Intracranial and intravascular brain activity recording and targeted energy delivery to the brain

Abstract

Systems and methods are provided for treating neurological conditions by delivering focused ultrasound to selected brain regions using intracranially positioned devices. In some examples, systems methods, and devices for intracranially and intravascularly delivering energy to the brain of a subject with one or more medical conditions, can include intravascularly delivering a device to an intracranial vein adjacent brain tissue, intravascularly and intracranially sensing brain activity signals from the brain tissue, and intravascularly and intracranially delivering energy to the brain tissue to treat the one or more conditions.

Description

103241.007505 / 25-11006INTRACRANIAL AND INTRAVASCULAR BRAIN ACTIVITY RECORDING AND TARGETED ENERGY DELIVERY TO THE BRAINCROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 706,582, filed October 11, 2024, the entirety of which is incorporated by reference herein for any and all purposes. All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.BACKGROUND

[0002] Over 80 million Americans suffer with brain disorders such as Parkinson's disease, essential tremor. Tourette's syndrome, epilepsy, depression, obsessive-compulsive disorder (OCD), substance use disorders, and chronic pain. Patients with Parkinson’s disease, essential tremor, epilepsy, depression, OCD, substance use or eating disorders fail non-invasive treatments over one third of the time. For example, transcranial focused ultrasound is a non-invasive treatment, but tire skull attenuates ultrasound strongly and unpredictably, precluding delivery of a controlled ultrasound dose into tire brain. After failed non-invasive treatments, options include irreversible brain lesioning or deep brain stimulation (DBS). The overwhelming majority of patients for which DBS is an option are not being treated, for one or more reasons. For example, the invasiveness of the procedure requires a hole be drilled into the skull and electrodes implanted; a percentage of affected individuals understandably are willing to undergo such an invasive treatment; a small proportion of clinicians are willing to refer their patients for invasive treatments; and DBS is limited in the extent of the brain that can be targeted for energy delivery once implanted. Approaches are needed that can provide infonnation about a patient’s response to energy delivered to their brain and / or treat brain disorders that don't require an invasive procedure.SUMMARY

[0003] Aspects of tire present disclosure provide systems, methods, and devices for treating neurological conditions by delivering focused ultrasound to selected brain regions using intracranially positioned devices. In some examples, systems methods, and devices for intracranially and intravascularly delivering energy to the brain of a subject with one or more medical conditions, can- 1 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 include intravascularly delivering a device to air intracranial vein adjacent brain tissue, intravascularly and intracranially sensing brain activity signals from the brain tissue, and intravascularly and intracranially delivering energy to the brain tissue to treat the one or more conditions.

[0004] In another example, a method of intracranially and intravascularly delivering energy to neural tissue of a subject with one or more conditions to treat one or more conditions can include: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, the device including an expandable scaffold, a plurality of electrodes coupled to the expandable scaffold, and a plurality of ultrasound transducers coupled to tire expandable scaffold, wherein the plurality of ultrasound transducers are distributed about the scaffold; intravascularly and intracranially sensing brain activity signals from the brain tissue with tire plurality of electrodes; and based on and in response to the sensed brain activity signals, intravascularly and intracranially delivering energy to brain tissue with the plurality of ultrasound transducers to treat tire one or more conditions.

[0005] In yet another example, a method of delivering energy to neural tissue of a subject with one or more conditions to treat the one or more conditions can include: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, wherein the device comprises an expandable scaffold and a plurality of electrodes; intravascularly and intracranially sensing brain activity signals from brain tissue with the plurality of electrodes; and based on and in response to the intravascularly and intracranially sensed brain activity signals, extracranially delivering energy to brain tissue to treat the one or more conditions.

[0006] An expandable medical device can include an expandable and collapsible stent, a plurality of electrodes coupled to the stent, and a plurality of ultrasound transducers coupled to the stent. A system for energy delivery’ can include a first device comprising a plurality of electrodes; a second device comprising a plurality of ultrasound transducers; and a processing device in communication with the first device and the second device, wherein the processing device is configured to receive sensed signals from the plurality of electrodes, and wherein the processing device is configured to deliver energy to the plurality of ultrasound transducers to cause focused therapeutic ultrasound energy to be delivered from the plurality of ultrasound transducers to treat one or more conditions treatable with the application of ultrasound energy to brain tissue.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 illustrates a representation of intracranial venous vasculature.

[0008] FIG. 2 illustrates a deep brain simulation system.- 2 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-11006

[0009] FIG. 3 illustrates an example method in which a device is positioned in the inferior sagittal sinus (ISS).

[0010] FIG. 4 illustrates an example method in which a stimulating device and a recording device are positioned in the ISS.

[0011] FIG. 5 illustrates a first device placed in the superior sagittal sinus (SSS), and a second device is placed in the internal cerebral vein (ICV).

[0012] FIG. 6 illustrates an expandable device positioned in the SSS and a non-expandable device positioned in the ISS.

[0013] FIG. 7 illustrates an example method in which three devices are used to record brain signals, and two device in different vessels are used to direct ultrasound stimulating energy to the target brain region.

[0014] FIG. 8 illustrates a first device, including ultrasound wave detecting and electrical signal detection, placed in the ISS and a second device, including electrodes and ultrasound transducers, placed in the SSS.

[0015] FIG. 9 illustrates an intracranial and intravascular device placed in the ISS.

[0016] FIG. 10 illustrates an example of brain electrical activity via stereo electroencephalogram (EEG) and intravascularly placed devices with sensing electrodes.

