U.S. patent application number 11/369281 was filed with the patent office on 2006-08-17 for solid hydrogel coupling for ultrasound imaging and therapy.
This patent application is currently assigned to University of Washington. Invention is credited to Peter Kaczkowski, Roy W. Martin, Misty Noble, Adrian Prokop, Shahram Vaezy.
Application Number | 20060184074 11/369281 |
Document ID | / |
Family ID | 29712058 |
Filed Date | 2006-08-17 |
United States Patent
Application |
20060184074 |
Kind Code |
A1 |
Vaezy; Shahram ; et
al. |
August 17, 2006 |
Solid hydrogel coupling for ultrasound imaging and therapy
Abstract
The present invention employs hydrogels as acoustic couplings
for clinical applications of ultrasound imaging and therapy, but is
particularly applicable to high intensity focused ultrasound (HIFU)
based therapy. While other materials can be used, it has been
determined that polyacrylamide is sufficiently robust and
transmissive to withstand the high temperatures encountered in HIFU
therapy. One embodiment of a hydrogel coupling is configured in
shape and size (length) to ensure that a focal region of an
ultrasound transducer is disposed proximate the target area when
the distal tip of the transducer is in contact with tissue. These
couplings can be shaped to correspond to the beam focus
characteristics of specific transducers. Water can be applied to
hydrate the tip of the hydrogel coupling during use, and medication
absorbed into the hydrogel material can be applied to the tissue in
contact with the distal surface of the hydrogel.
Inventors: |
Vaezy; Shahram; (Seattle,
WA) ; Prokop; Adrian; (Lynnwood, WA) ; Martin;
Roy W.; (Anacortes, WA) ; Kaczkowski; Peter;
(Seattle, WA) ; Noble; Misty; (Seattle,
WA) |
Correspondence
Address: |
LAW OFFICES OF RONALD M ANDERSON
600 108TH AVE, NE
SUITE 507
BELLEVUE
WA
98004
US
|
Assignee: |
University of Washington
Seattle
WA
|
Family ID: |
29712058 |
Appl. No.: |
11/369281 |
Filed: |
March 7, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10449819 |
May 30, 2003 |
7070565 |
|
|
11369281 |
Mar 7, 2006 |
|
|
|
60384566 |
May 30, 2002 |
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Current U.S.
Class: |
601/2 ;
600/439 |
Current CPC
Class: |
A61B 8/4281 20130101;
A61K 41/0028 20130101; A61P 35/00 20180101; A61N 7/02 20130101;
A61B 2017/2253 20130101; A61K 49/226 20130101 |
Class at
Publication: |
601/002 ;
600/439 |
International
Class: |
A61H 1/00 20060101
A61H001/00; A61B 8/12 20060101 A61B008/12 |
Goverment Interests
GOVERNMENT RIGHTS
[0002] The research for this invention was funded with grants from
the National Institutes of Health (No. 5R01-HL064208-02) and from
the Department of the Navy (No. N00014-96-1-0630). The U.S.
government may have certain rights in this invention.
Claims
1. A method for using a dimensionally stable hydrogel mass to
acoustically couple an ultrasound transducer with at least one of a
target and a physical boundary associated with the target, wherein
the ultrasound transducer is configured to apply high intensity
focused ultrasound (HIFU) to a target, the method comprising the
steps of: (a) selecting an input power level and a duration to be
used to energize the ultrasound transducer; (b) providing a
dimensionally stable hydrogel mass capable of maintaining its
structural integrity when coupled to the ultrasound transducer used
at the input power level and for the duration selected; (c)
coupling a proximal surface of the dimensionally stable hydrogel
mass to an outer surface of the ultrasound transducer; (d) coupling
an outer extent of a distal surface of the dimensionally stable
hydrogel mass to at least one of the target and a physical boundary
separating the target from the distal surface of the dimensionally
stable hydrogel mass; and (e) energizing the ultrasound transducer
according at the input power level and for the duration
selected.
2. The method of claim 1, further comprising the step of hydrating
the distal surface of the dimensionally stable hydrogel mass, to
prevent damage to the distal surface of the dimensionally stable
hydrogel mass caused by the HIFU.
3. The method of claim 1, further comprising the step of delivering
a medicinal agent to at least one of the target and the physical
boundary, after coupling the outer extent of the distal surface of
the dimensionally stable hydrogel mass to at least one of the
target and the physical boundary.
4. The method of claim 1, wherein the step of providing a
dimensionally stable hydrogel mass comprises the step of selecting
a dimensionally stable hydrogel mass having a shape and size so
that a length between the proximal surface and the outer extent of
the distal surface of the dimensionally stable hydrogel mass
ensures that a focal region of the ultrasound transducer is
disposed proximate to the target.
5. The method of claim 1, wherein the step of providing a
dimensionally stable hydrogel mass comprises the step of selecting
a dimensionally stable hydrogel mass having a melting point
sufficiently high, and an acoustical absorbance sufficiently low to
enable the dimensionally stable hydrogel mass to maintain its
structural integrity when coupled with the ultrasound transducer,
when: (a) the outer extent of the distal surface of the
dimensionally stable hydrogel mass is disposed proximate to a focal
region of the ultrasound transducer; (b) the ultrasound transducer
is energized for a period ranging from about 1 second to about 100
seconds; and (c) an intensity of an acoustical beam generated by
the ultrasound transducer ranges from about 100 W/cm.sup.2 to about
10,000 W/cm.sup.2.
6. The method of claim 1, wherein the step of coupling the proximal
surface of the dimensionally stable hydrogel mass to the outer
surface of the ultrasound transducer comprises the step of using a
retaining housing to removably couple the dimensionally stable
hydrogel mass to the ultrasound transducer, the retaining housing
substantially encompassing the dimensionally stable hydrogel mass,
except for the proximal surface and the outer extent of the distal
surface of the dimensionally stable hydrogel mass.
7. The method of claim 6, wherein the step of coupling the proximal
surface of the dimensionally stable hydrogel mass to the outer
surface of the ultrasound transducer comprises the step of
removably coupling the dimensionally stable hydrogel mass to the
ultrasound transducer.
8. The method of claim 7, further comprising the step of removing
the dimensionally stable hydrogel mass after each use, to enable a
replacement dimensionally stable hydrogel mass to be coupled to the
ultrasound transducer.
9. The method of claim 7, wherein further comprising the step of
removing and disposing of the dimensionally stable hydrogel mass
after using the dimensionally stable hydrogel mass in conjunction
with the target, and repeating steps (a)-(e) of claim 68 to apply
ultrasound to a different target.
10. A method for making a dimensionally stable hydrogel mass to
acoustically couple an ultrasound transducer configured to apply a
high intensity focused ultrasound (HIFU) to a target, wherein the
dimensionally stable hydrogel mass includes a proximal surface
configured to removably couple with the ultrasound transducer and a
distal surface having an outer extent configured to couple with at
least one of a target and a physical boundary separating the target
from the ultrasound transducer, the method comprising the steps of:
(a) mixing appropriate quantities of at least one monomer capable
of forming a dimensionally stable hydrogel mass and a quantity of
water sufficient to hydrate the at least one monomer that will be
polymerized, to form a mixture; (b) introducing the mixture into a
mold; (c) enabling the mixture in the mold to polymerize, forming
the dimensionally stable hydrogel mass; and (d) removing the
dimensionally stable hydrogel mass from the mold.
11. The method of claim 10, wherein: (a) the step of mixing
comprises the step of adding an agent for inducing polymerization
of each monomer in the mixture; and (b) the step of enabling the
mixture in the mold to polymerize comprises waiting a period of
time sufficient for the polymerization induced by each agent to
reach completion.
12. The method of claim 10, wherein the step of enabling the
mixture in the mold to polymerize includes the step of irradiating
the mixture in the mold with light having a wavelength selected to
induce polymerization of the mixture.
13. The method of claim 10, wherein the step of mixing comprises
the step of including at least one monomer selected to produce a
dimensionally stable hydrogel mass having a melting point
sufficiently high, and an acoustical absorbance sufficiently low to
enable the dimensionally stable hydrogel mass to maintain its
structural integrity, when: (a) the outer extent of the distal
surface of the dimensionally stable hydrogel mass is disposed
proximate to a focal region of the ultrasound transducer; (b) the
ultrasound transducer is energized for a period ranging from about
1 second to about 100 seconds; and (c) an intensity of an
acoustical beam generated by the ultrasound transducer ranges from
about 100 W/cm.sup.2 to about 10,000 W/cm.sup.2.
14. The method of claim 10, further comprising the step of adding a
medicinal agent to the mixture before the mixture is introduced
into the mold, such that the dimensionally stable hydrogel mass
produced includes a medicinal agent.
15. The method of claim 10, further comprising the step of adding a
medicinal agent to the dimensionally stable hydrogel mass after it
has polymerized.
16. The method of claim 10, wherein the mold comprises a volume
corresponding to a size and a shape desired for the dimensionally
stable hydrogel mass, and the step of introducing the mixture into
the mold comprises the step of introducing the mixture into a
volume corresponding to the size and shape desired for the
dimensionally stable hydrogel mass.
17. The method of claim 10, wherein the mold comprises a reservoir
in fluid communication with a volume corresponding to a size and
shape desired for the dimensionally stable hydrogel mass, and the
step of introducing the mixture into the mold comprises the step of
introducing the mixture into the reservoir, such that the volume is
filled with the mixture flowing from the reservoir, leaving at
least a portion of the mixture in the reservoir.
18. The method of claim 17, further comprising the step of
inhibiting the polymerization of the mixture in the reservoir while
the mixture in the volume is polymerizing, to enable additional
mixture from the reservoir to flow into the volume, accommodating
shrinkage of the mixture in the volume, as the mixture in the
volume polymerizes.
19. The method of claim 18, wherein the step of inhibiting the
polymerization of the mixture in the reservoir comprises the step
of stirring the mixture in the reservoir.
20. The method of claim 17, wherein the reservoir is disposed above
the volume and is coupled to the volume through a fluid
channel.
21. The method of claim 17, further comprising the step of removing
any undesired portion of the dimensionally stable hydrogel mass
after the step of removing the dimensionally stable hydrogel mass
from the mold.
Description
RELATED APPLICATIONS
[0001] This application is a divisional application based on prior
copending application Ser. No. 10/449,819 filed May 30, 2003, which
itself is based on a prior copending provisional application, Ser.
No. 60/384,566, filed on May 30, 2002, the benefit of the filing
dates of which is hereby claimed under 35 U.S.C. .sctn..sctn.
119(e) and 120.
FIELD OF THE INVENTION
[0003] The present invention generally relates to a hydrogel based
coupling for use in ultrasonic imaging and therapy, and method for
use of the same, and more specifically, pertains to a dimensionally
stable hydrogel that remains stable when transmitting relatively
high intensity ultrasound to a therapy site, and a method for using
the same.
BACKGROUND OF THE INVENTION
[0004] Ultrasound is widely used for imaging a patient's internal
structures without risk of exposure to potentially harmful
radiation, as may occur when using X-rays for imaging. The first
recorded use of ultrasound for imaging was by Dr. Karl Dussik, a
Psychiatrist working at a hospital in Bad Ischl, Austria, who
employed ultrasound to locate brain tumors. He used two opposed
probes, including one for transmitting ultrasound waves, and the
other for receiving them. With these probes, he transmitted an
ultrasound beam through a patient's skull, and used the received
signal to visualize the cerebral structure by measuring the
ultrasound beam attenuation. He published a description of his
technique in 1942, in an article entitled, "Hyperphonography of the
Brain."
