U.S. patent application number 17/588373 was filed with the patent office on 2022-05-19 for brain navigation lead.
This patent application is currently assigned to Alpha Omega Engineering Ltd.. The applicant listed for this patent is Alpha Omega Engineering Ltd.. Invention is credited to Adi BALAN, Hagai BERGMAN, Jubran ELFAR, Oren A. GARGIR, Zvi ISRAEL, Benjamin MATTER, Paul MCSHERRY, Omer NAOR, Steven SCOTT, Imad YOUNIS.
Application Number | 20220151537 17/588373 |
Document ID | / |
Family ID | 1000006110657 |
Filed Date | 2022-05-19 |
United States Patent
Application |
20220151537 |
Kind Code |
A1 |
NAOR; Omer ; et al. |
May 19, 2022 |
BRAIN NAVIGATION LEAD
Abstract
A brain navigation device, comprising: a lead with an elongated
lead body; at least one macro-electrode contact positioned on an
outer surface on the lead; wherein the at least one macro-electrode
contact is located at the distal part of said lead; and wherein the
at least one macro-electrode contact is configured to be used
during lead navigation.
Inventors: |
NAOR; Omer; (Kiryat-Tivon,
IL) ; BALAN; Adi; (Haifa, IL) ; BERGMAN;
Hagai; (Jerusalem, IL) ; YOUNIS; Imad;
(Nazareth Ilit, IL) ; GARGIR; Oren A.; (Calgary,
CA) ; ISRAEL; Zvi; (Jerusalem, IL) ; ELFAR;
Jubran; (Nazareth, IL) ; MCSHERRY; Paul;
(Woodbury, MN) ; SCOTT; Steven; (Excelsior,
MN) ; MATTER; Benjamin; (Ham Lake, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Alpha Omega Engineering Ltd. |
Nof HaGalil |
|
IL |
|
|
Assignee: |
Alpha Omega Engineering
Ltd.
Nof HaGalil
IL
|
Family ID: |
1000006110657 |
Appl. No.: |
17/588373 |
Filed: |
January 31, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16084664 |
Sep 13, 2018 |
11234632 |
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PCT/IL2017/050328 |
Mar 14, 2017 |
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17588373 |
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PCT/US2016/031448 |
May 9, 2016 |
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16084664 |
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62459415 |
Feb 15, 2017 |
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62459422 |
Feb 15, 2017 |
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62307835 |
Mar 14, 2016 |
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62159336 |
May 10, 2015 |
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Current U.S.
Class: |
1/1 ;
607/116 |
Current CPC
Class: |
A61B 2562/0209 20130101;
A61B 5/24 20210101; A61B 5/7217 20130101; A61B 5/374 20210101; A61B
2562/046 20130101; A61B 5/377 20210101; A61N 1/36067 20130101; A61B
2562/043 20130101; A61N 1/0534 20130101; A61B 5/6868 20130101; A61B
2562/182 20130101; A61B 2562/0223 20130101 |
International
Class: |
A61B 5/377 20060101
A61B005/377; A61B 5/00 20060101 A61B005/00; A61B 5/24 20060101
A61B005/24 |
Claims
1. A method for inferring at least one trajectory inside a brain
tissue, comprising: recording a plurality of signals from said
brain tissue by electrodes positioned at different spatial
locations inside the brain and along the insertion trajectory of a
lead; analyzing said signals by functionally mapping brain tissue
surrounding said insertion trajectory; inferring at least one
additional axis shifted trajectory or part of an additional axis
shifted trajectory at a distance from said insertion trajectory
based on said functionally mapping; delivering an indication during
or after said recording regarding said inferred at least one
additional trajectory.
2. A method according to claim 1, wherein said delivering comprises
delivering said indication with a location of the at least one
additional axis shifted trajectory.
3. A method according to claim 1, wherein said delivering comprises
delivering an indication for a more effective alternative
trajectory.
4. A method according to claim 1, wherein said analyzing comprises
calculating a series of functional tags based on the recorded
plurality of signals, and associating each functional tag of the
series of functional tags to a depth position along the insertion
trajectory.
5. A method according to claim 4, wherein said inferring comprises
calculating functional tags associated with said at least one
additional axis shifted trajectory or said part of an additional
trajectory using signals recorded from a specific combination of
said electrodes of said lead.
6. A method according to claim 5, wherein said at least one
additional axis shifted trajectory comprises a plurality of
additional axis shifted trajectories, each with different
associated functional tags for a similar depth position.
7. A method according to claim 1, wherein said analyzing comprising
separately analyzing each of said plurality of signals, and wherein
said inferring comprising inferring a plurality of axially-shifted
trajectories in a distance of at least 0.5 mm from said lead.
8. A method according to claim 1, further comprising updating an
insertion step size of said lead based on said functionally mapping
of said brain tissue following said analyzing.
9. A method according to claim 1, wherein said recording comprising
recording directional signals from sources located inside the brain
in a distance of at least 0.2 mm from a measuring electrode on said
lead.
10. A method according to claim 1, wherein said analyzing
comprising analyzing said plurality of signals in a single
multi-channel model by a multi-channel algorithm, and wherein
inferring comprising inferring a single trajectory based on the
results of said multi-channel algorithm.
11. A method according to claim 1, wherein said recording comprises
recording a plurality of directional signals by at least one
micro-electrode contact and at least one macro-electrode contact of
said electrodes of said lead.
12. A method according to claim 1, wherein said plurality of
signals comprises a plurality of directional signals, and wherein
said recording comprises recording said plurality of directional
signals by at least one micro-electrode contact and at least one
macro-electrode contact of said lead.
13. A method according to claim 1, wherein said plurality of
signals comprises a plurality of directional signals, and wherein
said recording comprises recording said plurality of directional
signals by at least two micro-electrode contacts or at least two
macro-electrode contacts, of said lead.
14. A brain navigation system, comprising: a lead having an
elongated lead body with a distal end shaped to penetrate into
brain tissue, comprising at least two electrodes located at
different angular positions on a circumference of said elongated
lead body, wherein said at least two electrodes are configured to
record directional electrical signals from brain tissue surrounding
said lead during navigation of said lead along an insertion
trajectory; a control system electrically connected to said lead,
wherein said control system is configured to: receive said
directional electrical signals from said at least two electrodes;
analyze said received directional electrical signals to
functionally map said brain tissue during navigation of said lead,
based on said recorded electrical signals; and infer at least one
additional axis shifted trajectory or part of an additional axis
shifted trajectory at a distance from said insertion trajectory
based on said functionally mapping; a display, wherein said display
delivers an indication with a location of said at least one
additional axis shifted trajectory or said part of an additional
axis-shifted trajectory.
15. A system according to claim 14, wherein said delivered
indication comprises a location of said inferred at least one
additional axis shifted trajectory or said part of an additional
axis shifted trajectory.
16. A system according to claim 14, wherein said control system
analyzes the received directional electrical signals by calculating
a series of functional tags and infers said at least one additional
trajectory or part of said additional trajectory by associating
said series of functional tags with different depth locations along
said at least one additional trajectory.
17. A system according to claim 16, wherein said at least one
additional axis shifted trajectory comprises a plurality of
additional axis shifted trajectories, and wherein said control
system infers said plurality of additional axis shifted
trajectories by associates different functional tags of said
calculated functional tags for a similar depth position for each of
said plurality of additional axis shifted trajectories.
18. A system according to claim 14, wherein said at least two
electrodes comprise at least two macro-electrode contacts or at
least two micro-electrodes.
19. A system according to claim 14, wherein said at least two
electrodes comprise at least one micro-electrode and at least one
macro-electrode contact located at different angular positions on
an outer surface of said lead body.
20. A system according to claim 14, wherein said at least one
additional axis-shifted trajectory is an axis shifted trajectory
inferred at a distance of at least 0.5 mm from said electrodes.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 16/084,664 filed on Sep. 13, 2018, which is a
National Phase of PCT Patent Application No. PCT/IL2017/050328
having International Filing Date of Mar. 14, 2017, which claims the
benefit of priority under 35 USC .sctn. 119(e) of U.S. Provisional
Patent Application Nos. 62/459,415 and 62/459,422, both filed on
Feb. 15, 2017, and 62/307,835 filed on Mar. 14, 2016. PCT Patent
Application No. PCT/IL2017/050328 is also a Continuation-in-Part
(CIP) of PCT Patent Application No. PCT/US2016/031448 having
International Filing Date of May 9, 2016, which claims the benefit
of priority under 35 USC .sctn. 119(e) of U.S. Provisional Patent
Application No. 62/159,336 filed on May 10, 2015.
[0002] The contents of the above applications are all incorporated
by reference as if fully set forth herein in their entirety.
FIELD AND BACKGROUND OF THE INVENTION
[0003] The present invention, in some embodiments thereof, relates
to a brain navigation lead and system and/or parts thereof and,
more particularly, but not exclusively, to a brain navigation lead
comprising electrode contacts and configured to measure electrical
activity of brain tissue.
[0004] Electric field application to the brain is under increasing
use for such varied purposes as treatment of neurological and
psychiatric conditions. A typical electrical brain stimulation
system comprises a pulse generator operatively connected to the
brain by a lead. Prior to electric field application, an electrode
is used to determine the desired target location for electric field
application. Then, the navigation lead is removed and a second
electrode for applying the electric field is inserted.
SUMMARY OF THE INVENTION
[0005] Following are some examples of some embodiments of the
invention. Features of one example may be combined with one or more
features and/or other examples:
[0006] Example 1. A brain navigation device, comprising:
[0007] a lead having an elongated lead body
[0008] at least one macro-electrode contact positioned on an outer
surface on said lead;
[0009] wherein said at least one macro-electrode contact is located
at the distal part of said lead;
[0010] and wherein said at least one macro-electrode contact is
configured to be used during lead navigation.
[0011] Example 2. The device according to example 1, wherein said
lead is used for navigation in the spinal cord.
[0012] Example 3. The device according to example 1, further
comprising at least one microelectrode contact, wherein said at
least one microelectrode contact and said at least one
macro-electrode contact are configured to be used during lead
navigation.
[0013] Example 4. The device according to example 1, wherein said
at least one macro-electrode contact is configured to be used
during lead navigation through brain tis sue.
[0014] Example 5. The device according to example 3, wherein said
at least one micro-electrode contact is located at the distal tip
of said lead.
[0015] Example 6. The device according to example 1, wherein said
at least one macro-electrode contact are configured to apply an
electric field.
[0016] Example 7. The device according to example 3, wherein said
at least one micro-electrode contact is located distally to said at
least one macro-electrode contact.
[0017] Example 8. The lead according to example 1, wherein said at
least one macro-electrode contact comprises at least one ring
electrode contact and/or at least one segmented electrode
contact.
[0018] Example 9. A method for recording and applying an electric
field to brain tissue using brain navigation lead, comprising:
[0019] selecting at least one electrode contact and/or at least one
macro-electrode contact adjacent to a desired tissue region and/or
facing a desired direction;
[0020] recording electrical activity of said desired tissue;
and
[0021] applying an electric field to said desired tissue.
[0022] Example 10. The method of example 9, further comprising:
[0023] recording electrical activity of desired tissue following
electric field application.
[0024] Example 11. The method of example 9, further comprising:
[0025] determining electric field application parameters based on
recorded electrical activity.
[0026] Example 12. The method according to example 9, further
comprising:
[0027] determining desired depth for electric field application
based on recorded electrical activity.
[0028] Example 13. A brain navigation lead with an elongated body,
comprising:
[0029] at least one electrode contact positioned on the outer
surface of said lead;
[0030] at least one marker located at the proximal end of said lead
in a position that remains visible to a user during a lead
navigation process;
[0031] wherein said marker indicates a relative orientation of said
at least one electrode contact relative to brain tissue surrounding
said lead when said lead is inserted into the brain.
[0032] Example 14. The lead according to example 13, wherein said
marker is shaped and sized to be aligned with an alignment marker
of an external device associated with said lead.
[0033] Example 15. The lead according to example 14, wherein said
external device is selected from a list consisting of a lead
holder, a DBS-ruler or a cannula.
[0034] Example 16. The lead according to example 13, wherein said
marker comprises at least two visually detectable markers which
indicate an angle between two points on said outer surface on said
lead.
[0035] Example 17. The lead according to example 13, wherein said
marker includes a line, an arrow, an ellipsoid or a rectangle.
[0036] Example 18. The lead according to example 13, wherein said
marker is attached to said lead using a reflow process.
[0037] Example 19. A brain navigation lead with an elongated body,
comprising:
[0038] at least one electrode contact positioned on the outer
surface of said lead; at least one orientation sensor;
[0039] wherein said sensor indicates a relative spatial orientation
of said at least one electrode contact relative to brain tissue
surrounding said lead when said lead is inserted into the
brain.
[0040] Example 20. The lead according to example 19, wherein said
sensor is located within 30 mm of said electrode contact.
[0041] Example 21. The lead according to example 19, wherein said
sensor is electrically connected to a system, wherein said system
determines the position in space of signals recorded by said
electrode contact based on indications from said sensor.
[0042] Example 22. The lead of example 19, wherein said sensor is
connected to an external control system via electrical wires.
[0043] Example 23. The lead of example 19, wherein said sensor
comprises a wireless sensor configured to transmit signals to a
wireless receiver positioned outside of the head by wireless
communication.
[0044] Example 24. The lead of example 19, wherein said sensor
comprises at least one coiled wire and wherein said sensor detects
changes in the resistance of said coiled wire when said lead
rotates.
[0045] Example 25. The lead of example 19, wherein said sensor is a
magnetic sensor which senses external magnetic fields transmitted
by a device positioned outside of the head.
[0046] Example 26. The lead of example 19, wherein said sensor is a
gravitational sensor configured to sense changes in gravitational
field following rotation of said lead.
[0047] Example 27. The lead of example 19, wherein said sensor
comprises a radio-frequency sensitive receiver configured for
receiving different wireless signals from at least two spaced apart
transmitters positioned outside of the brain.
[0048] Example 28. A brain navigation lead with an elongated body,
comprising:
[0049] at least one electrode positioned on the outer surface of
said lead;
[0050] a distal coupler fixed within the internal lumen of said
lead;
[0051] wherein said distal coupler further comprising at least one
channel and/or at least one opening sized and shaped to accurately
direct said at least one electrode to a desired position on said
outer surface of said lead during the manufacturing of the
lead.
[0052] Example 29. The lead of example 28, wherein said distal
coupler comprises at least two channels shaped and sized to
accurately direct at least two electrodes to at least two different
positions with a desired angle on the circumference of said
lead.
[0053] Example 30. A brain navigation lead with an elongated body,
comprising:
[0054] at least one electrode positioned on the outer surface of
said lead;
[0055] at least one electrically conductive wire connected to said
electrode and positioned within the internal lumen of said
lead;
[0056] a flexible electro-magnetic shield made from conductive
material positioned within said internal lumen at least partly
between said conducting wires and an internal surface of said
elongated body;
[0057] wherein said shield is shaped and sized to shield said
conducting wires from external electro magnetic fields.
[0058] Example 31. The lead of example 30, wherein said shield
comprises a conductive braided shield or a coiled shield or a
conductive mesh shield.
[0059] Example 32. The lead of example 30, wherein said shield
covers at least 70% of the length of said conductive wires.
[0060] Example 33. The lead of example 32, wherein said shield
covers at least 70% of the circumference of said conductive
wires.
[0061] Example 34. The lead of example 30, wherein said shield
comprises at least one connector for connecting said shield to an
amplifier.
[0062] Example 35. The lead of example 30, wherein said shield
comprises thin electrically conducting wires with a diameter
smaller than 100 micron.
[0063] Example 36. A brain navigation lead, comprising:
[0064] an elongated lead body having a distal section and a
proximal section;
[0065] at least one electrode contact positioned on the outer
surface of said lead; at least one twisting sensor;
[0066] wherein said twisting sensor detects a relative twist of
said distal section relative to said proximal section when said
lead is inserted into the brain.
[0067] Example 37. The lead of example 36, wherein said twisting
sensor comprises a fiber optic twist sensor, positioned at least
partly along the lead axis.
[0068] Example 38. The lead of example 36, wherein said twisting
sensor comprises at least one coiled wire and wherein said sensor
detects changes in the resistance of said coiled wire when said
lead twist.
[0069] Example 39. The lead of example 36, further comprising at
least one marker located at the proximal section of said lead in a
position that remains visible to a user during a lead navigation
process,
[0070] wherein said twisting sensor detects a relative twist of
said distal section relative to said marker.
[0071] Example 40. A system for aligning an electrode lead
comprising:
[0072] a lead having at least one marker located in a visible
region on the outer surface of said lead;
[0073] an external element shaped and sized to be connectable to
said lead to prevent the rotation of said lead, wherein said
external element comprising an alignment feature;
[0074] wherein said marker is shaped and sized to be aligned with
said alignment feature before said external element is connected to
said lead to prevent a rotation of said lead relative to said
external element.
[0075] Example 41. The system of example 40, wherein said external
element is a cannula surrounding at least partly said lead, wherein
said cannula comprising an opening sized and shaped to allow
visualization of said marker of said lead through said opening.
[0076] Example 42. The system of example 41, wherein said external
element is a DBS-ruler.
[0077] Example 43. A method for inferring at least one trajectory
inside a brain tissue, comprising:
[0078] recording a plurality of signals from said brain tissue by
electrodes positioned at different spatial locations inside the
brain and along the insertion trajectory of a lead;
[0079] analyzing said signals by functionally mapping brain tissue
surrounding said insertion trajectory;
[0080] inferring at least one additional trajectory or part of an
additional trajectory at a distance from said insertion trajectory
based on said functionally mapping.
[0081] Example 44. The method of example 43, further comprising
updating an insertion step size of said lead based on said
functionally mapping of said brain tissue following said
analyzing.
[0082] Example 45. The method of example 43, wherein said recording
comprising recording directional signals from sources located
inside the brain in a distance of at least 0.2 mm from a measuring
electrode on said lead.
[0083] Example 46. The method of anyone of example 43 to 45,
wherein said analyzing comprising separately analyzing each of said
plurality of signals, and wherein said inferring comprising
inferring a plurality of trajectories in a distance of at least 0.5
mm from said lead.
[0084] Example 47. The method of anyone of example 43 to 45,
wherein said analyzing comprising analyzing said plurality of
signals in a single multi-channel model by a multi-channel
algorithm, and wherein inferring comprising inferring a single
trajectory based on the results of said multi-channel
algorithm.
[0085] Example 48. A method for updating a model of a functional
brain tissue map, comprising:
[0086] providing a model of a functional brain tissue map, wherein
said map comprises functionally tagged brain tissue regions;
[0087] electronically collecting functional-labeled brain tissue
data from surgical procedures and/or imaging procedures; and
[0088] updating said model based on the collected
functional-labeled brain tissue data.
[0089] Example 49. The method of example 48, wherein said updating
comprising updating said model based on rules or a table of
rules.
[0090] Example 50. The method of example 48 or 49, comprising using
said updated model in an online mapping procedure during a
surgery.
[0091] Unless otherwise defined, all technical and/or scientific
terms used herein have the same meaning as commonly understood by
one of ordinary skill in the art to which the invention pertains.
Although methods and materials similar or equivalent to those
described herein can be used in the practice or testing of
embodiments of the invention, exemplary methods and/or materials
are described below. In case of conflict, the patent specification,
including definitions, will control. In addition, the materials,
methods, and examples are illustrative only and are not intended to
be necessarily limiting.
