Patent Grant
11291502
Various embodiments of the invention pertain generally to generating passageways through tissue and to treatment or monitoring of intraosseous nerves (“ION”s), and more particularly to creating paths in bone and to treatment (e.g., modulation) of basivertebral nerves within vertebral bodies of the spine.
Back pain is a very common health problem worldwide and is a major cause for work-related disability benefits and compensation. Back pain may arise from strained muscles, ligaments, or tendons in the back and/or structural problems with bones or spinal discs. The back pain may be acute or chronic. Treatments for chronic back pain vary widely and include physical therapy and exercise, chiropractic treatments, rest, pharmacological therapy such as pain relievers or anti-inflammatory medications, and surgical intervention such as vertebral fusion, discectomy or disc repair. Existing treatments can be costly, addictive, temporary, ineffective, and/or can increase the pain or require long recovery times.
Although accessing the vertebral segments of the spine through the pedicle and into the lateral/anterior section of the body of the vertebra is a primary method of placing a treatment device or neuromodulation device (e.g. a bone cement delivery device, a chemical agent delivery device, and/or an RF probe) into the vertebra, it can be difficult to place a probe in the posterior midline section of the vertebra. Furthermore, accessing the posterior midline section of the Si segment of the spine can be difficult with a straight linear access route. In one embodiment, a probe or other treatment device (e.g., neuromodulation device) advantageously may be capable of navigating to the posterior section of the Si vertebral segment, as well as to the same target area within a lumbar vertebral segment. In addition, in accordance with several embodiments, vertebral segments in the cervical and thoracic regions of the spine may also be targeted.
In order to accurately and predictably place a treatment device (e.g., neuromodulation device such as an energy or fluid delivery catheter or probe) in the posterior section of a lumbar vertebral body, a sacral vertebral body or other level vertebral body, the device or probe may navigate to the target area through varying densities of bone in some embodiments. However, due to the varying densities of bone, it can be difficult to navigate a device or probe in bone and ensure its positioning will be in the posterior (e.g., posterior to the midline) or posterior midline section of the vertebral body. The neuromodulation devices described herein can be configured to perform any of the method steps recited herein.
Several embodiments of the invention are directed to systems and methods to deploy and navigate a flexible treatment instrument, such as a neuromodulation device (e.g., a radiofrequency (RF) bipolar probe, a microwave energy delivery device, or a fluid or agent delivery device) within bone. In accordance with several embodiments, a system and method for generating a path in bone that predictably follows a predetermined curved path are provided. Several embodiments herein are primarily directed to navigating through the bone of a vertebral member of the spine, and particularly to treat the basivertebral nerve (BVN) of a vertebral member. The treatment may also be applied to any tissue segment of the body.
In accordance with several embodiments, this invention advantageously facilitates navigation of a curve or angle within varying densities of cancellous bone and creation of a straight channel at the end of the navigated curve or angle.
In accordance with several embodiments, a method of therapeutically treating a vertebral body having an outer cortical bone region and an inner cancellous bone region, and a basivertebral nerve having a trunk extending from the outer cortical bone region of the vertebral body into the inner cancellous region of the vertebral body and a plurality of branches extending from the trunk to define a basivertebral nerve junction or terminus, comprises the steps of: a) inserting one or more energy devices into the vertebral body, and b) exclusively depositing energy within the inner cancellous bone region of the vertebral body between, but exclusive of, the basivertebral nerve junction and the outer cortical bone region, to denervate the basivertebral nerve. In some embodiments, the method comprises depositing, or delivering, energy, fluid, or other substance at or proximate (e.g., posterior to) the basivertebral nerve junction, or terminus. In some embodiments, a delivery probe for delivering a non-energy therapeutic is provided instead of, or in addition to, the energy device.
In some embodiments, a tube-within-tube system comprises a deployable curved tube (e.g. comprised of Nitinol or other flexible, elastic, or shape memory material) that deploys from a straight cannula. The tube can be pre-curved to create an angular range of approximately 0° to approximately 180° (e.g., from approximately 45° to approximately 110°, from approximately 15° to approximately 145°, from approximately 30° to approximately 120°, from approximately 60° to approximately 90°, from approximately 10° to approximately 45°, overlapping ranges thereof, or any angle within the recited ranges), when fully deployed from the straight cannula. The design of the curve can be such that a flexible element (e.g., probe carrying a treatment device) can navigate through the angular range of deployment of the curved tube. The curved tube can allow the flexible element to navigate through a curve within cancellous bone tissue without veering off towards an unintended direction.
