USOO78O1603B2
`
`(12) United States Patent
`Westlund et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 7,801,603 B2
`Sep. 21, 2010
`
`(54) METHOD AND APPARATUS FOR
`OPTIMIZING VAGAL NERVESTIMULATION
`USING LARYNGEALACTIVITY
`
`(75) Inventors: Randy Westlund, River Falls, WI (US);
`Anthony V. Caparso, St. Louis Park,
`MN SS Mark Bly, Falcon Heights,
`
`(73) Assignee: systemales Inc., St. Paul,
`
`(*) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 1032 days
`M
`YW-
`y
`yS.
`(21) Appl. No.: 11/469,551
`
`(22) Filed:
`
`Sep. 1, 2006
`
`(65)
`
`Prior Publication Data
`US 2008/OO58.874 A1
`Mar. 6, 2008
`
`(51) Int. Cl.
`(2006.01)
`A6 IN L/36
`(52) U.S. Cl. ............................................. 607/2: 607/46
`(58) Field of Classification Search ................... 600/23;
`607/41, 47, 72, 1, 46
`See application file for complete search history.
`References Cited
`U.S. PATENT DOCUMENTS
`
`(56)
`
`4, 1989 Zealear et al.
`4,817,628 A
`5, 1992 Goldfarb ..................... 6O7/48
`5,111,814 A
`5,263,491 A * 1 1/1993 Thornton .................... 600,587
`5,275,159 A
`1/1994 Griebel
`
`5,590,241 A 12/1996 Parket al.
`5,865,759 A
`2f1999 Koblanski
`6,721,603 B2
`4/2004 Zabara et al. ................. 6O7/46
`7,069,082 B2 * 6/2006 Lindenthaler ................ 6O7/41
`2002fO1694.85 A1 11, 2002 Pless et al.
`2003/O1494.57 A1
`8/2003 Tcheng et al.
`2005/0010265 A1
`1/2005 B aru et al.
`2005, 0107843 A1
`5.2005 McDermott et al.
`FOREIGN PATENT DOCUMENTS
`WO WO-2008030348 A1
`3f2008
`OTHER PUBLICATIONS
`h
`ional
`fU
`f
`licati
`PCT App ication No. PCT/US2007/018696, International Searc
`Report mailed Jan. 21, 2008, 4pgs.
`PCT Application No. PCT/US2007/018696, Written Opinion mailed
`Jan. 21, 2008, 7 pgs.
`“European Application Serial No. 07837286.9”. Office Action
`mailed Sep. 29, 2009, 2 pgs.
`* cited b
`cited by examiner
`Primary Examiner Carl H Layno
`Assistant Examiner Brian T. Gedeon
`(74) Attorney, Agent, or Firm—Schwegman, Lundberg &
`Woessner, P.A.
`
`ABSTRACT
`(57)
`A neural stimulation system delivers neural stimulation to the
`vagus nerve and senses a signal indicative oflaryngeal activ
`ity resulting from the neural stimulation. The signal indicative
`of laryngeal activity is used, for example, to guide electrode
`placement, determine stimulation threshold, detect lead/elec
`trode problems, detect neural injury, and monitor healing
`processing following the electrode placement inside the body
`of a patient.
`
`39 Claims, 12 Drawing Sheets
`
`
`
`R
`
`2-A
`
`2
`
`EXTERNAL
`SYSTEM
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 1
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sheet 1 of 12
`Sheet 1 of 12
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`US 7,801,603 B2
`US 7,801,603 B2
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`WALSAS
`
`////
`{bi
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`Sep. 21, 2010
`Sep. 21, 2010
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`WNYALXS
`
`
`
`
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 2
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 2
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sheet 2 of 12
`Sheet 2 of 12
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`US 7,801,603 B2
`US 7,801,603 B2
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`WAISAS
`
`---------
`
`
`
`
`
`
`
`
`
`Sep. 21, 2010
`Sep. 21, 2010
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`WNYSLXS
`
`2/4/
`Clty
`
`----
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p.3
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 3
`
`

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`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 3 of 12
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`US 7,801,603 B2
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`
`
`2.
