disposed longitudinally over a support element that is
substantially coincidental with a central axis of the catheter. A
power source external to the catheter is coupled to the one or more
transducers. In particular, the ultrasound applicator is configured
to be positioned at a treatment location to deliver high-intensity
ultrasound energy sufficient to heat and destroy a fibroid tissue
mass located at or near the treatment location.
[0040] In one embodiment of the current aspect, the applicator
comprises an array of two to five transducers disposed adjacent
each other in a longitudinal array, and preferably an array of
three to four transducers.
[0041] Further aspects of the invention will be brought out in the
following portions of the specification, wherein the detailed
description is for the purpose of fully disclosing preferred
embodiments of the invention without placing limitations
thereon.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)
[0042] The invention will be more fully understood by reference to
the following drawings which are for illustrative purposes
only:
[0043] FIG. 1A is a diagram of a healthy uterus.
[0044] FIG. 1B is a diagram of a uterus with fibroids.
[0045] FIG. 2 illustrates a laparoscopic approach to treating
fibroids in accordance with the present invention.
[0046] FIG. 3 further illustrates the laparoscopic procedure with
the ultrasound applicator of the present invention positioned
adjacent the target fibroid.
[0047] FIG. 4 shows a hysteroscopic procedure in accordance with
the present invention.
[0048] FIG. 5 shows a distal tip of a conformable ultrasound
applicator of the present invention.
[0049] FIG. 6 illustrates a liquid-cooled applicator.
[0050] FIGS. 7A-7D illustrate side views of various ultrasound
element configurations.
[0051] FIG. 8 illustrates a flow diagram of an exemplary fibroid
treatment process in accordance with the present invention.
[0052] FIG. 9 illustrates angular and axial control of power
deposition (P.sup.2) and heating from in vivo measurements of
temperature and zones of thermal coagulation.
[0053] FIG. 10 shows a plot of ultrasound energy distribution of a
200 degree applicator.
[0054] FIG. 11 is a graph of the treatment depth across the axial
position of the applicator.
[0055] FIG. 12A-12C show a simulation of the radial depth into
tissue for one, two, and three element applicators.
[0056] FIG. 13 illustrates the 3-D distribution of a 2-transducer
applicator.
[0057] FIG. 14 illustrates MRI images of the thermal dose delivered
to tissue during application.
[0058] FIG. 15 illustrates test results for temperature and thermal
dose measurements of a 2.4 mm OD ultrasound applicator.
[0059] FIG. 16 illustrates an exemplary test set up for testing the
ultrasound applicator of the present invention on an ex-vivo human
fibroid sample.
[0060] FIGS. 17-19 illustrate the results of the heating trial in a
human uterine fibroid using a 4-element applicator with 360 degree
heating pattern inserted in a 13 g catheter with 60 ml/min flow
rate.
[0061] FIG. 20 illustrates a sagittal slice through thermal lesion,
visualized after 20 minutes in a 2% TTC solution.
[0062] FIGS. 21 and 22 illustrate transverse slices through thermal
lesions (as visualized using TTC stain) generated in human uterine
fibroids using a 3-element applicator with a 180 degree directional
heating pattern, inserted in a 3.7 mm OD catheter with 60 ml/min
flow rate.
[0063] FIG. 23 illustrates untreated tissue showing lighter,
heterogeneous and slightly granular chromatin, and visible nuclear
features.
[0064] FIG. 24 shows treated tissue indicating hyperchromatic
nuclei.
[0065] FIG. 25 illustrates a three.times.10 mm transducer
applicator and resulting tissue lesion.
[0066] FIG. 26 illustrates a four.times.10 mm transducer applicator
and resulting tissue lesion.
[0067] FIG. 27 illustrates a lesion created by a two.times.10 mm
transducer applicator with 180.degree. directional
distribution.
[0068] FIG. 28 illustrates a lesion created by a 180.degree.
directional distribution applicator and insertion point.
DETAILED DESCRIPTION OF THE INVENTION
[0069] Referring more specifically to the drawings, for
illustrative purposes the present invention is embodied in the
apparatus and method generally shown in FIG. 2 through FIG. 28. It
will be appreciated that the apparatus may vary as to configuration
and as to details of the parts, and that the method may vary as to
the specific steps and sequence, without departing from the basic
concepts as disclosed herein.
[0070] FIG. 2 illustrates the overall schema for laparoscopic
interstitial ultrasound thermal treatment of a uterine fibroid 30
embedded in myometrium 16, following procedures similar to those
used for laparoscopic myomectomy or recent RF/cryotherapy ablation
studies, providing a simple and minimally-invasive treatment
technique.
[0071] Multiple access ports 46 (generally three to five) for the
laparoscope 40 and surgical instrumentation (e.g. catheter 44) may
be placed within the abdominal wall 48, and the abdominal cavity
pressurized with gas. The uterus 22 may be positioned with a
standard manipulator 42 and a path to the fibroid 30 cleared.
[0072] The ultrasound applicator 50 may be centered or placed
eccentric within fibroid 30 using standard manipulators to position
tissues prior to insertion. Positioning of applicator 50 to the
treatment site may be affected via a working channel of laparoscope
40, or via a dedicated port as shown in FIG. 2.
