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| United States Patent Application |
20050240126
|
| Kind Code
|
A1
|
|
Foley, Jessica L.
; et al.
|
October 27, 2005
|
Ultrasound guided high intensity focused ultrasound treatment of nerves
Abstract
A method for using high intensity focused ultrasound (HIFU) to treat
neurological structures to achieve a desired therapeutic affect.
Depending on the dosage of HIFU applied, it can have a reversible or
irreversible effect on neural structures. For example, a relatively high
dose of HIFU can be used to permanently block nerve function, to provide
a non-invasive alternative to severing a nerve to treat severe
spasticity. Relatively lower doses of HIFU can be used to reversible a
block nerve function, to alleviate pain, to achieve an anesthetic effect,
or to achieve a cosmetic effect. Where sensory nerves are not necessary
for voluntary function, but are involved in pain associated with tumors
or bone cancer, HIFU can be used to non-invasively destroy such sensory
nerves to alleviate pain without drugs. Preferably, ultrasound imaging
synchronized to the HIFU therapy is used to provide real-time ultrasound
image guided HIFU therapy of neural structures.
| Inventors: |
Foley, Jessica L.; (Seattle, WA)
; Vaezy, Shahram; (Seattle, WA)
; Little, James W.; (Seattle, WA)
|
| Correspondence Name and Address:
|
LAW OFFICES OF RONALD M ANDERSON
600 108TH AVE, NE
SUITE 507
BELLEVUE
WA
98004
US
|
| Assignee Name and Adress: |
University of Washington
Seattle
WA
|
| Serial No.:
|
016701 |
| Series Code:
|
11
|
| Filed:
|
December 16, 2004 |
| U.S. Current Class: |
601/2 |
| U.S. Class at Publication: |
601/002 |
| Intern'l Class: |
A61H 005/00; A61H 001/00; A61H 001/02 |
Goverment Interests
[0002] This invention was funded at least in part with a grant (No.
DAMD-17-02-2-0014) from the U.S. Army, and the U.S. government may have
certain rights in this invention.
Claims
The invention in which an exclusive right is claimed is defined by the
following:
1. A method for using high intensity focused ultrasound (HIFU) to provide
therapy to a treatment site corresponding to a portion of a nervous
system of a patient, the treatment site being spaced apart from a HIFU
therapy device, comprising the steps of: (a) determining an appropriate
treatment site associated with the nervous system of the patient to be
treated to achieve a desired non-permanent therapeutic effect; (b)
selecting a dose of HIFU required to achieve the desired non-permanent
therapeutic effect; (c) positioning the HIFU therapy device such that a
focal point of the HIFU therapy device is disposed adjacent to the
treatment site; (d) verifying that the focal point of the HIFU therapy
device is properly positioned relative to the treatment site, and if not
repositioning the HIFU therapy device until the HIFU therapy device is
properly positioned relative to the treatment site; and (e) energizing
the HIFU therapy device to provide the dose of HIFU required to achieve
the desired non-permanent therapeutic effect.
2. The method of claim 1, further comprising the steps of: (a) using
ultrasound imaging to obtain an ultrasound image of the treatment site
during therapy; and (b) synchronizing the HIFU therapy device and the
ultrasound imaging such that noise in the ultrasound image arising from
the HIFU therapy device does not prevent visualization of the focal point
in the ultrasound image during therapy.
3. The method of claim 1, wherein the non-permanent therapeutic effect
comprises blocking nerve conduction to achieve a cosmetic effect.
4. The method of claim 1, wherein the non-permanent therapeutic effect
comprises blocking nerve conduction to provide anesthesia of a nerve.
5. The method of claim 1, wherein the non-permanent therapeutic effect
comprises blocking nerve conduction to alleviate pain.
6. The method of claim 1, wherein the non-permanent therapeutic effect
comprises blocking nerve conduction to treat spasticity.
7. The method of claim 1, wherein the step of determining the appropriate
treatment site comprises the step of selecting a nerve as the treatment
site.
8. The method of claim 1, wherein the step of determining the appropriate
treatment site comprises the step of selecting a nerve ganglia as the
treatment site.
9. The method of claim 1, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
determining the dose of HIFU required to partially block nerve conduction
at the treatment site.
10. The method of claim 1, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
determining the dose of HIFU required to completely block nerve
conduction at the treatment site.
11. The method of claim 1, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the step of using magnetic resonance imaging to
determine a position of the focal point relative to the treatment site.
12. The method of claim 1, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) using ultrasound imaging to
obtain an ultrasound image of the treatment site; and (b) energizing the
HIFU therapy device at a power level that is insufficient to induce
damage at the treatment site, but is sufficient to enable the focal point
to be visualized in the ultrasound image.
13. The method of claim 1, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) positioning an ultrasound
imaging device and the HIFU therapy device such that the focal point lies
within an image plane provided by the ultrasound imaging device; (b)
providing an indication of where the focal point lies within an
ultrasound image generated by the ultrasound imaging device, such that
the focal point can be visualized in the ultrasound image, even when the
HIFU therapy device is not energized; (c) fixing a position of the
ultrasound imaging device relative to the HIFU therapy device, such that
movement of either device will not move the focal point out of the image
plane; (d) obtaining the ultrasound image of the treatment site; and (e)
manipulating at least one of the ultrasound imaging device, the HIFU
therapy device, and a frame used to secure the position of the ultrasound
imaging device relative to the HIFU therapy device until the indication
of the focal point is properly positioned relative to the treatment site.
14. The method of claim 1, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) identifying what type of
physiological reaction should occur if the focal point of the HIFU
therapy device is properly positioned relative to the treatment site when
the HIFU therapy device is energized to stimulate the nervous system of
the patient, to achieve an identified physiological reaction; (b)
energizing the HIFU therapy device at a power level that is insufficient
to induce damage at the treatment site but is sufficient to stimulate the
nervous system of the patient; (c) observing any physiological reaction
to achieve an observed physiological reaction; and (d) determining if the
identified physiological reaction corresponds to the observed
physiological reaction, and if so, concluding that the focal point of the
HIFU therapy device is properly positioned relative to the treatment
site.
15. The method of claim 1, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) using an imaging device to
obtain an image of the treatment site and adjacent areas; (b) tracking a
position of the imaging device; (c) tracking a position of the HIFU
therapy device; (d) based on the positions of the imaging ultrasound
transducer and the HIFU therapy device, introducing an icon into the
image, the icon corresponding to a predicted position of the focal point
based on the positions of the imaging device and the HIFU therapy device;
and (e) manipulating the position of at least one of the imaging device
and the HIFU therapy device until the icon coincides with the treatment
site in the image.
16. A method for using high intensity focused ultrasound (HIFU) to provide
therapy to a treatment site corresponding to a portion of a nervous
system of a patient, the treatment site being spaced apart from a HIFU
therapy device, comprising the steps of: (a) determining an appropriate
treatment site to be treated to achieve a desired therapeutic effect; (b)
selecting a dose of HIFU required to achieve the desired therapeutic
effect, the desired therapeutic effect comprising blocking nerve
conduction for at least one of the following purposes: (i) to alleviate
pain; (ii) to provide a palliative treatment for cancer; (iii) to treat
spasticity; (iv) to provide an anesthetic effect; and (v) to provide a
cosmetic effect; (c) positioning the HIFU therapy device such that a
focal point of the HIFU therapy device is disposed adjacent to the
treatment site; (d) verifying that the focal point of the HIFU therapy
device is properly positioned relative to the treatment site, and if not,
repositioning the HIFU therapy device until the HIFU therapy device is
properly positioned relative to the treatment site; and (e) energizing
the HIFU therapy device to provide the dose of HIFU to the treatment site
that is required to achieve the desired therapeutic effect.
17. The method of claim 16, further comprising the steps of: (a) using
ultrasound imaging to obtain an ultrasound image of the treatment site
during therapy; and (b) synchronizing the HIFU therapy device and the
ultrasound imaging such that noise in the ultrasound image arising from
the HIFU therapy device does not prevent visualization of the focal point
in the ultrasound image during therapy.
18. The method of claim 16, wherein the step of determining the
appropriate treatment site comprises the step of selecting at least one
of a nerve and a nerve ganglia as the treatment site.
19. The method of claim 16, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting the dose of HIFU required to partially block nerve conduction
at the treatment site.
20. The method of claim 16, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting the dose of HIFU required to completely block nerve conduction
at the treatment site.
21. The method of claim 16, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting the dose of HIFU required to permanently block nerve conduction
at the treatment site.
22. The method of claim 16, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting the dose of HIFU required to temporarily block nerve conduction
at the treatment site.
23. The method of claim 16, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) using ultrasound imaging to
obtain an ultrasound image of the treatment site; and (b) energizing the
HIFU therapy device at a power level that is insufficient to induce
damage at the treatment site, but is sufficient to enable the focal point
to be visualized in the ultrasound image.
24. The method of claim 16, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) identifying a type of
physiological reaction that should occur if the focal point of the HIFU
therapy device is properly positioned relative to the treatment site when
the HIFU therapy device is energized to stimulate the nervous system of
the patient, yielding an identified physiological reaction; (b)
energizing the HIFU therapy device at a power level that is insufficient
to induce damage at the treatment site, but is sufficient to stimulate
the nervous system of the patient; (c) observing any physiological
reaction to achieve an observed physiological reaction; and (d)
determining if the identified physiological reaction corresponds to the
observed physiological reaction, and if so, concluding that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site.
25. The method of claim 16, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) positioning an ultrasound
imaging device and the HIFU therapy device such that the focal point lies
within an image plane provided by the ultrasound imaging device; (b)
providing an indication of where the focal point lies within the image
plane, such that the focal point can be visualized in the image plane
even when the HIFU therapy device is not energized; (c) fixing a position
of the ultrasound imaging device relative the HIFU therapy device, such
that movement of either device will not move the focal point out of the
image plane; (d) obtaining an ultrasound image of the treatment site; and
(e) manipulating at least one of the ultrasound imaging device, the HIFU
therapy device, and a frame used to secure the position of the ultrasound
imaging device relative to the HIFU therapy device, until the indication
of the focal point is properly positioned relative to the treatment site.
26. The method of claim 16, wherein the step of verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site comprises the steps of: (a) using an imaging device to
obtain an image of the treatment site; (b) tracking a position of the
imaging device; (c) tracking a position of the HIFU therapy device; (d)
based on the positions of the imaging device and the HIFU therapy device,
introducing an icon into the image, the icon corresponding to a predicted
position of the focal point based on the positions of the imaging device
and the HIFU therapy device; and (d) manipulating the position of at
least one of the imaging device and the HIFU therapy device until the
icon coincides with the treatment site in the image.
27. A method for using ultrasound to simultaneously image a target area
and to provide therapy to a treatment site disposed within said target
area, the treatment site corresponding to a portion of a nervous system,
thereby inducing a desired therapeutic effect, comprising the steps of:
(a) positioning an imaging ultrasound transducer so as to enable an image
of the target area to be obtained, and positioning a therapeutic
ultrasound transducer so that a focal point corresponding to the
therapeutic ultrasound transducer generally coincides with a portion of
the target area; (b) energizing the imaging ultrasound transducer to
generate an ultrasound image of the target area; (c) selecting the
treatment site from within the ultrasound image; (d) energizing the
therapeutic ultrasound transducer to produce pulses of high intensity
focused ultrasound (HIFU) therapeutic waves to induce the desired
therapeutic effect; (e) synchronizing the HIFU therapeutic waves relative
to imaging waves produced by the imaging ultrasound transducer, such that
noise in the ultrasound image from the HIFU therapeutic waves is
displayed in a specific portion of the displayed target area; and (f)
enabling a user to shift the noise arising from the HIFU therapeutic
waves to a portion of the ultrasound image that does not correspond to
the treatment site, thereby enabling the treatment site to be observed in
real-time as the HIFU therapeutic waves are administered to the treatment
site.
28. The method of claim 27, wherein the desired therapeutic effect
comprises blocking nerve conduction for at least one of the following
purposes: (a) to alleviate pain; (b) to treat spasticity; (c) to provide
an anesthetic effect; and (d) to provide a cosmetic effect.
29. The method of claim 27, further comprising a step of selecting a dose
of HIFU required to achieve the desired therapeutic effect before
energizing the therapeutic ultrasound transducer.
30. The method of claim 27, wherein the step of selecting a dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting a dose that will result in a temporary therapeutic effect.
31. The method of claim 27, wherein the step of selecting a dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting a dose that will result in a partial blockage of nerve
conduction.
32. The method of claim 27, further comprising a step of verifying a
position of the focal point relative to the target area before energizing
the therapeutic ultrasound transducer to induce the desired therapeutic
effect, to reduce a risk that non-target structures will be damaged.
33. The method of claim 32, wherein the step of verifying a position of
the focal point relative to the target area comprises the steps of: (a)
tracking a position of the imaging ultrasound transducer while producing
the ultrasound image of the target area; (b) tracking a position of the
therapeutic ultrasound transducer, (c) based on the positions of the
imaging ultrasound transducer and the therapeutic ultrasound transducer,
introducing an icon into the ultrasound image, the icon corresponding to
a predicted position of the focal point based on the positions of the
imaging ultrasound transducer and the therapeutic ultrasound transducer;
and (d) manipulating the position of at least one of the imaging
ultrasound transducer and the therapeutic ultrasound transducer until the
icon coincides with the treatment site in the ultrasound image.
34. The method of claim 32, wherein the step of verifying a position of
the focal point relative to the target area comprises a steps of: (a)
identifying a type of physiological reaction that should occur if the
focal point of the therapeutic ultrasound transducer is properly
positioned relative to the treatment site and the therapeutic ultrasound
transducer is energized to stimulate the nervous system, yielding an
identified physiological reaction; (b) energizing the therapeutic
ultrasound transducer at a power level that is insufficient to induce
damage but is sufficient to stimulate the nervous system; (c) observing
any physiological reaction to achieve an observed physiological reaction;
and (d) determining if the identified physiological reaction corresponds
to the observed physiological reaction, and if so, concluding that the
focal point of the therapeutic ultrasound transducer is properly
positioned relative to the treatment site.
35. The method of claim 32, wherein the step of verifying a position of
the focal point relative to the target area comprises the step of
energizing the therapeutic ultrasound transducer at a power level that is
insufficient to induce damage, but is sufficient to enable the focal
point to be visualized in the ultrasound, before energizing the
therapeutic ultrasound transducer at a power level sufficient to achieve
the desired therapeutic effect.
36. The method of claim 32, wherein the step of verifying a position of
the focal point relative to the target area comprises the steps of: (a)
positioning the imaging ultrasound transducer and the therapeutic
ultrasound transducer such that the focal point lies within an image
plane provided by the imaging ultrasound transducer; (b) providing an
indication of where the focal point lies within the ultrasound image,
such that the focal point can be visualized in the ultrasound image even
when the therapeutic ultrasound transducer is not energized; (c) fixing a
position of the imaging ultrasound transducer relative to the therapeutic
ultrasound transducer, such that movement of either device will not move
the focal point out of the ultrasound image; and (d) manipulating at
least one of the imaging ultrasound transducer, the therapeutic
ultrasound transducer, and a frame used to secure the position of the
imaging ultrasound transducer relative to the therapeutic ultrasound
transducer until the indication of the focal point is properly positioned
relative to the treatment site.
37. A method for using ultrasound to simultaneously image a target area
and to provide therapy to a treatment site disposed within said target
area, the treatment site comprising a portion of the nervous system,
comprising the steps of: (a) using an imaging ultrasound transducer to
obtain an ultrasound image of the target area; (b) selecting the
treatment site from the ultrasound image; and (c) using an therapeutic
ultrasound transducer to direct high intensity focused ultrasound (HIFU)
at the treatment site, the therapeutic ultrasound transducer and the
imaging ultrasound transducer being synchronized such that any noise in
the ultrasound image arising from the HIFU does not obscure visualization
of the treatment site in the ultrasound image, enabling the treatment
site to be observed in real-time as the HIFU is administered to the
treatment site.
38. The method of claim 37, wherein the therapy comprises blocking nerve
conduction.
39. The method of claim 38, wherein the nerve conduction is blocked
temporarily.
40. The method of claim 38, wherein the nerve conduction is blocked to
alleviate pain.
41. The method of claim 38, wherein the nerve conduction is blocked to
treat spasticity.
42. The method of claim 38, wherein the nerve conduction is blocked to
provide an anesthetic effect.
43. The method of claim 38, wherein the nerve conduction is blocked to
provide a cosmetic effect.
44. The method of claim 37, further comprising a step of verifying a
position of a focal point of the therapeutic ultrasound transducer
relative to the treatment site before energizing the therapeutic
ultrasound transducer to provide therapy, to reduce a risk that
non-target structures will be damaged.
45. The method of claim 44, wherein the step of verifying a position of
the focal point relative to the treatment site comprises the steps of:
(a) tracking a position of the imaging ultrasound transducer while
producing the ultrasound image; (b) tracking a position of the
therapeutic ultrasound transducer; (c) based on the positions of the
imaging ultrasound transducer and the therapeutic ultrasound transducer,
introducing an icon into the ultrasound image, the icon corresponding to
a predicted position of the focal point based on the positions of the
imaging ultrasound transducer and the therapeutic ultrasound transducer;
and (d) manipulating the position of at least one of the imaging
ultrasound transducer and the therapeutic ultrasound transducer until the
icon coincides with the treatment site in the ultrasound image.
46. The method of claim 44, wherein the step of verifying a position of
the focal point relative to the treatment site comprises the steps of:
(a) identifying what type of physiological reaction should occur if the
focal point of the therapeutic ultrasound transducer is properly
positioned relative to the treatment site and the therapeutic ultrasound
transducer is energized to stimulate the nervous system, yielding an
identified physiological reaction; (b) energizing the therapeutic
ultrasound transducer at a power level that is insufficient to induce
damage but is sufficient to stimulate the nervous system; (c) observing
any physiological reaction to achieve an observed physiological reaction;
and (d) determining if the identified physiological reaction corresponds
to the observed physiological reaction, and if so, concluding that the
focal point of the therapeutic ultrasound transducer is properly
positioned relative to the treatment site.
47. The method of claim 44, wherein the step of verifying a position of
the focal point relative to the target area comprises the step of
energizing the therapeutic ultrasound transducer at a power level that is
insufficient to induce damage at the treatment site, but is sufficient to
enable the focal point to be visualized in the image provided by the
imaging ultrasound transducer, before energizing the therapeutic
ultrasound transducer at a power level sufficient to achieve the desired
therapeutic effect.
48. A method for using high intensity focused ultrasound (HIFU) to provide
therapy to a treatment site associated with a nervous system of a
patient, the treatment site being spaced apart from a HIFU therapy
device, comprising the steps of: (a) determining an appropriate treatment
site associated with the nervous system of the patient to be treated to
achieve a desired therapeutic effect; (b) selecting a dose of HIFU
required to achieve a desired therapeutic effect; (c) using an ultrasound
imaging device to obtain an image of the treatment site; (d) positioning
the HIFU therapy device such that a focal point of the HIFU therapy
device is disposed adjacent to the treatment site; (e) energizing the
HIFU therapy device at a power level that is insufficient to induce
damage at the treatment site, but is sufficient to enable the focal point
to be visualized in the image provided by the ultrasound imaging device
to verify that the focal point of the HIFU therapy device is properly
positioned relative to the treatment site, and if not, repositioning the
HIFU therapy device until the HIFU therapy device is properly positioned
relative to the treatment site; and (f) energizing the HIFU therapy
device to provide the dose of HIFU required to achieve the desired
therapeutic effect.