[0005] Medical diagnostic equipment specially manufactured for
using ultrasound became available in the 1950s. An ultrasound
examination is a safe diagnostic procedure that uses high frequency
sound waves to produce an image of the internal structures of a
patient's body. Many studies have shown that these sound waves are
harmless and may be used with complete safety, even to visualize
the fetus in pregnant women, where the use of X-rays would be
inappropriate. Furthermore, ultrasound examinations are sometimes
quicker and typically less expensive than other imaging
techniques.
[0006] More recently, the use of high intensity focused ultrasound
(HIFU) for therapeutic purposes, as opposed to imaging, has
received significant attention in the medical community. HIFU
therapy employs ultrasound transducers that are capable of
delivering 1,000-10,000 W/cm.sup.2 to a focal spot, in contrast to
diagnostic imaging ultrasound, where intensity levels are usually
below 0.1 W/cm.sup.2. A portion of the energy from these high
intensity sound waves is transferred to the targeted location as
thermal energy. The amount of thermal energy thus transferred can
be sufficiently intense to cauterize undesired tissue, or to cause
necrosis of undesired tissue (by inducing a temperature rise to
beyond 70.degree. C.) without actual physical charring of the
tissue. Tissue necrosis can also be achieved by mechanical action
alone (i.e., by cavitation that results in mechanical disruption of
the tissue structure). Further, where the vascular system supplying
blood to an internal structure is targeted, HIFU can be used to
induce hemostasis. The focal region of this energy transfer can be
tightly controlled so as to obtain necrosis of abnormal or
undesired tissue in a small target area without damaging adjoining
normal tissue. Thus, deep-seated tumors can be destroyed with HIFU
without surgical exposure of the tumor site.
[0007] A particular advantage of HIFU therapy over certain
traditional therapies is that HIFU is less invasive. The current
direction of medical therapy is progressively toward utilizing
less-invasive and non-operative approaches, as is evident from the
increasing use of laparoscopic and endoscopic techniques.
Advantages include reduced blood loss, reduced risk of infection,
shorter hospital stays, and lower health care costs. HIFU has the
potential to provide an additional treatment methodology consistent
with this trend by offering a method of non-invasive surgery. Also,
HIFU enables transcutaneous tumor treatment without making a single
incision, thus avoiding blood loss and the risk of infection.
Furthermore, HIFU therapy may be performed without the need for
anesthesia, thereby reducing surgical complications and cost. Most
importantly, these treatments may be performed on an outpatient
basis, further reducing health care cost, while increasing patient
comfort.
[0008] The use of HIFU for the destruction of tumors is a
relatively new technique. The first clinical trials were performed
on patients with hyperkinetic and hypertonic disorders (symptoms of
Parkinson's disease). HIFU was used to produce coagulation necrosis
lesions in specific complexes of the brain. While the treatment was
quite successful, monitoring and guidance of the HIFU lesion
formation was not easily achieved (as reported by N. T. Sanghvi and
R. H. Hawes, (1994) "High-intensity focused ultrasound,"
Gastrointestinal Endoscopy Clinics of North America, 4:
383-95).
[0009] Two HIFU-based systems have been developed for the treatment
of benign prostatic hyperplasia (BPH) in humans (see the report by
E. D. Mulligan, T. H. Lynch, D. Mulvin, D. Greene, J. M. Smith, and
J. M. Fitzpatrick, (1997) "High-intensity focused ultrasound in the
treatment of benign prostatic hyperplasia," Br J Urol, 70: 177-80).
These systems are currently in clinical use in Europe and Japan,
and are undergoing clinical trials in the United States. Both
systems use a transrectal HIFU probe to deliver 1,000-2,000
W/cm.sup.2 to the prostate tissue through the rectum wall. No
evidence of damage to the rectal wall has been observed during a
rectoscopy, performed immediately after HIFU treatment (as reported
by S. Madersbacher, C. Kratzik, M. Susani, and M. Marberger, (1994)
"Tissue ablation in benign prostatic hyperplasia with high
intensity focused ultrasound," Journal of Urology, 152: 1956-60,
discussion 1960-61). Follow-up studies have shown decreased
symptoms of BPH (i.e., increased urinary flow rate, decreased
post-void residual volume, and decreased symptoms of irritation and
obstruction (see S. Madersbacher, C. Kratzik, N. Szabo, M. Susani,
L. Vingers, and M. Marberger, (1993) "Tissue ablation in benign
prostatic hyperplasia with high-intensity focused ultrasound,"
European Urology, 23: 1: 39-43).
[0010] HIFU has also been studied for the de-bulking of malignant
tumors (C. R. Hill and G. R. ter Haar, (1995) "Review article: high
intensity focused ultrasound--potential for cancer treatment," Br J
Radiol, 68: 1296-1303), prostate cancer (S. Madersbacher, M.
Pedevilla, L. Vingers, M. Susani, and M. Marberger, (1995) "Effect
of high-intensity focused ultrasound on human prostate cancer in
vivo," Cancer Research, 55: 3346-51), and testicular cancer (S.
Madersbacher, C. Kratzik, M. Susani, M. Pedevilla, and M.
Marberger, (1998) "Transcutaneous high-intensity focused ultrasound
and irradiation: an organ-preserving treatment of cancer in a
solitary testis," European Urology, 33: 195-201) are among the
cancers currently being investigated clinically for potential
treatment with HIFU. An extensive clinical study to
extracorporeally treat a variety of stage 4 cancers is underway in
England (as noted by A. G. Visioli, I. H. Rivens, G. R. ter Haar,
A. Horwich, R. A. Huddart, E. Moskovic, A. Padhani, and J. Glees,
(1999) "Preliminary results of a phase I dose escalation clinical
trial using focused ultrasound in the treatment of localized
tumors," Eur J Ultrasound, 9: 11-18). The cancers involved include
prostate, liver, kidney, hipbone, ovarian, breast adenoma, and
ocular adenoma. No adverse effects, except one case of skin burn,
have been observed.
[0011] An important component in any type of ultrasound therapy
system is the mechanism for coupling the acoustic energy into the
tissue. Good acoustic coupling is necessary to efficiently transfer
the ultrasound energy from the transducer to the treatment site.
The ideal acoustic coupler is a homogenous medium that has low
attenuation and acoustic impedance similar to that of the tissue
being treated. Due to its desirable acoustic transmission
characteristics, water has commonly been used as the coupling
medium in many therapeutic applications of ultrasound.
[0012] In previous hemostasis studies in which HIFU has been used
to arrest bleeding of injured blood vessels and organs, the HIFU
transducer was contained within a water-filled, conical, plastic
housing with a thin, polyurethane membrane at the tip. This coupler
was designed for superficial treatments, since it places the HIFU
focus only several millimeters beyond the tip of the cone. While
this coupling method has been useful for hemostasis experiments, it
has many drawbacks that would make it impractical for a clinical
setting. These disadvantages include degassing, sterilization,
circulation, and containment issues. Due to the limitations of the
current HIFU applicators, an alternative coupling medium is
desirable.
[0013] Previous studies have shown hydrogels to be efficient
coupling media for diagnostic ultrasound. Hydrogels are
hydrophilic, cross-linked, polymer networks that become swollen by
absorption of water. The high WC and favorable mechanical
properties of hydrogels have made them attractive for a wide range
of biomedical applications, including soft contact lenses,
maxillofacial reconstruction, burn dressings, and artificial
tendons. Since hydrogels consist mostly of water, they inherently
have low attenuation and acoustic impedance similar to tissue. They
can be formed into rigid shapes and have relatively low material
costs.
[0014] Unlike the ultrasound transmission gels typically used for
diagnostic scans, hydrogels can have consistencies similar to soft
rubber, and can be formed into relatively rigid, three-dimensional
(3-D) shapes. It would be desirable to provide hydrogel based
couplings, methods for producing such hydrogel couplings, and
methods for using such hydrogel couplings, wherein each coupling
and each method is specifically configured for use in HIFU
applications. It should be understood that because of the
significant increase in power in HIFU as opposed to imaging, HIFU
applications require much more robust couplers that can withstand
the higher energy conveyed through the material, than is required
in diagnostic or imaging applications.
[0015] Polyacrylamide (PA) gel has been employed as an acoustic
coupler for non HIFU applications. The structure and properties of
polyacrylamide have been extensively researched for the past 30
years. Currently, its most common biomedical application is gel
electrophoresis for the separation of charged macromolecules. PA
gel can have a very high WC, ranging from 70% to greater than 90%
water by weight. The gel can be prepared relatively easily and
quickly at room temperature. In addition, PA has been used for a
variety of biomedical applications, and has been shown in many
studies to have very good biocompatibility. An important
consideration for any blood-contacting device is its resistance to
causing thrombosis on its surface. Experiments have shown PA to
exhibit no platelet adhesion. A recent clinical study that
investigated the use of a PA-based blood filtration technique
showed the material to have good blood compatibility, with no signs
of hemolysis or blood clotting. It would thus be desirable to
develop PA gel-based coupling materials, a method for making such
materials, and a method for using such materials, where the
materials are specifically configured for HIFU therapy
applications.
SUMMARY OF THE INVENTION
[0016] A first aspect of the present invention is directed to a
hydrogel coupling adapted to be disposed between an ultrasound
transducer and a target, for use in acoustically coupling an
ultrasound transducer with at least one of the target and a
physical boundary associated with the target. Desirable targets
might include surface tissue on a patient, as well as sub-dermal
areas within a patient's body. Thus, the physical boundary can be
the dermal layer of a patient, and the target area can be a
sub-dermal area, so that the acoustic transducer must be coupled
with the dermal layer. The acoustical energy generated by the
transducer must then move through the coupling, through the dermal
layer (the physical boundary), and be focused on the target.
[0017] Furthermore, the target or physical boundary may also
represent the wall of an internal body cavity. For example, a probe
including an ultrasound transducer and a hydrogel coupling in
accord with the present invention may be inserted into a body
cavity, so that the hydrogel coupling acoustically couples the
acoustic transducer to the wall of the body cavity. Depending on
the focal length of the ultrasound transducer, the focal region can
be proximate the wall, in which case the wall is the target. In
other cases, the focal region can be beyond the wall, in which case
the wall is the physical boundary, and the target is beyond the
wall.
[0018] In some cases, a probe may be surgically inserted into a
patient, such that the hydrogel coupling of the present invention
couples to internal tissues. As with the cavity wall noted above,
such internal tissue can be considered either a boundary or a
target, depending on the focal length of the acoustic transducer
and the size and shape of the hydrogel coupling, and the location
of the tissue to be treated.
[0019] In a first aspect of the present invention, the hydrogel
coupling includes a dimensionally stable hydrogel mass having a
proximal surface configured to be disposed adjacent to an
ultrasound transducer, and a distal surface configured to
acoustically couple with at least one of a target and a physical
boundary associated with a target. A distance between the proximal
surface and an outer extent of the distal surface of the
dimensionally stable hydrogel mass (i.e., its length) is selected
to ensure that a focal region of an ultrasound transducer is
disposed proximate a target. In some cases, the target will be
proximate a boundary such as a dermal layer or a cavity wall, and
the distance will differ from the focal length of the acoustic
transducer by a relatively small amount. In other cases, the target
will be disposed beyond such a boundary, and the distance will be
selected to ensure that when the dimensionally stable hydrogel mass
is disposed between the acoustic transducer and the boundary, such
that when the acoustic transducer is coupled with the boundary, the
focal region of the acoustic transducer is proximate the target.
