U.S. patent application number 17/746354 was filed with the patent office on 2022-09-08 for enhanced needle array and therapies for tumor ablation.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. The applicant listed for this patent is BOSTON SCIENTIFIC SCIMED, INC.. Invention is credited to HONG CAO, MATTHEW RYAN DEWITT, BRUCE R. FORSYTH, TIMOTHY A. OSTROOT.
Application Number | 20220280228 17/746354 |
Document ID | / |
Family ID | 1000006351442 |
Filed Date | 2022-09-08 |
United States Patent
Application |
20220280228 |
Kind Code |
A1 |
FORSYTH; BRUCE R. ; et
al. |
September 8, 2022 |
ENHANCED NEEDLE ARRAY AND THERAPIES FOR TUMOR ABLATION
Abstract
Novel and versatile apparatuses for delivering one or more of
thermal ablation and irreversible electroporation therapies to
target tissue. In some examples, a device includes at its distal
end a plurality of electrodes that can be advanced or retracted to
pierce patient tissue, with a variable position and size shaft
electrode provided near the distal end of the device to allow
manipulation of therapy fields to achieve various tissue
destruction field shapes. A number of method of use examples are
described as well.
Inventors: |
FORSYTH; BRUCE R.; (HANOVER,
MN) ; DEWITT; MATTHEW RYAN; (CHARLOTTESVILLE, VA)
; CAO; HONG; (MAPLE GROVE, MN) ; OSTROOT; TIMOTHY
A.; (COKATO, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BOSTON SCIENTIFIC SCIMED, INC. |
Maple Grove |
MN |
US |
|
|
Assignee: |
BOSTON SCIENTIFIC SCIMED,
INC.
Maple Grove
MN
|
Family ID: |
1000006351442 |
Appl. No.: |
17/746354 |
Filed: |
May 17, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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16254879 |
Jan 23, 2019 |
11364070 |
|
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17746354 |
|
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62620873 |
Jan 23, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2018/00029
20130101; A61B 2018/1475 20130101; A61B 2018/00547 20130101; A61B
18/1482 20130101; A61B 2018/00577 20130101; A61M 5/158 20130101;
A61B 2018/00107 20130101; A61B 2018/143 20130101; A61N 1/327
20130101; A61B 2018/00178 20130101; A61B 2018/00613 20130101; A61B
18/1477 20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14; A61N 1/32 20060101 A61N001/32; A61M 5/158 20060101
A61M005/158 |
Claims
1. A system for destruction of tissue comprising: a cannula having
a proximal end and a distal end and containing a plurality of
tissue penetrating elongate electrodes therein, the electrodes
being extendible beyond the distal end of the cannula; an inner
shaft formed from a dielectric polymer disposed over the cannula
and carrying a shaft electrode formed from a conductive metal, the
shaft electrode disposed near the distal end of the cannula at a
spacing distance from the distal end of the cannula, wherein the
inner shaft is moveable relative to the cannula to adjust the
spacing distance; electrical connectors including at least one
electrical connector electrically coupled to at least one of the
elongate electrodes, and at least one electrical connector
electrically coupled to the shaft electrode; and a sheath movable
relative to the shaft electrode and inner shaft and adapted to
control exposure of the shaft electrode to patient tissue.
2. The system of claim 1 wherein the cannula includes a fluid
delivery lumen and a distal portion of the cannula comprises one or
more apertures for fluid infusion, further wherein the one or more
apertures for fluid infusion are located on a first side of the
cannula, and the shaft electrode is located on a second side of the
cannula, such that the apertures and shaft electrode occupy
opposing sides of the cannula within a single axial region of the
cannula.
3. The system of claim 1 wherein at least one of the tissue
penetrating elongate electrodes comprises a dielectric coating on a
first side of a portion thereof.
4. The system of claim 1 wherein the plurality of tissue
penetrating electrodes includes at least a first tissue penetrating
electrode having a first electrical connection and a second tissue
penetrating electrode having a second electrical connection,
wherein the first and second electrical connections are separately
addressable.
5. The system of claim 4 wherein the sheath is adapted to cover a
radial portion of the shaft electrode to facilitate directional
control of an output electrical field between a selected one or
more of the first and second tissue penetrating electrodes and a
portion of the shaft electrode.
6. The system of claim 1 wherein the plurality of tissue
penetrating electrodes includes at least a first tissue penetrating
electrode having a first mechanical coupling and a second tissue
penetrating electrode having a second mechanical coupling, wherein
the first and second mechanical couplings are separately actuatable
to allow the first and second tissue penetrating electrodes to be
advanced independent of one another.
7. The system of claim 1 wherein the shaft electrode is cylindrical
and extends around the inner shaft.
8. The system of claim 1 wherein the sheath covers the inner
shaft.
9. The system of claim 1 wherein the shaft electrode has a proximal
end on the inner shaft and a distal end on the inner shaft, and the
sheath covers the inner shaft and sheath.
10. A system for destruction of tissue comprising: a cannula having
a proximal end and a distal end and containing a plurality of
tissue penetrating elongate electrodes therein, the electrodes
being extendible beyond the distal end of the cannula; an inner
shaft formed from a dielectric polymer disposed over the cannula
and carrying a shaft electrode formed from a conductive metal, the
shaft electrode disposed near the distal end of the cannula, the
inner shaft being moveable relative to the cannula to enable a
distance from the shaft electrode to the distal end of the cannula
to be adjustable; and a plurality of electrical connectors
including at least one electrical connector electrically coupled to
at least one of the elongate electrodes, and at least one
electrical connector electrically coupled to the shaft electrode;
wherein the shaft electrode is disposed at a spacing distance from
the distal end of the cannula, wherein the spacing distance is
adjustable.
11. The system of claim 10 wherein the plurality of tissue
penetrating elongate electrodes includes at least a first tissue
penetrating electrode having a first mechanical coupling and a
second tissue penetrating electrode having a second mechanical
coupling, wherein the first and second mechanical couplings are
separately actuatable to allow the first and second tissue
penetrating electrodes to be advanced independent of one
another.
12. The system of claim 10 wherein the cannula includes a fluid
delivery lumen and a distal portion of the cannula comprises one or
more apertures for fluid infusion, further wherein the one or more
apertures for fluid infusion are located on a first side of the
cannula, and the shaft electrode is located on a second side of the
cannula, such that the apertures and shaft electrode occupy
opposing sides of the cannula within a single axial region of the
cannula.
13. The system of claim 10 wherein at least one of the tissue
penetrating elongate electrodes comprises a dielectric coating on a
first side of a portion thereof.
14. The system of claim 10 wherein the plurality of tissue
penetrating electrodes includes at least a first tissue penetrating
electrode having a first electrical connection and a second tissue
penetrating electrode having a second electrical connection,
wherein the first and second electrical connections are separately
addressable.
15. The system of claim 14 wherein the sheath is adapted to cover a
radial portion of the shaft electrode to facilitate directional
control of an output electrical field between a selected one or
more of the first and second tissue penetrating electrodes and a
portion of the shaft electrode.