[0073] Pre-operative imaging studies, direct magnified
visualization, and/or the use of intraoperative ultrasound imaging
can be used to determine treatment parameters a priori and verify
device placement, with Doppler ultrasound able to localize feeding
vasculature for targeting.
[0074] Referring to FIG. 3, the ultrasound therapy device 50 of the
present invention is configured for insertion directly into the
fibroid 30 during laparoscopic surgery. The device 50 may comprise
a rigid introducer sheath 62 configured to be inserted into the
fibroid 30. The device 50 may also comprise thermometry sensors 66
that deployable within the target volume of the fibroid 30. The
sheath 62 may be retracted once the high-powered ultrasound
applicator 50 is inserted to a predetermined depth.
[0075] The applicator 50 of the present invention includes
substantial power output (30-50 W/cm.sup.2 applied power) with
controlled heating of larger tumor volumes.
[0076] High-powered ultrasound may be applied via one or more
ultrasound transducers 64 positioned at the distal tip of the
applicator 50, and may be applied at preset power levels and
duration to conform therapy to the target zone 70 for the thermal
lesion. Applicator transducers 64 may be at least one of the
following: tubular, planar, or arcuate. The applicator 50
preferably includes a deployable pre-shaped thermocouple
temperature probe 66 (e.g. nitinol hypodermic tubing, pre-shaped by
heat fixation) that is integrated with the introducer sheath 62 and
designed to deploy into the target zone 70. Deployable temperature
sensing via sensor array 66 provides treatment verification and
feedback so that only the desired treatment region or target zone
is affected. Furthermore, additional protection can be instituted
by placing a small air-gap or acoustic blocking or shielding
material 68 between the applicator and the area to be protected
(e.g. bowel 72 or bladder 52).
[0077] As shown in FIG. 4, applicator 80 may be configured to
deliver treatment hysteroscopically via vaginal access 24 into
uterus 22. Applicator 80 may be configured and shaped specifically
for this type of procedure, or may be configured to be used
interchangeably for laparoscopy or hysteroscopy.
[0078] FIG. 5 illustrates an ultrasound applicator 90 configured to
be compliant to bend at a point proximal to distal tip 92 and the
applicator elements 64. In this configuration, the applicator may
comprise a compliant memory material (e.g. nitinol) at location 96
so that the distal tip 92 may be bent at an angle .theta. with
respect to proximal section 94 as desired by the physician
according to the anatomy of the patient and location of the
fibroid, and retain its shape throughout the procedure. In an
alternative configuration (not shown), the applicator tip 92 may be
steerable by inclusion of one or more guidewires extending from the
proximal end of the catheter to the distal tip. Thus, the
applicator tip may be bent to the desired shape while the
applicator is positioned at the treatment location within the
patient's body by pulling on the guidewire.
[0079] The applicator 50, 80, 90 is preferably configured to
withstand the rigors of laparoscopic surgery, and have support
systems and control, manipulators and procedures, specific tooling,
treatment feedback and control schemes, and treatment planning
schemes based upon pre-operative and/or intra-operative imaging
studies, treatment modeling, on-line real-time thermal dose
monitoring/control.
[0080] FIG. 6 illustrates a high intensity catheter-cooled
interstitial ultrasound applicator 100 of the present invention. A
plurality of transducers 64 are positioned at or near the distal
tip 112 of a multi-lumen catheter 102. The number of transducers
may vary from 1 to over 5, but preferably range from 2-4
transducers. The transducers are generally cylindrical or tubular
members that fit sequentially over polymide support tube 110. Each
of the transducers may be separated by a coating 122, which may
comprise, for example, a lamination of an epoxy, silicone adhesive
and polyester layers or combination of the above. Other
layering/materials may be also be used as desired.
[0081] Catheter 102 preferably comprises inbound and outbound
lumens 106 (e.g. multi-lumen catheter) for cooling water flow 106.
The cooling liquid (e.g. water) may be cycled at and around the
transducers 64 via inlet port 120 and outlet port 118 at proximal
end 116 of the catheter. The cooling liquid may be cycled within a
polyester balloon 108 to achieve active water-cooling of the
transducer crystals 64. RF power lines 104 may be feed out port 114
for quick-connect leads 124 or like connection.
[0082] The applicators 50, 100 may be configured in three primary
size configurations: 1) smaller applicators with a 14-15 g
needle/catheter (1.8-2.1 mm OD), 2) larger diameter devices
utilizing 8-9 g catheters (3.8-4.2 mm OD) (e.g. placed through a
laparoscope 40 working channel), and 3) revision of a 2.4 mm
diameter 13 g device to increase power handling. The smaller 14-15
g catheters generally represent a lower size limit for applicators
with the proposed high powers, and can be used with existing
instrumentation for laparoscopic and hysteroscopic approaches.
Though these smaller sizes are preferred for insertion, the two
larger devices may be beneficial for attaining maximum power
handling capability, and can be used with larger trocars and
modified approaches for laparoscopic, and hysteroscopic insertion
(similar sizes are currently used clinically for cryotherapy
probes).
[0083] Fabrication of the applicators may be achieved with use of
tubular piezoceramic ultrasound transducers 64 located around
polymide tubing 100 (see FIG. 6), with an operating frequency of
approximately 7 MHz.