49. A method for using high intensity focused ultrasound (HIFU) to treat
spasticity by applying HIFU to a treatment site corresponding to a
portion of a nervous system of a patient, the treatment site being spaced
apart from a HIFU therapy device, comprising the steps of: (a)
determining an appropriate treatment site associated with the nervous
system of the patient to treat spasticity; (b) selecting a dose of HIFU
required to achieve a desired therapeutic effect; (c) positioning the
HIFU therapy device such that a focal point of the HIFU therapy device is
disposed adjacent to the treatment site; (d) verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site, and if not, repositioning the HIFU therapy device until
the HIFU therapy device is properly positioned relative to the treatment
site; and (e) energizing the HIFU therapy device to provide the dose of
HIFU required to achieve the desired therapeutic effect.
50. A method for using high intensity focused ultrasound (HIFU) to
alleviate pain by applying HIFU to a treatment site corresponding to a
portion of a nervous system of a patient, the treatment site being spaced
apart from a HIFU therapy device, comprising the steps of: (a)
determining an appropriate treatment site associated with the nervous
system of the patient to alleviate pain; (b) selecting a dose of HIFU
required to achieve a desired therapeutic effect; (c) positioning the
HIFU therapy device such that a focal point of the HIFU therapy device is
disposed adjacent to the treatment site; (d) verifying that the focal
point of the HIFU therapy device is properly positioned relative to the
treatment site, and if not, repositioning the HIFU therapy device until
the HIFU therapy device is properly positioned relative to the treatment
site; and (e) energizing the HIFU therapy device to provide the dose of
HIFU required to achieve the desired therapeutic effect.
51. The method of claim 50, wherein the step of selecting the dose of HIFU
required to achieve the desired therapeutic effect comprises the step of
selecting a dose of HIFU that will result in both thermal and mechanical
interactions with the treatment site.
52. A method for using high intensity focused ultrasound (HIFU) to provide
an anesthetic effect by applying HIFU to a treatment site corresponding
to a portion of a nervous system of a patient, the treatment site being
spaced apart from a HIFU therapy device, comprising the steps of: (a)
determining an appropriate treatment site associated with the nervous
system of the patient to provide the anesthetic effect; (b) selecting a
dose of HIFU required to achieve a desired therapeutic effect; (c)
positioning the HIFU therapy device such that a focal point of the HIFU
therapy device is disposed adjacent to the treatment site; (d) verifying
that the focal point of the HIFU therapy device is properly positioned
relative to the treatment site, and if not, repositioning the HIFU
therapy device until the HIFU therapy device is properly positioned
relative to the treatment site; and (e) energizing the HIFU therapy
device to provide the dose of HIFU required to achieve the desired
therapeutic effect.
53. A method for using high intensity focused ultrasound (HIFU) to provide
a cosmetic effect by applying HIFU to a treatment site corresponding to a
portion of a nervous system of a patient, the treatment site being spaced
apart from a HIFU therapy device, comprising the steps of: (a)
determining an appropriate treatment site associated with the nervous
system of the patient to provide the cosmetic effect; (b) selecting a
dose of HIFU required to achieve a desired therapeutic effect; (c)
positioning the HIFU therapy device such that a focal point of the HIFU
therapy device is disposed adjacent to the treatment site; (d) verifying
that the focal point of the HIFU therapy device is properly positioned
relative to the treatment site, and if not, repositioning the HIFU
therapy device until the HIFU therapy device is properly positioned
relative to the treatment site; and (e) energizing the HIFU therapy
device to provide the dose of HIFU required to achieve the desired
therapeutic effect.
54. The method of claim 53, were in the step of determining an appropriate
treatment site associated with the nervous system of a patient comprises
the steps of: (a) identifying musculature associated with the cosmetic
effect to be achieved; and (b) identifying the portion of the nervous
system controlling the musculature so identified, the portion so
identified being determined to be the appropriate treatment site.
55. A probe for administering high intensity focused ultrasound (HIFU)
therapy to a neural structure within a patient's body, wherein a tissue
mass is disposed between the probe and the neural structure, comprising:
(a) a supporting structure; and (b) a HIFU transducer disposed at the
distal end of the supporting structure, the HIFU transducer having been
configured to achieve a focal region that is larger than a
cross-sectional area of the neural structure to be treated, such that a
lesion induced by a single application of HIFU will substantially
encompass a portion of the neural structure coinciding with the focal
region, so that only a single application of HIFU is required to block
conduction of the neural structure.
56. A method for using high intensity focused ultrasound (HIFU) to provide
therapy to a treatment site corresponding to a portion of a nervous
system of a patient, the treatment site being disposed substantially
adjacent to a HIFU therapy device, comprising the steps of: (a)
determining an appropriate treatment site associated with the nervous
system of the patient to be treated to achieve a desired non-permanent
therapeutic effect; (b) selecting a dose of HIFU required to achieve the
desired non-permanent therapeutic effect; (c) positioning the HIFU
therapy device such that the HIFU therapy device is substantially
adjacent to do treatment site and a focal point of the HIFU therapy
device coincides with the treatment site; (d) visually verifying that the
focal point of the HIFU therapy device is properly positioned relative to
the treatment site, a distal portion of the HIFU therapy device generally
coinciding with the focal point of the HIFU therapy device, and if not,
repositioning the HIFU therapy device until the HIFU therapy device is
properly positioned relative to the treatment site; and (e) energizing
the HIFU therapy device to provide the dose of HIFU required to achieve
the desired non-permanent therapeutic effect.
Description
RELATED APPLICATIONS
[0001] This application is based on a prior copending provisional
application Ser. No. 60/529,916, filed on Dec. 16, 2003, the benefit of
the filing date of which is hereby claimed under 35 U.S.C. .sctn. 119(e).
Further, this application is a continuation-in-part application of prior
copending application Ser. No. 10/770,350, filed on Feb. 2, 2004, which
itself is a continuation-in-part application of prior copending
application Ser. No. 10/166,795, filed on Jun. 7, 2002 and now issued as
U.S. Pat. No. 6,716,184, which itself is a divisional application of
prior copending application Ser. No. 09/397,471, filed on Sep. 17, 1999
and now issued as U.S. Pat. No. 6,425,867, the benefit of the filing
dates of which is hereby claimed under 35 U.S.C. .sctn. 120.
FIELD OF THE INVENTION
[0003] The present invention is directed to a method of using high
intensity focused ultrasound (HIFU) to treat neurological conditions,
such as spasticity and pain, using high intensity focused ultrasound, and
preferably using real-time imaging to properly focus the high intensity
focused ultrasound.
BACKGROUND OF THE INVENTION
[0004] HIFU has emerged as a precise, non-surgical, minimally-invasive
treatment for benign and malignant tumors. At focal intensities
(1000-10000 W/cm.sup.2) that are 4-5 orders of magnitude greater than
that of diagnostic ultrasound (approximately 0.1 W/cm.sup.2), HIFU can be
applied percutaneously to induce lesions (i.e., localized tissue
necrosis) at a small, well defined region (approximately 1 mm) deep
within tissue, while leaving intervening tissue between the HIFU
transducer and the focal point substantially unharmed. Tissue necrosis is
a result of tissue at the focal point of the HIFU beam being heated to
over 70.degree. C. in a very short period of time (generally less than
one second). Tissue necrosis also results from cavitation activity, which
causes tissue and cellular disorganization. HIFU is currently being used
clinically for the treatment of prostate cancer and benign prostatic
hyperplasia, as well as the treatment of malignant bone tumors and soft
tissue sarcomas. Clinical trials are currently being conducted for HIFU
treatment of breast fibroadenomas, and various stage-4 primary and
metastatic cancerous tumors of the kidney and liver.
[0005] Therapeutic uses of HIFU have generally been directed at destroying
undesired masses of tissue, to necrose tumors, coagulate bleeding, and
address urological and gynecological disorders. Most references teach
that one must use extreme care when using HIFU to treat tissue near a
nerve, to avoid undesirably damaging the nerve. There are however,
several medical conditions where it would be desirable to treat a nerve.
For example, a temporary blocking of a nerve would prevent transmission
of pain signals through that nerve, and could therefore be used for pain
management. Temporary or permanent blockage by the nerve could also be
used to treat spasticity.
[0006] Spasticity is a complication associated with disorders of the
central nervous system (CNS), such as multiple sclerosis, cerebral palsy,
stroke, and traumatic injury to the brain or spinal cord, and is
displayed by uncontrollable muscle contractions. Spasticity due to trauma
results from the generation of hyperactive nerve reflexes in pathways
below the site of spinal cord or brain damage. It is estimated that over
500,000 individuals in the U.S. and over 12 million worldwide are
affected by spasticity, many of whom suffer from severe spasticity, which
includes violent and immobilizing spasms, despite paralysis in the lower
limbs due to spinal cord injury or disease. Severe spasticity can also
affect those with multiple sclerosis, traumatic brain injury, stroke, and
cerebral palsy, among other CNS disorders. Many of these individuals
retain voluntary function of the hyperactive nerve reflexes, but the
interfering spasticity limits this function and compromises quality of
life by causing pain and disrupting sleep.
[0007] The cause of spasticity is thought to involve hyperactivity of
stretch reflexes. One proposed neuronal mechanism is that inhibitory
portions of the reflex arc are impaired and thus, reflex muscle
contractions may be unintentionally excited and proceed in a less
controlled manner. Another proposed neuronal mechanism is that Ia
afferents of the stretch reflex sprout new synapses on motoneurons in
response to loss of normal supraspinal input due to a CNS disorder; as a
result, the sprouted Ia afferents exert exaggerated synaptic excitation
of motoneurons causing spasticity.
[0008] Mild or moderate spasticity can often be managed with physical
methods (e.g., stretching, bracing) or oral spasmolytic medications
(e.g., baclofen, tizanidine). However, these treatments are not adequate
in the 25% to 50% of patients with sever spasticity. Treatments for
severe spasticity include intramuscular blocks with botulinum toxin
(BTX), which is often injected into 1 or 2 muscles with localized severe
spasticity. For example, spasticity in ankle plantarflexor muscles
causing clonus can be reduced with BTX injection into the gastrocnemius
and soleus muscles. However, BTX has only modest effects in reducing
spasticity. Only 1 or 2 large muscles can be injected because of concerns
about systemic effects that could paralyze respiratory muscles, the
duration of benefit is only 3-6 months, and repeated injections may be
less effective because antibodies to BTX can develop.
[0009] Chemical nerve blocks with phenol or alcohol are also common
treatments of severe spasticity. These chemical blocks can be applied to
both peripheral nerves and spinal nerves to provide treatment of
spasticity that is either localized to a specific muscle group or more
widespread. The disadvantages to chemical nerve blocks include the risk
of infection due to needle insertion, the difficulty in titration of the
effect of treatment, and a risk (10 to 30%) of transient dysesthesias.
[0010] For very extreme cases of spasticity, patients often undergo
peripheral surgery for cutting nerves or tendons, spinal cord surgery for
cutting dorsal roots (dorsal rhizotomy) or cutting the spinal cord itself
(i.e., longitudinal myelotomy). Other treatments of spinal nerve roots
include intrathecal phenol and paravertebral alcohol neurolytic blocks.
Paravertebral injections with alcohol carry the risk of infection and the
risk of ascending myelopathy if the injected alcohol enters a dural root
sleeve. Intrathecal phenol injections carry significant risks, such as
the risk of disrupting bowel, bladder, and sexual function, the risk of
infection, and the risk of ascending myelopathy because of migration of
the phenol. Dorsal rhizotomy and lumbar myelotomy carry all of the risks
associated with major surgery (i.e., risks associated with general
anesthesia and the risk of infection). A less invasive, radio frequency
rhizotomy uses thermo-coagulation of spinal nerves to control spasticity,
although the risk of infection is still associated with this technique
because the technique requires needle insertion.
[0011] Most current treatment options for severe spasticity are primarily
used for patients with no preserved voluntary function, because these
treatments (BTX chemical nerve blocks, and the extreme case of nerve
transection surgeries) have a non-selective effect on the local nerves
and/or muscles. The result will be suppression of voluntary function in
the treated region, either temporarily or permanently. Another treatment
option, intrathecal baclofen infusion via a subcutaneous pump, has been
used to treat patients who retain limited voluntary function. Such
treatment (a continuous intrathecal infusion of the spasmolytic
medication baclofen around the lumbar spinal cord) has been successful in
reducing spastic contractions while preserving voluntary function,
although the mechanism of its selectivity is not well understood. Despite
its effectiveness, the invasiveness of the procedure and cost of the
implantation procedure and the pump itself make other alternative
procedures (such as nerve blocks and intramuscular blocks) more
attractive for patients with no voluntary function.
[0012] Current treatments of spasticity can be classified as those that
suppress voluntary function (intramuscular injections, nerve blocks,
surgical treatments) and those that can retain voluntary function
(stretching, oral medications, and intrathecal baclofen). Only stretching
and oral medications are non-invasive treatments, and those treatments
are ineffective for severe spasticity. Therefore, it would be desirable
to provide a new, non-invasive treatment for severe spasticity. It would
further be desirable to employ a non-invasive treatment that can achieve
a relatively temporary partial conduction block, a relatively permanent
partial conduction block, a relatively temporary complete conduction
block, and a relatively permanent complete conduction block.
[0013] Severe chronic pain is a common clinical neurological condition.
Such pain can be associated with some forms of cancer (particularly bone
cancer), pain caused by peripheral nerve injury such as herpetic
neuralgia, and some arthritis pain such as spinal facet arthropathies.
Current treatments of pain include oral medications (e.g., morphine),
local neurolytic alcohol injections, and thermo-coagulation of nerves.
Similar to the treatments of spasticity, these methods are invasive, are
often less effective than desired, and often have undesirable side
effects. It would therefore be further desirable to provide a
non-invasive method of treatment for sensory nerves in pain management.
[0014] Ultrasound has previously been used to treat less severe pain in
physical therapy settings, in which the ultrasound beam is typically
unfocused and of relatively low intensity compared to HIFU. The diffuse
energy may act to soothe pain by providing heat to the area, acting no
differently than a warn bath or massage. It would be desirable to provide
a method for alleviating pain using HIFU by treating nerves with HIFU to
achieve both thermal and mechanical interaction with nerves.
SUMMARY OF THE INVENTION
[0015] The present invention is a method for using HIFU to treat the
nervous system. In a particularly preferred embodiment of the invention,
ultrasound imaging is synchronized to the HIFU therapy to achieve
real-time ultrasound image guided HIFU therapy of the nervous system.
Alternatively, MRI can be used to image the nervous system as it is being
treated with HIFU. The treatment site in the nervous system is selected
based on the type of therapeutic effect desired. HIFU therapy of the
nervous system can be utilized to achieve a treatment for spasticity, to
alleviate pain, to provide an anesthetic effect, and to provide a
cosmetic effect.
[0016] Regardless of the desired therapeutic effect, HIFU therapy of
neural structures preferably includes the following steps. First, a
specific treatment site in the nervous system is selected. The specific
treatment site will be selected based on a thorough knowledge of anatomy
and a thorough understanding of the portions of the neural structure that
need to be targeted to achieve the desired therapeutic effect. An
understanding of how HIFU interacts with the specific portion of the
neural structure being targeted is required, including the relevant
dosage of HIFU required to achieve the desired therapeutic effect.
Empirical studies have indicated that relatively lower levels of HIFU can
induce reversible therapeutic effects in neural structures, whereas
relatively higher levels of HIFU can induce permanent therapeutic effects
in neural structures. Once the specific treatment site has been
identified, the appropriate dosage is selected. Just as a physician needs
to understand a pharmacological dose required to achieve a desired
therapeutic effect, a HIFU clinician will need to understand (preferably
based on empirical studies) the HIFU dosage required to achieve the
desired therapeutic effect.
[0017] Once the treatment site and the dosage have been selected, a HIFU
therapy probe is positioned adjacent to the treatment site such that the
focal point of the HIFU transducer is directed toward the selected
treatment site. The HIFU therapy probe can be positioned externally of
the patient, or inside the body cavity of the patient. Either position
will facilitate a non-invasive procedure. Of course, the HIFU therapy
probe can be invasively disposed adjacent to the treatment site within
the body, however, a specific advantage of HIFU therapy of nerves is the
ability to induce a therapeutic effect without an invasive procedure. In
one aspect of the invention, HIFU transducers having a fixed focal length
will be utilized. When using such HIFU transducers, an understanding of
the anatomical position of the selected treatment site and knowledge of
the focal length of the HIFU transducer will enable a clinician to select
an appropriate position for the HIFU therapy probe. In another embodiment
of the invention, the HIFU therapy probe will include an array of HIFU
transducers, enabling variable focal lengths to be achieved. When using
such a HIFU therapy probe, understanding of the anatomical location of
the selected treatment site and a thorough understanding of the
characteristics of the variable focal lengths can be used to similarly
enable a clinician to select an initial positioning of the HIFU therapy
probe.
[0018] Because it is possible that an improperly positioned HIFU therapy
probe could inadvertently damage non-target tissue, preferably, the
position of the focal point of the HIFU therapy transducer relative to
the treatment site is verified before HIFU therapy of the nervous system
is initiated. Several different techniques or combinations thereof can be
used to provide such verification. A first technique involves using an
imaging technology such as ultrasound or MRI to obtain an image of the
treatment site. Based on an understanding of the geometry of the HIFU
transducer, an icon can be introduced into this image to indicate the
relative position of the focal region of the HIFU transducer, by
understanding the position of the HIFU transducer relative to the imaging
instrumentation. One aspect of this technique is to couple an ultrasound
imaging probe and the HIFU therapy probe to a frame, such that the
relative positions of the imaging probe and the HIFU therapy probe do not
change (this can also be achieved by combining imaging and therapy
transducers on a single probe, where the positions of the transducers are
fixed relative to the probe). The position of the focal point of the HIFU
transducer in an image provided by the ultrasound imaging probe can be
determined geometrically, or empirically, by using a gel phantom. An icon
can be introduced into the ultrasound image (for example, by placing a
transparent sheet over the ultrasound image and introducing the icon onto
the transparent sheet). The ultrasound imaging probe (being still coupled
to the frame and the HIFU therapy probe, so that the relative positions
of the probes do not change, since changing their relative positions at
this point would render the icon inaccurate) is then used to image the
treatment site. The ultrasound imaging probe is manipulated until the
icon coincides with the selected treatment site. Because the ultrasound
imaging probe and the HIFU therapy probe are coupled to the frame,
movement of the ultrasound imaging probe will result in a corresponding
movement of the HIFU therapy probe. Ensuring that the icon coincides with
the treatment site can be used to verify that the HIFU therapy probe is
properly positioned relative to the treatment site before initiating HIFU
therapy of the nervous system. In still other embodiments of the
invention, sophisticated tracking systems are employed to provide the
clinician an indication of where the focal point of the HIFU transducer
is, relative to the patient, by providing an image of the patient with an
icon in the image indicating the position of the focal point.