16. The system of claim 10 wherein the plurality of tissue
penetrating electrodes includes at least a first tissue penetrating
electrode having a first mechanical coupling and a second tissue
penetrating electrode having a second mechanical coupling, wherein
the first and second mechanical couplings are separately actuatable
to allow the first and second tissue penetrating electrodes to be
advanced independent of one another.
17. The system of claim 10 wherein the shaft electrode is
cylindrical and extends around the inner shaft.
18. The system of claim 10 wherein the sheath covers the inner
shaft.
19. The system of claim 10 wherein the shaft electrode has a
proximal end on the inner shaft and a distal end on the inner
shaft, and the sheath covers the inner shaft and sheath.
20. A system for destruction of tissue comprising: a cannula having
a proximal end and a distal end and containing a plurality of
tissue penetrating elongate electrodes therein, the electrodes
being extendible beyond the distal end of the cannula; moveable
electrode means disposed over the cannula, the moveable electrode
means being moveable relative to the cannula to enable a distance
from the moveable electrode means to the distal end of the cannula
to be adjustable; a plurality of electrical connectors including at
least one electrical connector electrically coupled to at least one
of the elongate electrodes, and at least one electrical connector
electrically coupled to the shaft electrode; cover means for
adjustably covering all, a portion of, or none of the moveable
electrode means.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 16/254,879, filed Jan. 23, 2019, which claims
the benefit of and priority to US Provisional Patent Application
No. 62/620,873, filed Jan. 23, 2018, each titled ENHANCED NEEDLE
ARRAY AND THERAPIES FOR TUMOR ABLATION, the disclosures of which
are incorporated herein by reference.
BACKGROUND
[0002] A variety of therapy modalities have been researched and
used for destruction of tumors in the body. Cryoablation and
thermal ablation use cold and heat, for example, to destroy tissue.
Thermal ablation can be effective and very useful, but has proven
difficult to control, particularly in spatial terms. Thermal
ablation is not particularly selective in terms of which tissue it
will destroy, hampering post-therapy recovery as useful tissue
structure such as vasculature is destroyed along with targeted
tissue.
[0003] Electroporation has been used in various forms to treat
targeted tissue. Electroporation operates by applying electrical
pulses that cause cell membranes to alter, creating pores. Above a
first threshold electrical field, the cell membranes begin to form
pores. Above a second, higher threshold field, those pores can
become irreversible, leading to cell death. Thus, there are two
forms of electroporation, reversible electroporation and
irreversible electroporation (IRE). Reversible electroporation can
be used in conjunction with the infusion of drugs or other agents
which pass through reversibly created pores, where the infused
drug/agent then causes selective cell death, however, such added
agents can have systemic side effects on the patient.
[0004] New and alternative devices and methods of applying therapy
are desired which can combine the beneficial uses of IRE and
thermal ablation, as well as reversible electroporation.
OVERVIEW
[0005] The present inventors have recognized, among other things,
that a problem to be solved is a need for new devices that provide
greater physician control over the shaping and use of electrical
pulses for IRE and thermal ablation. In some examples, the present
invention provides devices that allow a physician to manipulate the
exposed electrode surfaces on a tissue destruction apparatus. The
present inventors have also recognized that it may be desirable for
a physician to be able to combine IRE and one or more additional
therapies such as thermal ablation and/or ablation through (or
augmented by) the injection of fluids containing drugs, biologics,
or other substances.
[0006] A first illustrative, non-limiting example takes the form of
a system for destruction of tissue comprising a cannula having a
proximal end and a distal end and containing a plurality of tissue
penetrating elongate electrodes therein, the electrodes being
extendible beyond the distal end of the cannula; a shaft electrode
disposed near the distal end of the cannula; electrical connectors
including at least one electrical connector electrically coupled to
at least one of the elongate electrodes, and at least one
electrical connector electrically coupled to the shaft electrode;
and a sheath movable relative to the shaft electrode and adapted to
control exposure of the shaft electrode to patient tissue.
[0007] Additionally or alternatively, the shaft electrode has a
length, and the sheath may be moveable to control how much of the
length of the shaft electrode is exposed.
[0008] Additionally or alternatively, the shaft electrode extends
radially about a portion of the cannula, and the sheath may be
moveable to control radial exposure of the shaft electrode.
[0009] Additionally or alternatively, the cannula may include a
fluid delivery lumen and a distal portion of the cannula may
comprise one or more apertures for fluid infusion. In some
examples, the one or more apertures for fluid infusion are located
on a first side of the cannula, and the shaft electrode is located
on a second side of the cannula, such that the apertures and shaft
electrode occupy opposing sides of the cannula within a single
axial region of the cannula.
[0010] Additionally or alternatively, at least one of the tissue
penetrating elongate electrodes may comprise a fluid delivery lumen
therethrough.
[0011] Additionally or alternatively, at least one of the tissue
penetrating elongate electrodes may comprise a dielectric coating
on a first side of a portion thereof.
[0012] Additionally or alternatively, the shaft electrode may be
disposed at a spacing distance from the distal end of the cannula,
wherein the spacing distance is adjustable.
[0013] Additionally or alternatively, the shaft electrode may be
cylindrical and extend the entire way around the cannula.
[0014] Additionally or alternatively, wherein the shaft electrode
may extend about only a portion of the cannula.
[0015] Additionally or alternatively, the plurality of tissue
penetrating electrodes may include at least a first tissue
penetrating electrode having a first electrical connection and a
second tissue penetrating electrode having a second electrical
connection, wherein the first and second electrical connections are
separately addressable.
[0016] Additionally or alternatively, the sheath may be adapted to
cover a radial portion of the shaft electrode to facilitate
directional control of an output electrical field between a
selected one or more of the first and second tissue penetrating
electrodes and a portion of the shaft electrode.
[0017] Additionally or alternatively, the plurality of tissue
penetrating electrodes may include at least a first tissue
penetrating electrode having a first mechanical coupling and a
second tissue penetrating electrode having a second mechanical
coupling, wherein the first and second mechanical couplings are
separately actuatable to allow the first and second tissue
penetrating electrodes to be advanced independent of one
another.
[0018] A second illustrative, non-limiting example takes the form
of a system for destruction of tissue comprising: a cannula having
a proximal end and a distal end and containing a plurality of
tissue penetrating elongate electrodes therein, the electrodes
being extendible beyond the distal end of the cannula; a shaft
electrode disposed near the distal end of the cannula; and a
plurality of electrical connectors including at least one
electrical connector electrically coupled to at least one of the
elongate electrodes, and at least one electrical connector
electrically coupled to the shaft electrode; wherein the shaft
electrode is disposed at a spacing distance from the distal end of
the cannula, wherein the spacing distance is adjustable.
[0019] Additionally or alternatively, the plurality of tissue
penetrating electrodes may include at least a first tissue
penetrating electrode having a first mechanical coupling and a
second tissue penetrating electrode having a second mechanical
coupling, wherein the first and second mechanical couplings are
separately actuatable to allow the first and second tissue
penetrating electrodes to be advanced independent of one
another.