[0084] For achieving high power output, the tubular ultrasound
transducers 64 may vary by the type of piezoceramic material, size
of the transducer crystal, power handling capability, uniformity of
wall thickness, efficiency optimization, electrical impedance,
frequency, piezoelectric activity, electro-acoustic conversion
efficiency, consistent power output, and robust coverings.
Piezoceramic material selection may be based on maximum power
handling and crystal displacement characteristics, using
comparisons between PZT-4 and PZT-8.
[0085] Transducer 64 diameter may be determined by the size
restriction of the external catheter, using 1.0-1.5 mm OD tubular
transducers for the smaller 13-15 g catheters, and larger
transducers of 3.0-3.5 mm OD to maximize power output for the
larger catheters. Transducer 64 lengths may range from
approximately 6-20 mm, and be configured to have the appropriate
balance between axial power potential and electrical impedance.
[0086] The catheter-cooled ultrasound applicator 100 may utilize
Celcon (acetal copolymer) for the implant catheter 102 material.
While this material has been sufficient for low to moderate power
applications, it may be limited at higher powers due to acoustic
properties that partially block energy transmission. Suitable
catheter materials, e.g. thermoplastics such as polycarbonate,
polyether (Pebax and Hytrel), nylon 6-6, polyethylene, and
polypropylene, may be selected based on a number of material
properties. Criteria used to select the materials may include both
acoustic properties (acoustic attenuation and impedance) and
thermal properties (thermal conductivity, melting temperature, and
deflection temperature), as well as overall stiffness/durability of
the material and its ability to be extruded, and the optimal
combination of these material properties to maximize power output.
The diameter and thickness of the catheter 102 material are
configured for the appropriate applicator dimensions to provide a
robust delivery device while minimizing blockage of energy
transmission.
[0087] The cooling system, mechanisms, and flow schemes of the
applicator 50 are configured to achieve levels of convective
cooling necessary to allow higher levels of applied power (30-50
W/cm.sup.2 applied power).
[0088] The transducers 64 may also be shaped to provide controlled
and directed heating of tissue, and maintain control and
directionality of tissue heating at higher power levels.
Specifically, the shape may be configured to maintain longitudinal
control (heating control along the length of the applicator 50) and
angular control (heating around the applicator 50). Multiple
transducer elements (for example, but not limited to 1-5
transducers) may be used to achieve heating lengths of 5 cm or
greater, as well as to control the length of heating with
individual power to each transducer element with collimated
acoustic output.
[0089] The applicators may be fabricated using transducers with
360.degree. angular acoustic output to maximize the potential
treatment volume and the uniformity of circumferential heating. In
this case, access to the fibroid is such that the applicator 50,
80, 90 may be positioned within a central location in the fibroid,
and wherein the fibroid is not directly adjacent sensitive
organs.
[0090] As shown in FIGS. 7A-7C, the applicators may also be
fabricated using transducers that are sectored to provide a
specific angular acoustic region (i.e. 60.degree. to 180.degree.)
for placement at the periphery of a target region, selectively
destroying the tissue on one side while preserving critical tissue
(e.g. bladder, rectum) on the other side. This configuration is
ideal where access to a central location within the fibroid 30 is
not available, and to protect anatomy that is adjacent or near the
fibroid 30.
[0091] FIG. 7D illustrates an example of an arcuate transducer 156
having a concave transmission surface 158 configured to produce a
focal zone extending outside of the outer diameter of the catheter
102 into the tissue under treatment. The radius r of the concave
surface is configured to be larger than the radius of the catheter
102 to ensure that focus CL (the focused beam path center line for
the transducer along the axis of the catheter) is outside the
catheter 102. The radius r may be varied so that the beam path CL
focuses on a desired location away from the catheter 102. In this
configuration, the applicator may be swept across a path to treat a
volume of tissue. For example, the applicator may be placed
adjacent a fibroid 30 outer surface with the surface 158 and beam
path CL pointing inward toward the center of the fibroid. The
applicator may then be swept around the fibroid outer surface to
treat the entire volume of the fibroid.
[0092] As shown in FIG. 7A, element 64 may comprise two notches 130
in the surface of the element to electrically isolate a first
portion (half) 132, from a second portion 134. As shown in FIG. 7A,
the notches 130 are 180.degree. apart from each other, allowing an
180.degree. distribution pattern from side 132. Only one side may
be wired (e.g. section 132) or both may be individually wired for
selective and independent control of each section 132, 134.
[0093] As shown in FIG. 7B, applicator element 140 may have three
or more notches 130 to have additional sections 140, 142, 144 for
individual control. As shown in FIG. 7B, section 142 is configured
to emit a 120.degree. distribution beam. Each segment may be
operated independently and/or concurrently, and adjusted according
to different levels (e.g. power from 0 to max, frequency, and
emission time) for desired coagulation or distribution.
[0094] Referring to FIG. 7C, element 150 may be configured to have
electrical covering 154 etched and removed to have emitting section
154 to have a less than 360.degree. distribution.
[0095] The general durability and robustness of the ultrasound
applicator 50 are a factor of the thermal thresholds and mechanical
thresholds for both transducers 64 and delivery devices.
