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WO2025158351A1 - Thérapie par neurostimulation utilisant de multiples conducteurs positionnés pour fournir une détection améliorée de signaux physiologiques - Google Patents

Thérapie par neurostimulation utilisant de multiples conducteurs positionnés pour fournir une détection améliorée de signaux physiologiques

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Publication number
WO2025158351A1
WO2025158351A1 PCT/IB2025/050782 IB2025050782W WO2025158351A1 WO 2025158351 A1 WO2025158351 A1 WO 2025158351A1 IB 2025050782 W IB2025050782 W IB 2025050782W WO 2025158351 A1 WO2025158351 A1 WO 2025158351A1
Authority
WO
WIPO (PCT)
Prior art keywords
lead
endovascular
sensing
physiological signals
location
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/IB2025/050782
Other languages
English (en)
Inventor
Rene A. MOLINA
Thaddeus S. Brink
Benjamin P. Isaacson
Nicholas D. BUSE
Abby Beuning Holt Becker
Caleb Cole ZARNS
David E. Linde
Scott R. Stanslaski
Julia P. SLOPSEMA
Varun Umesh KASHYAP
Mark Ashby
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medtronic Inc
Original Assignee
Medtronic Inc
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Filing date
Publication date
Application filed by Medtronic Inc filed Critical Medtronic Inc
Publication of WO2025158351A1 publication Critical patent/WO2025158351A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters
    • A61N1/36139—Control systems using physiological parameters with automatic adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
    • A61B5/6868—Brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation
    • A61N1/0534—Electrodes for deep brain stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36064—Epilepsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36067—Movement disorders, e.g. tremor or Parkinson disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

Definitions

  • Embodiments relate to neurostimulation therapy and more particularly to neurostimulation therapy that uses multiple leads positioned in to provide improved sensing of physiological signals.
  • DBS deep brain stimulation
  • a distal end of a lead is implanted into the brain of the patient at a target location.
  • the proximal end of the lead is coupled to an implantable medical device such as a neurostimulator that produces electrical stimulation signals that are delivered by one or more electrodes of the lead to the brain and/or that senses physiological signals captured by the one or more electrodes of the lead within the brain.
  • the neurostimulation therapy may be optimized for a given patient by sensing the physiological signals within the brain.
  • the sensing may be in a passive context where no stimulation is being applied such as to capture a baseline.
  • the sensing may be in conjunction with stimulation to capture information that may be considered in the future and/or may be used in near real time to control the stimulation such as with adaptive DBS.
  • issues with sensing may arise due to various difficulties. For instance, the structure and/or condition of the brain may result in the sensing lead being placed in a less than ideal location for sensing the relevant physiological signals. As another example, the capability of the sensing lead may degrade over time or fail altogether.
  • Embodiments address issues such as these and others by providing neurostimulation therapy sensing with multiple leads positioned to provide improved sensing capability for a given patient’s anatomy and condition.
  • multiple leads for sensing various combinations of electrodes for sensing may be attempted and the combination providing the best biomarker resolution can be chosen to use for therapy.
  • placement of the multiple leads can be selected to provide additional features such as indirect monitoring of an area of interest within the brain where one or both leads are outside of the area of interest or replacing the sensing function of one lead using the sensing function of another lead in close proximity.
  • the multiple leads may be of the same type, such as DBS leads, or of different types such as a first lead that is a DBS lead outside of within the brain and outside of blood vessels and a second lead that is an endovascular lead within a blood vessel of the brain.
  • Embodiments provide a method of providing neurostimulation therapy.
  • the method involves sensing physiological signals with a non-endovascular lead having at least one distal electrode at a first location outside of a blood vessel within a brain of a patient.
  • the method further involves sensing physiological signals with an endovascular lead having at least one distal electrode at a second location within the blood vessel of the brain of the patient.
  • Embodiments provide a method of providing neurostimulation therapy.
  • the method involves sensing physiological signals with a first lead having a plurality of distal electrodes at a first location within a brain of a patient.
  • the method involves sensing physiological signals with a second lead having a plurality of distal electrodes at a second location within the brain of a patient. While sensing the physiological signals with the first lead and the second lead, the method further involves iterating through combinations of at least one distal electrode of the first lead with at least one distal electrode of the second lead to find a combination that provides a best biomarker resolution.
  • Embodiments provide a method of providing neurostimulation therapy.
  • the method involves sensing physiological signals with a first lead having a distal electrode at a first location within a brain of a patient.