Cancellous bone density varies from person to person. Therefore, creating a curved channel within varying density cancellous bone may not predictably or accurately support and contain a treatment device as it tries to navigate the curved channel. With some embodiments, the flexible element is deployed into the bone through the curved tube, which supports the flexible element as it traverses through the curve, thereby preventing the flexible element from channeling its own path. When the flexible element (e.g., energy or agent delivery probe) departs from the tube, it can do so in a linear direction towards the target zone or location. In accordance with several embodiments, this design allows the user to predictably and accurately deploy the flexible element (e.g., treatment device) towards the target zone or location regardless of the density of the cancellous bone.
One embodiment of the invention comprises a system for channeling a path into bone. The system may comprise a trocar having a central channel and an opening at its distal tip, and a cannula sized to be received in the central channel and to be delivered to the distal opening. The cannula may comprise a deflectable or deformable tip with a preformed curve such that the tip straightens while being delivered through the trocar and transitions to a curve (e.g., regains its preformed curve) upon exiting and extending past the distal opening of the trocar to generate a curved path in the bone corresponding to the preformed curve of the deflectable or deformable tip. At least the distal tip or distal section of the cannula may comprise a resiliently deformable material (such as Nitinol or other shape memory material). The cannula may comprise a central passageway or lumen having an internal diameter configured to allow a treatment device to be delivered through the central passageway to a location beyond the curved path in the bone.
In one embodiment, the system further includes a straight stylet configured to be installed in the trocar, wherein the straight stylet comprises a sharp distal tip that is configured to extend beyond the distal opening of the trocar to pierce the bone as the trocar is being delivered to a treatment location within the bone (e.g., within the inner cancellous bone region of a vertebral body).
Additional embodiments of the system may further include one or more straightening stylets configured to be introduced in the cannula, wherein the straightening stylet comprises a rigid construction configured to straighten the distal tip of the curved cannula when positioned in the trocar. In some embodiments, the straightening stylet further comprises a sharp distal end to pierce the bone, and the straightening stylet and curved cannula are installed or inserted in the trocar in place of the straight stylet as the trocar is delivered into the bone.
In some embodiments, the system further comprises a curved stylet having an outer radius sized to fit within the central passageway of the curved cannula. The curved stylet is configured to be installed or inserted in the curved cannula while the curved cannula is extended past the distal opening of the trocar, the curved stylet configured to block the distal opening of the curved cannula while being delivered into the bone. In some embodiments the curved stylet advantageously has a curved distal end corresponding to the curve of the curved cannula.
In one embodiment, the curved stylet has a sharp distal tip configured to extend past the curved cannula to pierce the bone as the cannula is delivered past the distal opening of the trocar. The curved stylet may also advantageously comprise an angled distal tip configured to further support and maintain the curved stylet radius as it is delivered past the distal opening of the trocar and into bone. The curved stylet and the curved cannula may have mating proximal ends (e.g., visual indicia or corresponding physical mating elements) that align the curve of the curved stylet with the curve of the curved cannula. In one embodiment, the angled distal tip is blunt or non-sharp.
In one embodiment, the system further includes a straight channeling stylet configured to be installed in the curved cannula after removing the curved stylet, wherein the straight channeling stylet is flexibly deformable to navigate the curved cannula yet retain a straight form upon exiting the curved cannula. The straight channeling stylet may have a length longer than the curved cannula such that it creates a linear path beyond the distal end of the curved cannula when fully extended. Curved and/or straightening stylets may be used for non-spinal embodiments.
In accordance with several embodiments, a method for channeling a path into bone to a treatment location in the body of a patient is provided. The method includes, in one embodiment, inserting a trocar having a central channel and an opening at its distal tip into a region of bone at or near the treatment location, and delivering a cannula through the central channel and to the distal opening. In one embodiment, the cannula comprises a deflectable or deformable tip with a preformed curve such that the tip straightens while being delivered through the trocar and transitions to a curve (e.g., regains its preformed curve) upon exiting the trocar, and extending the cannula past the distal opening of the trocar to generate a curved path in the bone corresponding to the preformed curve of the deflectable tip. In some embodiments, a treatment device may be delivered through a central passageway or lumen in the cannula to the treatment location beyond the curved path. The treatment device may facilitate or effect energy delivery, fluid delivery, delivery of an agent, etc.