Longer focal lengths will require a dimensionally stable hydrogel
mass having a greater length. By selecting a dimensionally stable
hydrogel mass having an appropriate length, the focal region will
overlap the target.
[0020] Preferably, the proximal surface of the dimensionally stable
hydrogel mass is further configured to conform to an outer surface
of an ultrasound transducer. In some embodiments, the proximal
surface is convex in shape. The distal surface of the dimensionally
stable hydrogel mass can be shaped as desired. Beneficial distal
surface shapes include concave surfaces, convex surfaces and flat
surfaces. The body of the dimensionally stable hydrogel mass (i.e.,
the portion between the proximal and distal surfaces) can be shaped
as desired. A generally cone shaped, dimensionally stable hydrogel
mass is likely to be preferred, since the acoustic beam from an
ultrasonic transducer configured for applying HIFU is generally
focused to a cone shape, starting out with a broad footprint near
the ultrasonic transducer, and narrowing to a small focal region.
Dimensionally stable hydrogel masses in the shapes of cones and
truncated cones have been empirically determined to be useful.
[0021] In at least one embodiment, the dimensionally stable
hydrogel mass is substantially transparent, to avoid blocking a
view of a target when in use. This characteristic facilitates the
use of the hydrogel coupling, since a clinician will be able to see
through the dimensionally stable hydrogel mass, to verify where the
outer extent of the distal surface is contacting the boundary or
the target.
[0022] Some embodiments of hydrogel couplings in accord with the
present invention include a retaining housing configured to
removably couple the dimensionally stable hydrogel mass to an
ultrasound transducer. Thus, dimensionally stable hydrogel masses
can be used, removed, discarded, and replaced with another
dimensionally stable hydrogel mass. Preferably, the retaining
housing substantially conforms to an outer surface of the
dimensionally stable hydrogel mass. The retaining housing can
substantially enclose the dimensionally stable hydrogel mass,
except for the outer extent of the distal surface and the proximal
surface. The retaining housing is preferably formed from a polymer
material.
[0023] The dimensionally stable hydrogel mass can be made from
poly(2-hydroxyethyl methacrylate), PA, or combinations thereof.
When PA is used to produce dimensionally stable hydrogel masses, an
amount of acrylamide monomer employed in the mass can be varied
such that an acoustical impedance of the dimensionally stable
hydrogel mass substantially corresponds to an acoustical impedance
of at least one of the target and the physical boundary associated
with the target with which the dimensionally stable hydrogel mass
is to acoustically couple.
[0024] One particularly beneficial embodiment of a hydrogel
coupling in accord with the present invention includes a
dimensionally stable hydrogel mass having a melting point that is
sufficiently high, and an acoustical absorbance that is
sufficiently low to enable the dimensionally stable hydrogel mass
to maintain its structural integrity when employed to couple an
acoustic transducer with at least one of a target and a physical
boundary associated with a target, under the following conditions:
(a) the transducer is energized for a period ranging from about 1
second to about 100 seconds; and, (b) the intensity of the
acoustical beam generated by the transducer ranges from about 100
W/cm2 to about 10,000 W/cm2.
[0025] Other embodiments of the present invention will include
means to hydrate the dimensionally stable hydrogel mass. The mass
can be hydrated with a fluid channel having a proximal end
configured to be coupled to a water supply, and having a distal end
disposed adjacent to the outer extent of the distal surface. Such a
fluid channel is preferably included within the dimensionally
stable hydrogel mass. For embodiments that include a retaining
housing, at least a portion of the fluid channel can be coupled
with, or integral to, the retaining housing.
[0026] Yet another embodiment of the first aspect of the present
invention includes means to deliver a medicinal agent outside the
distal surface of the dimensionally stable hydrogel mass, which
includes a fluid channel having a distal end configured to be
coupled to a fluid supply of a medicinal agent, the fluid channel
having a distal end extending through the distal surface,
alternatively, a quantity of a medicinal agent disposed within the
dimensionally stable hydrogel mass.
[0027] When the dimensionally stable hydrogel mass includes the
medicinal agent, the medicinal agent can be distributed
substantially evenly throughout the dimensionally stable hydrogel
mass, or can be distributed proximate the distal surface of the
dimensionally stable hydrogel mass.
[0028] A related aspect of the present invention is directed to a
hydrogel coupling that is adapted to be disposed between an
ultrasound transducer and at least one of a target and a physical
boundary associated with a target, to acoustically couple the
ultrasound transducer with at least one of the target and the
physical boundary associated with the target. In this second aspect
of the present invention, the dimensionally stable hydrogel mass
has a melting point that is sufficiently high, and an acoustical
absorbance that is sufficiently low to enable the dimensionally
stable hydrogel mass to maintain its structural integrity when
employed to couple an acoustic transducer to at least one of the
target and the physical boundary associated with a target, under
the following conditions: (a) the transducer is energized for a
period ranging from about 1 second to about 100 seconds, and (b)
the intensity of the acoustical beam at the focal region of the
transducer ranges from about 100 W/cm.sup.2 to about 10,000
W/cm.sup.2.
[0029] In common with each embodiment of the first aspect of the
invention, in each embodiment of the second aspect of the invention
the dimensionally stable hydrogel mass has a proximal surface
configured to be disposed adjacent to an ultrasound transducer, and
a distal surface configured to acoustically couple with at least
one of the target and the physical boundary associated with the
target. However, in each embodiment of this second aspect of the
invention, the separation between the first and second portion is
not required to be controlled, although if desired, it can be.
[0030] As with the first aspect of the invention, the distal and
proximal surfaces of the dimensionally stable hydrogel mass can be
configured as desired, so that the proximal surface is configured
to conform to an outer surface of an ultrasound transducer, and the
distal surface may be convex, concave, or flat.
[0031] Yet another aspect of the present invention is directed to a
kit containing components to be used to acoustically couple an
ultrasound transducer with a target, wherein the ultrasound
transducer is configured to apply HIFU to a target. The kit
includes at least a dimensionally stable hydrogel mass having a
proximal surface configured to be disposed adjacent to an
ultrasound transducer that is designed to produce HIFU applied to a
target, and a distal surface having an outer extent configured to
acoustically couple with at least one of a target and a boundary
associated with the target, where the boundary is disposed between
the ultrasound transducer and the target. The kit also includes at
least a sealed package configured to maintain the dimensionally
stable hydrogel mass in a hydrated condition until the
dimensionally stable hydrogel mass is removed from the sealed
package in preparation for use.
[0032] In at least one embodiment, the sealed package is further
configured to maintain the dimensionally stable hydrogel mass in a
sterile condition until the dimensionally stable hydrogel mass is
removed from the sealed package in preparation for use. The sealed
package is preferably hermetically sealed and/or vacuum-sealed.
[0033] Some embodiments of such a kit will include instructions for
using the dimensionally stable hydrogel mass to couple an
ultrasound transducer with a target, to facilitate an application
of HIFU to a target. The instructions will at least inform users
how to maintain the distal surface of the dimensionally stable
hydrogel mass in a hydrated condition. At least one embodiment of
the kit will include a semisolid or fluidic coupling medium to be
used to enhance an acoustic coupling of the lower surface of the
dimensionally stable hydrogel mass to an outer surface of an
ultrasound transducer that will apply HIFU.
[0034] The kit can include any combination of: (1) a retaining
housing configured to removably couple the dimensionally stable
hydrogel mass with an ultrasound transducer; (2) means to hydrate
the distal surface of the dimensionally stable hydrogel mass; (3)
means to deliver a medicinal fluid proximate the distal surface of
the dimensionally stable hydrogel mass; and, (4) a fluid channel
having a proximal end configured to couple to a fluid supply, and a
distal end configured to be disposed proximate the distal end of
the dimensionally stable hydrogel mass.
[0035] Still another aspect of the present invention is directed to
a method for using a dimensionally stable hydrogel mass to
acoustically couple an ultrasound transducer with at least one of a
target and a physical boundary associated with the target, wherein
the ultrasound transducer is configured to apply HIFU to a target.
The method includes the steps of selecting an input power level and
a duration to be used to energize the ultrasound transducer, and
providing a dimensionally stable hydrogel mass capable of
maintaining its structural integrity when used to couple the
ultrasound transducer with at least one of the target and a
physical boundary associated with the target, using the input power
level and for the duration selected. Further steps of the method
include coupling a proximal surface of the dimensionally stable
hydrogel mass to an outer surface of the ultrasound transducer and
coupling an outer extent of the distal surface of the dimensionally
stable hydrogel mass to at least one of the target and the physical
boundary separating the target from the distal surface of the
dimensionally stable hydrogel mass.
[0036] Once the coupling is complete, the step of energizing the
ultrasound transducer at the selected input power level and for the
selected duration is performed, the dimensionally stable hydrogel
mass acoustically coupling the acoustic transducer to at least one
of the target and a physical boundary separating the target from
the distal surface of the dimensionally stable hydrogel mass.
[0037] Additional steps can include hydrating the distal surface of
the dimensionally stable hydrogel mass, to prevent damage to the
distal surface of the dimensionally stable hydrogel mass by the
HIFU, and/or delivering a medicinal agent to at least one of the
target and the physical boundary, after coupling the distal surface
of the dimensionally stable hydrogel mass to at least one of the
target and the physical boundary.
[0038] In at least one embodiment, the step of providing a
dimensionally stable hydrogel mass includes the step of selecting a
dimensionally stable hydrogel mass in which a length between the
lower surface and the distal surface of the dimensionally stable
hydrogel mass will ensure that a focal region of the ultrasound
transducer is disposed proximate the target.
[0039] In other embodiments, the step of providing a dimensionally
stable hydrogel mass includes the step of selecting a dimensionally
stable hydrogel mass that has a melting point sufficiently high,
and an acoustical absorbance sufficiently low to enable the
dimensionally stable hydrogel mass to maintain its structural
integrity when employed to couple an acoustic transducer to a
target, under the following conditions: (a) the transducer is
energized for a period ranging from about 1 second to about 100
seconds, and (b) the intensity of the acoustical beam at the focal
region of the transducer ranges from about 100 W/cm2 to about
10,000 W/cm2.
[0040] The step of coupling a proximal surface of the dimensionally
stable hydrogel mass to an outer surface of the ultrasound
transducer can include the step of using a retaining housing to
removably couple the dimensionally stable hydrogel mass with the
ultrasound transducer. The retaining housing substantially
encompasses each surface of the dimensionally stable hydrogel mass,
except for the proximal surface and the outer extent of the distal
surface.
[0041] Still another aspect of the present invention is directed to
a method for making a dimensionally stable hydrogel mass to
acoustically couple with an ultrasound transducer configured to
apply HIFU to a target, wherein the dimensionally stable hydrogel
mass includes a proximal surface configured to couple with an
ultrasound transducer and a distal surface configured to couple
with at least one of a target and a physical boundary separating
the target from the ultrasound transducer. The method includes the
steps of providing at least one monomer capable of forming a
dimensionally stable hydrogel mass when polymerized and hydrated,
providing an agent for inducing polymerization of the at least one
monomer, providing a quantity of water sufficient to hydrate the
quantity of the at least one monomer that will be polymerized, and
providing a mold configured to form a dimensionally stable hydrogel
mass to a desired size and shape.
[0042] The dimensionally stable hydrogel mass is produced by mixing
appropriate quantities of each monomer, the agent for inducing
polymerization, and water together to form a mixture, introducing
the mixture into the mold, and allowing the mixture to polymerize
in the mold. Once polymerization is complete, the dimensionally
stable hydrogel mass is removed from the mold.