[0092] As will be appreciated by one skilled in the art, some
embodiments of the present invention may be embodied as a system,
method or computer program product. Accordingly, some embodiments
of the present invention may take the form of an entirely hardware
embodiment, an entirely software embodiment (including firmware,
resident software, micro-code, etc.) or an embodiment combining
software and hardware aspects that may all generally be referred to
herein as a "circuit," "module" or "system".
[0093] Furthermore, some embodiments of the present invention may
take the form of a computer program product embodied in one or more
computer readable medium(s) having computer readable program code
embodied thereon. Implementation of the method and/or system of
some embodiments of the invention can involve performing and/or
completing selected tasks manually, automatically, or a combination
thereof. Moreover, according to actual instrumentation and
equipment of some embodiments of the method and/or system of the
invention, several selected tasks could be implemented by hardware,
by software or by firmware and/or by a combination thereof, e.g.,
using an operating system.
[0094] For example, hardware for performing selected tasks
according to some embodiments of the invention could be implemented
as a chip or a circuit. As software, selected tasks according to
some embodiments of the invention could be implemented as a
plurality of software instructions being executed by a computer
using any suitable operating system. In an exemplary embodiment of
the invention, one or more tasks according to some exemplary
embodiments of method and/or system as described herein are
performed by a data processor, such as a computing platform for
executing a plurality of instructions. Optionally, the data
processor includes a volatile memory for storing instructions
and/or data and/or a non-volatile storage, for example, a magnetic
hard-disk and/or removable media, for storing instructions and/or
data. Optionally, a network connection is provided as well. A
display and/or a user input device such as a keyboard or mouse are
optionally provided as well.
[0095] Any combination of one or more computer readable medium(s)
may be utilized for some embodiments of the invention. The computer
readable medium may be a computer readable signal medium or a
computer readable storage medium. A computer readable storage
medium may be, for example, but not limited to, an electronic,
magnetic, optical, electromagnetic, infrared, or semiconductor
system, apparatus, or device, or any suitable combination of the
foregoing. More specific examples (a non-exhaustive list) of the
computer readable storage medium would include the following: an
electrical connection having one or more wires, a portable computer
diskette, a hard disk, a random access memory (RAM), a read-only
memory (ROM), an erasable programmable read-only memory (EPROM or
Flash memory), an optical fiber, a portable compact disc read-only
memory (CD-ROM), an optical storage device, a magnetic storage
device, or any suitable combination of the foregoing. In the
context of this document, a computer readable storage medium may be
any tangible medium that can contain, or store a program for use by
or in connection with an instruction execution system, apparatus,
or device.
[0096] A computer readable signal medium may include a propagated
data signal with computer readable program code embodied therein,
for example, in baseband or as part of a carrier wave. Such a
propagated signal may take any of a variety of forms, including,
but not limited to, electro-magnetic, optical, or any suitable
combination thereof. A computer readable signal medium may be any
computer readable medium that is not a computer readable storage
medium and that can communicate, propagate, or transport a program
for use by or in connection with an instruction execution system,
apparatus, or device.
[0097] Program code embodied on a computer readable medium and/or
data used thereby may be transmitted using any appropriate medium,
including but not limited to wireless, wireline, optical fiber
cable, RF, etc., or any suitable combination of the foregoing.
[0098] Computer program code for carrying out operations for some
embodiments of the present invention may be written in any
combination of one or more programming languages, including an
object oriented programming language such as Java, Smalltalk, C++
or the like and conventional procedural programming languages, such
as the "C" programming language or similar programming languages.
The program code may execute entirely on the user's computer,
partly on the user's computer, as a stand-alone software package,
partly on the user's computer and partly on a remote computer or
entirely on the remote computer or server. In the latter scenario,
the remote computer may be connected to the user's computer through
any type of network, including a local area network (LAN) or a wide
area network (WAN), or the connection may be made to an external
computer (for example, through the Internet using an Internet
Service Provider).
[0099] Some embodiments of the present invention may be described
below with reference to flowchart illustrations and/or block
diagrams of methods, apparatus (systems) and computer program
products according to embodiments of the invention. It will be
understood that each block of the flowchart illustrations and/or
block diagrams, and combinations of blocks in the flowchart
illustrations and/or block diagrams, can be implemented by computer
program instructions. These computer program instructions may be
provided to a processor of a general purpose computer, special
purpose computer, or other programmable data processing apparatus
to produce a machine, such that the instructions, which execute via
the processor of the computer or other programmable data processing
apparatus, create means for implementing the functions/acts
specified in the flowchart and/or block diagram block or
blocks.
[0100] These computer program instructions may also be stored in a
computer readable medium that can direct a computer, other
programmable data processing apparatus, or other devices to
function in a particular manner, such that the instructions stored
in the computer readable medium produce an article of manufacture
including instructions which implement the function/act specified
in the flowchart and/or block diagram block or blocks.
[0101] The computer program instructions may also be loaded onto a
computer, other programmable data processing apparatus, or other
devices to cause a series of operational steps to be performed on
the computer, other programmable apparatus or other devices to
produce a computer implemented process such that the instructions
which execute on the computer or other programmable apparatus
provide processes for implementing the functions/acts specified in
the flowchart and/or block diagram block or blocks.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0102] Some embodiments of the invention are herein described, by
way of example only, with reference to the accompanying drawings.
With specific reference now to the drawings in detail, it is
stressed that the particulars shown are by way of example and for
purposes of illustrative discussion of embodiments of the
invention. In this regard, the description taken with the drawings
makes apparent to those skilled in the art how embodiments of the
invention may be practiced.
[0103] In the drawings:
[0104] FIG. 1 is a general flow chart of a lead implantation
process, according to some embodiments of the invention;
[0105] FIG. 2 is a block diagram describing main lead components
and attached devices, according to some embodiments of the
invention;
[0106] FIG. 3A is a detailed flow chart of the navigation and
electric field application process, according to some embodiments
of the invention;
[0107] FIGS. 3B-3C are schematic views of a system for brain
navigation implantation, recording and electric field application,
according to some embodiments of the invention;
[0108] FIG. 3D is a schematic view of a lead inserted into a brain,
connected to a recording system, according to some embodiments of
the invention;
[0109] FIG. 3E is a schematic view of a lead inserted into a brain,
connected to an IPG, according to some embodiments of the
invention;
[0110] FIG. 3F is a schematic view of a lead with an orientation
marker, according to some embodiments of the invention;
[0111] FIGS. 3G-3H are schematic views of a DBS-ruler with an
external alignment element, according to some embodiments of the
invention;
[0112] FIGS. 3I-3J are schematic views of a lead and a lead holder
inserted into a DBS-ruler, according to some embodiments of the
invention;
[0113] FIG. 3K is a schematic view of a lead with a marker
positioned within a guiding cannula, according to some embodiments
of the invention;
[0114] FIGS. 3L and 3M are schematic views of an electrode holder
and a lead inside the lead holder, according to some embodiments of
the invention;
[0115] FIG. 3N is a flow chart describing a process for aligning a
lead, according to some embodiments of the invention;
[0116] FIGS. 4A-4J are schematic views of brain navigation lead
embodiments, according to some embodiments of the invention;
[0117] FIG. 5A is a schematic illustration of a brain navigation
lead embodiment, according to some embodiments of the
invention;
[0118] FIG. 5B is a block diagram of a lead with an orientation
element, according to some embodiments of the invention;
[0119] FIGS. 5C and 5D are schematic views of a lead with an
orientation sensor, according to some embodiments of the
invention;
[0120] FIG. 5E is a schematic view of a lead with an orientation
sensor inside the brain, according to some embodiments of the
invention;
[0121] FIG. 6 is a detailed flow chart describing the process of
recording and electric field application, according to some
embodiments of the invention;
[0122] FIGS. 7A-7G are schematic views of electrode contact
combinations for electric field application, according to some
embodiments of the invention;
[0123] FIG. 8 is a schematic view of a directional recording
process, according to some embodiments of the invention;
[0124] FIGS. 9A-9B are schematic views showing multi-polar
recording, according to some embodiments of the invention;
[0125] FIG. 10 is a schematic view of macro-electrode contacts,
according to some embodiments of the invention;
[0126] FIGS. 11A-11G are schematic views showing electric fields
generated by electrode contacts, according to some embodiments of
the invention;
[0127] FIGS. 12A-12B are schematic views showing inter-connecting
lead wires, according to some embodiments of the invention;
[0128] FIGS. 13A and 13B are schematic views of lead electrodes
which generate multiple spatially differentiated recording
trajectories from the lead's single insertion trajectory, according
to some embodiments of the invention;
[0129] FIG. 13C is a schematic view of a functionally mapped
trajectory, according to some embodiments of the invention;
[0130] FIG. 13D is a schematic view showing the generation of
multiple spatially differentiated mapping results from multiple
signal recordings, according to some embodiments of the
invention;
[0131] FIG. 13E is a schematic view showing the generation of a
single trajectory from multiple signals recordings, according to
some embodiments of the invention;
[0132] FIGS. 14A-14C are flow charts of processes for generating a
single or more trajectories from multiple signal recordings,
according to some embodiments of the invention;
[0133] FIG. 15 is a schematic cross-section of a distal coupler,
according to some embodiments of the invention;
[0134] FIG. 16A is a schematic upper-view cross section of a lead
with an internal electro-magnetic shield, according to some
embodiments of the invention; and
[0135] FIG. 16B is a schematic side-view cross section of a lead
with an internal electro-magnetic shield, according to some
embodiments of the invention.
DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION
[0136] The present invention, in some embodiments thereof, relates
to a brain navigation lead and, more particularly, but not
exclusively, to brain navigation lead comprising electrode contacts
and configured to measure electrical activity of brain tissue.
[0137] An aspect of some embodiments relates to a brain navigation
lead for electrical activity mapping and delivery of an electric
field, having at least one micro-electrode contact located at the
distal end of the lead, and at least one macro-electrode contact
located at a more proximal location on the lead relative to the at
least one microelectrode. In some embodiments, the electrode is
positioned along the lead body. In some embodiments, the brain
navigation lead comprises at least one micro-electrode contact
located at the lead tip and at least three macro-electrode contacts
distributed along the lead circumference and located at a more
proximal location on the lead relative to the micro-electrode
contact. Optionally, brain navigation lead comprises at least three
micro-electrode contacts distributed along the lead circumference
at the distal end of the lead, and at least three macro-electrode
contacts distributed along the lead circumference, in a more
proximal location on the lead relative to the micro-electrode
contacts.
[0138] In some embodiments, lead comprises a micro-electrode
contact in its distal tip, at least one additional micro-electrode
contact proximally to the distal tip contact, and at least one
macro-electrode contact positioned proximally to the at least one
additional micro-electrode contact. In some embodiments,
macro-electrode contacts are positioned proximally to
micro-electrode contacts.
[0139] In some embodiments, micro-electrode contacts are configured
to sense electrical activity of brain tissue and macro-electrode
contacts are configured to apply an electrical field to brain
tissue. Alternatively, micro-electrode contacts and/or
macro-electrode contacts are configured to apply an electric field
to brain tissue.
[0140] Optionally, microelectrode contacts and/or macro-electrode
contacts are configured to sense electrical activity of brain
tissue.
[0141] In some embodiments, the lead is configured to be connected
to an external recording device and to an implanted pattern
generator (IPG). This allows using the same lead for both
navigating into a desired target location, and for applying an
electric field to a brain tissue, for example for deep brain
stimulation (DBS). Therefore, there is no need to replace the
navigation lead with a different stimulation lead, which often
prolongs the implantation procedure, and may reduce the DBS
treatment efficacy, due to accumulation of errors in the
replacement process.
[0142] Alternatively, the lead is configured to be connected to an
IPG for both navigation and therapeutic electric field application,
for example electric field application for deep brain
stimulation.
[0143] In some embodiments, micro-electrode contacts and/or
macro-electrode contacts distributed along the lead circumference
are configured to sense electrical activity of brain tissue from
different directions around the lead. Optionally, micro-electrode
contacts and/or macro-electrode contacts distributed along the lead
circumference are configured to apply an electric field to brain
tissue in different directions.
[0144] An aspect of some embodiments relates to a brain navigation
lead configured to be connected to an IPG that has fewer channel
outputs than lead contacts, by short circuiting at least two lead
contacts and connecting the short circuited contacts to a single
IPG channel output. For example, short-circuiting is required when
connecting a lead with 8 macro-contacts to an IPG with 4 channels.
In some embodiments, if a brain navigation lead contains 2 ring
macro-contacts and 2 segmented rings of 3 contacts each, e.g. in a
1-3-3-1 configuration, or any permutation, then the 3 segments may
be short-circuited to connect to a single IPG output, and the lead
may then be substantially equivalent to a 4-rings (1-1-1-1) lead.
In some embodiments, by short-circuiting electrode contacts, it is
possible to apply a similar electric field through the combined
electrode contacts to a larger area of brain tissue.
[0145] An aspect of some embodiments relates to a method for
navigating a lead to a desired depth, by mapping brain tissue
electrical activity using at least one electrode contact located at
the distal end of the lead, determining a desired depth for
electric field application and positioning at least one electrode
contact at the desired depth. In some embodiments, the electrode
contact used for electric field application is located at a more
proximal location on the lead, relative to the mapping electrode
contact which is located at the distal end of the lead.
[0146] In some embodiments, at least one microelectrode contact
and/or at least one macro-electrode contact located on the lead are
used for electrical activity mapping for determining a desired
depth for electric field application. In some embodiments, a
desired depth for electric field application is determined based on
electrical activity measured by the lead and on parameters measured
by at least one other sensor and/or as part of an analysis, for
example an EEG analysis.
[0147] In some embodiments, electrode contacts distributed along
the circumference of the lead are configured to map brain tissue
electrical activity by sensing and recording electrical activity
from different directions around the lead. In some embodiments,
this electrical mapped activity is used to generate a depth
signature, while the lead moves into the brain tissue. In some
embodiments, the depth signature is generated based on at least one
electric field applied to the brain tissue. In some embodiments,
the electric field is applied through at least one micro-electrode
contact and/or at least one macro-electrode contact. In some
embodiments, the depth signature of a desired electric field
application target is used to confirm that an electrode is placed
at the desired target area, prior to an electric field application
using an implanted pattern generator (IPG).
[0148] In some embodiments, electric field application followed by
mapping of the tissue electrical activity is used to determine the
IPG electric field application parameters. In some embodiments
these parameters include for example, which electrode contacts to
use, pulse-width, pulse repetition frequency (PRF), and pulse
amplitude. In some embodiments, electrical activity mapping by
electrode contacts on the lead includes indirectly evaluating a
neural correlate of muscle rigidity and severity of tremor before
and during electric field application. Alternatively, evaluating a
neural correlate of muscle rigidity and severity of tremor before
and during electric field application is performed by other
sensors.
[0149] In some embodiments, directed electrical activity recording
and electric field application is used to predict at least one
desired insertion trajectory for insertion of additional electrode
leads. In some embodiments, directed electrical activity recording
and electric field application is used to predict at least one
desired insertion trajectory for positioning an electrode-contact
in a desired location.
[0150] In some embodiments, recording while applying an electric
field allows evaluating the effect of applied electric field on the
tissue during lead navigation.
[0151] In some embodiments, recording while applying an electric
field allows evaluating the effect of applied electric field on the
tissue to determine desired depth and/or electric field application
parameters for a second electric field application, for example by
an IPG device.
[0152] An aspect of some embodiments relates to determining the
twist of the lead and/or the spatial orientation of at least one
electrode on the lead by non-imaging techniques. In some
embodiments, the spatial orientation is determined using at least
one orientation element positioned on said lead. In some
embodiments, the at least one orientation element delivers an
indication regarding to the spatial orientation of at least one
microelectrode and/or at least one macro electrode positioned on
the distal end of said lead, relative to the tissue surrounding
said lead. Alternatively or additionally, the orientation element
delivers an indication regarding to the relative spatial
orientation between the at least one microelectrode and the at
least one macro electrode. Optionally, the orientation element
delivers an indication regarding to the orientation of at least one
microelectrode and/or at least one macro electrode relative to a
reference point on said lead and/or relative to an external
reference point.
[0153] According to some embodiments, by visualizing and/or sensing
the orientation element an indication is provided regarding the
rotation of the lead. Alternatively or additionally, visualization
and/or sensing of the orientation element provides an indication
regarding the rotation of an electrode or electrode wiring. In some
embodiments, the indication is a numerical indication which for
example, indicates the rotation angle of the lead and/or one of the
electrodes. Alternatively, the indication indicates any change from
a desired orientation.
[0154] According to some embodiments, the orientation element
comprises at least one marker positioned on a section of said lead
which is located outside of said brain. Optionally the marker is
positioned on the proximal end of the lead. In some embodiments,
the marker is shaped and sized to provide a visual indication to a
user regarding the spatial orientation of at least one electrode of
the lead positioned inside the brain. Alternatively or
additionally, the marker position is measured by a device. In some
embodiments, the indication delivered by the marker is measured by
an external sensor or by an external machine. In some embodiments,
the marker provides an indication regarding the rotation or
twisting of the lead and/or electrodes and/or electrode wires.
[0155] According to some embodiments, the orientation element for
example the marker is aligned according to an alignment marker
positioned on an external element connected to the lead, for
example a lead holder or a DBS-ruler. In some embodiments, once the
marker is aligned the lead position is fixed relative to the
external element, for example to prevent relative rotation of the
lead. Alternatively, the marker is aligned according to an
alignment marker positioned on an external element which is
proximal to the lead, for example an alignment marker positioned on
a cannula surrounding the lead.
[0156] In some embodiments, the marker is aligned according to
instructions of a software, for example an alignment software. In
some embodiments, the software provides instructions regarding a
desired orientation of the marker, for example a desired
orientation that leads to a desired measuring or treatment by
electrodes positioned on the lead. Alternatively, a user enters a
desired electrode coordinates and/or a desired orientation of the
lead to the software. Optionally, the software provides
instructions to the user how to modify the orientation of the
marker in order to reach the desired electrode coordinates.
[0157] According to some embodiments, the orientation element
comprises an orientation or twisting sensor positioned on the lead.
In some embodiments the sensor detects the twisting of the lead or
at least part of the lead, for example the distal section of the
lead. In some embodiments, the sensor detects the twisting of the
distal section relative to the surrounding tissue or an external
reference point. Alternatively or additionally, the sensor detects
the twisting of the distal section of the lead relative to the
proximal section, optionally relative to a marker positioned on the
proximal section of the lead. In some embodiments, the sensor is
electrically connected to an orientation detection circuitry and/or
a control circuitry of the lead via electrical wiring.
Alternatively, the orientation sensor is connected to the control
circuitry via wireless communication, for example Bluetooth, wifi,
or infra-red communication.
[0158] In some embodiments, the baseline orientation of the sensor
is calibrated before the insertion of the lead relative to at least
one electrode on the lead. Alternatively, or additionally, the
baseline orientation of the sensor is calibrated relative to an
external reference point, for example relative to an external
element connected to the lead. Optionally, the external reference
point is an external element positioned in a close distance, for
example up to 10 cm from the lead, for example a cannula inserted
into the brain near the lead or surrounding the lead.
[0159] In some embodiments, the orientation and/or the twisting of
the lead and/or the orientation of the lead electrodes is
determined based on changes in the electrical properties of the
sensor, for example changes in the resistance of the sensor. In
some embodiments, the sensor comprises at least one electrically
conductive wire coiled inside the lead body, optionally inside the
lead lumen. In some embodiments, when the lead rotates in the same
direction as the coiled wire direction, the coiled wire is
stretched and the electrical resistance increases. Alternatively,
when the lead rotates in an opposite direction to the coiled wire
direction, the coiled wire tension is reduced and the electric
resistance of the wire decreases.