`
`ACTIVITY SENSOR
`R
`
`ACCEEROMETER
`
`TO STMULATION
`ELECTRODES
`
`EXTERNAL SYSTEM
`
`NEURAL SIMULATION
`ANALY7ER
`25
`
`2
`
`PROCESSING
`CIRCUIT
`
`LARYNGEAL
`ACTIVITY
`INPUT
`
`NEURAL
`stan
`
`NEURAL
`STMULATION
`CIRCUIT
`
`EXTERNAL
`CONTROLLER
`
`USER
`INTERFACE
`
`Awf
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 4
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 4 of 12
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`US 7,801,603 B2
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`A2)
`
`EXTERNAL SYSTEM
`
`NEURAL STIMULATION
`ANALYZER
`25
`
`2
`
`PROCESSING
`
`ARYNGEAL
`ACTIVITY
`INPUT
`
`NEURAL
`STIMULATION
`INPUT
`
`EXTERNAL
`TELEMETRY
`CIRCUIT
`
`EXTERNAL
`CONTROLLER
`
`USER
`INTERFACE
`
`A2S)
`
`
`
`
`
`
`
`A.
`
`ACTIVITY SENSOR
`3.
`
`ACCEEROMETER
`
`TELEMETRY
`CIRCUIT
`
`2A
`&
`
`A.
`
`|MPLANTABLE
`MEDICAL DEVICE
`AA
`
`NEURAL
`SIMULATION
`CIRCUIT
`
`MPLANT
`TELEMETRY
`CIRCUIT
`
`TO STIMULATION
`ELECTRODES
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 5
`
`

`

`Sheet 5 of 12
`Sheet 5 of 12
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`US 7,801,603 B2
`US 7,801,603 B2
`2-64)
`
`U.S. Patent
`U.S. Patent
`
`
`
`Sep. 21, 2010
`Sep. 21, 2010
`
`poe
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 6
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 6
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sep. 21, 2010
`Sep. 21, 2010
`
`US 7,801,603 B2
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`Sheet 6 of 12
`Sheet 6 of 12
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`US 7,801,603 B2
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`
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`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 7
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 7
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 7 of 12
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`US 7,801,603 B2
`
`92
`
`LEAD STATUS
`ANALY7ER
`
`9
`
`NEURAL
`INJURY
`ANALY7ER
`
`TO 350
`
`TO 550
`
`TO 550
`
`TO 530
`
`TO 529 OR 429
`
`TO 550
`
`
`
`PROCESSING CIRCUIT
`
`96)
`
`FROM 525
`
`CIRCUIT
`
`6.
`
`96M -
`
`STIMULATION
`THRESHOLD ANALY/ER
`
`NERVE
`CAPTURE
`THRESHOLD
`963
`
`96A
`
`COMPARATOR
`
`STMULATION
`INTENSITY
`CONTROLLER
`
`FROM 526
`
`PRESENTATION
`PROCESSING
`CIRCUIT
`
`Aw.4
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 8
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 8 of 12
`
`US 7,801,603 B2
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`
`
`USER INTERFACE
`
`PESENTATION
`DEVICE
`
`WA
`
`AUDIO PRESENTATION
`DEVICE
`
`A5
`
`FROM 927
`
`VISUAL PRESENTATION
`DEVICE
`
`AT
`
`SCREEN
`
`GAUGE
`
`USER INPUT
`DEVICE
`
`TO 329 OR 429
`
`/W//
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 9
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 9 of 12
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`US 7,801,603 B2
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`
`
`
`
`MCWN
`NARA - \-
`SW
`
`FROM ACTIVITY
`SENSOR
`
`5A
`N.
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 10
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 10 of 12
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`US 7,801,603 B2
`
`e-A2).
`
`2)
`
`
`
`SENSING A SIGNAL INDICATIVE OF LARYNGEAL ACTIVITY
`
`DEVERING THE NEURAL STIMULATION TO THE WACUS NERVE
`
`CONDITIONING THE SIGNAL INDICATIVE OF ARYNCEAL ACTIVITY
`
`ANAYZING AN EFFECT OF THE DEVERY OF THENEURAL STIMULATION
`
`PRESENTING INDICATORS OF THE LARYNCEAL ACTIVITY
`AND THE DEVERY OF THE NEURAL STIMULATION
`
`/W/?
