U.S. patent application number 15/923591 was filed with the patent office on 2020-09-17 for systems and methods for analyzing electrical stimulation and selecting or manipulating volumes of activation.
The applicant listed for this patent is Boston Scientific Neuromodulation Corporation. Invention is credited to Hemant Bokil.
Application Number | 20200289834 15/923591 |
Document ID | / |
Family ID | 1000005059753 |
Filed Date | 2020-09-17 |
United States Patent
Application |
20200289834 |
Kind Code |
A9 |
Bokil; Hemant |
September 17, 2020 |
SYSTEMS AND METHODS FOR ANALYZING ELECTRICAL STIMULATION AND
SELECTING OR MANIPULATING VOLUMES OF ACTIVATION
Abstract
A system for identifying potential portions of a body in which
electrical stimulation to treat a condition or disorder affects at
least one symptom of the condition or disorder, stimulation effect,
or side effect performs the following acts: obtaining, for each of
multiple stimulation instances, an estimation of a region of the
body stimulated during the stimulation instance and a score for
each of at least one symptom, stimulation effect, or stimulation
side effect; and determining, for each of multiple portions of the
body using the scores and the estimates in a permutation test, a
likelihood that stimulation of that portion of the body affects at
least one symptom, stimulation effect, or stimulation side effect.
In other embodiments, the system sets up a relationship between the
outcomes of stimulation and influence of a particular part of the
body on the outcome, and derives this influence using a
pseudoinverse.
Inventors: |
Bokil; Hemant; (Santa
Monica, CA) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Boston Scientific Neuromodulation Corporation |
Valencia |
CA |
US |
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Prior
Publication: |
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Document Identifier |
Publication Date |
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US 20190282820 A1 |
September 19, 2019 |
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Family ID: |
1000005059753 |
Appl. No.: |
15/923591 |
Filed: |
March 16, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15163581 |
May 24, 2016 |
9956419 |
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15923591 |
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62166569 |
May 26, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G16H 40/63 20180101;
A61N 1/37247 20130101; A61N 1/0534 20130101; A61N 1/025
20130101 |
International
Class: |
A61N 1/372 20060101
A61N001/372; A61N 1/02 20060101 A61N001/02; G16H 40/63 20060101
G16H040/63 |
Claims
1. A system for identifying portions of a body in which electrical
stimulation of that portion of the body to treat a condition or
disorder affects at least one symptom of the condition or disorder,
stimulation effect, or stimulation side effect, the system
comprising: a computer processor configured to: obtain N
stimulation instances, wherein N is an integer greater than one,
and, for each stimulation instance, an outcome score for at least
one symptom of the condition or disorder, stimulation effect, or
stimulation side effect; select M portions of the body, wherein M
is an integer greater than one; estimate, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance; generate a matrix, wherein the matrix is
either a) a N.times.M matrix with entries au or b) a M.times.N
matrix with entries a.sub.ji, wherein i is an integer ranging from
1 to N and corresponds to an i.sup.th stimulation instance and j is
an integer ranging from 1 to M and corresponds to a j.sup.th
portion of the body, wherein a.sub.ij or a.sub.ji, respectively, is
0 if the j portion of the body is not stimulated during the
i.sup.th stimulation instance and is a non-zero value if the
j.sup.th portion of the body is stimulated during the i.sup.th
stimulation instance; determine a pseudoinverse of the matrix to
estimate an influence of each of the M portions of the body on the
outcome scores for the N stimulation instances; and store or
display the estimated influences to identify which portions of the
body, when electrically stimulated, affect the at least one symptom
of the condition or disorder, stimulation effect, or stimulation
side effect.
2. The system of claim 1, wherein estimating, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance comprises estimating, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance based on stimulation parameters used during
the stimulation instance.
3. The system of claim 1, wherein obtaining N stimulation instances
comprises obtaining the N stimulation instances from a plurality of
patients.
4. The system of claim 1, wherein the computer processor is further
configured to generate a score vector comprising the outcome scores
for the N stimulation instances.
5. The system of claim 4, wherein determining the pseudoinverse of
the matrix comprises determining an influence vector using the
pseudoinverse and the score vector, wherein each entry in the
influence vector corresponds to a different portion of the
body.
6. The system of claim 5, wherein the entries of the influence
vector indicate a relative influence of the corresponding portions
of the body relative to the at least one symptom of the condition
or disorder, stimulation effect, or stimulation side effect.
7. The system of claim 5, wherein determining the influence vector
comprises determining the influence vector by the formula
I=A.sup.+S, wherein A.sup.+ is the pseudoinverse of the matrix, S
is the score vector, and I is the influence vector.
8. The system of claim 1, wherein a.sub.ij or a.sub.ji is 1 if the
j.sup.th portion of the body is stimulated during the i.sup.th
stimulation instance.
9. A non-transitory computer-readable medium having
processor-executable instructions for identifying portions of a
body in which electrical stimulation of that portion of the body to
treat a condition or disorder affects at least one symptom of the
condition or disorder, stimulation effect, or side effect, the
processor-executable instructions when installed onto a device
enable the device to perform actions, including: obtaining N
stimulation instances, wherein N is an integer greater than one,
and, for each stimulation instance, an outcome score for at least
one symptom of the condition or disorder, stimulation effect, or
stimulation side effect; selecting M portions of the body, wherein
M is an integer greater than one; estimating, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance; generating a matrix, wherein the matrix is
either a) a N.times.M matrix with entries a.sub.ij or b) a
M.times.N matrix with entries a.sub.ji, wherein i is an integer
ranging from 1 to N and corresponds to an i.sup.th stimulation
instance and j is an integer ranging from 1 to M and corresponds to
a j portion of the body, wherein a.sub.ij or a.sub.ji,
respectively, is 0 if the j.sup.th portion of the body is not
stimulated during the i.sup.th stimulation instance and is a
non-zero value if the j.sup.th portion of the body is stimulated
during the i.sup.th stimulation instance; determining a
pseudoinverse of the matrix to estimate an influence of each of the
M portions of the body on the outcome scores for the N stimulation
instances; and storing or displaying the estimated influences to
identify which portions of the body, when electrically stimulated,
affect the at least one symptom of the condition or disorder,
stimulation effect, or stimulation side effect.
10. The non-transitory computer-readable medium of claim 9, wherein
estimating, for each of the N stimulation instances and for each of
the M portions of the body, whether that portion of the body was
stimulated during that stimulation instance comprises estimating,
for each of the N stimulation instances and for each of the M
portions of the body, whether that portion of the body was
stimulated during that stimulation instance based on stimulation
parameters used during the stimulation instance.
11. The non-transitory computer-readable medium of claim 9, wherein
obtaining N stimulation instances comprises obtaining the N
stimulation instances from a plurality of patients.
12. The non-transitory computer-readable medium of claim 9, wherein
the actions further include generating a score vector comprising
the outcome scores for the N stimulation instances.
13. The non-transitory computer-readable medium of claim 12,
wherein determining the pseudoinverse of the matrix comprises
determining an influence vector using the pseudoinverse and the
score vector, wherein each entry in the influence vector
corresponds to a different portion of the body.
14. The non-transitory computer-readable medium of claim 13,
wherein the entries of the influence vector indicate a relative
influence of the corresponding portions of the body relative to the
at least one symptom of the condition or disorder, stimulation
effect, or stimulation side effect.
15. The non-transitory computer-readable medium of claim 13,
wherein determining the influence vector comprises determining the
influence vector by the formula I=A.sup.+S, wherein A.sup.+ is the
pseudoinverse of the matrix, S is the score vector, and I is the
influence vector.
16. A system for selecting or manipulating volumes of activation
for electrical stimulation, the system comprising: a computer
processor configured to: present a graphical user interface that
includes at least one user-activatable button selected from a union
button, an intersection button, or a subtraction button; display at
least two volumes of activation; and in response to user activation
of the at least one user-activatable button, display a union, an
intersection, or a subtraction of at least two of the at least two
volumes of activation.
17. The system of claim 16, wherein the graphical user interface
includes a union button, an intersection button, and a subtraction
button.
18. The system of claim 16, wherein the at least two volumes of
activation further contain metadata associated with the at least
two volumes of activation.