[0019] Another technique that can be used to verify that the HIFU therapy
probe is properly positioned relative to the treatment site involves
initially positioning the HIFU therapy probe and then using imaging
ultrasound to obtain an image of the treatment site. The HIFU therapy
probe is then energized at a relatively low setting, using an
insufficient amount of energy to induce damage at the focal point of the
HIFU therapy transducer, while still using sufficient energy to change
the echogenicity of tissue at the focal point. Empirical studies have
indicated that relatively low levels will induce a change in echogenicity
in tissue without inducing any apparent damage. This change in
echogenicity can be detected in the ultrasound image. Because HIFU
introduces significant noise into ultrasound image, it is important that
the ultrasound imaging system and the HIFU therapy probe be synchronized,
so that the treatment site can be visualized in the ultrasound image.
This technique can be used independently of the icon technique discussed
above, or as further verification that the icon actually does represent
the actual focal point of the HIFU transducer.
[0020] Still another technique that can be used to verify that the focal
point of the HIFU therapy transducer coincides with the desired treatment
site is to provide a short HIFU burst, and then to observe any
physiological response to the short HIFU burst before the HIFU therapy is
initiated. Empirical studies have shown that there are portions of the
nervous system that react to HIFU with a characteristic physiological
response, much like a physician can induce a knee-jerk response by
lightly striking a knee in a specific anatomical location. The HIFU
clinician will apply a relatively short burst of HIFU and monitor for any
such characteristic physiological reaction. If the expected physiological
reaction occurs, it provides an indication that the HIFU therapy probe is
properly positioned relative to the treatment site. It should be noted
that this technique provides a less qualified verification than the
techniques described above and thus appears to be better suited to
applications of relatively low dosage of HIFU that do not induce
permanent therapeutic effects.
[0021] Once the clinician has verified that the HIFU therapy probe is
properly positioned, the therapy is provided according to the dosage
levels previously determined. The clinician can then determine whether
the desired therapeutic effect has been achieved, and if not, additional
therapy can be provided. If the desired therapeutic effect has been
achieved, the HIFU therapy probe is removed. Again, several different
techniques can be used to determine whether the desired therapeutic
effect has been achieved. Preferably, the treatment site will be imaged
in real-time using synchronized ultrasound so that the formation of the
lesions at the treatment site can be monitored. The experienced clinician
will be able to then determine, based on the successful formation of
lesions, whether the desired therapeutic effect has likely been achieved.
Other techniques of determining whether the desired therapeutic effect
has been achieved can alternatively be implemented. If the desired
therapeutic effect is the treatment of spasticity, the patient can be
monitored to determine if spasticity is reduced. If the desired
therapeutic effect is the reduction of pain, the patient can be
questioned to determine if the pain has been alleviated. If the desired
therapeutic effect is to provide an anesthetic effect, again, the patient
can be questioned to determine if any anesthetic effect has been induced,
and if so, to what degree. If the desired therapeutic effect is to
provide a cosmetic effect (for example, neural structures controlling the
facial muscles that are currently treated with Botox to provide a more
youthful appearance could instead be treated with HIFU to achieve a
similar effect), the patient's appearance can be evaluated to determine
if the desired cosmetic effect has been achieved
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0022] The foregoing aspects and many of the attendant advantages of this
invention will be 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:
[0023] FIG. 1A (prior art) schematically illustrates an ultrasonic image
generated during the simultaneous use of ultrasound for imaging and for
providing HIFU therapy in a conventional manner, wherein noise due to the
HIFU beam obscures the entire image;
[0024] FIG. 1B schematically illustrates an ultrasonic image generated
during the simultaneous use of ultrasound for imaging and therapy,
wherein pulsing of the HIFU limits the resulting noise to a portion of
the image;
[0025] FIG. 1C schematically illustrates an ultrasonic image generated
during the simultaneous use of ultrasound for imaging and therapy,
wherein synchronized pulsing of the HIFU is used to shift the noise
caused by the HIFU beam away from a treatment site displayed in the
image;
[0026] FIG. 2 is a block diagram illustrating the components of a system
capable of the simultaneous use of ultrasound for imaging and therapy, in
accord with the present invention;
[0027] FIGS. 3A(1)-3D(4) illustrate timing and synchronization patterns
that enable the simultaneous use of ultrasound for imaging and therapy;
[0028] FIG. 4 illustrates yet another timing and synchronization pattern
for synchronizing the HIFU and imaging scans;
[0029] FIG. 5A is a schematic block diagram of a 3D imaging and HIFU
therapy system that enables the HIFU therapy to be applied at selected
treatment sites in a 3D image of a target area;
[0030] FIG. 5B is a block diagram schematically illustrating the elements
of a system for use with the present invention to facilitate free hand
visualization of the focal point of a HIFU beam during therapy; and
[0031] FIG. 5C schematically illustrates an exemplary image provided by
the system of FIG. 5B, enabling a clinician to determine how to
manipulate a spatial relationship between an imaging probe and a therapy
probe to ensure visualization of the focal point of a HIFU beam during
therapy;
[0032] FIG. 6A schematically illustrates a HIFU therapy probe including a
hydrogel standoff/coupling being employed to deliver HIFU
transcutaneously to a sub dermal neural target;
[0033] FIG. 6B schematically illustrates an ultrasound imaging probe and a
HIFU therapy probe being used together to achieve transcutaneous image
guided HIFU therapy of a neural target in accord with the present
invention;
[0034] FIG. 6C schematically illustrates an ultrasound imaging probe, a
HIFU therapy probe and a needle being used together to achieve
transcutaneous image guided HIFU therapy of a neural target in accord
with the present invention, the needle being readily visible in the
ultrasound image and facilitating guidance of the HIFU therapy;
[0035] FIG. 7 is a flowchart illustrating the logical steps implemented in
a method for using HIFU therapy to treat the nervous system in accord
with the present invention;
[0036] FIG. 8A is a photograph of a HIFU therapy probe and ultrasound
imaging probe coupled to a frame to ensure that the focal region of the
HIFU therapy probe can be visualized in the imaging plane of the
ultrasound imaging probe, this HIFU therapy device being used in
empirical studies;
[0037] FIG. 8B schematically illustrates a transparent sheet configured to
overlay an ultrasound image generated by the ultrasound imaging probe of
FIG. 8A, with an icon indicating the position of the focal region in the
ultrasound image, so that the focal region can be visualized even when
the LIEU therapy probe is not energized;
[0038] FIG. 8C schematically illustrates the HIFU therapy device of FIG.
8A being used with a gel phantom to enable the focal region of the HIFU
transducer to be visualized in an ultrasound image via an icon;
[0039] FIG. 8D is an ultrasound image generated using the HIFU therapy
device of FIG. 8A, with interference from the HIFU transducer being
shifted away from the visualization of the focal region of the HIFU
transducer, clearly showing the icon coinciding with a lesion formed by
the HIFU;
[0040] FIG. 9A schematically illustrates a rabbit's leg coupled to a
strain gauge to facilitate empirical studies of HIFU therapy applied to
the sciatic nerve of a rabbit;
[0041] FIG. 9B schematically illustrates measurement electrodes employed
to measure nerve conduction in conjunction with empirical studies of HIFU
therapy applied to the sciatic nerve of a rabbit;
[0042] FIG. 9C schematically illustrates a HIFU therapy probe and
ultrasound imaging probe being used to achieve ultrasound image guided
HIFU therapy of the sciatic nerve of a rabbit;
[0043] FIG. 9D schematically illustrates how the focal region of the HIFU
therapy probe of FIG. 9C is scanned across the sciatic nerve of the
rabbit, enabling a HIFU transducer having a relatively small focal region
to treat a relatively larger neural structure;
[0044] FIG. 9E is a photograph of the HIFU therapy device of FIG. 8A being
used to apply therapeutic ultrasound the sciatic nerve of a rabbit via an
incision;
[0045] FIGS. 10A and 10B are pressure field maps of the HIFU transducer of
FIG. 8A which were used to determine the axial and lateral full-width,
half-maximum dimensions of the focal region of the HIFU transducer,
[0046] FIGS. 11A-11H are ultrasound images obtained during empirical
studies of HIFU therapy of the sciatic nerve of a rabbit using the HIFU
device of FIG. 8A;
[0047] FIGS. 12A-12F are photographs of HIFU induced lesions on the
sciatic nerve of a rabbit produced during the about noted empirical
studies;
[0048] FIG. 13 is a cross-sectional image of rabbit tissue showing a HIFU
induced lesion extending through the sciatic nerve into adjacent muscular
tissue;
[0049] FIGS. 14A &14B, 14C & 14D, 15A & 15B, and 16A & 16B, are
microscopic images of rabbit neural tissue before and after
(respectively) HIFU therapy;
[0050] FIGS. 16C & 16D are microscopic images of rabbit neural tissue
after HIFU therapy;
[0051] FIG. 17 schematically illustrates a different HIFU therapy probe
being used to achieve HIFU therapy of the sciatic nerve of a rabbit in
another empirical study;
[0052] FIG. 18 graphically illustrates compound nerve action potentials
before after HIFU therapy of the sciatic nerve of a rabbit;
[0053] FIG. 19 graphically illustrates compound nerve action potentials as
a function of increasing doses of HIFU therapy of the sciatic nerve of a
rabbit;
[0054] FIG. 20 graphically illustrates the threshold voltage stimulus red
to produce a force response as a function of increasing duration of HIFU
therapy of the sciatic nerve of a rabbit;
[0055] FIG. 21 graphically illustrates a mean force response to electrical
stimulation distal to proximal of application of HIFU therapy of the
sciatic nerve of a rabbit;
[0056] FIG. 22 schematically illustrates HIFU therapy of the femoral nerve
of a pig in a plurality of different sites;
[0057] FIG. 23 is a photograph of HIFU induced neural lesions in the
femoral nerve of a pig;
[0058] FIG. 24 graphically illustrates compound nerve action potentials
for a plurality of different HIFU doses applied to the sciatic nerve of a
rabbit;
[0059] FIG. 25 schematically illustrates yet another HIFU therapy device
being used to achieve ultrasound image guided HIFU therapy of the sciatic
nerve of a rat, in which the focal region of the HIFU transducer is
larger than the neural treatment site;
[0060] FIG. 26 schematically illustrates another HIFU therapy device being
used to achieve direct guided HIFU therapy of the sciatic nerve of a rat
in which the focal region of the HIFU transducer is larger than the
neural treatment site; and
[0061] FIG. 27 schematically illustrates still another HIFU therapy device
being used to achieve direct guided HIFU therapy of a neural structure,
in which the focal region of the HIFU transducer is larger than the
neural structure.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0062] Overview of the Present Invention
[0063] The present invention is directed to a method for using HIFU to
treat nerves. Nerves can be targeted to alleviate pain, to provide an
anesthetic effect, or to reduce spasticity. HIFU treatment of nerves
offers potential to replace Botox (i.e., BTX) injections to achieve a
cosmetic effect, as discussed in greater detail below. Depending on the
dose of HIFU delivered to the nerve, a relatively temporary blockage or a
relatively permanent blockage can be achieved. Furthermore, depending on
how much of a nerve is treated, a partial conductive block or a complete
conductive block can be achieved. Because of the relatively small size of
nerves, and the potential for HIFU beams to damage non-target tissue, it
is particularly important to accurately position the focal point of the
HIFU transducer on a carefully selected portion of the nervous system
before beginning treatment. It is also important to be able to visualize
the focal point of the HIFU beam in real-time, to ensure that the focal
point is properly positioned relative to a target nerve, and to monitor
treatment to ensure that damage to non-target tissue does not occur (or
such damage is minimal). A particularly preferred embodiment of the
present invention synchronizes ultrasound imaging with HIFU to achieve
ultrasound image guided HIFU therapy of nerves. Alternatively, Magnetic
Resonance Imaging (MRI) can be used instead of ultrasound. MRI imaging
does have a small latency (and thus, is not "real-time" imaging), but the
latency is sufficiently small so that MRI is usable to achieve image
guided HIFU therapy of nerves.
[0064] Various combinations of HIFU transducers and imaging transducers
can be beneficially employed. The HIFU transducer and imaging transducer
can be integrated into a single instrument. A separate HIFU therapy probe
and ultrasound imaging probe can be employed. Depending on the location
of the nerve being targeted, one or more of the HIFU transducer and
imaging transducer can be disposed external of the patient, or in a body
cavity of the patient. For embodiments in which the HIFU transducer and
imaging ultrasound transducer are implemented on separate probes, the use
of a frame to maintain the proper spatial orientation between the probes
is useful. In the following description, a synchronization technique
useful to enable real-time ultrasound image guided HIFU therapy to be
achieved is described. The techniques of using HIFU to treat nerves in
accord with the present invention is then discussed in detail, including
a discussion of relevant empirical data.
[0065] The terms "therapeutic transducer," "HIFU transducer," and "high
intensity transducer," as used herein and in the claims that follow, all
refer to a transducer that is capable of being energized to produce
ultrasonic waves that are much more energetic than the ultrasonic pulses
produced by an imaging transducer, and which can be focused or directed
onto a discrete location, such as a treatment site in a target area.
However, in at least one embodiment of the present invention, not all
ultrasonic waves produced by such a transducer are necessarily at a high
intensity, as is explained below.
[0066] The present invention is directed to using HIFU therapy to treat
neural structures. The term neural structures is intended to encompass
all anatomical structures associated with nervous systems including
peripheral nerves, sensory nerves, spinal root nerves, nerve endings,
motor endplates, all other nerves, and regions of the brain. Many of the
examples included below specifically refer to treating a nerve (as
opposed to a different neural structure); however, such examples are not
intended to limit the invention. It should be understood that the present
invention can be applied to neural structures in general, and not simply
to nerves alone.
[0067] Synchronizing Imaging and HIFU to Achieve Real-Time Image Guided
Therapy
[0068] When administering HIFU therapy, it is very desirable to be able to
observe a treatment site, to ensure that lesions induced by the HIFU
therapy are being produced at the desired location. Failure to properly
aim the HIFU beam will result in undesired tissue necrosis of non-target
tissue. From a practical standpoint, this goal has not proven easy to
accomplish when ultrasound is used to visualize the focal point, because
the HIFU beam used for therapy completely saturates the signal provided
by the imaging transducer. One analogy that might help to make this
problem clear relates to the relative intensities of light. Consider the
light coming from a star in the evening sky to be equivalent to the low
power imaging ultrasound waves that are reflected from a target area
toward the imaging transducer, while the light from the sun is equivalent
to the HIFU generated by the therapy transducer. When the sun is out, the
light from the stars is completely overwhelmed by the light from the sun,
and a person looking into the sky is unable to see any stars, because the
bright light from the sun makes the dim light coming from the stars
substantially imperceptible. Similarly, the HIFU emitted by the therapy
transducer completely overwhelms the ultrasonic waves produced by the
imaging transducer, and any ultrasonic image generated is completely
saturated with noise caused by the HIFU emitted from the therapeutic
transducer.
[0069] FIG. 1A illustrates an ultrasound image 10 in which a scanned image
field 12 is completely obscured by noise 14, as is typical during the
simultaneous reception of energy from a reflected imaging pulse and a
HIFU wave (neither shown). In regard to ultrasound image 10, a clinician
may desire to focus the HIFU wave on a treatment site 18. However,
because noise 14 completely saturates scanned image field 12, it is
virtually impossible to accurately focus the HIFU wave onto treatment
site 18. If the therapy transducer is completely de-energized, noise 14
is eliminated from the scanned image field. However, under these
conditions, the focal point of the HIFU wave will not be seen, and thus,
the HIFU wave cannot be accurately focused on treatment site 18. While
some change in echogenicity at the HIFU focal point will persist for a
time after the HIFU wave is no longer present, any change in a position
of the therapy transducer (or treatment site 18) will not register until
the therapeutic transducer is re-energized, and thus, the HIFU wave
cannot be focused in real-time.
[0070] Some prior art systems have included a targeting icon in an
ultrasound image to indicate the position of the known focal point of a
specific HIFU transducer in a scanned image. While this icon may be
helpful in determining whether the HIFU was previously focused, it still
does not enable a clinician to observe real-time results. Once the HIFU
therapeutic transducer is energized, the scanned ultrasound image is
completely saturated with noise, and the clinician cannot monitor the
progress of the treatment without again de-energizing the HIFU
therapeutic transducer.
[0071] FIG. 1B illustrates one technique in which the effect of noise
disrupting the ultrasound image is reduced. In FIG. 1B, the HIFU wave
generated by the therapeutic transducer has been pulsed. This technique
produces an ultrasound image 20, in which the location of noise 24 in a
scanned field 22 is a function of the interference between the pulsed
HIFU wave generated by the therapy transducer and the ultrasonic imaging
ultrasound pulses generated by the scanning transducer. In FIG. 1B, noise
24 substantially masks a treatment site 28. This result will not occur in
all cases, because to an observer, noise 24 will move across scanned
field 22 as the interference between the HIFU waves and the imaging
pulses varies in time. Pulsing of the HIFU wave alone can thus enable the
clinician to view a noise-free image of the treatment site only when
noise 24 is randomly shifted to a different part of scanned field 22,
away from the treatment site. However, this pulsing of the HIFU beam
generates an image that is extremely distracting to a clinician, as noise
24 flickers across scanned field 22, making it difficult to concentrate
and difficult to consistently determine where the focal point of the HIFU
wave is relative to the treatment site, in real-time.