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 11
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 11 of 12
`
`US 7,801,603 B2
`
`SW
`A
`
`SETTING ASTIMULATION INTENSITY
`(S) TO AN INTIAL INTENSTY
`
`DELIVERING NEURAL STIMULATION ATS
`
`R
`
`RA
`
`DETECTING A NERVE CAPTURE USING THE
`SIGNAL INDICATIVE OF LARYNGEA ACTIVITY
`
`RS
`
`YES <1CAPTURED?
`NO
`
`DETERMINING F SHAS REACHED A MAXIMUMS
`
`R2
`
`YES <Gs
`
`INCREASINGS: S = S + AS
`
`REPOSITIONING THE STIMULATION
`ELECTRODE, ETC.
`
`DECREASINGS: S = S - ASI,
`
`2A
`
`26
`
`
`
`
`
`DELVERING THE NEURAL STIMULATION ATS
`
`
`
`R
`
`DETECTING A NERVE CAPTURE USING
`THE SIGNAL INDICATIVE OF LARYNCEAL ACTIVITY
`
`S2,
`YES
`
`CAPTURED?
`
`NO
`SETING STMULATION THRESHOLD (ST) TOS
`PRIOR TO THE LAST DECREASE: ST = S + AS
`
`3A
`
`/W /.7
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 12
`
`

`

`U.S. Patent
`
`Sep. 21, 2010
`
`Sheet 12 of 12
`
`US 7,801,603 B2
`
`-1A)
`
`A)
`
`
`
`SENSING ASICNAL INDICATIVE OF LARYNCEAL ACTIVITY
`
`DELIVERING THE NEURAL STIMULATION TO THE WAGUS NERVE
`
`OPTIMIZING THE DELIVERY OF THE NEURAL
`STIMULATION DURING DEVICE IMPLANTATION
`
`POSITIONING ASTIMULATION ELECTRODE
`
`OPTIMIZING STIMULATION PARAMETERS
`
`A32
`
`AA
`
`MONTORING AND TTRATING THE DEVERY OF
`THE NEURAL STIMULATION AFTER THE DEVICE IMPLANTATION
`AAA,
`
`OPTIMIZING STIMULATION PARAMETERS
`
`MONITORING ALEAD/ELECTRODE STATUS
`
`DETECTING ANEURAL INJURY
`
`MONITORING A HEALING PROCESS
`
`AAAA
`
`AAA6
`
`AA
`
`/7//
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 13
`
`

`

`US 7,801,603 B2
`
`1.
`METHOD AND APPARATUS FOR
`OPTIMIZINGVAGAL NERVESTIMULATION
`USING LARYNGEALACTIVITY
`
`TECHNICAL FIELD
`
`This document relates generally to neural stimulation and
`particularly to a system and method for optimizing Vagal
`nervestimulation using an activity sensor that senses a signal
`indicative of laryngeal activity.
`BACKGROUND
`
`Vagal nervestimulation has been applied to modulate vari
`ous physiologic functions and treat various diseases. One
`example is the modulation of cardiac functions in a patient
`Suffering heart failure or myocardial infarction. The myocar
`dium is innervated with sympathetic and parasympathetic
`nerves including the cardiac branches of the vagus nerve.
`Activities in the vagus nerve, including artificially applied
`electrical stimuli, modulate the heart rate and contractility
`(strength of the myocardial contractions). Electrical stimula
`tion applied to the vagus nerve is known to decrease the heart
`rate and the contractility, lengthening the systolic phase of a
`cardiac cycle, and shortening the diastolic phase of the car
`diac cycle. This ability of the vagal nervestimulation is uti
`lized, for example, to control myocardial remodeling.
`In addition to treating cardiac disorders such as myocardial
`remodeling, vagal nerve stimulation is also know to be effec
`tive in treating disorders including, but not limited to, depres
`Sion, anorexia nervosa/eating disorders, pancreatic function,
`epilepsy, hypertension, inflammatory disease, and diabetes.
`The intended therapy outcomes of vagal nerve stimulation in
`treating Such disorders may be difficult to measure, either
`acutely or chronically, for purposes of therapy titration or
`optimization. Therefore, there is a need for titrating or opti
`mizing Vagal nerve stimulation using parameters other than
`the intended therapy outcomes.