19. The system of claim 18, wherein the graphical user interface
further comprises a search button.
20. The system of claim 19, wherein the acts further include in
response to user activation of the search button, allowing the user
to indicate one or more search terms; and searching metadata of a
set of volumes of activation using the one or more search terms to
identify one or more volumes of activation with metadata
corresponding to the one or more search terms.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 15/163,581, filed May 24, 2016, which claims the benefit
under 35 U.S.C. .sctn. 119(e) of U.S. Provisional Patent
Application Ser. No. 62/166,569, filed May 26, 2015, both of which
are incorporated herein by reference.
FIELD
[0002] The present invention is directed to the area of implantable
electrical stimulation systems and methods of making and using the
systems. The present invention is also directed to systems for
determining regions of the body for stimulation or for selecting or
manipulating volumes of activation, as well as methods of making
and using the systems.
BACKGROUND
[0003] Implantable electrical stimulation systems have proven
therapeutic in a variety of diseases and disorders. For example,
spinal cord stimulation systems have been used as a therapeutic
modality for the treatment of chronic pain syndromes. Peripheral
nerve stimulation has been used to treat chronic pain syndrome and
incontinence, with a number of other applications under
investigation. Functional electrical stimulation systems have been
applied to restore some functionality to paralyzed extremities in
spinal cord injury patients. Stimulation of the brain, such as deep
brain stimulation, can be used to treat a variety of diseases or
disorders.
[0004] Stimulators have been developed to provide therapy for a
variety of treatments. A stimulator can include a control module
(with a pulse generator), one or more leads, and an array of
stimulator electrodes on each lead. The stimulator electrodes are
in contact with or near the nerves, muscles, or other tissue to be
stimulated. The pulse generator in the control module generates
electrical pulses that are delivered by the electrodes to body
tissue.
BRIEF SUMMARY
[0005] One embodiment is a system for identifying portions of a
body in which electrical stimulation of that portion of the body to
treat a condition or disorder affects at least one of at least one
symptom of the condition or disorder, stimulation effect, or side
effect. The system includes a computer processor configured and
arranged to perform the following acts: obtaining, for each of a
plurality of stimulation instances, an estimation of a region of
the body stimulated during the stimulation instance and a score for
each of at least one symptom of the condition or disorder,
stimulation effect, or stimulation side effect; determining, for
each of a plurality of portions of the body using the scores and
the estimates in a permutation test, a likelihood that stimulation
of that portion of the body affects at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect; and storing or displaying the determined likelihoods to
identify which portions of the body, when electrically stimulated,
affect the at least one of the at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect.
[0006] Another embodiment is a non-transitory computer-readable
medium having processor-executable instructions for identifying
portions of a body in which electrical stimulation of that portion
of the body to treat a condition or disorder affects at least one
of at least one symptom of the condition or disorder, stimulation
effect, or side effect, the processor-executable instructions when
installed onto a device enable the device to perform actions,
including: obtaining, for each of a plurality of stimulation
instances, an estimation of a region of the body stimulated during
the stimulation instance and a score for each of at least one
symptom of the condition or disorder, stimulation effect, or
stimulation side effect; determining, for each of a plurality of
portions of the body using the scores and the estimates in a
permutation test, a likelihood that stimulation of that portion of
the body affects at least one symptom of the condition or disorder,
stimulation effect, or stimulation side effect; and storing or
displaying the determined likelihoods to identify which portions of
the body, when electrically stimulated, affect the at least one of
the at least one symptom of the condition or disorder, stimulation
effect, or stimulation side effect.
[0007] Yet another embodiment is a method for identifying portions
of a body in which electrical stimulation of that portion of the
body to treat a condition or disorder affects at least one of at
least one symptom of the condition or disorder, stimulation effect,
or side effect. The method includes obtaining, for each of a
plurality of stimulation instances, an estimation of a region of
the body stimulated during the stimulation instance and a score for
each of at least one symptom of the condition or disorder,
stimulation effect, or stimulation side effect; determining, for
each of a plurality of portions of the body using the scores and
the estimates in a permutation test, a likelihood that stimulation
of that portion of the body affects at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect; and storing or displaying the determined likelihoods to
identify which portions of the body, when electrically stimulated,
affect the at least one of the at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect.
[0008] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, further
including obtaining the plurality of stimulation instances and, for
each stimulation instance, a set of stimulation parameters.
[0009] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, obtaining an
estimation of a region of the body stimulated during the
stimulation instance includes estimating the region of the body
stimulation during the stimulation instance based on stimulation
parameters used during the stimulation instance.
[0010] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, determining a
likelihood includes forming a matrix for a selected portion of the
body and for a selected symptom of the condition or disorder,
stimulation effect, or stimulation side effect, the matrix
including a plurality of rows and columns, where one of the columns
or rows corresponds to each stimulation instance, where, for each
of a plurality of the stimulation instances, a first entry in a
column or row indicates whether the selected portion of the body is
stimulated in that stimulation instance and a second entry in the
column or row corresponds to the score for the selected symptom of
the condition or disorder, stimulation effect, or side effect for
that stimulation instance. In at least some embodiments of the
system, non-transitory computer-readable medium, or method
described above, determining a likelihood further includes
determining a likelihood that a null hypothesis is invalid, where
the null hypothesis is that the selected portion of the body does
not influence the scores for the selected symptom of the condition
or disorder, stimulation effect, or side effect. In at least some
embodiments of the system, non-transitory computer-readable medium,
or method described above, determining a likelihood further
includes determining a difference between scores where the
preselected portion of the body is stimulated and scores where the
preselected portion of the body is not stimulated. In at least some
embodiments of the system, non-transitory computer-readable medium,
or method described above, determining a likelihood further
includes randomizing the second entries with respect to the first
entries to form a plurality of additional matrices. In at least
some embodiments of the system, non-transitory computer-readable
medium, or method described above, determining a likelihood further
includes generating a distribution based on the matrix and the
plurality of additional matrices.
[0011] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, obtaining the
plurality of stimulation instances includes obtaining the plurality
of stimulation instances from a plurality of patients.
[0012] A further embodiment is a system for identifying portions of
a body in which electrical stimulation of that portion of the body
to treat a condition or disorder affects at least one of at least
one symptom of the condition or disorder, stimulation effect, or
stimulation side effect. The system includes a computer processor
configured and arranged to perform the following acts: obtaining N
stimulation instances, where N is an integer greater than one, and,
for each stimulation instance, an outcome score for each of at
least one symptom of the condition or disorder, stimulation effect,
or stimulation side effect; selecting M portions of the body, where
M is an integer greater than one; estimating, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance; generating a matrix, where the matrix is
either a) a N.times.M matrix with entries a.sub.ij or b) a
M.times.N matrix with entries a.sub.ji, where i is an integer
ranging from 1 to N and corresponds to the i.sup.th stimulation
instance and j is an integer ranging from 1 to M and corresponds to
a j.sup.th portion of the body, where a.sub.ij or a.sub.ji,
respectively, is 0 if the j.sup.th portion of the body is not
stimulated during the i.sup.th stimulation instance and is a
non-zero value if the j.sup.th portion of the body is stimulated
during the i.sup.th stimulation instance; determining a
pseudoinverse of the matrix to estimate an influence of each of the
M portions of the body on the outcome scores for the N stimulation
instances; and storing or displaying the estimated influences to
identify which portions of the body, when electrically stimulated,
affect the at least one of the at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect.