[0072] FIG. 1C illustrates an ultrasound image 30 in which a HIFU wave
from a therapy transducer has been both pulsed and synchronized with
respect to the ultrasonic imaging pulses from an imaging transducer, to
ensure that noise 34 does not obscure a treatment site 38. In ultrasound
image 30, noise 34 has been shifted to a location within a scanned field
32 of the image that is spaced apart from treatment site 38, by
selectively adjusting both the pulsing and the synchronization of the
HIFU wave relative to the image pulses. Preferably, noise 34 is shifted
completely away from treatment site 38, enabling the clinician to view a
noise-flee, stable image of treatment site 38 that clearly shows the
location of the focal point of the HIFU wave relative to the treatment
site. Thus, the HIFU wave can be focused in real-time onto treatment site
38, and a clinician can, in real-time, view the therapeutic effects of
the HIFU wave on treatment site 38. It will therefore be apparent that a
clinician can de-energize the therapeutic transducer, terminating the
generation of the HIFU wave as soon as a desired therapeutic effect has
been achieved at the treatment site. In this manner, undesired effects on
non-target tissue can be minimize
[0073] FIG. 2 illustrates a block diagram of an embodiment of the present
invention that synchronizes the image and HIFU waves required for the
simultaneous imaging and therapy in real-time. An ultrasound imaging
machine 40 is an ultrasound imaging system of the type that is well known
to those of ordinary skill in the art and can be purchased from vendors
such as ATL Inc., of Bothell, Wash. An imaging probe 44 that is also of a
type well known to those of ordinary skill in the art is connected to
ultrasound imaging machine 40 via a cable 42. Imaging probe 44 generates
ultrasonic imaging pulses that propagate to the target area, are
reflected from structure and tissue within the body, and are received by
the imaging probe. The signal produced by the imaging probe in response
to the reflected ultrasound waves is communicated to the ultrasound
imaging machine through cable 42 and processed to provide a visual
representation of the structure and tissue that reflected the ultrasonic
imaging pulses. An imaging beam sector 46 from imaging probe 44 is
identified in the Figure by dash lines. Also included in the present
invention is a therapeutic transducer 60. When excited, this therapeutic
transducer generates HIFU waves that are focused at a particular point of
interest, i.e., a treatment site within a patient's body. In FIG. 2, the
path of a HIFU beam 62 is indicated by dotted lines. HIFU beam 62 narrows
to a focal point 64. Those of ordinary skill in the art will recognize
that position of focal point 64 relative to therapeutic transducer 60 is
a function of the geometry of the therapeutic transducer and will
normally depend upon the application. For example, a therapeutic
transducer that will be used to apply HIFU therapy to the nervous system
of a patient from within a body will have a different optimum focal point
than a therapeutic transducer used to apply treatment to the nervous
system from outside a patient's body. It should also be understood that
therapeutic transducers having a fixed focal length can be employed, or
an array of therapeutic transducers having a variable focal length can be
employed. While arrays of therapeutic transducers require more
sophisticated control systems, such arrays offer the benefit of enabling
therapy probes having multiple focal lengths to be achieved. When a
therapy probe having a fixed focal length is employed, and an initial
positioning of that therapy probe does not result in the focal point of
the therapy transducer being incident on the designed portion of the
nervous system, in general the therapy probe itself will need to be
repositioned until the focal point of the therapy transducer is properly
positioned relative to the nervous system. When a therapy probe including
an array of therapy transducers having variable focal lengths is
employed, and the initial positioning of the therapy probe does not
result in the focal point of the therapy transducers being properly
positioned relative to the nervous system, the array can be manipulated
to vary the focal length of the therapy transducers until the focal point
is properly positioned. Of course, there may be times when the initial
positioning is so far off that the therapy probe itself still must be
moved.
[0074] It should be noted that ultrasound imaging machine 40 differs from
prior art systems in several ways, including its inclusion of a
synchronization output signal 48. Preferably, ultrasound imaging machine
40 is modified to enable synchronization output signal 48 to be obtained.
Because such a synchronization output signal has not been required for
prior art ultrasonic imaging applications, provision of a synchronization
output signal has generally not been made in prior art ultrasound imaging
machines. If a prior art imaging machine that has not been modified to
provide synchronization output signal 48 is used, the synchronization
output signal can instead be derived from the ultrasonic imaging signal
conveyed by cable 42.
[0075] Synchronization output signal 48 is supplied to a synchronization
delay circuit 50. Synchronization delay circuit 50 enables the user to
selectively vary the initiation of each HIFU wave with respect to each
sequence of ultrasonic imaging pulses that are generated to form an
ultrasonic image. Referring to FIG. 1C, delay 50 enables a user to vary
the position of noise 34 in scanned field 32, so that the noise is moved
away from treatment site 38, to a different portion of scanned field 32.
The user is thus provided a noise-flee image of treatment site 38.
[0076] A HIFU duration circuit 52 is used to control the duration of the
HIFU wave. A longer duration HIFU wave will apply more energy to the
treatment site. Generally, the more energy that is applied to a treatment
site, the faster a desired therapeutic effect will be achieved. However,
it should be noted that if the HIFU wave is too long, the duration of
noise 34 as shown in ultrasound image 30 will increase and can extend
into the next ultrasound imaging pulse to obscure treatment site 28, or
may completely obscure ultrasound image 30, generating a display very
similar to ultrasound image 10 in FIG. 1A. Thus, the user will have to
selectively adjust HIFU duration circuit 52 to obtain a noise-free image
of treatment site 38, while providing a sufficient level of energy to the
treatment site to effect the desired therapeutic effect in an acceptable
time.
[0077] A HIFU excitation frequency generator 56 is used to generate the
desire frequency for the HIFU wave, and a power amplifier 58 is used to
amplify the signal produced by the HIFU excitation frequency generator to
achieve the desired energy level of the HIFU wave; power amplifier 58 is
thus adjustable to obtain a desired energy level for the HIFU wave.
Optionally, a stable synchronization signal generator 66 can be used to
synchronize the HIFU wave to the imaging ultrasonic wave, instead of
using synchronization output signal 48 from ultrasound imaging machine
40. Stable synchronization signal generator 66 can be used to provide a
stable synchronizing pulse to initiate the HIFU wave, and the timing of
this stable synchronizing pulse can be selectively varied until a
noise-free image of the treatment site has been obtained. A drawback of
using stable synchronization signal generator 66 instead of
synchronization output signal 48 is that any change in the timing of the
ultrasound imaging pulses, such as is required to scan deeper within
tissue, will require an adjustment to stable synchronization signal
generator 66 that would not be required if synchronization output signal
48 were used. The processor will be able to automatically find a stable
synchronization signal using information from the movement of the noise.
[0078] FIGS. 3A(1)-3D(4) and FIG. 4 provide further detail for the
synchronization and pulsing features of the present invention. FIG. 3A(1)
shows ultrasound imaging pulses 46a produced by imaging machine 40 and
imaging probe 44 that are used to acquire an ultrasound image of a target
area (such as ultrasound image 30 of FIG. 1C). A synchronization pulse
48a is shown in FIG. 3A(2). It should be noted that synchronization pulse
48a is illustrated as occurring before the generation of ultrasound
imaging pulses 46a; however, the timing of synchronization pulse 48a
relative to the imaging pulses is not critical, so long as it is stable.
Synchronization pulse 48a merely establishes a timing reference point,
from which a delay 50a (shown in FIG. 3A(3)), used for the initiation of
the HIFU wave, is set such that noise from the HIFU wave in an ultrasonic
image generated by imaging pulses 46a is shifted away from the image of
the treatment site. Delay 50a is not fixed; instead, it is adjusted by
the user until a noise-free image of the treatment site is obtained.
[0079] A HIFU duration 52a, shown in FIG. 3A(4), determines the duration
of the HIFU wave. HIFU duration 52a may be very brief as shown in FIG.
3A(4), or extended, as shown in FIGS. 3B(4) and 3C(4). An increase in the
duration of the HIFU wave will cause a greater portion of an ultrasound
image to be obscured by noise, and may cause the HIFU wave to interfere
with the image of the treatment site. In FIG. 3A(4), delay 52a is very
short, and the resulting noisy region in the ultrasound image is very
small. However, a short duration HIFU wave means a correspondingly small
amount of HIFU energy will be delivered to the treatment site, thus
increasing the length of the treatment. A clinician must balance the
length of HIFU duration needed to maintain a noise-free image of the
treatment site against the time required to complete the therapy. It
should be noted that as an alternative to using HIFU duration 52a to
control the HIFU excitation frequency generator to variably set the
duration of the HIFU wave, the HIFU excitation frequency generator itself
can be adjusted to control the duration.
[0080] FIGS. 3B(1)-3C(4) similarly illustrate timing patterns that
incorporate different settings for the delay relating to the initiation
of the HIFU wave (delay 50b in FIG. 3B(3), and delay 50c in FIG. 3C(3))
and the delay relating to the duration of the HIFU wave (duration 52b in
FIG. 3B(4), and duration 52c in FIG. 3C(4)). FIGS. 3D(1)-3D(4) illustrate
a timing pattern that enables a longer duration HIFU wave (thus more
energy applied to the treatment site) to be used, while still enabling a
noise-free image of the treatment site to be generated. In FIG. 3D(1),
ultrasound imaging pulses 46a and 46b appear to be much shorter than in
FIGS. 3A(1), 3B(1) and 3C(1), but actually are of the same duration, as
the scales of FIGS. 3D(1)-3D(4) have been significantly increased.
Synchronization pulse 48a of FIG. 3D(2) is obtained and used as described
above. A delay 50d in FIG. 3D(3) is set to obtain a noise-free image of
the treatment site, also as described above; however, as clarified below,
not all of these synchronization pulses govern the image that is
produced, because duration 52d dominates. The significant difference
between FIGS. 3D(1)-3D(4) and FIGS. 3A(1)-3C(4) is that duration 52d has
been significantly increased in FIG. 3D, such that a very long burst of
HIFU energy is emitted, almost to the point of continuous emission. Here,
the noise-free imaging occurs only every seventh image, during
interrogation wave 46b. By adjusting duration 52, more or fewer images
will experience interference, and therefore, various duty cycle lengths
for HIFU exposure can be accommodated. It should be noted that as the
number of images interfered with by the HIFU wave increases (here, 6 out
of 7 images), the resulting image of the target area will arguably
provide less real-time feedback. However, the actual time between visible
images of the treatment site may be so short as to appear to occur in
real-time. But, at very high settings for the HIFU duration (such as
would cause the HIFU wave to interfere with 99 out of 100 images of the
treatment site), the advantages associated with real-time imaging of the
treatment site are diminished. Thus, the HIFU duration will preferably
not be set so high as to negate the benefits of real-time imaging of the
treatment site and its ability to provide the clinician with immediate
feedback concerning the effect of the therapy on the treatment site.
[0081] FIG. 4 illustrates another timing sequence that shows the
relationships between ultrasound imaging pulses 46d, a synchronization
pulse 48b, a delay 50e, and a HIFU duration 52e. In this timing sequence,
synchronization pulse 48b occurs during the ultrasound imaging pulses
46d, rather than preceding the ultrasound imaging pulses, as shown in
FIGS. 3A-3D. As noted above, the position of each synchronization pulse
48b relative to the ultrasound imaging pulses is not critical, since
delay 50e is adjusted to shift the noise away from the image of the
treatment sight. Again, the duration of the HIFU wave (and thus, the
energy applied to the treatment sight) is varied either by adjusting
duration 52e, as shown in FIG. 4, or by adjusting the HIFU excitation
generator.
[0082] Imaging of HIFU Focal Point
[0083] It will often be important for a clinician to be able to confirm
that the focal point of a HIFU transducer is directed at a desired
treatment site before initiating HIFU therapy. It has been determined
that if the energy level of a HIFU transducer is reduced to a level less
than a level that would cause any damage to tissue, the focal point of
the HIFU transducer will still be evident within the target area
displayed in the image developed from the reflected ultrasound signal
produced and received by the ultrasound imaging transducer. The focal
point will appear as a bright spot in the displayed image and will
rapidly fade over time. Thus, it is possible for a clinician to move the
HIFU transducer as necessary to shift the focal point to a desired
treatment site in the target area being imaged by the ultrasound imaging
transducer and to see the focal point in the image as a bright spot that
moves as the position of the HIFU transducer is changed. Only after the
focal point is positioned on a desired treatment site will the clinician
increase the energy of the ultrasound pulses produced by the HIFU
transducer to a level sufficient to achieve the desired therapeutic
effect, e.g., to a level sufficient to necrose tissue, to cause
hemostasis, or to otherwise treat a neural structure by thermal and
mechanical effects. It should be noted that the ultrasound imaging
transducer is not receiving the ultrasound signal produced by the HIFU
transducer that is reflected by the tissue, but instead, is imaging the
effect of the change in echogenicity of the tissue caused by the
relatively low energy ultrasound burst produced by the HIFU transducer.
This technique can be used with any of the HIFU based therapy methods
discussed below.
[0084] A further advantage of the preceding technique for imaging the
focal point of a HIFU transducer can be achieved by storing the image of
each successive treatment site, which will appear as a bright area in the
image produced by the ultrasound imaging transducer system. For example,
a storage type display, which is readily available, can be used for this
purpose. By storing the image of each treatment site to which the HIFU
therapy has previously been administered during a current session, it is
possible for a clinician to target spaced-apart treatment sites in the
target area, thereby ensuring the HIFU therapy has been administered to
all of the desired portion of a tumor or other structure in the patient's
body. Since each previous treatment site will be visible in the image, it
will be apparent that a desired pattern of treatment sites can readily be
laid down over the tumor or other structure of interest. The change in
echogenicity caused by a relatively high energy therapeutic HIFU wave
will be brighter and persist longer in the display, enabling the
clinician to easily distinguish between a current prospective focus point
for the next treatment site produced using the low energy pulse) and the
previous treatment sites to which the higher energy HIFU therapy has
already been administered.
[0085] Exemplary Imaging and Tracking Systems
[0086] In FIG. 5A, a block diagram is illustrated for a system 200 that
enables imaging of a target area in 3D and storing of the locations of
treatment sites to which the HIFU therapy has been administered in the 3D
image as a HIFU therapy session proceeds. The system includes a 3D image
data processor and display 202, an image acquisition section 204, a
magnetic field sensor 206, a magnetic field generator 208, and
six-dimensional (6D) electronic processing circuitry 210. The latter
three components are employed to track the imaging target area and the
HIFU focal point as they are redirected in the 3D space and are part of a
6D measurement system (i.e., three spatial coordinates for the 3D
orthogonal axes and three angles of rotation around these three
orthogonal axes). A 6D measurement system is commercially available from
Ascension Technology, Burlington, Vt. This 6D measurement system uses 6D
electronic processing circuitry 210 and magnetic field generator 208 to
produce time sequential orthogonally oriented magnetic fields covering a
general area as indicated in the Figure by the dash line that encompasses
the region of magnetic field. Magnetic field sensor 206 is mounted on a
combined imaging and HIFU therapy probe 212 in a fixed manner relative to
imaging and HIFU transducers 214. The magnetic field sensor detects the
magnetic field strength in 3D sequentially produced by the magnetic field
generator. The 6D electronic processing circuitry uses the information
from the magnetic field sensor and the known magnetic fields that were
produced to compute the 3D position and the three angular orientations
around the three orthogonal axes of the magnetic field sensor (and thus,
of the combined imaging and HIFU therapy probe) with respect to the
magnetic field generator, yielding the 6D information. The 6D information
is supplied to 3D image data processor and display 202 at a rate
sufficient to enable movement of the magnetic field sensor to be tracked
in the displayed 3D image of the target area. With information derived
from calibrating system 200 with the imaging probe, the position of the
target area and the HIFU transducer focal point can be related to a 3D
spatial point, so long as magnetic field sensor 206 is within the range
of the magnetic field produced by magnetic field generator 208. 3D image
data processor and display 202 also receive ultrasound image information
from an ultrasound imaging machine 216 through image acquisition section
204. It uses this information to develop and display 3D information. An
ultrasound imaging machine 216 provides the synchronization signal to a
HIFU control and electrical energy generating system 218, as discussed
above. The remaining component in FIG. 5A is a physiological information
acquisition section 220, which enables synchronization of the imaging and
HIFU therapy with physiological activity, such as respiration or cardiac
activity (provided by an electrocardiogram system--not shown). Use of the
physiological information avoids problems associated with movement of the
patient's body due to physiological activity. For example, 3D imaging and
HIFU therapy can be controlled so that they are implemented only at the
end of expiration in the breathing cycle, since motion of the patient is
more repeatable then than at mid inspiration. A physiological sensor such
as a respiration detector (not shown), which is well known in the art can
provide the information for this section of the system.
[0087] While system 200 has been described in conjunction with a single
probe that includes both an imaging transducer and a therapy transducer,
those of ordinary skill in the art will readily recognize that system 200
can be modified to track the positions of separate imaging probes and
therapy probes.
[0088] Yet another aspect of the present invention is directed to a system
and method that enable free hand registration of the imaging and therapy
probes, which can be employed to target portions of the nervous system
for HIFU therapy. FIG. 5B schematically illustrates a system 450 that
facilitates such free hand registration. System 450 includes a HIFU
therapy probe 452, an ultrasound imaging probe 456, a tracking system
454, and a display 460. It should be understood that any type of HIFU
therapy probe (configured for internal or external use), and any type of
ultrasound imaging probe (configured for internal or external use), can
be used in connection with system 450. Instead of using a physical or
mechanical frame to maintain a spatial relationship between the HIFU
therapy probe and the ultrasound imaging probe, system 450 relies on
tracking system 454 to ensure that the spatial relationship between the
HIFU therapy probe and the ultrasound imaging probe enables the focal
point of the HIFU therapy probe to be visualized in the imaging plane
generated by the ultrasound imaging probe. Tracking system 454 includes a
processor that is able to keep track of the spatial relationship between
the ultrasound imaging probe and the HIFU therapy probe. Such tracking
systems are commercially available and can be obtained from companies
such as Ascension Technology, of Milton, Vt. Tracking systems for medical
instruments are available based on several different technologies,
including acoustic, light, and magnetic based tracking systems, any of
which could be used to implement tracking system 454. Magnetic based
tracking systems (e.g., the Ascension PC BIRD.TM.) that could be used for
medical instruments are available from Mind Flux of Roseville, Australia.
[0089] System 450 functions as follows. HIFU therapy probe 452 and
ultrasound imaging probe 456 are positioned relative to a patient 458.
The clinician can view an image 462 on display 460. Image 462 includes a
representation of patient 458, and the relative locations of ultrasound
imaging probe 456 and HIFU therapy probe 452. Preferably image 462 will
include a visual representation of the imaging plane provided by
ultrasound imaging probe 456, and the HIFU beam generated by HIFU therapy
probe 452. The clinician can determine from image 462 whether ultrasound
imaging probe 456 and HIFU therapy probe 452 are properly aligned, so
that the focal point of the HIFU beam can be visualized in an image
provided by the ultrasound imaging probe. If the probes are not properly
aligned, image 462 will provide the clinician a reference for determining
how to reposition one or both of ultrasound imaging probe 456 and HIFU
therapy probe 452, so that the focal point of the HIFU beam can be
visualized in the ultrasound image. Depending on the size of display 460,
the ultrasound image provided by ultrasound imaging probe 456 can be
displayed along with image 462, or a separate display can be provided to
display the ultrasound image generated by ultrasound imaging probe 456.
The astute observer will recognize that image 462 corresponds to FIG. 6B,
which is described in greater detail below.
[0090] FIG. 5C is an enlarged view of display 460, including an image 463.
The relative positions of ultrasound imaging probe 456, patient 458, and
HIFU therapy probe 452 are presented in image 463. An image plane 466
provided by ultrasound imaging probe 456, a HIFU beam 468 provided by
HIFU therapy probe 452, and a focal point 464 can be visualized in image
463. An optional message 470 informs the clinician that the probes are
not properly aligned, which is apparent, because imaging plane 466 and
beam 468 do not overlap, and further, because focal point 464 does not
lie within image plane 466. While monitoring display 460 and image 463,
the clinician can change the relative positions of ultrasound imaging
probe 456 and HIFU therapy probe 452, until focal point 464 lies within
imaging plane 466.
