Neural stimulation system and methodPriority statement
This patent application claims priority from U.S. provisional patent application No. 63/371,496, entitled "NEUROSTIMULATION SYSTEMS AND METHODS," filed on 8.15 of 2022, which is incorporated herein by reference in its entirety.
Incorporated by reference
All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Background
Brain electrical stimulation has proven to be a potentially effective treatment for many brain diseases, including epilepsy, migraine, fibromyalgia, major depression, stroke rehabilitation, and parkinson's disease. External stimuli tend to be non-focused and direct cortical stimulation is often highly invasive, involving craniotomy or drilling holes in the skull to target specific cortical locations. It would be beneficial to find a brain stimulation solution that provides a surgical procedure that targets cortical stimulation without the need to penetrate the skull.
Brain electrical stimulation can be achieved in several ways. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses a coil to deliver a series of high-energy magnetic pulses to the brain, thereby inducing current flow in the cortex below the coil. rTMS has been shown to be effective in the treatment of major depressive disorder and other psychotic disorders. However, it is not easily guided to a specific location and involves large, expensive equipment to generate large current pulses to the coil. rTMS is not portable and requires a treatment administrator to provide treatment to the patient.
Transcranial direct current stimulation (tDCS) uses electrodes outside the head to deliver a small amount of current to the brain. tDCS was originally used for stroke recovery and has shown promise in treating some mental disorders and improving cognition. Electrodes are placed on the skin surface outside the subject's head near the region of interest for stimulation. Most of the current is split between the electrodes, as the skull is a very effective electrical insulator. However, a portion of the current does cause current flow in the brain, which may increase or decrease neuronal excitability and alter brain function. The exact method of action is not known. the tDCS amperage is limited by the excitability of the nerves in the scalp, which can lead to patient discomfort if the current setting is too high.
Vagal stimulation includes electrically stimulating the vagus nerve in the neck of the patient. This can be accomplished by using electrodes on the skin, which may create a painful sensation in the patient, or by surgically implanting the electrodes near the vagus nerve, which typically implants the power source elsewhere in the body. This involves an important surgical procedure and has shown efficacy in the treatment of epilepsy and depression.
Deep Brain Stimulation (DBS) uses electrodes implanted bilaterally and placed in the basal ganglia, cerebellum, anterior main nucleus, central middle nucleus, caudate nucleus, thalamus or subthalamic region. Stimulation may also be delivered subcortical. The delivery of stimulation sequences is useful in the treatment of many diseases including epilepsy, parkinson's disease, and major depressive disorder. DBS is often a very invasive procedure requiring a long lead to penetrate the skull with multiple electrodes near the tip. This procedure is considered a major procedure and is not generally used unless other methods have been used up.
Direct Cortical Stimulation (DCS) is similar to DBS except that the leads are located on the cortical surface, either subdural or extradurally. The electrodes are secured in place using sutures. Such techniques typically involve removing a portion of the skull to access the cortical surface and, possibly, make room for a power source. DCS has been shown to have efficacy in the treatment of epilepsy and neuropathic pain. (Shanechi et al, 2013) describes a brain-computer interface that uses EEG to automatically titrate medications during medication-induced coma. (Liu et al, 2006) automatically adjusts anesthetic during surgery using the electroencephalogram Bispectral Index (BIS) calculated from EEG. ASPECT MEDICAL the process of the preparation of the pharmaceutical composition, inc. company is to develop for the device of the application. In addition DRAGER MEDICAL, inc. An aeus (Zeus) for closed-loop anesthetic ventilation was developed. (Doufas et al, 2003) use an automated response test to optimize propofol administration during conscious sedation. Phillips (US 9,872,996, US10,780,286) use a subcutaneous pulse generator and conductive paths through the skull at multiple locations to create a current loop. The Phillips method and apparatus still involve at least two boreholes in the skull.
Approximately 40% of untreated aneurysms eventually rupture. Rupture may be prevented by a technique called coil embolization (embolization), which prevents blood from entering the aneurysm. However, up to 5% of coil-embolized aneurysms may still rupture. Mortality from aneurysmal subarachnoid hemorrhage (aSAH) is 40% -50%, with the daily lives of most survivors relying on others. Late cerebral ischemia (DCI) is the initial bleeding event after rupture of a cerebral aneurysm, which is one of the most important causes of death and poor neurological prognosis. Nervous system monitoring is critical for early DCI detection and intervention. Drug-induced hypertension reversed the existing neurological deficit in 70% of patients by early discovery of DCI (PRESENTING DEFICIT). Clinical examination and intermittent transcranial doppler ultrasound and CT are most commonly used to detect DCI, but they rely on the patient to visit a clinic and reserve valuable resources, thereby significantly delaying the response.