[0096] The applicator 50 of the present invention is optimized for
maximum transducer power output, electro-acoustic efficiency, and
acoustic beam intensity distributions. Power may be applied to
transducers using a 16-channel amplifier system (0-50 W/channel,
frequency range 6-10 MHz, Advanced Surgical Systems).
[0097] For the proposed application in treating fibroids, high
levels of power will be applied for approximately 5-15 minutes.
Performance criteria may include power application of 30-50
W/cm.sup.2 or more for 5 minutes with at least 40% conversion
efficiency, or more.
[0098] Referring back to FIG. 6, the therapy delivery system of the
present invention may include a computer 128 driving a common
software interface using LabView and C++ to control RF amplifiers
(four or sixteen channel) 126 and a 32 channel temperature
measurement system. Software functionality may include user input
control of RF power and frequency control for each channel,
recording forward/reflected power levels, data logging amplifier
parameters, and alarms at pre-set reflected power thresholds.
Thermometry software may include multi-sensor temperature sensing,
e.g. of sensor array 66, for computing cumulative thermal dose,
data logging, and color bars to indicate status of each temperature
point (i.e., sublethal, lethal, max threshold). Embedded and C++
software may be used for amplifier control and temperature/dose
monitoring and feedback.
[0099] FIG. 8 illustrates an exemplary flow diagram for the uterine
tumor treatment process of the present invention. First, the
applicator (50, 80, 100, etc) is positioned to the treatment site
at step 160. Direct optical visualization using a
laproscope/hysteroscope, and/or via real-time ultrasound image
guidance may be used to direct the applicator toward the target
region.
[0100] The treatment parameters (e.g. power, time, frequency) are
then input at step 162 into the computer 128. These parameters are
generally a function of the treatment volume, geometry and location
of the lesion, and may be assessed with a pre-operation
evaluation.
[0101] The power is then activated to the applicator at step 164.
Generally, this will take approximately 5-10 minutes, and thermal
monitoring may be performed throughout this step. Preferably, the
energy is directed toward feeding blood vessels and maintained at
the target vasculature until temperatures sufficient to collapse
and/or destroy the vasculature are obtained. Thus, it may be
sufficient to just heat a portion of the fibroid to obtain the
desired therapeutic effect. The applicator may also be swept across
a region of the fibroid 30 if needed. Temperature feedback may be
obtained via the deployable thermal sensors 66. In addition, the
extent of arterial occlusion or other effects of thermal therapy
may be assessed non-invasively during or following heating by
diagnostic techniques such as Doppler ultrasound imaging of the
treated vascular region with contrast media for cases where the
vasculature is targeted, fluoroscopy with contrast, MRI T1 contrast
enhanced imaging, or contrast enhanced CT imaging. Other monitoring
methods include acoustic harmonic motion imaging, pattern
recognition analysis of backscatter image data, and acoustic
elasticity imaging;
[0102] If occlusion is deemed insufficient, the applicator may be
turned on to reheat the target tissue. High-temperature thermal
ablation with coagulation of major structural proteins (large
thermal doses), or just thermal necrosis alone (low temperatures or
thermal exposures) can be used.
[0103] At step 166, the power is then turned off, and the device is
removed after target destruction has been completed.
[0104] Design criteria for the applicators of the present
invention, such as introducer sheaths, catheter OD limits,
stiffness constraints, device length, and additional supporting
instrumentation, are based on the unique aspects of laparoscopic
and hysteroscopic surgeries.
[0105] The applicator 50 is configured to treat tissue based on
target tissue parameters (e.g. fibroid), and features of the
ultrasound transducer (size, frequency, and efficiency), beam
distribution, power levels, catheter material, convective cooling,
may be varied to account for tissue thermal properties, and dynamic
changes in tissue perfusion and ultrasound absorption during
thermal exposure.
[0106] The acoustic attenuation of fibroids is different than
typical soft tissue, and can range from low for necrotic cores to
quite high due to the high collagen composition and possibly
calcification; the attenuation has been reported to range from
0.9-2.2 dB/cm/MHz, and increase to 1.7-3.3 dB/cm/MHz after HIFU
ablation.
[0107] Applied power sequences and cooling schemes may also be
varied to best control thermal energy penetration to either
maximize the thermal lesion 30 size, or to constrain treatment to
within a specific radial distance for safety reasons. This includes
applied power sequence (ramp, step, pulsed), applied power
requirements, and treatment duration.
Experiment #1
[0108] Ultrasound interstitial applicators were evaluated for
interstitial hyperthermia for combination with radiation or drug
therapy, as well as localized thermal ablation. The interstitial
ultrasound applicators utilized arrays of small tubular ultrasound
radiators, designed to be inserted within plastic implant catheters
typically used for interstitial HDR brachytherapy. Water-flow was
used during power application to couple the ultrasound and improve
thermal penetration. Multi-transducer devices were evaluated with
transducer diameters between 1.2 mm-3.5 mm and outer catheter
diameters between 2.1 mm (14 gauge) and 4.0 mm (12 Fr),
respectively, with 1.5 mm OD transducers and 13 g (2.4 mm OD)
catheters the most common configuration. The applicators were
fabricated with multiple tubular segments, with separate power
control, so that the power deposition or heating pattern could be
adjusted in real time along the applicator axis.