[0017] FIG. 11 illustrates another example of brain electrical activity via stereo (EEG) and intravascularly placed devices with sensing electrodes.

[0018] FIG. 12 illustrates an example of transcranial focused ultrasound (tFUS) and transcranial magnetic stimulation (TMS) mapping with direct brain readouts via stereo EEG.

[0019] FIG. 13 illustrates another example pf transcranial focused ultrasound (tFUS) and transcranial magnetic stimulation (TMS) mapping with direct brain readouts via stereo EEG.

[0020] FIG. 14 illustrates an example graft device.

[0021] FIG. 15 illustrates an end view of an intracranial device.

[0022] FIG. 16 illustrates another end view example of an intracranial device.DETAILED DESCRIPTION

[0023] The disclosure describes methods, devices and / or systems that are adapted to provide information about a response to energy delivered to a patient’s brain and / or treat brain disorders without requiring an invasive procedure such as DBS. The disclosure is related to methods that include minimally-invasive delivery of one or more devices (e.g., implants) intracranially and intravascularly, wherein the one or more devices are adapted to sense / record brain activity signals and / or deliver- 3 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 energy to the brain to improve one or more brain disorders. An exemplary advantage of tire approaches herein is that the one or more devices can be used to precisely and responsively deliver energy to brain circuits intravascularly to improve one or more brain disorders / conditions. The devices herein that are positioned within the vasculature of the cranium can be intended to be permanently implantable, temporarily implanted and subsequently removed, or temporarily positioned within the vasculature during an initial patient procedure and removed during tire same procedure. Any of the medical devices herein, regardless of the duration in which it is placed within the intracranial vasculature of an individual, can be referred to herein as a “device.”

[0024] Some methods herein include sensing brain activity signals from one or more target brain regions, and once biomarker signals are detected that are indicative of the onset of or anticipatory of a condition (e.g., urge), the method includes delivering stimulating energy to at least reduce the severity of the condition. The methods, systems and devices herein thus have very broad application in the delivery of energy to targeted regions of the brain to treat a wide variety of conditions that are treatable with delivered energy.

[0025] In alternative methods, the method can include stimulating a region of the brain and recording / sensing brain activity signals from the stimulated region or a different region to understand if the delivered energy had a desirable outcome. For example, the approaches herein can be considered a therapeutic trial to determine one or more regions in an individual’s brain (or where in a group of individuals’ brains) that responds to energy delivery treatment. This approach can be used to detennine how one or more of a person’s brain regions respond to treatment for one or more conditions (e.g., mapping at least a portion of their brain).

[0026] FIG. 1 illustrates a representation of intracranial venous vasculature with larger vessels labeled. FIG. 1 also illustrates exemplary device 10 positioned in a superior sagittal sinus (SSS), exemplary device 12 positioned in an internal cerebral vein, and exemplary’ device 14 positioned in a basal vein of rosenthal (BVR). Devices herein can be positioned in any of the vessels shown, which can depend on the region of the brain targeted for sensing and / or stimulating.

[0027] While exemplary devices are shown in the Figures and discussed herein, any of the devices herein can have a variety of configurations and structural properties. For example, devices herein can be expandable or include an expandable component (e.g., an expandable stent or stent-like device; an inflatable balloon), or they may not be expandable, such as an elongate, non -expandable device (e.g., a “stick” or wire). Devices herein can include a plurality of discrete expandable portions axially spaced but coupled together, such as by an intervening connector (e.g., wire). Any of the expandable devices herein can include a stent or stent-like expandable structure (e.g., an expandable scaffold) that is- 4 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 adapted to be collapsed to a delivery configuration (e.g., within a delivery device such as a guide catheter or sheath) and expandable to an expanded state within the vasculature for use. Any of the expandable devices herein that can be temporarily positioned can include an inflatable structure (e.g., balloon) and a plurality of electrodes and / or ultrasound transducers carried by the inflatable structure, such as a flexible circuit (“flex circuit) carried by a balloon (e.g., similar to concepts in U.S. Pat. 10,350,005).

[0028] The devices herein can include at least one of a plurality of electrodes or a plurality of ultrasound transducers, which can be multi -directional focused ultrasound (fUS) micro-transducers, an example of which is shown in FIG. 2. FIG. 2 illustrates an exemplary device 20 that is adapted to be positioned intravascularly within the cranium and can be used according to any of the methods herein. Device 20 is adapted to be expandable between a collapsed deli ven configuration and an expandable configuration for use, and includes an expandable scaffold structure 22 that includes a plurality of defonnable and elongate elements 21, which together fonn the scaffold 22. The particular scaffold structure 22 of device 20 can have a wide variety of designs, which can be incorporated from tire field of stents or other expandable medical devices. The pattern of scaffold 22, however, if coupled to (directly or indirectly) a plurality of electrodes and / or transducers, needs to reliably expand and maintain the functionality of the electrodes and / or transducers when in use. As shown in this example, both electrodes 24 and micro-transducers 26 are secured to scaffold 22 at locations where a plurality of elongate elements 21 come together or meet, or at least come nearer toward each other even if they don’t connect directly, as shown. Any of tire plurality of ultrasound transducers herein (e.g. transducers 26) coupled to or carried by a common device (e.g., device 20), which together can be referred to as a transducer array. The electrodes and ultrasound transducers herein can individually be coupled to wires that are coupled to an energy delivery device, such as any of the secondary devices herein.