[0160] In some embodiments, the sensor comprises two electrically
conductive wires, where each of the wires is coiled in an opposite
direction. In some embodiments, when the lead rotates in one
direction, the electric resistance of one of the wires is increases
while the electric resistance of the second wire decreases.
[0161] In some embodiments, the orientation element is a sensor
which detects changes in radio-frequency fields surrounding the
sensor. In some embodiments, the radio-frequency fields, are
generated from at least two sources with a fixed position in space.
In some embodiments, the radio-frequency fields have different
parameter values, for example different frequencies. In some
embodiments, the orientation sensor detects the two different
radio-frequency fields and detects changes between the two fields.
In some embodiments, rotation or twisting of the lead changes the
values of the received fields or a relation between the received
fields.
[0162] In some embodiments, the orientation element is a magnetic
field sensor positioned on the lead. In some embodiments, the
magnetic field sensor measures a magnetic field generated from an
external source, optionally located outside of the head. In some
embodiments, when the measured electric field is changes, for
example when the lead is rotated or twisted, an indication is
provided to the user and/or to an external machine.
[0163] In some embodiments, the sensor is an optical fiber twist
sensor which measures the twist or torsion of the lead. In some
embodiments, a system connected to the sensor measures the
differences in light properties and/or in light parameter values
between the light inserted into the lead and the light reflected
from the lead. In some embodiments, the changes include for example
the amount of light reflected compared to the amount of light
projected into the lead.
[0164] An aspect of some embodiments relates to functionally
mapping brain tissue surrounding a lead based on signal recorded by
electrodes on the lead. In some embodiments, the functionally
mapping results are used for inferring at least part of an
additional trajectory positioned in a distance from a lead
insertion trajectory. In some embodiments, the additional
trajectory is inferred based on directional signals received from
brain tissue surrounding the lead insertion trajectory. In some
embodiments, a plurality of functionally mapped trajectories or
part of trajectories, for example a part of the trajectory that
faces an electrode or group of electrodes or the distal section of
the lead are inferred. Alternatively, a single trajectory or part
of a trajectory, for example a part of the trajectory that faces an
electrode or group of electrodes or the distal section of the lead
is inferred from multiple directions signals, optionally using a
multi-channel algorithm.
[0165] In some embodiments, the recorded signals from the
surrounding tissue are functionally tagged using a set of rules or
a table of rules. In some embodiments the set or the table of rules
is generated using machine learning algorithms or using a
statistical-based analysis or by any other manual, semi-automatic
or automatic methods.
[0166] In some embodiments, an indication is provided to a user
during or after the insertion of the lead regarding an alternative,
and optionally a more optimal insertion trajectory based on the
functional mapping described above. Optionally, an indication is
provided to a user regarding a preferred orientation of the lead
relative to the surrounding tissue for delivery of a DBS treatment,
based on the functional mapping of the surrounding tissue.
[0167] An aspect of some embodiments relates to directing at least
one electrode to a desired position on the lead surface during the
manufacturing of the lead. In some embodiments, the electrode is
directed by at least one channel and/or at least one opening
located in the lead lumen. In some embodiments, the at least one
channel and/or at least one opening are formed in a distal coupler
positioned in the lumen of the lead. In some embodiments, the
distal coupler accurately directs at least one microelectrode to a
desired position on the circumference of the lead. Alternatively or
additionally, the distal coupler directs a microelectrode to a
desired position in the distal tip of the lead. Optionally, the
distal coupler comprises at least two channels for directing at
least two electrodes to at least two different positions on the
lead circumference.
[0168] An aspect of some embodiments relates to reducing external
electro-magnetic noise in recorded signals from an electrode lead
by shielding electrode conductors placed in the internal lumen of
the lead from outside electro-magnetic fields and optionally from
adjacent electrodes. In some embodiments, a lead comprises a
flexible electrically conductive shield positioned between the
electrode conductors and the lead internal surface. Optionally the
lead covers at least 70%, for example 80, 85, 90, 95% or any
intermediate or larger coverage percentage of the conductor's
length and/or circumference. In some embodiments, the shield
comprises a braided shield or a mesh shield, optionally made from
electrically conductive wires. In some embodiments, the shield
allows, for example to twist the lead during the navigation process
and to shield the internal electrode conductors from external
electro-magnetic fields.
[0169] In some embodiments, the shield is comprised of thin
electrically conducting wires with a diameter smaller than 150
microns, for example 110, 100, 90 microns or any intermediate or
smaller diameter. In some embodiments, the braided shield is
comprised of similar thin electrically conducting wires. In some
embodiments, the shield is shaped and sized to fit inside a lead
having a diameter of at least 1 mm, for example 1.1, 1.2, 1.27, 1.3
or 1.4 mm or any intermediate or larger diameter. In some
embodiments, if the shield increases the rigidity of the lead, then
the rigidity of the lead is adjusted by using a different polymer
which is less rigid to produce the lead. In some embodiments, if
the shield is found to increase lead stiffness excessively, a more
compliant material is selected for the lead body to achieve the
desired overall mechanical stiffness.
[0170] In some embodiments, the shield is made by spinning a thin
wire or a plurality of thin wires held side-by-side into a coil. In
some embodiments, the coil is shaped and sized to be inserted into
a gap between the signal conductors and the external wall of the
lead.
[0171] In some embodiments, the shield comprises at least one
connector, for example a male and/or a female connector to allow
electrical connection to an external recording unit, for example a
differential amplifier. In some embodiments, the external
electro-magnetic signal is electrically directed by the shield to
the differential amplifier and is optionally used to subtract at
least some of the noise signal from the signals recorded by the
lead electrodes.
[0172] In some embodiments, the shield comprises at least one
channel shaped and sized for directing a single electrode
conductor. In some embodiments, the single channel is used for
directing each electrode a desired positioned on the lead outer
surface and/or for shielding each electrode conductor from the rest
of the electrode conductors.
[0173] An aspect of some embodiments relates to an electrode lead
with an internal distal coupler. In some embodiments, a distal
coupler comprises at least one channel sized and shaped to hold at
least one electrode. Alternatively or additionally, the channel
holds at least one electrode wire. In some embodiments, when the
electrode or the electrode wire is positioned within the channel,
the distal coupler is introduced into an internal lumen of a lead.
Alternatively, a lead or at least a section of the lead, for
example the distal section of the lead is formed around the distal
coupler. In some embodiments, a polymer is casted around the distal
coupler and over the wires. In some embodiments, the distal coupler
serves to protect the electrode wires during the formation of the
lead.
[0174] In some embodiments, the lead and/or the system and/or the
methods described herein are used for navigation in other tissues
of the body, for example in the spinal cord.
[0175] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not
necessarily limited in its application to the details of
construction and the arrangement of the components and/or methods
set forth in the following description and/or illustrated in the
drawings and/or the Examples. The invention is capable of other
embodiments or of being practiced or carried out in various
ways.
Exemplary General Lead Implantation Process
[0176] According to some embodiments, when a person suffers from a
neurological condition it is possible to perform an electrical
intervention to alleviate some of his symptoms. This is done by
insertion of an electrode to a desired target in the brain and
applying an electric field by the electrode to the brain
tissue.
[0177] Reference is now made to FIG. 1 depicting a general
electrode implantation process according to some embodiments of the
invention. According to some exemplary embodiments, when a person
suffers from a neurological condition, for example Parkinson's
disease, he is being diagnosed by an expert in the field in 102. In
some embodiments, during diagnosis 102, a magnetic resonance
imaging (MRI) or other imaging tests are performed to identify
brain regions relevant to the specific neurological condition. In
some embodiments, during the imaging test, the exact position
coordinates of brain targets that can be used for an electrical
intervention are determined.
[0178] According to some exemplary embodiments, after a position of
electric intervention brain targets is determined, a cannula is
inserted through a hole in the skull. In some embodiments, a lead
carrying electrode contacts is inserted through the cannula into
the brain in 104. In some embodiments, the lead penetrates the
brain with its distal end, facing the tissue. In some embodiments,
the cannula and the lead are pushed through the brain tissue
manually or using a motorized device.
[0179] According to some exemplary embodiments, the cannula and the
lead are navigated in 106 through the brain tissue to reach the
desired targets coordinates that were determined in 102.
Alternatively, the cannula and/or the lead are navigated to
different desired brain targets, as determine by an expert in the
field. In some embodiments, lead insertion trajectory is determined
based on recorded electrical activity of the adjacent tissue using
lead electrode contacts. In some embodiments, lead is inserted
and/or retracted through the brain tissue based on recorded
electrical activity of the adjacent tissue using lead electrode
contacts. In some embodiments, lead insertion trajectory is
determined based on electrical activity measured by the lead
electrode contacts following electric field application. In some
embodiments, lead insertion trajectory is determined based on
recorded electrical activity as measured by sensors not connected
to the navigation lead.
[0180] According to some embodiments, navigation in 106 is based on
recording and electric field application by the lead contacts.
[0181] According to some exemplary embodiments, electrode contacts
positioned on the lead measure the electrical activity of the brain
tissue facing the electrode contacts in 108. In some embodiments,
the measured electrical activity is recorded by a recording device
connected to the lead by wires. In some embodiments, the recording
device is positioned outside of the patient's body. Alternatively,
the recording system is positioned within the patient's body.
Optionally the recording system is configured to apply an electric
field through the lead electrode contacts, for example an implanted
pattern generator (IPG). According to some exemplary embodiments,
electrical activity recording is performed by at least one
electrode contact of the lead.
[0182] Optionally, electrical activity is performed after an
electric field is applied by at least one electrode contact to a
desired brain region.
[0183] According to some exemplary embodiments, after the lead has
reached a desired brain target for applying an electric field, lead
wires are disconnected from the recording device and are
re-connected to an electric field generator device, for example an
IPG device. Alternatively, a controller within the recording device
signals a pulse generator component within the device to generate
an electric field. In some embodiments, the generated electric
field is delivered to the brain tissue through electrode contacts
placed on the lead surface, facing the brain tissue. In some
embodiments, the applied elected field generated by the IPG is used
for Deep Brain Stimulation (DBS). In some embodiments, the applied
electric field is used to alleviate the symptoms of neurological
conditions, for example Parkinson's disease.
Exemplary System
[0184] Reference is now made to a system for electrical activity
recording and/or application of an electric field to brain tissue,
according to some embodiments of the invention. According to some
exemplary embodiments, lead 200 comprises at least one micro
electrode contact 204 and at least one macro-electrode contact 202,
and is configured to be inserted into brain tissue. In some
embodiments, lead 200 is configured to measure electrical activity
of brain tissue using at least one micro electrode contact 204,
and/or at least one macro electrode contact 202. Preferably, lead
200 is configured to measure and/or record electrical activity
using both micro electrode contacts and macro-electrode
contacts.
[0185] According to some exemplary embodiments, lead 200 is
connected via wires 210 to recording device 206 during the lead
navigation process. In some embodiments, recording device 206 is
also configured to generate an electric field to be delivered by
wires 210 to lead 200. In some embodiments, the electric field is
applied by at least one micro electrode contact 204 and/or at least
one macro electrode contact 202 to the brain tis sue.
[0186] According to some exemplary embodiments, wires 210 are
configured to be connected to both recording system 206 and to IPG
208. In some embodiments, once navigation has ended, wires 210 are
disconnected from recording device 206 and are connected to IPG
208. In some embodiments, IPG 208 is configured to generate an
electric field, to be delivered by wires 210 to lead 200. In some
embodiments, the electrical field generated by IPG 208 is delivered
to the brain tissue by at least one micro electrode contact 204,
and/or at least one macro electrode contact 202 positioned on lead
200.
[0187] According to some exemplary embodiments, the electric field
delivered to the brain tissue is electric current. In some
embodiments, the applied electric field or the electric current is
composed of repeating millisecond-scale pulses.
Exemplary Detailed Lead Implantation Method
[0188] According to some exemplary embodiments, a patient suffering
from a neurological condition is diagnosed by an expert in the
field. In some embodiments, if the patient's condition can be
treated by electric field application to specific brain regions,
the patient undergoes an imaging test, for example an MRI tests to
identify the exact location of these brain regions. In some
embodiments, once the brain region locations are determined an
electrode for applying an electric field is navigated to these
regions. However, since the brain moves, the brain regions
locations as determined by the MRI test can be changed. In some
embodiments, to improve the accuracy of brain region locations, a
lead electrode is inserted to the brain to record the electric
activity of desired brain regions, prior to insertion of a second
electrode for applying the electric field.
[0189] Reference now is made to FIG. 3A depicting a detailed lead
implantation process according to some embodiments of the
invention. According to some exemplary embodiments, a patient
suffering from a neurological condition, that its symptoms can be
alleviated by electric field application, is diagnosed by an expert
in the field. In some embodiments, the patient undergoes an MRI or
a CT test to identify the regions where the electric field should
be applied, followed by a microelectrode recording (MER)
procedure.
[0190] According to some exemplary embodiments, the patient is
prepared for a microelectrode recording (MER) procedure in 402 by
attaching a stereotactic frame and associated apparatus to the
patient's scalp, and identifying the insertion point on the scalp.
Then, in some embodiments, a cannula is inserted through the skull
into the brain in 404, to provide mechanical support for a lead to
be inserted through the cannula. In some embodiments, the cannula
is made from an electrical conductive material, for example metal.
In some embodiments, the cannula is inserted to the brain to a
position that is found proximal to the pre-determined anatomical
implantation target.
[0191] According to some exemplary embodiments, after the cannula
insertion in 404, a lead containing at least one micro-electrode
contact and at least one macro-electrode contact is inserted
through the cannula, to the brain in 406. In some embodiments, the
lead is inserted with its distal end at the front, to a desired
depth, that was determined during a previously performed imaging
test, for example an MRI test. In some embodiments, the lead is
connected via wires at its proximal end, which is the end closer to
the patient's skull, to a recording device located outside the
patient's body. In some embodiments, the lead is connected using a
wireless connection to the recording device. Optionally, the
recording device is located in or attached to the patient's
body.
[0192] According to some exemplary embodiments, the lead is
inserted by a controlled micro-drive with step sizes of 0.05 mm at
most, for example 0.01 mm. Alternatively, the lead is inserted
continuously into the brain. In some embodiments, during the
insertion of the lead through the cannula, the lead distal end is
found outside the cannula in the last 5-40 mm, preferably the last
10-25 mm.
[0193] According to some exemplary embodiments, measuring the
electrical activity of brain tissue is performed by at least one
micro-electrode contact and/or at least one macro-electrode.
Alternatively, measuring the electrical activity of brain tissue is
performed by at least two micro-electrode contacts. Optionally,
measuring the electrical activity of brain tissue is performed by
at least two macro-electrode contacts. In some embodiments, the
desired combination of electrode contacts to be used for measuring
the electrical activity of brain tissue is pre-determined.
[0194] Alternatively, the desired combination of electrode contacts
is determined during the measuring process. In some embodiments,
the electrical activity of the brain tissue is measured while the
lead continuously inserted into the brain. In some embodiments, the
lead is twisted or rotated in a desired angle or orientation during
the measurement of the electrical activity.
[0195] According to some exemplary embodiments, measuring the
electrical activity of brain tissue is performed in combination
with application of an electric field to the brain tissue. The
applied electrical field is delivered to the tissue by at least one
micro-electrode contact and/or at least one macro-electrode
contact.
[0196] According to some exemplary embodiments, the electrical
activity of the brain tissue is measured and used to determine the
electric field application parameter values of an IPG.
Alternatively, the electric field application parameter values of
the IPG are determined based on electrical activity measurement of
the brain tissue following an electric field application.
[0197] According to some exemplary embodiments, the measured
electrical activity of the brain tissue is recorded in the
recording device. In some embodiments, the measured electrical
activity is recorded and stored in a memory circuitry connected to
the recording device.
[0198] According to some exemplary embodiments, measuring the
electrical activity of brain tissue in 408 is performed by
micro-electrode contacts at the distal end of the lead, during the
insertion of the lead into the brain. In some embodiments,
electrical activity of brain tissue is measured to determine a
desired depth for applying an electric field to the tissue. The
electric field is applied by a more proximal electrode contact,
which is placed at the desired depth.
[0199] According to some exemplary embodiments, once the desired
depth is determined and/or the desired target is determined, the
cannula is retracted in 410. In some embodiments, a stylet wire is
removed from the lead lumen prior to cannula retraction. In some
embodiments, the cannula is used with at least one micro-electrode
contact and/or at least one macro electro contact to measure the
electrical activity of the brain tissue in 408. According to some
exemplary embodiments, the cannula is retracted such that its lower
end is extracted to a desired height above the desired target.
According to some embodiments, after the cannula is retracted, the
lead is fixed to the patient's skull. Alternatively, the lead is
fixed to the brain tissue.
[0200] Optionally, the lead is fixed to an apparatus located
outside the patient's skull, for example to a mechanical fixation
device.
[0201] According to some exemplary embodiments, a verification
process is performed in 412 after lead is fixed. In some
embodiments, fixation is performed that at least one
micro-electrode contact and/or at least one macro-electro contact
to be used for electric field application, are placed at the
desired depth. Alternatively, fixation is performed to make sure
that at least one micro-electrode contact and/or at least one
macro-electro contact to be used for electric field application are
placed at the desired target. According to some exemplary
embodiments, verification is performed by measuring the electrical
activity of the brain tissue at the desired depth and/or target.
Then, the measured electrical activity is compared to a previously
recorded electrical activity to make sure that the electrode
contacts are at the desired target.
[0202] According to some exemplary embodiments, after the desired
target and/or depth is verified in 412, the lead wires are
disconnected from the recording device, and are connected to an IPG
device in 414. In some embodiments, after the IPG is connected to
the lead wires it generates an electric field, for example an
electric current, that is delivered through at least one
micro-electrode contact and/or at least one macro-electrode contact
to the desired brain tissue target.
Exemplary System for Implantation and Navigation
[0203] Reference is now made to FIGS. 3B and 3C depicting a system
for implantation and navigation of a brain navigation lead
according to some embodiments of the invention. According to some
exemplary embodiments, a system for implantation and navigation of
a brain navigation lead comprises lead 500, having electrode
contacts 502 at its distal end, which penetrates first through the
brain tissue. In some embodiments, lead 500 is placed within
cannula 504, which penetrates through the brain tissue until a
desired depth is reached. In some embodiments, lead 500 is
connected via adapter 506 to extension cable 508. In some
embodiments, for example as shown in FIG. 3C, extension cable 508
connects lead 500 to an external device 510. In some embodiments,
extension cable 508 can be replaced to allow connection of lead 500
to external devices with varying number of connections. In some
embodiments, external device is a recording system. Alternatively,
external device 510 is an IPG for generating electrical pulses, for
example for DBS. Optionally, external device 510 is configured both
for recording and for generating electrical pulses.
Exemplary Lead in the Brain
[0204] Reference is now made to FIG. 3D depicting a lead in a brain
during a navigation and/or recording, according to some embodiments
of the invention.
[0205] According to some embodiments, lead 512 is inserted into
brain 516 to a desired depth. In some embodiments, lead 512
comprises insert stylet wire 514 in lead 512 lumen. In some
embodiments, lead 512 is connected to a recording system 520 via
cable 518. In some embodiments, system 520 is configured to measure
and/or record electrical activity. In some embodiments, system 520
is configured to record electric activity and to generate an
electric field to be delivered by lead 512 to brain 516.