[0109] The ultrasound energy emanating from each transducer section
was highly collimated within the borders of each segment so that
the axial length of the therapeutic temperature zone remained well
defined by the number of active elements over a large range of
treatment duration and applied power levels. FIG. 9 illustrates
angular and axial control of power deposition (P.sup.2) and heating
from in vivo measurements of temperature and zones of thermal
coagulation. Thus the applicators of the present invention are
ideally suited to tailor temperature distribution in response to
anatomy, dynamic changes in perfusion, etc.
[0110] Furthermore, the angular or rotational heating pattern, as
modified by sectoring the transducer surface, was tested. For
example, active zones can be selected (i.e., 90.degree.,
180.degree., or 360.degree.) to produce angularly selective heating
patterns. FIG. 10 illustrates the angular distribution of a
200.degree. applicator. Thus, the orientation of the directional
applicators of the present invention can be used to protect
critical normal tissue or dynamically rotated and power adjusted to
more carefully tailor the regions of heating.
[0111] FIG. 11 illustrates the radial depth of the lesion across
the axial position of the applicator with respect to the three
elements. The multi-element ultrasound applicators were
demonstrated to produce contiguous zones of therapeutic
temperatures or coagulation between applicators with separation
distances of 2-3 cm, while maintaining protection in non-targeted
areas. For the interstitial ultrasound devices with tubular
sources, the radial penetration of energy falls off as 1/r with
exponential attenuation and compares favorably to the 1/r2 losses
of RF needles and 1/rn (n=1-3) losses of microwave antenna. The
spatial control along the length of these ultrasound applicators is
superior to all other interstitial devices, with axial control
defined by active elements over a large range of applied power and
durations. Operating at high power levels, single applicators can
generate substantial size thermal lesions ex vivo and in vivo up to
21-25 mm radial distance, within 5-10 min treatment times, while
maintaining axial and angular control of lesion shape. These
ultrasound applicators provide the highest level of
controllability, and provide more uniform and penetrating heating
than all other interstitial heating techniques.
[0112] Because of the higher power levels of the applicator 50, the
efficiency and maximum sustainable acoustic output power are
important parameters to characterize. The total acoustic power
output and conversion efficiency may be measured for varying
applicators/transducers using force-balance techniques modified for
a cylindrical radiation source. The acoustic efficiency as a
function of frequency may then be determined for each applicator 50
using static force-balance measurements. High power output
characteristics may then be measured at the frequency of maximum
efficiency.
[0113] The quality and pattern of the ultrasound energy output may
be assessed with acoustic beam distributions. Rotational beam plots
(output at 360.degree. around the applicator) may also be measured
by 3-D scanning of a calibrated hydrophone system (to measure the
acoustic pressure-squared). This distribution of energy output is
proportional to the power deposition within tissue, and is
therefore a significant characterization to determine thermal
therapy potential. Axial, radial, and circumferential fields may be
evaluated using iso-intensity contours. These results may also be
correlated to shapes of thermal coagulation produced during heating
trials ex vivo uterine tissue.
[0114] Biothermal acoustic models were developed by our group to
study ultrasound applicators for hyperthermia and thermal therapy.
The transient finite-difference model is based upon the Pennes
Bioheat equation in cylindrical and Cartesian coordinate system. In
order to improve accuracy, the model incorporates dynamic tissue
changes in response to accumulation of thermal dose. Specifically,
when a t.sub.43=300 min the blood perfusion reduces to zero and at
t.sub.43=600 min the acoustic attenuation increases 1.5-2 times.
This dynamic approach has been used to model transurethral67 and
interstitial ultrasound applicators and shown to be in excellent
agreement with experiment. The thermal dose distribution using the
high-temperature therapy t.sub.43=240 min is used to define the
boundary of thermal necrosis.
[0115] The multi-layered model accepts variable convective heat
transfer coefficients, heat capacity, thermal conductivity,
density, perfusion, and acoustic attenuation within applicator
structures and surrounding tissue. The power deposition is
determined by either numerical solution of the Rayleigh-Sommerfield
diffraction integral using the rectangular radiator method, or by
empirical determination of geometric distributions from beam
plots.
[0116] Simulation of sweeping or rotation of the applicator during
the treatment was also performed. The 2D and 3D models have been
applied to simulate the anticipated heating patterns. FIG. 12
illustrates maximum temperature contours and lesion shapes for r-z
simulations of an interstitial ultrasound applicator heating in
vivo thigh muscle for 3 min with (a) one, (b) two, (c) three active
transducers. The solid black contour lines represent simulated
lesion shapes, and the dashed contour lines represent experimental
in vivo measurements of lesions generated after 3 min of heating
with 30 W/cm2 applied electrical power per element in pig thigh
muscle. FIG. 13 illustrates 3D calculations for a two element
interstitial applicator.
[0117] The ultrasound applicators of the present invention are
amenable to accurate MR image-based treatment planning and thermal
monitoring similar to MR-guided focused ultrasound procedures. As
shown in FIG. 14, MR thermal imaging can be used to map the
temperature elevations and thermal dose (outer contour line) during
the application of power/treatment, as demonstrated for
high-temperature application in vivo (3 slices, 6 mm apart). FIG.