SUMMARY
There is provided a device for electrically stimulating a brain of a subject, the device comprising a housing adapted for implantation against a skull of the subject, a first electrode disposed on or in the housing, a probe coupled to the housing and configured to extend through a borehole in the skull into the brain of the subject, a second electrode disposed on the probe and configured to deliver electrical stimulation to a target area of the brain and to sense electrical signals of the brain, and electronics disposed in the housing and configured to generate electrical pulses, initiate EEG recording of the brain of the subject, and communicate with an external device, wherein the device is configured to record EEG signals of the brain in response to an EEG recording request from the external device.
In one aspect, the probe is flexible.
In some aspects, the apparatus includes an insulating seal configured to fill a space between the borehole and the probe. In one aspect, the insulating seal prevents fluid flow and current flow around the intracranial electrode.
In some aspects, the first electrode comprises a ring electrode. In some aspects, the ring electrode is integrated into the housing.
In one aspect, the electronic device is configured to generate a current pulse between the first electrode and the second electrode.
In one aspect, the current pulse is configured to follow a path from the second electrode, through the target area, through a conductive path at a location in the skull spaced from the burr hole, and under the scalp to the first electrode.
In some aspects, the electronics are further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity over a Delta (Delta) frequency range of approximately 1-4 Hz.
In other aspects, analyzing the EEG signal further includes identifying reduced Alpha activity in an Alpha (Alpha) frequency range of approximately 8-13 Hz.
In one aspect, the device is configured to wirelessly transmit the EEG signals to an external device.
In some aspects, the external device is further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.
In another aspect, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
In some aspects, the device is configured to wirelessly transmit the EEG signals to the cloud computing device.
In one aspect, the cloud computing device is further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.
In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
There is also provided a system comprising two or more devices according to claim 1.
In some aspects, the two or more devices are configured to collectively record EEG signals of the brain of the subject in response to an EEG recording request from an external device.
There is provided a system for electrically stimulating a brain of a subject, comprising a plurality of implantable neurostimulators configured for implantation within the subject, each of the implantable neurostimulators comprising, a housing adapted for implantation against a skull of the subject, a first electrode disposed on or in the housing, a probe coupled to the housing and configured to extend through a borehole in the skull into the brain of the subject, a second electrode disposed on the probe and configured to deliver electrical stimulation to a target area of the brain and to sense electrical signals of the brain, and electronics disposed in the housing and configured to generate electrical pulses, initiate EEG recording of the brain of the subject, and communicate with an external device, wherein the system is configured to record EEG signals of the brain with the plurality of implantable neurostimulators in response to an EEG recording request from the external device.
In one aspect, the probe is flexible.
In some aspects, each stimulator of the system includes an insulating seal configured to fill a space between the borehole and the probe. In one aspect, the insulating seal prevents fluid flow and current flow around the intracranial electrode.
In some aspects, the first electrode comprises a ring electrode. In some aspects, the ring electrode is integrated into the housing.
In one aspect, the electronic device is configured to generate a current pulse between the first electrode and the second electrode.
In one aspect, the current pulse is configured to follow a path from the second electrode, through the target area, through a conductive path at a location in the skull spaced from the burr hole, and under the scalp to the first electrode.
In some aspects, the electronics are further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.
In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
In one aspect, the system is configured to wirelessly transmit the EEG signals to an external device.
In some aspects, the external device is further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.
In another aspect, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
In some aspects, the system is configured to wirelessly transmit the EEG signals to the cloud computing device.
In one aspect, the cloud computing device is further configured to analyze the EEG signals to identify cerebral hemorrhage in the target area.
In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.
In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
A method of monitoring an aneurysm in a brain of a subject is provided comprising initiating EEG recordings in one or more implanted neurostimulator devices with an external device, analyzing the EEG recordings to identify cerebral hemorrhage in the brain, and indicating to the subject or medical provider that cerebral hemorrhage has been identified.
In some aspects, one or more neurostimulator devices are implanted into the brain of the subject prior to the initiating step.
In some aspects, the method includes transmitting the EEG recording from the one or more implanted neurostimulator devices to a remote server.
In one aspect, the analyzing step is performed in a remote server.