[0206] Reference is now made to FIG. 3E depicting a lead in a brain
during electric field application, according to some embodiments of
the invention. According to some exemplary embodiments, lead 512 is
connected to IPG 524 via cable 522.
[0207] Alternatively, cable 522 is configured to connect lead 512
to recording system 520.
Exemplary Orientation Marker
[0208] According to some exemplary embodiments, the orientation of
at least one electrode on the lead relative to the surrounding
tissue is determined by a component connected to the lead or that
is part of the lead. In some embodiments, the orientation of the
electrode is aligned and fixed prior to lead insertion, for example
to ensure recording of directional signals from a desired direction
and by a desired electrode. According to some exemplary
embodiments, the lead comprises at least one orientation marker
which allows, for example to monitor the orientation of the lead
within the brain. In some embodiments, the orientation marker
allows to, for example to insert the lead into the brain in a
desired orientation. In some embodiments, lead orientation relates
to an angular direction of at least one microelectrode and/or at
least one macro electrode on the lead.
[0209] In some embodiments, determining of the angular directions
of the microelectrodes and/or the macro electrodes allows, for
example to associate signals recorded by these electrodes for
mapping the tissue and/or generating the resulted map with
objective stereotactic coordination.
[0210] Reference is now made to FIG. 3F describing a lead, for
example a navigation lead with an orientation marker, according to
some embodiments of the invention.
[0211] According to some exemplary embodiments, lead 530 has an
elongated tubular lead body 536 comprising a distal section 532 and
a proximal section 534. In some embodiments, lead 530 comprises at
least one visual marker 538. In some embodiments, at least part of
the marker 538 is positioned at the proximal section 534 of the
lead 540, in an area which remains visible to a user during the
insertion of the lead and/or during DBS treatment. In some
embodiments, the marker is visible through at least one opening or
a window in elements surrounding the lead, for example a cannula.
In some embodiments, the marker 538 is shaped and sized, optionally
as a line, an arrow, an ellipsoid or a dot along the lead body axis
to provide a visual indication to a user. In some embodiments, the
marker 538 is engraved and/or drawn on the outer surface of lead
body 536.
[0212] In some embodiments, the marker 538 is aligned with at least
one electrode positioned in an area which is hidden from the user
during lead insertion and/or during treatment. Optionally, the
marker 538 is aligned with at least one electrode positioned in the
distal section 532 of the lead 530.
[0213] According to some exemplary embodiments, the orientation
marker is aligned with an external alignment component. In some
embodiments, the external alignment marking is a line, an arrow, an
ellipsoid or a dot drawn on a tool designed for that purpose, or on
a modified tool such as a DBS-ruler, which is used to determine the
insertion depth of a DBS lead.
[0214] Reference is now made to FIGS. 3G-3H, depicting a DBS-ruler
with an external alignment component, according to some embodiments
of the invention. According to some exemplary embodiments,
DBS-ruler 540 comprises an elongated body 542 further comprising an
axial channel 544 along the elongated body 542. In some
embodiments, DBS-ruler comprising a depth measuring scale 546 for
determining the insertion depth of a lead, for example lead 530
coupled to the DBS-ruler 540. In some embodiments, DBS-ruler 540
comprising an external alignment component 550 with an alignment
marking 552 positioned above channel 544.
[0215] In some embodiments, DBS-ruler comprising an asymmetrical
opening 548 which is perpendicular to the channel 544 and is shaped
and sized to allow insertion of a lead coupling element, for
example a lead holder, in a specific orientation. Optionally, the
asymmetrical opening 548 is shaped for example as a D or any other
asymmetrical shape to prevent the rotation of the lead holder after
the lead holder is inserted into the asymmetrical opening.
[0216] Reference is now made to FIGS. 3I and 3J depicting alignment
of a lead within a DBS-ruler, according to some embodiments of the
invention. According to some exemplary embodiments, once the lead
holder is inserted into the asymmetrical opening 548, the lead
holder clamps 554 are loosened, for example to allow rotation of
the lead 530 relative to the lead holder and/or relative to the
DBS-ruler 540. In some embodiments, the lead 530 is rotated until
marker 538 is aligned with alignment marking 552. In some
embodiments, once the marker is aligned with the alignment marking,
the lead holder clamps 554 are tightened, for example to prevent
the rotation of the lead 530. Alternatively or additionally, a
fixation element coupled to the DBS-ruler, for example ruler screw
556 is turned, for example to prevent the rotation of the lead
holder relative to the DBS-ruler.
[0217] According to some exemplary embodiments, the external
alignment feature comprises a window or an opening in a tube. In
some embodiments, the opening in the tube allows a user to verify
the alignment by visualizing the marker line through the opening.
Optionally, the marker is ellipsoid and fits the window in some
areas. In some embodiments, the marker line visualized through the
window is aligned with a marker positioned on the outer surface of
the tube. In some exemplary embodiments, the external alignment
feature is drawn or engraved on one of the tools of the
stereotactic implantation, for example the electrode holder, and/or
the lead-holder and/or a cannula used for the insertion of the lead
into the tissue.
[0218] Reference is now made to FIG. 3K depicting a lead with a
marker that is aligned relative to a cannula alignment marking
according to some embodiments of the invention. According to some
exemplary embodiments, lead 530 is placed within a cannula, for
example guiding cannula 580. In some embodiments, the lead is
rotated within the cannula until a lead marker 538 is aligned with
a cannula alignment marking 584. In some embodiments, the lead
marker 538 is visible through a window 582 in the cannula body.
[0219] According to some exemplary embodiments, during the process
of inserting the lead into the brain, the orientation marker is
visible to the user, for example to allow the user to determine the
electrodes orientation and/or to verify that the electrodes
orientation is a desired orientation. In some embodiments, the
orientation marker is visible through a window, for example as
shown in FIG. 3K.
[0220] According to some exemplary embodiments, a plurality of
markers, for example 2, 3, 4, 5, 6 or any larger number of markers
are positioned on different angular directions. A possible
advantage of the plurality of markers is that they can be used for
alignment in one of several possible directions. For example, if a
user desires the center of a first electrode to face the anterior
anatomical direction, a marker with a first color, e.g. blue, is
aligned to an external alignment feature. In some embodiments, if
the user desires the center of the first electrode to face the
antero-medial (i.e. at 45 degrees angles to anterior direction and
medial direction) anatomical direction, a line with a second color
can be aligned to an external alignment feature. In some
embodiments, the lead is inserted in an orientation in which the
first marker, which was initially aligned with an external
alignment feature, is not conveniently observed, for example when
the marker faces a piece of equipment that occludes it, yet a
second marker on the lead is conveniently observable and provides
an indication to the user that the desired alignment is maintained.
This indication can be based on alignment to a second external
alignment feature present on one of the tools of the stereotactic
implantation. In some embodiments, the alignment is based on
pattern and/or a design of the marker and/or of the alignment
feature.
[0221] Additionally or optionally, the plurality of markers are
repeated along the lead axis, for example to allow convenient
observation in relation to other equipment, e.g. "electrode
holder", or "Ben-Gun" or insertion cannula. In some embodiments,
when the markers are on a single angular orientation and optionally
at different heights, they also serve to indicate that the lead is
not twisted, or undergoes torsion, and to verify that the angular
orientation is maintained along the lead axis.
[0222] Reference is made to FIGS. 3L and 3M, depicting lead
alignment relative to an external alignment element with a
plurality of alignment markings, according to some embodiments of
the invention. According to some exemplary embodiments, an external
alignment element, for example electrode holder 586, comprises
openings 590 sized and shaped to allow insertion of a lead. In some
embodiments, the electrode holder comprises one or more alignment
markings 594, optionally associated with each of the openings 590.
Additionally, the electrode holder 586 comprises an asymmetrical
opening 588 which is sized and shaped to allow insertion of a lead
holder in a single orientation through the asymmetrical opening
588.
[0223] According to some exemplary embodiments, a lead can be
inserted through anyone of openings 590 and to be aligned using the
alignment markings that are associated with the specific opening.
In some embodiments, for example as shown in FIG. 3M, the marker
538 of lead 530 is aligned according to alignment marking 594 on
the surface of electrode holder 586. In some embodiments, once the
marker 538 is aligned, at least one screw of fixation screws 596
connected to the electrode holder 586 is tightened to prevent the
relative rotation of the lead.
[0224] Reference is now made to FIG. 3N describing a process for
determining and fixing the orientation of a lead, according to some
exemplary embodiments of the invention.
[0225] According to some exemplary embodiments, the lead is placed
in a lead holder at 600. In some embodiments, the lead holder is
connected to a measuring device at 602, for example a DBS-ruler. In
some embodiments, the lead holder is connected to the DBS-ruler in
a way that allows only a single pre-determined orientation. In some
embodiments, the relative rotation of the lead holder is restricted
when the lead holder is connected to the DBS-ruler.
[0226] According to some exemplary embodiments, the lead
orientation is modified relative to an external alignment marking
at 604. In some embodiments, the lead orientation is modified by
aligning the orientation marker on the lead with at least one
external alignment marker of an external element, for example an
electrode holder or a cannula, to reach a desired orientation of
the electrodes.
[0227] According to some exemplary embodiments, the lead
orientation is fixed at 606. In some embodiments, the lead
orientation is fixed relatively to the external element, for
example relative to the lead holder. In some embodiments, the lead
orientation is fixed by closing lead holder attachment means, for
example lead holder clamps or screws of an electrode holder. In
some embodiments, after the lead orientation is fixed, the lead and
the lead holder are positioned in a desired orientation relative to
the DBS-ruler, and relative to each other.
[0228] According to some exemplary embodiments, the lead and/or the
lead holder are coupled to a stereotactic device at 608. In some
embodiments, the lead is coupled in a way that allows visibility of
the marker, for example for monitoring the lead orientation during
lead insertion, navigation and/or treatment.
[0229] According to some exemplary embodiments, the orientation
marker is produced using techniques that maintain the
biocompatibility of the device. In some embodiments, the
orientation marker is produced using a laser device which emits
laser beams to accurately and locally heat the lead body. In some
embodiments, the heating changes the color or the reflectibility of
the marker surface in a desired shape and/or location on the lead.
Optionally, the laser beams are directed towards a metal and/or a
polymer component disposed on the lead body, for example a platinum
ring, a platinum/iridium alloy ring, a titanium ring, or another
shape on a similarly biocompatible metal or polymer. In some
embodiments, the resulting shape on the disposed component serves
as the orientation marker.
[0230] In some embodiments, the orientation marker is marked on the
lead by an ink, and then optionally covered by a transparent
polymer. In some embodiments, the transparent polymer is applied
using a reflow technique in which the polymer is heated to the
melting point and applied over the ink marking where it cools and
remains. Alternatively, the marker is produced from a polymer, for
example mylar or polyurethane, which can be either dyed to a
desired color or printed on with a certain color, or otherwise
prepared to have a color that is different from the color of the
lead, such that it serves as an orientation marker. In some
embodiments, this polymer marker is attached to the lead body using
the reflow technique.
[0231] A possible advantage of determining the orientation and/or
the relative position of the lead electrodes, is that it allows to
better use the multiple contacts disposed on the lead, for example
by understanding in which stereotactic direction the more optimal
navigation trajectory is found during the surgery, or which contact
would optimally be used to emit directional current for optimal
therapeutic effect. Optimal therapeutic effect could generally mean
a satisfactory attenuation of the disease symptoms, such as e.g.
tremor, rigidity, akinesia, etc., while incurring minimal or zero
side effects on the patient, such as muscle activation, dysarthria,
paresthesia, etc.
Exemplary Lead
[0232] According to some exemplary embodiments, a brain navigation
lead has a distal end, which is the lead end that penetrates first
through the brain tissue, and a proximal end, which is the lead end
located closer to the upper side of the skull. In some embodiments,
the brain navigation lead comprises at least one microelectrode
contact and at least one macro-electrode contact.
[0233] According to some exemplary embodiments, macro-electrodes
and microelectrodes are connected to wires within the lead, which
connects them to electrode contacts on the outer surface of the
lead. In some embodiments, micro-electrode contacts are positioned
distally to macro-electrode contacts. In some embodiments, lead
comprises a micro-electrode at its distal tip. In some embodiments,
macro-electrode contacts are positioned along the circumference of
the lead.
[0234] According to some embodiments, micro-electrodes are
configured to sense electric signals from single neurons and/or
neural cell populations residing in small volumes, for example in
0.1.times.0.1.times.0.1 mm.sup.3. On the other hand, in some
embodiments, macro-electrodes are configured to sense electric
signals, for example local field potential (LFP) originating from
neuronal population residing in large volumes. Preferably,
macro-electrodes are configured to deliver electric field, for
example electric current to brain tis sue.
[0235] Reference is now made to FIGS. 4A-4J depicting leads having
different organizations of micro-electrode and macro-electrode
contacts, according to some embodiments of the invention. According
to some exemplary embodiments, for example as shown in FIG. 4A,
lead 700 comprises a single micro-electrode contact 706 at distal
end 702 tip, and 4 ring macro-electrode contacts spaced apart along
the longitudinal axis of the lead closer to proximal end 704.
[0236] According to some exemplary embodiments, for example as
shown in FIG. 4B, lead 700 comprises 4 ring macro-electrodes
contacts spaced apart along longitudinal axis 711, at least one
micro electrode contact 706 near the distal tip of the lead, and at
least 2 micro-electrode contacts 707, distributed along the
circumference of lead 700.
[0237] According to some exemplary embodiments, for example as
shown in FIG. 4C, lead 700 comprises 4 spaced apart ring
macro-electrode contacts distributed along the longitudinal axis of
lead 700, at least 3 micro-electrode contacts 709 distributed along
lead 700 circumference. In addition, lead 700 further comprises a
single micro-electrode contact 706 at its distal end tip.
[0238] According to some exemplary embodiments, for example as
shown in FIG. 4C, lead 700 comprises at least one micro electrode
contact, at distal end 702 of the tip, and at least two
micro-electrode contacts 718, located proximally to contact 706,
distributed along the circumference of lead 700. In some
embodiments, both micro-electrode contact 706 and contacts 718 are
positioned near distal end 702 of lead 714.
[0239] In some embodiments, lead 700 further comprises two ring
macro-electrodes contacts 708 and 2 rows of segmented
macro-electrodes contacts 716. Each row of segmented macro
electrode contacts includes at least 3 contacts distributed along
lead 700 circumference.
[0240] According to some exemplary embodiments, for example as
shown in FIG. 4E, lead 700 comprises at least 3 micro electrode
contacts 706 at its distal end 702. In some embodiments, lead 700
further comprises segmented macro-electrode contacts 716 organized
in four spaced apart rows along the longitudinal axis of lead 700
with at least two macro-electrodes contacts 716 for a segmented
ring.
[0241] According to some exemplary embodiments, for example as
shown in FIG. 4F, lead 700 comprises 4 rows of macro-electrode
contacts 716, with at least 3 contacts per row. In some
embodiments, lead 700 further comprises 6 micro-electrode contacts
706 (only 3 contacts are visible) distributed along the
circumference of lead 700 distal end 702. In this organization, 3
out of the 6 micro-electrode contacts are aligned with the center
of a macro-electrode contact, and 3 micro-electro contacts are
aligned with a gap between two adjacent macro-contacts.
[0242] According to some embodiments, a brain navigation lead
comprises a combination of both ring macro-electrode contacts and
segmented macro electrode contacts. In some embodiments, segmented
microelectrode contacts are distributed along at least one row
which is located in a distal position relative to ring
macro-electrode contacts. Alternatively, segmented macro-electrode
contacts are distributed along at least one row which is located in
a proximal position relative to ring macro-electrode contacts.
Optionally, at least one row of segmented macro-electrode contacts
is located between two ring macro-electrode contacts. In some
embodiments, at least one segmented macro-electrode contact is
positioned in a row along the longitudinal axis of the lead. In
some embodiments, this organization of ring and segmented macro
electrode contacts, allow a more accurate application of electric
field to the brain tissue, compared to a lead having only ring
macro electrode contacts.
[0243] According to some exemplary embodiments, for example as
shown in FIG. 4G, lead 700 comprises at least 4 micro-electrode
contacts 706 in its distal 702 end, and at least 6 ring
macro-electrode contacts 708, proximal to micro-electrode contacts
706.
[0244] In some embodiments, lead 700 further comprises segmented
macro-electrode contacts 718 positioned between micro-electrode
contacts 706 and ring macro-electrode contacts 708. In some
embodiments, segmented contacts 718 are positioned in at least one
row along lead 700 longitudinal axis, facing a desired portion of
brain tissue. In some embodiments, facing a desired direction
allows segmented contacts 718 to apply an electric field in a
desired direction, for example direction 720 and not in the
opposite direction 722. In some embodiments, segmented contacts 718
are positioned very close to adjacent macro-electrode contacts. In
some embodiments, ring macro-electrode contacts are positioned very
close to each other. In some embodiments, segmented macro-electrode
contacts and/or ring macro-electrode contacts have a relatively
narrow width.
[0245] According to some embodiments, a brain navigation lead
comprises segmented macro electrode-contacts positioned in a spiral
curve along the lead outer surface. In some embodiments the spiral
curve comprises a single spiral electrode contact. According to
some exemplary embodiments, for example as shown in FIG. 4H, lead
700 comprises micro-electrode contacts 706 at its distal 702 end,
and segmented macro-electrode contacts positioned in a spiral curve
along lead 700 outer surface.
[0246] According to some embodiments, a brain navigation lead
comprises at least two ring macro-electrode contacts, where one of
the two ring macro-electrode contacts is positioned in angle
relative to the other rind macro-electrode contact.
[0247] According to some exemplary embodiments, for example as
shown in FIG. 4I, lead 700 comprises micro electrode contacts 706
at its distal 702 end, and at least two ring macro-electrode
contacts proximal to the micro-electrode contacts. In some
embodiments, one ring macro-electrode contact 727 of at least two
ring macro-electrode contact is positioned in a desired angle 724
relative to a second ring macro-electrode contact 727.
[0248] According to some embodiments, for example as shown in FIG.
4J a brain navigation lead comprises at least one macro-electrode
contact, with a varying width along the circumference of the lead.
According to some exemplary embodiments, lead 700 comprises at
least one micro-electrode contact 706 at its distal end, and at
least one ring macro-electrode contact 726 with a varying width
more proximal to micro-electrode contact 706.
[0249] Reference is now made to FIGS. 5A-5E depicting a brain
navigation lead according to some embodiments of the invention.
According to some exemplary embodiments, lead 800 comprises
micro-electrode contacts 810 at its distal end in the same
configuration as in FIG. 4C, and at least 1 row of macro-electrode
contacts, for example 4 rows of macro-electrode contacts, for
example as shown in FIG. 4D, proximally to micro-electrode contacts
810. In some embodiments, lead 800 is manufactured from an
electrical insulator material 808, and electrode contacts are
manufactured from an electrical conducting material, for example
copper. In some embodiments, the diameter 807 of lead 800 is
between 0.2-2.5 mm, for example 0.5-1.5 mm. In some embodiments
diameter 807 is 1.27 mm. In some embodiments, the length 806 of
lead 800 is between 50-600 mm, for example between 100-500 mm.
[0250] Alternatively, length 806 is between 20-100 mm.
[0251] Optionally, length 806 is 400 mm. In some embodiments, the
width 804 of each macro-electrode contact 802 is between 0.5-10 mm,
for example 0.6-2.5 mm.