  • the method involves detecting whether the sensed physiological signals have a signal characteristic that meets a threshold. If the signal characteristic does meet the threshold, then the method involves utilizing the sensed physiological signal from the first location for providing the neurostimulation therapy. If the signal characteristic does not meet the threshold, then the method involves sensing physiological signals with a second lead having a distal electrode in a second location within the brain of the patient and utilizing the sensed physiological signal from the second location for providing the neurostimulation therapy.
  • Embodiments provide an implantable medical system.
  • the system includes a non-endovascular lead having at least one distal electrode at a first location within a brain of a patient but outside of a blood vessel within the brain of the patient.
  • the system includes an endovascular lead having at least one distal electrode at a second location within the blood vessel of the brain of the patient.
  • the system further includes an implantable medical device coupled to the non-endovascular lead and the endovascular lead.
  • the implantable medical device has sensing circuiting to sense physiological signals with the non-endovascular lead and sense physiological signals with an endovascular lead.
  • Embodiments provide a system for providing neurostimulation therapy.
  • the system includes a first lead having at least one distal electrode at a first location within a brain of a patient.
  • the system includes a second lead having at least one distal electrode at a second location within the brain of the patient.
  • the system further includes an implantable medical device coupled to the first lead and the second lead.
  • the implantable medical device has sensing circuiting to sense physiological signals with the first lead and sense physiological signals with the second lead. While sensing the physiological signals with the first lead and the second lead, the implantable medical device iterates through combinations of at least one distal electrode of the first lead with at least one distal electrode of the second lead to find a combination that provides a best biomarker resolution.
  • Embodiments provide a system for providing neurostimulation therapy.
  • the system includes a first lead having at least one distal electrode at a first location within a brain of a patient.
  • the system includes a second lead having at least one distal electrode at a second location within the brain of the patient.
  • the system further includes an implantable medical device coupled to the first lead and the second lead.
  • the implantable medical device has a sensing circuit to sense physiological signals with the first lead and detect whether the sensed physiological signals have a signal characteristic that meets a threshold. If the signal characteristic does meet the threshold, then the implantable medical device utilizes the sensed physiological signal from the first location for providing the neurostimulation therapy.
  • the implantable medical device senses physiological signals with the second lead having a distal electrode in the second location within the brain of the patient and utilizing the sensed physiological signal from the second location for providing the neurostimulation therapy. DESCRIPTION OF THE DRAWINGS
  • FIG. 1 shows an example of a patient having an implantable medical system including two leads within the brain of the patient.
  • FIG. 2 shows an example of a relationship between an endovascular lead and a DBS lead positioned in relation to the target area to be sensed.
  • FIG. 3 shows an example of components of an external device that communicates with a neurostimulation device.
  • FIG. 4 shows an example of components of a neurostimulation device that may couple to the multiple leads to provide the sensing of physiological signals.
  • FIG. 5 shows an example of a workflow to provide the neurostimulation therapy by sensing the desired physiological signals using the multiple leads positioned according to the circumstances of the particular patient.
  • FIG. 6 shows an example of a data structure representing various combinations of sensing electrodes of the multiple leads and the resulting biomarker resolutions.
  • FIG. 7 shows an example of a data structure representing the electrodes of the multiple leads forming an array.
  • FIG. 8 shows an example of a workflow to implement a second lead as a replacement for a first lead when the sensing by the first lead becomes inadequate.
  • Embodiments provide an implantable medical system that uses two leads with each lead having a distal end located within the brain of the patient. Some embodiments utilize one or more techniques in conjunction with the positions of the distal ends of the multiple leads to provide improved sensing of physiological signals. Other embodiments utilize the second lead as a replacement to provide sensing of physiological signals when the first lead no longer provides adequate sensing.
  • the multiple leads may be of the same type while in other embodiments the multiple leads may be of different types, such as a DBS lead in combination with an endovascular lead within a blood vessel.
  • This disclosure describes example techniques to confirm the efficacy of forms of neurostimulation therapy.
  • the example techniques are described with respect to DBS, but the example techniques are not so limited and may be applied to other types of therapies and/or other anatomical locations.
  • Neurostimulation therapy, and DBS in particular, may provide relief for many different patient conditions such as movement disorders, epilepsy, obsessive compulsive disorder (OCD), depression, and others.
  • OCD obsessive compulsive disorder
  • Movement disorders may be found in patients with Parkinson's disease, multiple sclerosis, and cerebral palsy, among other conditions. Delivery of electrical stimulation by a medical device to one or more sites in a patient, such as within the brain, may help alleviate, and in some cases, eliminate symptoms associated with these movement disorders and other conditions.