[0029] In some examples, the electrodes and the ultrasound transducers (whether on the same device or separate devices) can be in separate electrical communication (e.g. via one or more wires) with one or more secondary devices. For example, one or more electrode wires (e.g., a recording lead) can be coupled to a secondary device, and one or more transducer wires (e.g., a stimulating lead) can be coupled to the secondary device or a different secondary device.

[0030] In any of the methods or systems herein, a device can include a plurality of electrodes but not any ultrasound transducers, a device can include a plurality of ultrasound transducers but not any electrodes, or a device can include both a plurality of ultrasound transducers and a plurality of electrodes (e.g., device 20).- 5 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006

[0031] Devices herein that include a transducer array can be used to direct focused energy or target the ultrasound energy depending on the brain region is need of energy delivery. For example, a subset of the transducers can be activated depending on where the targeted brain region is relative to the position of the device. In this way, devices herein can direct focused ultrasound stimulating energy to a variety of brain region depending on the need. Devices herein can thus include many ultrasound transducers to facilitate directing focused energy to as many brain regions as possible.

[0032] An exemplary advantage of some methods herein that electrically sense brain activity signals with electrodes (e.g.. electrodes 24) and stimulate brain tissue with ultrasound energy from ultrasound transducers (e.g., transducers 26) is that the ultrasound energy does not create the noise that occurs when stimulating and sensing with electrodes. In use, methods herein can electrically sense (with electrodes) while stimulating with ultrasound energy (from the same or different device) without creating the amount of noise created when electrically stimulating and sensing at the same time. Tire stimulating ultrasound energy does not interfere with the electrode sensing, allowing the two to occur simultaneously.

[0033] In any of the methods of use herein, sensing can occur during at least one of before, during, or after stimulation.

[0034] In methods of use herein, devices can be positioned to be able to record from and / or stimulate the “cingulum area,” a bilateral region of tire brain that includes the "cingulate cortex" and "cingulum bundle." Additionally, even if recording from the cingulum area, the recording can capture signals from engaging distant neurons. For example, recording from the cingulum area can capture brain activity signals from engaging neurons that are distant in the orbitofrontal cortex or ventral striatum that are directly connected to the cingulum area. Similarly, methods herein can record only from a superior frontal gyrus (with a device positioned in the SSS), while also capturing signals from the engagement of neurons in the cingulate cortex that is directly connected to it.

[0035] In some exemplary methods, the nucleus accumbens is targeted, optionally from a device positioned in the BVR. ICV. or ISS. One aspect of the disclosure is electrographic closed-loop ultrasonic stimulation via the basal vein of rosenthal to the nucleus accumbens and adjacent ventral basal ganglia.

[0036] In methods herein, one or more devices, or portions of a system of devices, can be placed in at least one of an SSS, an ISS, an ICV, a BVR, a VG. an STS, a CS, a TS, an SS, an IYV or an OS.

[0037] Any of the devices herein can be in wired communication with a secondary device placed outside of the cranium and which can be adapted to provide power and / or information (uni-directional or bi-directional) with the one or more intravascular devices. FIG. 2 illustrates a DBS system, meant to- 6 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 illustrate a location of a secondary device placed subcutaneously, and which can be in wired or wireless communication with tire devices herein (e.g., wired via jugular vein). Alternatively, a secondary device can be positioned inside the heart (intracardiac) that powers the devices (wireless or wired connection).

[0038] Methods herein can include positioning a single device intravascular and intracranially, wherein the single device can be used for both sensing (e.g., with electrodes) and delivering focused ultrasound energy to stimulate (w ith an array of transducers, wherein the energy can be focused as needed). FIG. 3 represents an exemplary method wherein an expandable stent-like device (e.g., device 20) is positioned in the ISS, and is both recording via electrodes and focusing ultrasound energy to a targeted region of the brain to stimulate the targeted brain tissue with a plurality of ultrasound transducers. As illustrated, stimulation is initiated based on and in response to the iEEG recordings.

[0039] Methods herein can include positioning a plurality of devices intravascular and intracranially, w herein each device is adapted to at least one of sense or stimulate, and wherein each device can include at least one of a plurality of electrodes and a plurality of transducers. For example, one device can record signals and one device can deliver stimulating energy via a transducer array. FIG. 4 illustrates an exemplary method in w hich a stimulating device is positioned in the ISS, and a recording device is positioned in the ISS proximal to the stimulating device, as shown. Any "stimulating device" herein can also include electrodes, and any “recording" device herein can also include a transducer array.

[0040] While FIG. 4 show s a plurality of devices within the same vessel (in this example the ISS), methods herein that include placing a plurality of devices can place the devices in different vessels. For example, FIG. 5 shows a first device placed in the SSS, and a second device placed in the ICV. Both devices are in w ired communication with a secondary devices via the w ired connection as shown. One or both of the devices can be used to direct ultrasound stimulating energy to the brain region of interest as shown, or one of the devices can be primarily for recording. For example, the device in the ICV can be used to record the region of interest due to its proximity, while the device in the SSS, which can include more transducers due to a potentially larger vessel size, can be used to deliver focused energy to the target brain region.

[0041] FIG. 6 illustrates a first expandable device (e.g., device 20) positioned in the SSS and a second non-expandable device (e.g., a stick or wire with electrodes) positioned in the ISS. Both devices are in wired communication with a secondary’ device with the wired communication as shown. In response to recorded signals from the second device in the ISS, the first device in the SSS delivers directed and focused stimulating ultrasound energy to the target brain region, as shown.- 7 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-11006

[0042] FIG. 7 shows aii additional exemplary method in which three devices are used to record brain signals, and two device in different vessels are used to direct ultrasound stimulating energy to the target brain region. In this example, devices in the SSS and ISS are each used to record and stimulate, as shown, while a third device in the ISS is used only in recording brain activity signals, as shown. As shown, the stimulating energy is based on and in response the iEEG recordings.