In one embodiment, inserting a trocar into a region of bone comprises inserting a stylet into the trocar such that the stylet extends beyond the distal opening of the trocar, and inserting the stylet and trocar simultaneously into the region of bone such that the stylet pierces the bone as the trocar is being delivered to a treatment location.
In one embodiment, delivering a cannula through the central channel comprises inserting a straightening stylet into the central passageway of the cannula and inserting the straightening stylet and straightened cannula simultaneously into the trocar. In one embodiment, the straightening stylet comprises a rigid construction configured to straighten the curved distal tip of the cannula. In one embodiment, the straightening stylet further comprises a sharp distal end to pierce the bone. In one embodiment, the straightening stylet and cannula are installed simultaneously along with the trocar as the trocar is delivered into the bone.
In one embodiment, extending the cannula past the distal opening is performed by inserting a curved stylet into the central passageway of the curved cannula such that a distal tip of the curved stylet extends to at least the distal opening of the curved cannula and simultaneously extending the curved cannula and curved stylet from the distal end of the trocar such that the curved stylet blocks the distal opening of the curved cannula while being delivered into the bone.
In some embodiments, the curved stylet has a curved distal end corresponding to the curve of the curved cannula such that the curved stylet reinforces the curved shape of the curved cannula as the curved cannula is extended past the distal opening of the trocar. The curved stylet may have a sharp distal tip so that when the curved stylet extends past the distal opening of the curved cannula the curved stylet is configured to pierce the cancellous bone tissue as the curved cannula is delivered past the distal opening of the trocar. In some embodiments, the distal tip of the curved stylet is angled and/or blunt.
In accordance with some embodiments, the curved stylet is then removed from the curved cannula, and a straight channeling stylet is inserted into the curved distal end of the cannula. The straight channeling stylet can be flexibly deformable to navigate the curved cannula, yet retain a straight form upon exiting the curved cannula. The straight channeling stylet can advantageously be longer than the curved cannula to create a linear channel beyond the distal tip of the curved cannula.
In some embodiments, the trocar is inserted through a cortical bone region and into a cancellous bone region of a vertebral body, and the curved cannula is extended though at least a portion of the cancellous bone region to a location at or near a target treatment location. A target treatment location may comprise a basivertebral nerve within the vertebra, and treatment may be delivered to the target treatment location to modulate (e.g., denervate, ablate, stimulate, block, disrupt) at least a portion of the basivertebral nerve (e.g., terminus or junction or a portion of the basivertebral nerve between the terminus or junction and the posterior wall). In one embodiment, a portion of the basivertebral nerve is modulated by delivering focused, therapeutic heating (e.g., a thermal dose) to an isolated region of the basivertebral nerve. In another embodiment, a portion of the basivertebral nerve is modulated by delivering an agent to the treatment region to isolate treatment to that region. In accordance with several embodiments of the invention, the treatment is advantageously focused on a location of the basivertebral nerve that is upstream of one or more branches of the basivertebral nerve.
Several embodiments may include a kit for channeling a path into bone. The kit comprises a trocar having a central channel and opening at its distal tip, and a cannula selected from a set of cannulas sized to be received in the central channel and delivered to the distal opening. The cannula may have a deflectable or deformable distal tip with a preformed curve such that the tip straightens while being delivered through the trocar and regains its preformed curve upon exiting and extending past the distal opening of the trocar to generate a curved path in the bone corresponding to the preformed curve of the deflectable tip. The cannula may comprise a central passageway or lumen having an internal diameter configured to allow a treatment device to be delivered through the central passageway or lumen to a location beyond the curved path within bone, wherein the set of cannulas comprises one or more cannulas that have varying preformed curvatures at the distal tip.