`SUMMARY
`
`10
`
`15
`
`25
`
`30
`
`35
`
`A neural stimulation system delivers neural stimulation to
`the vagus nerve and senses a signal indicative of laryngeal
`activity resulting from the neural stimulation. The signal
`indicative of laryngeal activity is used, for example, to guide
`electrode placement, determine stimulation threshold, detect
`lead/electrode problems, detect neural injury, and monitor
`healing processing following the electrode placement inside
`the body of a patient.
`In one embodiment, a neural stimulation system includes
`an activity sensor and a neural stimulation analyzer. The
`activity sensor senses a signal indicative of laryngeal activity.
`The neural stimulation analyzer includes a laryngeal activity
`input to receive the signal indicative of laryngeal activity, a
`neural stimulation input to receive a signal indicative of the
`delivery of the neural stimulation to the vagus nerve, and a
`processing circuit. The processing circuit processes the signal
`indicative of laryngeal activity for analyzing the neural stimu
`lation system using the signal indicative of laryngeal activity.
`In one embodiment, a neural stimulation system includes
`an activity sensor, a signal conditioning circuit, a neural
`stimulation circuit, and a presentation device. The activity
`sensor senses a signal indicative of laryngeal activity. The
`signal conditioning circuit conditions the signal indicative of
`laryngeal activity. The neural stimulation circuit delivers neu
`ral stimulation to the vagus nerve. The presentation device
`presents indicators of the laryngeal activity and the delivery
`of the neural stimulation.
`
`40
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`45
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`50
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`55
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`60
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`65
`
`2
`In one embodiment, a method for applying neural stimu
`lation is provided. A signal indicative of laryngeal activity is
`sensed. The neural stimulation is delivered to the vagus nerve.
`The signal indicative of laryngeal activity is conditioned to
`isolate laryngeal activity resulting from the delivery of the
`neural stimulation.
`This Summary is an overview of some of the teachings of
`the present application and not intended to be an exclusive or
`exhaustive treatment of the present subject matter. Further
`details about the present subject matter are found in the
`detailed description and appended claims. Other aspects of
`the invention will be apparent to persons skilled in the art
`upon reading and understanding the following detailed
`description and viewing the drawings that form a part thereof.
`The scope of the present invention is defined by the appended
`claims and their legal equivalents.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`The drawings illustrate generally, by way of example, Vari
`ous embodiments discussed in the present document. The
`drawings are for illustrative purposes only and may not be to
`scale.
`FIG. 1 is an illustration of an embodiment of a neural
`stimulation system and portions of an environment in which
`the neural stimulation system is used.
`FIG. 2 is an illustration of another embodiment of the
`neural stimulation system and portions of the environment in
`which the neural stimulation system is used.
`FIG. 3 is a block diagram illustrating an embodiment of
`portions of a circuit of the neural stimulation system of FIG.
`1.
`FIG. 4 is a block diagram illustrating an embodiment of
`portions of a circuit of the neural stimulation system of FIG.
`2.
`FIG. 5 is an illustration of an embodiment of a laryngeal
`activity sensor assembly of the neural stimulation system.
`FIG. 6 is an illustration of another embodiment of the
`laryngeal activity sensor assembly of the neural stimulation
`system.
`FIG. 7 is an illustration of an embodiment of an activity
`sensor including a sensor base.
`FIG. 8 is an illustration of another embodiment of the
`activity sensor including the sensor base.
`FIG. 9 is a block diagram illustrating an embodiment of a
`processing circuit of a neural stimulation analyzer of the
`neural stimulation system.
`FIG. 10 is a block diagram illustrating an embodiment of a
`user interface of the neural stimulation system.
`FIG. 11 is an illustration of an embodiment of an external
`programmer of the neural stimulation system.
`FIG. 12 is a flow chart illustrating an embodiment of a
`method for analyzing effect of vagal nervestimulation using
`a signal indicative of laryngeal activity.
`FIG. 13 is a flow chart illustrating an embodiment of a
`method for automatically determining a stimulation thresh
`old for the Vagal nervestimulation using the signal indicative
`of laryngeal activity.