[0043] External Devices

[0044] Any of the secondary’ devices herein (e.g., chest implantable pulse generators (IPGs)) that can be in wired or wireless communication with one or more devices can also be adapted to communicate with an external device (e.g., physician device), which can optionally be used to power the secondary device (using known transcutaneous power approaches such as induction) and / or provide information to the secondary device. For example, a digital set of instructions (a “prescription”) can be communicated from an external device to the internal system of devices that includes patient specific delivery parameters to effectively target the brain region(s) of interest. For example, based on the location of implanted devices and the target brain region of interest, a digital prescription (optionally personalized for the patient) can be transcutaneously transmitted to the internal secondary device, and yvhich can facilitate activating a subset of the transducers to direct the stimulating energy to the region of the patient’s brain that can best respond to the energy to most effectively treat the disorder / condition. The secondary device can thus be adapted to receive, store, and cause the delivery of electrical signals to the one or more devices to initiate the prescribed stimulation energy to treat the disorder.

[0045] As set forth above, some methods include sensing / recording from brain regions of interest to detect a biomarker of a condition, and in response, delivery stimulating energy to reduce the severity of the condition. Any detectable electrical biomarker can thus be sensed, and based on and in response, direct focused energy to tire brain region of interest.

[0046] Methods herein can include determining an optimal location for the one or more devices (which can be a stimulating and / or sensing device). For example only, a device (optionally expandable) with electrodes can be positioned in a vessel (e.g., an SSS, an ISS), and used to sense brain activity signals from adjacent tissue. If signals can be detected that are indicative of a knoyvn condition, it can be determined that the placement is sufficient to detect the condition in the future, and the device can be left in place (e.g., pennanently) and used to detect the biomarker signals. Tire same device or a different device can be used to apply stimulation energy to the brain region of interest. If signals are not detected that are indicative of the conditions, the device can be moved (optionally re-- 8 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-11006 collapsed if expandable) to a different location within the vessel, or to a different vessel, and the process can be repeated until a satisfactory location is achieved.

[0047] In some uses, it may not be necessary to sense to determine a proper location for a stimulation device. For example, a stimulation device can be intravascularly positioned (e.g., in an SSS) in a patient in a test setting (in-patient) and prompted in a way to trigger the condition (e.g. shown a type of desired food). Upon a craving, for example, directed and controlled energy can be delivered to a variety of brain regions until the craving subsides, and it can be determined that those particular energy delivery parameters work well for tire patient. If tire stimulation device includes a plurality of transducers, for example, those parameters can be stored in tire secondary device, or they can be updated from time to time as needed, such as during a recalibration process.

[0048] Any of tire approaches herein can also be used to help with other technologies. For example only, methods and devices herein can be used to optimize extracranially delivered energy to, for example, titrate tire externally delivered energy, or better direct or guide the extracranially delivered energy. Additionally, for example, the methods herein can be used to guide titration of therapeutics such as Ozempic.

[0049] While the disclosure herein focuses on venous placement, methods herein can be practiced that place one or more device within on the arterial side of the vasculature.

[0050] As set forth above, devices herein can be permanently implanted or they can be removed after initial placement. Expandable devices (e.g., stent, balloons) can be configured to be recaptured within a delivery device (e.g.. a guide catheter) after expansion. This can be useful to remove the device completely, or move it to a different location. Expandable devices can include recapture features that allow it to be grasped to a recapture tool and re-collapsed for removal or repositioning.

[0051] Exemplary access routes to gain access to the cerebral vasculature include the femoral vein, IVC, SVC, jugular vein, or subclavian vein.

[0052] While examples above include devices adapted to record signals with electrodes, devices herein can optionally include piezoelectrical material that adapts the device to detect ultrasound, which can be delivered form a different device that is optionally placed intravascularly. For example, a device herein can comprise a relatively thin flexible wire with piezoelectrical material that can detect ultrasound directly, which can be used to determine how much applied ultrasound energy is reaching the piezoelectrical material. In these examples, the ultrasound detecting device is placed in one vessel and an ultrasound delivery device is placed in a second vessel, and when ultrasound energy is applied from the delivery- device, the ultrasound detecting or sensing device detects ultrasound waves and provides an indicator of how much ultrasound I s detected. Devices configured to detect ultrasound- 9 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 can also, however, include electrodes to sense electrical signals. FIG. 8 illustrates an example in which a device that includes ultrasound wave detecting (e.g., piezoelectrical material) and electrical signal detection is placed in the ISS, and an expandable device with electrodes and ultrasound transducers is placed in the SSS. Both devices are in wired connected with secondary device via wired connections, as shown. Both devices are adapted to sense iEEG, tire SSS device is configured to apply directed ultrasound energy to target brain region, and tire ISS device is adapted to sense ultrasound waves.

[0053] FIG. 9 illustrates an alternative example of an intracranial and intravascular device (which can be any of the devices herein adapted to sense electrical signals) placed in the ISS and adapted to record iEEG of the cingulum area, as well as externally applied energy that is applied based on in response to the sensed brain activity data which in this example is transcranial focused ultrasound to target a particular region of the brain.

[0054] FIG. 10 illustrates an alternative example of recording brain electrical activity via stereo EEG and intravascularly placed devices with sensing electrodes, as well as transcranial focused ultrasound and intravascular ultrasound stimulation using any of tire intravascular devices herein.