[0091] It should be noted that image 463 is a two-dimensional (2D) image,
and those of ordinary skill in the art will readily recognize that even
if the HIFU beam and the imaging plane overlap in two dimensions, they
may not overlap in three dimension. When image 463 indicates that the
imaging plane and the HIFU beam overlap, a clinician can view the
ultrasound image provided by the ultrasound imaging probe, to determine
whether the focal point of the HIFU beam can actually be visualized in
the ultrasound image. If not, an indication is provided that the spatial
relationship and orientation between the imaging plane and the HIFU beam
are not properly aligned, and the clinician can further manipulate the
relative positions of the imaging probe and/or the HIFU therapy probe,
until the focal point of the HIFU beam both overlaps the imaging plane in
image 463 and can be visualized in the ultrasound image provided by the
ultrasound imaging probe. It should be also understood that tracking
system 454 can provide additional images from different perspectives (or
image 463 could be rotated by tracking system 454) to provide feedback to
a clinician indicating which direction the ultrasound imaging probe
and/or the therapy probe should be manipulated, so that the HIFU beam can
be visualized in the image provided by the ultrasound imaging probe.
[0092] System 450 offers several advantages, including ease-of-use, the
ability to visualize complex treatment strategies, and the ability to
visualize complex nervous system geometries.
[0093] Use of Anesthetic Agent to Enhance Image of Low Power HIFU at a
Treatment Site
[0094] While operating a HIFU transducer at a substantially reduced power
to determine the location of its focal point within a target area will
produce a bright spot visible in the image, it may sometimes be desirable
to enhance the visibility of the focal point in the image--in either a 2D
or 3D image. The change in echogenicity of the tissue due to the
administration of a relatively low power HIFU wave to the tissue enables
the location to be seen in the image of the target area. However, it is
believed that a substantially brighter spot showing where the HIFU wave
(at low power) was focused can be achieved if an anesthetic agent or
other blood soluble agent having a relatively high vapor pressure has
previously been administered to the patient. Use of such agents, which
will readily vaporize when exposed to the slight elevated temperatures
caused by low power ultrasound acting on tissue, should produce small
bubbles at the focal point of the HIFU transducer. These bubbles will
produce a substantially brighter spot in the ultrasound image and at an
even lower energy level of the HIFU transducer than the spots produced by
the low energy HIFU waves when no such agent has been administered to the
patient. Reduction of the HIFU energy to an even lower level when
determining the focal point will further ensure that the focal point of
the HIFU transducer can be seen in the ultrasound image produced by the
imaging transducer without risk of damage to tissue that is not intended
to be treated.
[0095] Advantage of Simultaneous, Real-Time Imaging
[0096] Major advantages in achieving real-time imaging of therapeutic HIFU
while it is being applied are: (1) the HIFU treatment can be stopped when
a HIFU induced lesion has grown to the point at which it begins to extend
beyond the desired treatment site, so that the HIFU focal point can then
be repositioned to another treatment site and HIFU therapy reactivated;
(2) the focal point of the HIFU wave can be observed in the image due to
changes in the echogenicity of the tissue at the focal point, which are
apparent in the images of the target area, providing an instant feedback
that can enable a clinician to adjust the focal point onto a desired
treatment site; (3) the HIFU focal point can be adjusted during the
administration of the HIFU therapy to compensate for tissue movement
within the patient's body due to breathing or for other reasons; (4)
real-time visualization of a treatment site is very reassuring to the
medical therapist, in confirming that the HIFU energy is being applied to
the correct position (and that healthy tissue is not being damaged); (5)
the combined imaging and therapeutic treatment can be accomplished much
faster than in the past, when it was necessary to render treatment, stop
the treatment, image the site, and then continue the treatment.
[0097] Two methods for HIFU therapy visualization are MRI and ultrasound,
and both can be used to image the nervous system. Ultrasound imaging has
the advantage of requiring less expensive and more portable
instrumentation, compared with MRI. Empirical studies have shown that
synchronized ultrasound imaging provides real-time imaging of the HIFU
treatment MRI provides imaging visualization of the HIFU thermal field
and coagulated region within about five seconds of treatment and is thus
not truly a real-time visualization. But, the MRI latency may be
acceptable, particularly if MRI enables greater resolution to facilitate
treatment of very fine neural structures. With ultrasound imaging,
treating multiple sites within the nervous system, or treating a neural
structure larger than the focal region of the HIFU transducer, is
facilitated, since the HIFU-induced hyperechoic spot remains after
treatment for a duration dependent on the exposure intensity.
Furthermore, treatment dosimetry, and not just treatment location, can be
determined, since the hyperechoic spot size is proportional to the size
of the lesion created, which is important with respect to the treatment
of the nervous system using HIFU, because initial studies have indicated
a dose effect. As described in greater detail below, nerve conduction can
be disrupted on a relatively temporary basis or on a relatively permanent
basis depending on the dose of HIFU delivered to the nerve.
[0098] Useful Therapy Probes, Imaging Probes, and Frames
[0099] The present invention for treating a portion of the nervous system
using HIFU therapy can be implemented using a variety of different
ultrasound imaging probes and ultrasound therapy probes. Combination
probes, where the therapeutic ultrasound transducer and the imaging
ultrasound transducer are combined on a single probe are particularly
useful if the combination probe is intended to be introduced into a body
cavity. In such combination probes, the spatial relationship between the
imaging transducer and the HIFU transducer is generally static, because
both the scanning transducer and the HIFU transducer are combined in a
single instrument. Movement of the probe will generally not move the
focal point of the HIFU transducer out of the imaging plane of the
scanning traducer, because both transducers are part of the combination
probe. Some combination probes are based on prior art imaging probes to
which a therapy head has been retrofitted, while other combination probes
integrate the imaging and therapy transducers into a single new device.
[0100] The present invention can also be implemented using separate
imaging probes and therapy probes. One advantage of using separate
imaging probes and therapy probes is that ultrasound imaging probes are
relatively ubiquitous, and many medical offices already have access to
ultrasound imaging probes and ultrasound imaging systems. Thus, the
ability to simply purchase an ultrasound therapy probe to enable image
guided HIFU therapy of the nervous system will likely reduce the cost of
implementing this new treatment method. When separate imaging probes and
therapy probes are employed, it may be beneficial to utilize a frame or
bracket to maintain a desired spatial orientation between the imaging
probe and the therapy probe, particularly when the tracking systems
described above are not employed. When such a frame is employed, before
therapy is initiated, the clinician will verify that the focal point of
the therapy probe will lie within the image plane of the imaging probe.
This step can either be established geometrically (by understanding the
beam geometry of the ultrasound imaging probe and the HIFU therapy probe,
and then ensuring that the probes are positioned so that the beams
overlap) or empirically. An icon can be added to an ultrasound image
generated by the imaging probe to represent the predicted location of the
focal point of the HIFU beam. The clinician can then manipulate the
position of the combined instruments until the icon overlies the desired
treatment point in the ultrasound image. The position of the icon
verifies that the focal point of the HIFU transducer will coincide with
the desire to treatment site. As discussed in greater detail hereinbelow,
the clinician can then employ one of several additional techniques to
verify that the focal point is indeed properly positioned before
initiating therapy, if so desired.
[0101] Having described a technique for synchronizing HIFU with ultrasound
imaging to enable visualization of the focal point of the HIFU beam
during therapy, exemplary tracking systems, probes and frames, the
following discussion covers the use of HIFU therapy to treat the nervous
system. In accord with the present invention, HIFU therapy can be
employed to alleviate pain, to provide an anesthetic effect, to treat
spasticity, and to provide a cosmetic effect.
[0102] HIFU Therapy Applied to the Nervous System
[0103] FIG. 6A illustrates an exemplary use of HIFU therapy applied to the
nervous system of the patient in accord with the present invention. In a
HIFU therapy probe 65, an acoustic coupling 67 is attached to a therapy
transducer 68 that is mounted to a handle 70. A lead 72 couples the
transducer to a power supply (not shown). In FIG. 6, probe 65 is being
used to apply HIFU to a nerve 82 proximate to a dermal layer 76 of a
patient (not otherwise shown). While many different acoustic transducers
are suitable for HIFU applications, many HIFU transducers exhibit a
generally conical-shaped beam 74, and a substantially smaller, generally
elliptical focal region 78. When probe 65 is positioned so that focal
region 78 is coincident to nerve 82, and therapy transducer 68 is
energized, HIFU therapy of nerve 82 is achieved.
[0104] As described in greater detail below, depending on the duration and
power levels of HIFU employed, the therapy can result in a partial
blockage of nerve function, a complete blockage of nerve function, a
relatively temporary blockage of nerve function, or a relatively
permanent blockage of nerve function. It should be understood that nerve
82 is intended simply as a schematic representation of an exemplary nerve
and is not intended to represent any specific nerve structure. It should
also be understood that suitably configured HIFU therapy probes for
treating neural structures could be used inside a patient's body
(inserted either via a body cavity or incision) and are not limited to
external use. The use of an external HIFU therapy probe or a HIFU therapy
probe configured for insertion into a body cavity are preferred to
inserting HIFU therapy probes into the body via an incision, because the
two former techniques are less invasive than the latter technique.
[0105] 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.
[0106] Several different types of acoustic couplings are known. Acoustic
viscous coupling gels can be smeared over the distal end of the probe and
on the patient's skin (or tissue layer in a body cavity) to facilitate
acoustic coupling. Water is an excellent acoustic coupling medium, and
water filled sacks or envelopes are often disposed between an acoustic
transducer and the skin layer to facilitate acoustic coupling. While the
use of aqueous filled membranes is well known, there are some
disadvantages to using aqueous filled membranes for acoustic coupling.
These disadvantages include a requirement for degassing the aqueous
solution (the presence of gas bubbles will significantly impede
transmission of the ultrasound waves), sterilization concerns, and
containment issues. Hydrogels are solids having a particularly high water
content, and are efficient coupling media for diagnostic ultrasound.
Hydrogels are hydrophilic, cross-linked, polymer networks that become
swollen by absorption of water. The high water content 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. 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, 3D shapes. In one preferred embodiment of
the present invention, acoustic coupling 67 is implemented as a hydrogel
coupling. It should be understood, however, that acoustic coupling 67 can
also be implemented as a viscous ultrasound transmission gel or an
aqueous filled membrane.
[0107] Acoustic transducer 68 has a fixed focal length. That is, focal
region 78 is separated from acoustic transducer 68 by a fixed distance
(absent any interactions with matter that would tend to deflect the
acoustic waves responsible for focal region 78). Yet, the present
invention is not limited to the use of fixed focal length acoustic
transducers, and phased arrays of acoustic transducers having variable
focal lengths can also be employed. However, a fixed focal length
acoustic transducer can be utilized to achieve a robust, relatively
simple, and useful HIFU therapy probe. In applications where a fixed
focal length acoustic traducer is used for HIFU therapy, acoustic
coupling 67 can be used to control the position of focal region 78
relative to the patient. If a relatively thicker acoustic coupling 67 is
employed, focal region 78 will be disposed closer to dermal layer 76,
while if a relatively thinner acoustic coupling 67 is employed, the focal
region will penetrate further below the dermal layer and deeper into the
subcutaneous target. Thus, the thickness of acoustic coupling 67 can be
used to control the position of the focal region relative to a patient's
tissue. As noted above, hydrogels can be formed into relatively rigid, 3D
shapes and are relatively inexpensive. Thus, a plurality of hydrogel
couplings of different thicknesses can be provided to enable HIFU therapy
probe 65 to deliver HIFU to treatment sites disposed at various distances
from dermal layer 76. This effect is readily apparent in FIG. 6B, in
which an acoustic coupling 67a replaces acoustic coupling 67 of FIG. 6A,
and focal region 78 now coincides with a different portion of nerve 82.
In FIG. 6B, an ultrasound imaging probe 84 generates an image plane 86.
Focal region 78 lies within image plane 86, so that focal region 78 can
be visualized in an ultrasound image provided by image ultrasound imaging
probe 84 during therapy, using the synchronization method described
above.
[0108] FIG. 6C schematically illustrates a needle 80 positioned at the
nerve to be treated. Such a needle can be used to introduce nerve block
agents, such as alcohol, to enhance a conduction block achievable via
HIFU therapy alone. In addition to being used to introduce a therapeutic
agent into the treatment area, needle 80 can be readily visualized in an
ultrasound image and can be used as a reference to facilitate guidance of
the HIFU therapy. The needle can also be used to introduce micro-bubbles
into the treatment site to induce cavitation, which will tend to increase
the efficiency of the HIFU therapy. The introduction of bubbles to the
treatment site enhances therapy in a number of ways. First, such
micro-bubbles can be readily visualized in the ultrasound image,
enhancing the image of the treatment site. Second, such micro-bubbles can
be used to lower the cavitation threshold at the treatment site and
enable lower HIFU energies to be used to achieve the same therapeutic
effect provided by higher energy HIFU. The lower energy HIFU is less
likely to introduce undesirable damage to adjacent tissue, which is quite
important if sensitive structures are disposed near the neural treatment
site.
[0109] Also included in FIG. 6C is a blood vessel 253 into which contrast
agents 255 have been introduced. Blood vessel 253 is disposed relatively
close to nerve 82, and a clinician will want to ensure that the HIFU
therapy of nerve 82 does not inadvertently damage blood vessel 253.
Introducing ultrasound contrast agents (or MRI contrast agents if MRI is
being used to visualize the treatment site) into blood vessel 253 will
enable the blood vessel to be more readily visualized, so that the
clinician can ensure that the focal point of the HIFU transducer does not
impinge on blood vessel 253. Furthermore, by providing real-time and
ultrasound guided HIFU therapy, the clinician can monitor the ultrasound
image of the treatment site during therapy, and if any lesion induced by
the HIFU therapy begins to expand undesirably close to blood vessel 253,
the clinician can terminate the therapy.
[0110] FIG. 7 shows a flowchart 390 that indicates a sequence of logical
steps to perform HIFU therapy on the nervous system. As noted above, such
therapy can be used to treat spasticity, to alleviate pain, to achieve an
anesthetic effect, or achieve a cosmetic effect. The steps indicated in
FIG. 7 can be used for any of these purposes. In a block 392, a treatment
site associated with the nervous system is selected, while in a block
394, a specific dose is selected. The particular treatment site will be a
function of the type of therapy being implemented. If the therapy is to
alleviate pain, then a nerve or nerve ganglia involved in the conduction
of pain signals will be selected. Those of ordinary skill in the art will
readily recognize that the step of choosing an appropriate treatment site
must be carried out very carefully. Preferably, the treatment site
selected will maximize a beneficial therapeutic effect, while minimizing
any undesired effects. For example, assume that the HIFU therapy is
intended to alleviate pain in an extremity (such as a hand). Many
different nerves are involved in the conduction of sensory signals from
the arm to the brain, and any of those nerves can be used to interrupt
the pain signals from the hand. Selecting a nerve close to the brain will
likely result in interrupting the transmission of signals in the nervous
system that are unrelated to the pain sensation being transmitted from
this extremity. Selecting a nerve very close to the site where the pain
signals originate will still block the conduction of pain signals from
the extremity to the brain, but will be much less likely to interfere
with the transmission of other sensory signals. The deter ination of an
appropriate dose will preferably be based on empirical studies, much in
the way that pharmacological doses are selected. Thus, selection of a
treatment site and dose will be based not only on a thorough knowledge of
anatomy and the nervous system, but also on empirical studies that
substantiate that the proposed treatment will achieve the desired
therapeutic effect.
[0111] In a block 395, the therapy probe is positioned such that the focal
region (or focal point) of the therapy transducer is incident on the
treatment site selected. Determining where the therapy probe should be
positioned will be a function of the anatomical position of the nerve and
at the focal length of the therapy transducer. Verification of the
anatomical position of the treatment site can be carried out in a
pre-therapy exam using imaging technologies such as ultrasound or MRI.
Based on the identified location of the treatment site, and the known
focal length of the therapy transducer, an optimal position for the
therapy probe can be fairly accurately established. In a block 396, the
accuracy of the positioning of the therapy probe relative to the
treatment site (and more importantly, the position of the focal point
relative to the treatment site) is evaluated to verify that the therapy
probe is properly positioned. As described in detail below, several
different techniques can be used to verify that the therapy probe, and
the focal point of the therapy transducer, are properly positioned
relative to the treatment site. Once the proper positioning of the
therapy probe has been verified, in a block 398, the therapy transducer
is energized using the dose information determined in block 394, to
provide HIFU therapy to the nervous system. In a decision block 400, the
treatment site and/or patient are evaluated to determine whether the
desired therapeutic effect has been achieved. Such an evaluation
preferably includes imaging the treatment site during therapy using
ultrasound (to achieve real-time image guided therapy). Or this
evaluation may alternatively be based on MRI imaging of the treatment
site, which as noted above, incurs a latency problem. As discussed in
detail above, real-time image guided therapy is preferred, because the
clinician may monitor the treatment site in real-time and halt the
therapy if the thermal and mechanical effects (such as lesion formation)
extend beyond the identified treatment site. Thus, real-time image guided
therapy provides the clinician the assurance that therapy can be halted
if the therapeutic effect desired begins to extend beyond the selected
treatment site. Empirical studies establishing a dose response for HIFU
as applied to the nervous system will provide a margin of safety, however
real-time image guiding of HIFU therapy will provide an additional
measure of safety.
[0112] Such an evaluation may also be based on monitoring the patient's
physiological responses. For example, if HIFU therapy is being used to
alleviate pain, the patient can be questioned to determine if the level
of pain has decreased. If HIFU therapy is being used to control
spasticity, the patient can be monitored for a period of time after the
therapy to determine if the spasticity has decreased. If HIFU therapy is
being used to provide an anesthetic effect, the patient can be queried to
determine if any anesthetic effect has been achieved, and if so, if such
an effect has reached the desired intensity. If HIFU therapy is being
used as an alternative to Botox therapy to achieve a cosmetic effect
(i.e., a temporary paralysis of nerves controlling facial muscles to
reduce wrinkles and simulate a more youthful appearance), the effect of
the therapy on the patient's cosmetic appearance can be evaluated. If it
is determined that the therapy has successfully achieved the desired
result, then in a block 402, the therapy probe is removed. If it is
determined that the desired therapeutic effect has not yet been achieved,
additional therapy can be provided.
[0113] As noted in the details of block 396 (shown in FIG. 7), several
different techniques can be used to verify that the focal point of the
HIFU transducer coincides with the selected treatment site in the nervous
system. In a block 396a, a combination of imaging and HIFU beam geometry
are used to verify that the focal point properly coincides with the
selected treatment site. As indicated above, the focal length of a HIFU
transducer is a well-defined parameter. Referring now to FIG. 6B, if the
relative positions of therapy probe 65 and imaging probe 84 are known,
the relative position of focal region 78 within imaging plane 86 can be
determined. An icon can be introduced into the ultrasound image provided
by imaging probe 84 to indicate the anticipated position of focal region
78 (based on the relative positions of the therapy probe in the imaging
probe, and the known characteristics of the focal length). If the
ultrasound image from imaging probe 84 indicates that focal region 78
does not properly coincide with the selected treatment site, therapy
probe 65 and imaging probe 84 can be moved in concert until the icon
corresponding to the predicted position of the focal region properly
coincides with the selected treatment site. If the therapy transducer and
imaging transducer are implemented as a single probe, any movement of the
imaging transducer will result in a corresponding movement of the therapy
traducer. If the imaging transducer and the therapy transducer are
implemented as separate instruments, care must be taken so that any
movement of the imaging probe is matched by a corresponding movement of
the therapy probe (unless a sophisticated tracking system such as those
described above is used to independently track and display the positions
of each probe). This result can be achieved by using a frame to couple
the imaging probe to the therapy probe. In this event, any movement of
the imaging probe used to ensure that the icon representing the focal
region of the HIFU transducer coincides with the desired treatment site
will result in a corresponding motion of the therapy probe. While this
technique has been specifically described as using ultrasound imaging,
those of ordinary skill in the art will really recognize that MRI could
be used in place of ultrasound imaging to achieve the same result.