[0043] In at least one embodiment, the mold includes reservoir and
a mold volume which are in fluid communication. The mold volume
conforms to the desired size and shape of the dimensionally stable
hydrogel mass to be produced. In such an embodiment, the mixture is
introduced into the mold via the reservoir, until the mold volume
is filled with the mixture, and additional mixture is in the
reservoir. Polymerization of the mixture in the reservoir is
inhibited, while polymerization of the mixture in the mold volume
is allowed. The polymerization reduces the volume of the mixture in
the mold volume, so that more of the mixture in the reservoir flows
into the mold volume and polymerizes. Once the mold volume is
filled with a polymerized dimensionally stable hydrogel mass, the
mixture in the reservoir volume is allowed to polymerize. The
dimensionally stable hydrogel mass is removed from the mold, and
any undesired portion of the dimensionally stable hydrogel mass
(i.e. the portion corresponding to the reservoir) is removed.
[0044] In at least one embodiment, the step of inhibiting the
polymerization of the mixture in the reservoir includes the step of
stirring the mixture in the reservoir. Preferably, the reservoir is
disposed above a portion of the mold volume corresponding to the
distal surface of the desired dimensionally stable hydrogel mass.
The reservoir can be shaped to produce a dimensionally stable
hydrogel mass whose distal surface is convex, flat, or concave.
[0045] The method preferably uses at least one monomer and an agent
for inducing polymerization, which have been selected to produce a
dimensionally stable hydrogel mass that has a desired melting point
and a desired acoustical absorbance, so as to enable the
dimensionally stable hydrogel mass to maintain its structural
integrity when employed to couple an acoustic transducer to a
target under predefined conditions.
[0046] A fluid channel is preferably formed within the
dimensionally stable hydrogel being produced.
[0047] Optionally, the method can include the step of adding a
medicinal agent to the mixture before the mixture is introduced
into the mold, such that the dimensionally stable hydrogel mass
produced includes a medicinal agent. The medicinal agent can be
added to the dimensionally stable hydrogel mass after it has
polymerized.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0048] 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:
[0049] FIG. 1 (Prior Art) schematically illustrates dimensions and
beam characteristics of a 3.5 MHz acoustic transducer that is
capable of being used for HIFU therapeutic applications;
[0050] FIG. 2A schematically illustrates an exemplary shape for
hydrogel couplings in accord with the present invention;
[0051] FIG. 2B schematically illustrates how closely the exemplary
shape of the hydrogel coupling shown in FIG. 2A corresponds to the
focused beam characteristics of the acoustic transducer of FIG.
1;
[0052] FIG. 3A schematically illustrates a polyacrylamide (PA) gel
coupler in accord with the present invention, produced using 10%
acrylamide monomer;
[0053] FIG. 3B schematically illustrates a PA gel coupler in accord
with the present invention, produced using 15% acrylamide
monomer;
[0054] FIG. 3C schematically illustrates a PA gel coupler in accord
with the present invention, produced using 20% acrylamide
monomer;
[0055] FIG. 4A is a graphical representation of sound speed in PA
hydrogel couplings versus acrylamide concentration, showing a
linear data fit;
[0056] FIG. 4B is a graphical representation of sound speed in PA
hydrogel couplings versus acrylamide concentration, showing a
polynomial data fit;
[0057] FIG. 5A is a graphical representation of the acoustic
impedance of PA hydrogel couplings versus acrylamide concentration,
showing a linear data fit;
[0058] FIG. 5B is a graphical representation of the acoustic
impedance of PA hydrogel couplings versus acrylamide concentration,
showing a polynomial data fit;
[0059] FIG. 6A is a graphical representation of the attenuation
coefficient of PA hydrogel couplings versus acrylamide
concentration, showing a linear data fit;
[0060] FIG. 6B is a graphical representation of the attenuation
coefficient of PA hydrogel couplings versus frequency for different
acrylamide concentrations, showing a polynomial data fit;
[0061] FIG. 6C is a graphical representation of the attenuation
coefficient of a 15% PA hydrogel coupling versus gel
temperature;
[0062] FIG. 7 schematically illustrates each component of a
three-part gel mold with the mold in an unassembled state, wherein
the mold is configured to produce a substantially cone shaped
hydrogel coupling, in accord with the present invention;
[0063] FIG. 8 schematically illustrates the three-part gel mold of
FIG. 7 in an assembled state;
[0064] FIGS. 9A-9C schematically illustrates the three-part gel
mold of FIG. 7 being filled with a mixture that polymerizes to form
the solid hydrogel coupling;
[0065] FIGS. 10A and 10B schematically illustrate the top portion
of the three-part gel mold of FIG. 7, to show how the shape of the
top portion of the mold determines the shape of the distal surface
of the hydrogel coupling produced by the mold;
[0066] FIGS. 11A-11D schematically illustrate how changes to the
top portion of the three-part gel mold of FIG. 7 affect the shape
of the distal surface of the hydrogel coupling produced by the
mold;
[0067] FIG. 12A schematically illustrates a hydrogel coupling in
accord with the present invention, coupled to an acoustic
transducer that is mounted on a probe;
[0068] FIG. 12B schematically illustrates the hydrogel coupling,
acoustic transducer, and probe of FIG. 12A being employed to
deliver HIFU to a target location on the dermal layer of a
patient;
[0069] FIG. 12C schematically illustrates the probe and acoustic
transducer of FIGS. 12A and 12B, and a different hydrogel coupling,
in accord with the present invention, having a length selected so
that a focal region of the acoustic transducer extends to a target
underneath the dermal layer of the patient, to deliver HIFU to the
sub-dermal target;
[0070] FIG. 13A schematically illustrates an exploded view of a
probe including an acoustic transducer, a hydrogel coupling, and a
restraining housing;
[0071] FIG. 13B schematically illustrates the probe of FIG. 13A,
with the hydrogel coupling secured to the acoustic transducer by
the restraining housing;
[0072] FIG. 13C schematically illustrates beam characteristics
achieved by the probe of FIG. 13B when the acoustic transducer is
energized;
[0073] FIG. 14A schematically illustrates an exploded view of the
probe of FIG. 13A, a different hydrogel coupling, and a different
restraining housing;
[0074] FIG. 14B schematically illustrates the probe of FIG. 14A
with the different hydrogel coupling secured to the acoustic
transducer using the different restraining housing;
[0075] FIG. 15A schematically illustrates an acoustic transducer
and a hydrogel coupling, in accord with the present invention, the
hydrogel coupling having a length that is selected so that a focal
region of the acoustic transducer overlaps a desired target, when
the outer extent of the distal surface of the hydrogel coupling is
brought into contact with a surface overlying the target;
[0076] FIGS. 15B-15G each schematically illustrates a hydrogel
coupling in accord with the present invention, each different
hydrogel having a different length, such that an outer extent of
the distal surface of each hydrogel coupling is offset from a focal
region of an acoustic transducer by a different amount;
[0077] FIG. 16 is a representation of a plurality of Schlieren
images of ultrasound field produced by the 3.5 MHz spherically
concave transducer of FIG. 1, showing the image when now hydrogel
coupling is used in comparison to the images for different length
hydrogel couplings;
[0078] FIG. 17A schematically illustrates a hydrogel coupling and
an external fluid channel, wherein the external fluid channel is
employed to hydrate the tip of the hydrogel coupling;
[0079] FIG. 17B schematically illustrates a hydrogel coupling, a
restraining housing, and an external fluid channel attached to the
restraining housing;
[0080] FIG. 17C schematically illustrates a hydrogel coupling with
an internal fluid channel;
[0081] FIG. 18A schematically illustrates a hydrogel coupling with
a medicinal agents dispersed within the hydrogel coupling;
[0082] FIG. 18B schematically illustrates the hydrogel coupling of
FIG. 18A responding to an acoustical beam passing through the
hydrogel coupling, showing how the acoustical beam drives the
medicinal agent out of the hydrogel coupling;
[0083] FIG. 18C schematically illustrates a hydrogel coupling with
medicinal agent disposed substantially adjacent to the tip of the
hydrogel coupling, and showing an optional fluid channel used to
deliver a medicinal agent to the tip;
[0084] FIG. 19 schematically illustrates a kit in accord with the
present invention, which includes at least a hydrogel coupling, and
may optionally include one or more of a restraining housing,
instructions, and coupling gel for coupling the hydrogel coupling
with an acoustic transducer;
[0085] FIG. 20 is a flowchart of the sequence of logical steps
employed to utilize a hydrogel coupling in accord with one aspect
of the present invention, wherein the hydrogel coupling must be
sufficiently robust not to breakdown or melt in HIFU
applications;
[0086] FIG. 21 is a flowchart of the sequence of logical steps
employed to utilize a hydrogel coupling in accord with another
aspect of the present invention, wherein the hydrogel coupling has
a length that ensures the focal region of the acoustic transducer
is proximate the target;
[0087] FIG. 22 is a flowchart of the sequence of logical steps
employed to produce a hydrogel coupling having a length that
ensures the focal region of the acoustic transducer is proximate
the target; and
[0088] FIG. 23 is a flowchart of the sequence of logical steps
employed to produce a hydrogel coupling using a mold that has a
reservoir and a mold volume, and which accommodates shrinkage of
the hydrogel material during polymerization.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0089] The present invention relates to utilizing solid hydrogels
as acoustic couplings for clinical applications of ultrasound
imaging and therapy, particularly HIFU based therapy. Various
aspects of the present invention are disclosed in regard to
different embodiments of hydrogel based couplings, methods for
using such couplings, and methods for fabricating such
couplings.
[0090] In the course of developing the present invention, hydrogel
couplings in accord with the present invention were evaluated by
using such hydrogel couplings to acoustically couple a known
acoustic transducer to a variety of targets. As shown in FIG. 1,
the specific acoustic transducer employed was a prior art HIFU
transducer 10 (SU-102-01) obtained from Sonic Concepts
(Woodinville, Wash.). The single element, spherically concave
transducer has a center frequency of 3.5 MHz. Its aperture diameter
and radius of curvature are 35 mm and 55 mm, respectively,
providing an f-number of 1.57. Field mapping of the focal region
showed the 6 dB focal width and focal depth to be 1.0 mm and 10.6
mm, respectively. The basic beam characteristics of this acoustic
transducer are also shown in FIG. 1.
[0091] It should be understood that the present invention is not
limited to use with the specific transducer employed in the
empirical testing. While other acoustic transducers suitable for
HIPU applications may have different specifications (i.e. different
aperture diameters, different curvatures, different f-numbers, and
different focal regions), many acoustic transducers suitable for
HIFU application will exhibit a generally conical shaped beam 12,
and a substantially smaller focal region 14.
[0092] FIG. 2A shows a hydrogel coupling 16 having a generally
conical shape. A lower surface 20 is preferably configured to
couple easily in good acoustic contact with an ultrasound
transducer. Coupling is most readily achieved if the shape of
proximal surface 20 corresponds to the shape of an outer surface of
the transducer. However, a mismatch of shapes is not fatal, if
sufficient liquid or gel based coupling media is disposed between
the outer surface of the transducer and the proximal surface of
hydrogel coupling 16. As many HIFU transducers exhibit a generally
conical shaped beam, hydrogel couplings having similar shapes are
particularly well suited for coupling such transducers to targets.
In the empirical studies performed in conjunction with the
development of the present invention, the dimensions selected for
the cone shaped hydrogel coupling substantially corresponded to the
beam dimensions shown in FIG. 1. A hydrogel coupling configured to
couple a transducer having different beam dimensions can similarly
be produced having dimensions substantially corresponding to the
beam dimensions of a specific transducer.