`FIG. 14 is a flow chart illustrating an embodiment of a
`method for monitoring and titrating the Vagal nervestimula
`tion acutely and chronically using the signal indicative of
`laryngeal activity.
`
`DETAILED DESCRIPTION
`
`In the following detailed description, reference is made to
`the accompanying drawings which form a part hereof, and in
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 14
`
`

`

`3
`which is shown by way of illustration specific embodiments
`in which the invention may be practiced. These embodiments
`are described in sufficient detail to enable those skilled in the
`art to practice the invention, and it is to be understood that the
`embodiments may be combined, or that other embodiments
`may be utilized and that structural, logical and electrical
`changes may be made without departing from the spirit and
`scope of the present invention. References to “an”, “one', or
`“various embodiments in this disclosure are not necessarily
`to the same embodiment, and Such references contemplate
`more than one embodiment. The following detailed descrip
`tion provides examples, and the scope of the present invention
`is defined by the appended claims and their legal equivalents.
`This document discusses a system providing for optimiza
`tion of Vagal nerve stimulation using a laryngeal activity
`sensor. The optimization includes, for example, optimization
`of electrode placement, automatic threshold determination or
`Verification, monitoring of lead/electrode status, detecting of
`neural injury, and monitoring a healing process that follows
`the electrode placement. In many applications of vagal nerve
`stimulation, the target response (intended outcome) may be
`difficult to monitor and analyze for the purpose of therapy
`optimization. For example, a transvenous lead is used to
`deliver Vagal nervestimulation for controlling cardiac remod
`eling. The transvenous lead includes one or more electrodes at
`its distal end to be placed within an internal jugular vein
`adjacent to the vagus nerve in the cervical region. The internal
`jugular vein is a large vessel providing for a wide range of
`possible electrode positions. It is practically difficult to use
`effects of the Vagal nerve stimulation in cardiac remodeling
`for guidance in the electrode placement and stimulation
`parameter adjustment.
`On the other hand, it is known that Vagal nerve stimulation
`causes vibration of the larynx through the recurrent laryngeal
`nerves, which are branches of the vagus nerve that innervate
`the larynx. Thus, laryngeal activity, including the magnitude
`and frequency of the vibration of the larynx, provides for an
`indication of whether the vagus nerve is activated by neural
`stimulation. This allows for optimization of therapy without
`the need to monitor and analyze the target response (such as
`cardiac remodeling) of the Vagal nerve stimulation.
`The present subject matter is applicable to stimulation of
`the vagus nerve using various energy forms and various signal
`morphology. In one embodiment, Vagal nerve stimulation
`includes delivery of electrical pulses to the vagus nerve to
`artificially elicit action potentials in that nerve. In other
`embodiments, vagal nerve stimulation includes delivery of
`any form of energy that is capable of eliciting or modulating
`neural activities in the nervous system, Such as mechanical,
`thermal, optical, chemical, and biological energies.
`The present Subject matter is applicable to neural stimula
`tion systems providing for activation and/or inhibition of the
`vagus nerve for treatment of various disorders including, but
`not limited to, cardiac remodeling, depression, anorexia ner
`Vosa/eating disorders, pancreatic function, epilepsy, hyper
`tension, inflammatory disease, and diabetes. In general, the
`present Subject matter is applicable to any system providing
`for Vagal nerve stimulation in which the neural stimulation
`results in detectable laryngeal activity.
`While delivery of neural stimulation through a transvenous
`lead having one or more electrodes placed in an internal
`jugular vein adjacent to the vagus nerve in the cervical region
`is specifically discussed in this document as an example, the
`present Subject matter is applicable to any lead and/or elec
`trode configuration and placement for Vagal nerve stimula
`tion. Optimization of electrode placement and stimulation
`parameters using laryngeal activity is particularly useful
`
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`US 7,801,603 B2
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`4
`when the target response of the neural stimulation is difficult
`to measure acutely and/or when the intended stimulation site
`is difficult to locate precisely without a substantially invasive
`Surgical procedure.