[0114] Yet another technique for verifying that the focal point of the
HIFU transducer coincides with the selected treatment site involves the
use of relatively low power HIFU combined with imaging, as indicated in a
block 396b. As noted above, even a relatively low power HIFU wave will
change the echogenicity of the target at the focal point of the HIFU
transducer. This change in echogenicity can be identified using imaging
ultrasound. Thus, in this technique, the HIFU transducer is energized at
a power setting selected to change the echogenicity of the treatment area
at the focal point as well as minimize any therapeutic effects, so that
if the focal point is not correctly aligned, minimal undesirable effects
on non-target tissue will occur. Empirical studies have indicated that
relatively low levels of HIFU will change the echogenicity of the
treatment site without any other appreciable effects on non-targeted
tissue (i.e., no tissue necrosis or noticeable damage). This change in
echogenicity persists briefly, so that the change can be detected by
using imaging ultrasound after a relatively short burst of low power HIFU
has been delivered. Alternatively, the synchronization techniques
described above can be used in real-time to visualize the treatment site
as the low level HIFU is being delivered. Regardless of the approach
used, the change in echogenicity in the ultrasound image is identified to
determine whether the therapy probe is properly positioned so that the
focal region coincides with the selected treatment site. If not, the
therapy probe is repositioned, and an additional verification step is
performed, until the change in echogenicity induced by the relatively low
power HIFU burst coincides with the desired treatment site. This
verification technique can be used in connection with a frame, thereby
ensuring that the spatial orientation between the imaging probe in the
therapy probe remained fixed, or this technique can be used in freehand
registration of the probes without requiring a sophisticated tracking
system, as described above.
[0115] Still another technique to verify that the therapy probe is
properly positioned so that the focal region of the therapy transducer
coincides with the selected treatment site is based on applying a
relatively short burst of HIFU and monitoring the patients physiological
reaction, as indicated in a block 396c. Depending on the nerve or other
portion of the nervous system that is being targeted, a specific and
well-defined physiological reaction may result based on delivering HIFU
therapy to the treatment site. An analogy to this technique would be the
well-known knee-jerk response a physician can induce in a patient by
lightly striking the patients knee in a particular anatomical location.
Where such well-defined physiological responses to the application of
HIFU exist and are empirically identified, they can be used to verify
that the focal region of the therapy transducer is probably positioned
relative to the treatment site. Because this technique does not provide
actual visual verification (via medical imaging) that the focal region of
the HIFU transducer actually coincides with the desired treatment site,
this technique is likely to be better suited to providing relatively
lower doses of HIFU therapy that do not result in permanent effects. As
discussed in greater detail below, empirical evidence indicates that a
well-defined dose response between a level of HIFU therapy applied and an
induced therapeutic effect on the nervous system can be identified.
Empirical evidence indicates that based on the dose, the therapeutic
effect can be temporary (i.e., a non-permanent interruption of nerve
conduction) or permanent. When this verification technique is used in
combination with the relatively lower doses of HIFU that enable
non-permanent therapeutic effects to be achieved, if the expected
physiological response is indicated even when the desired treatment site
has not been accurately targeted, there is little danger that an
undesirable permanent effect will result.
[0116] Yet another method to determine if HIFU therapy of the nervous
system has been successful is to measure the physiological response of
the treated neural structure to electrical simulation, to determine if
conduction of neural impulses through that neural structure have been
blocked. A blockage indicates successful treatment
[0117] HIFU Therapy and Dose Response
[0118] For each potential clinical application of HIFU, the biological
effects on the specific tissue of interest must be determined in order to
achieve the desired clinical outcome. Different parameters of HIFU can
result in variable effects on the tissue, such as a peripheral nerve. To
enable the use of HIFU to produce effects on the nerve, ranging from
partial conduction block to irreversible axonal degeneration (to treat a
range of severities of spasticity), HIFU parameters can be appropriately
varied to achieve these effects. HIFU application to a specific structure
within the body (i.e., to a tumor or nerve) can be described using the
standard treatment parameter of "dose." In this paradigm, the HIFU dose
is quantified in a similar way as in other forms of medical treatment
involving applying energy to tissue, i.e., as the intensity I
(W/cm.sup.2) multiplied by the duration t (s) of the exposure
(Dose=I.times.t) in units of J/cm.sup.2. Dose is an important parameter
in the production of biological effects during HIFU treatment.
Furthermore, different tissues in the body absorb acoustic energy at
different rates (different absorption coefficients) and thus, the same
HIFU dose may result in different biological effects when applied to a
range of tissue types. It is therefore important to investigate the
dose-dependence of the specific tissue (i.e., neural structures) of
interest, varying both intensity and duration, in order to develop the
most optimal treatment plans to produce the desired biological effects.
[0119] It is believed that manipulating the HIFU dose will achieve a
graded effect on the nerve and the suppression of its function. Higher
intensities, resulting in lesion formation of an entire nerve fiber or
bundle, will completely block the nerve conduction for the nerve or
bundle, much as a surgical separation of the nerve would. Intermediate
intensities, damaging less of the nerve structure, will cause less (or
reversible) suppression of nerve function. Either dose response has
clinical application. A permanent nerve block would provide an effect
essentially like severing the nerve, such that the spasticity or pain
associated with a specific nerve would be prevented indefinitely. Any
voluntary function provided by this nerve would also be eliminated.
Therefore, this effect would be useful primarily for patients who no
longer have voluntary function, such as those with a complete transection
of the spinal cord, yet having spasticity and/or pain. Where empirical
dose studies indicate levels of HIFU with reversible effects, such dose
could be employed to treat spasticity or pain without hindering the
voluntary function of a patient. Particularly with respect of achieving
an anesthetic effect or a cosmetic effect, the empirical identification
of HIFU doses resulting in reversible effects for particular neural
structures is required.
[0120] Empirical Studies
[0121] A series of in vivo studies have been completed that support the
conclusion that HIFU can provide a range of effects on peripheral nerves
that appear to be controllably variable from a partial conduction block
to a complete conduction block (acute effects), and from a reversible
block, to irreversible axonal degeneration (chronic effects). The initial
work focused on developing an ultrasound image-guided HIFU system and a
HIFU protocol to completely suppress the function of the sciatic nerve
complex of rabbits. Investigation of the long-term effects of such
complete blocks has also begun, indicating axonal degeneration as a
chronic effect of HIFU treatment. Furthermore, initial results of acute
studies using rabbit and pig femoral nerves have indicated the likelihood
of partial conduction block as an acute effect of HIFU treatment with
variable exposure parameters.
[0122] 1.sup.st Study: Complete Conduction Block of the Rabbit Sciatic
Nerve Complex
[0123] One empirical study used ultrasound image-guided HIFU to target and
suppress the function of the sciatic nerve complex of rabbits in vivo.
The results of this study support the conclusion that ultrasound image
guided HIFU can be used to locate, target, and treat peripheral nerves to
treat severe spasticity. Such a technique will provide a
non-pharmacological, non-invasive alternative to surgical severing of
nerves.
[0124] FIG. 8A is a photograph of the system employed, which included an
ultrasound imaging transducer 84a (CL10-5, Philips HDI-1000.TM., Philips
Ultrasound, Bothell, Wash.) and a HIFU transducer 68a (SU-107.TM., Sonic
Concepts, Woodinville, Wash.), each transducer being coupled to a custom
frame 88 to ensure that the geometrical orientations of the two beam
patterns were coplanar, enabling a HIFU focus 78a of HIFU beam 74a to be
visualized in an image plane 86a. Note that frame 88 includes adjustments
along the x and z axis, as well as an angular adjustment, as respectively
indicated by arrows x, z, and .theta.. The compact linear array imaging
transducer employed has a broadband frequency of 5-10 MHz. The 3.2 MHz
single-element HIFU transducer has a focal length of 3.5 cm. Specially
molded polyacrylamide based hydrogels (not shown in FIG. 8A, but see
FIGS. 6A and 6B) were employed to provide efficient coupling of the HIFU
energy into tissue, enabling transmission of the HIFU beam to its focal
zone and formation of a lesion encompassing the nerve. The gel standoffs
also enabled proper positioning of the HIFU focus at the depth of the
sciatic nerve, as described above in connection with FIGS. 6A and 6B.
[0125] The HIFU transducer and imaging transducer were synchronized as
discussed above, to enable the visualization of the HIFU focus within the
ultrasound image. The synchronization enabled the HIFU focal region to be
seen in the window between the interference bands created by the
overlapping on-time of the HIFU and the imaging. This method of
synchronization enables the precise visualization of the HIFU focus as it
formed a hyperechoic region in the ultrasound image. Once the HIFU and
imaging transducers were secured to the frame, a tissue-mimicking phantom
was used to determine where the focus appeared in an ultrasound image
generated with the imaging transducer. As indicated in FIG. 8B, an icon
89 was marked on a transparent sheet 87 overlaying an ultrasound image
85, for use as a reference for later imaging, where icon 89 corresponds
to the HIFU focus. As long as the relative positions of the HIFU
transducer and imaging transducer are not changed (i.e., the ultrasound
imaging transducer end of the HIFU transducer remain coupled to the
frame), transparent sheet 87 can be used to identify the position of the
HIFU focus before the HIFU transducer is energized by placing the
transparent sheet (including the icon) over an image of the target area
obtained using the ultrasound imaging transducer. In more sophisticated
systems, this icon could be generated electronically in the ultrasound
image (or other image, see FIG. 5C and the related text).
[0126] FIG. 8C schematically illustrates HIFU transducer 68a, and imaging
transducer 84a secured to frame 88 and disposed adjacent to a gel phantom
91. The HIFU transducer is energized to generate a lesion 93 in the gel
phantom. Generally elliptical icon 89 is added to a transparent sheet as
discussed above. FIG. 8D is a photograph of ultrasound image 95,
including a lesion 99 and interference bands 97. Ultrasound image 95 was
generated after moving frame 88 (with the therapy and imaging transducers
in their same relative positions) to a treatment subject (a rabbit as
described below) and obtaining a pre-therapy ultrasound image. The
overlay sheet including icon 89 (described in connection with FIG. 8B)
was then placed over the pre-therapy ultrasound image, and the position
of the frame (and the therapy and imaging transducers attached to the
frame) was manipulated until icon 89 coincided with the desired treatment
location. HIFU transducer 68a was energized during real-time imaging
(note interference bands 97), and lesion 99 was generated in the location
indicated by the icon verifying that the use of a gel phantom, an icon,
and a frame enable accurate prediction of the focal region of the HIFU
beam.
[0127] In the first empirical study, eleven New Zealand white rabbits were
anesthetized and the sciatic nerve complexes of both legs were treated
with HIFU. Each animal was oriented on a surgical table 107 as
schematically indicated in FIG. 9A, such that its leg 103 was stabilized
and perpendicularly coupled to a tension force gauge 105 (FGV-2A.TM. from
Shimpo, in Itasca, Ill.). The proper orientation was achieved by placing
the animal on its side with the top leg supported by the weight of
custom-designed polycarbonate surgical table 107. The custom-designed
surgical table included a plurality of holes 113 to enable the strain
gauge to be selectively positionable. Pins (not separately shown) could
be inserted into theses holes to secure the strain gauge, thereby rigidly
attaching the force gauge to the table to prevent movement during the
experiment. A strap 111 was tied around the foot of the rabbit at the
metatarsal joint and connected directly to the force gauge. A 3 cm
incision was then made in the skin transversely across the leg at the
mid-thigh level. The skin was pulled back to expose the lateral hamstring
muscle. For this terminal study, HIFU was applied through a
polyacrylamide gel coupler, directly to the surface of the lateral
hamstring muscle (with the nerve complex positioned under the muscle
layer) in order to eliminate the problems that can occur when HIFU must
transmit through the skin. The primary goal of this empirical study was
to couple the high energy beam into the muscle tissue such that the beam
would focus at a treatment site 119 in sciatic nerve complex 82a, as
indicated in FIG. 9B. Effective coupling is achieved by minimizing the
impedance mismatch between the ultrasound transducer, gel coupler, and
the skin. The formation of air pockets between the gel coupler and the
skin can result in a significant impedance mismatch. The reflection of
the high energy beam at this air interface would direct much of the
energy on the skin, leading to burns. Rabbits have a very fine layer of
hair covering their legs, which is difficult to remove completely, and
any remaining hair can result in air pockets between the coupling medium
and the skin. This issue is not present in humans, and much better HIFU
coupling can be achieved with human skin. Later rabbit studies achieved
adequate skin preparation, and successfully transmitted HIFU through the
rabbit skin to provide a non-invasive treatment of the nerve.
[0128] As schematically shown in FIG. 9B, the tip of an anodal stimulating
electrode 115 (Teflon-coated except for the exposed tip; Teca, DMG50.TM.,
Oxford Instruments Medical Inc., Hawthorne, N.Y.) was inserted
subcutaneously near the hip bone, and a similar cathodal stimulating
electrode 117 was positioned near the nerve just below the sciatic notch,
via sequential repositioning as electrical stimulation intensity through
the tip of the needle was reduced. The settings of the electrical
stimulator (Model S88.TM., Grass Telefactor and, West Warwick, R.I.)
included 1 pulse/s with 50 ms duration and an initial voltage of 15 V.
The force response of the plantarflexion muscles in the rabbit foot to
this electrical stimulus was measured with the force gauge. The voltage
of the electrical stimulus was lowered to assure that the baseline muscle
response was still strong, even at voltages below 5 V. Once a strong
baseline force response was observed (approximately 0.55 N), the
electrodes were removed so that HIFU treatment could begin.
[0129] The image-guided HIFU device of FIG. 8A was placed on the surface
of the lateral hamstring muscle (with a layer of ultrasonic coupling gel
between the HIFU probe and the muscle) and oriented so that the sciatic
nerve complex, which was under the muscle, could be viewed transversely
in the ultrasound image, as is schematically indicated in FIG. 9C. A gel
coupler 67b was attached to HIFU transducer 68a. Gel coupler 67b was
selected to have a thickness such that the HIFU could be targeted into
the muscle just below the nerve (as indicated by the position of the
focus marked on the overlying transparent sheet, as described in
connection with FIG. 8B). The nerve complex was again located in the
ultrasound image, through visualization of the cross section of the
complex as a hyperechoic structure between the muscles of the leg, and
the treatment plan was confirmed HIFU was targeted initially at a point
121 in the muscle tissue immediately adjacent to the nerve, and treatment
was applied such that the lesion progressed upward (towards the
transducer) through the nerve and into the upper muscle, as indicated by
a point 123. An arrow 127 indicates the direction of scanning. The
acoustic output of the transducer for all experiments was 60 W at a duty
cycle of 55%, and an acoustic intensity of 1480-1850 W/cm2 (ISATA,
spatial-average, temporal-average). A scanning rate of HIFU application
(0.5-0.6 mm/s) was used to ensure that the entire nerve complex was
treated (the nerve complex was 3-4 times larger than the HIFU focal
region). HIFU treatment continued until the HIFU focus had been scanned
across the entire nerve complex, as evidenced by the progression of the
hyperechoic spot in the image (note the cylindrical shape formed by
scanning the generally elliptical focal region). The nerve was again
stimulated using the near-nerve electrodes by positioning the electrodes
proximal to the HIFU treatment site. If any force response remained, the
nerve was retreated with HIFU. The experiment was complete when no force
response remained. A successful block was indicated by no force response
to stimulation of the nerve proximal to the HIFU site, yet a strong force
response, approximately 0.55 N, to stimulation (at voltages less than 5
V) of the nerve distal to the HIFU site. FIG. 9D is substantially similar
to FIG. 9C, and shows the scanning motion from another perspective, with
knee 125 being visible in FIG. 9D.
[0130] FIG. 9E is a photograph of the above-described procedure. An
incision 129 has been made in rabbit leg 103, and frame 88, HIFU
transducer 68a, and imaging transducer 84a (not visible in FIG. 9E) are
positioned adjacent the incision, such that a gel coupling 67b contacts
the muscle tissue to acoustically couple the HIFU transducer to the
muscle tissue.
[0131] After euthanization, segments of the sciatic nerve complex (1 cm
length) at the HIFU treatment site, as well as 2 cm proximal and distal
to the site, were taken for histology. Tissue samples from six animals
were fixed in formalin for light microscopy and samples from three
animals were fixed in 3% glutaraldehyde for transmission electron
microscopy (TEM); time from HIFU treatment to nerve fixation was 30 to 60
min.
[0132] Because the rabbit sciatic nerve complex runs loosely between two
muscles of the leg, any movement of the muscle layers (needed for
immediate observation of the HIFU lesion encompassing the nerve) could
disrupt the morphology of the nerve and the adjacent tissue. To enable
measurement of the volumes of the lesions, the legs of two animals (four
legs) were frozen upon sacrifice to keep the tissue morphology intact. On
the following day, the legs were cut in thin slices (2-5 mm) to expose
the cross-sectional views of the lesions formed by HIFU treatment. Images
of each slice of the lesions were taken using a digital camera (Canon USA
Inc., Lake Success, N.Y.) and their areas were determined using the image
analysis software ImageJ.TM. (NIH, Bethesda, Md.). The approximate
volumes of the lesions were estimated by adding the volumes of each
slice.
[0133] The nerve samples fixed in formalin were embedded in paraffin, cut
in either cross section or longitudinally with respect to the axons,
stained with hematoxylin and eosin (to observe nuclei of Schwann cells)
or Masson's trichrome (to observe myelin layers), and observed with a
light microscope (DMLS, Leica Microsystems Inc., Barmockburn, Ill.). The
samples fixed in 3% glutaraldehyde were cut in cross section into 2 mm
pieces, stained with 1% osmium tetroxide and 1% uranyl acetate,
dehydrated with a series of increasing concentrations of ethanol, and
embedded in plastic (3:2 ratio of Spurr's epoxy propylene oxide). The
samples were cut in semi-thin sections (1 .mu.m), post stained with
Richard's stain (methylene blue/azure II), to observe myelin and axon
organization, and observed with a light microscope (Leica DMLS). Samples
were then cut in thin sections (.about.100 nm) and observed with a
transmission electron microscope (EM 420T) operating at 120 kV.