14 demonstrates thermal ablative temperatures in perfused tissue
from cooled 3.5 mm OD transducer array.
[0118] To test the ultrasound applicator devices, heating trials
were conducted in ex vivo uterine fibroid tissue, obtained directly
after surgical removal (hysterectomy or myomectomy). Because
fibroids do not naturally develop in the uterine tissue of other
mammals, there is no satisfactory animal model to test the
applicator performance in a more realistic in vivo environment.
Although there is no blood flow in the ex vivo and in vitro tissue
samples, imaging studies of uterine fibroids have shown that
perfusion in the fibroid tissue is typically low, especially in the
center of the tumor where the vasculature has been replaced by a
necrotic core. Such heating trials provide a controlled
experimental environment where detailed and repeatable tests can be
conducted for direct comparison of applicator performance (which is
considerably more difficult to achieve in vivo). Thus, the use of
ex vivo uterine tissue samples provides the best approximation to
the clinical case.
[0119] The heating trials were performed with a 2.4 mm OD
ultrasound applicator inserted into a pathologic fibroid tissue
sample, which was placed in a temperature-controlled waterbath
(37.degree. C.). Arrays of miniature thermocouple probes were
placed in the tissue, using a template to ensure proper alignment.
The probes were multiple junction constantan-manganin sensors,
encased in thin-walled polyimide tubing, and inserted within 22-g
thin walled needles for minimal thermal conduction and ultrasound
artifact. The thermocouples were used to measure radial and axial
temperature distributions (and resulting thermal dose) in the
tissue, and were recorded using a 32-channel thermometry system
with fast data acquisition interfaced to a computer. Placement
verification was performed using a portable fluoroscopic unit.
Multiple heating trials will be performed with varied applicator
parameters of applied power levels, heating times, coolant flows,
and active transducer elements for each applicator under test.
Following sonication, the tissue was sliced along the transverse
and longitudinal axes to measure the boundary and volume of visible
thermal coagulation.
[0120] The measured radial temperature distributions after 10
minutes of heating using a three element hyperthermia applicator
are shown in FIG. 15. As shown in FIG. 15, large volumes of tissue
(2.5-3.0 cm radius.times.3.0 cm length, or .about.85 cm.sup.3) were
thermally destroyed (e.g. temperature>50.degree. C., lethal
thermal dose>240 min) using this approach.
Experiment #2
[0121] A family of interstitial ultrasound applicators was
fabricated using 2-4 cylindrical piezo-ceramic crystal transducers
(PZT-4) with outer diameters (OD) of 1.5 or 2.5 mm and lengths of
10-15 mm. The configurations tested were 1.5 mm OD.times.10 mm long
transducers in linear arrays of two, three and four adjacent
transducers, an array of three 2.5 mm OD.times.15 mm long adjacent
transducers, and an array of one 2.5 mm OD.times.15 mm long
transducer adjacent to two 2.5 mm OD.times.10 mm transducers.
[0122] The operating frequencies of the transducers ranged from 6.5
to 8 MHz. For some of the applicators, the transducers were
sectored to produce a 180.degree. actively acoustic sector for
directional power deposition. The transducers were mounted on
support structures, and a bio-inert plastic layer was applied for
electrical and biological insulation. The 1.5 mm OD applicators
were inserted into 13 gage brachytherapy catheters (2.4 mm OD), and
the 2.5 mm OD applicators into custom PET catheters (3.7 mm OD).
Degassed water was circulated through the applicators to cool the
transducers during operation, to couple the ultrasound energy to
the tissue, and to potentially control temperature at the
tissue-catheter interface allowing for greater radial penetration
of thermal energy.
[0123] Measurements of electrical impedance (Z) and acoustic
efficiency (.eta.) were obtained for each transducer. Z was
measured as a function of frequency (5.ltoreq.f.ltoreq.10 MHz)
using a network analyzer (Hewlett Packard Model #3577A). .eta. was
measured as a function of frequency using the force balance
technique for cylindrical radiators, and is determined as the ratio
of acoustic output power to the applied electrical power.
Measurements for the applicators were made with no catheters in
place then repeated with the applicators inserted in catheters with
a water flow rate of 40 ml/min.sup.-1. These were used to determine
the optimal driving frequencies, and to determine how much acoustic
energy is being delivered to the tissue.
[0124] The acoustic efficiency data for each transducer type is
summarized in Table 1. As expected, there was a 30-40% decrease in
.eta. when the applicators were placed in the catheters due to loss
of acoustic energy in the catheter wall.