  • bradykinesia i.e., slow physical movement
  • rhythmic hyperkinesia e.g., tremor
  • nonrhythmic hyperkinesia e.g., tics
  • akinesia i.e, a loss of physical movement.
  • Movement disorders may be found in patients with Parkinson's disease, multiple sclerosis, and cerebral palsy, among other conditions. Delivery of electrical stimulation by a medical device to one or more sites in a patient, such as within the brain, may help alleviate, and in some cases, eliminate symptoms associated with these movement disorders and other conditions.
  • FIG. 1 shows a typical environment for an implantable medical system 100 being used to provide neurostimulation therapy such as DBS therapy.
  • the implantable medical system 100 is installed onto a body 110 of a patient.
  • the implantable medical system 100 of this example includes a an implantable medical device such as a neurostimulator 102 that has either been installed externally on the patient or has been implanted into a subcutaneous or subfascial pocket 112.
  • a first medical lead 104 such as an endovascular lead which may be combined with an extension, is routed between a target stimulation site within the brain 111 of the patient and the neurostimulator 102.
  • the first lead 104 has a distal end 103 and distal electrodes thereon positioned within the brain 111 in proximity to the target location for the stimulation and/or sensing to be applied.
  • the lead 104 can be implanted in a less invasive way relative to a DBS lead by being introduced into a blood vessel that travels into the brain 111 and branches into the location that is in proximity to the target area.
  • FIG. 1 also shows a location and related aspects of a second lead 105, such as a conventional DBS lead that is a non-endovascular lead as the DBS lead 105 is present outside of the blood vessels of the brain 111.
  • the DBS lead 105 extends from the neurostimulator 102 in the conventional manner, beneath the skin, and to a location on the skull of the patient where a hole 113 is created to allow the DBS lead 105 to pass through the skull to enter the brain 111 in area 106 beneath the hole 113.
  • the DBS lead 105 can then be routed in a non- endovascular way outside of any blood vessel to the target area within the brain 111 where a distal end 108 with electrodes is positioned.
  • FIG. 2 shows an example of a more detailed view of the target area as a subregion 208 within the brain 111 that is distinct from an adjacent subregion 210.
  • the distal end 103 of the endovascular lead 104 is located in proximity to the subregion 208.
  • the endovascular lead 104 including the distal end 103 with electrodes 204 is present within a blood vessel 202 that passes in proximity to the target area 208 of the brain 111.
  • the endovascular lead 104 is capable of providing neurostimulation therapy in the form of electrical neurostimulation signals and/or sensing of physiological signals from one or more electrodes 202 that interact with the brain 111 in proximity to the target area 208 as indicated by region of interaction 212.
  • One or more of the electrodes 204 of the lead 104 may be used for sensing electrical physiological signals from the area in proximity to the target area 208 such as to measure effects of the neurostimulation therapy.
  • the distal end 108 of the DBS lead 105 has a typical DBS lead position relative to the target subregion 208 that is a different position than the distal end 103 of the endovascular lead 104.
  • the DBS lead 105 is capable of providing neurostimulation therapy in the form of electrical neurostimulation signals from one or more electrodes 206 that propagate into the brain 111 in proximity to the target area 208 as indicated by stimulation and/or sensing region 214.
  • One or more of the electrodes 206 of the lead 105 may be used for sensing electrical physiological signals from the area in proximity to the target subregion 208 such as to further measure effects of the neurostimulation therapy.
  • the region of stimulation and/or sensing 212 and region of stimulation and/or sensing 214 can together provide a relatively large volume of neural activation and monitoring within the subregion 208 while remaining substantially confined to the subregion 208 and avoiding subregion 210 so as to not produce unwanted effects in subregion 210. Because the subregion 208 may be relatively small or adjacent to sensitive brain structures, only the distal end 108 of a single DBS lead 105 may be positioned at the subregion 208.
  • the presence of the endovascular lead 104 and distal end 103 within the blood vessel 202 in the location in proximity to the subregion 208 avoids the need for the stimulation and/or sensing region 214 to expand to such a degree that it would encroach into the subregion 210 in order to reach the portion of the subregion 208 where the stimulation and/or sensing region 212 is located.
  • the multiple leads 104, 105 with their respective distal ends 103, 108 in proximity to the subregion 208 minimize undesired stimulation leakage into the subregion 210.
  • non-endovascular leads such as DBS lead
  • DBS lead may be placed in primary locations that include but are not limited to the subthalamic nucleus (STN), globus pallidus internus (Gpi), anterior nucleus of thalamus (ANT), ventralis intermediate nucleus (VIM), ventral capsule/ventral striatum (VC/VS), or pedunculopontine nucleus (PPN).