[0093] Hydrogel coupling 16 thus substantially corresponds to the
beam dimensions of a specific transducer, and a distal surface 18
of hydrogel coupling 16 extends into the focal region of the
transducer. While the shape of the hydrogel coupling is not
required to substantially match the beam dimensions of a transducer
in each aspect of the present invention, in at least some
embodiments the dimensions of the hydrogel coupling will
substantially match the dimensions of the beam from a selected
transducer. As will be described in greater detail below, in some
aspects of the present invention, the dimensions of the hydrogel
coupling are manipulated specifically to achieve a shape differing
from the beam dimensions of a transducer for a specific
purpose.
[0094] FIG. 2B clearly illustrates that hydrogel coupling 16
substantially corresponds to the focal characteristics of beam 12,
which is generated by transducer 10a Transducer 10a differs from
transducer 10 in that it is mounted in a base 15, whereas a base is
not shown in connection with transducer 10. Those of ordinary skill
in the art will recognize that the upper curved surface of a
transducer can be accommodated in bases of various sizes and
shapes. The base used with transducer 10a facilitates mounting the
transducer to a probe, as discussed below.
[0095] In FIG. 2B, hydrogel coupling 16 is coupled with transducer
10a. The outer extent of distal surface 18 is disposed proximate
focal region 14. It should be understood that hydrogel coupling 16
must be sufficiently robust to endure HIFU applications without
melting or damage that would cause distal surface 18 (disposed
proximate the focal region) to fail to maintain acoustic coupling
with the tissue of a patient. When a hydrogel coupling has
dimensions substantially similar to the beam dimensions of a
specific transducer, the outer extent or tip of the distal surface
of the coupling will be disposed proximate the focal region. That
portion of the coupling will be exposed to temperatures
significantly greater than those experienced by couplings used to
couple imaging transducers to targets. Thus, while a particular
coupling material might be acceptable for coupling imaging
transducers to targets, the same material will be unable to
withstand such use in HIFU applications. Empirical data supports
the conclusion that structural failure can occur in couplings made
of mediums such as agar. The high temperatures at the tip or outer
extent of the distal surface of a coupling adjacent to the focal
region of a HIFU transducer can lead to cracking, melting, and loss
of structural integrity of the distal surface at that location.
Thus, care must be taken when selecting a material to be employed
as a coupling for HIFU applications. Many materials suitable for
coupling an imaging transducer to a target will be unable to
withstand the temperatures encountered in coupling HIFU transducers
to a target.
[0096] One aspect of the present invention is directed to a
hydrogel coupling wherein the specific hydrogel is selected to
ensure that the hydrogel coupling is sufficiently robust for use in
HIFU applications. The material selected must have sufficient
transmissivity to avoid overheating as a result of absorbing
ultrasound energy. In other words, it is important that the
coupling material deliver as much as possible of the HIFU energy to
the focal region and not absorb the energy.
[0097] The energy deposited in a coupling medium disposed proximate
the focal region of a transducer can be calculated as follows: T =
2 .times. .alpha. .times. .times. It .rho. .times. .times. c m + T
0 ( 1 ) ##EQU1## where T is the temperature after a time t, T.sub.0
is the temperature at the start of HIFU application (t=0), I is the
temporal average intensity, t is time, .alpha. is the absorbance
coefficient in Nepers/cm, .rho. is the density of the medium, and
c.sub.m is the specific heat per unit mass. The majority of
attenuation (more than 95%) can be attributed to absorbance, and as
a result, the absorbance is assumed to be approximately equal to
the attenuation.
[0098] The above equation is useful in the investigation of
different coupling agents for HIFU devices that require the
position of the HIFU focus to be close to the tip of the coupling
agent. Typical values that could be used in the above equations are
as follows: [0099] HIFU intensity, I, on the order of 1000
W/cm.sup.2 [0100] HIFU application time, t, on the order of 100
seconds [0101] Density, .rho., on the order of 1 g/ml [0102]
Specific heat per unit mass, c.sub.m is, on the order of 6.5 J/g
for PA [0103] Attenuation coefficient, .alpha., on the order of
0.035 Np/cm, at 3 MHz for PA Therefore, the temperature rise
determined from the above equation is:
T-T.sub.0.apprxeq.1000.degree. C.
[0104] This relatively great temperature increase does not occur in
clinical settings. The counteracting parameters are thermal
convection dissipating energy out of the HIFU focus, and cooling
due to blood flow. However, the equation does demonstrate that a
large temperature increase in the coupling medium can be expected
at or near the focus. A robust coupling medium must be able to
handle large temperature increases by having a high melting point,
as well as having a low attenuation that reduces the temperature
increase.
[0105] According to a first aspect of the present invention,
hydrogels used to produce hydrogel couplings are selected to ensure
that when the hydrogel coupling is used in conjunction with an
acoustic transducer in accord with certain parameters, and with a
portion of the hydrogel coupling disposed proximate the focal
region of the transducer, the dimensionally stable hydrogel mass
forming the coupling has a melting point that is sufficiently high,
and an acoustical absorbance that is sufficiently low to enable the
dimensionally stable hydrogel mass to maintain its structural
integrity. The parameters are: (a) the transducer is energized for
a period ranging from about 1 second to about 100 seconds; and, (b)
the intensity of the acoustical beam generated by the transducer
ranges from about 100 W/cm.sup.2 to about 10,000 W/cm.sup.2.
[0106] Empirical testing has determined that acrylamide monomers
can be employed to produce PA hydrogels that fall within the ranges
noted above. The structure and properties of PA have been
extensively researched for the past 30 years. Currently, its most
common biomedical application is for gel electrophoresis, for the
separation of charged macromolecules. While there are many
different hydrogels available, PA hydrogels exhibit other desirable
properties, in addition to having characteristic within the ranges
noted above. PA hydrogels can have very high WC, ranging from 70%
to more than 90% water by weight and can be prepared relatively
easily and quickly at room temperature. The mechanical properties
of PA hydrogels, and therefore their acoustic properties, can be
varied in a straightforward manner simply by changing the overall
concentration of acrylamide monomer in the material. In addition,
PA has been used for a variety of biomedical applications and has
been shown in many studies to have very good biocompatibility.
[0107] An important consideration for any blood-contacting device
is its resistance to causing thrombosis on its surface. Experiments
have shown PA to exhibit no platelet adhesion. A recent clinical
study that investigated the use of a PA-based blood filtration
technique showed the material to have good blood-compatibility,
with no signs of hemolysis or blood clotting. Moderate material
costs and straightforward manufacturing methods enable inexpensive,
custom-designed, disposable HIFU coupling devices to be made from
PA gels.
[0108] FIGS. 3A-3C schematically represent three PA gel test plugs
fabricated in order to gain empirical data about hydrogel couplings
suitable for HIFU applications. Each sample has a diameter of 2.5
cm and a height of approximately 3 cm. Stiffness and transparency
increase with acrylamide concentration. Note that plug 22a was
formed using acrylamide monomer at a concentration of 10%, and is
slightly opaque as indicated by the shading in this plug. Plug 22b
was formed using acrylamide monomer at a concentration of 15%, and
is more transparent, as indicated by the diminished shading in plug
22b. Plug 22c was formed using acrylamide monomer at a
concentration of 20%, and is substantially transparent, as
indicated by the lack of shading. The procedure for producing the
gel plugs is explained in detail below. This procedure was also
employed for producing generally cone-shaped PA hydrogel couplings,
as well as PA hydrogel couplings having other shapes. Substantially
transparent couplings have the advantage of enabling a clinician to
see through the coupling, to better view the target area.
[0109] A summary of the process for making the PA gels employed in
the present invention is set forth below. Those of ordinary skill
in the art will recognize that modifications to the process
described below can readily be made.
[0110] To form a rigid, 3-D hydrogel, a cross-linking agent is used
to hold the long polymer chains together in a matrix.
Bisacrylamide, also known as N,N'-methylenebis(acrylamide), is the
cross-linker preferably used in the formation of PA. The
bisacrylamide molecule consists of two acrylamide residues joined
at their amide groups by a methyl group. The two acrylamide
residues participate in the polymerization reaction as though they
were two independent monomers.
[0111] For PA gels used for electrophoresis, this buffering agent
is used to adjust the pH of the gel to pH 8. In PA gel
electrophoresis, the pH of the medium is important in determining
the charges on the biological molecules used. The pH of the
solution may affect the protonation state of the -NH.sub.2 groups
of the acrylamide monomers. With respect to the present invention,
the influence of pH was not investigated, but was simply kept
constant for each gel. Because the production of PA electrophoresis
gels is well known, the same pH level was employed in making PA for
use in the present invention. The buffer solution employed was
Trizma base, also called Tris(hydroxymethyl)aminomethane, and
Trizma hydrochloride, also called Tris(hydroxymethyl)aminomethane
hydrochloride.
[0112] Ammonium persulfate (APS) was employed as an initiator for
polymerization, since it is a source of free radicals. In solution,
APS forms the persulfate ion, S.sub.2O.sub.8.sup.2-. This common,
water-soluble initiator is one of the strongest chemical oxidizing
agents known.
[0113] TEMED, also known as N,N,N',N'-Tetramethylethylenediamine
catalyzes the radical formation process. APS and TEMED form a redox
system, where APS is the oxidizing agent and TEMED is the reducing
agent. Although the redox initiation mechanism of the
persulfate-TEMED system is not well understood, it is likely that
TEMED forms a free radical in addition to the persulfate free
radical, and that both radicals are involved in the initiation
process.
[0114] The APS-TEMED redox system is a type of thermal initiator.
For a 15% -weight in volume PA gel, the maximum temperature during
polymerization was about 61.degree. C. The proportion of APS-TEMED
initiator to total solution determines the rate at which
polymerization occurs. Polymerization rate increases with an
increasing proportion of the initiator. In addition, reaction rate
and temperature increase with the concentration of acrylamide in
solution. Thus, higher-concentration gels tend to polymerize at a
faster rate and reach higher temperatures during polymerization
than lower-concentration gels.
[0115] The physical properties of PA vary according to the
concentration of acrylamide monomer in the gel. Acrylamide
concentrations used in gathering empirical data relating to the
present invention ranged from 10% to 20% weight in volume (w/v).
The percent concentration was determined by the ratio of the mass
of total acrylamide to the volume of pre-polymerized solution. An
aqueous solution of 40% w/v acrylamide with a 19:1 monomer to
cross-linker ratio (LIQUI-GEL; ICN Biomedicals, Aurora, Ohio) was
used to prepare the gels. The hydrogels were formed in solution by
the free radical, chain-reaction polymerization process noted
above. The initiated solution was transferred to either a
cylindrical mold (see FIGS. 3A-3C), or to a substantially
cone-shaped mold (see FIGS. 7 and 8) which are described below. The
cylindrical mold was primarily employed to produce plugs for
material testing and characterization, while the cone shaped mold
was employed to produce hydrogel couplings that were tested with
the acoustic transducer described in connection with FIG. 1. With
respect to the cylindrical mold, the mold was kept upright, so that
the gel's top face formed parallel to the bottom face. Each gel
plug was allowed to polymerize for about 25 to 30 minutes. The
resulting cylindrical gel plugs were 2.5 cm in diameter and
approximately 3 cm in height (FIGS. 3A-3C). A difficulty associated
with using hydrogels is that they dehydrate when left exposed to
ambient air, and swell when placed in water due to increased
absorption of the water. Therefore, the gels were either tested
within one hour after polymerization, or stored in vacuum-sealed,
plastic bags for later use.