In some embodiments, the one or more cannulas have a varying preformed radius at the distal tip. In addition, the one or more cannulas may each have distal tips that terminate at varying angles with respect to the central channel of the trocar. The length of the distal tips may also be varied. The angle of the distal tip with respect to the central channel of the trocar may vary from 0 degrees to 180 degrees. In accordance with several embodiments, t (e.g., from 10 degrees to 60 degrees, from 15 degrees to 45 degrees, from 20 degrees to 80 degrees, from 30 degrees to 90 degrees, from 20 degrees to 120 degrees, from 15 degrees to 150 degrees, overlapping ranges thereof, or any angle between the recited ranges). The kit may further include a straight stylet configured to be installed in the trocar, the straight stylet comprising a sharp distal tip that is configured to extend beyond the distal opening of the trocar to pierce the bone as the trocar is being delivered to a treatment location within the bone. The kits may be adapted for non-spinal embodiments.
In some embodiments, the kit includes a set of curved stylets having an outer radius sized to fit within the central passageway of the curved cannula, wherein each curved stylet is configured to be installed in the curved cannula while the curved cannula is extended past the distal opening of the trocar. The curved stylet may be configured to block the distal opening of the curved cannula while being delivered into the bone. In one embodiment, each curved stylet may have a varying curved distal end corresponding to the curve of a matching curved cannula in the set of curved cannulas.
In some embodiments, the kit includes a set of straight channeling stylets wherein one of the set of stylets is configured to be installed in the cannula after removing the curved stylet. The straight channeling stylet can be flexibly deformable to navigate the curved cannula yet retain a straight form upon exiting the curve cannula. Each of the straight channeling stylets can have a varying length longer than the curved cannula such that the straight channeling stylet creates a predetermined-length linear path beyond the distal end of the curved cannula when fully extended.
In accordance with several embodiments, a system for channeling a path into bone comprising a trocar with a proximal end, a distal end and a central channel disposed along a central axis of the trocar and extending from the proximal end toward the distal end is provided. The trocar, in one embodiment, comprises a radial opening at or near the distal end of the trocar, the radial opening being in communication with the central channel. In some embodiments, the system further comprises a curveable or steerable cannula sized to be received in said central channel and delivered from the proximal end toward said radial opening. In several embodiments, the curveable cannula comprises a curveable and/or steerable distal end configured to be extended laterally outward from the radial opening in a curved path extending away from the trocar, and a central passageway having a diameter configured allow a treatment device (e.g., probe, catheter) to be delivered through the central passageway to a location beyond the curved path.
In several embodiments, the curveable cannula comprises a proximal end having a proximal body. In one embodiment, the proximal end of the trocar comprises a housing. The housing may comprise a proximal recess configured to allow reciprocation (e.g., alternating back-and-forth motion or other oscillatory motion) of the proximal body of the curveable cannula. The proximal recess of the housing may be in communication with the central channel of the trocar. In several embodiments, a proximal body of the curveable cannula is configured to be releasably restrained with respect to translation within the trocar housing. In several embodiments, the system comprises a probe sized to fit within the central channel of the cannula. The probe may comprise a proximal end configured to be releasably restrained with respect to translation within the proximal body of the curveable cannula. In one embodiment, the probe comprises mating threads that mate with corresponding mating threads of a distal recess of the drive nut so as to allow controlled translation of the probe with respect to the drive nut.
In several embodiments, a spine therapy system is provided. In one embodiment, the system comprises a trocar having a proximal end, a distal end and a central channel. The central channel can be disposed along a central axis of the trocar and extend from the proximal end toward the distal end. In one embodiment, the trocar comprises a radial opening at or near the distal end of the trocar, the radial opening being in communication with the central channel. In one embodiment, the trocar is configured to be deployed through a cortical bone region and into a cancellous bone region of a vertebral body. In one embodiment, a curveable cannula is configured (e.g., sized) to be received in said central channel and delivered from the proximal end toward the radial opening. The curveable cannula may comprise a central passageway and a curveable and/or steerable distal end configured to be extended laterally outward from the radial opening in a curved path extending away from the trocar. The curved path may be generated through at least a portion of the cancellous bone region of the vertebral body. In one embodiment, a treatment device or probe is configured to be delivered through the central passageway to a location beyond the curved path. The trocar, curveable cannula, and/or treatment device can have a sharp distal end or tip configured to penetrate bone tissue. In some embodiments, the distal ends of the trocar, curveable cannula, and/or treatment device are rounded or blunt. In some embodiments, the distal ends of the trocar or curved or curveable cannula have a full radius on the inside and/or outside diameter to prevent other devices from catching when being pulled back into the distal end after being delivered out of the distal end.