[0020] A third illustrative, non-limiting example takes the form of
a method of ablating a tissue region using a cannula having a shaft
with proximal and distal ends, and one or more tissue penetrating
electrodes passing through the shaft and moveable relative to the
shaft, the method comprising: inserting the cannula to place the
distal end of the shaft at a desired location near a target tissue;
advancing at least one of the one or more tissue penetrating
electrodes beyond the distal end of the shaft to pierce tissue;
delivering a first waveform adapted to cause thermal ablation in a
first region relatively nearer to the at least one tissue
penetrating electrode; delivering a second waveform adapted to
cause irreversible electroporation in a second region relatively
more distant from the at least one tissue penetrating
electrode.
[0021] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may have a shaft electrode thereon
and the cannula comprises a sheath adapted to be moveable relative
to the shaft to cover or uncover all or portions of the shaft
electrode, and the method further comprises manipulating the sheath
to expose a first area of the shaft electrode while the first
waveform is delivered, and manipulating the sheath to expose a
second area of the shaft electrode while the second waveform is
delivered, wherein the first and second areas are different from
one another, further wherein each of the first and second waveforms
are delivered using at least one of the at least one tissue
penetrating electrodes and the shaft electrode as opposing poles
for an electrical output.
[0022] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may comprise a fluid infusion lumen
having an opening near the distal end thereof, and the method
further comprises infusing a fluid through the fluid infusion lumen
prior to delivering the first waveform, the fluid adapted to dampen
a thermal effect of the first waveform for a first volume of
tissue.
[0023] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may comprise a fluid infusion lumen
having an opening near the distal end thereof, and the method
further comprises infusing a fluid through the fluid infusion lumen
prior to delivering the first waveform, the fluid adapted to
enhance a thermal effect of the first waveform for a first volume
of tissue.
[0024] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may comprise a fluid infusion lumen
having an opening near the distal end thereof, and the method
further comprises infusing a fluid through the fluid infusion lumen
prior to delivering the second waveform, the fluid adapted to
enhance the electrical effect of the second waveform.
[0025] Additionally or alternatively to the third illustrative,
non-limiting example, the step of delivering the first waveform may
be performed prior to delivering the second waveform.
[0026] Additionally or alternatively to the third illustrative,
non-limiting example, the step of delivering the first waveform may
be performed after delivering the second waveform.
[0027] Additionally or alternatively to the third illustrative,
non-limiting example, the first and second waveforms may be each
delivered repeatedly by alternating between the first and second
waveforms.
[0028] Additionally or alternatively to the third illustrative,
non-limiting example, the first waveform may be delivered using a
first of the at least one tissue penetrating electrodes, and the
second waveform may be delivered using a second of the at least one
tissue penetrating electrodes.
[0029] Additionally or alternatively to the third illustrative,
non-limiting example, the first waveform may be delivered
repeatedly in a first therapy set, and the second waveform may be
delivered repeatedly in a second waveform set.
[0030] Additionally or alternatively to the third illustrative,
non-limiting example, the method may further comprise repositioning
the electrodes after the first therapy set and before the second
therapy set.
[0031] Additionally or alternatively to the third illustrative,
non-limiting example, at least the second waveform may induce each
of reversible and irreversible electroporation, and the method
comprises infusing a fluid adapted to cause cell death to a region
affected by the reversible electroporation.
[0032] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may have a shaft electrode thereon
and the cannula may comprise a sheath adapted to be moveable
relative to the shaft to cover or uncover all or portions of the
shaft electrode, wherein the method further comprises applying a
grounding pad to the patient, wherein the first waveform is
delivered using the grounding pad and at least one of the at least
one tissue penetrating electrodes as the electrodes for therapy
delivery, and the second waveform is delivered using the shaft
electrode and at least one of the at least one tissue penetrating
electrodes.
[0033] Additionally or alternatively to the third illustrative,
non-limiting example, the method may further comprise manipulating
the sheath relative to the shaft electrode to expose or cover the
shaft electrode between delivery of the first and second
waveforms.
[0034] Additionally or alternatively to the third illustrative,
non-limiting example, the shaft may have a shaft electrode thereon
and the cannula may comprise a sheath adapted to be moveable
relative to the shaft to cover or uncover all or portions of the
shaft electrode, and the method further comprises applying a
grounding pad to the patient, wherein the first waveform is
delivered using the shaft electrode and at least one of the at
least one tissue penetrating electrodes, and the second waveform is
delivered using the grounding pad and at least one of the at least
one tissue penetrating electrodes as the electrodes for therapy
delivery.
[0035] Additionally or alternatively to the third illustrative,
non-limiting example, the method may further comprise manipulating
the sheath relative to the shaft electrode to expose or cover the
shaft electrode between delivery of the first and second
waveforms.
[0036] A fourth illustrative, non-limiting example takes the form
of a method of ablating a tissue region using a cannula having a
shaft with proximal and distal ends, and one or more tissue
penetrating electrodes passing through the shaft and moveable
relative to the shaft, the method comprising: inserting the cannula
to place the distal end of the shaft at a desired location near a
target tissue; advancing at least one of the one or more tissue
penetrating electrodes beyond the distal end of the shaft to pierce
tissue; and delivering a waveform adapted to cause thermal ablation
in a first region relatively nearer to the at least one tissue
penetrating electrode and irreversible electroporation in a second
region relatively more distant from the at least one tissue
penetrating electrode.
[0037] Additionally or alternatively to the fourth illustrative,
non-limiting example, the step of delivering a waveform induces
reversible electroporation in a third region and the method may
further comprise infusing a fluid adapted to cause cell death to a
region affected by the reversible electroporation.
[0038] Each of these non-limiting examples can stand on its own, or
can be combined in various permutations or combinations with one or
more of the other examples.
[0039] This overview is intended to provide an introduction to the
subject matter of the present patent application. It is not
intended to provide an exclusive or exhaustive explanation of the
invention. The detailed description is included to provide further
information about the present patent application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] In the drawings, which are not necessarily drawn to scale,
like numerals may describe similar components in different views.
Like numerals having different letter suffixes may represent
different instances of similar components. The drawings illustrate
generally, by way of example, but not by way of limitation, various
embodiments discussed in the present document.
[0041] FIG. 1 shows an approximation of different therapy
modalities associated with a combination of electrical field
strength and pulse duration;
[0042] FIG. 2 shows a prior art "Leveen" needle;
[0043] FIGS. 3-7 show illustrative example therapy apparatuses;
[0044] FIGS. 8-11 show an illustrative therapy apparatus with
manipulation of an electrode;
[0045] FIGS. 12-13 show illustrative effects of different therapy
modes with different electrode configurations;
[0046] FIGS. 14A-14B show a tumor being treated by an illustrative
device;
[0047] FIG. 15 is a block flow diagram illustrating various
examples; and
[0048] FIGS. 16-20 show a number of therapy sequences.
DETAILED DESCRIPTION
[0049] FIG. 1 shows an approximation of different biophysical
responses dependent on the amplitude-time relationship of delivered
electrical pulses. The thresholds between cellular responses (10,
20, 30) operate generally as a function of the applied field
strength and pulse duration. Below a first threshold 10, no effect
occurs; between the first threshold 10 and a second threshold 20,
reversible electroporation occurs. Above the second threshold 20,
and below a third threshold 30, primarily irreversible
electroporation (IRE) occurs. Above a third threshold 30, the
effects begin to be primarily thermal. Thus, for example, at a
given field strength and duration there may be no effect (location
12), and extending the duration of the field application can yield
reversible electroporation (location 22), irreversible
electroporation (location 32), and thermal ablation (location
40).