[0013] Another embodiment is a non-transitory computer-readable
medium having processor-executable instructions for identifying
portions of a body in which electrical stimulation of that portion
of the body to treat a condition or disorder affects at least one
of at least one symptom of the condition or disorder, stimulation
effect, or stimulation side effect, the processor-executable
instructions when installed onto a device enable the device to
perform actions, including: obtaining N stimulation instances,
where N is an integer greater than one, and, for each stimulation
instance, an outcome score for each of at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect; selecting M portions of the body, where M is an integer
greater than one; estimating, for each of the N stimulation
instances and for each of the M portions of the body, whether that
portion of the body was stimulated during that stimulation
instance; generating a matrix, where the matrix is either a) a
N.times.M matrix with entries au or b) a M.times.N matrix with
entries a.sub.ji, where i is an integer ranging from 1 to N and
corresponds to the i.sup.th stimulation instance and j is an
integer ranging from 1 to M and corresponds to a j.sup.th portion
of the body, where au or a.sub.ji, respectively, is 0 if the
j.sup.th portion of the body is not stimulated during the i.sup.th
stimulation instance and is a non-zero value if the j.sup.th
portion of the body is stimulated during the i.sup.th stimulation
instance; determining a pseudoinverse of the matrix to estimate an
influence of each of the M portions of the body on the outcome
scores for the N stimulation instances; and storing or displaying
the estimated influences to identify which portions of the body,
when electrically stimulated, affect the at least one of the at
least one symptom of the condition or disorder, stimulation effect,
or stimulation side effect.
[0014] Yet another embodiment is a method for identifying portions
of a body in which electrical stimulation of that portion of the
body to treat a condition or disorder affects at least one of at
least one symptom of the condition or disorder, stimulation effect,
or stimulation side effect. The method includes obtaining N
stimulation instances, where N is an integer greater than one, and,
for each stimulation instance, an outcome score for each of at
least one symptom of the condition or disorder, stimulation effect,
or stimulation side effect; selecting M portions of the body, where
M is an integer greater than one; estimating, for each of the N
stimulation instances and for each of the M portions of the body,
whether that portion of the body was stimulated during that
stimulation instance; generating a matrix, where the matrix is
either a) a N.times.M matrix with entries a.sub.ij or b) a
M.times.N matrix with entries a.sub.ji, where i is an integer
ranging from 1 to N and corresponds to the i.sup.th stimulation
instance and j is an integer ranging from 1 to M and corresponds to
a j.sup.th portion of the body, where a.sub.ij or a.sub.ji,
respectively, is 0 if the j.sup.th portion of the body is not
stimulated during the i.sup.th stimulation instance and is a
non-zero value if the j.sup.th portion of the body is stimulated
during the i.sup.th stimulation instance; determining a
pseudoinverse of the matrix to estimate an influence of each of the
M portions of the body on the outcome scores for the N stimulation
instances; and storing or displaying the estimated influences to
identify which portions of the body, when electrically stimulated,
affect the at least one of the at least one symptom of the
condition or disorder, stimulation effect, or stimulation side
effect.
[0015] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, estimating,
for each of the N stimulation instances and for each of the M
portions of the body, whether that portion of the body was
stimulated during that stimulation instance includes estimating,
for each of the N stimulation instances and for each of the M
portions of the body, whether that portion of the body was
stimulated during that stimulation instance based on stimulation
parameters used during the stimulation instance. In at least some
embodiments of the system, non-transitory computer-readable medium,
or method described above, obtaining N stimulation instances
includes obtaining the N stimulation instances from a plurality of
patients. In at least some embodiments of the system,
non-transitory computer-readable medium, or method described above,
further including generating a score vector including the outcome
scores for the N stimulation instances. In at least some
embodiments of the system, non-transitory computer-readable medium,
or method described above, determining a pseudoinverse of the
matrix includes determining an influence vector using the
pseudoinverse and score vector, where each entry in the influence
vector corresponds to a different portion of the body. In at least
some embodiments of the system, non-transitory computer-readable
medium, or method described above, the entries of the influence
vector indicate a relative influence of the corresponding portions
of the body relative to the at least one symptom of the condition
or disorder, stimulation effect, or stimulation side effect.
[0016] A further embodiment is a system for selecting or
manipulating volumes of activation for electrical stimulation. The
system includes a computer processor configured and arranged to
perform the following acts: presenting a graphical user interface
that includes at least one user-activatable button selected from a
union button, an intersection button, or a subtraction button;
displaying at least two volumes of activation; and in response to
user activation of the at least one user-activatable button,
displaying a union, an intersection, or a subtraction of at least
two of the at least two volumes of activation.
[0017] Another embodiment is a non-transitory computer-readable
medium having processor-executable instructions for selecting or
manipulating volumes of activation for electrical stimulation, the
processor-executable instructions when installed onto a device
enable the device to perform actions, including: presenting a
graphical user interface that includes at least one
user-activatable button selected from a union button, an
intersection button, or a subtraction button; displaying at least
two volumes of activation; and in response to user activation of
the at least one user-activatable button, displaying a union, an
intersection, or a subtraction of at least two of the at least two
volumes of activation.
[0018] Yet another embodiment is a method for selecting or
manipulating volumes of activation for electrical stimulation. The
method includes presenting a graphical user interface that includes
at least one user-activatable button selected from a union button,
an intersection button, or a subtraction button; displaying at
least two volumes of activation; and in response to user activation
of the at least one user-activatable button, displaying a union, an
intersection, or a subtraction of at least two of the at least two
volumes of activation.
[0019] In at least some embodiments of the system, non-transitory
computer-readable medium, or method described above, the graphical
user interface includes a union button, an intersection button, and
a subtraction button. In at least some embodiments of the system,
non-transitory computer-readable medium, or method described above,
the volumes of activation further contain metadata associated with
the volumes of activation. In at least some embodiments of the
system, non-transitory computer-readable medium, or method
described above, the graphical user interface further includes a
search button. In at least some embodiments of the system,
non-transitory computer-readable medium, or method described above,
the acts further include in response to user activation of the
search button, allowing the user to indicate one or more search
terms; and searching metadata of a set of volumes of activation
using the one or more search terms to identify one or more volumes
of activation with metadata corresponding to the one or more search
terms.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] Non-limiting and non-exhaustive embodiments of the present
invention are described with reference to the following drawings.
In the drawings, like reference numerals refer to like parts
throughout the various figures unless otherwise specified. For a
better understanding of the present invention, reference will be
made to the following Detailed Description, which is to be read in
association with the accompanying drawings, wherein:
[0021] FIG. 1 is a schematic view of one embodiment of an
electrical stimulation system, according to the invention;
[0022] FIG. 2 is a schematic side view of one embodiment of an
electrical stimulation lead, according to the invention;
[0023] FIG. 3 is a schematic block diagram of one embodiment of a
system for determining stimulation parameters, according to the
invention;
[0024] FIG. 4 is a schematic flowchart of one embodiment of a
method of identifying portions of a body for electrical
stimulation, according to the invention;
[0025] FIG. 5A is a schematic illustration of one embodiment of a
matrix for use in the method of FIG. 4, according to the
invention;
[0026] FIG. 5B is a schematic illustration of one embodiment of a
randomized matrix for use in the method of FIG. 4, according to the
invention;
[0027] FIG. 5C is a schematic illustration of one embodiment of a
distribution of values obtained using the method of FIG. 4,
according to the invention;
[0028] FIG. 6 is a schematic flowchart of one embodiment of another
method of identifying portions of a body for electrical
stimulation, according to the invention;
[0029] FIG. 7A is a schematic illustration of one embodiment of a
matrix for use in the method of FIG. 6, according to the
invention;
[0030] FIG. 7B is a schematic illustration of one embodiment of a
score vector for use in the method of FIG. 6, according to the
invention;
[0031] FIG. 8A is a schematic illustration of one embodiment of a
determination of an influence vector using the method of FIG. 6,
according to the invention;
[0032] FIG. 8B is a schematic illustration of one embodiment of
another determination of an influence vector using the method of
FIG. 6, according to the invention;
[0033] FIG. 9A is a schematic illustration of one embodiment of a
graphical user interface for selecting or manipulating volumes of
activation, according to the invention;
[0034] FIG. 9B is a schematic illustration of the graphical user
interface of FIG. 9A in which the union of two volumes of
activation is presented, according to the invention;
[0035] FIG. 9C is a schematic illustration of the graphical user
interface of FIG. 9A in which the intersection of two volumes of
activation is presented, according to the invention; and
[0036] FIG. 9D is a schematic illustration of the graphical user
interface of FIG. 9A in which the subtraction of one volume of
activation from another volume of activation is presented,
according to the invention.
DETAILED DESCRIPTION
[0037] The present invention is directed to the area of implantable
electrical stimulation systems and methods of making and using the
systems. The present invention is also directed to systems for
determining regions of the body for stimulation or for selecting or
manipulating volumes of activation, as well as methods of making
and using the systems.