[0134] Beam profiles of the acoustic pressure field of the 3.2-MHz HIFU
transducer in both the axial and lateral dimensions were obtained as
indicated in FIGS. 10A and 10B, which represent maps of pressure fields
associated with HIFU transducer 68a. The grey-scale on the maps
represents the dB difference from the maximum measured pressure
amplitude. The map of FIG. 10A represents an axial cross section of the
beam path where the full-width, half-maximum (FWHM boundary denotes the
focal region of the transducer. Focal dimension in the axial direction is
5.1 mm. FIG. 10B corresponds to a lateral cross section of the beam path
at the HIFU focus. The FWHM boundary indicates that the lateral focal
dimension is 0.76 mm. Thus, the focal dimensions of the HIFU beam,
specified as the axial and lateral (FWHM) dimensions of the pressure
field were measured to be 5.1 mm and 0.76 mm, respectively. Therefore,
the area of a lateral cross section of the HIFU beam directly at the
focus was calculated to be 0.0045 cm2. This area was the spatial area of
the beam that had approximately the same pressure distribution and would
also correspond to the area of tissue that would receive the same energy
distribution with HIFU application. In addition, this area was much
smaller than the cross-sectional area of the rabbit sciatic nerve
complex, and thus, scanning was required to treat the entire
cross-sectional area of the nerve complex. There is a linear relationship
between acoustic power and electrical power for the HIFU transducer, and
the efficiency of the transducer (conversion of electrical to acoustic
power) was measured to be 85%. For the 60 W of acoustic power and the 55%
duty cycle used in the in vivo studies, and taking into account the
attenuation through the gel coupler (having an attenuation coefficient of
about 0.6 dB/cm) and the rabbit muscle (having an attenuation coefficient
of about 2.5 dB/cm), the intensity at the focus was determined to be
about 1480-1850 W/cm2, dependent upon the depth of the nerve into the leg
(nominally 2-2.5 cm) and the thickness of the corresponding gel coupler
(nominally 1-1.5 cm). Such intensities have been shown to produce
coagulative necrosis in tissue within 1 second of HIFU application. The
temperature at the face of the transducer, with HIFU of 60 W acoustic
power at 55% duty cycle and duration of 40 seconds, increased from a
baseline of 21.3.degree. C. to 35.9.degree. C. The temperature returned
to baseline 10 minutes after treatment ceased. The electrical powers
(forward and reflected) varied within only 1 W as temperatures were
increased.
[0135] Successful targeting and conduction block was achieved in 100% of
the 22 nerve complexes of the 11 rabbits treated. The duration of HIFU to
achieve complete conduction block was 36.+-.14 seconds (mean.+-.SD).
High-resolution ultrasound (CL10-5) provided visualization of the sciatic
nerve complex and guidance to target the HIFU treatment. The treatment of
the nerve was monitored using ultrasound imaging, as shown in FIGS.
11A-11D. The nerve complex was imaged in cross section and observed as a
round hyperechoic structure between the two major muscles of the leg as
indicated in the ultrasound image of FIG. 11A. The HIFU focus was
targeted just below the nerve for the initiation of the treatment is
indicated by the ultrasound image of FIG. 11B. As the device was scanned
across the nerve complex, the lesion formation was visualized by the
progression of the hyperechoic region in the image is indicated by the
ultrasound image of FIG. 11C. After HIFU treatment had been completed,
the lesion remained visible in the image for several minutes, as
indicated by the ultrasound image of FIG. 11D.
[0136] FIGS. 11E-11H are ultrasound images of the rabbit sciatic nerve
complex taken in the first study before, during, and after HIFU
treatment. These are the same ultrasound images as shown in FIGS.
11A-11D, without the introduction of the HIFU transducer into the
ultrasound image and are presented together on one drawing sheet for easy
comparison. The ultrasound image of FIG. 11E shows nerve complex 82a, the
adjoining muscle tissue, and points 121 and 123 where the HIFU therapy is
to begin and end, respectively (to ensure that the entire cross-sectional
area of the nerve is treated, the focal region of the HIFU being
substantially smaller than the cross-sectional area of the nerve). The
ultrasound image of FIG. 11F shows synchronized HIFU interference bands
97, nerve complex 82a, and lesion 99a after two seconds of HIFU therapy.
The ultrasound image of FIG. 11G shows synchronized HIFU interference
bands 97, nerve complex 82a, and lesion 99a after ten seconds of HIFU
therapy. The ultrasound image of FIG. 11H shows the nerve, muscles, and
lesion after HIFU therapy.
[0137] Conduction block was indicated by complete suppression of the force
response to electrical stimulation of the nerves. Surgical exposure of
the nerves showed a clear presence of HIFU lesions on each sciatic nerve
complex, as indicated in the photographs of FIGS. 12A and 12B (the
photograph of FIG. 12B is simply a higher magnification image of the
photograph of FIG. 12A). The lesions appeared white in comparison to the
normal pink color of the tissue. Both a nerve lesion 99b and a muscle
lesion 99c are visible in FIG. 12A (as described above, the focal region
of the HIFU transducer was swept across the nerve, with an initial focal
point coinciding with muscle tissue immediately adjacent to one side of
the nerve, and ending in muscle tissue immediately adjacent to an
opposite side of the nerve). FIGS. 12C-12F are additional images of
ultrasound image guided HIFU induced nerve lesions generated in the first
study. Conduction block of all nerve complexes that were surgically
exposed was confirmed by observing a complete absence of force response
to nerve stimulation proximal to the HIFU site, but a strong force
response (approximately 0.55 N) to stimulation distal to the HIFU site.
[0138] Thin slicing of the frozen rabbit legs exposed lesions that
completely encompassed the nerves. A cross-sectional image of one lesion
is presented in FIG. 13. The estimated volumes of the lesions were
determined to be 2.8+1.4 cm3 (mean+SD). Such large lesions indicate
significant collateral damage to the adjacent muscle which is undesirable
for a clinical treatment. By decreasing the time of HIFU treatment, in
preparation for the long-term study (discussed below), it is possible to
reduce the damage to adjacent tissue.
[0139] FIGS. 14A-14D are light microscopy images of nerves, stained with H
& E (FIGS. 14A and 14B) or Masson's trichrome (FIGS. 14C and 14D), and
observed longitudinally. All scale bars equal 20 .mu.m. In FIG. 14A, the
untreated section of nerve shows many nuclei of Schwann cells. In FIG.
14B, the HIFU-treated section of nerve appears disorganized. Thick arrows
133 show holes in the structure of the nerve and there are few Schwann
cell nuclei 139 present. In FIG. 14C, which represents an untreated
section of nerve, arrow 143 shows the untreated nerve is characterized by
relatively thick myelin layer. In contrast, in FIG. 14D, the HIFU-treated
section of nerve appears disorganized and arrows 135 point to areas of
myelin disruption. These longitudinal sections of HIFU-treated nerves,
stained by H&E or Masson's trichrome, clearly show disruption of myelin
sheaths and axons across fascicles of the nerve (arrows 133 in FIG. 14B
and arrows 135 in FIG. 14D. The number of staining Schwann cell nuclei
139 are reduced in the HIFU-treated sections, as indicated by comparing
FIG. 14B with the untreated nerve sections shown in FIG. 14A. The HIFU
treatment could have caused apoptosis or necrosis of the cells.
[0140] In the nerve cross sections stained with osmium and Richard's stain
(FIGS. 15A and 15B), the HIFU treatment appeared to have caused axon
swelling with myelin thinning and disruption, as indicated by arrows 141
in FIG. 15B, as compared to the untreated nerve sections shown in FIG.
15A. Most axons in the HIFU-treated sections showed abnormal dark
staining within the axoplasm, which may have been due to disruption of
the myelin sheath and accumulation of myelin in the axoplasm. The images
of FIGS. 15A and 15B were generated using light microscopy. Richard's
stain is methylene blue/azure II. The scale bars in the image are equal
16 .mu.m. The untreated section of nerve in FIG. 15A shows a thick layer
of myelin surrounding individual axons (see arrow 145), whereas in the
HIFU-treated section of nerve in FIG. 15B clearly show areas of axonal
demyelination and cell destruction.
[0141] FIGS. 16A and 16B show TEM images (magnification of 2300.times.) of
axons of a normal, untreated section of a rabbit nerve (FIG. 16A) and a
HIFU-treated section of the same rabbit nerve (FIG. 16B). It appears that
the myelin layers surrounding HIFU-treated axons are disorganized and
broken, allowing accumulation of myelin in the axoplasm of the nerve
cells. The scale bars equal 6 .mu.m. Note that FIG. 16A (normal,
untreated nerve section) shows thick and organized myelin layers
surrounding individual axons, while FIG. 16B (HIFU treated nerve section)
shows disorganized and broken myelin layers surrounding individual axons.
[0142] The results of the first in vivo study indicate that HIFU at
intensity of about 1480-1850 W/cm2 can effectively block conduction in
the sciatic nerve complex of rabbits within 36 seconds+14 seconds
(mean+SD). Therefore, the mean dose applied to the nerve and its adjacent
tissue was about 49,300-62,900 J/cm2. This first empirical study also
demonstrated the capability of commercially available high-resolution
ultrasound imaging to identify the nerve complex and guide and monitor
the HIFU treatment of the complex.
[0143] The biological mechanism of nerve block appears to be a combination
of demyelination, axon disruption, and other structural damage to the
nerve fibers, although the exact mechanism of HIFU bioeffects for
neurolysis remains to be determined. Mechanisms of tissue damage by HIFU
have been previously reported as being either thermal or mechanical. The
large increase in temperature in the tissue at the site of the HIFU focus
can lead to coagulative necrosis of the tissue. The blanching of the
nerve at the site of the HIFU treatment, as well as the lesion in the
surrounding muscle, was evidence of coagulative necrosis and thermal
effect. It is also likely that cavitation (formation, growth, and
collapse of micro-sized bubbles) plays a role in the structural damage
evident from the histological examination. The high intensities
(1480-1850 W/cm2) calculated at the focus of the HIFU transducer are
likely sufficient to induce cavitation within the nerve and muscle
tissue. The rupture of myelin sheaths of axons of the nerves (FIG. 15B)
is likely the result of this mechanical action of HIFU. Boiling of
ambient liquids can also result from the high temperatures generated in
the tissue with HIFU application. Boiling bubbles can then act as nuclei
for the generation of or enhancement of cavitation. Both cavitation and
boiling are also believed to be involved in the enhancement of
hyperechogenicity in the region of the ultrasound image corresponding to
the HIFU focus. Although their involvement is assumed, the role of
thermal and mechanical effects of HIFU in the conduction block of
peripheral nerves is not fully understood at this time; and future
studies are being planned to determine the prevalence of these mechanisms
when using different doses of HIFU.
[0144] As noted above, histological results at 30 to 60 minutes after HIFU
treatment show partial disruption of myelin and axons in the nerve. The
abnormally dark staining of axoplasm in the osmium and Richard's stain
cross sections (FIG. 15B) indicates disruption of myelin sheaths and
accumulation of myelin in the axoplasm. TEM images in FIGS. 16A and 16B
support this conclusion by showing the accumulation of disorganized and
broken myelin in the axoplasm of nerve cells (FIG. 16B). Myelin
disruption was evident from longitudinal nerve sections as well, shown by
arrows 135 in FIG. 14D. HIFU also seems to disrupt the nuclei of Schwann
cells, as can be seen by comparing Schwann cell nuclei 139 in FIGS. 14A
and 14B. Schwann cells are responsible for myelination and remyelination
in peripheral nerves. Without healthy Schwann cells, the nerve fibers are
likely to have difficulty repairing myelin disruption caused by HIFU.
Disruption of myelin and axons may lead to distal axon degeneration.
Whether HIFU disruption of peripheral nerve is sufficient to lead to axon
degeneration will be determined in long-term studies, currently underway.
[0145] To determine the long-term effects of HIFU treatment on the nerve
complex, it is important to note the distinction between a force response
to electrical stimulation distal to the HIFU treatment site and one
proximal to the site. The initial disruption of the nerve by HIFU blocks
the transmission of excited signals as they travel along axons from
locations proximal to the treatment site to locations distal to the site.
Therefore, stimulating the nerve proximal to the site will not result in
a force response. However, the axon segments distal to the site are still
viable after HIFU treatment and transmission along this area of the nerve
is not blocked, a normal force response to stimulation is generated. If
HIFU damage is irreversible, it could result in axon degeneration distal
to the HIFU site over a period of days.
[0146] This first empirical study preliminary (acute rabbit study)
provides a proof of concept for image guided HIFU therapy to treat the
nervous system, to achieve a conduction block of a nerve. The study
proved the sciatic nerve complex of rabbits could be treated using an
ultrasound image guided HIFU device. While this first study indicates
that HIFU therapy can be used to treat spasticity, it must be noted that
determination of a threshold HIFU intensity and duration (dose) of
treatment that will suppress function in the nerves is necessary for
effective clinical application of HIFU to treat spasticity. Long-term
studies will indicate whether the current protocol of HIFU provides a
permanent block, caused by irreversible, axonal degeneration of the
nerves, or only a temporary, reversible conduction block. Either case has
clinical application. A permanent block would provide an effect
essentially like severing the nerve, such that the spasticity or pain
associated with a specific nerve would be absent indefinitely. Any
voluntary function provided by this nerve would also be eliminated.
Therefore, this effect would be useful primarily for patients who no
longer have function, such as those with a complete transection of the
spinal cord, yet have spasticity and/or pain. If the effect is
reversible, it may indicate that there are protocols of HIFU treatment
that could simply lessen the presence of spasticity or pain without
hindering the voluntary function of a patient. This initial acute study
showed the capability of very high HIFU doses of about 49,300-62,900
J/cm.sup.2 to produce a complete conduction block of the rabbit sciatic
nerve.
[0147] 2.sup.nd Study: Verification of Irreversible Block of the Rabbit
Sciatic Nerve Complex
[0148] Treatment of spasticity sometimes requires permanent blockage of
nerve function. The next study sought to determine a protocol of HIFU
treatment that would irreversibly suppress the function in the nerve, to
be used as a permanent treatment of patients with severe spasticity and
no voluntary function. This study assessed the function of the nerve in
response to electrical stimulation as much as 14 days after the HIFU
treatment, assuming that if nerve function does not reappear after this
time, HIFU has damaged axons of the nerve to such an extent that they
have undergone Wallerian degeneration. Should function be restored at any
time point within 14 days of HIFU treatment, this result is an indication
that HIFU simply disrupted the nerve fibers enough to reversibly block
conduction without subsequent axonal degeneration. As noted above, both
cases have clinical utility for the treatment of patients with
spasticity.
[0149] The ultrasound image-guided HIFU device that was used in the
1.sup.st study described above (see FIGS. 8A, 9C and 9E) was also used in
the 2.sup.nd long-term study. There were only slight differences in the
preparation of the animal and the application of HIFU to the nerve. To
minimize the complications that could arise during the animal's recovery,
no incisions were made in the rabbit skin. A new technique of preparing
rabbit skin for transcutaneously HIFU therapy was developed. This
technique involved shaving with an electric razor, 1-2 applications of
depilatory cream (5 min each), and adding a thin layer of mineral oil
between the polyacrylamide gel coupler and the skin. With each animal,
the sciatic nerve complex was visualized using ultrasound imaging as a
hyperechoic structure (Philips HDI-1000, CL10-5 probe), and HIFU
treatment of 1500-1930 W/cm.sup.2 was applied to the nerve. This range of
intensities was determined previously to enable immediate visualization
of a hyperechoic spot in the ultrasound image and complete block of the
nerve, with minor collateral damage to adjacent tissue. For each rabbit,
the protocol was to apply HIFU in 5 second intervals (10-20 seconds of
total treatment) to the nerve complex until no force response of the
plantarflexion muscles to electrical stimulation remained. A new package
of needle electrodes and a fresh polyacrylamide gel coupler for the HIFU
transducer were used for each animal. After completion of treatment, the
animal was then allowed to recover from anesthesia. Each animal was
monitored in the animal facility twice daily (for first 5 days) and its
force response to electrical stimulation of the sciatic nerve was
measured with an endpoint at 15 days. The animal also had its force
response measured at the intermediate time points of 2 and 7 days post
HIFU treatment. Only minor anesthesia was used at these intermediate time
points to control unwanted movement of the rabbit.
[0150] At the designated time endpoint of 15 days post-treatment, each
animal was anesthetized, the nerve complex electrically stimulated
percutaneously with near-nerve needle electrodes and the response of
plantarflexion muscles was measured with a force transducer. The nerve
complex was exposed and the force response to electrical stimulation
proximal and distal to the HIFU site was measured. The animal was
euthanized, and samples of the nerve and adjacent muscle were surgically
harvested for future histological analysis.
[0151] The sciatic nerve complexes of the right legs of two New Zealand
white rabbits have been treated using this protocol. One rabbit was
treated with two 5-second exposures of HIFU at 1930 W/cm.sup.2 (58% duty
cycle; 19,500 J/cm.sup.2), and the result was complete suppression of the
force response (kick) to electrical stimulation (15 V). The hyperechoic
spot was immediately visualized in the ultrasound image during each
treatment. For one rabbit, after four different 5-second treatments of
HIFU at 1500 W/cm.sup.2 (58% duty cycle; 30,000 J/cm.sup.2), the force
response of the leg to electrical stimulation (15 V) was approximately
30% of the initial force response. It was concluded that the HIFU
treatment should be terminated at that point to avoid formation of large
lesions of muscle necrosis. The hyperechoic spot was visualized during
these treatments, but only towards the end of each 5-second treatment.
After 2 days, the HIFU-treated sciatic nerves of the animals were
electrically stimulated and the force response of the plantarflexion
muscles was measured. Complete block was observed in both animals, since
no force response was indicated. Again, at 7 and 15 days post-treatment,
the force response of both animals was measured and no response remained.
Finally, at 15 days post-treatment, terminal surgery was performed for
both animals. Upon exposure and stimulation of their sciatic nerves, both
proximal and distal to the HIFU treatment site, no force response of the
plantarflexion muscles remained, indicating axonal degeneration. These
results indicated that the nerves remained blocked at 15 days
post-treatment. Additionally, this duration of conduction block resulted
in degeneration of distal axons of the nerve, indicated by the
suppression of the force response to distal stimulation. The histological
response of the nerves have not yet been evaluated to confirm this distal
axonal degeneration. It is also important to note that Wallerian
degeneration is used as an indication of irreversible suppression.
Regeneration of nerves is possible, although investigating this would
have required several months of post-HIFU observation of nerve conduction
and function.
[0152] The long-term response of nerves is indicated by the light
microscopy images in FIGS. 16C and 16D. The proximal portion of the nerve
has axons that appear normal, as indicated in FIG. 16C. The distal
portion of the nerve has several vacant sites, where axons were
originally, indicating the degeneration of axons, as indicated in FIG.
16D. A total of 12 rabbits have been treated according to the protocol of
the 2.sup.nd study, and the animals have survived to either 0, 7, 14, or
15 days post HIFU treatment. The mean HIFU treatment time to achieve
complete conduction block of the sciatic nerve was 10.5.+-.4.9 seconds.
Complete conduction block remained in all treated nerves at their
designated endpoints. The mean lesion volume was 1.6.+-.1.1 cm.sup.3.
[0153] 3.sup.rd Study: Electrophysiological Acute Study of Partial
Conduction Block
[0154] The goal of this study was to begin to explore the effects of HIFU
of various doses on the peripheral nerve, particularly the physiological
effects. It was hypothesized that a proportional relationship between
HIFU dose and the suppression of the nerve conduction in response to
electrical stimulation would be observed.