In another aspect, the method includes generating a report regarding the analyzed EEG and transmitting the report to a medical provider of the subject.
In one aspect, EEG recording is initiated by a smart phone, tablet, or PC.
In some examples, the analyzing step is performed locally on one or more implanted neurostimulator devices.
In one example, analyzing the EEG record further includes identifying increased slow wave activity within a delta frequency range of approximately 1-4 Hz.
In another example, analyzing the EEG record further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.
In another example, the method includes providing electrical stimulation to the brain with one or more implanted neurostimulator devices.
Brief Description of Drawings
Fig. 1 shows a neurostimulator device.
Fig. 2A-2B show EEG recordings of a subject with an aneurysm.
Fig. 3 is a diagram showing one or more neurostimulators implanted near an aneurysm.
Fig. 4A-4E illustrate a method of monitoring an aneurysm using one or more implanted neurostimulators.
Fig. 5A-5B show a series of EEG recordings of a subject with an aneurysm.
Detailed Description
While certain embodiments have been provided and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It should be understood that various alternatives to the embodiments described herein may be employed and are part of the invention described herein.
The present disclosure provides a minimally invasive solution to on-demand cortical EEG recording. Quantitative EEG (qEEG) analysis provides evidence of ischemic events and can be detected using automated machine learning algorithms. Ischemia can lead to an increase in slow wave activity and a decrease in alpha power in the infarct zone.
Fig. 1 shows an embodiment in which a neurostimulator device 104 is implanted under a scalp 101 of a subject and includes a housing 110, a probe-shaped intracranial lower electrode 106 inserted into a borehole in a skull 102, and a subcutaneous ring electrode 105 disposed around the housing 110 or integrated into the housing 110. In one embodiment, the subcoranial electrode 106 may comprise a screw adapted to be screwed into the skull of the subject. The system may further comprise an electrically insulating seal 111, the electrically insulating seal 111 being configured to fill a space between the device and an inner wall of the borehole, which prevents fluid flow and current flow around the intracranial electrode. The housing 110 may be configured to rest on the surface of the skull and may include a current or voltage pulse generator to generate a current pulse between the subcutaneous electrode and the intracranial electrode. Due to the high impedance of the skull 102, most of the current is forced to follow a path 107, which path 107 proceeds from the lower skull electrode through the target area 112 of the brain 103, through the conductive path 108 in the skull at a location separate from the burr hole, and back to the subcutaneous ring electrode 105 along a path 109 under the scalp.
In one embodiment, the device 104 may include electronics, such as a voltage or current pulse generator, configured to generate a current waveform between the intracranial electrode 106 and the subcutaneous ring electrode 105. The device may also include a power source such as a battery or capacitor, or alternatively may be externally powered using wireless power transfer (e.g., inductive coupling). The electronics may also include one or more processors, microcontrollers, or CPUs configured to control the operation of the device and process and/or evaluate the data sensed by the electrodes. In some embodiments, the electronics can further include a memory configured to store recorded data and/or instructions related to the operation of the device and/or sensed parameters of the patient (e.g., EEG). For example, the electronics may be disposed or positioned within the housing 110. In some embodiments, the electronics are located external to the device and the subject. In these embodiments, the current pulses may be generated ex vivo, wherein the percutaneous leads transmit the current pulses to the subcutaneous/intracranial electrodes. The electronics may further include wireless communication electronics to facilitate communication between the neurostimulator device and an external device. In some embodiments, the external device may include a smart phone, a computer, a tablet computer, or the like. In some embodiments, the external device may be configured to control operation of the neurostimulator device. For example, in one embodiment, a smart phone, tablet, or pc may be configured to turn on or off the function of the neurostimulator device, such as initiating EEG recording or stimulation therapy.
The device may be configured to record an EEG and automatically determine the natural frequency from the EEG record and specify pulse frequency, pulse amplitude, pulse shape, pulse width or pulse duty cycle, among other parameters. The recorded EEG may also be transmitted wirelessly to an external module, such as a mobile device running a software application that determines the natural frequency and specifies pulse frequency, pulse amplitude, pulse shape, pulse width or pulse duty cycle, as well as other parameters, and transmits the parameters to the device.