[0038] Suitable implantable electrical stimulation systems include,
but are not limited to, a least one lead with one or more
electrodes disposed on a distal end of the lead and one or more
terminals disposed on one or more proximal ends of the lead. Leads
include, for example, percutaneous leads and paddle leads. Examples
of electrical stimulation systems with leads are found in, for
example, U.S. Pat. Nos. 6,181,969; 6,516,227; 6,609,029; 6,609,032;
6,741,892; 7,244,150; 7,450,997; 7,672,734; 7,761,165; 7,783,359;
7,792,590; 7,809,446; 7,949,395; 7,974,706; 8,175,710; 8,224,450;
8,271,094; 8,295,944; 8,364,278; 8,391,985; and 8,688,235; and U.S.
Patent Applications Publication Nos. 2007/0150036; 2009/0187222;
2009/0276021; 2010/0076535; 2010/0268298; 2011/0005069;
2011/0004267; 2011/0078900; 2011/0130817; 2011/0130818;
2011/0238129; 2011/0313500; 2012/0016378; 2012/0046710;
2012/0071949; 2012/0165911; 2012/0197375; 2012/0203316;
2012/0203320; 2012/0203321; 2012/0316615; 2013/0105071; and
2013/0197602, all of which are incorporated by reference. In the
discussion below, a percutaneous lead will be exemplified, but it
will be understood that the methods and systems described herein
are also applicable to paddle leads.
[0039] A percutaneous lead for electrical stimulation (for example,
deep brain or spinal cord stimulation) includes stimulation
electrodes that can be ring electrodes or segmented electrodes that
extend only partially around the circumference of the lead or any
combination thereof. The segmented electrodes can be provided in
sets of electrodes, with each set having electrodes
circumferentially distributed about the lead at a particular
longitudinal position. For illustrative purposes, the leads are
described herein relative to use for deep brain stimulation, but it
will be understood that any of the leads can be used for
applications other than deep brain stimulation, including spinal
cord stimulation, peripheral nerve stimulation, or stimulation of
other nerves and tissues.
[0040] Turning to FIG. 1, one embodiment of an electrical
stimulation system 10 includes one or more stimulation leads 12 and
an implantable pulse generator (IPG) 14. The system 10 can also
include one or more of an external remote control (RC) 16, a
clinician's programmer (CP) 18, an external trial stimulator (ETS)
20, or an external charger 22.
[0041] The IPG 14 is physically connected, optionally via one or
more lead extensions 24, to the stimulation lead(s) 12. Each lead
carries multiple electrodes 26 arranged in an array. The IPG 14
includes pulse generation circuitry that delivers electrical
stimulation energy in the form of, for example, a pulsed electrical
waveform (i.e., a temporal series of electrical pulses) to the
electrode array 26 in accordance with a set of stimulation
parameters. The implantable pulse generator can be implanted into a
patient's body, for example, below the patient's clavicle area or
within the patient's buttocks or abdominal cavity. The implantable
pulse generator can have eight stimulation channels which may be
independently programmable to control the magnitude of the current
stimulus from each channel. In some embodiments, the implantable
pulse generator can have more or fewer than eight stimulation
channels (e.g., 4-, 6-, 16-, 32-, or more stimulation channels).
The implantable pulse generator can have one, two, three, four, or
more connector ports, for receiving the terminals of the leads.
[0042] The ETS 20 may also be physically connected, optionally via
the percutaneous lead extensions 28 and external cable 30, to the
stimulation leads 12. The ETS 20, which has similar pulse
generation circuitry as the IPG 14, also delivers electrical
stimulation energy in the form of, for example, a pulsed electrical
waveform to the electrode array 26 in accordance with a set of
stimulation parameters. One difference between the ETS 20 and the
IPG 14 is that the ETS 20 is often a non-implantable device that is
used on a trial basis after the neurostimulation leads 12 have been
implanted and prior to implantation of the IPG 14, to test the
responsiveness of the stimulation that is to be provided. Any
functions described herein with respect to the IPG 14 can likewise
be performed with respect to the ETS 20.
[0043] The RC 16 may be used to telemetrically communicate with or
control the IPG 14 or ETS 20 via a uni- or bi-directional wireless
communications link 32. Once the IPG 14 and neurostimulation leads
12 are implanted, the RC 16 may be used to telemetrically
communicate with or control the IPG 14 via a uni- or bi-directional
communications link 34. Such communication or control allows the
IPG 14 to be turned on or off and to be programmed with different
stimulation parameter sets. The IPG 14 may also be operated to
modify the programmed stimulation parameters to actively control
the characteristics of the electrical stimulation energy output by
the IPG 14.
[0044] The CP 18 allows a user, such as a clinician, the ability to
program stimulation parameters for the IPG 14 and ETS 20 in the
operating room and in follow-up sessions.
[0045] The CP 18 may perform this function by indirectly
communicating with the IPG 14 or ETS 20, through the RC 16, via a
wireless communications link 36. Alternatively, the CP 18 may
directly communicate with the IPG 14 or ETS 20 via a wireless
communications link (not shown). The stimulation parameters
provided by the CP 18 are also used to program the RC 16, so that
the stimulation parameters can be subsequently modified by
operation of the RC 16 in a stand-alone mode (i.e., without the
assistance of the CP 18).
[0046] For purposes of brevity, the details of the RC 16, CP 18,
ETS 20, and external charger 22 will not be further described
herein. Details of exemplary embodiments of these devices are
disclosed in U.S. Pat. No. 6,895,280, which is expressly
incorporated herein by reference. Other examples of electrical
stimulation systems can be found at U.S. Pat. Nos. 6,181,969;
6,516,227; 6,609,029; 6,609,032; 6,741,892; 7,949,395; 7,244,150;
7,672,734; and 7,761,165; 7,974,706; 8,175,710; 8,224,450; and
8,364,278; and U.S. Patent Application Publication No.
2007/0150036, as well as the other references cited above, all of
which are incorporated by reference.
[0047] FIG. 2 illustrates one embodiment of a lead 110 with
electrodes 125 disposed at least partially about a circumference of
the lead 110 along a distal end portion of the lead and terminals
135 disposed along a proximal end portion of the lead.
[0048] The lead 110 can be implanted near or within the desired
portion of the body to be stimulated such as, for example, the
brain, spinal cord, or other body organs or tissues. In one example
of operation for deep brain stimulation, access to the desired
position in the brain can be accomplished by drilling a hole in the
patient's skull or cranium with a cranial drill (commonly referred
to as a burr), and coagulating and incising the dura mater, or
brain covering. The lead 110 can be inserted into the cranium and
brain tissue with the assistance of a stylet (not shown). The lead
110 can be guided to the target location within the brain using,
for example, a stereotactic frame and a microdrive motor system. In
some embodiments, the microdrive motor system can be fully or
partially automatic. The microdrive motor system may be configured
to perform one or more the following actions (alone or in
combination): insert the lead 110, advance the lead 110, retract
the lead 110, or rotate the lead 110.
[0049] In some embodiments, measurement devices coupled to the
muscles or other tissues stimulated by the target neurons, or a
unit responsive to the patient or clinician, can be coupled to the
implantable pulse generator or microdrive motor system. The
measurement device, user, or clinician can indicate a response by
the target muscles or other tissues to the stimulation or recording
electrode(s) to further identify the target neurons and facilitate
positioning of the stimulation electrode(s). For example, if the
target neurons are directed to a muscle experiencing tremors, a
measurement device can be used to observe the muscle and indicate
changes in tremor frequency or amplitude in response to stimulation
of neurons. Alternatively, the patient or clinician can observe the
muscle and provide feedback.
[0050] The lead 110 for deep brain stimulation can include
stimulation electrodes, recording electrodes, or both. In at least
some embodiments, the lead 110 is rotatable so that the stimulation
electrodes can be aligned with the target neurons after the neurons
have been located using the recording electrodes.
[0051] Stimulation electrodes may be disposed on the circumference
of the lead 110 to stimulate the target neurons. Stimulation
electrodes may be ring-shaped so that current projects from each
electrode equally in every direction from the position of the
electrode along a length of the lead 110. In the embodiment of FIG.