[0155] A single element, 3.5 MHz spherically curved HIFU transducer with a
diameter of 23 mm and a focal length of 35 mm was used in this study. Two
New Zealand white rabbits were anesthetized and their femoral nerves
exposed. Pairs of stimulating and recording electrodes were hooked to the
nerve in each rabbit at a distance of approximately 1.0 cm apart. The
proximal stimulating electrode pair was connected to a Grass stimulator
(S88), and the more distal recording pair was connected to an
oscilloscope. The stimulator was set to deliver square pulses of 9 V
amplitude and 6 ms duration at a rate of 3.8 pulses/s. Normal compound
nerve action potentials (CNAP) were evoked at this same rate.
[0156] Continuous wave HIFU of increasing dose (increasing power levels at
consistent duration of 5 seconds) was then applied to the nerve (between
the two pairs of electrodes). The transducer was held stationary for
durations of 5 seconds at each dose to allow a lesion to form. The
transducer was coupled to the nerve using a water-filled plastic conical
housing attachment as shown in FIG. 17. As indicated in this Figure, a
probe 201 including the above both transducer includes a water filled
plastic cone 203 to serve acoustic coupling. The tip of plastic cone 203
was applied directly to nerve 82a so that HIFU was focused just beyond
the tip of the plastic cone, thereby generating a lesion 205. The
electrical power was recorded for each application of HIFU, and the
corresponding CNAPs were recorded, and the waveforms were saved.
[0157] An upper portion of FIG. 18 (marked A) graphically illustrates the
CNAP signal before HIFU application, while a lower portion of FIG. 18
(marked B) graphically illustrates the CNAP signals corresponding to
application of HIFU of 7200 J/cm.sup.2. FIG. 19 shows the suppression of
the signal amplitude as HIFU of increasing dose was applied. HIFU
application produced suppression of the signal. As the dose increased,
the suppression was more pronounced (a maximum decrease of amplitude by
87%). The nerve appeared damaged and discolored after HIFU treatments at
doses of 6250 J/cm.sup.2 and above. The lesions corresponding to the HIFU
application approximated the cross section of the nerves; however, the
focal size of the HIFU beam did not allow equal distribution of energy
across the entire nerve. It is important to note that the signal was not
completely suppressed even after application of HIFU at higher doses.
This remaining signal still enabled generation of a force response,
albeit a weakened response. This result is indicative of a partial
conduction block. Further studies using rats as the annual model are
planned to verify these results. Rather than steadily increasing the HIFU
dose applied to a single nerve, future studies will apply different doses
of HIFU to different nerves so that effects can be better correlated with
dose.
[0158] 4.sup.th Study: Functional Investigation Acute Study of Partial
Conduction Block
[0159] The purpose of this study was to investigate the effects of
different doses of HIFU on the rabbit sciatic nerve, particularly the
force response of the plantarflexion muscles in response to stimulation
of the nerve. It was hypothesized that higher doses of HIFU would lead to
a greater suppression of the force response to electrical stimulation.
[0160] The ultrasound image-guided HIFU device used in the 1.sup.st and
2.sup.nd studies described above was also employed in the 4.sup.th study.
The procedure used in this study was identical to that described in the
1.sup.st study, except that the HIFU transducer was held stationary
during treatment, rather than being scanned across the nerve.
Furthermore, the voltage threshold stimulus to produce a force response
of the plantarflexion muscles was determined as a function of HIFU dose.
The sciatic nerves of this rabbits (six nerves) were treated.
[0161] For all rabbits, as the dose of HIFU application was increased (by
increasing the duration of HIFU application), the voltage threshold for
the stimulation of plantarflexion muscle contraction (to approximately
the same force level) also increased to a maximum of 100-300%. These
results, graphically illustrated in FIG. 20, represent the response of
one nerve, suggest a partial conduction block, since a much greater
stimulus voltage was required for the desired muscle contraction.
Additionally, the maximum force response of the plantarflexion muscles
both before and after HIFU application was measured. The force was
weakened after HIFU application, but unlike in the 1.sup.st study
discussed above, the muscle response was not completely suppressed. Upon
exposure of the nerve, the force response was measured when applying
stimulation directly to the nerve, both proximal and distal to the site
of HIFU treatment. For all six legs, the force response to proximal
stimulation was lower than that from distal stimulation. The mean distal
and proximal responses are shown in FIG. 21. These results seem to
indicate a partial conduction block of the sciatic nerve. However, the
small number of nerves treated and the variance of treatment times do not
yield statistically significant results. These variable effects of HIFU
application on the functional behavior of the nerve complex suggest a
need for more thorough investigation of the range of axonal effects that
may result from variable HIFU exposure parameters. It appears that HIFU
is capable of producing both partial and complete conduction block of the
rabbit sciatic nerve.
[0162] 5.sup.th Study: Pig Electrophysiological Acute Study of Partial
Conduction Block
[0163] The purpose of this study was to continue investigating a range of
HIFU doses on the electrophysiological and functional properties of
peripheral nerves. The length of the pig femoral nerve allowed several
HIFU applications on each nerve.
[0164] Sections of both femoral nerves of one pig were treated with
5-second applications of HIFU. An intraoperative, 5.7 MHz HIFU transducer
with a titanium solid-cone applicator was used in this study. The same
direct-contact approach as shown in FIG. 17 was used, except with a
titanium applicator rather than a water-filled cone. The diagram in FIG.
22 shows the positions on one nerve where the HIFU treatments of various
doses were applied. 7500 J/cm.sup.2 was applied at location 207; 6250
J/cm.sup.2 was applied at location 209; 5000 J/cm.sup.2 was applied at
location 211; and 3750 J/cm.sup.2 was applied at location 213. FIG. 23
illustrates the HIFU induced lesions on one nerve using various doses of
HIFU.
[0165] The plot in FIG. 24 shows the average amplitude of the CNAPs that
were recorded from the nerves in response to electrical stimulation after
each HIFU treatment, normalized to the initial amplitude of CNAPs before
HIFU application. For both nerves, the amplitude of the action potentials
increased with the initial HIFU treatments and eventually decreased after
further applications at higher doses. For the left leg, additional 7500
J/cm.sup.2 treatments were applied to the nerve in an attempt to suppress
the signal further (total doses of 22,500 and 30,000 J/cm.sup.2). The
signal did begin to decrease, but did not completely disappear.
Additionally, the force response to electrical stimulation remained,
although it was weaker as the HIFU treatment progressed. Even when a
significant lesion was visible on the nerve, the force response and CNAPs
were not completely suppressed. Such behavior of the nerve is indicative
of a partial conduction block due to HIFU treatment. The variability of
the HIFU effects are likely due to the focal size of the HIFU beam
employed, which did not provide uniform distribution of energy across the
entire cross section of the nerve.
[0166] Preferred HIFU Therapy Device Designs Based on the Results of the
Empirical Studies
[0167] Based on the empirical studies, HIFU therapy probes to be utilized
to achieve permanent neural blockage will preferably be a HIFU transducer
whose focal cross-sectional area of the HIFU beam is sufficiently great
to enable equal distribution of the energy across an entire nerve being
treated. One design criteria to achieve this larger focal region will be
designing HIFU transducers to have medium focusing characteristics,
rather than the strong focusing characteristics. The HIFU transducer
having strong focusing characteristics that was used in the above
empirical studies provided a HIFU focus with a cross section no greater
than 1 mm, as shown in FIGS. 13A and 13B. Unless the cross section of the
nerve to be treated is much smaller than 1 mm, there may not be a
consistent dose received by different portions of the nerve. To develop a
HIFU transducer for targeting a specific nerve, the mean diameter and
depth of nerves from a variety of different test subjects will be
measured, to ensure that the HIFU transducers have sufficient focal
length. As noted above, gel couplers having different standoff
thicknesses can be used to obtain different depths of penetration into
tissue with fixed focal length HIFU transducers. The focal length of the
fixed focus to HIFU transducer is controlled by the radius of curvature
of the transducer. Based on anatomical studies for a specific neural
treatment site, the fixed focal length should be slightly greater than
the depth of the nerve, so that the fixed focus will reach the deep edge
of the nerve when a small standoff or gel coupling (.about.1 cm thick) is
disposed between the HIFU transducer and the tissue. Preferably the focal
region of the HIFU transducer designed to achieve a permanent conduction
block in a nerve will have a focal width larger than the nerve diameter
to enable the HIFU to completely encompass the nerve, as shown in FIG.
25. For a nerve diameter of 1-2 mm, a HIFU focal width of approximately 3
mm would be preferable. The following equation describes the relationship
between the parameters of the transducer and the focal width (w): 1 w =
2.44 ( l f D )
[0168] where l.sub.f is the focal length (radius of curvature), D is the
diameter, and .lambda. is the wavelength of the ultrasound beam. For
example, a 3 MHz transducer with a diameter of 3 cm and a focal length of
3 cm would have a theoretical focal width of 1.2 mm. By increasing the
ratio of the focal length to the diameter (F-number) or by decreasing the
frequency, the focal width will increase. A 1 MHz transducer with the
same F-number would have a theoretical focal width of 3.7 mm. It is
important to note that these theoretical values are typically larger than
the actual measured values. The most accurate values are those measured
from the pressure field of the HIFU beam, however theoretical values must
be used for initial construction of the device. It is also possible to
design an acoustic lens (typically aluminum) to attach to the face of the
transducer that could defocus the beam slightly to produce the larger
focal size. Specifying different frequencies focal widths, focal lengths,
diameters, and acoustic lenses, the resulting HIFU beam patterns will be
determined using both theoretical analysis and computer simulation. The
parameters of the HIFU transducer chosen will be those that produce the
most optimal beam pattern. Output intensities preferably will range from
about 50-2000 W/cm.sup.2.
[0169] Different neural targets will require HIFU transducers with
different focal lengths to reach the appropriate depth of the nerves into
the body. Different nerves, located in different regions of the body,
require different transducer characteristics. Another important design
consideration is that any therapy transducer and imaging transducer
employed exhibit in appropriate acoustic window, enabling ultrasound
imaging and HIFU to adequately reach the target neural structure without
disrupting other important anatomical structures, such as blood vessels.
Targeting areas that have small windows for the propagation of ultrasound
energy require both the HIFU and imaging probes to have small footprints
or beam dimensions. For the treatment of peripheral nerves, such as the
tibial or peroneal nerves, a preferred device will be able to image from
the side or back of the thigh and treat from the back of the thigh
(midway between hip and knee). There are areas where no major blood
vessels are located that could provide the safest treatment paths.
[0170] Two HIFU devices that have been proposed for the application of
HIFU therapy to the sciatic nerve of a rat are shown in FIGS. 25 and 26.
Each device includes a HIFU transducer designed to have a focal region
larger than the cross-sectional area of a sciatic nerve 227 of a rat 233,
to ensure that only a single application of HIFU is required to treat the
entire cross-sectional area of the nerve. FIG. 25 schematically
illustrates a device for the ultrasound image guided remote (i.e.,
transcutaneous) application of HIFU, including a HIFU transducer 227, an
imaging transducer 225, a frame 223 (for ensuring the spatial orientation
between the therapy transducer in the imaging transducer remains
unchanged once an icon corresponding to the focal region of the HIFU
transducer is introduced into an ultrasound image generated by the
imaging transducer), and a convex-shaped water standoff 231 (a
polyurethane membrane inflated with degassed water) attached to the face
of the transducer. Standoff 221 acoustically couples the HIFU transducer
to the lateral hamstring muscle and can be inflated to a desired height
to enable positioning of the focus on the nerve without having to
reposition the HIFU therapy probe (which is coupled to the frame). A
constant flow of water through the standoff enables cooling of the
transducer as well. Imaging transducer 225 can be implemented using a
high-resolution imaging probe (preferably CL10-5, Philips HDI-1000.TM.),
so that the HIFU focus will be in the image plane.
[0171] FIG. 26 schematically illustrates a HIFU device for the
direct-contact application of HIFU and includes HIFU transducer 211 and a
plastic cone 235. Cone 235 is filled with degassed water and is attached
to the face of the transducer to acoustically couple the HIFU transducer
directly to the target (which requires an incision to enable access to
the nerve). Cone 235 extends along the HIFU beam path to the focus so
that the focal zone is just beyond the tip of the cone, which enables
visual guidance of the HIFU treatment to the nerve. Several different
types of conic attachments can be used for direct contact HIFU therapy of
neural structures. Hydrogel cones, aluminum cones, water filled cones,
and titanium cones can be beneficially employed.
[0172] Significantly, focal region 229 provided by HIFU transducer 211 is
larger than the cross-sectional area of the nerve to the HIFU transducer
has been designed to treat. As a result, energizing the HIFU transducer
will produce a lesion larger in cross-sectional area than the nerve, so
that the nerve can be completely blocked with only a single application
of HIFU.
[0173] FIG. 27 schematically illustrates a HIFU therapy probe 237
specifically designed to treat a neural structure 249. Probe 237 includes
a HIFU transducer 241 that has been specifically designed to have a focal
region 247 larger in size than a cross-sectional area of neural structure
249. A power lead 239 electrically couples probe 237 to a power supply
(not shown). A standoff 243 acoustically couples HIFU transducer 241 to a
patients dermal layer 76. As discussed above, standoff 243 can be
implemented using a fluid-filled sack or by hydrogel coupling.
Manipulating a volume of fluid in standoff 243 when the standoff is
implemented as a fluid filled sack will enable focal region 247 to be
moved relative to neural structure 249 without requiring probe 237 to be
moved. Also as noted above, when standoff 243 is implemented as a
hydrogel coupling, hydrogel couplings of different sizes can be used to
vary the depth to which focal region 247 penetrates beyond dermal layer
76. While not specifically shown, it should be understood that probe 237
is preferably synchronized to an ultrasound imaging probe to achieve
ultrasound image guided HIFU therapy of neural structures.
[0174] While targeting in the empirical studies was achieved using a frame
to couple the imaging transducer and the ultrasound therapy transducer
together, and using a tissue-mimicking phantom gel to introduce an icon
(via a transparent overlay) representing the focal region of the HIFU
transducer into an image generated by the imaging transducer, as noted
above, other techniques can be employed. Other embodiments of the
invention might instead incorporate tracking of the ultrasound focus
using software controlled by position sensors on the imaging and HIFU
transducers. Ultrasound contrast agents or specifically, labeled
particles that bind to substances in the nerve can improve its initial
detection. The incorporation of 3D ultrasound imaging into such
embodiments will also improve the detection of the nerve complex and the
estimation of its volume to plan a more localized and effective HIFU
treatment. These improvements will enable individuals with relatively
little experience in the sonography of nerve structure to identify and
treat it.
[0175] Embodiments that enable a variable depth of focusing into the
patient can be beneficially employed. These embodiments will use coupling
methods employing variable volume fluid coupling medium (unlike the stiff
polyacrylamide gel) to enable dynamic adjustment of the HIFU transducer
with this medium. Alternatively, a HIFU array will enable electronic
focusing at a range of depths, providing a more localized HIFU treatment
to a nerve or other structure of interest without affecting much of the
adjacent tissue. For areas near sensitive tissue, such as blood vessels
or the spinal cord, extremely localized treatment is important to prevent
adverse effects.
[0176] Clinical Applications
[0177] As noted above, HIFU holds promise as a more cost-effective, lower
risk treatment for severe spasticity. Higher HIFU intensities appear to
completely block the nerve conduction, but intermediate intensities are
likely to cause only minimal suppression. Either case has clinical
application. A permanent block would provide an effect essentially like
severing the nerve, so that the spasticity or pain associated with a
specific nerve would be eliminated indefinitely. Any voluntary function
provided by this nerve would also be eliminated. Therefore, this effect
would be useful primarily for patients who no longer have voluntary
function, such as those with a complete transection of the spinal cord,
yet having spasticity and/or pain. Non-permanent blocks achieved with
lower dosages can be used to reduce the spasticity without permanently
hindering the voluntary function of a patient. Patients with cerebral
palsy, multiple sclerosis, incomplete spinal cord injury, and traumatic
nerve injury often retain voluntary function yet it is limited by the
presence of spasticity. Partial or temporary suppression of conduction in
the overexcited nerves could lessen the spasticity and possibly improve
the mobility of the patients.
[0178] The empirical studies targeted and treated peripheral nerves that
are often part of an overactive reflex between motor synapses in the
muscle and signals generated in the brain or spinal cord. An alternative
method to suppress this overactive activity is to apply HIFU treatment
directly to the nerve roots as they extend from the spinal cord. These
are very sensitive structures that are in close proximity to the spinal
cord, and a more precise localized method of HIFU treatment, such as
graded neurolysis, would be best suited for this procedure.
[0179] With respect to using HIFU as a treatment for pain, many clinical
problems cause individuals to experience pain generated in sensory
nerves. These nerves are often unnecessary for normal sensory functions,
such as those associated with tumors. Pain is often associated with
cancer. For example, pain associated with bone cancer is typically severe
and is known to involve a unique sensitization of the nervous system.
Rather than taking heavy doses of pain medications (i.e., morphine) that
cause nausea and other undesired side effects, the HIFU therapy of
sensory nerves can provide a non-invasive method to alleviate the pain
associated with sensory nerves. By destroying the nerves that create the
pain, the patient's quality of life is improved without drugs. Thus, one
aspect of the present invention is to provide a palliative treatment for
cancer.
[0180] Ultrasound guided HIFU can also be used as treatment of
musculoskeletal injuries, by targeting musculoskeletal structures rather
than nerves. Ultrasound guided HIFU therapy can be used to detect and
treat musculoskeletal injuries including tears in tendons, ligaments, and
cartilage. Ultrasound's use in injuries of the musculoskeletal system has
been more limited to diffuse ultrasound of physical therapy range
intensities (1-10 W/cm3).
[0181] One application of the present invention would be treating a nerve
having a larger cross-sectional area larger than the focal region of the
HIFU traducer by scanning the focal region from one edge of the neural
structure to the opposite edge (see FIG. 9C). This scanning technique can
be used to achieve relatively large volumes of affected tissue relatively
quickly (for example, the empirical studies employed a scanning rate of
about 0.5-0.6 mm/second with HIFU durations of about 36 seconds).
Previous techniques for inducing necrosis in tumors via HIFU have
required relatively long treatment times. Using this scanning technique,
even large sized tumors could be treated in a matter of seconds or
minutes. Prior art methods of using HIFU for tumor treatment report
treatment times of several minutes to hours to achieve large volumes
(greater than 1 cubic centimeter) of necrosis, because they rely on the
formation of several individual lesions approximately 1 mm.times.1 cm
stacked next to each other. The duration of HIFU to form each lesion may
be 5 seconds, but the time between each lesion formation is about 2
minutes. This protocol leads to very long treatment times. The scanning
method of the present invention can significantly decrease the time that
patients have to undergo a HIFU procedure to achieve a comparable result.
[0182] Although the present invention has been described in connection
with the preferred form of practicing it and modifications thereto, those
of ordinary skill in the art will understand that many other
modifications can be made to the present invention 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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