[0252] Alternatively, width 804 is between 0.8-8 mm. Optionally,
width 804 is 1.5 mm. In some embodiments, the space 809 between
each macro-electrode contact 802 is between 0.1-50 mm, for example
0.2-7 mm. Alternatively, space 809 is between 0.5-20 mm.
Optionally, space 809 is 0.5 mm.
[0253] According to some embodiments, macro-electrode contact width
is between 0.1-3 mm, for example 0.5-1.5 mm. Optionally,
macro-electrode contact width is between 0.1-1.5 mm. According to
some embodiments, macro electrode contact diameter is between 0.2-2
mm, for example 1.3 mm.
[0254] According to some exemplary embodiments, micro-electrode
contacts have a diameter between 5-50 micron, for example 25
micron.
[0255] According to some embodiments, the longitudinal distance
between macro-electrode contacts is between 0.1-3 mm, for example
0.5 mm. According to some embodiments, the longitudinal distance
from the bottom ring macro-electrode contact to a distal tip
micro-electrode contact is between 0.6-3 mm, for example 1.5
mm.
[0256] According to some exemplary embodiments, the longitudinal
distance from the bottom ring macro-electrode contact to at least 3
micro-electrode contacts located along the circumference of the
lead is 0.2-0.9 mm, for example 0.5-0.7 mm.
[0257] According to some embodiments, the distance between
macro-electrode contacts on the lead circumference is 50-200
micron, for example 100 micron. In some embodiments, the distance
between micro-electrode contacts on the arc is 0.6-2 mm, for
example 1 mm.
[0258] According to some embodiments, the angular distance between
6 micro-electrode contacts on the lead circumference is .pi./3
between the centers of the contacts. In some embodiments, the
angular distance between 3 micro-electrode contacts on the lead
circumference is 2/3.pi..
[0259] According to some embodiments, the micro-electrode contacts
are unipolar. In some embodiments, each micro-electrode contact is
connected by a single wire. In some embodiments, measuring
electrical activity can be bi-polar if potential is fed from two
nearby contacts into two inputs of a differential amplifier.
Exemplary Orientation Sensor
[0260] According to some exemplary embodiments, at least one sensor
is positioned on the lead to determine the orientation of the
electrodes, for example directional electrodes on the lead or the
twisting of the lead by a non-imaging technique. In some
Alternatively or optionally, if the electrode is helical then the
sensor provides an indication regarding the depth of the electrode
based on the orientation of the electrode. In some embodiments, the
sensor is positioned proximally to the distal tip of the lead, for
example in a distance of up to 50 mm from the distal tip.
Alternatively, the sensor is positioned proximally to at least one
electrode or electrode contact of the lead. In some embodiments,
the lead comprises both a sensor proximally to the distal tip and
at least one sensor proximally to an electrode on the lead
circumference. In some embodiments, the sensor measures the lead
orientation using a magnetic field, strain-related changes in
resistance, radio-frequency transmission, radio-frequency
reception, ultrasound transmission/reception, ultrasound reflection
using an external sensor or optical transmission/reception, for
example infra-red.
[0261] Reference is now made to FIG. 5B, depicting a lead with an
orientation sensor and a marker according to some exemplary
embodiments of the invention.
[0262] According to some exemplary embodiments, a lead 811
comprising an elongated body 812, optionally a tubular or a
cylindrical body with a distal section 813 and a proximal section
814. In some embodiments, the lead 811 comprising at least one
electrode, for example a microelectrode or a macro electrode at the
distal section 813. In some embodiments, the electrode 815 is
electrically connected by electrical wiring, delivered through
lumen 818 of the body 812 to a recording circuitry 823 of a control
system 819.
[0263] According to some exemplary embodiments, lead 811 comprising
an orientation sensitive element, for example an orientation sensor
816 positioned within the lumen 818 or on surface of the body 812.
In some embodiments, the sensor 816 is electrically connected to an
orientation detection circuitry 825 of control system 819.
[0264] In some embodiments, when orientation sensor detects a
change in the orientation of the lead and/or electrodes, for
example, rotation or twisting of the lead, the sensor 816 delivers
a signal to orientation circuitry 825. In some embodiments, the
orientation circuitry 825 is under the control of control circuitry
821 which delivers an indication to the user regarding the change
in orientation through interface 829.
[0265] According to some exemplary embodiments, the orientation
sensor 816 is a gravitational sensor, which detects changes in the
effect of the gravitational field. In some embodiments, these
changes occur when the orientation of the sensor relative to the
ground, or relative to a gravitational base line value is
changed.
[0266] According to some exemplary embodiments, the orientation
sensor 816 detects changes in resistance of electrode wires or
sensor wires. In some embodiments, wires are coiled in a specific
direction inside the lumen 818 of the lead 811. In some
embodiments, when the lead turns in a direction similar to the
coiling direction, the wires are stretched and the resistance is
increased. Alternatively, when the lead rotates in a direction
opposite to the coiling direction, the resistance is decreased.
[0267] According to some exemplary embodiments, the orientation
sensor 816 is a magnetic sensor, which detects changes in a
magnetic field surrounding the sensor. In some embodiments, a
magnetic field 831 is applied by an external electromagnetic field
generator 829, positioned outside of the head. In some embodiments,
sensor 816 detects changes in the magnetic field as a function of
the orientation of the lead, for example changes that occur during
the rotation or twisting of the lead.
[0268] According to some exemplary embodiments, the orientation
sensor 816 detects changes in radiofrequency signals transmitted
from at least two spaced apart transmitters. In some embodiments,
the radiofrequency signals received by the sensor change as a
function of the distance of the orientation sensor 816 from each of
the transmitters.
[0269] According to some exemplary embodiments, control system 819
comprises memory 827, for example for storing orientation values of
the lead, base line values of lead orientation, recorded signals
from the orientation sensor and/or from the electrode 815.
[0270] According to some exemplary embodiments, lead 811 comprising
a marker 817, for example marker 538 shown in FIGS. 3F, 3I and 3J.
In some embodiments, marker 817 is positioned in the proximal
section 814 of the lead 811, and is optionally remains visible
throughout the lead navigation process and/or the DBS treatment. In
some embodiments, the marker 817 is aligned with at least one
alignment feature of a device connected or associated with the lead
811.
[0271] According to some exemplary embodiments, the lead 811
comprise both an orientation sensor 816 and a marker 817. In some
embodiments, the marker is used to align the lead 811 relative to a
reference point before lead insertion, and the orientation sensor
is used to monitor the orientation of the lead during the
navigation or treatment procedures. In some embodiments, the marker
is used to determine the orientation of the proximal section 814 of
the lead, while the orientation sensor 816 is used to determine the
orientation of the distal section 813 of the lead 811 which is
hidden from a user during the lead navigation process and DBS
treatment.
[0272] Reference is now made to FIGS. 5C and 5D depicting a lead
with an orientation sensor, according to some embodiments of the
invention.
[0273] According to some exemplary embodiments, for example as
shown in FIG. 5C a lead 820 comprises at least one sensor 826 for
measuring the orientation of at least one microelectrode, for
example microelectrode 830 and/or at least one macro electrode, for
example macro electrode 828 on the lead. In some embodiments, the
sensor is positioned at the distal section 824 of the lead,
optionally in a close distance, for example up to 20 mm from one of
the electrodes. Alternatively, the sensor 826 is located at any
position along the lead 820. In some embodiments, the sensor 826 is
electrically connected by electric wire 832 to system 834. In some
embodiments, the sensor 826 transmits signals that are associated
with the lead orientation and/or with the orientation of one of the
electrodes via wire 832 to system 834. In some embodiments, the
system 834 determines the orientation of the lead and/or electrodes
based on the signals and optionally provides an indication to the
user regarding this orientation. In some embodiments, sensor 826 is
electrically connected to at least one additional orientation
sensor positioned on the lead 820.
[0274] According to some exemplary embodiments, for example as
shown in FIG. 5D, lead 836 comprises a wireless orientation sensor
838. In some embodiments, wireless orientation sensor is positioned
in a close distance of up to 20 mm from the closest microelectrode
842 or the closest macro electrode 840. Alternatively, the wireless
orientation sensor is located at any position along the lead 820.
In some embodiments, the wireless orientation sensor 838 transmits
wireless signals, for example wifi, Bluetooth to a receiver 844 of
system. Alternatively, the sensor is a passive component, and the
system can wirelessly sense the orientation of the sensor for
example, by transmitting electro-magnetic or ultrasonic waves, or
by inducing a magnetic field and measuring the disturbance caused
by the sensor, or by the sensor detecting a magnetic field which is
spatially encoded such that the spatial location can be inferred
from the magnetic field properties.
[0275] According to some exemplary embodiments, the orientation
sensor is optionally in communication with one or more additional
sensors placed outside the brain, for example on the scalp or dura,
or on a more superficial layer of the brain e.g. cortex. In some
embodiments, the one or more additional sensors are optionally
coupled to one or more cannulas which are inserted into the brain
in the procedure. Alternatively, the cannulas are in contact with
the patient body excluding the head, or not in contact with the
patient body at all. In some embodiments, the at least one
additional sensor is used to receive or transmit a signal, for
example by way of a magnetic field, radio-frequency transmission or
receiving, ultrasound transmission/reception or optical
transmission/reception (e.g. infra-red). In some embodiments, the
coupled reception-transmission performed by the first sensor placed
on the lead distal end, and the second sensor placed outside of the
brain allows, for example to infer the orientation of the lead
distal end and the macro electrodes and/or micro electrodes
disposed on it.
[0276] In some embodiments, the first sensor placed on the lead
distal end is a passive component, and the second sensor placed
outside is used to wirelessly sense the orientation of the first
sensor for example by transmitting electro-magnetic or ultrasonic
waves, or by inducing a magnetic field and measuring the
disturbance caused by the first sensor.
[0277] Reference is now made to FIG. 5E depicting a lead with an
orientation sensor and an additional sensor which is placed outside
of the brain, according to some embodiments of the invention.
[0278] According to some exemplary embodiments, lead 848 comprises
an orientation sensor 852 positioned in a close distance from
electrodes 847. In some embodiments, sensor 852 transmits signals
to system 850 which also receives signals from at least one
external sensor 854 which is position outside of the brain. In some
embodiments, the external sensor 854 is positioned inside or
outside the skull. In some embodiments, the external sensor is
positioned on any part of the body or in a distance from the body.
In some embodiments, the external sensor 854 communicates with
orientation sensor 852 by transmitting and/or receiving signals
from the orientation sensor 852 which is positioned inside the
brain. In some embodiments, system 850 determines the position
and/or the orientation of the lead and/or lead electrodes based on
signals derived from both the orientation sensor 852 and the
external sensor 854.
Exemplary Fiber Optic Twist Sensor
[0279] According to some exemplary embodiments, the sensor is an
optical fiber twist sensor which allows detection of the twist or
torsion of the lead. In some embodiments, the optical fiber twist
sensor is positioned along the lead axis, and optionally reaches
the distal section of the lead. In some embodiments, a system
connected to the sensor measures the differences in light
properties and/or in light parameter values between the light
inserted into the lead and the light reflected from the lead. In
some embodiments, the changes include for example the amount of
light reflected from a fiber optic positioned inside the lead
compared to the amount of light projected into the lead.
[0280] Exemplary resistance-sensitive orientation sensor According
to some exemplary embodiments, the orientation sensor measures
changes in wire resistance that indicate torsion, which is rotation
around the lead axis ("roll") of one part of the lead with respect
to another part of the lead. In some embodiments, the conduction of
the wire is generally affected by the wire length and cross
section, according to the equation R=.mu.L/A, where .rho. is the
specific resistivity, L is the length and A is the cross sectional
area. When a wire is stretched, L increases while A decreases, both
leading to an increase in resistance, an effect utilized in strain
gages. When we coil a wire inside the lead body it has an initial
resistance R1. If the lead is rotated in the same direction as the
wire is coiled, i.e. giving it a "roll" about its axis in that
direction, the wire is stretched and the resistance increases.
Rotating the lead in the opposite direction would reduce the
tension on the wire and decrease its stretch, thus reducing the
resistance of the wire.
[0281] In some embodiments, two wires are coiled in opposite
directions, such that for lead rotation in one direction, the
resistance of the first wire would increase while the resistance of
the second wire would decrease. Lead rotation in the opposite
direction would lead to an opposite effect, whereby the resistance
of the first wire would decrease while the resistance of the second
wire would increase. The same would be true if more than one wire
is coiled in each direction, for example if 2 or more wires are
coiled in one direction, and 2 or more wires are coiled in the
opposite direction in the lead body.
[0282] According to some exemplary embodiments, as these changes in
resistance are small, on the order of 1% or less, sensing these
changes requires an electrical circuitry sensitive to such changes
must be used. This circuitry may be based on differential changes
in the resistance of several resistor elements, such as the well
known Wheatstone bridge circuit. For the typical small strains and
resistance changes that can be expected in this application, and
assuming no temperature changes, when an external voltage V is
applied to the balanced Full Wheatstone bridge circuit the voltage
measured by the circuit, e, is given by
e = G .times. F 4 .function. [ 1 - 2 + 3 - 4 ] .times. E
##EQU00001##
Where GF is the Gage Factor, a material property relating the
change in resistance to the strain .epsilon.
G .times. F = d .times. R / R , ##EQU00002##
.epsilon.=dL/L, and .epsilon..sub.1, .epsilon..sub.2,
.epsilon..sub.3, .epsilon..sub.4 are the strains experienced by 4
elements, or coiled wires in our case. As may be understood from
the equation, rotating the lead in one direction would lead to a
positive voltage measurement, e>0, while rotation in the
opposite direction would lead to a negative voltage measurement,
e<0. Increasing the input voltage, E, and using materials with
high GF, leads to increased measurement sensitivity. Similarly, a
Half Wheatstone bridge may be used, in which two resistor elements
are sensitive to strain and two are "dummy" resistors with fixed
resistance values, and could be outside the lead body. Then the
measured voltage would follow the equation:
e = G .times. F 4 .function. [ 1 - 2 ] .times. E ##EQU00003##
Similarly, a quarter Wheatstone bridge may be used, in which only
one element is a strain sensitive element and the other three are
fixed "dummy" resistors, and then the measurement follows:
e = G .times. F 4 .times. 1 .times. E ##EQU00004##
These circuits are known in the art and additional modifications
may be applied to counter the effect of temperature changes during
the measurement, or other effects.
[0283] According to some exemplary embodiments, strain sensitive
wires may be used without being coiled within the lead body.
Instead, two or four strain sensitive elements may be placed on the
lead surface from within or without. These gages typically have a
specific direction in which they are sensitive to strain, and
should placed such that their sensitive direction is not parallel
to the lead axis. Two gages can be placed with a 90 degrees angle
between them, both at 45 degrees to the lead axis. Four gages can
be placed such that two have their strain sensitive directions
aligned, and the other two have their strain sensitive directions
aligned, with the first pair at 90 degrees angles to the second
pair, and each pair at 45 degrees to the lead axis. This
configuration is similar to the so-called "rosette" strain-gage
configuration for measuring strains in a plane. In each of these
configurations, a type of Wheatstone bridge or similar circuitry is
required for performing a measurement.
Exemplary Electromagnetic-Orientation Sensor
[0284] According to some exemplary embodiments, the orientation
sensor comprises an electromagnetic-sensitive sensor.
Electromagnetic positioning of a catheter has been previously
described in the art, for example U.S. Pat. No. 7,197,354 entitled
"System for Determining the Position and Orientation of a
Catheter", which allows for positioning in X, Y & Z and
indicating direction changes in "pitch" and "yaw" directions, but
not in the "roll" direction--that is not in twisting around the
lead axis. In U.S. Patent Application Publication No. 2010/0324412,
entitled "Catheter With Obliquely-Oriented Coils" and U.S. Pat. No.
6,593,884, entitled "Intrabody Navigation System for Medical
Applications", using multiple sensors is described for sensing the
roll of a medical device. In U.S. Patent Application Publication
No. 2017/0049357 a single sensor is described for detecting roll in
a medical devices.
[0285] The principle underlying these sensors is that one or more
coils within the lead is sensitive to electromagnetic induction. In
some embodiments, this sensitivity is enhanced by the sensor having
a ferromagnetic core around which the one or more coils are wound.
In some embodiments, an external transmitter transmits an
electromagnetic field, which causes a current response in the coil
sensor, according to the principle of electromagnetic induction, or
Faraday's law. By detecting this current the local electromagnetic
field in the sensor surroundings is inferred, and the positioning
is based on the system transmitting a spatially-varying magnetic
field. Thus, the location in space is encoded by the local
electromagnetic field, and detecting this field allows to decode
the position in which the sensor is located.
[0286] In some embodiments, the differential sensitivity to fields
that have different axes, i.e. that have a different flux with
respect to the X, Y & Z axis, allows for example to infer the
pitch and yaw of the device. In some embodiments, the induced
current is maximal when the flux is maximal, i.e. when the
direction of maximal change in magnetic field is perpendicular to
the coil axis. In some embodiments, a symmetric coil, i.e. a coil
wound symmetrically around the core, can thus detect the position
in X, Y & Z coordinates, as well as the pitch and yaw, but not
the roll of the device. In order to sense the roll of the device,
it is required to have a coil that is wound about an axis that is
not aligned with the lead axis, and at least two components with
different winding angles with respect to the lead axis. These
components may be separate coils, or a coil with two portions
having different winding angles.
[0287] In some embodiments, when the coil is wound at an angle to
the lead axis, it responds maximally to a field with maximal flux
not parallel to the lead axis, but to the coil axis. When the lead
rotates about its axis, i.e. undergoes roll, the coil's preferred
direction changes as its own axis is changed due to the lead roll.
When there are present at different longitudinal locations on the
lead body two components, e.g. two coils with different preferred
directions, the differential measurement from the two of them can
be used to infer the absolute roll of the lead, in the absence of
torsion. When torsion is present such that there is a twist in the
lead between the two components, there is a change in the
relationship between the two measurements. Thus the relation
between the two components itself may be observed, and used to
indicate torsion of the lead.
[0288] According to some exemplary embodiments, when combined with
the lead orientation marker, which indicates the orientation of the
proximal part of the lead, the torsion indication is sufficient to
infer the lead distal tip orientation. For example: a lead is
inserted in the left hemisphere, such that the left side of the
lead is in a lateral direction and the right side of the lead is in
a medial direction. The lead proximal end is oriented such that
distal electrode #1 should be in the anterior direction, and the
torsion is indicated to be 45 degrees in the clockwise direction.
Then it is inferred that electrode #1 is facing the antero-medial
direction. If the torsion is indicated to be 90 degrees in the
counter-clockwise direction, electrode #1 is inferred to face the
lateral direction. This is irrespective of how the torsion is
indicated, by wire resistance changes, single or multiple coil
electromagnetic induction, or another technique.
[0289] In another example, the orientation sensor comprises an
electromagnetic field detector which includes a ferromagnetic core
having a perforation and at least one winding wound around the
ferrous core. In some embodiments, the perforation provides
communication between a first side of the ferrous core and a second
side of the ferrous core, for example the first side faces a
proximal side of the catheter and the second side faces a distal
side of the catheter. The winding produces a current according to
the electromagnetic field, wherein the ferrous core increases the
sensitivity of the electromagnetic field detector to the
electromagnetic field, by increasing a proportionality factor
between the current and the electromagnetic field.