[0055] Figs. 11-13 illustrate alternative examples (similar to Fig. 10) of recording brain electrical activity via stereo EEG and intravascularly placed devices with sensing electrodes, as well as transcranial focused ultrasound and intravascular ultrasound stimulation using any of the intravascular devices herein. In Fig. 11, an expandable stent is shown in tire SSS with both electrical recording electrodes, and ultrasound transducers for focused ultrasound stimulation. Fig. 12 illustrates an example of transcranial focused ultrasound (tFU S) and transcranial magnetic stimulation (TMS) mapping with direct brain readouts via stereo EEG. Fig. 13 illustrates another example pf transcranial focused ultrasound (tFUS) and transcranial magnetic stimulation (TMS) mapping with direct brain readouts via stereo EEG.

[0056] In alternative examples, any of the devices herein can comprise a scaffold structure coupled to a graft or substrate member, similar to stent grafts designs, mere examples of which are described in U.S. Pat. No. 11. 285,029, which is fully incorporated by reference herein for all purposes. A graft member can comprise one or more types of material, and can include one or more layers of material. For example only, an inner graft layer can be secured to inner surfaces of a scaffold member, and an outer graft layer can be secured outer surfaces of a scaffold member, such that the scaffold is sandwiched between layers. Alternatively, a first graft layer can be secured to outer scaffold surfaces and a second graft layer (same or different material as first layer) can be secured the first layer outside the first layer. Graft members can be secured to the scaffold using a number of known techniques.- 10 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006

[0057] For devices including a graft / substrate member, the one or more transducers can be secured to an outer surface of the graft member, and / or to the scaffold. Having a graft or substrate member can provide more options for having a larger number of ultrasound transducers on the device, allowing for more brain regions to be targeted with controlled focused energy stimulating delivery. Additionally or alternatively, one or more electrodes can be coupled to an outer surface of the graft member to face outward and sense brain activity signals from adjacent neural tissue from within the vasculature. For systems with multiple devices, one or more devices can be a graft device (that includes a graft member) and one or more devices may not be a graft devices (e.g.. just a scaffold, or just a nonexpandable elongate member).

[0058] Any of the graft devices herein can be adapted to be completely self-expandable (e.g., from within a delivery device such as a guide catheter), completely expandable with a different device (e.g., balloon-expandable), or a combination thereof (e.g., partially self-expandable and then fully expanded with a balloon or other expansion member).

[0059] FIG. 14 illustrates an example of a graft device, which is included in U.S. Pat. No. 11. 285,029, and is incorporated herein to illustrate an exemplary graft member coupled to a scaffold. Devices herein that include electrodes and / or transducers can have a similar construction conceptually, and can include electrodes and / or transducers coupled to an outer surface of the cylindrical graft member and / or scaffold (depending on if the graft covers the outer surface of the scaffold or not).

[0060] Additionally, any of the devices herein can include one or more on-board energy source (e.g., battery) that can be used to power electrodes, transducers, and any other electronic equipment part of the device. On board energy sources can be included in non-expandable devices (e.g., the energy source is carried by and coupled to an elongate device) and expandable devices. If an expandable device does not include a graft or other substrate member, an energy source can be coupled to one or more inner surfaces of a scaffold, for example. An energy source may not be completely rigidly fixed to a scaffold if some relative movement therebetween is needed during expansion / collapse of tire scaffold. Energy sources can be in wired communication with one or electrodes and / or transducers.

[0061] FIG. 15 represents an end view of an intracranial device, which can include one or more electrodes and / or transducers (not shown), and illustrates an exemplary energy source coupled to the device on an inner surface of the device. The intracranial device in FIG. 15 can be in an expanded state within any of the intracranial vessels herein (not shown).

[0062] FIG. 16 represents an end view of an intracranial device, which can include one or more electrodes and / or transducers (not shown), and illustrates an exemplary energy source coupled to the- 11 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-11006 device on an inner surface of the device. FIG. 16 represents a thickness to the device, which can indicate one or more components, such as a scaffold coupled to one or more graft materials.

[0063] The vessel in which the device is to be placed can influence the type of device that is placed. For example, an SSS is generally larger than an ISS, which can allow a device with more components, such as more transducers, including an energy source versus not including an energy source, etc. For example only, a device placed within an SSS can include multiple expandable sections axially spaced apart but coupled with a connector (e.g., a wire), wherein such a design can allow for more flexibility along the length of the entire device compared to having a single continuous scaffold structure. However, and for example only, an ISS, while relatively smaller than an SSS, can be occluded without significant complications to the patient. In such cases, for example, a device with more components (e.g., many transducers, many electrodes, an energy source, etc.) can be placed in an ISS when there is an acceptable level of risk of occlusion.

[0064] Additionally, and without being limiting to location, the uniqueness of the anatomical relationship between the ISS and the bilateral cingulum area can provide significant benefits for recording from and / or stimulating to the cingulum area from the ISS. For example, intracranial device placement in the ISS can facilitate more reliable recording / sensing from the cingulate due to the close proximity of the ISS and surrounding cingulum area, as discussed herein. Additionally or alternatively, and while other vessel placement is possible, intracranial device placement in the ISS can, in some applications, facilitate more effective stimulation to tire cingulum area due to tire close proximity of the ISS and tire cingulum area.

[0065] Additionally, intracranial devices herein can be adapted to deliver one or more therapeutic and / or diagnostic agents from within the vessel. For example, one or more components of the device can be impregnated with agents, either an outer surface of a scaffold and / or a graft member, similar to drug eluting stents and balloons. For example only, antithrombotic drugs can be delivered to the vessel via the device, which can help reduce tire risk of or treat a thrombosis following implant placement.