Bulk Properties
[0116] Water content (WC) and density were measured for gels with
varying acrylamide concentrations. WC was determined for acrylamide
concentrations of 10%, 15%, and 20% w/v. Six gel samples were
tested for each concentration. Density was measured for
concentrations of 10%, 12.5%, 15%, 17.5%, and 20% w/v. Seven gel
samples were tested for each concentration.
[0117] The WC was determined by comparing the mass of the hydrated
gel immediately after polymerization, mh, to the mass of the
dehydrated gel, md.
[0118] Water content was calculated using the following formula: WC
= m h - m d m h .times. 100 ( 2 ) ##EQU2##
[0119] The measured values of the bulk and acoustic properties of
PA gel at various concentrations are listed in Table 1.
TABLE-US-00001 TABLE 1 Acryl. WC(%) .rho.(g/cm.sup.3) c(m/s)
Z(Mrayl) .alpha.(dB/cm) N = 7 Conc. N = 6 N = 7 N = 7 N = 7 1 MHz 2
MHz 3 MHz 4 MHz 5 MHz 10% 87.0 +/- 1.024 +/- 546 +/- 1.583 +/-
0.077 +/- 0.115 +/- 0.206 +/- 0.300 +/- 0.437 +/- 0.8 0.006 2 0.008
0.039 0.033 0.031 0.037 0.058 12.5% -- 1.031 +/- 558 +/- 1.607 +/-
0.099 +/- 0.179 +/- 0.259 +/- 0.386 +/- 0.523 +/- 0.005 2 0.008
0.027 0.043 0.043 0.037 0.051 15% 81.6 +/- 1.038 +/- 568 +/- 1.628
+/- 0.121 +/- 0.185 +/- 0.331 +/- 0.495 +/- 0.698 +/- 1.0 0.004 2
0.005 0.027 0.042 0.037 0.042 0.112 17.5% -- 1.043 +/- 582 +/-
1.649 +/- 0.119 +/- 0.249 +/- 0.376 +/- 0.540 +/- 0.760 +/- 0.005 2
0.009 0.051 0.036 0.033 0.036 0.029 20% 76.0 +/- 1.052 +/- 595 +/-
1.679 +/- 0.142 +/- 0.236 +/- 0.413 +/- 0.647 +/- 0.873 +/- 1.1
0.003 2 0.004 0.020 0.047 0.046 0.066 0.041
[0120] The density, p of the gel immediately after polymerization
was calculated by dividing the mass of the gel by its volume. Mass
was measured with an electronic scale, and volume was measured
using a water displacement technique.
[0121] The WC of PA decreased from 87% to 76% as a linear function
of increasing acrylamide concentration. The density of the gel was
found to be slightly greater than the density of water, increasing
from 1.02 to 1.05 g/ml as a linear function of increasing
acrylamide concentration.
Acoustic Properties of PA Hydrogels
[0122] Sound speed, c (m/s), acoustic impedance, Z (Mrayl), and
attenuation, .alpha. (dB/cm), were measured for gels of five
different acrylamide concentrations: 10%, 12.5%, 15%, 17.5%, and
20% w/v. For each concentration, seven gel samples were tested at
25.degree. C. In addition, acoustic properties were measured for
one 15% w/v acrylamide gel sample at different temperatures,
ranging from 23.degree. C. to 45.degree. C.
[0123] A pulse transmission technique was used to measure the
attenuation coefficient and speed of sound in the PA samples.
Calculations were based on the well known substitution method,
where two acoustic paths are compared. The sample path contained
the gel sample with approximately two centimeters of water on
either side, and the reference path contained only water. The
attenuation coefficient was measured at frequencies of 1 MHz to 5
MHz.
[0124] For the concentration range tested, the acoustic properties
of PA increased as linear functions of increasing acrylamide
concentration. Sound speed ranged from 1546 to 1595 m/s for 10% and
20% w/v gels, respectively (FIG. 4A). Acoustic impedance ranged
from 1.58 to 1.68 Mrayl (FIG. 5A). Attenuation ranged from 0.08 to
0.14 dB/cm at 1 MHz (FIG. 6A). Linear regression showed that the
rate of increase in attenuation coefficient with concentration was
larger at higher frequencies. A plot of attenuation coefficient
versus frequency showed that attenuation was not a linear function
of frequency (FIG. 6B). While a second order polynomial fit the
data well, the data did not show a strictly frequency-squared
dependence, as is the case for water. Sound speed and impedance
were shown to increase with temperature, while attenuation was
shown to decrease with temperature (FIGS. 4B, 5B, and 6C).
Thermal Properties of PA Hydrogels
[0125] The thermal conductivity, k (W/m/oC), and specific heat
capacity, Cp (J/kg/oC), of PA were measured by monitoring the
thermal dissipation of a heat impulse. A nickel-chromium heating
wire was pulled taut through the center of a custom-made
measurement cell. The initiated PA solution was poured into the
measurement cell (approximately a cube with 5 cm edges) and allowed
to polymerize into the hydrogel. Four needle T-type thermocouples
(Omega Engineering Inc., Stamford, Conn.) were inserted into the
gel parallel to the heating wire. The thermocouples were placed at
different radial distances from the wire, ranging from 4 mm to 11
mm. The exact distances from their junctions to the heating wire
were measured using an ultrasound imaging system (a model HDI
1000.TM. from ATL Corp., Bothell, Wash.). A LabVIEW.TM. (National
Instruments, Austin, Tex.) program controlled the length of the
current pulse delivered to the heating wire, and recorded the four
thermocouple temperatures over time.
[0126] The following equation, which is based on Fourier's law of
heat conduction in cylindrical coordinates, was used to determine
the radial temperature distribution at some time after heating: ln
.times. .times. ( Tt ) = .times. .times. r 2 4 .times. .chi.t + ln
.times. .times. ( Q 4 .times. .pi. .times. .times. L .times.
.times. .rho. .times. .times. C p .times. .chi. ) .times. .times.
.chi. .times. k .rho.C p ( 3 ) ##EQU3## where T (.degree. C.) was
the temperature elevation from ambient at some radial distance, r
(m), from the wire; t (s) was the time after heating at which the
measurement was made; Q (J) was the total deposited heat (J); L (m)
was wire length; .rho. (kg/m.sup.3) was the density of the gel; and
.chi. (m.sup.2/s) was the thermal diffusivity of the gel. This
equation assumes that the time until measurement was significantly
larger than the heating time, and that the diameter of the wire is
negligible.
[0127] Thermal properties were measured for three different
acrylamide concentrations: 10%, 15%, and 20% w/v. Heat was applied
for 5 s, which resulted in a temperature rise of about 1.degree. C.
at 4 mm from the wire. Ln(Tt) versus r.sup.2/t was graphed for each
of the four thermocouple positions. By fitting a line to the data,
the slope and intercept were used to calculate C.sub.p and k. Two
independent experiments were peformed for each acrylamide
concentration.
[0128] The thermal conductivity and specific heat capacity did not
vary measurably with acrylamide concentration over the range
tested. The overall average thermal conductivity and specific heat
capacity of PA, 0.84 W/m/.degree. C. and 6470 J/kg/.degree. C.
respectively, were found to be slightly higher than the
corresponding values for water, 0.61 W/m/.degree. C. and 4178
J/kg/.degree. C.
Power Efficiency
[0129] Power efficiency was measured to determine the effectiveness
of the PA coupler in delivering focused ultrasound into water.
Overall power efficiency, E.sub.Overall, of the transducer-coupler
device was defined as the ratio of output acoustic power delivered
to a water bath, to input electrical power supplied to the
transducer. E.sub.Overall was defined as:
E.sub.Overall=E.sub.Transducer.times.E.sub.Coupler (4) where
E.sub.Transducer was the transducer efficiency, and E.sub.Coupler
was the coupler efficiency. E.sub.Transducer was determined by
measuring output acoustic power for the transducer without any
coupler attached. The efficiency of the coupler could then be
calculated from Equation 3. A test was performed to determine how
acrylamide concentration affected the power efficiency of the
device. For comparison, a water-filled coupling cone, with the same
dimensions as the full-length gel couplers, was also tested. The
couplers were attached to the 3.5 MHz HIFU transducer. A reflecting
radiation force balance (a model UPM-DT-IOE.TM. from Ohmic
Instruments Co., Easton, Md.) was used to measure the output
acoustic power for five input electrical power levels, ranging from
2 W to 90 W. Output power was plotted versus input power, and
overall efficiency was calculated as the slope of the best-fit line
to the data. Efficiency was measured for full-length, convex-tip,
gel couplers with 10%, 15%, and 20% acrylamide concentrations.
These data were compared to theoretical efficiencies based on the
attenuation in the gel. The theoretical efficiency of the gel,
E.sub.Coupler Theory, was calculated using the following equation:
E.sub.Coupler Therory=exp(-2.alpha.d) (5) where {acute over
(.alpha.)} (nepers/cm) was the measured attenuation coefficient of
the gel at 3.5 MHz, and d (5.2 cm) was the length of the gel. For
this calculation, it was assumed that loss of acoustic power was
due only to attenuation in the gel coupler. Attenuation due to
water was assumed to be negligible.
[0130] Table 2 lists the measured and theoretical power efficiency
for the different couplers. The transducer efficiency was measured
at 55.8%. Attaching the 5.2 cm gel cone to the transducer dropped
the overall efficiency to between 22.4% and 28.6%, for 20% and 10%
acrylamide concentrations, respectively. Normalizing the overall
efficiency to the transducer efficiency showed the gel cones to
have coupler efficiencies from 40.1% to 51.3%. For comparison, the
coupler efficiency of the water-filled cone was measured to be
65.3%. The measured coupler efficiency of the gel cone was 14% to
23% less than its calculated theoretical efficiency. The
attenuation coefficient used for PA at 3.5 MHz was calculated from
polynomials fit to the measured attenuation data, and was found to
be 0.029, 0.046, and 0.059-nepers/cm, for 10%, 15%, and 20%
acrylamide, respectively. TABLE-US-00002 TABLE 2 Measured Measured
Theoretical Overall Coupler Coupler Coupler Type Efficiency (%)
Efficiency (%) Efficiency (%) No Coupler 55.8 100 100 Water-Filled
Cone 36.4 65.3 100 10% Acryl. 5.2 cm 28.6 51.3 74.2 15% Acryl. 5.2
cm 26.3 47.3 61.7 20% Acryl. 5.2 cm 22.4 40.1 53.8
Beneficial Properties of PA Hydrogel Couplings
[0131] The favorable acoustic properties of PA make the material a
good coupling medium for applications of both therapeutic and
diagnostic ultrasound. The gel is a homogeneous material that
consists mostly of water. It has low attenuation, with sound speed
and acoustic impedance similar to that of tissue. Due to the gel's
ideal impedance, minimal reflections will occur at the gel-tissue
interface. An advantage of the PA coupling is that its acoustic
properties vary linearly with acrylamide concentration. Acoustic
characterization of the material is, therefore, a straightforward
process, if gel concentration is known, making it relatively easy
to match the impedance of specific tissue in a patient's body.
[0132] A PA coupler has several properties that make it desirable
for HIFU applications. The acoustic properties vary linearly with
acrylamide concentration, which allows for straightforward
modification of the gel's acoustic and impedance characteristics.
The PA coupler's acoustic impedance can be matched to a particular
tissue simply by varying the acrylamide concentration. In
transcutaneous HIFU applications, reducing impedance mismatch at
the gel-tissue interface can diminish the occurrence of skin burns
caused by reflections and standing waves. Matching sound speed of a
PA coupling to a specific tissue type can reduce adverse effects
caused by refraction of the ultrasound beam at the gel-tissue
interface. In some HIFU applications, this issue may be of
substantial importance, since a shift in the position of the focus
can result in undesirable damage to surrounding normal tissue.