[0050] As described in U.S. Pat. No. 6,010,613, a transmembrane
potential in the range of about one volt is needed to cause
reversible electroporation, however the relationship between pulse
parameters such as timing and duration and the transmembrane
potential required for reversible electroporation remains an
actively investigated subject. The required field may vary
depending on characteristics of the cells to be treated. At a macro
level, reversible electroporation requires a voltage in the level
of hundreds of volts per centimeter, with irreversible
electroporation requiring a still higher voltage. As an example,
when considering in vivo electroporation of liver tissue, the
reversible electroporation threshold field strength may be about
360 V/cm, and the irreversible electroporation threshold field
strength may be about 680 V/cm, as described in U.S. Pat. No.
8,048,067. Generally speaking, a plurality of individual pulses are
delivered to obtain such effects across the majority of treated
tissue; for example, 2, 4, 8, 16, or more pulses may be
delivered.
[0051] The field for electroporation has typically been applied by
delivering a series of individual pulses each having a duration in
the range of tens to hundreds of microseconds. For example, U.S.
Pat. No. 8,048,067 describes a series of eight 100 microsecond
pulses delivered at 1 second intervals. The '067 patent describes
analysis and experiments performed to illustrate that the area
between lines 20 and 30 in FIG. 1 actually exists, and that a
non-thermal IRE method can be achieved.
[0052] The tissue membrane does not return instantaneously, from a
porated state. As a result, the application of pulses close
together in time can have a cumulative effect as described, for
example, in U.S. Pat. No. 8,926,606. In addition, a series of
pulses can be used to first porate a cell membrane and then move
large molecules through generated, reversible pores, as described
in US PG Patent App. Pub No. 2007/0025919.
[0053] While U.S. Pat. No. 8,048,067 discusses performing IRE
without thermal effects, and U.S. Pat. No. 8,926,606 discusses
achieving IRE without delivering pulses that exceed line 20 of FIG.
1 and using cumulative effects of closely spaced pulses, the
present invention in some examples is directed at the use of
multiple regions of FIG. 1. For example, a single device using
either one output circuit having programmable or reconfigurable
features, or a single device having a plurality of output circuits
tuned to different regions (in terms of voltage, pulse width, or
other parameters), may be used to purposefully deliver both thermal
and non-thermal ablation therapies. Tuning and tailoring the
outputs, including the use of different electrode combinations and
therapy parameters, may allow thermal ablation in one spatial
region and IRE or other ablation in a second spatial region. Thus,
some examples are directed to new and distinct devices that can be
manipulated and optimized for delivering therapy within any of the
regions shown in FIG. 1. Still further examples combine these
concepts to provide a device suited to delivering multiple and
distinct therapies such as by achieving IRE pulses in one therapy
regimen with a first device configuration, and achieving thermal
effects in another therapy regimen using a second device
configuration. Additional combinations and details are discussed
below.
[0054] FIG. 2 shows a prior art "Leveen" needle. As described in
U.S. Pat. No. 5,855,576, the device comprises an insertable portion
100 having a shaft 104 that extends to a plurality of tissue
piercing electrodes 102 that can be extended or retracted once a
target tissue 112 of a patient 110 is accessed. The proximal end of
the apparatus is coupled by an electrical connection 106 to a power
supply 108, which can be used to supply RF energy. Typically, the
Leveen needle would be used to deliver thermal ablation to the
target tissue. As described in the '576 patent, a return electrode
in the form of a plate or plates may be provided on the patient's
skin, a return electrode could be provided as another tissue
piercing electrode, or a return electrode may be provided on the
shaft 104 near its distal end, proximal of the tissue piercing
electrodes 102. Enhancements on the original design can be found,
for example, in U.S. Pat. No. 6,638,277, which discusses
independent actuation of the tissue piercing electrodes 102, both
in terms of movement of the electrodes as well as separately
electrically activating individual ones of the electrodes. The U.S.
Pat. Nos. 5,855,576 and 6,638,277 patents are incorporated herein
by reference.
[0055] FIGS. 3-7 show illustrative example therapy apparatuses.
Referring now to FIG. 3, a device 200 is shown having a main shaft
portion 210, with a moveable insulative sheath 220 coaxially
disposed therein. The sheath 220 partly surrounds an inner shaft
230 that carries a return electrode 232, which may be referred to
herein also as a shaft electrode 232. The inner shaft surrounds a
needle carrier 240 that has the tissue piercing electrodes 242
contained therein. The tissue piercing electrodes 242 are
extendible beyond the distal end of the device 200, and
particularly beyond the distal end of the inner shaft 230. Aside
from the electrodes 232, 242, the remaining elements that are
exposed to the patient's tissue are generally not conductive, being
formed, for example, of dielectric polymers; the electrodes may be
for example, titanium, stainless steel, gold, or other conductive
metals, for example. Those skilled in the art will recognize
various materials that may be used in addition to those noted.
[0056] In use, the position of the return electrode 232 can be
adjusted relative to the distal tip 244 of the needle carrier 240
as indicated at 234, so as to affect the resulting electric field
distribution and corresponding tissue response. In some examples,
the distal tip 244 of the needle carrier 240 may be pointed or
sharpened to allow it to pierce into the targeted tissue prior to
advancement of the tissue piercing electrodes 242. The sheath 220
can be manipulated to advance or retract it relative to the return
electrode 232. In this example, therefore, the return electrode 232
can be covered by the sheath 220 and thereby insulated from tissue
to allow use in a unipolar mode, or may be partly covered by the
sheath 220 to limit the exposed surface area of the return
electrode 232. In addition, the distance between the return
electrode and the distal end 244 of the needle carrier 240 may be
manipulated as well.
[0057] FIG. 4 shows another example. Here the device or cannula 250
includes a moveable sheath 260 that can be advanced or retracted as
indicated at 262, as well as tissue piercing electrodes 280 which
are again configured to be advanced and/or retracted beyond the
distal end of the device or cannula 250 and in particular the
needle carrier or inner shaft 270. The needle carrier or inner
shaft 270 has a return electrode 272 (which may also be referred to
as a shaft electrode) thereon on one side, and one or more fluid
infusion apertures as shown at 274. The fluid infusion apertures
274 may be as shown, at about the same longitudinal location on the
inner shaft 270 as the shaft electrode 272, or may be distal and/or
proximal thereto, if desired. One or more lumens within the inner
shaft 270 can be used to deliver fluid to the fluid infusion
apertures 274. The shaft electrode 272 can be placed on one side of
the device for use in generally single sided lesion formation,
which is commonly used for example in prostate treatments where the
therapy catheter is introduced next to, rather than into, the
target tissue. If desired, one or more of the tissue piercing
electrodes 280 may include a fluid lumen therein to allow delivery
of a fluid through the tissue piercing electrodes 280. For example,
the tissue piercing electrodes may the take form of a hypotube.