`FIG. 1 is an illustration of an embodiment of a neural
`stimulation system 100 and portions of an environment in
`which system 100 is used. System 100 includes an activity
`sensor 110 for sensing laryngeal activity, a transvenous lead
`112 for delivering vagal nerve stimulation, and an external
`system 120 coupled to activity sensor 110 via a cable 111 and
`coupled to lead 112 via a cable 118. External system 120
`allows for optimization of the Vagal nerve stimulation using
`the sensed laryngeal activity.
`Lead 112 is a transvenous lead having a proximal end 114,
`a distal end 113, and an elongate body 115 coupled between
`proximal end 114 and distal end 113. Proximal end 114
`includes a connector 117. In the illustrated embodiment, dis
`talend 113 includes stimulation electrodes 116A-B. As illus
`trated in FIG. 1, a body 101 includes a neck 102, a right
`internal jugular vein 104A, a left internal jugular vein 104B,
`a right subclavian vein 105A, and a left subclavian vein 105B.
`Lead 112 is inserted using techniques similar to those
`employed in implanting cardiac pacing leads. During the
`insertion, distal end 113 enters the left subclavian vein 105B
`through an incision, advances in the subclavian veins 105B
`and then 105A toward right internal jugular vein 104A, enters
`right internal jugular vein 104A, advances in right internal
`jugular vein 104A until electrodes 116A-B reach one or more
`vagal nervestimulation sites. After distal end 113 is in right
`internal jugular vein 104A, stimulation electrodes 116A-B
`are positioned, and repositioned when necessary, using lead
`112 and/or a lead insertion tool such as a stylet, a guide wire,
`or a guide catheter.
`Electrodes 116A-B allow neural stimulation to be deliv
`ered to a vagus nerve 106, which is adjacent to right internal
`jugular vein 104A in the cervical region. Activity sensor 110
`is placed on the neck over the larynx to sense a signal indica
`tive of laryngeal activity. The laryngeal activity is used as a
`measure of response of vagus nerve 106 to the neural stimu
`lation delivered to vagus nerve 106. In various embodiments,
`the laryngeal activity is monitored for placement of Stimula
`tion electrodes such as electrodes 116A-B, optimization of
`stimulation parameter Such as those controlling stimulation
`intensity (e.g., stimulation amplitude, frequency, duration,
`and duty cycle), and detection or monitoring of various events
`that affect the response of vagal nerve 106 to the neural
`stimulation.
`As illustrated in FIG. 1, proximal end 114 remains outside
`of body 101, Such as during an operation of implantation of
`lead 112 and an implantable medical device such as one
`discussed below with reference to FIG. 2. This allows elec
`trodes 116A-B to be placed as desired before connecting
`proximal end 114 to the implantable medical device. Proxi
`mal end 114 includes a connector 117 coupled to a connector
`119 of cable 118 to allow delivery of the neural stimulation
`from external system 120. External system 120 allows a user
`Such as a physician or other caregiver to control the delivery
`of neural stimulation via lead 112 and monitor the signal
`indicative of larynx sensed by activity sensor 110.
`The configuration of system 100 shown in FIG. 1 is an
`example presented for illustrative purposes. The present Sub
`ject matter generally includes monitoring and optimization of
`Vagal nerve stimulation delivered using any electrode con
`figuration using any signal that indicates laryngeal activity
`resulting from the Vagal nerve stimulation. For example, lead
`112 may include one or more stimulation electrodes, and an
`electrode pair for delivering the neural stimulation may
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 15
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`include two electrodes on lead 112 oran electrode on lead 112
`and a reference electrode not necessarily adjacent to the vagus
`nerve. In one embodiment, the reference electrode is a skin
`patch electrode for acute use. In one embodiment, in addition
`to, or instead of stimulation electrodes on lead 112 one or
`more nerve cuff electrodes each surrounding vagus nerve 106
`are used. In one embodiment, electrodes 116A-B are placed
`in the left interval jugular vein 104B. During the insertion,
`distal end 113 enters the left subclavian vein 105B or right
`subclavian vein 105A through an incision, enters left internal
`jugular vein 104B from right subclavian vein 105A, advances
`in left internal jugular vein 104B until electrodes 116A-B
`reach one or more Vagal nerve stimulation sites.