[0133] Due to its low attenuation, PA couplings have acceptable
power transfer efficiency. Since efficiency decreases with
increasing coupler length, it might be advantageous to use
transducers with short focal distances for superficial HIFU
treatments.
Beneficial Properties of Hydrogel Couplings
[0134] Hydrogels in general have the advantages associated with
being a solid coupling material. Unlike water-filled couplers,
there are no problems with containment and leakage of the hydrogel
coupling medium. Using an appropriate mold, couplings can be formed
to fit to a specific HIFU transducer. Their shape and size can also
be modified for a particular application. For transcutaneous
applications, the depth of the focus below the tissue interface can
be adjusted by using couplings with different lengths, as described
in detail below. For intraoperative hemostasis applications, the
shape and height of the cone tip can be varied to achieve more
effective treatments. Modifying the tip shape is done by selecting
an appropriate mold, as described below.
[0135] The coupling need not be permanently attached to a HIFU
transducer. Unlike prior art aluminum couplers, which were held to
the PZT element by epoxy, the coupling can be temporarily attached
with a thin layer of water or sonography gel and readily replaced
with a different coupling. The disposable nature of the coupling is
ideal for HIFU applications in which the focus is near the distal
tip of the coupling. While a gel may ultimately sustain some HIFU
or mechanically related damage to its tip, this damage does not
permanently impair the transducer for further use, since a new
coupling can readily replace the current one.
[0136] While PA hydrogels have been empirically tested and proven
capable of being used for HIFU applications, it is expected that
other hydrogel materials, and or mixtures of different hydrogels
will be identified as being sufficiently robust to be employed as a
coupler for HIFU applications. For example, poly(2-hydroxyethyl
methacrylate), or pHEMA, is likely to be a useful hydrogel for HIFU
applications.
[0137] The functional tests noted above were performed on conical
PA couplings designed to fit to the transducer described in
connection with FIG. 1 (a 3.5 MHz, spherically concave, single
element, HIFU transducer with a 5.5 cm focal length and a 3.5 cm
aperture diameter). Such conically shaped couplings were produced
using a custom-built three part mold 30, which is shown in FIGS. 7
and 8. The gel cones had spherically convex bases that matched the
curvature of the transducer. Full-length or truncated conical
plastic housings held the gel couplers to the transducer.
Full-length, flat-tip cones were 4.9 cm long, which placed the
center of the HIFU focus 0.6 cm from the tip. The tip shape and
height can be varied to place the focus at different distances from
the tip. For the majority of the tests, convex tips 0.3 cm in
height were used, which placed the center of the HIFU focus about
0.3 cm from the tip.
[0138] Referring once again to FIGS. 7 and 8, the three part mold
includes a base portion 32, a middle portion 34, and a top portion
36. Base portion 32 is configured to match the concave outer
surface of the transducer, and thus includes a concave surface 40.
Base portion 32 can be modified to achieve a mold configured to
produce a hydrogel coupling for a different transducer having a
distal surface with a different shape or dimension. Preferably, the
proximal surface of the hydrogel coupling produced by mold 30
corresponds to the shape of the outer surface of the transducer
with which the hydrogel mass is to be used. FIG. 7 shows a hydrogel
coupling 38 seated in base portion 32.
[0139] Middle portion 34 is substantially cone shaped, to match the
focal characteristics of the exemplary transducer, as shown in
FIGS. 1 and 2B, discussed above. Of course, other shapes can be
employed, as desired. Top portion 36 includes a tip molding portion
42, which as described in detail below can be modified to achieve a
desired shape for the outer extent or tip of the distal surface of
a hydrogel coupling produced using mold 30. Top portion 36 also
includes a drip channel 44 coupling a reservoir 46 in fluid
communication with a mold volume 48. Mold volume 48 is defined by
base portion 32, middle portion 34 and top portion 36.
[0140] The function of reservoir 46 is illustrated in FIGS. 9A-9C.
In FIG. 9A, a liquid mixture (such as the acrylamide monomer based
mixture disclosed above) is introduced into reservoir 46 of mold
30. In FIG. 9B, the mixture within the mold volume is allowed to
polymerize, while polymerization of the mixture in the reservoir is
inhibited. An exemplary technique to prevent polymerization is
agitating or stirring the mixture in the reservoir. Those of
ordinary skill in the polymer arts will appreciate that other
techniques for inhibiting the mixture in reservoir may be
appropriate. For example, some polymer reactions are initiated by
illuminating with light of an appropriate wavelength (dental
polymers used to replace mercury amalgams are an example). Thus,
inhibiting polymerization might involve preventing light of that
wavelength from reaching the mixture in the reservoir, while light
is applied to the mixture in the mold volume. It should be noted
that while the PA hydrogel described in detail above represents an
exemplary hydrogel, mold 30, and variants of mold 30, can be used
to form other hydrogel materials into acoustic couplings, and thus
the technique for inhibiting the polymerization in the reservoir
will be dictated by the initiator used to induce polymerization in
the specific reaction and material employed.
[0141] As hydrogels polymerize, they shrink. The solid portion
shown in FIG. 9B represents the original mixture introduced into
the mold volume. If no additional mixture was introduced into the
mold volume, the shape of the finished hydrogel would not be as
desired (i.e., an upper tip 50 would be missing). However, as the
mixture originally introduced into the mold volume polymerizes and
shrinks, additional liquid mixture from reservoir flows into the
mold volume and polymerizes.
[0142] Once the mold volume is filled with polymerized mixture
(i.e., a hydrogel) the mixture in the reservoir is allowed to
polymerize. The mold is taken apart, and the portion of the
hydrogel within the reservoir (and within the drip channel coupling
the reservoir to the mold volume) can be trimmed away.
[0143] It should be noted that while mold 30 performed admirably
for laboratory purposes, mass production of hydrogel couplings will
likely be achieved using molds specifically adapted for high speed
production. Clearly, the present invention is not limited to
manufacture specifically using mold 30, or even to three part
molds.
[0144] FIGS. 10A-11D provide details on how modifying top portion
36 can enable hydrogel couplings having distal surfaces of
different configurations to be achieved. To achieve good coupling
with a target or a boundary disposed between the target and the
transducer, the distal surface of the hydrogel coupling should
closely conform to the surface of the target or boundary,
respectively. While coupling gels can be used to fill any gaps,
closely matched surfaces enhance coupling and ease of use.
[0145] In FIGS. 10A and 10B, top portion 36 comprises an outer ring
36a and an inner portion 36b. Inner portion 36b includes the
reservoir and the drip channel described above (reference numbers
omitted to simplify the Figure, see FIG. 8). A surface 54a
determines the shape of the tip of the distal surface of the
hydrogel coupling produced.
[0146] While not specifically shown, ring 36a and middle portion 34
can rotatably couple together using threads in an area 62. The
dimensions of ring 36a and middle portion 34 can be configured at
area 62 such that ring 36a is press fit onto middle portion 34
securely enough so that the mold does not come apart while molding
the PA material, but loosely enough so that the ring can be removed
after the mold is used, to disassemble the mold. Also, note that
ring 36a and inner portion 36b are notched at area 64, to enable
inner portion 36b to be held securely in position, as shown in FIG.
10B.
[0147] FIGS. 11A-11D illustrate inner portions of different shapes,
and the tip of the distal surface of a hydrogel coupling that is
achieved using that inner portion. In FIG. 11A, inner portion 36b
can be employed to produce a hydrogel coupling having a tip on
distal surface 54b that is a full convex, corresponding to a full
concave surface 54a on the bottom of inner portion 36b. A useful
radius of curvature for surface 54a is about 4.8 mm.
[0148] In FIG. 11B, inner portion 36c can be employed to produce a
hydrogel coupling having a tip on distal surface 56b that is a
short convex, conforming to a short concave surface 56a on the
bottom of inner portion 36c. A useful radius of curvature for
concave surface 56a is 7.3 mm.
[0149] In FIG. 11C, inner portion 36d can be employed to produce a
hydrogel coupling having a tip on distal surface 58b that is flat,
conforming to a flat 58a, while in FIG. 11D, inner portion 36e can
be employed to produce a hydrogel coupling having a tip on distal
surface 60b that is concave, conforming to a convex surface 60a. A
useful radius of curvature for convex surface 60a is 7.3 mm.
[0150] It should be understood that the dimensions of the
curvatures suggested above are intended to be exemplary, and not
limiting on the present invention. Of course, other shapes can be
employed in a mold to achieve any desired hydrogel coupling
shape.
[0151] FIG. 12A illustrates an exemplary use of hydrogel couplings
in accord with the present invention. In a probe 65, a conical
hydrogel coupling 66 is attached to an acoustic transducer 68,
mounted to a handle 70. A lead 72 couples the transducer to a power
supply 74. In FIG. 12B, probe 65 is being used to apply HIFU to a
target proximate a dermal layer 76 of a patient (not otherwise
shown). Focal region 14 is proximate to (within) the dermal layer.
In such a configuration, the distal surface of coupling 66 is
disposed proximate to the focal region of the transducer. Thus, it
is important for the hydrogel to be sufficiently robust to maintain
its structural integrity during application of HIFU therapy. It
should be understood that probe 65 could be used inside a patient's
body, inserted via a body cavity or incision, and is not limited to
external use. The significance of probe 65 is that the focal region
of the transducer is disposed proximate to the distal surface of
the hydrogel coupling so that the tip of the hydrogel coupling is
immediately adjacent to the treatment site. Thus, the HIFU can be
easily aimed by observing the tip of the distal surface of the
hydrogel coupling.
[0152] A probe 65a shown in FIG. 12C is different, in that the
distal surface of a hydrogel coupling 66a is not disposed
immediately adjacent to or proximate to the focal region of the
transducer. Hydrogel coupling 66a is significantly shorter, such
that when the tip of the hydrogel coupling lies against the dermal
layer of the patient, the focal region of the transducer is within
a subcutaneous target 78. Selecting an even shorter hydrogel
coupling would enable the focal region to penetrate further below
the dermal layer and deeper into the subcutaneous target, while
selecting a longer hydrogel coupling will bring the focal region
closer to the dermal layer. Thus if the location of the target is
known, a hydrogel coupling of an appropriate length can be
selected, so as to ensure that the focal region of the transducer
is disposed proximate to the desired target. When shorter hydrogel
couplings are used, less robust hydrogels can be employed, because
the distal surface is no longer proximate to the focal region,
where the highest temperatures are likely to be encountered.
[0153] FIGS. 13A-13C illustrate how a restraining housing 80a can
be used to removably secure hydrogel coupling 66 to transducer 68.
FIG. 13A is an exploded view illustrating how restraining housing
80a fits over hydrogel coupling 66. In FIG. 13B, the restraining
housing has been secured to transducer 68 (or handle 70), thereby
mounting hydrogel coupling 66 in place. Restraining housing 80a is
open at its conical end, so that a tip of distal surface 82 of the
hydrogel coupling is exposed and extends beyond the restraining
housing. FIG. 13C shows transducer 68 being energized, resulting in
acoustical waves 84. Note that the focal region of the transducer
is proximate to the upper extent of distal surface 82 of the
hydrogel coupling.
[0154] FIGS. 14A and 14B show a shorter restraining housing 80b
being used to couple a shorter hydrogel coupling 86 to the same
transducer. FIG. 14A is an exploded view illustrating how
restraining housing 80b fits over hydrogel coupling 86, while FIG.