  • STN subthalamic nucleus
  • Gpi globus pallidus internus
  • ANT anterior nucleus of thalamus
  • VIM ventralis intermediate nucleus
  • VC/VS ventral capsule/ventral striatum
  • PPN pedunculopontine nucleus
  • the endovascular lead may be positioned in a secondary location within a blood vessel within or adjacent to the same subregion 208, or elsewhere for indirect monitoring discussed further below. Examples of this secondary location include but are not limited to the Thalamostriate vein, the internal cerebral vein, the basal vein
  • the data structure of FIG. 6, and the multi -lead array of FIG. 7 various techniques may be employed to utilize the multiple leads like those shown in FIG. 2 to improve the sensing of the physiological signals. For instance, electrode combinations involving the multiple leads that provide increased biomarker resolution may be determined and used for therapy. Furthermore, the multiple leads may be placed in strategic locations to indirectly monitor an inaccessible region of the brain 111. Additionally, the multiple leads may be used as an array to achieve source separation of mixed signals where multiple sources of physiological signals are present in the region being sensed. Another use of the multiple leads includes using one lead as a replacement for the other lead that may have become degraded or inoperable for sensing purposes.
  • FIG. 2 may also represent a configuration where an inaccessible region of the brain 111 is being indirectly monitored using the first and second leads 104, 105.
  • the first and second leads 104, 105 being used for indirect monitoring may be of the same type or of different types, such as having an endovascular lead and a non-endovascular lead such as a DBS lead.
  • One lead may be positioned so that the distal electrodes are located at a sub-cortical location of the brain 111 while the distal electrodes of the other lead are located at a cortical margin location of the brain 111 where the region being indirectly monitored is separate from the sub-cortical location and the cortical margin location.
  • the signal of the target network of the inaccessible region in then extrapolated based on what is sensed at the two leads in the different disconnected regions.
  • direct sensing may occur at via one lead with a distal end at the STN and another lead with a distal end at the PPN to indirectly identify modulation associated with movement.
  • FIG. 3 shows an example of the components of an external device 114 that communicates with the neurostimulator 102 to provide programming that controls the neurostimulation therapy including stimulation and/or sensing functions and to obtain information collected by the neurostimulator 102.
  • the external device 114 may take various forms, such as a handheld tablet, a personal computer, and the like.
  • the several components of the external device 114 include a processor 302 as well as a communication circuitry 304 and an input/output circuitry 310.
  • the processor 302 interacts with the communication circuitry 304 and input/output circuitry 310 to provide the operations of the implantable medical device 102.
  • a power supply, not shown in FIG. 3, such as a battery or a utility power interface may also be included to provide electrical power to the various components.
  • the processor 302 performs various logical operations when interacting with the other components. These operations may involve utilizing the communication circuitry 304 to exchange data with the implantable medical device 102 and to produce relevant displays of information and receive relevant input from a user, such as a clinician or patient, viewing the displays. For instance, the data produced from sensing the physiological signals may be shared with the external device 114 at a future time or in near real-time for purposes of displaying the information to the clinician.
  • the processor 302 may be of various forms such as a general purpose programmable processor, application specific processor, hardwired digital logic, and/or various combinations.
  • the processor 302 may utilize operational memory that is internal, external (not shown), or a combination of the two and may also utilize a storage device to retain data and programming in a long-term, non-volatile fashion.
  • the communication circuitry 304 includes both a transmitter circuit 306 and a receiver circuit 308 for sending and receiving wireless signals.
  • the communication circuitry 304 is either wirelessly tethered or tethered by wire to the intermediary device 116 over the communication link 120.
  • the communication link may utilize a wireless protocol such as the Bluetooth® protocol.
  • the communication link 120 may be wired and rely upon telemetry where the intermediary device 116 is a telemetry head held in very close proximity to the implantable medical device 102.
  • any link with a sufficiently short latency to allow the clinician to react to changes in the patient may also be used, including remote/intemet connected management.
  • the input/output circuitry 310 allows the external device 114 to interact with users, including clinicians or the patient, or other devices.
  • the input/output circuitry 310 may provide outputs such as a visual display on a screen, audio, and the like.
  • the input/output circuitry 310 may provide inputs such as a keyboard or keypad, a mouse and/or touch screen, and the like.