Fig. 2A shows EEG power distribution over multiple frequency ranges for a patient with local cerebral hemorrhage in the left posterior region, as shown. The frequency ranges may include a delta frequency range (1-4 Hz), a theta frequency range (4-8 Hz), an alpha frequency range (8-13 Hz), and a beta frequency range (13-25 Hz). As shown, the EEG of the brain indicates an increase in slow wave activity at cerebral hemorrhage locations in the delta frequency range (1-4 Hz) and a decrease in alpha activity in the alpha frequency range (8-13 Hz), as indicated by reference numerals 214 and 216, respectively. The devices of the present disclosure may be configured to identify areas of the brain where slow wave activity increases in the delta frequency range and/or alpha activity decreases in the alpha frequency range to identify cerebral hemorrhage and/or other traumatic brain events.
Fig. 2B shows EEG recordings of the same patient taken at multiple locations within the brain, including locations FP1、FP2、F3、F4、F7、F8、FZ、CZ、C3、C4、T3、T4、T5、T6、PZ、P3、P4、O1 and O2. Again, this detailed EEG plot shows a decrease in alpha power and an increase in delta/theta power in the area of cerebral hemorrhage injury (e.g., in the left posterior region of the brain).
Referring to fig. 3, one or more neurostimulator devices 104 (such as the neurostimulator device 104 of fig. 1) may be positioned above or near an aneurysm 112 in a patient's brain. By positioning the neurostimulator device precisely near the aneurysm, the device is able to record as high quality EEG as possible just at the cerebral cortex. In some implementations, only a single neurostimulator device 104 is placed near the aneurysm. In other embodiments, a plurality of neurostimulator devices are placed near the aneurysm. The devices may each be individually configured to record EEG signals of the brain. In some embodiments, the devices may collectively or cooperatively collect and record EEG signals from the brain.
Fig. 4A-4E illustrate a general sequence of events including implantation and use of one or more neurostimulator devices for aneurysm monitoring. The procedure may be used with patients having a history or risk of aneurysms or other brain events. Referring to fig. 4A, a surgeon or other medical provider may implant a neurostimulator device into the patient's brain at a location that is appropriate for an aneurysm. The procedure may be a simple surgical procedure, for example, for 20 minutes or less. In some embodiments, implantation may be performed at an outpatient site. In some embodiments, the neurostimulator may be implanted such that the probe-shaped intracranial electrode (from fig. 1) is inserted into a burr hole in the skull, and the subcutaneous ring electrode and/or housing is positioned against the skull and under the scalp.
Referring to fig. 4B, at some time after implantation, the patient may begin to experience symptoms of an aneurysm leaking or rupture. For example, the patient may begin to feel symptoms associated with rupture of the aneurysm, including neck stiffness, sleepiness, confusion, dizziness, balance problems, difficulty speaking, weakness in the arms or legs, or lack of sensation, etc.
Referring to fig. 4C, the patient may initiate EEG recordings in one or more implanted neurostimulator devices 104. In one example, the EEG recording may be initiated wirelessly via an external electronic device 118 (such as a smart phone, tablet computer, or pc). In other embodiments, the patient may initiate EEG recording by interacting directly with the neurostimulator device (e.g., by pressing a button on the device or on hardware or a lead extending from the device to another location on the patient's body). Once activated, the one or more implanted neurostimulators may be configured to record the EEG of the patient's brain. The EEG may be recorded for a predetermined period of time. In some examples, the recorded time may be customized by a medical provider or user, such as with an external electronic device.
In fig. 4D, the recorded EEG may be transmitted wirelessly from the implanted device itself or from an external device (e.g., a smart phone, tablet, or pc) to a remote or cloud-based server 120 or another computing system 122. The remote server may include one or more processors configured to automatically analyze the recorded EEG using one or more algorithms, including machine learning algorithms, to detect slow waves in the affected area and generate a report. The report may be, for example, an electronic report that includes details of the EEG recording and/or instructions or subsequent steps to be performed by the patient or medical provider. In some embodiments, the recorded EEG may be analyzed directly on the implanted stimulator, or alternatively in an external device of the patient.
In fig. 4E, the report may be transmitted to a medical clinic 124 or physician associated with the patient. For example, the transmission to the medical clinic 124 may include one or more computers, smartphones, or tablets of the medical clinic.
If analysis of the recorded EEG indicates that a breach or leak has occurred, an alert may be raised to the clinic, medical provider, and/or patient. The clinic and/or medical provider may be instructed to contact the patient to immediately assess and focus on ruptured or leaking aneurysms.