Exemplary Recording and Stimulation
[0290] Reference is now made to FIG. 6 depicting a process of
recording and/or stimulation (electric field application) according
to some embodiments of the invention. According to some exemplary
embodiments, a brain navigation lead is inserted to a brain in a
close proximity to a desired pre-determined brain tissue target in
900. In some embodiments, lead comprises micro-electrode contacts
at its distal end, and macro-electrode contact closer to the
proximal lead end compared to the micro electrode contacts. In some
embodiments this allows to use micro-electrode contacts for
recording as they are the first contacts to face the brain tissue
as the lead moves in the predetermined insertion trajectory.
[0291] According to some exemplary embodiments, during the
navigation and recording process, the lead is connected to an
external device via non-implanted extension cable. In some
embodiments, the external device is an IPG configured for both
generating electric field and recording electrical activity of
brain tissue. In some embodiments this external device is
configured to record signals arriving from electrode contacts on
the lead. Alternatively, the external system is configured to apply
an electric field through electrode contacts on the lead and record
the electrical activity of the brain tissue following the electric
field application.
[0292] In some embodiments, the external device is configured to
measure and/or measure parameters from other sensors.
[0293] According to some exemplary embodiments, recording
parameters are determined in 902. Alternatively, recording and
electric field application parameters are determined in 902.
Optionally, recording and/or electric field application parameters
are determined and/or modified during the navigation process.
[0294] According to some exemplary embodiments, the electrode
contacts to be used for recording and/or electric field
applications are determined in 904. In some embodiments, lead
comprises both micro-electrode contacts and macro-electrode
contacts, and any combination of micro electrode contacts and/or
macro-electrode contacts can be used for measuring electrical
activity of brain tissue. Alternatively, any combination of
micro-electrode contacts and/or macro-electrode contacts can be
used for electrical field application. According to some exemplary
embodiments, the distribution of macro and micro electrode
contacts, along several positions on the lead outer surface and at
several angular positions on the lead circumference allow
directional recording of desired brain tissue regions around the
lead. Optionally, the distribution of macro and micro electrode
contacts, along several positions on the lead outer surface and at
several angular positions on the lead circumference allow
directional electric field application to desired brain tissue
regions around the lead.
[0295] According to some exemplary embodiments, after determining
which electrode contacts to use for recording, the external device
starts to record brain tissue electric activity as the lead
penetrates into the brain tissue in 908. In some embodiments,
recording is preformed from different combination of
micro-electrode contacts and/or macro electrode contacts facing
different brain tissue regions, in a form of directional recording.
In some embodiments, directional recording is based on the
differences between signals arriving from different locations. In
some embodiments the recorded signals have the spectral properties
of spike signals (300-20 kHz), local field potentials (0.001-600
Hz), or can be found in a broad spectrum (0.001-100 kHz). In some
embodiments, sensing electrical activity from different origins is
based on both the location of electrode contacts used for sensing,
and/or on the polarity of the measurement. According to some
exemplary embodiments, directional recording is used to sense
electrical signals from different origins in space, and process
these signals to preferred directions in space.
[0296] According to some exemplary embodiments, measuring and
recording electrical activity follows electric field application to
the brain tissue in 906. In some embodiments, the external device
connected to the lead electrode contacts is configured to apply an
electric field through at least one electrode contact to the brain
tissue. In some embodiments, after the electric field was applied,
the external device measures the electrical activity of the tissue
following the electric field application. In some embodiments,
electrical activity measurement is performed using the same
electrode contact used for electric field application.
Alternatively, electrical activity measurement is performed by
other electrode contacts. Alternatively, electrical activity
measurement is performed by combining the electrode contact used
for electric field application and other electrode contacts located
on the lead. In some embodiments, electric field application and/or
measurement of electrical activity in 906 is performed using
electrode contacts positioned in a desired direction on the outer
surface of the lead. In some embodiments, electric field
application and/or measurement of electrical activity in 906 is
performed using at least one micro-electrode contact and/or at
least one macro-electrode contact. In some embodiments, electric
field application and/or measurement of electrical activity in 906
is performed using at least one micro-electrode and the electrical
conducting cannula.
[0297] Alternatively, electric field application and/or measurement
of electrical activity in 906 is performed using at least one
macro-electrode and the electrical conducting cannula.
[0298] According to some exemplary embodiments, combining electric
field application and measurement of electrical activity in 906 is
used to determine electric pulses parameters generated by an IPG,
for example pulse width, pulse repetition frequency, and pulse
amplitude. In some embodiments, combining electric field
application and measurement of electrical activity in 906 as
described herein, can be used to determine which electrode contacts
will be used for electric field application by the IPG, for example
for DBS of desired brain targets.
[0299] According to some exemplary embodiments, based on electrical
activity measured and recorded in 906 or 908, the desired depth is
determined to position electrode contact for electric field
application in 910. In some embodiments, recorded electrical
activity is used to determine additional lead insertion
trajectories for additional leads in 910. In some embodiments,
during the insertion the electrical activity of adjacent tissue is
measured by lead electrode contacts and is used to generate a depth
fingerprint for desired locations along the insertion trajectory in
910.
[0300] In some embodiments, depth fingerprints of several locations
can be analyzed and combined to a general electrical activity map
of neuronal populations along the insertion path or at desired
locations.
[0301] According to some exemplary embodiments, recorded electrical
activity is used to modify the lead insertion trajectory, as
determined by an automatic navigation algorithm. In some
embodiments, based on the recorded electrical activity signals,
lead is either inserted or retracted until a desired location is
reached. In some embodiments, lead insertion trajectory is modified
based on measured electrical activity signals following electric
field application by electrode contacts on the lead.
[0302] According to some embodiments, electric field application
parameters are determined based on electrical activity recordings
following a previous electric field application. In some
embodiments, this is a feedback loop where electric field is
applied, and the recorded electrical activity of the tissue
following the electric field application is used to determine the
parameters of a second electric field application.
[0303] In some embodiments, the parameters for the initiating
electric field application are predetermined and stored in the
electric field application device.
[0304] According to some exemplary embodiments, previously recorded
electrical activity signals are used to select the electrode
contacts for electric field application and/or the desired tissue
region for directed electric field application.
[0305] According to some exemplary embodiments, the lead and
connected devices are configured to apply an electrical field using
at least one electrode contact on the lead, and to measure and
record electrical activity using another at least one electrode
contact, simultaneously. In some embodiments, simultaneously
electric field application and electrical activity measurement
allow to examine the effect of the applied electric on neuronal
activity. The examination provides the feedback required for
evaluating the efficacy of the applied electric field parameters,
for example lead depth, selection of electrode contacts, amplitude
of the current delivered by each contact to the tissue, and
temporal application pattern.
[0306] According to some exemplary embodiments, the measured
electrical activity is used to determine the optimal depth for
electric field application by the IPG. In some embodiments, the
measured electrical activity is used to generate a depth
fingerprint, for tissue regions along the lead insertion
trajectory. In some embodiments, the depth fingerprint is used to
determine at least one additional lead insertion trajectory.
[0307] Reference is now made to FIGS. 7A-7G depicting different
electrode contacts combinations for directional electric field
application, according to some embodiments of the invention.
According to some embodiments, an electric field is applied by at
least two electrode contacts on the lead, and induces electrical
activation of neural cells located at the direction of the applied
electric field. In some embodiments, the neurons electrical
activation is relative to the current density of the applied
electrical field at their location. In some embodiments, each pair
of micro-electrode contacts, applies an electric field in a
different direction, and therefore can activate different neuronal
populations. According to some exemplary embodiments, for example
as shown in FIG. 7A, directional electric field 1006 is emitted by
micro-electrode contact 1006 located at the lead circumference, and
is returned by micro-electrode contact 1002 located at the distal
tip of the lead. Alternatively, directional electric field is
applied by any combination of two micro-electrode contacts
positioned on the lead. In some embodiments, directional electric
field 1006 activates neuron 1008 found in the tissue region
affected by the electric field, but does not activate neuron 1010
which is located outside the affected region.
[0308] According to some exemplary embodiments, for example as
shown in FIG. 7B, when using a different pair of micro-electrode
contacts, in this case two adjacent micro-electrode contacts,
electric field 1012 activates different neurons then in FIG. 7A. In
some embodiments, electric field 1012 activates neuron 1014 found
in the tissue region affected by electric field 1012, but does not
activate neuron 1016 which is located outside the affected
region.
[0309] According to some embodiments, a single micro-electrode
contact is combined with a conducting element attached to the lead,
for example a cannula through which the lead is inserted most of
the way towards the target. According to some exemplary
embodiments, for example as shown in FIG. 7C, lead 1024 having a
similar electrode contacts distribution as lead 700 in FIG. 4C is
used to apply an electric field to brain tissue. In some
embodiments, lead 1024 applies an electric field, for example
current, through micro-electrode 1020, and uses cannula 1018 for
current return. The resulted electric field is much larger,
compared to electric fields 1012 and 1006 of FIGS. 7B and 7A,
respectively.
[0310] According to some embodiments, a multi polar electric field
is applied by at least two micro-electrode contact, and is returned
by at least two macro electrode contacts, for example a ring and a
segmented macro electrode contact. According to some exemplary
embodiments, for example as shown in FIG. 7D, lead 1026 comprises
at least 6 micro-electrode contacts located distal to segmented
macro-electrode contacts and ring macro-electrode contacts. In some
embodiments, micro-electrode contacts 1034 and 1030 are used to
emit an electric field, for example by applying current, and
macro-electrode contacts 1028 and 1032 are used for current
return.
[0311] According to some exemplary embodiments, an electric field
is applied by combining at least one micro-electrode contact and at
least one macro-electrode contact. According to some exemplary
embodiments, for example as shown in FIG. 7E, an electric field is
applied by segmented macro-electrode contact 1036 for example by
applying current, and micro-electrode contact 1038 is used for
current return. Alternatively, for example as shown in FIG. 7F, an
electric field is applied by micro-electrode contact 1038, and
macro-electrode contact 1036 is used for current return.
[0312] In some embodiments, for example as shown in FIG. 7E, due to
the different sizes of the contacts, the current density, as well
as the charge density near the micro-electrode is higher than near
the macro-electrode, and the cathodal effect of this configuration
will be more spatially selective than the cathodal effect. In FIG.
7F, the relations between cathodal and anodal spatial selectivity
are reversed.
[0313] According to some exemplary embodiments, for example as
shown in FIG. 7G, depicting a scheme for multi-polar electric field
application, contacts 1040 are used to deliver an electric field to
tissue 1048, for example as current, and contacts 1042 are used for
current return. In some embodiments, each of contacts 1040 are
connected to an independent source 1044, and the current from each
source 1044 flows through general network 1046 before reaching
contacts 1040.
Exemplary Micro-Electrodes Directional Recording
[0314] According to some embodiments, a navigation lead having
micro-electrode contacts on its outer surface is configured to
directional record electrical activity of cells in a tissue region
close to each micro-electrode contact. Reference now is made to
FIG. 8 depicting directional recording of electrical activity by
micro-electrode contacts. According to some exemplary embodiments,
at least 2 microelectrode contacts distributed along the lead
circumference are adjacent to two different tissue regions. In some
embodiments, a microelectrode contact, for example micro-electrode
contact 1052, measures and/or records the electrical activity of
adjacent neuronal cells, for example neuronal cell 1054. In some
embodiments, neuronal cell 1054 is characterized by generating
intense, high-frequency spiking, and therefore micro-electrode
contact 1052 senses electric potential 1060 that has
characteristics of high power, and frequent spikes. On the other
hand, in some embodiments, micro-electrode contact, for example
micro-electrode contact 1056 is adjacent to neuronal cells, for
example neuronal cell 1056 which does not generate spikes or that
generates low frequency spikes. In some embodiments,
micro-electrode 1050 is adjacent to neuronal cell 1056 and senses
an electric potential 1058 that has characteristics of low-power,
infrequent spikes.
Exemplary Macro-Electrodes Recording
[0315] According to some embodiments, navigation lead comprises
macro-electrode contacts distributed along the lead circumference
and is configured to measure electrical activity of neuronal cells
adjacent to the macro-electrode contact. In some embodiments, at
least one macro-electrode contact is referenced to at least another
macro-electrode contact. In some embodiments, at least two
macro-electrode contacts are referenced to a third macro-electrode
contact. Reference is now made to FIG. 9A depicting a combination
of two macro-electrode contacts referenced to a third
macro-electrode contact according to some embodiments of the
invention. According to some exemplary embodiments, a navigation
lead comprises micro electrode contacts at its distal end, for
example micro-electrode contact 1068, and segmented macro-electrode
contacts 1062, 1064, and 1066 distributed along the lead
circumference. In some embodiments, electrical activity of neuronal
cells is measured by a combination of macro-electrode contact 1062
and 1066, and is referenced by electrical activity measured by
macro-electrode contact 1064.
[0316] Reference is now made to FIG. 9B depicting multi-polar
electrical activity measuring and/or recording by a combination of
at least two macro-electrode contacts according to some embodiments
of the invention. According to some embodiments, macro-electrode
contact 1070 is combined with macro-electrode contact 1074 to
measure electrical activity of tissue adjacent to the electrode
contacts. In some embodiments, the combined macro-electrode
contacts are referenced by at least one macro-electrode contact,
for example macro-electrode contact 1072.
Exemplary Macro-Electrode Contacts
[0317] According to some embodiments, macro-electrode contacts are
shaped in different geometric designs and are configured to be
placed on the outer surface of a navigation lead.
[0318] Reference now is made to FIG. 10 depicting different
geometrical design of macro-electrode contacts, according to some
embodiments of the invention.
[0319] According to some embodiments, a navigation lead comprises
at least one micro-electrode contact 1076 and at least one
segmented macro-electrode contact 1078 on its outer surface. In
some embodiments, macro-electrode contact 1078 is shaped in the
form of a square or a rectangle 1080. In some embodiments,
macro-electrode contact 1078 is shaped in the form of a circle 1082
or as an ellipsoid 1084.
[0320] In some embodiments, macro-electrode contact 1078 is shaped
in the form of a polygon, for example hexagon 1086. In some
embodiments, macro-electrode contact 1078 is shaped in the form of
a parallelogram 1088 or trapezoid 1090. In some embodiments,
macro-electrode contact 1078 is shaped to have at least one
internal edge to increase current transfer efficiency, as in 1092.
Alternatively, macro-electrode contact 1078 is shaped in the form
of a polygon with round corners to mitigate edge effects occurring
in corners, where the current density may increase sharply.
Exemplary Current Density
[0321] According to some embodiments, a navigation lead comprising
at least micro electrode contact and at least one macro-electrode
contact is configured to apply an electric field in the form of a
current to brain tissue, by using at least one micro electrode
contact to emit current, and at least one micro-electrode contact
or at least one macro-electrode contact for current return.
Alternatively, at least on macro-electrode contact is used to emit
current and at least one micro-electrode contact or at least one
macro-electrode contact for current return.
[0322] Reference is now made to FIG. 11A depicting electric field
application in the form of electric current, by two macro-electrode
contacts according to some embodiments of the invention. According
to some embodiments, electric field 1104 is applied in the form of
a electric current by lead 1102. In some embodiments, a segmented
ring macro-electrode contact 1100 is used to emit electric current,
and ring macro-electrode contact 1098 is used for current return.
Alternatively, ring macro-electrode contact 1098 is used to emit
electric current, and segmented ring macro-electrode contact 1100
is used for current return. FIG. 11B is a magnified view of FIG.
11A. Black lines 1106 indicate lines along which electric currents
of equal amplitude flow from the emitting contact to the return
contact.
[0323] Reference is now made to FIG. 11C depicting electric field
application in the form of electric current by two segmented ring
macro-electrode contacts according to some embodiments of the
invention. According to some exemplary embodiments, electric field
1108 is applied in the form of electric current by segmented ring
macro-electrode contact 1112, and is returned by segmented ring
macro-electrode contact 1110. Alternatively, segmented ring
macro-electrode contact 1110 is used to emit electric current, and
segmented ring macro-electrode contact 1112 is used for current
return. FIG. 11D is a magnified view of FIG. 11C. Black lines 1106
indicate lines along which electric currents of equal amplitude
flow from the emitting contact to the return contact.
[0324] Reference is now made to FIG. 11E depicting electric field
application in the form of electric current by two segmented
macro-electrode contacts, with a ring macro-electrode contact
positioned between them, according to some embodiments of the
invention. According to some exemplary embodiments, electric field
1120 is applied in the form of electric current by segmented ring
macro-electrode contact 116, and is returned by segmented ring
macro-electrode contact 1114. In some embodiments, between the two
segmented macro-electrode contacts there is at least one ring
macro-electrode contact 1118.
[0325] Reference now is made to FIG. 11F depicting electric field
application in the form of electric current by ring macro-electrode
contacts, according to some embodiments of the invention. According
to some exemplary embodiments, electric field 1122 is applied in
the form of electric current by ring macro-electrode contact 1126,
and is returned by ring macro-electrode contact 1124. In some
embodiments, between the two ring macro-electrode contacts there
are at least two rows of segmented macro electrode contacts 1128.
In some embodiments, the electric field is asymmetrical, with the
field on one side of the lead is negligible compared to the field
on the other side. In FIG. 11F the current density is in
Ampere/cm3, and the colors designate the value of the current
density.
[0326] Reference now is made to FIG. 11G depicting electric field
application in the form of electric current by ring macro-electrode
contacts, according to some embodiments of the invention. According
to some exemplary embodiments, electric field 1130 is applied in
the form of electric current by ring macro-electrode contact 1138,
and is returned by ring macro-electrode contact 1134. In some
embodiments, between the two ring macro-electrode contacts there is
at least one segmented macro electrode contact 1136. In some
embodiments, an additional ring macro electrode contact 1140 can
serve for current return. In some embodiments, these results in
significant variations in the field along the longitudinal
direction with a bi-modal distribution of the density field, i.e.
there are two maxima, or two distinct regions in which the field is
maximal, along the longitudinal axis. In addition, the electric
field is asymmetrical, with the field on one side of the lead is
negligible compared to the field on the other side. In FIG. 11G the
current density is in Ampere/cm3, and the colors designate the
value of the current density.
Exemplary Short Circuitry
[0327] According to some embodiments, navigation lead is configured
to be connected to an external recording device during lead
insertion and navigation. In some embodiments, after the lead is in
a desired location, the external device is disconnected and the
lead is connected to an IPG. In some embodiments, the lead is
configured to be connected to IPG devices that have fewer channels
than lead contact wires. Therefore lead wires are interconnected or
short circuited to allow connection to an IPG device with few
output channels.
[0328] Reference is now made to FIGS. 12A and 12B depicting a
navigation lead connected to an external device for recording, and
to an IPG device, according to some embodiments of the invention.
According to some exemplary embodiments, lead 1140 comprises at
least one micro-electrode contact 1142, and at least one
macro-electrode contact, for example electrode contact 1144. In
some embodiments, lead 1140 is connected to a recording device
1146, that has at least one input channel 1148, for example 6 input
channels, via lead wires 1150, 1152, 1154, 1156, and 1158 during
the lead navigation step. In some embodiments, once lead 1140 is in
a desired depth and/or at a desired target tissue, device 1146 is
disconnected and lead wires are connected to IPG 1164. In some
embodiments, IPG 1164 has at least one output channel, for example
3 output channels 1166. In some embodiments, to allow connection of
5 lead wires to 3 output channels in IPG 1154, lead wires 1156 and
1154 are interconnected to a combined wire 1160, and lead wires
1152 and 1150 are interconnected to combined wire 1162.