  • the input/output circuitry 310 allows users to enter information such as programming details, stimulation parameters, and other information to be provided from the external device 114 to the neurostimulator 102 as well as review information such as physiological data sent from the neurostimulator 102 to the external device 114.
  • the components of the neurostimulator 102 are contained within a housing that isolates and protects the components from the surrounding environment. Typically, the housing is a biocompatible material that forms a hermetically sealed container.
  • the components of the neurostimulator 102 include a processor 402 as well as a communication circuitry 404.
  • a stimulation circuitry 410 is also present to generate the stimulation signals for the first and second leads used to provide the stimulation therapy, and sensing circuitry 412 is present to sense the physiological signals relevant to the stimulation therapy, such as the local field potential signals and/or other biomarkers, using the first and second leads.
  • the processor 402 interacts with the communication circuitry 404, stimulation circuitry 410, and sensing circuitry 412 to provide the operations of the neurostimulator 102.
  • the implantable medical device 102 also includes a power source, such as an on-board battery, to provide electrical power to these components.
  • the processor 402 performs various logical operations when interacting with the other components to provide the stimulation and/or sensing functions of the neurostimulation therapy.
  • Examples of the logical operations of the neurostimulator 102 and processor 402 in combination with those of the external device 114 and processor 302 are shown in the workflow example of FIG. 5.
  • the processor 402 may be of various forms such as a general purpose programmable processor, application specific processor, hardwired digital logic, and/or various combinations.
  • the communication circuitry 404 includes both a transmitter circuit 406 and a receiver circuit 408 for sending and receiving wireless signals. This allows the processor 402 to receive information such as programming, stimulation parameters, sensing configurations and the like from the external device 114. This also allows the processor 402 to send information such as sensed physiological signal data to the external device 114.
  • the stimulation circuitry 410 in the example shown allows the implantable medical device 102 to interact with the brain tissue of the patient 110.
  • the stimulation circuitry 410 may produce stimulation signals that include stimulation pulses of a given amplitude, such as a given electrical current amplitude.
  • the stimulation circuitry 410 may alter the stimulation amplitude, frequency, and pulse width of the stimulation therapy as requested by the processor 402 to provide effective stimulation therapy, such as effective adaptive deep brain stimulation.
  • One manner of providing effective stimulation therapy may utilize feedback in the form of sensed physiological signals.
  • Sensing circuitry 412 senses these physiological signals such as local field potential signals and/or other biomarkers and provides the sensed signal to the processor 402.
  • the sensing circuitry 412 may be used to sense local field potential signals during the ongoing application of stimulation signals. For instance, the sensed local field potential signals are analyzed by the processor 402 in order to then request stimulation amplitude changes by the stimulation circuitry 410 when providing adaptive DBS. The processor 402 compares the sensed local field potential signal power to the physiological thresholds to determine whether to alter the stimulation amplitude.
  • a proximal end of the endovascular lead 104 including electrical connectors 404 may be coupled to the neurostimulator 102.
  • the neurostimulator may then configure the stimulation circuitry 410 and sensing circuitry 412 so that stimulation outputs 114 may be electrically coupled to one or more of the electrical connectors 404 when providing stimulation signals while sensing inputs 413 may be electrically coupled to one or more of the electrical connectors 404 when sensing physiological signals.
  • a proximal end of the DBS lead 105 and electrical connectors thereon are similarly coupled to the neurostimulator 102.
  • FIG. 5 shows an example 500 of logical operations that may be performed by the implantable medical device 102 to optimize sensing of physiological signals by finding a combination of electrodes of the first and second leads 104, 105 that provides a best biomarker resolution.
  • a waiting period may be employed to resolve edema, achieve lead stabilization, and/or find optimal stimulation settings.
  • the implantable medical device 102 may begin concurrently sensing with the first and second leads 104, 105 to confirm the maximum viability of signal biomarkers and to further confirm that there is sufficient neural substrate to elicit an evoked response.
  • the implantable medical device 102 may begin concurrently sensing physiological signals with the first and second leads 104, 105. Specifically, the implantable medical device may begin iterating through the possible combinations of electrodes of the first and second leads to provide sensing of physiological signals at an operation 502. This sensing may be in a passive context where the physiological signals are innate as no stimulation is being provided to evoke the signals. Alternatively, the sensing of operation 502 may be occurring in conjunction with stimulation being output by combinations of electrodes of the first and/or second leads 104, 105. Furthermore, the implantable medical device 102 may also be iterating through various combinations of stimulation parameters and electrodes at operation 504 in an effort to produce a desirable therapeutic effect as determined by the sensing occurring at operation 502.