[0058] The fluid infusion apertures may be used to deliver a fluid
that enhances the electrical conductivity of the surrounding tissue
in some examples. In other examples, a fluid may be infused that
contains a drug, macromolecules, biologic, or other substance which
will affect cell properties in one or more ways. For example,
macromolecules that disrupt cellular function may be injected, with
the intent being to have cells uptake the macromolecules while
porated to lead to cell death. In another example, a cationic
polymer may be injected, which may increase the susceptibility of
the cellular membrane to poration, as described in U.S. Provisional
Patent Application Ser. No. 62/585,849, titled IRREVERSIBLE
ELECTROPORATION THROUGH A COMBINATION OF SUBSTANCE INJECTION AND
ELECTRICAL FIELD APPLICATION.
[0059] In some examples, a fluid infusion may comprise saline, or
may include dextrose, each of which will affect the conductivity of
the surrounding tissue. For example, saline enhances conductivity
and dextrose reduces conductivity. In another example, a fluid may
be infused that will limit the scope of therapeutic effect of a
thermal or IRE therapy by, for example, cooling an area of tissue
or limiting current flow or electrical field propagation. For
example, biocompatible mineral oil may be used, as it would limit
electrical propagation by having non-conductive properties. A
glycol mixture at a low concentration may be used to provide a
combination of cooling and electrical resistance. In still another
alternative, distilled water may be infused, reducing ion
concentration, or a reverse osmosis or ion-exchange may be used.
For example, a therapy apparatus may have a membrane facilitating
reverse osmosis or ion exchange therethrough, reducing ion
concentration and thereby increasing localized resistance. A
cooling apparatus may be included, such as fluid pumping system,
vaporizer or other apparatus, such as in U.S. Pat. Nos. 6,428,534
and 7,850,681, the disclosures of which are incorporated herein by
reference), as cooling reduces ion mobility. At least with fluid
infusion examples, the delivery of such fluids can affect the ratio
of extracellular to intracellular conductivity and thereby change
the local electric field across a plasma membrane.
[0060] FIG. 5 shows another illustrative therapy apparatus. Here,
the device or cannula 300 has a moveable sheath 310 therein having
a window as indicated at 312. The sheath 310 in this example can be
moved longitudinally 314 as well as rotated 316 over the inner
shaft 320 having electrodes 322, 324 thereon, where the electrodes
322, 324 may be separately addressable if desired. Tissue
penetrating electrodes 326, 328 may again be configured to be
advanced or retracted, individually or as a group, as desired, and
may also be individually addressable electrodes for the device.
Thus, for example, the apparatus of FIG. 5 may allow various
combinations of electrodes for therapy delivery such as: [0061]
Between electrodes 322 and 324 [0062] Between electrode 322 and
either of electrodes 326, 328 [0063] Between electrode 324 and
either of electrodes 326, 328 [0064] Between electrodes 326 and 328
[0065] Between electrodes 322/324 held electrically in common and
electrodes 326/328 also electrically in common [0066] Using only a
portion of electrode 322, 324, or the union of electrodes 322, 324,
as covered at least partly by sheath 312, and one, the other, or
both of electrodes 326, 328 For example, during a first therapy
application, a union of the piercing electrodes 326, 328 may serve
as a pole opposed to a union of electrodes 322, 324, delivering an
IRE field in a series of pulses (such as, for example, 8 pulses of
100 microsecond duration at 800 volts per centimeter delivered at
about 1 Hz), followed by a second therapy application of thermal
ablation output directed to the inner shaft 320 using electrodes
322, 324 as opposing poles (for example, 8 pulses of 10 millisecond
duration at 800 volts per centimeter delivered at about 10 Hz).
Other pairings and sequences may be used.
[0067] Turning now to FIG. 6, another illustrative therapy
apparatus is shown. Here, the device or cannula 350 has a sheath
360 that may be manipulated relative to the inner shaft 370. The
inner shaft 370 carries a shaft electrode at 372 and has fluid
infusion apertures 374 that can be used to inject fluid 376. In
this example, the tissue piercing electrode array 380 (which may be
advanced or retracted individually or as a group, and which may be
electrically addressed individually or in pairs, groups, subgroups
or as an entire array) is further tailored to allow manipulation of
electrode surface area. For example, tissue piercing electrode 382
has a retractable insulative sheath 384 thereon, as does electrode
392. One of the tissue piercing electrodes has a sheath extending
over its entire length as indicated at 388, with the sheath 388
retractable as indicated at 386. Another of the tissue piercing
electrodes is itself retracted as shown at 390. The ability to
separately address and control the exposed surface area of at least
some of the tissue piercing electrodes facilitates greater
physician control. Now, for example, individual addressing allows
separate field definition as indicated at 394 and 396, allowing
greater targeting of the therapy field. In an example, the targeted
and individualized fields 394, 396 may be used to deliver thermal
ablation in a locally controlled space, while IRE is delivered in a
therapy regimen that uses more of the tissue penetrating electrodes
ganged together, for example. In this way, the thermal ablation can
be targeted in areas where sensitive tissue is not present (such as
vascular tissue), while IRE can be used more broadly to allow more
selective killing of cells, if desired.
[0068] FIG. 7 shows an illustrative system. The system 400 includes
a therapy device 410 having a relatively complex handle structure
including individual actuators 410 for manipulating the tissue
piercing electrodes (individually, as groups, or as the entire
array) at the distal tip of the apparatus, and a separate actuator
414 for controlling a sheath that selectively limits the exposed
surface area of the return electrode. Electrical cord 416 couples
to a signal generator 418, while a fluid coupling 420 is linked to
a fluid source 422. The distal portion of the therapy device 410 is
shown at 430 and may incorporate any of the designs in FIGS. 3-6,
above, or FIGS. 8-11, below.
[0069] FIGS. 8-11 show an illustrative therapy apparatus with
manipulation of an electrode. A sheath 450 is shown having a window
at 452. The sheath may be, for example, a 0.005-inch polyimide
tube, though any design or material may be used instead of
polyimide of such thickness; other insulative polymers may be used,
for example. The inner shaft 460 carries shaft electrode 462. The
shaft electrode may be, for example, a titanium or medical grade
stainless steel element, and may be a ring electrode or a
directional electrode as shown in examples above. A conductor 464,
such as a stainless-steel conductor, can be provided through shaft
460 which may be, for example, a multi-lumen tube of any suitable
material such as polyimide, poly-ether block amide, or other
suitable material. In one configuration, as shown in FIG. 9, the
sheath 450 may completely cover the electrode 462 by having the
window 452 proximal of the electrode 462. Advancing the sheath 450
as shown in FIG. 10 allows a selected and reduced area of the
electrode 462 to be exposed through window 452. Retracting the
sheath 450 as shown in FIG. 11 allows the entire electrode 462 to
be exposed.