[0066] Aspects

[0067] The following Aspects are illustrative only and do not serve to limit the scope of the present disclosure or the appended claims. Any part or parts of any one or more Aspects can be combined with any part or parts of any one or more other Aspects.

[0068] Aspect 1. A method of intracranially and intravascularly delivering energy to the brain of a subject with one or more medical conditions, comprising: intravascularly delivering a device to an intracranial vein adjacent brain tissue; intravascularly and intracranially sensing brain activity signals- 12 of 24 -103241.007505X4926-8410-8914.1103241.007505 / 25-11006 from the brain tissue: and intravascularly and intracranially delivering energy to the brain tissue to treat the one or more conditions.

[0069] Aspect 2. The method of Aspect 1, wherein sensing brain activity signals and delivering energy to the brain tissue are performed with at least two different devices, wherein the at least two different devices are in communication with a common energy device.

[0070] Aspect 3. The method of Aspect 2, wherein a first device of the at least two different devices is placed in a first vein and a second device of the at least two different devices is placed in a second vein.

[0071] Aspect 4. The method of Aspect 2, wherein a first device of the at least two different devices and a second device of the at least two different devices are placed in the same vein.

[0072] Aspect 5. The method of any one of Aspects 1-4, wherein the sensing and delivering steps are perforated with a common device, wherein tire common device comprises an expandable device, and w herein the expandable device comprises a plurality of electrodes and a plurality of ultrasound transducers coupled to a scaffold of the expandable device.

[0073] Aspect 6. The method of Aspect 1, further comprising determining whether an energy deliver}’ device is in an adequate position within a vein, and if the energy deliver}' device is not in the adequate position, moving tire energy deliver}’ device prior to the delivering energy step.

[0074] Aspect 7. Tire method of any one of Aspects 1-6, further comprising any one or more steps of any of Aspects 8 - 29.

[0075] Aspect 8. A method of intracranially and intravascularly delivering energy to neural tissue of a subject with one or more conditions to treat one or more conditions, comprising: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, the device including an expandable scaffold, a plurality of electrodes coupled to the expandable scaffold, and a plurality of ultrasound transducers coupled to the expandable scaffold, wherein tire plurality of ultrasound transducers are distributed about the scaffold; intravascularly and intracranially sensing brain activit signals from the brain tissue with the plurality of electrodes; and based on and in response to the sensed brain activity signals, intravascularly and intracranially delivering energy to brain tissue with the plurality of ultrasound transducers to treat the one or more conditions.

[0076] Aspect 9. The method of Aspect 8, w herein intravascularly delivering the device to an intracranial vein comprises delivering the device to one of a superior sagittal sinus (SSS), an inferior sagittal sinus (ISS), an internal cerebral vein (ICV), a basal vein of Rosenthal (BVR), a vein of Galen (VG), or a straight sinus (STS).- 13 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006

[0077] Aspect 10. The method of any one of Aspects 8-9, further comprising communicating at least one of the sensed brain activity signals or information indicative of the sensed brain activity signals, with wired or wireless communication, to a processing device configured to process the signals or the information indicative of the sensed brain activity signals.

[0078] Aspect 11. The method of Aspect 10, wherein the processing device is subcutaneously implanted, optionally an implantable pulse generator (IPG).

[0079] Aspect 12. Hie method of Aspect 0, wherein the processing device is extracranial.

[0080] Aspect 13. The method of any one of Aspects 8-12, further comprising processing the sensed brain activity signals or information indicative of the sensed brain activity signals, and wherein delivering the energy is based on the processing step.

[0081] Aspect 14. The method of any one of Aspects 8-13, further comprising processing the sensed brain activity signals or information indicative of the sensed brain activity signals, and determining a patient state that comprises one or more of an impulse control state, a pain state, and a mood disorder state.

[0082] Aspect 15. The method of Aspect 14, wherein delivering the energy is in response to and based on the determined patient state.

[0083] Aspect 16. The method of any one of Aspects 8-15, wherein sensing brain activity signals from tire neural tissue with tire plurality of electrodes comprises sensing cingulum area signals with the plurality of electrodes.

[0084] Aspect 17. The method of any one of Aspects 8-16, wherein sensing brain activity signals from the neural tissue with the plurality of electrodes comprises sensing brain activity signals from the anterior cingulate cortex (ACC) with the plurality of electrodes.

[0085] Aspect 18. The method of any one of Aspects 8-17, wherein delivering energy to brain tissue with the plurality of ultrasound transducers comprises delivering focused ultrasound energy to brain tissue with at least a subset of the plurality of ultrasound transducers.

[0086] Aspect 19. The method of any one of Aspects 8-18, wherein delivering energy to brain tissue with the plurality of ultrasound transducers comprises delivering energy to the cingulate cortex.

[0087] Aspect 20. The method of any one of Aspects 8-19, wherein delivering the device comprises delivering the device to a basal vein of rosenthal (BVR), and wherein delivering energy comprises delivering energy to a nucleus accumbens (NA).

[0088] Aspect 21. Tire method of any one of Aspects 8-20, further comprising detennining, based on the sensed brain activity signals, if the device is properly placed for the delivering energy step.- 14 of 24 -103241.007505X4926-8410-8914.1103241.007505 / 25-11006

[0089] Aspect 22. The method of any one of Aspects 8-21, wherein delivering energy to the brain tissue with the plurality of ultrasound transducers comprises delivering energy to the brain tissue with the device in a plurality of different intravascular positions.