  • the combinations of electrodes used during sensing may involve any number of electrodes of the first lead 104 and any number of electrodes of the second lead 105. Furthermore, the combinations may involve all combinations of electrodes sensing in a bipolar configuration as well as all combinations of electrodes sensing in a monopolar configuration. These possible combinations may include using at least one electrode of one lead, either the first or endovascular lead or the second or DBS lead, with a plurality of the electrodes of the other lead. These possible combinations may further include sensing using electrodes of only one lead 104, such as an endovascular lead, or electrodes of only the other lead 105, such as a DBS lead. These possible combinations may also further include using one or more electrodes in a mixed monopolar configuration where one or more electrodes of one of the leads, either the first or endovascular lead or the second or DBS lead, is used for common referencing.
  • a data structure 600 of FIG. 6 is discussed below where the sensed physiological signal data for each combination of electrodes of operation 502 may be stored at operation 506 of FIG. 5 and compared to rank the combinations and thereby find the combination providing the best biomarker resolution and/or signal quality at operation 508. Therapy may then proceed that uses the combination providing the best biomarker resolution for sensing the physiological signals of interest at operation 510.
  • the sensing threshold for finding the best biomarker resolution may be patient specific, specific to the disease type, and/or symptom specific and is a function of what is being monitored and measured. For example, a Beta decrease may be identified as being responsive to stimulation, medication, sleep, and so forth. Furthermore, a subjective determination may also be made by considering patient feedback in such an example.
  • the sensing of physiological signals may involve determining that the stimulated network within the brain modulates with the expected physiological response.
  • the sensed physiological signals may be analyzed regarding the Circuit of Papez, cortico-basal ganglia-thalmo-cortical loops.
  • the sensed physiological signals may be analyzed regarding forms of coupling such as phase amplitude coupling, granger causality, transfer functions, latency of propagation such as where a signal is induced or coupled into a different network than the network being directly stimulated.
  • Atypical resolution of at least 0.8uV/rtHz of Beta range local field potential is an example of a value that is considered a meaningful biomarker for Beta.
  • the data structure 600 showing a simplified version of the various combinations of sensing electrodes of the first and second leads 104, 105 is shown in FIG. 6.
  • the data structure is shown as containing columns 602 and 604 representing the electrode combinations being used and the biomarkers resolution provided by the electrode combinations.
  • Each row provides a particular electrode combination and the resulting biomarker resolution.
  • the first row uses electrode 0 of lead 1 and electrode 0 of lead 2 in a bipolar (“B”) sensing configuration.
  • B bipolar
  • row five uses electrode 0 of lead 1 to sense and electrode 0 of lead 2 for common referencing in a first monopolar (“Ml”) sensing configuration.
  • row nine uses electrode 0 of lead 1 and electrode 0 of lead 2 in a second monopolar (“M2”) sensing configuration such as where the electrodes of the first lead are providing common referencing.
  • row thirteen uses electrodes 0 and 1 of lead 1 and no electrode of lead 2 in a bipolar (“B”) sensing configuration.
  • row fourteen uses electrode 0 of lead 1, no electrode of lead 2, and the case (“C”) of the device 102 in a monopolar (“M”) sensing configuration. It will be appreciated that there are many combinations possible including using more than one electrode of one lead while also using more than one electrode of the other lead.
  • FIG. 7 shows an example of a data structure 700 representative of an electrode sensing array established by the distal electrodes of the multiple leads 104, 105 that may be utilized when attempting to separate sources of a sensed physiological mixed signal that has contributions from the multiple sources.
  • the columns 702, 704 of the array 700 represent the first and second leads 104, 105, respectively.
  • the rows 706, 708, 710, and 712 of the array 700 represent each electrode position on the first and second leads 104, 105.
  • column 702, row 706 shows the contribution of electrode 0 of lead one while column 704, row 706 shows the contribution of electrode 0 of lead two, and so on.
  • the source separation can then be performed such as at the external device by taking the data from the array and applying source separation algorithms to analyze the contributions of the elements of the sensing array.
  • source separation algorithms include principal component analysis (PCA), independent component analysis (ICA), denoising source separation (DSS), singular value decomposition (SVD), and the like.
  • FIG. 8 shows an example 800 of logical operations that may be performed in scenarios where one of the multiple leads serves as a replacement or back-up to a primary lead.
  • the implantable medical device 102 is sensing physiological signals using a first lead at an operation 802.
  • the sensing may be using the DBS lead 105 positioned within the tissue but outside of the blood vessels.
  • the processor of the implantable medical device 102 performs a comparison of the sensed physiological signal characteristic to a threshold.