In some embodiments, the implanted neurostimulator device may be adapted and configured to immediately provide stimulation therapy to the area of the ruptured or leaky aneurysm in response to EEG analysis or electronic reporting. The implanted devices are not only ideally positioned to record the EEG associated with the aneurysm, but they are also optimally positioned within the brain to potentially treat the aneurysm with stimulation therapy. Thus, in some embodiments, stimulation may be initiated manually or automatically in response to EEG recording and analysis identifying a ruptured or leaky aneurysm. In some embodiments, the patient may initiate the treatment, such as through an external device (e.g., smart phone, tablet, pc). In other embodiments, the medical provider may remotely initiate treatment after reviewing the report of the EEG. Alternatively, the system may be configured to automatically initiate treatment in response to identifying a ruptured or leaky aneurysm.
Fig. 5A shows a series of EEG recordings with an implanted neurostimulator over a period of time in a patient with local cerebral hemorrhage in the left posterior region (as in fig. 2A). In this example, three EEG recordings occur over the course of about 6 weeks. During this time, stimulation therapy was provided to the patient using the implanted neurostimulators described herein, and follow-up and EEG recordings showed improvements in speech, aggressiveness (motivation), sleep, and sensory improvement. Fig. 5B is a detailed EEG illustration showing improved alpha activity throughout the area. Slow wave activity is significantly reduced compared to normal rhythmic alpha waves.
When a feature or element is referred to herein as being "on" another feature or element, it can be directly on the other feature or element or intervening features or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, there are no intervening features or elements present. It will also be understood that when a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it can be directly connected, attached, or coupled to the other feature or element, or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected," "directly attached," or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or illustrated with respect to one embodiment, the features and elements so described or illustrated may be applied to other embodiments. Those skilled in the art will also recognize that a structure or feature disposed with reference to "adjacent" another feature may have portions that overlap or underlie the adjacent feature.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and/or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items, and may be abbreviated as "/".
Spatially relative terms, such as "under", "below", "lower", "over", "upper", and the like, may be used herein for ease of description to describe one element or feature's relationship to another element or feature as illustrated in the figures. It will be understood that spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the exemplary term "below" may encompass both an orientation of "above" and "below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, unless specifically stated otherwise, the terms "upward", "downward", "vertical", "horizontal", etc. are used herein for purposes of illustration.
Although the terms "first" and "second" may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms unless otherwise indicated by the context. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and, similarly, a second feature/element discussed below could be termed a first feature/element, without departing from the teachings of the present invention.
In this specification and the appended claims, unless the context requires otherwise, the term "comprise" and variations such as "comprises" and "comprising" mean that the various components may be used in combination in methods and articles of manufacture (e.g., compositions and apparatus, including devices and methods). For example, the term "comprising" will be understood to imply the inclusion of any stated element or step but not the exclusion of any other element or step.
As used herein in the specification and claims, including as used in the examples and unless otherwise specifically stated, all numbers may be considered as being preceded by the word "about" or "about" even if the term does not explicitly appear. The phrase "about" or "approximately" may be used in describing the magnitude and/or position to indicate that the value and/or position being described is within a reasonably expected range of values and/or positions. Any numerical values set forth herein should also be understood to include about or approximately that value unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It will also be understood that when a value is disclosed, a value that is "less than or equal to" the value, "a value that is" greater than or equal to "and possible ranges between the values are also disclosed, as would be well understood by those of skill in the art. For example, if the value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" are also disclosed (e.g., where X is a numerical value). It should also be understood that throughout this application, data is provided in a variety of different formats, and that the data represents endpoints and starting points and ranges for any combination of the data points. For example, if a particular data point "10" and a particular data point "15" are disclosed, it should be understood that greater than, greater than or equal to, less than or equal to, and equal to 10 and 15, and between 10 and 15, are considered disclosed. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, 11, 12, 13, and 14 are also disclosed.
While various illustrative embodiments have been described above, any of several modifications may be made to the various embodiments without departing from the scope of the invention as described in the claims. For example, in alternative embodiments, the order in which the various described method steps are performed may generally be changed, and in other alternative embodiments, one or more method steps may be skipped altogether. Optional features of the various apparatus and system embodiments may be included in some embodiments and not in others. Accordingly, the foregoing description is provided primarily for illustrative purposes and should not be construed to limit the scope of the invention as set forth in the claims.
The examples and descriptions included herein illustrate by way of illustration, and not by way of limitation, specific embodiments in which the subject matter may be practiced. As noted, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to, individually or collectively, herein by the term "application" merely for convenience and without intending to voluntarily limit the scope of this application to any single application or inventive concept if more than one is in fact disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.