In accordance with several embodiments, a method for channeling a path into bone to a treatment location in the body of a patient is provided. The bone may be within or proximal a vertebral body, or may be non-spinal (e.g., knee or other joints). In one embodiment, the method comprises inserting a trocar into a region of bone near the treatment location. In one embodiment, the trocar comprises a proximal end, a distal end, and a central channel disposed between the two ends. In one embodiment, the method comprises delivering a curveable cannula through the central channel and to a radial opening at or near the distal end of the curveable cannula. In one embodiment, the method comprises deploying the curveable cannula laterally outward from the radial opening in a curved path extending away from the trocar. In one embodiment, the method comprises steering the curveable cannula (e.g., via a pull cord coupled to the distal tip of the curveable cannula or via other steering mechanisms) to bias the curveable cannula in the curved path. Energy and/or another diagnostic or therapeutic agent is then optionally delivered to the treatment location.
In accordance with several embodiments, a method of treating back pain is provided. In some embodiments, the method comprises identifying a vertebral body for treatment (e.g., a target for treatment of chronic back pain). In some embodiments, the method comprises identifying a treatment zone, area or site within the inner cancellous bone region of the vertebral body. In some embodiments, the treatment zone, area or site is within a posterior section of the vertebral body (e.g., posterior to an anterior-posterior midline). In some embodiments, the treatment zone comprises a location corresponding to the mid-height of the vertebra from an anterior-posterior view. In some embodiments, a border of the treatment zone is at least 1 cm (e.g., between 1-2 cm, 2-3 cm, 3-4 cm, or more) from the posterior wall of the vertebral body. In some embodiments, the treatment zone is determined by measuring the distance from the posterior wall to the basivertebral foramen as a percentage of the total distance from the posterior wall to the anterior wall of the vertebral body.
In some embodiments, identifying a treatment zone is performed pre-operatively using imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) imaging modalities. In some embodiments, the treatment zone, site, or location corresponds to a location that is about mid-height between the superior and inferior endplate surfaces of the vertebral body (which may be identified by imaging methods from an anterior-posterior view). In some embodiments, the treatment zone, site or location is identified by measuring the distance from the posterior wall of the vertebral body to the basivertebral foramen from images (e.g., anteroposterior and/or lateral MRI or CT images) of the vertebral body as a percentage of the total distance from the posterior wall to the anterior wall of the vertebral body. In some embodiments, inserting the neuromodulation device within the treatment zone is performed under visualization (e.g., using fluoroscopy). In some embodiments, positioning a distal end portion of the neuromodulation device within the treatment zone comprises positioning the distal end portion (and any active elements such as electrodes located at the distal end portion) at a location corresponding to the measured distance percentage described above. In some embodiments, the percentage is a standardized distance percentage that is not individually measured for the individual subject or vertebral body being treated. In some embodiments, the treatment zone, site, or location corresponds to a location at or proximate (e.g., posterior to) a terminus of the basivertebral foramen.
In some embodiments, the method comprises inserting a curved cannula through the outer cortical bone region of the vertebral body and into the inner cancellous bone region of the vertebral body. The curved cannula can comprise a flexible catheter, tube, or other conduit having a pre-curved or steerable distal end. The curved cannula may comprise Nitinol, PEEK, or other thermoplastic, shape memory or resiliently deformable material. In some embodiments, the method comprises inserting a neuromodulation device within the curved cannula. The neuromodulation device can comprise an energy delivery device, a fluid delivery device, or an agent delivery device. The fluid may or may not comprise an agent, such as a chemical agent. In one embodiment, the chemical agent comprises a lytic agent.