[0329] In some embodiments, the combined wires are connected to IPG
1164 output channels, in addition to lead wires that were not
interconnected, for example lead wire 1158. According to some
embodiments, IPG 1146 comprises a charge density circuitry,
configured to check that the maximal charge density, which is
calculated as an integral of current over time, will not be
exceeded. According to some embodiments, each segmented
macro-electrode contact has its own contact wire. In some
embodiments, at least two segmented macro-electrode are
interconnected to generate a larger electrode contact, configured
to apply an electric field to a larger tissue area compared to the
electric field applied by a single segmented macro-electrode
contact. In some embodiments, combining macro-electrode contacts
allows to apply a similar electric field through several
macro-electrode contacts.
[0330] According to some embodiments, a element connector is used
to connect contact lead wires to recording device or to IPG device.
In some embodiments, the connector comprises electric contacts
according to the electric connection standards of the recording
device and/or the electric connection standards of the IPG. In some
embodiments, the connector element is configured to short-circuit
lead wires by interconnecting at least two wires to a single
combined wire.
[0331] In some embodiments, lead wires are connected to two cables,
one recording cable is connected to a recording device, and an IPG
cable is disconnected from the IPG during navigation. In some
embodiments, prior to electric field application by the IPG, lead
is disconnected from recording cable and is connected through IPG
cable to the IPG. In some embodiments, during electric field
application by the IPG, the recording cable is capped.
Exemplary Automatic Navigation and/or Mapping
[0332] According to some exemplary embodiments, automatic mapping
algorithms, for example as described in WO2016182997, record
signals received from the surrounding tissue along the lead
insertion trajectory, and provide, for example as an output signal
a functional "tag" or "state" associated with each or some depth
positions along the trajectory. In some embodiments, assigning a
tag for each or some depth position allows, for example to
functionally map the tissue along the lead insertion trajectory
and/or in a distance of up to 1 to 5 mm from the insertion
trajectory. The term "functional" here relates to the properties of
the tissue as inferred from the electrophysiological behavior of
the tissue, and is different from "anatomical" which relates to the
position of the tissue being mapped and its composition as can be
understood from available imaging contrast techniques.
[0333] According to some exemplary embodiments, the automatic
control of the micro drive which accurately inserts the lead into
the tissue is based on the automatic mapping algorithm. In some
embodiments, the automatic control means that based on the assigned
functional tag or tags, and optionally according to a set of
predetermined instructions, the drive step-size and/or or the drive
speed are updated. For example, when the tagging is such that the
lead is distant from a target which requires fine, high resolution
mapping, the step size and/or speed is automatically adjusted to be
large, e.g. 0.5 mm step size or larger, or 1 mm step size or
larger, or a speed of 0.5 mm per second or larger, or 0.25 mm per
second or larger, such that the time spent on mapping that region
is minimized. In some embodiments, when the tagging is such that
the lead is within or near a target area in which a high resolution
mapping is required, the step size and/or speed is automatically
adjusted to be small, e.g. 0.025 mm or smaller, or 0.1 mm or
smaller, or a speed of 0.01 mm per second or smaller, or 0.05 mm
per second or smaller, such that the target area is mapped with a
desired high resolution.
[0334] Reference is made to FIGS. 13A and 13B depicting the
identification of multiple spatially differentiated, or
axis-shifted trajectories inferred from a lead's single insertion
trajectory, according to some embodiments of the invention. In some
embodiments, at least one trajectory is inferred from at least two
insertion trajectories.
[0335] According to some exemplary embodiments, for example as
shown in FIG. 13A, lead 1300 is inserted into the brain tissue
along trajectory 1304. In some embodiments, at least one
microelectrode, for example microelectrodes 1302 and 1303 record
signals from the surrounding tissue at different depth positions
along the insertion trajectory 1304. In some embodiments, based on
the recorded signals from the microelectrodes, a plurality of
axis-shifted trajectories are mapped, for example trajectory 1306
which is based on signals from microelectrode 1303 and trajectory
1308 which is based on signals from microelectrode 1302.
[0336] According to some exemplary embodiments, for example as
shown in FIG. 13B a plurality of axis-shifted trajectories are
calculated by signals derived from bi-polar macro electrode pairs.
In some embodiments, a bi-polar pair of macro electrodes, for
example macro electrodes 1312 and 1314 record signals from the
surrounding tissue during the insertion of lead 1310 into the
brain. In some embodiments, an axis-shifted trajectory, for example
trajectory 1316 is calculated and/or determined based on the
bi-polar measured signals.
[0337] According to some exemplary embodiments, the functional
mapping, at each or in some depth positions is based on signals
recorded and processed to extract signal features. In some
embodiments, processing is comprised of rectification, for example
full-wave rectification and/or filtering and/or normalization with
respect to features extracted from previously recorded signals,
and/or 1/f correction and estimation of power spectral density. In
some embodiments, the signal features comprised of the mean signal
energy or magnitude, inferred from the root-mean-square (RMS) or
normalized root-mean-square (nRMS), signal power at a range of
frequency bands, for example, delta band [1-4 Hz], theta band [4-8
Hz], alpha band [8-12 Hz], beta band [12-35 Hz], and/or gamma band
[30-80] Hz, and/or high-gamma band [80-200 Hz].
[0338] A possible advantage of using the beta band is that the
activity in the basal ganglia is correlated with symptoms of
Parkinson's Disease (PD), and that stimulating the STN of a PD
patient leads to effective symptom relief when the stimulation is
delivered in a region of significant beta oscillations, according
to several studies. In some embodiments, using beta band filtering
for the processing of the signals allows, for example to identify
regions with significant beta oscillations and to direct the
therapeutic stimulation to these regions.
[0339] In some embodiments, the signal features may alternatively
or additionally include spike rates, typically based on detection
of neuronal action potentials (also called spikes), where the
detection is typically performed by calculating a positive or
negative amplitude threshold and detecting amplitudes that cross
the threshold. In some embodiments, The spike signals are usually
found in the 300 Hz-10 KHz frequency range, and can be related to
spikes probably elicited by a single neuron ("Single Unit
Activity", "SUA") or to spikes elicited by a local population of
neurons ("Multi Unit Activity", "MUA").
[0340] Reference is now made to FIGS. 13C and 13D, depicting
functional mapping of the brain tissue based on signals recorded
from a plurality of electrodes, according to some embodiments of
the invention.
[0341] According to some exemplary embodiments, for example as
shown in FIG. 13C the result of a functional tissue mapping is a
series of functional tags which are associated with specific depth
positions along the insertion trajectory of the lead. In some
embodiments, trajectory 1320 comprises different sections of
functional tags which are associated with specific depth locations,
for example section 1322 of the insertion trajectory is associated
with the tag of DLOR sub-region of the STN, and section 1324 is
associated with the tag VMNR sub-region of the STN.
[0342] According to some exemplary embodiments, for example as
shown in FIG. 13D, each of the tags is assigned to a depth position
based on recording measurements 1326 from the surrounding tissue
which are performed by at least one electrode or a combination of
electrodes on the lead. In some embodiments, each recording
electrode or combination of electrodes has a specific location on
the lead, as shown in 1332 which generates a different mapping
trajectory, for example trajectories 1328 and 1330 with different
associated tags for the same depth position. In some embodiments,
the difference in tagging between each trajectory is caused by the
variation in spatial location of the calculated trajectory with
respect to the trajectory of the lead central axis, for example
lead 1321 and/or the combination of the recording electrodes.
[0343] In some embodiments, the multiple mapping trajectories
provide a spatial mapping of the volume around the lead trajectory,
which is useful for the user to obtain a more comprehensive
understanding of the location of the lead relative to the
surrounding tissue, leading to better decision making with regards
to the optimal implantation location in the lead trajectory. For
example, a user might want to position the lead in desired distance
from specific brain targets to provide an optimal treatment. By
mapping the volume around the lead trajectory the user can learn
what is the distance and/or direction to these desired brain
targets and is there an alternative insertion trajectory that can
bring the lead to a desired position. Additionally, the spatial
mapping may also indicate preferred directions in regions up to 10
mm, for example 1, 3, 5, 7 mm or any intermediate or larger value
from the lead axis, such that directional stimulation current may
be directed in a preferred direction, or a different, more optimal
implantation trajectory may be inferred by the user or by an
algorithm operated by the system.
[0344] According to some exemplary embodiments, an analysis, for
example, statistical analysis, e.g. dynamic Bayesian network
analysis, is used to assign a functional tag for each or some depth
positions in the lead insertion trajectory. In some embodiments,
the analysis is based on a machine learning algorithm. In some
embodiments, the machine learning algorithm is capable of adjusting
parameters of an intrinsic model based on a database of examples
for example, to optimize algorithm outputs similarity to a human
expert output. In some embodiments, the machine learning algorithm
is used to train the system for example, to adjust model parameters
according to the database of input signals and output human expert
functional tagging, and optionally reach automatic mapping results
that are similar to the human expert mapping. In some embodiments,
the sub-thalamic nucleus target (STN), is assigned with a
functional tag selected from a list of "White Matter",
"Dorso-Lateral Oscialltory Region" (DLOR), "Ventro-Medial
Non-oscillatory Region" (VMNR), and/or "Substantia Nigra."
[0345] According to some exemplary embodiments, and further to
WO2016182997, the mapping algorithms include one or more of the
following Dynamic Bayesian Networks, artificial neural networks,
deep learning networks, structured support vector machine, gradient
boosting decision trees and long short term memory (LSTM) networks.
The method described in WO2016182997 is a generalization of the
Hidden Markov Model (HMM) and serves as another example of how to
utilize a trained system in the mapping process.
[0346] According to some exemplary embodiments, in this method,
based on recorded neurophysiological response by the lead, a
plurality of predetermined observation elements, and/or input
features, are calculated and Bayesian Networks are constructed for
each observation element thereby creating a Dynamic Bayesian
Network including the plurality of the predetermined observation
elements. In some embodiments, based on the Dynamic Bayesian
Network and the observation elements, the current location is
assigned with a functional tag, or state in the process model, with
the highest probability. Optionally, previously assigned tags are
updated upon recording neurophysiological data from a current
depth, for example by comparing the likelihoods of complete
alternative state paths from the beginning of the mapping process
to a current depth, and selecting the most likely state path.
[0347] In some embodiments, based on the Dynamic Bayesian Network,
a Factored Partially Observable Markov Decision Process is
constructed, wherein the Partially Observable Markov Decision
Process (POMDP) further comprises relations between the
predetermined observation elements; and based on the POMDP, the
micro drive step size and/or speed are updated such that further
advancement of the lead along the insertion trajectory is according
to the updated step size and/or speed.
[0348] In some embodiments, at least one alternative or additional
algorithm is used in the discrimination task, and/or in a
pre-processing stage, for example for preparing the data for
improving the training performance. In some embodiments, the at
least one alternative or additional algorithm includes Multi Class
SVM, Decision trees, boosted decision stumps, principal component
analysis and/or independent component analysis.
[0349] In some embodiments, signals recorded from at least one
microelectrode or at least one macro electrode of the lead are used
as input to the learning machines and to the algorithms. In some
embodiments, signals derived from bipolar and/or differential
and/or macro electrode LFP signals are used as input to the
learning machines and to the algorithms. In some embodiments,
signals derived from bipolar and/or differential and/or
microelectrode LFP signals are used as input to the learning
machines and/or to the algorithms. In some embodiments, signals
derived from microelectrode and/or macro electrode spike signals
are used as input to the learning machines and to the
algorithms.
[0350] Optionally, the learning machines use the above mentioned
algorithms for functionally tagging the tissue in the insertion
trajectory of the lead or any tissue surrounding the insertion
trajectory.
[0351] According to some exemplary embodiments, recording a
plurality of signals, optionally simultaneously, from different
macro electrodes and microelectrodes distributed along the lead
axis and on different positions on the circumference of the lead
allows for example, mapping of tissue which is based on signals
from sources located at different tissue depths and/or different
directions.
[0352] In some embodiments, the lead used to record the plurality
of signals has only micro contacts or microelectrodes positioned on
the lead surface, only macro contacts or macro electrodes disposed
on the lead surface, or at least one micro contact and at least one
macro contact disposed on its surface.
[0353] According to some exemplary embodiments, the mapping
algorithm is applied to each recorded signal separately, and
generates multiple mapping results, for example as shown in FIG.
13D. In some embodiments, these multiple mapping results represent
multiple trajectories and allow for example, to provide a better
support for a decision of a user regarding an optimal or a desired
stimulation or implantation target by functionally mapping the
brain tissue surrounding the lead.
[0354] According to some exemplary embodiments, the recorded
signals are combined together before applying the mapping
algorithm. In some embodiments, the mapping algorithm applied on
the combined signal is a multi-channel algorithm which takes into
consideration the different signal sources, optionally recorded
simultaneously, when generating the map. A possible advantage of
using the multi-channel algorithm is that the map is generated more
quickly since it is based on combined signals recorded in a shorter
time period compared to longer recordings of single signals.
[0355] The multi-channel algorithm may be constructed in several
ways. In some embodiments, the multi-channel algorithm is
constructed by starting from a single-channel algorithm, which
accepts a set of input features calculated from neurophysiological
signals recorded along a single recording trajectory, e.g. recorded
by a single electrode or a single bi-polar electrode pair, and
outputs the most likely tags per each depth. In some embodiments,
this single-channel algorithm is then expanded by expanding the
input features set to include input features recorded along the
multiple recording trajectories, e.g. by multiple electrodes or
multiple bi-polar electrode pairs. In some embodiments, expanding
the input features means defining a new model which is then trained
on a database of multi-channel recordings along insertion
trajectories in relevant surgical procedures. In some embodiments,
once trained, the algorithm accounts for the multiple signals
recorded on the multiple recording trajectories, and outputs the
most likely state for the current depth, or most likely state path
for the current and previous depths.
[0356] In some embodiments, the multi-channel algorithm differs
more substantially from a single-channel algorithm, as it
incorporates prior knowledge about relations between the different
channels. For example, two or more channels may be considered to be
related, e.g. by facing similar directions or opposite direction.
Then, in some embodiments, signal features derived from these
related channels may be jointly processed, or lumped together, to a
single input feature in the multi-channel algorithm. Alternatively
in some embodiments, specific signal features derived from two or
more channels may be lumped in one way, to obtain one lumped input
feature, and other signal features derived from the two or more
channels may be lumped in a different way to a second lumped input
feature. Further alternatively in some embodiments, knowledge of
the relation between channels may be used to define a set of rules,
or prior probability distributions, regarding the likelihood or
reliability of a possible observations. For example, it is may be
not likely that a first electrode, more proximal than a second
electrode to reach a certain deep neural structure before the
second electrode reaches that structure. Therefore, in some
embodiments, the prior probability distribution for an observation
that supports the proximal electrode is in the state related to the
deep neural structure, while the more distal electrode has not yet
reached that state, may be defined as very low, or even zero.
[0357] Reference is now made to FIG. 13E describing the generation
of a single trajectory which is based on multiple recording
measurements, according to some embodiments of the invention.
[0358] According to some exemplary embodiments, electrodes and/or
different electrode combinations record a plurality of signals 1326
along the insertion trajectory of lead 1321. In some embodiments,
the plurality of signals are combined and the combined signal is
used as an input for a multi-channel algorithm which generates a
single trajectory 1332 which includes functional tags for different
depth positions and for tissue placed in varying distances from the
lead 1321.
[0359] According to some exemplary embodiments, at least one
additional or alternative trajectory is selected following the
mapping procedure. In some embodiments the additional or
alternative trajectory is based on directional signals, for example
signals recorded by micro electrodes which face a specific
horizontal plane (i.e. perpendicular to axial) direction, and/or
based on macro electrodes which face a specific direction and/or
based on bi-polar signals between the micro or macro electrodes. In
some embodiments, the directional signals reflect neuronal activity
signals--LFPs and/or MUA signals-originating from specific
directions.
[0360] According to some exemplary embodiments, the functional
mapping of the directional signals indicate the user by a
functional map of the surrounding brain tissue that the alternative
trajectory is a better trajectory for delivery an efficient DBS
treatment. In some embodiments, the user is provided with an
indication in space for the location of the alternative
trajectory.
[0361] According to some exemplary embodiments, the directional
signals are analyzed manually or by a semi-automatic or by a fully
automatic algorithm to map and provide an indication for the more
effective alternative trajectory. In some embodiments,
identification of the more effective alternative trajectory is
based for example, on a better correlation between the mapping
results of the alternative trajectory and mapping results that were
found to be optimal for reaching a desired treatment outcome.
[0362] According to some exemplary embodiments, a semi-automatic
algorithm is an algorithm which requires, or allows, some user
input to perform its task. In some embodiments, a user must push or
hold a button to allow the system to continue its operation. In
some embodiments the user is required to actively approve the
algorithm's suggestion to perform a stimulation test at a specific
location, by clicking on a specific button in the software
interface. Alternatively or additionally, the user has the
capability to mark a specific recording at a specific location as
unusable, e.g. due to high levels of noise contamination, and thus
instruct the algorithm to disregard the signals recorded there.
[0363] According to some exemplary embodiments, the directional
signals are recorded from sources located at a distance of at least
0.2 mm from the measuring electrode contact, for example 0.4, 0.5,
0.6, 1, 1.2, 1.5, 2 mm or any intermediate or larger value. In some
embodiments, LFPs, bi-polar and/or differential LFPs signals are
sensitive to neuronal signal sources at these distances.
Additionally, LFPs, bi-polar and/or differential LFPs signals are
sensitive to signals originating from more proximal sources.
[0364] According to some exemplary embodiments, at least two types
of signals which are sensitive to distances >0.2 mm from the
measuring electrode are recorded. In some embodiments, one of the
signals is the MUA spiking activity of neuronal populations, which
is sensitive to sources as far as .about.0.5 mm. In some
embodiments, the second is LFPs, which are sensitive to sources as
far as centimeters from the measurement. Optionally, Bi-polar, or
differential (digital or analog computation) LFPs reject signals
from sources that are distant enough to arrive at a similar phase
to the two recording contacts, and thus are sensitive to signals
originating at sources at an intermediate and relevant range.
[0365] According to some exemplary embodiments, one way to
"isolate" the neuronal activity at such distances and different
directions, from the activity in the lead vicinity in its current
trajectory, is to compare between types of signals recorded on
several electrodes facing different directions. For example,
differential LFPs recorded between two electrodes at the same depth
but facing opposite directions will highlight signal sources
located along the virtual line connecting the two contacts and
extending to each direction. In some embodiments, this measurement
is combined with the SUA or MUA measurement in these electrodes,
which are sensitive to more local sources. For example, if the
differential LFP recording shows a significant relevant signal
component (e.g. high beta-power indicating potentially good DBS
target) and the MUA signals show no such component on one side and
a weak component on the second side, it can be inferred that the
source of the signal is located in the direction of the second
side, and not in the immediate vicinity of the lead (the MUA is
weak), but at a distance that is about the maximal MUA effective
distance. Alternatively, several mono-polar and bi-polar LFP
recordings are added and subtracted in such a way that highlights
signals originating at a specific direction, and possibly distance,
and may also alternatively be compared with SUA and MUA activity
from electrodes facing the specific directions and other directions
as reference.
[0366] In some embodiments, the at least one alternative trajectory
is identified at a distance of at least 0.5 mm from the electrode
contacts on the lead circumference, for example 0.8, 0.9, 1, 1.2,
1.5, 2 mm or any intermediate or larger distance from the electrode
contact. In some embodiments, the at least one alternative
trajectory is positioned in a distance of at least 1 mm from the
lead insertion trajectory, for example 1.2, 1.4, 1.5, 1.7, 2, 2.5
mm or any intermediate or larger distance from the lead insertion
trajectory.