[0070] FIGS. 12-13 show illustrative effects of different therapy
modes with different electrode configurations. FIG. 12 shows
variation in IRE field strength with variation of shaft electrode
length, using a homogenous medium model. A first example at 500
applies a 3000-volt output between a 2.5 mm shaft electrode 502 and
tissue piercing electrodes 504, with the boundaries of the IRE
field shown at 506. To ensure reliable IRE in the field boundary
506, in application, the output may be delivered for example as a
series of 4 to 20 pulses (or more) with durations in the 0.1 to 100
microsecond range (or more) at a frequency of 1 to 100 Hz (or more
or less), for example, 8 to 10 pulses of 5 microsecond duration at
10 Hz may be delivered. Using the same output voltage, a second
example at 520 assumes a 5 mm shaft electrode length 522. The IRE
field boundary 526 closely envelopes the tissue piercing electrodes
and can be seen to have widened and lengthened about the shaft
electrode 522. Extending the shaft electrode 542 length to 10 mm,
as shown at 540, again elongates the boundaries of the IRE field
boundary 546; it can be seen also that the field span surrounding
the tissue piercing electrodes 544 becomes larger as well. Again,
extending the shaft electrode 562 length to 15 mm changes the shape
of the IRE field boundary 566, adding still further to the margin
around the tissue piercing electrodes 564, but achieving a field
that narrows near the proximal end of the shaft electrode 562, as
seen at 568.
[0071] FIG. 13 shows thermal ablation boundaries using a monopolar
configuration. Here, a return plate electrode (not shown) is placed
on the skin of the patient, typically using a hydrogel or the like
to reduce tissue/electrode impedance, as the therapy device is used
to deliver output therapy. As shown at 600, at a relatively lower
voltage (such as 2000 volts) the thermal ablation boundaries 604
are generally limited to the region of the tissue piercing
electrodes. With increased voltage, as shown at 620 and 640, the
thermal ablation region expands quickly to develop a volume around
the tissue penetrating electrodes 622, 642.
[0072] The ability to manipulate the shape and volume of treatment
effectiveness can be used in a variety of ways. In some examples,
the shaft electrode size may be varied while a plurality of IRE
treatments take place, wherein the individual IRE treatments
comprise a plurality of applied pulses delivered as a set of
therapy pulses, and wherein the shaft electrode size and usage is
changed from one set to the next as by, for example, exposing more
or less of the shaft electrode from one set to the next, or by
switching from a monopolar to bipolar treatment mode by enabling or
disabling the shaft electrode. For example, thermal ablation
modalities can be difficult to control due to heat sink effects of
blood flow in nearby vasculature and/or the treatment device
itself. In the prior art, tract seeding can be prevented by
applying ablation therapy during retraction of the device to cause
a thin layer of tissue necrosis along the tract. Application of IRE
pulses in sets before or after the thermal treatment may target not
only the tissue adjacent to the electrodes themselves, but also
tissue that is located outside of the thermal treatment region
between two electrodes.
[0073] In some examples, IRE and thermal treatments are combined
into one overall therapy regimen as by, for example, alternating
between pulses of longer duration (which generate thermal effects)
and shorter duration (which generate IRE-type effects) within a
therapy pulse set. In another example, an IRE output is generated
after a thermal output and before adjustment of electrode position
to target a different area of the anatomy; for example, a sequence
of thermal output and IRE output may be followed by extending or
retracting an electrode or insulator over an electrode, with the
thermal output used to create larger volume effects and the IRE
output used to eliminate possible tract seeding.
[0074] In another example, IRE is used before thermal output. IRE
can reduce impedance in affected tissue. By first reducing
impedance, the thermal output of a subsequent stage can generate a
greater quantity of thermal affect with reduced voltage output, as
the lowered impedance allows higher current at a given voltage,
where it is recognized that the square of the current yields the
heating effect of a given therapy.
[0075] FIGS. 14A-14B shows a tumor being treated by an illustrative
device. In FIG. 14A, a therapy device or cannula 700 has been
inserted into a patient's tissue. A shaft electrode is shown at
702, with a moveable sheath 708 on the shaft as well to adjust the
area of the electrode 702 that is exposed to patient tissue.
[0076] A distal tip 704 of the cannula 700 has an angled or pointed
end to allow passage through the patient tissue. In some examples
the distal tip 704 is relatively sharp to allow it to pierce
through tissue; such an example is shown in FIG. 14A where the
distal tip 704 has been used to pierce a tumor 720 and surrounding
lesion 722. In other examples the distal tip 704 may be blunted to
allow atraumatic passage through a body lumen such as a biliary
duct, lymph vessel or duct, urethra, mammary duct, digestive
passageway, blood vessel, or other body passageway, as the case may
be. The distal tip 704 may be partly blunted to allow its use to
separate body tissue layers as it passes, for example, alongside
the outer capsule of a body organ such as the liver or kidney.
[0077] A plurality of tissue piercing electrodes or needle
electrodes are shown at 706. As can be seen, the cannula is
inserted 700 far enough into the tumor to place the shaft electrode
at least partly in the tumor, and the needle electrodes extend
beyond the tumor and lesion. Tract seeding in this example may
occur if abnormal cells from the tumor 720 stick to the needle
electrodes 706 as they pass out through the lesion and into
surrounding normal tissue, as well as by cells sticking to the main
body of the cannula 700 such as sheath 708 and shaft electrode 702
during removal or repositioning maneuvers. In either event, the
abnormal cells may be transported out of the tumor into surrounding
tissue, and so an ablation or cell destruction therapy that
destroys such cells in addition to the cells of the tumor 720 and
surrounding lesion 722 is desirable.
[0078] In an example, a plurality of distinct treatment steps take
place using differing parameters and electrodes to account for both
the extent of the tumor 720 and any potential tract seeding. For
example, currents 730 may be generated in a bipolar treatment stage
or stages between one or more of the tissue piercing or needle
electrodes 706 and the shaft electrode 702. Currents 732 may also
be generated in one or more monopolar treatment stages between an
external return electrode 740 and one or more of the needle
electrodes 706. Currents 734 may be generated in one or more
monopolar stages using the shaft electrode 702 and the external
return electrode 740. The external return electrode 740 may be, for
example, a grounding pad. The grounding pad or external return
electrode 740 may be placed in different positions for different
steps, to direct the electrical field in different directions, if
desired.
[0079] FIG. 14B illustrates results of several therapy steps using
distinct therapy modalities. For example, a first lesion field is
generated at 770 by the use of a monopolar thermal or IRE therapy
delivery using the needle electrodes 706 and an external return
electrode 740. A second lesion field is generated at 772 by the use
of a bipolar IRE or thermal therapy using most or all of the shaft
electrode 702 as one pole and one or more of the needle electrodes
706 as opposing pole(s). A third lesion field is generated at 774
using a monopolar IRE or thermal therapy delivered using a portion
of the shaft electrode 702 (for example, a lesser extent of the
shaft electrode 702 may be exposed during such delivery than is
shown in FIG. 14B) and an external return electrode 740. Depending
on the size and shape of the tumor 720, only two such fields may be
generated in some examples.
[0080] The present invention encompasses each combination of the
two monopolar and bipolar therapy modes, in either IRE or thermal
formats, in any desired order. The skilled person can readily
generate the complete matrix. For purposes of illustration,
however, following are some approaches that may be used in some
specific examples:
TABLE-US-00001 First Step/Type Second Step/Type Third Step/Type
772/IRE 770/Thermal (none) 770/Thermal 772/IRE (none) 772/IRE
770/Thermal 774/Thermal
For purposes of this illustration, the "IRE" therapy steps may have
thermal effects as well, but predominantly use IRE to cause cell
death; likewise, the predominant mode of cell death for the
"Thermal" therapy steps will be thermal though IRE may occur in
some cells as well. Factors that may differentiate Thermal from IRE
therapy may include duty cycle and field strength or amplitude.