14B is an assembled view. FIG. 14B also includes beam dimension 12
and focal region 14, illustrating that a distal surface 88 of
hydrogel coupling 86 is not disposed proximate to the focal
region.
[0155] FIGS. 15A-15G further illustrate how the length of a
hydrogel coupling can be selected to enable the focal region to be
disposed adjacent to a target. In FIG. 15A, a hydrogel coupling 90
is shown positioned over transducer 68. Coupling 90 has a length
92. By providing a plurality of couplers 94a-94f, each having a
different length, the position of the focal region relative to a
distal surface of the hydrogel coupling can be varied. Longer
hydrogel couplings (e.g., hydrogel coupling 94e) will result in
distal surfaces of the couplings being disposed closer to the focal
region. Shorter couplings (e.g., coupling 94a) will result in
distal surfaces of the hydrogel couplings being disposed farther
away from the focal region. As shown in FIG. 12C, the shorter the
coupling, the farther away the focal region will be from the distal
surface of the coupling, which will be brought into contact with
the surface of intervening tissue.
[0156] FIG. 16 illustrates Schlieren images obtained using hydrogel
couplings of varying lengths. Schlieren imaging was used to
visualize the ultrasound field emitted from the HIFU transducer
with the hydrogel coupler attached, and to determine if the gel
coupler was in any way distorting the HIFU field. Four 15% gel
cones of different shapes were tested: a 2 cm truncated cone; a 3
cm truncated cone; a full-length cone with flat tip; and a
full-length gel cone with convex rounded tip. A collimated beam of
light passed through an optically transparent tank containing
degassed water. The HIFU beam was directed into the water tank,
perpendicular to the light beam axis. The light leaving the tank
was focused and filtered, and the image was displayed on a
screen.
[0157] The images obtained showed that the HIFU field was
essentially unchanged by the presence of the various gel couplers.
For the full-length, flat and round tip couplers, the image of the
ultrasound field seemed to bleed down into the shadow of the
coupler tip. This effect was probably caused by diffraction of the
light beam.
[0158] As noted above, when the distal surface of a hydrogel
coupling is disposed proximate the focal region, particularly in
HIFU applications, intense temperatures and pressures can damage
the distal surface of the hydrogel coupling. As hydrogel couplings
include a large amount by weight of water, such temperatures and
pressures have been empirically shown to dry out the distal
surfaces, leading to damage to the surfaces. Thus, an aspect of the
present invention is the incorporation of means to hydrate (or
maintain the hydration of) the distal surfaces of the hydrogel
couplings. FIGS. 17A-17C illustrate several structures that can be
used to achieve such hydration. In FIG. 17A, a fluid channel 98 is
coupled with a water supply (not shown), and the other end of the
fluid channel is disposed adjacent to a tip 95 of the distal
surface of hydrogel 96. In FIG. 17B, a fluid channel 98a is
attached to a restraining housing 100 and is coupled with a water
supply (not shown); the other end of the fluid channel is disposed
adjacent to tip 95 of the distal surface of hydrogel 96. In the
embodiment illustrated in FIG. 17C, a fluid channel 102 is disposed
within hydrogel coupling 96a. Fluid channel 102 is coupled with a
water supply (not shown), and the other end of the fluid channel is
disposed adjacent to a tip 95a of the distal surface of hydrogel
96a, to enable the surface to be hydrated.
[0159] A unique advantage of using a hydrogel is the possibility of
introducing medication, such as antibiotics, into the hydrogel
coupling, and to administer such medications where the hydrogel
coupling contacts the tissue of a patient. During surgery, the
hydrogel coupler can be used to transfer antibiotics, in addition
to ultrasound, into the treatment site. FIGS. 18A-18C illustrate
several structures that can be used to achieve such medication. In
FIG. 18A, a hydrogel coupling 96b has a medicinal agent 104
distributed throughout the hydrogel. The agent can be added after
the hydrogel is produced. Hydrogels include many channels within
the hydrogel where such medicinal agents can be absorbed and
stored. It is expected that if the polymerization is not
detrimental to the medicinal agent, the medicine can be added
before the hydrogel is produced. In FIG. 18B, energizing a
transducer coupled to the hydrogel causes some of the medicinal
agent to be "pushed out" of tip 95b of the distal surface of the
hydrogel coupling. The effect of the therapeutic agent could be
either synergistic with, or independent of HIFU. Thus, the
therapeutic outcome can either be enhanced exponentially, or
arithmetically, depending on the choice of the therapeutic agent
and the HIFU dose.
[0160] In FIG. 18C, medicinal agent 104 has been distributed
proximate to a tip 95c of the distal surface, rather than
throughout hydrogel coupling 96c. A fluid channel 98a is shown as
an optional element and can be used to hydrate tip 95c of the
distal surface of hydrogel coupling 96c, or even to deliver
additional medicinal agents. If desired, fluid channel 98a could be
used as the sole method of delivering a medicinal agent.
[0161] As shown in FIG. 19, yet another aspect of the present
invention is a kit 110 containing components to be used for
acoustically coupling an ultrasound transducer with a target. Kit
110 includes at least a hydrogel coupling 112, having a proximal
surface configured to be disposed adjacent to an ultrasound
transducer, and a distal surface configured to acoustically couple
with at least one of a target and a boundary associated with the
target. The kit also includes at least a sealed package 122
configured to maintain the hydrogel coupling in a hydrated
condition until removed from the sealed package in preparation for
use. The sealed package can be hermetically sealed and/or
vacuum-sealed to maintain the contents of the package in a sterile
state and avoid loss of hydration of the hydrogel coupler.
[0162] Optionally, kit 110 includes instructions 118 for using the
hydrogel coupling to couple an ultrasound transducer with a target,
to facilitate an application of HIFU therapy. The instructions may
also inform users how to maintain the distal surface of the
dimensionally stable hydrogel coupling in a hydrated condition.
[0163] Another optional elements is coupling gel 116, which is a
semisolid or fluidic coupling medium used to enhance an acoustic
coupling of the proximal surface of the hydrogel coupling to an
outer surface of an ultrasound transducer that is used to
administer the HIFU therapy. Yet another optional element of such a
kit is a retaining housing 114, configured to removably couple the
hydrogel coupling with an ultrasound transducer.
[0164] Ideally, couplers with different cone heights and impedance
would be available to the physician. Accordingly, kits containing
different length hydrogel couplers (see FIGS. 15B-15G) will
preferably be available.
[0165] FIGS. 20-23 are flow charts illustrating sequences of
logical steps employed in carrying out the present invention. FIG.
20 illustrates the steps for using a hydrogel coupling sufficiently
robust to withstand the ultrasound intensities to be employed; FIG.
21 illustrates the steps for ensuring that a focal region of a
transducer is proximate a target; FIG. 22 illustrates the steps for
making a hydrogel coupling configured to ensure that a focal region
of a transducer is proximate a target; and FIG. 23 illustrates the
steps for producing a hydrogel that accomadates for shrinkage
during polymerization.
[0166] Referring to FIG. 20, a flow chart 120 begins in a block
122, in which a specific acoustic transducer is selected. In a
block 124, an input power level and a duration for energizing the
ultrasound transducer are selected. A block 126 refers to providing
a hydrogel coupling that is capable of maintaining its structural
integrity when used to couple the ultrasound transducer with at
least one of the target and a physical boundary associated with the
target under the input power level and duration selected. In at
least one embodiment, the hydrogel coupling provided has a length
that will ensure that a focal region of the ultrasound transducer
is disposed proximate the target.
[0167] In a block 128, the proximal surface of the hydrogel
coupling is coupled with an outer surface of the ultrasound
transducer, and in a block 130, the distal surface of the hydrogel
coupling is coupled with at least one of the target and a physical
boundary separating the target from the distal surface of the
hydrogel coupling. A restraining housing can be used to secure the
hydrogel coupling. Finally, in a block 132, the ultrasound
transducer is energized at the selected input power level and
duration. Additional steps can include hydrating the distal surface
of the dimensionally stable hydrogel mass, to prevent damage to the
tip of the distal surface of the dimensionally stable hydrogel mass
by the HIFU, and/or delivering a medicinal agent to at least one of
the target and the physical boundary, after coupling the distal
surface of the dimensionally stable hydrogel mass to at least one
of the target and the physical boundary. Referring now to FIG. 21,
a flow chart 134 begins in a block 136, where a specific ultrasound
transducer to be employed is selected. In a block 138, an input
power level and a duration are selected to energize the ultrasound
transducer. A block 140 indicates that a hydrogel coupling is
provided having a length that will ensure that a focal region of
the ultrasound transducer is disposed proximate to the target.
[0168] In a block 142, the proximal surface of the hydrogel
coupling is coupled with an outer surface of the ultrasound
transducer, and in a block 144, the distal surface of the hydrogel
coupling is coupled with at least one of the target and a physical
boundary separating the target from the distal surface of the
hydrogel coupling. As noted above, a restraining housing can be
used to secure the hydrogel coupling. Finally, in a block 146, the
ultrasound transducer is energized at the selected input power
level and duration.
[0169] Flow chart 148 of FIG. 22 illustrates the steps involved in
producing a hydrogel coupling having a length that will ensure a
focal region of a specific ultrasound transducer is disposed
proximate to the target. In a block 150 the monomer, or mixture of
monomers are selected from which the hydrogel will be produced. As
discussed above, acrylamide monomers can be beneficially employed.
However, the invention is not so limited, and other monomer(s) can
alternatively be employed. In a block 152, an agent is provided for
inducing polymerization of the at least one monomer, providing a
quantity of water sufficient to hydrate the quantity of the
selected monomer(s).
[0170] In a block 154, a mold configured to form a hydrogel
coupling having the desired size and shape is provided. The mold is
configured to produce a hydrogel coupling having a length that
ensures a focal region of a specific ultrasound transducer is
disposed proximate to the target, generally as described above. In
a block 156, the monomer, agent, and water are mixed together in
the appropriate amounts. Those of ordinary skill in the art will
recognize that many different components for producing hydrogels
are known. In a block 158, the mixture is introduced into the mold.
In a block 160, the mixture is allowed to polymerize, and in a
block 162, the hydrogel coupling is removed from the mold.
[0171] Referring now to FIG. 23, a flow chart 164 illustrates the
logical steps for producing a hydrogel coupling using a mold with a
reservoir to accommodate shrinkage. In a block 166, the monomer is
selected, and in a block 168, an agent for inducing polymerization
of the monomer, and water, are provided. In a block 170, a mold
configured to form a hydrogel coupling having the desired size and
shape is provided. The mold includes both a mold volume
corresponding to the size and shape of the desired hydrogel
coupling, and a reservoir in fluid communication with the mold
volume.
[0172] In a block 172, the monomer, the agent, and water are mixed
together in appropriate amounts. In a block 174, the mixture is
introduced into the mold. In a block 176, the mixture in the
reservoir is inhibited from polymerization, while in a block 178
the mixture in the mold volume is allowed to polymerize.
[0173] After the mixture in the mold volume polymerizes, the
mixture in the reservoir is allowed to polymerize, as indicated in
block 180. In a block 182, the hydrogel coupling is removed from
the mold, and the hydrogel coupling is trimmed in a block 184, to
remove the portion corresponding to the reservoir portion and
interconnection to the mold.
[0174] One beneficial property of hydrogels is that they are
dimensionally stable, solid appearing materials, in sharp contrast
to the semi-solid, paste-like coupling gels frequently used to
couple imaging transducers to tissue. In the claims that follow,
the term "dimensionally stable hydrogel mass" has been employed to
emphasize this property.
[0175] 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.
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