  • the comparison may include comparing a dynamic range of the sensed signal to a dynamic range threshold.
  • the comparison may be sensed maximum signal amplitude to an amplitude threshold.
  • a biomarker resolution threshold may be used.
  • therapy continues at operation 806 by using the sensed physiological signal from the first lead.
  • the implantable medical device 102 begins sensing using the second lead, such as a different DBS lead outside of the blood vessels or a different endovascular lead within a blood vessel, at operation 808. Therapy then continues at operation 810 by using the sensed physiological signal from the second lead.
  • a method of providing neurostimulation therapy comprising: sensing physiological signals with a non-endovascular lead having at least one distal electrode at a first location outside of a blood vessel within a brain of a patient; and sensing physiological signals with an endovascular lead having at least one distal electrode at a second location within the blood vessel of the brain of the patient.
  • non-endovascular lead comprises a plurality of distal electrodes at the first location and wherein while sensing the physiological signals with the non-endovascular lead and the endovascular lead, iterating through combinations of the plurality of distal electrodes of the non-endovascular lead with the at least one distal electrode of the endovascular lead to find a combination that provides a best biomarker resolution.
  • the endovascular lead comprises a plurality of distal electrodes at the second location and wherein while sensing the physiological signals with the non-endovascular lead and the endovascular lead, iterating through combinations of the at least one distal electrode of the non-endovascular lead with the plurality of distal electrodes of the endovascular lead to find a combination that provides a best biomarker resolution.
  • a method of providing neurostimulation therapy comprising: sensing physiological signals with a first lead having a plurality of distal electrodes at a first location within a brain of a patient; sensing physiological signals with a second lead having a plurality of distal electrodes at a second location within the brain of a patient; and while sensing the physiological signals with the first lead and the second lead, iterating through combinations of at least one distal electrode of the first lead with at least one distal electrode of the second lead to find a combination that provides a best biomarker resolution.
  • the method further comprises indirectly monitoring a region of the brain that is separate from the sub-cortical location and the cortical margin location by sensing physiological signals from the first lead and the second lead.
  • the first lead is a non- endovascular lead and the first location is outside a blood vessel within the brain and the second lead is an endovascular lead and the second location is within the blood vessel within the brain.
  • a method of providing neurostimulation therapy comprising: sensing physiological signals with a first lead having a distal electrode at a first location within a brain of a patient; detecting whether the sensed physiological signals have a signal characteristic that meets a threshold; if the signal characteristic does meet the threshold, then utilizing the sensed physiological signal from the first location for providing the neurostimulation therapy; if the signal characteristic does not meet the threshold, then sensing physiological signals with a second lead having a distal electrode in a second location within the brain of the patient and utilizing the sensed physiological signal from the second location for providing the neurostimulation therapy.
  • first lead is a non-endovascular lead and the first location is outside a blood vessel within the brain and the second lead is an endovascular lead and the second location is within the blood vessel within the brain.
  • a system for providing neurostimulation therapy comprising: a non-endovascular lead having at least one distal electrode at a first location within a brain of a patient but outside of a blood vessel within the brain of the patient; an endovascular lead having at least one distal electrode at a second location within the blood vessel of the brain of the patient; and an implantable medical device coupled to the non-endovascular lead and the endovascular lead, the implantable medical device having sensing circuiting to: sense physiological signals with the non-endovascular lead; and sense physiological signals with an endovascular lead.
  • non-endovascular lead comprises a plurality of distal electrodes at the first location and wherein while the implantable medical device senses the physiological signals with the non-endovascular lead and the endovascular lead, the implantable medical device iterates through combinations of the plurality of distal electrodes of the non-endovascular lead with the at least one distal electrode of the endovascular lead to find a combination that provides a best biomarker resolution.
  • the endovascular lead comprises a plurality of distal electrodes at the second location and wherein while the implantable medical device senses the physiological signals with the non-endovascular lead and the endovascular lead, the implantable medical device iterates through combinations of the at least one distal electrode of the non-endovascular lead with the plurality of distal electrodes of the endovascular lead to find a combination that provides a best biomarker resolution.
  • the non-endovascular lead comprises a plurality of distal electrodes at the first location and wherein while the implantable medical device senses physiological signals with the plurality of distal electrodes of the non-endovascular lead and the at least one distal electrode of the endovascular lead where the plurality of distal electrodes of the non-endovascular lead in combination with the at least one distal electrode of the endovascular lead establish a sensing array the implantable medical device separates the multiple sources contributing to the sensed physiological signals by analyzing the contributions of the sensing array.