Determination of whether thermal or IRE therapy has been effective
can be determined through staining using immune-histo-chemical
assays, which will illustrate differentiation between tissue
regions subject to different types of cell death. For example,
immunological response to IRE-cause cell death is distinguishable
from that for thermally destroyed cells; cells that survive and/or
are only subject to reversible electroporation will further show a
demarcation. If desired, an additional therapy mode may comprise
placing the shaft electrode 702 (or a portion thereof) electrically
in common with one or more of the needle electrodes in a monopolar
therapy mode, whether for IRE or thermal ablation.
[0081] In some examples a monopolar therapy mode is used for
thermal ablation using a lower voltage gradient, and a bipolar
therapy mode is used for IRE using a higher voltage gradient. For
example, two electrodes 2.5 cm apart can use a 2000-volt output to
exceed 650 V/cm field for IRE, while two electrodes 10 cm apart
using 1000-volt output will yield a 100 V/cm field, which is
sufficient to attain thermal effects if using longer pulse widths
and/or a higher duty cycle, with the combination reducing damage or
excitation on distant muscle or nerve fibers of the patient in
either case. In this example, the pulse-duration and field strength
relationship with thermal damage and irreversible electroporation
induction is harnessed to produce a therapeutic effect with
desirable damage modes.
[0082] As can be seen in FIG. 14B, while none of the individual
therapy steps completely encompasses the tumor 720, the combination
of modes and therapy steps captures the entire tumor as well as a
margin about the tumor 720, while also addressing the possibility
of tract seeding. The use of IRE in addition to thermal ablation
also addresses tract seeding that could otherwise be facilitated by
localized heat sink effects of the apparatus itself.
[0083] FIG. 15 is a block flow diagram illustrating various
examples. The overall method 800 may be subject to a number of
repetitions, both internally within the method and as separate
steps in a procedure to treat a patient. A therapy device is
inserted at 810. Insertion 810 may make use of an existing lumen or
channel of the patient (such as using a blood vessel or other
duct/vessel in the patient) or may comprise piercing tissue with an
instrument designed for such piercing. Once inserted to a location
that is desirable, the treatment apparatus may deploy one or more
electrodes, as indicated at 820. In some example, tissue piercing
electrodes, such as in the modified Leveen-style devices shown
above, may be extended out of internal lumens of the therapy device
to pierce tissue or otherwise position electrodes for use. A
therapy is then delivered, as indicated at 830. The therapy may be,
for example, an IRE therapy 832 in which monophasic or biphasic (or
triphasic or other multiphasic) electrical output is generated with
relatively high amplitudes (yielding fields of over 600 V/cm, for
example) and short pulsewidths (for example in the range of 0.1 to
100 microseconds) at a relatively lower duty cycle (such as 1 to
100 Hz--such as a duty cycle of less than 0.1%), which may avoid
thermal heating to yield predominantly IRE therapy. The therapy may
include injection of a fluid to enhance or modify effectiveness or
spatial effects of an applied electrical therapy, or may instead be
injection of an ablative fluid such as a fluid having limited
caustic effects, or cooling or heating effects, as indicated at
834. The therapy may be a thermal treatment, which may incorporate
somewhat lower pulse amplitudes (fields of less than 600 V/cm, for
example) at longer pulsewidths (for example, 10 microseconds to 100
milliseconds) at a relatively higher duty cycle (such as by
application of the pulses at a frequency of 10 Hz to 100 kHz, in
some examples to yield a duty cycle of greater than 0.1%). For
example, saline may be injected to reduce local tissue impedance,
increasing current flow for a given output voltage, such that both
an electrical output (832/836) is delivered and the fluid (834).
Some examples may use both IRE 832 and thermal ablation 836 from a
single output waveform by increasing pulsewidth and/or the duty
cycle of IRE outputs to cause thermal effects.
[0084] Within the illustrative example, after a therapy delivery at
830, the system proceeds to make an adjustment as indicated at 840
and then cycles back to the therapy step. For example, an
adjustment may include the injection of fluid 842, selecting,
deselecting, moving or modifying the exposed surface area of a
needle electrode 844, adjusting the position or exposed surface
area of a shaft electrode 846, or moving, adding or removing a
cutaneous or skin electrode 848. In an illustration, a therapy may
be delivered at 830 as a monopolar thermal ablation step 836, an
adjustment may be made at 840 by exposing a shaft electrode 846 and
removing or deselecting a skin electrode 848, and then delivering
therapy again at 830, this time using a bipolar IRE output with
shaft and needle electrodes.
[0085] In some examples a set quantity of therapy steps and
adjustments 830/840 may be performed and the method ends by exiting
the loop 830/840, proceeding to the end block 860. In other
examples, after one or more therapy steps 830, the method engages
an observation step 850, in which one or more observable features
are quantities or checked to determine progress or status of the
therapy. For example, block 850 may refer to temperature 852,
impedance 854, and/or an imaging modality 856 such as a CT image.
In some examples, impedance 854 may be checked between any selected
pair of electrodes such as between needle electrodes, between a
needle electrode and a shaft electrode, between a needle electrode
and a surface electrode, or between a probe electrode and an
electrode of the therapy apparatus, or between two probe
electrodes. It should be understood that as therapy progresses,
cell death may occur, releasing intercellular fluid into the
extracellular matrix and reducing impedance as cell death occurs,
making impedance 854 a useful observation. Also, as therapy
progresses, temperature 852 may be checked to ensure that
temperatures as measured using, for example a temperature sensor on
the therapy apparatus or a temperature sensor on a separate probe,
is in a desired range. For example, as cell death occurs, local
temperature may increase more greatly as local impedance drops and
current flows increase at a given voltage, making temperature a
useful measure of status. An image 856 may be used as well to
determine the status of a tumor or lesion. After observation 850,
an adjustment 840 may be made if desired or therapy 830 may resume.
If observation 850 shows satisfactory completion of treatment, the
method may go to the end block 860 if desired.
[0086] In one example, several iterations of thermal therapy
830/836 may be performed, with observation 850 used to determine
when the thermal therapy is sufficiently completed, and then an
additional therapy may be delivered as an IRE therapy 830/832 to
limit the possibility of tract seeding. Several additional examples
of therapy sequences follow in FIGS. 16-20.
[0087] FIG. 16 shows one example. A therapy apparatus is inserted
to a desired location at 900. Electrodes are advanced and
manipulated to desired positions relative to a tumor or other
target tissue, such as by establishing a perimeter near or around
the target tissue, as indicated at 902. A first electrical output
is provided as a first therapy step at 904, such as by delivering
IRE, thermal, or an output tailored to generate a combination
thereof. A second electrical output is provided as a second therapy
step at 906, such as by delivering IRE, thermal, or an output
tailored to generate a combination thereof. For example, an IRE
therapy may be delivered at 904 and a thermal therapy at 906, or
the other way around.