2, two of the electrodes 120 are ring electrodes 120. Ring
electrodes typically do not enable stimulus current to be directed
from only a limited angular range around of the lead. Segmented
electrodes 130, however, can be used to direct stimulus current to
a selected angular range around the lead. When segmented electrodes
are used in conjunction with an implantable pulse generator that
delivers constant current stimulus, current steering can be
achieved to more precisely deliver the stimulus to a position
around an axis of the lead (i.e., radial positioning around the
axis of the lead). To achieve current steering, segmented
electrodes can be utilized in addition to, or as an alternative to,
ring electrodes.
[0052] The lead 100 includes a lead body 110, terminals 135, and
one or more ring electrodes 120 and one or more sets of segmented
electrodes 130 (or any other combination of electrodes). The lead
body 110 can be formed of a biocompatible, non-conducting material
such as, for example, a polymeric material. Suitable polymeric
materials include, but are not limited to, silicone, polyurethane,
polyurea, polyurethane-urea, polyethylene, or the like. Once
implanted in the body, the lead 100 may be in contact with body
tissue for extended periods of time. In at least some embodiments,
the lead 100 has a cross-sectional diameter of no more than 1.5 mm
and may be in the range of 0.5 to 1.5 mm. In at least some
embodiments, the lead 100 has a length of at least 10 cm and the
length of the lead 100 may be in the range of 10 to 70 cm.
[0053] The electrodes 125 can be made using a metal, alloy,
conductive oxide, or any other suitable conductive biocompatible
material. Examples of suitable materials include, but are not
limited to, platinum, platinum iridium alloy, iridium, titanium,
tungsten, palladium, palladium rhodium, or the like. Preferably,
the electrodes are made of a material that is biocompatible and
does not substantially corrode under expected operating conditions
in the operating environment for the expected duration of use.
[0054] Each of the electrodes can either be used or unused (OFF).
When the electrode is used, the electrode can be used as an anode
or cathode and carry anodic or cathodic current. In some instances,
an electrode might be an anode for a period of time and a cathode
for a period of time.
[0055] Deep brain stimulation leads may include one or more sets of
segmented electrodes. Segmented electrodes may provide for superior
current steering than ring electrodes because target structures in
deep brain stimulation are not typically symmetric about the axis
of the distal electrode array. Instead, a target may be located on
one side of a plane running through the axis of the lead. Through
the use of a radially segmented electrode array ("RSEA"), current
steering can be performed not only along a length of the lead but
also around a circumference of the lead. This provides precise
three-dimensional targeting and delivery of the current stimulus to
neural target tissue, while potentially avoiding stimulation of
other tissue. Examples of leads with segmented electrodes include
U.S. Patent Application Publications Nos. 2010/0268298;
2011/0005069; 2011/0130803; 2011/0130816; 2011/0130817;
2011/0130818; 2011/0078900; 2011/0238129; 2012/0016378;
2012/0046710; 2012/0071949; 2012/0165911; 2012/197375;
2012/0203316; 2012/0203320; 2012/0203321, all of which are
incorporated herein by reference.
[0056] An electrical stimulation lead can be implanted in the body
of a patient (for example, in the brain or spinal cord of the
patient) and used to stimulate surrounding tissue. It is useful to
estimate the effective region of stimulation (often called a volume
of activation (VOA) or stimulation field model (SFM)) given the
position of the lead and its electrodes in the patient's body and
the stimulation parameters used to generate the stimulation. Any
suitable method for determining the VOA and for graphically
displaying the VOA relative to patient anatomy can be used
including those described in, for example, U.S. Pat. Nos.
8,326,433; 8,675,945; 8,831,731; 8,849,632; and 8,958,615; U.S.
Patent Application Publications Nos. 2009/0287272; 2009/0287273;
2012/0314924; 2013/0116744; 2014/0122379; and 2015/0066111; and
U.S. Provisional Patent Application Ser. No. 62/030,655, all of
which are incorporated herein by reference. Several of these
references also disclose methods and systems for registering an
atlas of body structures to imaged patient physiology.
[0057] A VOA can be determined based on a set of stimulation
parameters input into the system. The VOA can then be modified by
the user by modifying the stimulation parameters and determining
the new VOA from the modified stimulation parameters. This allows
the user to tailor the stimulation volume.
[0058] FIG. 3 illustrates one embodiment of a system for
determining electrical stimulation parameters. The system can
include a computing device 300 or any other similar device that
includes a processor 302 and a memory 304, a display 306, an input
device 308, and, optionally, the electrical stimulation system 312.
The system 300 may also optionally include one or more imaging
systems 310.
[0059] The computing device 300 can be a computer, tablet, mobile
device, or any other suitable device for processing information.
The computing device 300 can be local to the user or can include
components that are non-local to the computer including one or both
of the processor 302 or memory 304 (or portions thereof). For
example, in some embodiments, the user may operate a terminal that
is connected to a non-local computing device. In other embodiments,
the memory can be non-local to the user.
[0060] The computing device 300 can utilize any suitable processor
302 including one or more hardware processors that may be local to
the user or non-local to the user or other components of the
computing device. The processor 302 is configured to execute
instructions provided to the processor.
[0061] Any suitable memory 304 can be used for the computing device
302. The memory 304 illustrates a type of computer-readable media,
namely computer-readable storage media. Computer-readable storage
media may include, but is not limited to, nonvolatile,
non-transitory, removable, and non-removable media implemented in
any method or technology for storage of information, such as
computer readable instructions, data structures, program modules,
or other data. Examples of computer-readable storage media include
RAM, ROM, EEPROM, flash memory, or other memory technology, CD-ROM,
digital versatile disks ("DVD") or other optical storage, magnetic
cassettes, magnetic tape, magnetic disk storage or other magnetic
storage devices, or any other medium which can be used to store the
desired information and which can be accessed by a computing
device.
[0062] Communication methods provide another type of computer
readable media; namely communication media. Communication media
typically embodies computer-readable instructions, data structures,
program modules, or other data in a modulated data signal such as a
carrier wave, data signal, or other transport mechanism and include
any information delivery media. The terms "modulated data signal,"
and "carrier-wave signal" includes a signal that has one or more of
its characteristics set or changed in such a manner as to encode
information, instructions, data, and the like, in the signal. By
way of example, communication media includes wired media such as
twisted pair, coaxial cable, fiber optics, wave guides, and other
wired media and wireless media such as acoustic, RF, infrared, and
other wireless media.
[0063] The display 306 can be any suitable display device, such as
a monitor, screen, display, or the like, and can include a printer.
The input device 308 can be, for example, a keyboard, mouse, touch
screen, track ball, joystick, voice recognition system, or any
combination thereof, or the like.
[0064] One or more imaging systems 310 can be used including, but
not limited to, MRI, CT, ultrasound, or other imaging systems. The
imaging system 310 may communicate through a wired or wireless
connection with the computing device 300 or, alternatively or
additionally, a user can provide images from the imaging system 310
using a computer-readable medium or by some other mechanism.
[0065] The electrical stimulation system 312 can include, for
example, any of the components illustrated in FIG. 1. The
electrical stimulation system 312 may communicate with the
computing device 300 through a wired or wireless connection or,
alternatively or additionally, a user can provide information
between the electrical stimulation system 312 and the computing
device 300 using a computer-readable medium or by some other
mechanism. In some embodiments, the computing device 300 may
include part of the electrical stimulation system, such as, for
example, the IPG, CP, RC, ETS, or any combination thereof.
[0066] The methods and systems described herein may be embodied in
many different forms and should not be construed as limited to the
embodiments set forth herein.
[0067] Accordingly, the methods and systems described herein may
take the form of an entirely hardware embodiment, an entirely
software embodiment or an embodiment combining software and
hardware aspects. Systems referenced herein typically include
memory and typically include methods for communication with other
devices including mobile devices. Methods of communication can
include both wired and wireless communications methods. Wired
communication can include communication over a twisted pair,
coaxial cable, fiber optics, wave guides, or the like, or any
combination thereof. Wireless communication can include RF,
infrared, optical, acoustic, near field communication,
Bluetooth.TM., or the like, or any combination thereof.