  • the endovascular lead comprises a plurality of distal electrodes at the second location and wherein while the implantable medical device senses physiological signals with the at least one distal electrode of the non-endovascular lead and the plurality of distal electrodes of the endovascular lead where the at least one distal electrode of the non-endovascular lead in combination with the plurality of distal electrodes of the endovascular lead establish a sensing array the implantable medical device separates the multiple sources contributing to the sensed physiological signals by analyzing the contributions of the sensing array.
  • a system for providing neurostimulation therapy comprising: a first lead having at least one distal electrode at a first location within a brain of a patient; a second lead having at least one distal electrode at a second location within the brain of the patient; and an implantable medical device coupled to the first lead and the second lead, the implantable medical device having sensing circuiting to: sense physiological signals with the first lead; sense physiological signals with the second lead; and while sensing the physiological signals with the first lead and the second lead, iterating through combinations of at least one distal electrode of the first lead with at least one distal electrode of the second lead to find a combination that provides a best biomarker resolution.
  • a system for providing neurostimulation therapy comprising: a first lead having at least one distal electrode at a first location within a brain of a patient; a second lead having at least one distal electrode at a second location within the brain of the patient; and an implantable medical device coupled to the first lead and the second lead, the implantable medical device having sensing circuiting to: sense physiological signals with the first lead; detect whether the sensed physiological signals have a signal characteristic that meets a threshold; if the signal characteristic does meet the threshold, then utilize the sensed physiological signal from the first location for providing the neurostimulation therapy; and if the signal characteristic does not meet the threshold, then sense physiological signals with the second lead having a distal electrode in the second location within the brain of the patient and utilizing the sensed physiological signal from the second location for providing the neurostimulation therapy.
  • first lead is a non-endovascular lead and the first location is outside a blood vessel within the brain and the second lead is an endovascular lead and the second location is within the blood vessel within the brain.

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Abstract

L'invention concerne une thérapie par neurostimulation fournie à l'aide de multiples fils positionnés pour fournir une détection améliorée de signaux physiologiques pour un patient donné. Un système médical implantable utilise au moins deux fils, chaque fil ayant une extrémité distale située à l'intérieur du cerveau du patient. Une ou plusieurs techniques peuvent être utilisées conjointement avec les positions des extrémités distales des multiples conducteurs pour fournir une détection améliorée de signaux physiologiques. Le second fil peut être utilisé en tant que remplacement pour fournir une détection de signaux physiologiques lorsque le premier fil ne fournit plus de détection adéquate. Les multiples fils peuvent être du même type, tels que deux fils de DBS ou plus, ou les multiples fils peuvent être de différents types, tels qu'un fil de DBS en combinaison avec un fil endovasculaire à l'intérieur d'un vaisseau sanguin.
PCT/IB2025/050782 2024-01-26 2025-01-24 Thérapie par neurostimulation utilisant de multiples conducteurs positionnés pour fournir une détection améliorée de signaux physiologiques Pending WO2025158351A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050187589A1 (en) * 2004-02-20 2005-08-25 Scimed Life Systems, Inc. Method of stimulating/sensing brain with combination of intravascularly and non-vascularly delivered leads
US20180303595A1 (en) * 2015-10-20 2018-10-25 Nicholas Lachlan OPIE Endovascular device for sensing and or stimulating tissue
US20190046119A1 (en) * 2011-10-04 2019-02-14 Thomas James Oxley Methods for sensing or stimulating activity of tissue
US20200338350A1 (en) * 2019-04-23 2020-10-29 Medtronic, Inc. Probabilistic entropy for detection of periodic signal artifacts
US20210196964A1 (en) * 2019-12-31 2021-07-01 Medtronic, Inc. Brain stimulation and sensing

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050187589A1 (en) * 2004-02-20 2005-08-25 Scimed Life Systems, Inc. Method of stimulating/sensing brain with combination of intravascularly and non-vascularly delivered leads
US20190046119A1 (en) * 2011-10-04 2019-02-14 Thomas James Oxley Methods for sensing or stimulating activity of tissue
US20180303595A1 (en) * 2015-10-20 2018-10-25 Nicholas Lachlan OPIE Endovascular device for sensing and or stimulating tissue
US20200338350A1 (en) * 2019-04-23 2020-10-29 Medtronic, Inc. Probabilistic entropy for detection of periodic signal artifacts
US20210196964A1 (en) * 2019-12-31 2021-07-01 Medtronic, Inc. Brain stimulation and sensing

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