[0090] Aspect 23. The method of any one of Aspects 8-22, wherein, based on and in response to the sensed brain activity signals, intravascularly and intracranially delivering energy comprises controlling the direction of energy delivered from the plurality of transducers.

[0091] Aspect 24. Tire method of any one of Aspects 8-23, wherein sensing occurs during at least one of: before, during, or after delivering energy.

[0092] Aspect 25. The method of any one of Aspects 8-24, wherein sensing with the plurality of electrodes occurs while delivering energy to brain tissue with the plurality of ultrasound transducers.

[0093] Aspect 26. The method of any one of Aspects 8-25, wherein the device is at least one of: recapturable or re-collapsible within a delivery device.

[0094] Aspect 27. Tire method of any one of Aspects 8-26, wherein intravascularly delivering the device to the intracranial vein comprises delivering tire device to an inferior sagittal sinus (ISS), and wherein the device can release an anticoagulation agent following thrombosis.

[0095] Aspect 28. The method of any one of Aspects 8-27, further comprising providing power to the device from a subcutaneously positioned implant in wired or wireless communication with tire device.

[0096] Aspect 29. The method of any one of Aspects 8-28, wherein intravascularly delivering the device to the intracranial vein comprises utilizing one or more of: a femoral vein approach; a jugular approach, or a subclavian approach.

[0097] Aspect 30. A method of delivering energy to neural tissue of a subject with one or more conditions to treat the one or more conditions, comprising: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, wherein the device comprises an expandable scaffold and a plurality of electrodes; intravascularly and intracranially sensing brain activity signals from brain tissue with the plurality of electrodes; and based on and in response to the intravascularly and intracranially sensed brain activity signals, extracranially delivering energy to brain tissue to treat the one or more conditions.

[0098] Aspect 31. The method of Aspect 30, wherein extracranially delivering energy comprises at least one of transcranial focused ultrasound (tFUS) or transcranial magnetic stimulation (TMS).

[0099] Aspect 32. An expandable medical device, comprising: an expandable and collapsible stent; a plurality of electrodes coupled to the stent; and a plurality of ultrasound transducers coupled to the stent.- 15 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006

[0100] Aspect 33. The device of Aspect 32, further comprising a plurality of leads coupled to the device and coupled to an energy delivery device.

[0101] Aspect 34. The device of any one of Aspects 32-33, further comprising a connection to an energy del ivory device, wherein the connection supplies energy to any subset of the plurality of ultrasound transducers.

[0102] Aspect 35. The device of any one of Aspects 32-34, wherein tire plurality of ultrasound transducers are situated about tire scaffold to allow for directional or targeted ultrasound energy to be applied with the device.

[0103] Aspect 36. A system for energy delivery, comprising: a first device comprising a plurality of electrodes; a second device comprising a plurality of ultrasound transducers; and a processing device in communication with tire first device and tire second device, wherein the processing device is configured to receive sensed signals from the plurality of electrodes, and wherein the processing device is configured to deliver energy to the plurality of ultrasound transducers to cause focused therapeutic ultrasound energy to be delivered from the plurality of ultrasound transducers to treat one or more conditions treatable with the application of ultrasound energy to brain tissue.- 16 of 24 -103241.00750514926-8410-8914.1

Claims

103241.007505 / 25-11006What is Claimed:

1. A method of intracranially and intravascularly delivering energy to the brain of a subject with one or more medical conditions, comprising: intravascularly delivering a device to an intracranial vein adjacent brain tissue: intravascularly and intracranially sensing brain activity signals from the brain tissue; and intravascularly and intracranially delivering energy to the brain tissue to treat tire one or more conditions.

2. The method of claim 1, wherein sensing brain activity signals and delivering energy to the brain tissue are performed with at least two different devices, wherein the at least two different devices are in communication with a common energy device.

3. The method of claim 2, wherein a first device of the at least two different devices is placed in a first vein and a second device of the at least two different devices is placed in a second vein.

4. The method of claim 2, wherein a first device of the at least two different devices and a second device of the at least two different devices are placed in the same vein.

5. The method of claim 1, wherein the sensing and delivering steps are performed with a common device, wherein the common device comprises an expandable device, and wherein the expandable device comprises a plurality of electrodes and a plurality of ultrasound transducers coupled to a scaffold of the expandable device.

6. The method of claim 1, further comprising determining whether an energy delivery device is in an adequate position within a vein, and if the energy delivery device is not in the adequate position, moving the energy delivery device prior to the delivering energy step.

7. The method of claim 1, further comprising any one or more steps of any of claims 8 - 29.- 17 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-110068. A method of intracranially and intravascularly delivering energy to neural tissue of a subject with one or more conditions to treat one or more conditions, comprising: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, the device including an expandable scaffold, a plurality of electrodes coupled to the expandable scaffold, and a plurality of ultrasound transducers coupled to the expandable scaffold, wherein the plurality of ultrasound transducers are distributed about the scaffold; intravascularly and intracranially sensing brain activity signals from the brain tissue with the plurality of electrodes; and based on and in response to the sensed brain activity signals, intravascularly and intracranially delivering energy to brain tissue with the plurality of ultrasound transducers to treat tire one or more conditions.

9. The method of claim 8, wherein intravascularly delivering the device to an intracranial vein comprises delivering the device to one of a superior sagittal sinus (SSS), an inferior sagittal sinus (IS S), an internal cerebral vein (ICV), a basal vein of Rosenthal (BVR), a vein of Galen (VG), or a straight sinus (STS).