[0068] It would useful to determine desirable regions for delivery
of electrical stimulation to provide a therapeutic effect or to
determine regions to avoid stimulating to reduce or avoid a side
effect. In at least some instances, when an electrical stimulation
lead is implanted in a patient, the patient undergoes an assessment
in which different sets of stimulation parameters are tested and
assessed based on some rating scale (for example, the Unified
Parkinson's Disease Rating Scale (UPDRS)).
[0069] In addition, in at least some instances, the location of the
implanted lead within the patient's body can be determined using
postoperative imaging (for example, by a CT scan). The location of
the lead, and its corresponding electrodes, and the stimulation
parameters can be used to estimate the volume of tissue that is
stimulated using those parameters.
[0070] This data from a single patient or from multiple patients
can be evaluated to identify which portions of body (for example,
portions of the brain), when electrically stimulated, are likely to
affect at least one symptom of a treated condition or disorder or
produce a stimulation effect or produce a stimulation side effect.
When data from multiple patients is evaluated, the patients may be
drawn from the general population or can be selected based on one
or more criteria including, but not limited to, the condition or
disorder being treated, age, gender, residence, weight, ethnicity,
nationality, or the like or any combination thereof.
[0071] By understanding which portions of the body, when
electrically stimulated, are likely to produce an effect on a
symptom, some other stimulation effect, or a side effect, a
practitioner can select stimulation parameters that are likely to
stimulate (or not simulate) a portion of the body. It will be
recognized that these parameters represent estimates and, when
implemented, may be revised or modified upon actual testing in the
patient's body.
[0072] The present invention is directed, at least in part, to
evaluating data from patients to predict which portions of the body
can be stimulated to produce an effect on a symptom, a stimulation
effect, or a stimulation side effect. In some embodiments, a
permutation test can be used to evaluate multiple actual
stimulation instances and associated scores to evaluate which
portions of the body are likely to produce an effect on a symptom,
a stimulation effect, or a side effect when stimulated.
[0073] FIG. 4 outlines one embodiment of a method for identifying
portions of a body in which electrical stimulation to treat a
condition or disorder is likely to affect at least one symptom,
stimulation effect, or stimulation side effect. In step 402,
multiple actual stimulation instances are obtained. In at least
some embodiments, each stimulation instance includes a set of
stimulation parameters (for example, pulse width, pulse duration,
pulse frequency, pulse amplitude, and the like), values for those
stimulation parameters, and at least one score directed toward at
least one symptom, stimulation effect, or stimulation side effect.
As used herein, the term "stimulation parameter" is used to
indicate the a categorization of a parameter and the terms
"stimulation parameter value" or "value" are used to indicated the
actual value (for example, a numerical value) for the particular
stimulation parameter.
[0074] In at least some embodiments, each stimulation instance
includes the same stimulation parameters, although one or more of
the stimulation parameter values may be different. In other
embodiments, a different set of stimulation parameters may be
associated with one or more of the stimulation instances. For
example, some stimulation instances may include a stimulation pulse
width while other stimulation instances fail to include the
stimulation pulse width.
[0075] In at least some embodiments, each stimulation instance
includes score(s) for the same symptom(s), stimulation effect(s),
or stimulation side effect(s). In other embodiments, different
stimulation instances may have score(s) for different sets of
symptom(s), stimulation effect(s), or stimulation side
effect(s).
[0076] The stimulation instances can be from a single patient or
can be from multiple patients. In at least some embodiments, each
stimulation instance is directed to treating the same condition or
disorder. In other embodiments, different stimulation instances may
be directed to treating different conditions or disorders which may
be related or unrelated.
[0077] In step 404, the stimulation parameters of each stimulation
instance are used to estimate a region of the body that is
stimulated by these stimulation parameters. These estimates can
include, for example, estimates of axonal activation, estimates of
cell bodies that are activated, estimates of fiber pathways that
are activated, and the like or any combination thereof. In at least
some instances, the estimate is called a value of activation (VOA)
or stimulation field model (SFM) Examples of suitable methods for
making these estimations include, but are not limited to, those
described in U.S. Pat. Nos. 8,326,433; 8,675,945; 8,831,731;
8,849,632; and 8,958,615; U.S. Patent Application Publications Nos.
2009/0287272; 2009/0287273; 2012/0314924; 2013/0116744;
2014/0122379; and 2015/0066111; and U.S. Provisional Patent
Application Ser. No. 62/030,655, all of which are incorporated
herein by reference. It will be understood that other methods of
estimating the stimulation region that do not use the stimulation
parameters can also be employed.
[0078] In other embodiments, the stimulation instances are provided
to the system with an indication of the stimulation region. In such
embodiments, the system may not need to computer or estimate the
stimulation regions.
[0079] As the stimulation regions are computed or estimated, the
stimulation regions are optionally transformed to a common space
using the patients' imaging data, using an anatomical atlas, or
using any other suitable method for providing a common reference
frame for the stimulation regions. This enables overlay of all
stimulation regions for all stimulation instances into the common
reference frame.
[0080] In step 406, the likelihood that stimulation of each of one
or more selected portions of the body will affect a symptom,
stimulation effect, or stimulation side effect is analyzed. In at
least some embodiments, a body area of interest is divided into
volume elements ("voxels"). Each voxel can have a same volume or
the voxels can have different volumes. In some embodiments, voxels
are selected so that each voxel is only associated with a single
anatomical structure (for example, a single brain structure). The
voxels may cover the entire area of interest or only portions of
the area of interest. The voxels can be contiguous with each other
or non-contiguous.
[0081] A permutation test is used to determine a likelihood whether
stimulation of a particular voxel contributes to the score for a
particular symptom, stimulation effect, or stimulation side effect.
To illustrate one method of analyzing the likelihood that
stimulation of a voxel (which correspond to a portion of the body,
as described above) will affect a particular symptom, stimulation
effect, or stimulation side effect using a permutation test, a
matrix is created for that voxel and for that symptom, stimulation
effect, or stimulation side effect. As an example, a 2 column
matrix 500 can be created for each voxel for a single symptom,
stimulation effect, or stimulation side effect, as illustrated in
FIG. 5A. Each row of this matrix corresponds to a different
stimulation instance. In the illustrated example, there are N
stimulation instances. The entry for each row, A.sub.n, in the
first column of this matrix is 0 or 1 depending on whether the
voxel was stimulated (i.e., active) or not stimulated (i.e.,
inactive), respectively, for this stimulation instance. The entry
for each row, S.sub.n, in the second column is the corresponding
score that indicates, for example, the improvement or worsening of
the particular symptom, stimulation effect, or stimulation side
effect for that stimulation instance. It will be recognized that
the rows can instead be columns and columns can then be rows. A
similar matrix can be formed for each individual voxel. In
addition, similar matrices can be used to investigate other
symptoms, stimulation effects, or stimulation side effects.
[0082] A statistical analysis is performed using a permutation test
to assess whether a voxel's state of activation is influential on
the symptom, stimulation effect, or stimulation side effect. As an
example, the permutation test proceeds as follows: the difference
in average scores (or difference in scores or any other suitable
measure) between the active (first column=1) and inactive (first
column=0) states for each voxel is determined. Then, the entries in
the first column (or, alternatively, the second column) in the
matrix are randomized to produce a new matrix 500', as illustrated
in FIG. 5B where x, y, z, and w are different random integers in
the range from 1 to N. The difference in average scores between the
"active" (first column=1) and "inactive" (first column=0) states is
again calculated for this randomized matrix. This randomization and
difference determination process is repeated many times (for
example, at least 100, 500, 1000, 2000, 2500, 5000, or more times).
The resulting differences can be plotted as a distribution 502 of
the difference in scores between the "active" states (first
column=1) and "inactive" states (first column=0), as illustrated in
FIG. 5C. The permutation test is performed under the null
hypothesis that "the voxel's state (active or inactive) does not
influence the scores". The observed value 504 of the difference
between scores in the actual active and inactive state (which is
the first computed difference) is compared with this distribution.
If the observed value is unlikely to occur from this distribution,
the null hypothesis is declared invalid (i.e. the voxel does
influence the scores). If the null hypothesis is declared invalid,
it is likely that the voxel does influence the scores for the
selected symptom, stimulation effect, or stimulation side effect.