In various embodiments, the energy delivery device is configured to deliver radiofrequency energy, microwave energy, light energy, thermal energy, ultrasonic energy, and/or other forms of electromagnetic energy, and/or combinations of two or more thereof. In accordance with several embodiments, the energy is configured to heat tissue within bone (e.g., a vertebral body) sufficient to modulate (e.g., denervate, ablate) intraosseous nerves (e.g., basivertebral nerves or other nerves located partially or fully within bone). In other embodiments, the energy is configured to treat tissue outside the spine, for example in non-spinal joints or in non-orthopedic applications (e.g., cardiac, pulmonary, renal, or treatment of other organs and/or their surrounding nerves). The temperature of the energy may be in the range of between 40° C. and 100° C., between 50° C. and 95° C., between 60° C. and 80° C., between 75° C. and 95° C., between 80° C. and 90° C., overlapping ranges thereof, or any temperature between the recited ranges. In some embodiments, the temperature and length of treatment can be varied as long as the thermal dose is sufficient to modulate (e.g., at least temporarily denervate, ablate, block, disrupt) the nerve. In some embodiments, the length of treatment (e.g., delivery of energy) ranges from about 5 to about 30 minutes (e.g., about 5 to 15 minutes, about 10 to 20 minutes, about 15 to 25 minutes, about 20 to 30 minutes, overlapping ranges thereof, 15 minutes, or about any other length of time between the recited ranges). In some embodiments, the neuromodulation device comprises a sensor to measure nerve conduction of the nerve at the treatment zone.
The energy delivery device may comprise one or more probes (e.g., a radiofrequency probe). In some embodiments, the probe comprises one or more electrodes configured to generate a current to heat tissue within bone. In one embodiment, the probe comprises a bipolar probe having two electrodes. The two electrodes may comprise an active electrode and a return electrode. In one embodiment, the active electrode comprises a tip electrode positioned at the distal tip of the radiofrequency probe and the return electrode comprises a ring electrode spaced proximally from the active electrode with insulation material between the two electrodes. In one embodiment, the return electrode comprises a tip electrode positioned at the distal tip of the probe (e.g., a radiofrequency probe) and the active electrode comprises a ring electrode spaced proximally from the return electrode. The two electrodes may be spaced about 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm or 1 cm apart. In various embodiments, the electrodes comprise cylindrical electrodes, tip electrodes, plate electrodes, curved electrodes, circular electrodes, or other shapes. In some embodiments, the electrodes comprise an electrode array. In various embodiments, the frequency of the energy can be between about 100 kHz and 1 MHz, between 400 kHz and 600 kHz, between 300 kHz and 500 kHz, between 350 kHz and 600 kHz, between 450 kHz and 600 kHz, overlapping ranges thereof, or any frequency within the recited ranges.
In one embodiment, the energy delivery device comprises an ultrasound probe having one or more ultrasound transducers. The ultrasound probe may be configured to deliver high-intensity focused ultrasonic energy, low-intensity ultrasonic energy or other forms of ultrasonic energy sufficient to modulate the nerve. The ultrasound energy may be used for cavitation or non-cavitation. In one embodiment, the energy delivery device comprises a laser or light energy delivery device configured to deliver light energy sufficient to modulate the nerve. In one embodiment, the energy delivery device is configured to deliver radiation sufficient to modulate the nerve. In one embodiment, the energy delivery device comprises a microwave energy delivery device comprising one or more microwave antennas configured to deliver microwave energy sufficient to effect modulation of the nerve.
In one embodiment, a fluid delivery device is used to effect a temperature change in a location in the disc. For example, the fluid delivery device may be used to deliver a cryoablative fluid. In another embodiment, the fluid delivery device may be used to deliver a cooling fluid to cool a region in conjunction with a therapy that generates heat. In some embodiments, a distal portion of the curved cannula is shaped so as to guide a distal end of the neuromodulation device towards the midline of the vertebral body (or other treatment area outside the spine). In some embodiments, a proximal end of the fluid delivery device is coupled to a fluid source or reservoir (e.g., syringe, fluid pump). In some embodiments, the fluid delivery device comprises a catheter, tube, sleeve, needle, cannula, wicking device, or other conduit configured to deliver fluid. The fluid may comprise neurolytic agents, chemotherapy agents, radioactive substances, medications, drugs, pharmaceuticals, alcohols, acids, solvents, cooling agents, nerve blocking agents, and/or other chemical agents.