`FIG. 2 is an illustration of an embodiment of a neural
`stimulation system 200 and portions of the environment in
`which system 200 is used. System 200 differs from system
`100 primarily in that the neural stimulation is delivered from
`an implantable medical device 222 implanted in body 101. In
`one embodiment, FIGS. 1 and 2 illustrate different stages of
`implantation and use of an implantable neural stimulation
`system. FIG. 1 illustrates a system setup in the middle of an
`implantation procedure during which lead 112 is inserted
`with electrodes 116A-B placed to achieve desirable perfor
`mance of Vagal nervestimulation. FIG. 2 illustrates the sys
`tem set-up after the implantable neural stimulation system is
`fully implanted, such as during the end stage of the implan
`tation procedure when the implantable neural stimulation
`system is programmed for chronic use or during a follow-up
`examination during which the implantable neural stimulation
`system is adjusted if necessary.
`An activity sensor 210 represents an embodiment of activ
`ity sensor 110 that is capable of communicating with an
`external system 220 via a wireless link. In one embodiment,
`activity sensor 110 and external system 220 are electrically
`connected using a cable, and a communication link 211 rep
`resents the cable. In another embodiment, activity sensor 110
`and external system 220 are wirelessly coupled through
`telemetry Such as a radio-frequency electromagnetic telem
`etry link, and communication link 211 represents the telem
`etry link.
`Implantable medical device 222 delivers the neural stimu
`lation through one or both of electrodes 116A-B. After elec
`trodes 116A-B are placed, proximal end 114 of lead 112 is
`connected to implantable medical device 222 via connector
`117. In one embodiment, the housing of implantable medical
`device 222 functions as a reference electrode, and the neural
`stimulation can be delivered using any pair of electrodes
`selected from electrodes 116A-B and the housing of implant
`able medical device 222. In one embodiment, neural activity
`in vagus nerve 106 is sensed using any pair of electrodes
`selected from electrodes 116A-B and the housing of implant
`able medical device 222.
`In one embodiment, in addition to the neural stimulation
`circuit, implantable medical device 222 includes other moni
`toring ortherapeutic circuits or devices such as one or more of
`cardiac pacemaker, cardioverter/defibrillator, drug delivery
`device, and biological therapy device. External system 220
`provides for control of and communication with implantable
`medical device 222 by the user. External system 220 and
`implantable medical device 222 are communicatively
`coupled via a telemetry link 218. In one embodiment, external
`system 220 includes a programmer. In another embodiment,
`external system 220 is a patient management system includ
`ing an external device communicating with implantable
`medical device 222 via telemetry link 218, a remote device in
`a remote location, and a telecommunication network linking
`the external device and the remote device. The patient man
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`agement system allows access to implantable medical device
`222 from the remote location, for purposes Such as monitor
`ing patient status and adjusting therapies. In one embodiment,
`telemetry link 218 is an inductive telemetry link. In an alter
`native embodiment, telemetry link 218 is a far-field radio
`frequency telemetry link.
`FIG. 3 is a block diagram illustrating an embodiment of
`portions of a circuit of system 100, including an activity
`sensor 310 coupled to an external system 320 by cable 111.
`Activity sensor 310 is an embodiment of activity sensor 110
`and includes an accelerometer 331 to sense an acceleration
`signal being the signal indicative of laryngeal activity. Accel
`erometer 331 has characteristics Suitable for sensing the mag
`nitude and frequency of vibrations of the larynx that indicate
`activity in the vagus nerve when Vagal nerve stimulation is
`delivered. In one embodiment, accelerometer 331 represents
`a plurality of accelerometers allowing for selection of an
`acceleration signal as the signal indicative of laryngeal activ
`ity based on the signal quality. External system 320 includes
`a neural stimulation analyzer 324, a neural stimulation circuit
`328, an external controller 329, and a user interface 330.
`Neural stimulation analyzer 324 includes a laryngeal activity
`input 325, a neural stimulation input 326, and a processing
`circuit 327. Laryngeal activity input 325 receives the signal
`indicative of laryngeal activity from activity sensor 310 via
`cable 111. Neural stimulation input 326 receives a signal
`indicative of the delivery of the neural stimulation to the
`vagus nerve. Processing circuit 327 processes the signal
`indicative of laryngeal activity for analyzing the operation
`and performance of system 100 using that signal. Neural
`stimulation circuit 328 delivers the neural stimulation to
`stimulation electrodes such as electrodes 116A-B. External
`controller 329 controls overall operation of external system
`320, including the delivery of the neural stimulation from
`neural stimulation circuit 328. User interface 330 allows the
`user to control the neural stimulation and monitor the
`response of the vagus nerve to the neural stimulation using the
`signal indicative of laryngeal activity.