The likelihood of the observed value occurring in the distribution
can be used to determine or estimate a qualitative or quantitative
likelihood that the voxel influences the scores for the selected
symptom, stimulation effect, or stimulation side effect.
[0083] A permutation test can be performed for each voxel of
interest with respect to the selected symptom, stimulation effect,
or stimulation side effect. This process separates voxels between
those that are likely influential with respect to the selected
symptom, stimulation effect, or stimulation side effect and those
that are not likely influential. One or more of the influential
voxels can form a target volume for the given symptom, stimulation
effect, and stimulation side effect. A threshold criterion 506, or
multiple threshold criteria, (where the observed value 504 is
outside the threshold criterion) can be used to extract voxels at
different levels of significance.
[0084] The importance of using a permutation test here (as opposed
to a t-test) is that a permutation test provides a robust,
non-parametric approach to determine statistical significance of
the influence of a voxel on a particular symptom, stimulation
effect, and stimulation side effect.
[0085] In step 408, the this analysis of the voxels and their
influence on the selected symptom, stimulation effect, stimulation
side effect can be stored on a computer or other storage device and
can be displayed for review by a practitioner. The process can be
repeated for additional voxels and for additional symptoms,
stimulation effects, or stimulation side effects. A practitioner
can utilize the results of these analyses to identify portions of
the body that could be stimulated to produce a desirable treatment
of one or more symptoms or desirable stimulation effects or
portions of the body to avoid stimulating to reduce or eliminate
one or more side effects.
[0086] A user can then use the analysis of the voxels to identify a
proposed stimulation region and then select stimulation parameters
that will stimulate that region. In at least some embodiments, the
stimulation parameters can be provided to an implantable pulse
generator or external trial stimulator for generating electrical
stimulation. The electrical stimulation can be provided to a
patient using any suitable electrical stimulation system including
the stimulation system illustrated in FIG. 1.
[0087] In some embodiments, a pseudoinverse is used to evaluate
multiple actual stimulation instances and associated scores to
evaluate which portions of the body, when stimulated, contribute to
an outcome. The outcome can represent treatment of a symptom,
disease, or disorder; production of a stimulation effect;
production of a stimulation side effect; or the like.
[0088] FIG. 6 outlines one embodiment of a method for identifying
evaluate which portions of the body, when stimulated, are likely to
affect at least one symptom, stimulation effect, or stimulation
side effect. In step 602, multiple actual stimulation instances are
obtained. Each stimulation instance includes a set of stimulation
parameters (for example, pulse width, pulse duration, pulse
frequency, pulse amplitude, and the like), values for those
stimulation parameters, and at least one score directed toward an
outcome such as treatment of at least one symptom, disease, or
disorder; production of a stimulation effect; or production of a
stimulation side effect. As used herein, the term "stimulation
parameter" is used to indicate the a categorization of a parameter
and the terms "stimulation parameter value" or "value" are used to
indicated the actual value (for example, a numerical value) for the
particular stimulation parameter.
[0089] In at least some embodiments, each stimulation instance
includes the same stimulation parameters, although one or more of
the stimulation parameter values may be different. In other
embodiments, a different set of stimulation parameters may be
associated with one or more of the stimulation instances. For
example, some stimulation instances may include a stimulation pulse
width while other stimulation instances fail to include the
stimulation pulse width.
[0090] In at least some embodiments, each stimulation instance
includes score(s) for the same symptom(s), stimulation effect(s),
or stimulation side effect(s). In other embodiments, different
stimulation instances may have score(s) for different sets of
symptom(s), stimulation effect(s), or stimulation side
effect(s).
[0091] The stimulation instances can be from a single patient or
can be from multiple patients. In at least some embodiments, each
stimulation instance is directed to treating the same condition or
disorder. In other embodiments, different stimulation instances may
be directed to treating different conditions or disorders which may
be related or unrelated.
[0092] In step 604, the stimulation parameters of each stimulation
instance are used to estimate a region of the body that is
stimulated by these stimulation parameters. These estimates can
include, for example, estimates of axonal activation, estimates of
cell bodies that are activated, estimates of fiber pathways that
are activated, and the like or any combination thereof. In at least
some instances, the estimate is called a value of activation (VOA)
or stimulation field model (SFM) Examples of suitable methods for
making these estimations include, but are not limited to, those
described in U.S. Pat. Nos. 8,326,433; 8,675,945; 8,831,731;
8,849,632; and 8,958,615; U.S. Patent Application Publications Nos.
2009/0287272; 2009/0287273; 2012/0314924; 2013/0116744;
2013/0116748; 2014/0122379; and 2015/0066111; and U.S. Provisional
Patent Application Ser. No. 62/030,655, all of which are
incorporated herein by reference. It will be understood that other
methods of estimating the stimulation region that do not use the
stimulation parameters can also be employed.
[0093] In other embodiments, the stimulation instances are provided
to the system with an indication of the stimulation region. In such
embodiments, the system may not need to computer or estimate the
stimulation regions.
[0094] As the stimulation regions are computed or estimated, the
stimulation regions are optionally transformed to a common space
using the patients' imaging data, using an anatomical atlas, or
using any other suitable method for providing a common reference
frame for the stimulation regions. This enables overlay of all
stimulation regions for all stimulation instances into the common
reference frame.
[0095] In step 606, an analysis is preformed to identify portions
of the body that, when stimulated, will likely affect a symptom,
stimulation effect, or stimulation side effect. In at least some
embodiments, a body area of interest is divided into volume
elements ("voxels"). Each voxel can have a same volume or the
voxels can have different volumes. In some embodiments, voxels are
selected so that each voxel is only associated with a single
anatomical structure (for example, a single brain structure). The
voxels may cover the entire area of interest or only portions of
the area of interest.
[0096] The voxels can be contiguous with each other or
non-contiguous.
[0097] To illustrate one method of analyzing which voxels (which
correspond to portions of the body), when stimulated, will likely
affect a particular symptom, stimulation effect, or stimulation
side effect using a pseudoinverse calculation, a matrix is created
with each voxel representing a column and each stimulation instance
representing a row. (It will be understood that, alternatively, the
voxels could be assigned as rows and the stimulation instances
could be assigned as columns.) For N stimulation instances and M
voxels (i.e., portions of the body), the matrix is a N.times.M
matrix, A, with entries a.sub.ij (or a M.times.N matrix with
entries a.sub.ji if the alternative assignment of rows and columns
is used) where i is an integer ranging from 1 to N and corresponds
to the i.sup.th stimulation instance and j is an integer ranging
from 1 to M and corresponds to a j.sup.th portion of the body, as
illustrated in FIG. 7A. In this embodiment, au is 0 if the j.sup.th
portion of the body is not stimulated during the i.sup.th
stimulation instance and is a non-zero value (for example, one) if
the j.sup.th portion of the body is stimulated during the i.sup.th
stimulation instance.
[0098] In addition, a one column vector, S, of the scores is
generated with entries S.sub.i which is the score (i.e., outcome)
for the i.sup.th stimulation instance, as illustrated in FIG. 7B.
Based on these definitions of S and A, S=AI, where I is a one
column influence vector which indicates that influence that
stimulation of each voxel has on the observed outcomes. The
influence vector can then be determined as 1=A.sup.+S, wherein
A.sup.+ is the pseudoinverse of A. Methods for calculating,
estimating, or otherwise determining the pseudoinverse, A.sup.+, of
A are known and any suitable method can be used.
[0099] FIG. 8A illustrates one example of a 5.times.4 matrix A
which represents five stimulation instances and four voxels. The
matrix A has been filled out to indicate which voxels are
stimulated (a j=1) or not stimulated (a.sub.ij=0) during each
stimulation instance. The example also includes a score vector S
with scores S.sub.1 to S.sub.5. Using the pseudoinverse of A, an
influence vector can be obtained, as illustrated in FIG. 8A. The
entries in the influence vector correspond to the respective voxels
and can be used to indicate which voxels are most likely to
influence an overall outcome with respect to a particular symptom,
stimulation effect, or stimulation side effect.