[0367] In some embodiments, modifying the insertion trajectory to
an alternative trajectory in step smaller than 0.2 mm is less
practical, whereas alternative trajectories located at a distance
larger than 1 mm from the insertion trajectory are more practical
and valuable to the user.
Exemplary Functionally Mapping Methods
[0368] Reference is now made to FIG. 14A describing the
modification of an existing model for a functional tissue map using
machine learning techniques.
[0369] According to some exemplary embodiments, a model of a tissue
map which includes functional annotations of the tissue is provided
at 1402. In some embodiments, expert labeled data from surgical
procedures is collected at 1404 and stored optionally in a
database.
[0370] According to some exemplary embodiments, machine learning
algorithms are applied and modify the model provided at 1402 based
on the collected expert-data at 1406.
[0371] According to some exemplary embodiments, the modified model
or trained model is used for mapping during the surgery at 1408. In
some embodiments, the modified model is used in a surgery in a new
patient to provide online mapping of the tissue, based on the
recording of the electrical neuronal activity.
[0372] According to some exemplary embodiments, in machine
learning, there is usually a model, for example the model provided
at 1402, in which there are two or more states, and often the goal
is to distinguish between these states based on a set of input
features. This distinction is then used as the output of the
system, and it is based on an internal relation between the input
features and the model states.
[0373] In some embodiments, in order for the learning, or training,
to occur, a database is required, for example a database which
includes the expert-labeled data collected from surgical procedures
described at 1404, which can include examples of inputs and output,
and sometimes only the inputs. A software code defines a procedure,
by which the computer can train on the database ("training set"),
so that the relation between the input features and the output
states can be learned. The different machine learning methods
differ in the models they are based on, the type of relations
between inputs and outputs, and the procedures for training on the
training set.
[0374] An example for a machine learning method is the Hidden
Markov Model (HMM), in which the model describes a random process
occurring on a chain of states, which are generally not known
(hence hidden), and are associated with observations which are at
least partially known. Optionally, the relations between the
states, and between the states and observations are statistical.
That is, the transition from state -i- to state -j- can occur with
a certain probability, or can not occur, and similarly, there is a
probability for each observation K, given the process is at a given
state -j-. These two relations are given in the Transition Matrix,
T, in which element tij is the probability for transition from
state i state j, and in the Emission Matrix E, in which element eik
is the probability to see observation k, given the process is in
state i. Another parameter is the prior probability to begin in a
certain state-k-, .pi._k, before the first observation is
provided.
[0375] In some embodiments, the HMM model, as is defined by the
possible states and observations, is given to the system based on
prior knowledge. For example, for navigating in the STN, the states
can be White Matter, STN DLOR, STN VMNR and SNR. In some
embodiments, the observations are vectors of binned quantification
of signal features, in which the elements of the vector are the
measured variables, e.g. [Spike Rate, NRMS, Beta PSD, LFP Beta
power], and the values are their binned quantification e.g. [High,
Medium, Low, Low], or [5, 3, 1, 1]. In some embodiments, the
observations are structured in a sequence, and optionally the
required training is to learn the best relation between the
sequences of observations, which are the input and the sequences if
states which is the output. Once trained, the computer can use the
transition and emission matrices to estimate the most likely
sequence of states, given a sequence of observations.
[0376] In some embodiments, given a sequence of observations and
the matrices T, E & .pi., the most likely sequence of states is
found using the Viterbi algorithm, as is defined for example in "A
Tutorial on Hidden Markov Models and Selected Applications in
Speech Recognition", by LAWRENCE R. RABINER, published in
PROCEEDINGS OF THE IEEE, VOL. 77, NO. 2, February 1989. In short,
this algorithm applies the following steps: [0377] 1. Initialize:
for every state -i- calculate initial probability, .delta. and
backtrack value .psi.:
[0377] .delta..sub.1(i)=.pi..sub.ie.sub.iO (1)
.psi..sub.1(i)=0 [0378] 2. Recursion: for every state -j- and time
step -n-, calculate:
[0378]
.delta..sub.n(j)=max.sub.i{[.delta..sub.n-1(i)t.sub.ij]e.sub.jO(n-
)}
.psi..sub.n(j)=argmax.sub.i{.delta..sub.n-1(i)t.sub.ij} [0379] 3.
Termination: Find most likely last state (state at time step
n=N):
[0379] P*=max.sub.i{.delta..sub.N(i)}
S.sub.N*=argmax.sub.i{.delta..sub.N(i)} [0380] 4. Find most likely
sequence in backtrack:
[0380] S.sub.n*=.psi..sub.n+1{S.sub.n+1*}
[0381] In this description e & t are elements of the emission
and transition matrix respectively, {O(1), O(2), . . . , O(N)} is
the observation sequence and {S{circumflex over ( )}* (1),
S{circumflex over ( )}* (2), . . . , S{circumflex over ( )}* (N)}
is the most likely state sequence, given the model and the
observations.
[0382] According to some exemplary embodiments, there are generally
two types of possible learning methods--supervised and
unsupervised. In supervised learning, the database includes the
correct outputs as estimated by a human expert. The goal of
learning is then to apply a learning rule in order to tune the
model parameters, i.e. Transition matrix, Emission matrix and
initial state probability values in the case of HMM, which lead to
a minimal error between the output of the machine and of the human
expert. In unsupervised learning, the "true" values are not given,
and then the goal of learning is usually to reach convergence, i.e.
a situation in which applying the learning rule does not result in
a significant modification of model parameters.
[0383] In some embodiments, supervised learning can be carried out
by counting the occurrence frequencies. That is, scanning the
database and finding, e.g. the ratio between the number of times in
which the expert defined the HMM process to transition from state i
to state j, and the number of times the expert defined the HMM to
be in state i. This could be defined as the probability to
transition from state i to state j:
t ij ^ = # .times. { s n = i , s n + 1 = j } # .times. { s n = i }
##EQU00005##
The same can be done for the emission matrix and for the initial
probability array.
[0384] According to some exemplary embodiments, unsupervised
learning can be carried out by a variety of algorithms. A
well-known algorithm, used to train a variety of models with
different probability distributions, is the Expectation
Maximization algorithm. Another, less elaborate method is the
Maximum likelihood method. These are both known to data scientists
and engineers skilled in the art, and are also described in many
publications. For a detailed explanation of the Expectation
Maximization method for an HMM, the reader may turn to the paper by
LAWRENCE R. RABINER mentioned above.
[0385] Reference is now made to FIG. 14B describing the generation
of multiple mapped projections from multiple recorded signals,
according to some embodiments of the invention.
[0386] According to some exemplary embodiments, a lead in inserted
into the brain at 1410. In some embodiments, a navigational
algorithm initializes with initial determined step-size at 1412. In
some embodiments, a motorized drive inserts the lean into the brain
tissue according to the determined step size at 1414.
[0387] According to some exemplary embodiments, multiple signals
are recorded using multiple electrodes or electrode combinations at
1416. In some embodiments, the signals are analyzed separately at
1418, to generate multiple mapped trajectories. In some
embodiments, the location is determined for each signal trajectory
separately. In some embodiments, the step-size is determined based
on the determined location. In some embodiments, the location tag
calculated at the specific depth in 1418 is presented to the user
immediately after it is calculated. In some embodiments, the set of
tags calculated at current and previous locations is continually
displayed to the user. In some embodiments, the set of previously
calculated tags may be changed retroactively, based on signals
recorded and analyzed from a new location, leading to a
recalculation of tags in previous locations.
[0388] According to some exemplary embodiments, if the mapping is
finished at 1420, for example by an indication received from the
user, the system performs an additional step of inferring the
suspected optimal implantation location at 1422. In some
embodiments, if mapping continues then the drive inserts the lead
into the brain at 1414 according to the updated step size. The
system may finish the mapping may automatically, for example when
one or more mapping tags indicate exit of the electrode from the
target region.
[0389] Reference is now made to FIG. 14C describing generating a
single trajectory from multiple recordings, according to some
embodiments of the invention.
[0390] According to some exemplary embodiments, a lead is inserted
into the brain at 1424. In some embodiments, a navigational
algorithm is initialized with an initial step-size at 1426. In some
embodiments, the drive motor inserts the lead into the brain
according to the step size at 1428. In some embodiments, multiple
signals are recorded from the surrounding brain tissue by
electrodes or electrode combinations at 1430.
[0391] According to some exemplary embodiments, the recorded
signals are analyzed using a multi-channel model at 1432. In some
embodiments, based on the multi-channel model a single integrated
trajectory is generated and the location of different tissues and
functional regions surrounding the lead is determined. In some
embodiments, the location tag calculated in 1432 is presented to
the user immediately after it is calculated. In some embodiments,
the set of tags calculated at current and previous locations is
continually displayed to the user. In some embodiments, the set of
previously calculated tags may be changed retroactively, after
signals are recorded and analyzed from a new location, leading to a
recalculation of tags in previous locations.
[0392] Additionally or optionally, the step size is updated based
on the generated trajectory. In some embodiments, if the mapping
procedure is finished, for example if the mapping is stopped by the
user at 1434, then the system performs an additional step of
inferring the suspected optimal implantation location.
Alternatively, if mapping continues then the motor drive inserts
the lead into the brain at 1428 according to the updated
step-size.
Exemplary Distal Coupler
[0393] According to some exemplary embodiments, the lead, for
example the navigating lead comprises a distal coupler, positioned
in the distal end of the lead body, in a close proximity to the
lead's distal tip. In some embodiments, the distal coupler includes
at least one opening and/or at least one internal channel for
accurately directing at least one microelectrode to a desired
position on the lead circumference or to the lead tip.
Alternatively or additionally, the distal coupler allows for
example, to position a plurality of microelectrodes and/or macro
electrodes in a desired orientation relative to each other and/or
relative to a marking point on the lead circumference. In some
embodiments, accurately positioning the microelectrodes on the
outer surface of the lead is essential for generating accurate
maps, since each electrode is associated with a specific depth
position and orientation during the mapping process. For example,
in some embodiments the depth location should be accurate to 0.1
mm, so that the depth mapping would be considered very
accurate.
[0394] According to some exemplary embodiments, the distal coupler
is associated with micro electrodes formed from micro wires. In
some embodiments, the micro wires are electrically connected to an
electrode on the lead surface and then extend through the internal
lumen of the lead to be connected to a conductor and/or to an
acquisition system. In some embodiments, the micro wire is guided
through the channel and/or opening in the distal coupler to a
desired position on the external surface of the lead.
[0395] In some embodiments, at least two different electrodes are
guided through spaced apart channels and/or openings in the distal
coupler to desired positions on the lead external surface. In some
embodiments, the distal coupler allows for example, to accurately
position the at least two electrodes in desired positions on the
lead outer surface and/or in desired positions relative to each
other or relative to an external element connected to the lead.
[0396] Reference is now made to FIG. 15 depicting a distal coupler,
according to some embodiments of the invention.
[0397] According to some exemplary embodiments, lead 1500 comprises
a distal coupler 1502 positioned within the internal lumen 1504 of
the lead. In some embodiments, the distal coupler comprises at
least one channel 1506, for example an axial channel, which is
shaped and sized to direct at least one micro electrode to a
specific location on the lead surface. In some embodiments, channel
1506 directs microelectrode 1510 to a specific location on the
distal tip 1508 of the lead. Additionally or alternatively, the
distal coupler 1502 comprises at least one opening or at least one
channel for directing a micro electrode, for example microelectrode
1512 to a specific location on the lead circumference.
[0398] A possible advantage of the distal coupler is that it allows
a repetitive, predictable and good-yield process of locating the
electrodes on the lead surface for mapping the tissue with a
desired accuracy. In some embodiments, the distal coupler allows
different manufacturing processes. For example, the electrodes do
not have to be located inside a polymer lead body pre-processed to
have holes accurately placed. In some embodiments, the electrodes
are positioned on micro wires that are held by the distal coupler,
and then some material, for example a medical grade epoxy, is cast
over the wires and distal coupler according to a pre-determined
mold. In this case, the major part of the lead body is still
composed of a flexible biocompatible polymer, but the distal tip is
made from the cast material. A possible advantage of the casting
material is that it is more tolerant to further processing steps
such as grinding the material, to ensure that the electrodes are
flush to the lead body.
[0399] In some embodiments, the distal coupler also potentially
increases the manufacturing yield and the reliability of the
device, since the distal coupler allows the wires to be short and
protected and therefore less susceptible to damage during the
assembly process--hence higher yield- and less susceptible to
damage during the shipping and user handling of the device, hence
higher reliability.
Exemplary Internal Shield
[0400] According to some exemplary embodiments, the lead comprises
an internal shield, optionally in the form of a layer for shielding
the electrode conductors placed within the lead interior lumen from
external electro-magnetic fields. In some embodiments, the internal
shield is made from a conductive material, and functions as an
electro-magnetic shield or a Faraday cage which reacts with the
external electro-magnetic fields, and protects the internal
electrode conductors from the effect of these electro-magnetic
fields. This helps to improve the sensitivity by increasing the
signal-to-noise ratio of the measured signals.
[0401] In some embodiments, the signal-to-noise ratio is increased
when recording low frequency signals for example, LFP signals in
frequencies between 1-300 Hz, which are often highly contaminated
by external electro-magnetic noise. An example for a source for
such a noise is the electric network noise, which has a fundamental
component at about 50 or 60 Hz, and in harmonics of 100, 150, 200,
250 . . . or 120, 180, 240 etc.
[0402] According to some exemplary embodiments, the shield covers
at least 70% of the electrode conductors length along the lead
axis, for example 80%, 85% or 90% or any intermediate or larger
coverage percentage. In some embodiments, in order to reach an
optimal signal-to-noise ratio, the shield should provide coverage
>80% of the length of the electrode conductor, preferably
>90%.
[0403] Reference is now made to FIGS. 16A and 16B describing an
internal shield, according to some embodiments of the
invention.
[0404] According to some exemplary embodiments, lead 1600
comprising an internal electro-magnetic shield within the internal
lumen of the lead. In some embodiments, the shield is positioned
between the outer lead body 1602 and the conducting wires connected
to the electrodes. In some embodiments, the shield surrounds at
least 70% of the entire length of the conducting wires as described
above. In some embodiments, for example as shown in FIG. 16B, the
shield 1604 is electrically connected to an electrically conductive
section, for example plate 1610 on the outer surface of the lead
1600. In some embodiments, the conductive section is connected to a
differential amplifier that allows, for example to subtract
electrical noise received by the shield from the signals delivered
by the electrode wires. In some embodiments, the conductive section
is connected to the system ground.
[0405] According to some exemplary embodiments, the shield is an
electrically conductive braided or coiled shield or an electrically
conductive mesh material, optionally made from electrically
conductive wires. In some embodiments, the braided shield is shaped
and sized to be positioned inside the internal lumen of the lead,
and to surround at least part of the electrode conductors.
[0406] According to some exemplary embodiments, the shield
comprises at least one connector for example, a male and/or a
female connector for connecting the shield to an external system.
For example, in some embodiments the shield is electrically
connected to the recording system ground, and/or provides a
reference signal input for example, a reference signal input to a
differential amplifier. In some embodiments, the reference signal
input is subtracted from the delivered signal, for example to
remove electromagnetic noise from the delivered signal.
[0407] According to some exemplary embodiments, the shield
comprises at least one channel and/or at least one opening and
serves as a distal coupler for directing micro wires to a desired
location on the lead surface, as described above in the exemplary
distal coupler section.
[0408] It is expected that during the life of a patent maturing
from this application many relevant leads will be developed; the
scope of the term leads is intended to include all such new
technologies a priori.
[0409] As used herein with reference to quantity or value, the term
"about" means "within .+-.10% of".
[0410] The terms "comprises", "comprising", "includes",
"including", "has", "having" and their conjugates mean "including
but not limited to".
[0411] The term "consisting of" means "including and limited
to".
[0412] The term "consisting essentially of" means that the
composition, method or structure may include additional
ingredients, steps and/or parts, but only if the additional
ingredients, steps and/or parts do not materially alter the basic
and novel characteristics of the claimed composition, method or
structure.
[0413] As used herein, the singular forms "a", "an" and "the"
include plural references unless the context clearly dictates
otherwise. For example, the term "a compound" or "at least one
compound" may include a plurality of compounds, including mixtures
thereof.
[0414] Throughout this application, embodiments of this invention
may be presented with reference to a range format. It should be
understood that the description in range format is merely for
convenience and brevity and should not be construed as an
inflexible limitation on the scope of the invention. Accordingly,
the description of a range should be considered to have
specifically disclosed all the possible subranges as well as
individual numerical values within that range. For example,
description of a range such as "from 1 to 6" should be considered
to have specifically disclosed subranges such as "from 1 to 3",
"from 1 to 4", "from 1 to 5", "from 2 to 4", "from 2 to 6", "from 3
to 6", etc.; as well as individual numbers within that range, for
example, 1, 2, 3, 4, 5, and 6. This applies regardless of the
breadth of the range.
[0415] Whenever a numerical range is indicated herein (for example
"10-15", "10 to 15", or any pair of numbers linked by these another
such range indication), it is meant to include any number
(fractional or integral) within the indicated range limits,
including the range limits, unless the context clearly dictates
otherwise. The phrases "range/ranging/ranges between" a first
indicate number and a second indicate number and
"range/ranging/ranges from" a first indicate number "to", "up to",
"until" or "through" (or another such range-indicating term) a
second indicate number are used herein interchangeably and are
meant to include the first and second indicated numbers and all the
fractional and integral numbers therebetween.
[0416] Unless otherwise indicated, numbers used herein and any
number ranges based thereon are approximations within the accuracy
of reasonable measurement and rounding errors as understood by
persons skilled in the art.
[0417] As used herein the term "method" refers to manners, means,
techniques and procedures for accomplishing a given task including,
but not limited to, those manners, means, techniques and procedures
either known to, or readily developed from known manners, means,
techniques and procedures by practitioners of the chemical,
pharmacological, biological, biochemical and medical arts.
[0418] As used herein, the term "treating" includes abrogating,
substantially inhibiting, slowing or reversing the progression of a
condition, substantially ameliorating clinical or aesthetical
symptoms of a condition or substantially preventing the appearance
of clinical or aesthetical symptoms of a condition.
[0419] It is appreciated that certain features of the invention,
which are, for clarity, described in the context of separate
embodiments, may also be provided in combination in a single
embodiment. Conversely, various features of the invention, which
are, for brevity, described in the context of a single embodiment,
may also be provided separately or in any suitable subcombination
or as suitable in any other described embodiment of the invention.
Certain features described in the context of various embodiments
are not to be considered essential features of those embodiments,
unless the embodiment is inoperative without those elements.
[0420] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the spirit and broad scope of the appended claims.
[0421] It is the intent of the Applicant(s) that all publications,
patents and patent applications referred to in this specification
are to be incorporated in their entirety by reference into the
specification, as if each individual publication, patent or patent
application was specifically and individually noted when referenced
that it is to be incorporated herein by reference. In addition,
citation or identification of any reference in this application
shall not be construed as an admission that such reference is
available as prior art to the present invention. To the extent that
section headings are used, they should not be construed as
necessarily limiting. In addition, any priority document(s) of this
application is/are hereby incorporated herein by reference in
its/their entirety.
* * * * *