`FIG. 4 is a block diagram illustrating an embodiment of
`portion of a circuit of system 200, including an activity sensor
`410 coupled to an external system 420 via communication
`link 211 and an implantable medical device 422 coupled to
`external system 420 via telemetry link 218. Activity sensor
`410 is an embodiment of activity 210 and includes acceler
`ometer 331 and a sensor telemetry circuit 432. In the illus
`trated embodiment, communication link 211 is a telemetry
`link. Sensor telemetry circuit 432 transmits the sensed signal
`indicative of laryngeal activity to external system 420 via
`telemetry link 211. In another embodiment, communication
`link 211 is a cable providing an electrical connection between
`accelerometer 331 and laryngeal activity input 325. External
`system 420 includes neural stimulation analyzer 324, external
`telemetry circuit 438, external controller 429, and user inter
`face 330. External telemetry circuit 438 receives the signal
`indicative of laryngeal activity from activity sensor 410 via
`communication link 211 and communicates with implantable
`medical device 422 via telemetry link 218 to control the
`neural stimulation delivered from implantable medical device
`422. External controller 429 controls overall operation of
`external system 420, including the transmission of commands
`for controlling the neural stimulation delivered from the
`implantable medical device 422. Implantable medical device
`422 includes a neural stimulation circuit 434, an implant
`controller 435, and an implant telemetry circuit 436. Neural
`stimulation circuit 434 delivers the neural stimulation
`through stimulation electrodes such as electrodes 116A-B.
`Implant controller 435 controls the delivery of the neural
`
`Petitioner - Avation Medical, Inc.
`Ex. 1033, p. 16
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`US 7,801,603 B2
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`7
`stimulation and is responsive to the commands transmitted
`from external system 420. Implant telemetry circuit 436
`receives the commands from external system 420 via telem
`etry link 218 and when needed, transmits signals to external
`system 420 via telemetry link 218.
`FIG. 5 is an illustration of an embodiment of a laryngeal
`activity sensor assembly 540 that allows for a substantially
`stable attachment of an activity sensor on a patient’s neck
`over the larynx. Laryngeal activity sensor assembly 540
`includes an activity sensor 510 and a neck-bracing structure
`configured to hold activity sensor 510 on the neck over the
`larynx. Activity sensor 510 senses the signal indicative of
`laryngeal activity and represents any of activity sensors 110.
`210, 310, and 410. In the illustrated embodiment, a cable 511
`is connected to activity sensor 510 and has a connector 542 to
`provide electrical connections between activity sensor 510
`and external system 120 or 320. In a specific embodiment,
`cable 511 is detachably coupled to activity sensor 510. In
`another embodiment, activity sensor 510 is communicatively
`coupled to external system 220 or 420 via telemetry, and cable
`511 is not needed.
`Laryngeal activity sensor assembly 540 includes a neck
`brace 544 that is configured to wrap around a substantial
`portion of the neck and limits the movement of the neck. Neck
`brace 544 includes two ends 547A-B that are separated by a
`Substantial gap over an anterior portion of the neck. In one
`embodiment, neckbrace 544 is made of a material selected to
`limit the sensing of noise by activity sensor 510 by damping
`vibrations of environmental sources such as vibrations from
`equipment and activity of medical personnel. In one embodi
`ment, neck brace 544 is made of a substantially soft material
`such as foam. Neck brace 544 has an interior surface 545 and
`an exterior surface 546. Interior surface 545 is configured for
`contacting the neck. In one embodiment, as illustrated in FIG.
`5, neck brace 544 has a substantially even thickness between
`interior surface 545 and exterior surface 546. This thickness
`is, for example, between approximately 10 mm and 80 mm.
`Laryngeal activity sensor assembly 540 further includes
`two brackets 548-B each affixed onto one of en