10. The method of claim 8, further comprising communicating at least one of the sensed brain activity signals or information indicative of the sensed brain activity signals, with wired or wireless communication, to a processing device configured to process the signals or the information indicative of the sensed brain activity signals.

11. The method of claim 10. wherein the processing device is subcutaneously implanted, optionally an implantable pulse generator (IPG).

12. The method of claim 10, wherein the processing device is extracranial.

13. The method of claim 8, further comprising processing the sensed brain activity signals or information indicative of the sensed brain activity signals, and wherein delivering the energy is based on the processing step.- 18 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-1100614. The method of claim 8, further comprising processing the sensed brain activity signals or information indicative of the sensed brain activity signals, and determining a patient state that comprises one or more of an impulse control state , a pain state, and a mood disorder state.

15. The method of claim 14, wherein delivering the energy is in response to and based on the detennined patient state.

16. The method of claim 8, wherein sensing brain activity signals from the neural tissue with the plurality of electrodes comprises sensing cingulum area signals with the plurality of electrodes.

17. The method of claim 8, wherein sensing brain activity signals from the neural tissue with the plurality of electrodes comprises sensing brain activity signals from the anterior cingulate cortex (ACC) with the plurality of electrodes.

18. The method of claim 8, wherein delivering energy to brain tissue with the plurality of ultrasound transducers comprises delivering focused ultrasound energy to brain tissue with at least a subset of the plurality of ultrasound transducers.

19. The method of claim 8, wherein delivering energy to brain tissue with the plurality' of ultrasound transducers comprises delivering energy to the cingulate cortex.

20. Tire method of claim 8, wherein delivering the device comprises delivering tire device to a basal vein of rosenthal (BVR), and wherein delivering energy comprises delivering energy to a nucleus accumbens (NA).21 . The method of claim 8, further comprising determining, based on the sensed brain activity signals, if the device is properly placed for the delivering energy step.

22. The method of claim 8, wherein delivering energy to the brain tissue with the plurality of ultrasound transducers comprises delivering energy to the brain tissue with tire device in a plurality of different intravascular positions.- 19 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-1100623. The method of claim 8, wherein, based on and in response to the sensed brain activity signals, intravascularly and intracranially delivering energy comprises controlling the direction of energy delivered from the plurality of transducers.

24. The method of claim 8, wherein sensing occurs during at least one of: before, during, or after delivering energy.

25. The method of claim 8, wherein sensing with the plurality of electrodes occurs while delivering energy to brain tissue with the plurality of ultrasound transducers.

26. The method of claim 8, wherein the device is at least one of: recapturable or re-collapsible within a delivery device.

27. The method of claim 8, wherein intravascularly delivering the device to the intracranial vein comprises delivering the device to an inferior sagittal sinus (ISS), and wherein the device can release an anticoagulation agent following thrombosis.

28. The method of claim 8, further comprising providing power to the device from a subcutaneously positioned implant in wired or wireless communication with the device.

29. The method of claim 8, wherein intravascularly delivering the device to the intracranial vein comprises utilizing one or more of: a femoral vein approach; a jugular approach, or a subclavian approach.

30. A method of delivering energy to neural tissue of a subject with one or more conditions to treat the one or more conditions, comprising: intravascularly delivering a device to an intracranial vein and adjacent brain tissue, wherein the device comprises an expandable scaffold and a plurality of electrodes; intravascularly and intracranially sensing brain activity signals from brain tissue with the plurality of electrodes; and- 20 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-11006 based on and in response to the intravascularly and intracranially sensed brain activity signals, extracranially delivering energy to brain tissue to treat the one or more conditions.31 . The method of claim 30, wherein extracranially delivering energy comprises at least one of transcranial focused ultrasound (tFUS) or transcranial magnetic stimulation (TMS).

32. An expandable medical device, comprising: an expandable and collapsible stent; a plurality of electrodes coupled to tire stent; and a plurality of ultrasound transducers coupled to the stent.

33. The device of claim 32, further comprising a plurality of leads coupled to the device and coupled to an energy delivery device.

34. The device of claim 32, further comprising a connection to an energy delivery device, wherein tire connection supplies energy to any subset of the plurality of ultrasound transducers.

35. The device of claim 32, wherein the plurality of ultrasound transducers are situated about the scaffold to allow for directional or targeted ultrasound energy to be applied with the device.

36. A system for energy delivery, comprising: a first device comprising a plurality of electrodes; a second device comprising a plurality of ultrasound transducers; and a processing device in communication with tire first device and the second device, wherein tire processing device is configured to receive sensed signals from the plurality of electrodes, and wherein the processing device is configured to deliver energy to the plurality of ultrasound transducers to cause- 21 of 24 -103241.00750514926-8410-8914.1103241.007505 / 25-11006 focused therapeutic ultrasound energy to be delivered from the plurality of ultrasound transducers to treat one or more conditions treatable with the application of ultrasound energy to brain tissue.- 22 of 24 -103241.007505\4926-8410-8914.1103241.007505 / 25-1100637. A system for energy delivery, comprising: an expandable device comprising an expandable scaffold, a plurality of electrodes, and a plurality of ultrasound transducers; and a processing device in communication with the expandable device, wherein the processing device is configured to receive sensed signals from the plurality of electrodes, and configured to deliver energy to the plurality of ultrasound transducers to cause focused therapeutic ultrasound energy to be delivered from the plurality of ultrasound transducers to treat one or more conditions treatable with the application of ultrasound energy to brain tissue.- 23 of 24 -103241.00750514926-8410-8914.1

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