[0100] FIG. 8B illustrates one example of a 3.times.4 matrix A
which represents three stimulation instances and four voxels. The
matrix A has been filled out to indicate which voxels are
stimulated (a.sub.ij=1) or not stimulated (a.sub.ij=0) during each
stimulation instance. The example also includes a score vector S
with scores S.sub.1 to S.sub.3. Using the pseudoinverse of A, an
influence vector can be obtained, as illustrated in FIG. 8B. The
entries in the influence vector correspond to the respective voxels
and can be used to indicate which voxels are most likely to
influence an overall outcome with respect to a particular symptom,
stimulation effect, or stimulation side effect.
[0101] In step 608, the analysis of the voxels and their influence
on the selected symptom, stimulation effect, stimulation side
effect can be stored on a computer or other storage device and can
be displayed for review by a practitioner. The process can be
repeated for additional voxels and for additional symptoms,
stimulation effects, or stimulation side effects. A practitioner
can utilize the results of these analyses to identify portions of
the body that could be stimulated to produce a desirable treatment
of one or more symptoms or desirable stimulation effects or
portions of the body to avoid stimulating to reduce or eliminate
one or more side effects.
[0102] A user can then use the analysis of the voxels to identify a
proposed stimulation region and then select stimulation parameters
that will stimulate that region. In at least some embodiments, the
stimulation parameters can be provided to an implantable pulse
generator or external trial stimulator for generating electrical
stimulation. The electrical stimulation can be provided to a
patient using any suitable electrical stimulation system including
the stimulation system illustrated in FIG. 1.
[0103] A graphical user interface (GUI) can be used to visualize
and modify one or more VOAs. FIG. 9A shows a GUI 980 according to
an example embodiment of the present invention. The illustrated GUI
980 is simplified for purposes of illustration and illustrates two
VOAs 982a, 982b and several buttons 984, 986, 988, 990 for user
interaction to activate system functions. It will be understood,
however, that the GUI can include additional features including,
but not limited to, one or more of a representation of patient body
structures (e.g., portions of the patient brain or any other
anatomical region) which may obtained from images or represent
idealized structures based on an atlas or the like; a
representation of a lead or lead electrodes; additional buttons or
other structures for initiating GUI functions; information
regarding the patient, body structures, VOAs, stimulation
parameters, or the like; and so forth. Examples of GUIs that can be
modified to include the functions described herein can be found at,
for example, U.S. Pat. Nos. 8,326,433; 8,675,945; 8,831,731;
8,849,632; and 8,958,615; U.S. Patent Application Publications Nos.
2009/0287272; 2009/0287273; 2012/0314924; 2013/0116744;
2013/0116748; 2014/0122379; and 2015/0066111; and U.S. Provisional
Patent Application Ser. No. 62/030,655, all of which are
incorporated herein by reference.
[0104] The displayed VOAs can be two dimensional (as illustrated in
FIG. 9A) or three dimensional. In at least some embodiments, the
GUI is user-interactive, e.g., by point and click using an input
device such as a mouse, stylus, or even the user's finger, or by
keyboard manipulation, for selecting or deselecting buttons and the
like.
[0105] The illustrated GUI includes a union button 985, an
intersection button 986, a subtraction button 988, and a search
button 990. Other GUIs can include any combination of these buttons
and GUI elements as described in the references cited above.
[0106] In some embodiments, the system can allow visualization of
VOA's that can be calculated based on stimulation parameters and,
optionally, are associated with a patient. The VOA's can be tagged
with metadata that can be searched. Examples of metadata include,
but are not limited to, demographic information (e.g., gender, age,
race, nationality, height, weight, or the like of a patient
associated with the VOA), diagnosis, clinician notes, lead
position, stimulated body structures, or the like. The VOA's from
multiple patients may be maintained in a database and, at least in
some systems, the VOA's may be searchable based on one or more
metadata items. In at least some embodiments, the GUI 980 includes
a search button 990 that initiates a search procedure that allows
the user to input or select search parameters, such as the metadata
indicated above, in order to find and display one or more VOAs.
[0107] In some embodiments, the system may also allow the user to
perform operations on VOAs. For example, a GUI 980 can include a
union button 984 to form the union 982c of two or more VOAs 982a,
982b (FIG. 9A) as illustrated in FIG. 9B, an intersection button
986 to form the intersection 982d of two or more VOAs 982a, 982b
(FIG. 9A) as illustrated in FIG. 9C, or a subtraction button to
subtract one VOA 982b (FIG. 9A) from another VOA 982a (FIG. 9A) to
form a new VOA 982e, as illustrated in FIG. 9D of a VOA, or any
combination of these buttons. The resulting modified VOA can be
displayed in a GUI. For example, the user may request which voxels
are common to two or more VOAs and the GUI can display the
intersection of the two or more VOAs. As another example, the user
may request display of the union of two or more VOAs. As yet
another example, the user may request the intersection of VOA A
with VOA B followed by the union of this result with VOA C. In a
further example, the user may request the union of VOA A with VOA B
followed by the intersection with VOA C.
[0108] In at least some embodiments, if an intersection of two or
more VOAs is requested, the system may also determine and display
an indication of what fraction or percentage of one or more of the
VOAs remains in the intersection. In at least some embodiments, if
an intersection of two or more VOAs is requested, the system may
also determine and display an indication of what fraction or
percentage of one or more of the VOAs is excluded from the
intersection. In at least some embodiments, if one VOA is
subtracted from another VOA, the system may also determine and
display an indication of what fraction or percentage of one or more
of the VOAs remains. In at least some embodiments, if one VOA is
subtracted from another VOA, the system may also determine and
display an indication of what fraction or percentage of one or more
of the VOAs is removed or excluded from the result. Examples of
other calculations that can be performed for combinations of VOAs
can be found in U.S. Patent Application Publication No.
2013/0116748, incorporated herein by reference.
[0109] In at least some embodiments, the union, intersection, or
subtraction of two or more VOAs can also be displayed with one or
more anatomic structures (for example, brain structures), such as
those obtained using an atlas or using images from the patient or
from some other source. In at least some embodiments, if the union,
intersection, or subtraction of two or more VOAs includes at least
a threshold amount (for example, at least 25%, 33%, 50%, 67%, 75%,
or more) of a particular anatomic structure, the resulting VOA may
be modified, either automatically, manually, or with approval by
the user, to include the anatomic structure.
[0110] It will be understood that the system can include one or
more of the methods and GUIs described hereinabove with respect to
FIGS. 4-9D in any combination. The methods, systems, and GUIs
described herein may be embodied in many different forms and should
not be construed as limited to the embodiments set forth
herein.
[0111] Accordingly, the methods, systems, and GUIs described herein
may take the form of an entirely hardware embodiment, an entirely
software embodiment or an embodiment combining software and
hardware aspects. The methods described herein can be performed
using any type of processor or any combination of processors where
each processor performs at least part of the process.
[0112] It will be understood that each block of the flowchart
illustrations, and combinations of blocks in the flowchart
illustrations and methods disclosed herein, can be implemented by
computer program instructions. These program instructions may be
provided to a processor to produce a machine, such that the
instructions, which execute on the processor, create means for
implementing the actions specified in the flowchart block or blocks
disclosed herein. The computer program instructions may be executed
by a processor to cause a series of operational steps to be
performed by the processor to produce a computer implemented
process. The computer program instructions may also cause at least
some of the operational steps to be performed in parallel.
Moreover, some of the steps may also be performed across more than
one processor, such as might arise in a multi-processor computer
system. In addition, one or more processes may also be performed
concurrently with other processes, or even in a different sequence
than illustrated without departing from the scope or spirit of the
invention.
[0113] The computer program instructions can be stored on any
suitable computer-readable medium including, but not limited to,
RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM,
digital versatile disks ("DVD") or other optical storage, magnetic
cassettes, magnetic tape, magnetic disk storage or other magnetic
storage devices, or any other medium which can be used to store the
desired information and which can be accessed by a computing
device.
[0114] The above specification, examples and data provide a
description of the manufacture and use of the composition of the
invention. Since many embodiments of the invention can be made
without departing from the spirit and scope of the invention, the
invention also resides in the claims hereinafter appended.
* * * * *