[0125] FIG. 16 illustrates the test setup for human uterine
fibroids obtained immediately after removal during routine surgical
open myomectomies. The fibroids 202 were instrumented with an
interstitial ultrasound applicator 210 and six 20 gage thin-walled
spinal needles 212 placed at radial distances of 0.5, 1.0, 1.5,
2.0, 2.5, and 3.0 cm from the applicator 210, and scattered in
angle for thermometry. A 6 cm.times.8 cm.times.1 cm plexiglass
template 214 was used to ensure alignment of the applicator 210 and
spinal needles 212. The instrumented fibroid 202 was then placed in
a 37.degree. C. circulating waterbath 204, and allowed to reach
equilibrium. Custom, multi-junction contantan-manganin thermocouple
probes consisting of linear arrays of either four 50 .mu.m
junctions spaced at 2.5 mm, or seven 50 .mu.m junctions spaced at 5
mm, were inserted into the spinal needles. A 4 channel amplifier
with built-in function generator and power monitoring (Advanced
Surgical Systems, Inc.) was used to drive the transducers.
[0126] Several heating trials were performed to investigate the
effects of applicator 210 size (2.4 mm OD vs. 3.7 mm OD),
directional heating capability (180.degree. vs. 360.degree. heating
patterns), and number and size of active elements 64 (2-4
transducers) on thermal lesion formation (see Table 2).
Temperatures were recorded every 3 s at each sensor location (up to
27 data points) using a computer controlled data acquisition system
with in-line RF filtering.
[0127] FIGS. 17-19 illustrate the results of the heating trial in a
human uterine fibroid using a 4-element applicator with 360 degree
heating pattern inserted in a 13 g catheter with 60 ml/min flow
rate (f=8.2-8.5 MHz, 15 W to three elements for 8 minutes). FIG. 17
shows the measured transient temperature curves (each curve
represents the average of 4 sensors at each radial depth of 0.5,
1.0, 1.5, 2.0, 2.5, and 3.0 cm). FIG. 18 is a graph of the radial
temperature distribution after heating for 2, 4, 6 and 8 minutes,
and average accumulated thermal dose at each radial depth after
heating for 8 minutes. FIG. 19 is the temperature distribution
measured at 1 cm radial distance along the length of the applicator
with 3 active elements at 2 minute time intervals.
[0128] The accumulated iso-effect thermal dose was calculated from
the temperature-time history at each point according to:
t 43 = t = 0 t - final R T - 43 .DELTA. t ##EQU00001##
where t.sub.43 is the equivalent time at 43.degree. C., T is the
average temperature during time .DELTA.t, and R is a constant based
on the activation energy and absolute temperature from the
Arrhenius relationship (R=2 for T.gtoreq.43.degree. C., R=4 for
T<43.degree. C.).
[0129] After heating, the tissue was sliced into sections
approximately 5-10 mm thick. Since the thermal lesions were not
clearly visible, the tissue sections were placed into a 2% solution
of 2,3,5-triphenyltetrazolium chloride (TTC) for approximately 20
minutes. TTC is a tissue viability stain that allows for
visualization of acute, lethal tissue damage at a macroscopic
level. Measurements of visible thermal lesions were then obtained,
and the tissue sections then placed in a 10% buffered Formalin
solution for fixation, and later sectioning. Standard hematoxylin
and eosin (H&E) stained sections were obtained for histological
evaluation.
[0130] FIG. 20 illustrates a sagittal slice through thermal lesion
30, visualized after 20 minutes in a 2% TTC solution (measured
dimensions=3.5 cm diameter.times.3.9 cm long).
[0131] FIGS. 21 and 22 illustrate transverse slices through thermal
lesions (as visualized using TTC stain) generated in human uterine
fibroids using a 3-element applicator with a 180 degree directional
heating pattern, inserted in a 3.7 mm OD catheter with 60 ml/min
flow rate (f=6.6-7.6 MHz). FIG. 21 illustrates a directional lesion
produced by 15 W to two elements for 7 minutes (fibroid was at
thermal equilibrium in a 28.degree. C. waterbath; lesion radius=1.2
cm). Maximum temperatures measured at radial distances of 0.5, 1.0,
and 1.5 cm from the applicator are shown with corresponding
accumulated thermal dose.
[0132] FIG. 22 is a directional lesion produced by 15 W to three
elements for 15 minutes (lesion radius=1.7 cm). Maximum
temperatures measured at radial distances of 0.5, 1.0, 1.5, 2.0,
and 2.5 cm from the applicator are shown with corresponding
accumulated thermal dose. Position of the applicator and direction
of energy delivery are shown by the white circle with arrow for
both FIGS. 21 and 22.
[0133] FIGS. 23 and 24 illustrate H&E stained sections of human
uterine fibroid tissue (at 400.times. magnification). FIG. 23
illustrates untreated tissue showing lighter, heterogeneous and
slightly granular chromatin, and visible nuclear features. FIG. 24
shows treated tissue indicating hyperchromatic nuclei with no
visible features and homogenously dark chromatin. Cytoplasm also
appears slightly darker than the untreated tissue.
[0134] FIGS. 25-28 illustrate additional tests performed with
varying applicators and distribution patterns. FIG. 25 illustrates
a three-10 mm transducer applicator and resulting tissue lesion.
The size of the lesion in FIG. 25 is directly correlated to the
applicator transducer geometry, particularly when compared to the
lesion achieved by the four-10 mm transducer applicator shown in
FIG. 26. FIG. 27 illustrates a lesion created by a two-10 mm
transducer applicator with 180.degree. directional distribution.
FIG. 28 further illustrates a 180.degree. directional distribution
applicator applied at an insertion point.