In some embodiments, the method comprises advancing the distal end of the neuromodulation device out of a distal opening of said cannula and into the inner cancellous bone region of the vertebral body or treatment area. The distal opening may be an axial opening or a radial opening. In some embodiments, the method comprises positioning the distal end of said neuromodulation device within, at or proximate the treatment zone, area site, or location of the vertebral body or treatment area.
In some embodiments, the method comprises effecting modulation of at least a portion of a nerve (e.g., basivertebral nerve or intraosseous nerve) using the neuromodulation device. The modulation (e.g., neuromodulation) can comprise partial or complete and/or temporary or permanent blocking, disruption, denervation or ablation of the nerve. In various embodiments, the modulation comprises radiofrequency ablation, microwave energy ablation, chemical ablation, cryoablation, ultrasonic ablation, acoustic ablation, laser ablation, thermal ablation, thermal heating, cooling, mechanical severing, neuromodulation, and/or stimulation of the nerve. In one embodiment, stimulation of the nerve is performed to block the travel of signals indicative of pain. Stimulation may comprise mechanical, electrical, or electromechanical stimulation and may be performed by any of the modalities or methods described herein with reference to ablation or modulation. The stimulation may be continuous or pulsed. In various embodiments, the modulation may be performed by a radioactive implant or by an external radiation beam (e.g., electron beam, gamma-knife, etc.).
In accordance with several embodiments, a method of treating pain (e.g., back pain) is provided. In some embodiments, the method comprises identifying a treatment zone, such as a vertebral body for treatment (e.g., an identified source of pain or location likely to treat pain). In some embodiments, the treatment zone comprises a basivertebral residence zone within which a portion of the basivertebral nerve (e.g., main trunk, junction, terminus of basivertebral foramen, etc.) is likely to reside. In some embodiments, the treatment zone is identified without knowing the precise location of the basivertebral nerve. In some embodiments, the method comprises identifying a treatment zone, site, region or location within the inner cancellous bone region within a posterior section of the vertebral body. The posterior section may comprise a section posterior to an anterior-posterior midline or a region within a distance between about 10% and about 50%, between about 20% and about 50%, between about 10% and about 40% of the distance from the posterior wall. In some embodiments, the method comprises inserting a distal end portion of the neuromodulation device (e.g., energy and/or fluid delivery probe), and any active elements disposed thereon, within or proximate the treatment zone. In some embodiments, the method comprises thermally inducing modulation of a function of a basivertebral nerve within the vertebral body with the energy delivery probe.
In some embodiments, the method comprises generating a curved path within the inner cancellous bone region towards a midline of the vertebral body with a cannula having a pre-curved distal end portion to facilitate access to the posterior section of the vertebral body. In some embodiments, insertion of the neuromodulation device through a curved cannula allows for access straight through (e.g., concentrically through) the pedicle in a transpedicular approach instead of an off-center access, which may be difficult for some levels of vertebrae due to anatomic constraints. In some embodiments, the method comprises inserting the neuromodulation device within the curved path created by the cannula. In some embodiments, the cannula is shaped so as to guide a distal end portion of the neuromodulation device towards the midline of the vertebral body. In some embodiments, the method comprises inserting a stylet within the cannula that is adapted to penetrate bone tissue of the vertebral body beyond the curved path created by the cannula.
In accordance with several embodiments, a method of therapeutically heating a vertebral body to treat back pain is provided, In some embodiments, the method comprises identifying a residence zone of a basivertebral nerve within the inner cancellous bone region of the vertebral body. In some embodiments, the method comprises inserting two electrodes into the vertebral body. In some embodiments, the method comprises positioning the two electrodes within or proximate the residence zone. In some embodiments, the method comprises generating a heating zone between the two electrodes to heat the basivertebral nerve. For example, a first electrode may be activated to generate a current between the first electrode and a second electrode. The current may generate heat within the bone tissue. The heating zone may comprise an inner resistive heating zone and an outer conductive heating zone. In some embodiments, the heating zone is configured to have a radius or diameter between about 0.5 cm and 2 cm (e.g., 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1 cm, 1.1 cm, 1.2 cm, 1.3 cm, 1.4 cm, 1.5 cm, 1.6 cm, 1.7 cm, 1.8 cm, 1.9 cm, 2 cm). In accordance with several embodiments, forming heating zones (and in some cases, lesions) of a specific size and shape can be improved by adjusting parameters such as diameter and active length of electrodes, initial and steady-state power input, length of treatment, and device control temperature.