[0088] The method of FIG. 16, as well as any other of the examples
herein, may be further combined with additional therapy elements,
such as for example, the delivery of a laser ablation (by, for
example, inserting a separate optical instrument or including one
or more optical fibers in a therapy apparatus similar to those
shown above). For example, an optical therapy apparatus may be
inserted and used to perform laser-based ablation, with IRE then
delivered via electrodes on the laser apparatus to mitigate tract
seeding. Ultrasound or other vibrational therapy may be added as
well. For example, rather than an electrical therapy as the
"thermal" therapy, followed by IRE to deal with tract seeding
possibilities, an ultrasound instrument may be provided and used in
a first step, with electrodes provided thereon to allow use of IRE
to complete the procedure prior to withdrawal of the ultrasound
instrument. Thus, for each of the ultrasound and laser examples,
block 904 may instead be treated as deliver first therapy, where
the first therapy is ultrasound or laser therapy, followed by the
electrical output at 906.
[0089] FIG. 17 shows another example. Again, a therapy apparatus is
inserted 920 and electrodes thereof may be advanced and/or
manipulated into a desired use configuration. A first output, which
may be electrical as indicated at 924, is delivered. The electrodes
are then manipulated as indicated at 926 by, for example,
selecting, deselecting, moving, or adjusting the exposed surface
area thereof. A second output, which may be electrical, is then
delivered as indicated at 928. As with FIG. 16, the first or second
outputs may be IRE, thermal, or a combination thereof.
[0090] FIG. 18 shows another example. Here, a therapy apparatus is
inserted 940 and electrodes thereof may be advanced and/or
manipulated into a desired use configuration 942. A fluid is then
infused, as indicated at 944. The fluid may be provided to enhance,
augment, limit or otherwise affect the subsequent therapy steps. A
first output, which may be electrical as indicated at 946 is
delivered, and a second output, which may also be electrical as
indicated at 948, is then delivered. The therapy outputs, if
electrical, may be IRE, thermal, or a combination thereof. In the
example, the therapy outputs are different from one another in one
or more respects such as by having one adapted to predominantly
thermal effects, while the other is tailored to predominantly IRE
effects.
[0091] FIG. 19 shows a still further example. Here, a therapy
apparatus is inserted at 960, and electrodes thereof may be
advanced and/or manipulated into a desired use configuration as
noted at 962. Fluid infusion may follow at 964, followed by a first
therapy which may be electrical as indicated at 966. The electrodes
may again be advanced and/or manipulated, as indicated at 968.
Steps 962 and 968 may include, for example, advancing, retracting,
selecting, deselecting, and/or changing the exposed surface are of
one or more electrodes. Fluid management is performed at 970 by,
for example, infusing or extracting fluid, if desired. For example,
if saline is injected at 964 to reduce impedance and generate
increased current flow at a given voltage, extraction of the saline
(and at least some associated biological media with which the
saline will have mixed) may raise impedance for purposes of
delivering a second electrical output 972, thereby reducing heating
associated with the second output 972. Fluid may be extracted at
970 for purposes of determining whether therapy has been effective
at block 968, as the extracellular fluid constituents may indicate
whether cells have been destroyed or otherwise affected, for
example.
[0092] FIG. 20 shows another example. Here, a therapy apparatus is
inserted at 980 and electrodes thereof may be advanced and/or
manipulated into a desired use configuration as noted at 982. Fluid
is then infused as noted at 984, and a first set of electrical
outputs is delivered. For example, outputs to generate thermal
effects may be delivered as part of a first set, followed by
outputs to generate IRE effects, using different selection of
electrodes as desired within the therapy set 986. The electrodes
are then advanced and/or manipulated as indicated at 988, fluid
management 990 is performed (such as injecting or withdrawing
fluid), and a second electrical output set is delivered at 992. In
an example, the first and second electrical output sets comprise
each of thermal and IRE outputs, such that the possibility of tract
seeding is eliminated in block 986 prior to moving or manipulating
electrodes in block 988, as well as before ending the therapy
method at block 992.
[0093] The examples of FIGS. 16-20 are illustrative of a number of
combinations that may be possible with a versatile apparatus as
disclosed herein having the ability to manipulate shaft electrode
size and location during the procedure and, if desired, between
therapy delivery steps. The skilled artisan will appreciate
additional variations and adaptations that may be readily achieved
with this novel apparatus.
[0094] The above detailed description includes references to the
accompanying drawings, which form a part of the detailed
description. The drawings show, by way of illustration, specific
embodiments in which the invention can be practiced. These
embodiments are also referred to herein as "examples." Such
examples can include elements in addition to those shown or
described. However, the present inventors also contemplate examples
in which only those elements shown or described are provided.
Moreover, the present inventors also contemplate examples using any
combination or permutation of those elements shown or described (or
one or more aspects thereof), either with respect to a particular
example (or one or more aspects thereof), or with respect to other
examples (or one or more aspects thereof) shown or described
herein.
[0095] In the event of inconsistent usages between this document
and any documents so incorporated by reference, the usage in this
document controls.
[0096] In this document, the terms "a" or "an" are used, as is
common in patent documents, to include one or more than one,
independent of any other instances or usages of "at least one" or
"one or more." Moreover, in the following claims, the terms
"first," "second," and "third," etc. are used merely as labels, and
are not intended to impose numerical requirements on their
objects.
[0097] Method examples described herein can be machine or
computer-implemented at least in part. Some examples can include a
computer-readable medium or machine-readable medium encoded with
instructions operable to configure an electronic device to perform
methods as described in the above examples. An implementation of
such methods can include code, such as microcode, assembly language
code, a higher-level language code, or the like. Such code can
include computer readable instructions for performing various
methods. The code may form portions of computer program products.
Further, in an example, the code can be tangibly stored on one or
more volatile, non-transitory, or non-volatile tangible
computer-readable media, such as during execution or at other
times. Examples of these tangible computer-readable media can
include, but are not limited to, hard disks, removable magnetic or
optical disks, magnetic cassettes, memory cards or sticks, random
access memories (RAMs), read only memories (ROMs), and the
like.
[0098] The above description is intended to be illustrative, and
not restrictive. For example, the above-described examples (or one
or more aspects thereof) may be used in combination with each
other. Other embodiments can be used, such as by one of ordinary
skill in the art upon reviewing the above description.
[0099] The Abstract is provided to comply with 37 C.F.R. .sctn.
1.72(b), to allow the reader to quickly ascertain the nature of the
technical disclosure. It is submitted with the understanding that
it will not be used to interpret or limit the scope or meaning of
the claims.
[0100] Also, in the above Detailed Description, various features
may be grouped together to streamline the disclosure. This should
not be interpreted as intending that an unclaimed disclosed feature
is essential to any claim. Rather, inventive subject matter may lie
in less than all features of a particular disclosed embodiment.
Thus, the following claims are hereby incorporated into the
Detailed Description as examples or embodiments, with each claim
standing on its own as a separate embodiment, and it is
contemplated that such embodiments can be combined with each other
in various combinations or permutations. The scope of the invention
should be determined with reference to the appended claims, along
with the full scope of equivalents to which such claims are
entitled.
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