[0135] Results from this study demonstrated that thermal lesions
greater than 1.5-1.7 cm radial depth (3-3.5 cm diameter) and up to
5 cm in length (as evidenced by staining with TTC) could be
produced in human fibroid tissue in less than 10 min with 15 W of
applied electrical power. Further, therapeutic temperatures greater
than 50.degree. C., and potentially lethal thermal doses extended
beyond 2.0 cm radially from the applicator (>4 cm diameter).
Histological examination of heated tissue revealed hyperchromatic
nuclei with homogeneously dark chromatin, and no visible nuclear
features, as compared to untreated tissue.
[0136] In conclusion, high-Intensity interstitial ultrasound
thermal treatment of uterine fibroids can potentially be used to
access treatment of more fibroids and patients than possible with
existing technologies, and provide a safer easier approach with
lower morbidity, shorter treatment duration, and lower procedure
costs.
[0137] Interstitial ultrasound provides exceptional control over
the heating length and radial depth, and ability to have selective
heating patterns provides an innovative interstitial thermal
ablation technology that can be applied to treat fibroids more
consistently, more thoroughly, and faster following procedures that
can be routinely applied by gynecological surgeons. This superior
spatial control can be used to safely target a larger number of
fibroids than can be treated with existing ablative technology.
Interstitial ultrasound technology provides the ability to treat a
targeted fibroid region while simultaneously protecting other
non-targeted healthy tissue.
[0138] It is believed that thermal myolysis may preserve the
integrity of the uterine wall with uncomplicated full-term
pregnancies and uneventful vaginal deliveries post procedure are
reported. This indicates that minimally-invasive thermal ablation
of uterine fibroids may become a treatment of choice for women
still considering having children, significantly increasing the
number of patients that could benefit from precise and selective
high-intensity interstitial ultrasound treatment.
[0139] Only certain fibroids can be removed by laparoscopy. If the
fibroids are large, numerous, or deeply embedded in the uterus,
then an abdominal myomectomy or hysterectomy may be necessary. With
laparoscopic interstitial thermal ablation, these fibroids that are
too large for surgical removal can be treated in situ in a
minimally-invasive fashion. A single insertion of an interstitial
ultrasound applicator can treat larger fibroids than possible with
multiple insertions of existing technology.
[0140] In addition, it is proposed that thermal ablation and
resultant thermal fixation of tissue produces a faster less painful
recovery compared to the painful ischemic necrosis of fibroids and
uterine tissue encountered in patients post-UAE procedures.
[0141] Although the description above contains many details, these
should not be construed as limiting the scope of the invention but
as merely providing illustrations of some of the presently
preferred embodiments of this invention. Therefore, it will be
appreciated that the scope of the present invention fully
encompasses other embodiments which may become obvious to those
skilled in the art, and that the scope of the present invention is
accordingly to be limited by nothing other than the appended
claims, in which reference to an element in the singular is not
intended to mean "one and only one" unless explicitly so stated,
but rather "one or more." All structural, chemical, and functional
equivalents to the elements of the above-described preferred
embodiment that are known to those of ordinary skill in the art are
expressly incorporated herein by reference and are intended to be
encompassed by the present claims. Moreover, it is not necessary
for a device or method to address each and every problem sought to
be solved by the present invention, for it to be encompassed by the
present claims. Furthermore, no element, component, or method step
in the present disclosure is intended to be dedicated to the public
regardless of whether the element, component, or method step is
explicitly recited in the claims. No claim element herein is to be
construed under the provisions of 35 U.S.C. 112 unless the element
is expressly recited using the phrase "means for" or "step
for".
TABLE-US-00001 TABLE 1 Acoustic efficiency (.eta.) data for the
three transducer geometries used in this study. Measurements were
made without catheters, then repeated with catheters (flow rate =
40 ml/min). Transducer Description f (MHz) .eta. (no catheter)
.eta. (in catheter) Catheter 1.5 mm OD .times. 7.2 52% 32% 2.4 mm
OD 10 mm long 2.5 mm OD .times. 6.6 59% 35% 3.7 mm OD 10 mm long
2.5 mm OD .times. 7.6 62% 36% 3.7 mm OD 15 mm long
TABLE-US-00002 TABLE 2 Thermal lesion dimensions measured using
different applicator configurations # Elements Applicator/Catheter
Power (W) Time (min) Lesion Dimensions (cm) 4 1.5 mm OD/2.4 mm OD
15 per chan. 8 3.5 dia. .times. 5.0 long.sup.a 3 1.5 mm OD/2.4 mm
OD 15 per chan. 8 3.5 dia. .times. 3.9 long.sup.a 2 1.5 mm OD/2.4
mm OD 12 per chan. 8 1.5 rad. .times. 2.5 long.sup.b 3 2.5 mm
OD/3.7 mm OD 15 per chan. 15 1.7 rad..sup.b 2 2.5 mm OD/3.7 mm OD
15 per chan. 7 1.2 rad..sup.b,c Notes: .sup.a360 degree heating
pattern; .sup.b180 degree directional heating pattern; .sup.cTissue
was at thermal equilibrium in a 28.degree. C. waterbath rather than
a 37.degree. C. waterbath resulting in smaller lesion size
* * * * *