In some embodiments, inserting two electrodes into the vertebral body comprises inserting a first energy delivery probe having a first electrode within the inner cancellous bone region and positioning a second energy delivery probe having a second electrode within the inner cancellous bone region. In some embodiments, inserting two electrodes into the vertebral body comprises inserting a single energy delivery probe having two electrodes within the inner cancellous bone region.
In some embodiments, positioning the two electrodes within or proximate the residence zone comprises positioning the electrodes at a location such that a single heating treatment modulates (e.g., denervates, ablates) the entire basivertebral nerve system without requiring separate downstream modulation (e.g., denervation, ablation) treatments. In some embodiments, positioning the two electrodes of within or proximate the residence zone comprises positioning the two electrodes to straddle the residence zone. In some embodiments, positioning the two electrodes within or proximate the residence zone comprises positioning a first electrode on a first side of the vertebral body and positioning a second electrode on a second side of the vertebral body (wherein the first side and second side are on opposite sides of any line drawn through a midpoint of the vertebral body).
In accordance with several embodiments of the invention, methods and systems allow for positioning of a treatment device in contact with or in close proximity to a basivertebral nerve without knowing the precise location of the basivertebral nerve. In attempting to place at least one electrode in close proximity to the basivertebral nerve, the approaches disclosed in the teachings of the art are somewhat problematic. In particular, although the location of the basivertebral nerve is somewhat well known, the basivertebral nerve is radiolucent and so its precise location cannot be easily identified by an X-ray. Since the basivertebral nerve is also extremely thin, knowingly placing the electrode in close proximity to the basivertebral nerve may be problematic in some cases. Moreover, in one embodiment, since certain RF electrodes appear to heat only a fairly limited volume of bone, misplacement of the electrode vis-à-vis the basivertebral nerve may result in heating a volume of bone that does not contain the basivertebral nerve. “Close proximity” with regard to the intraosseous or basivertebral nerve can mean located at a position such that the nerve is modulated upon activation of the neuromodulation device or delivery of fluid or other substances by the neuromodulation device.
The terms “modulation” or “neuromodulation”, as used herein, shall be given their ordinary meaning and shall also include ablation, permanent denervation, temporary denervation, disruption, blocking, inhibition, therapeutic stimulation, diagnostic stimulation, inhibition, necrosis, desensitization, or other effect on tissue. Neuromodulation shall refer to modulation of a nerve (structurally and/or functionally) and/or neurotransmission. Modulation is not limited to nerves and may include effects on other tissue.
Several embodiments of the invention relate to the production of a large but well-controlled heating zone within bone tissue to therapeutically treat (e.g., modulate) an ION within the heating zone. Other embodiments provide modulation of non-spinal tissue (e.g., nerves).
Accordingly, some embodiments of the invention are advantageous because they allow the clinician to create a sufficiently large heating zone for therapeutically treating the ION (e.g., basivertebral nerve) without requiring direct access to the ION. Some embodiments of the invention are particularly advantageous because such embodiments: (i) do not require knowing the precise location of the ION, (ii) do not require directly accessing the ION, and/or (iii) have a controlled heating profile that allows a clinician to avoid heating adjacent structures such as the healthy adjacent cancellous bone tissue, the spinal cord or opposing vertebral endplates.
In accordance with several embodiments, a system for channeling a path into bone is provided. The system may comprise a trocar comprising a proximal end, a distal end and a central channel. In one embodiment, the central channel is disposed along a central axis of the trocar and extends from the proximal end toward the distal end. In one embodiment, the trocar comprises a distal opening at or near the distal end of the trocar, the distal opening being in communication with the central channel. The system may comprise a curved cannula sized to be received in the central channel and delivered from the proximal end toward the distal opening of the trocar. In one embodiment, the curved cannula comprises a straight tubular body at a proximal end of the curved cannula and a curved distal end. The curved distal end may be configured to be extended laterally outward from the distal opening in a curved path extending away from the trocar; wherein the curved cannula comprises a central passageway having a diameter configured to allow a probe to be delivered through the central passageway to a location beyond the curved path.
In some embodiments, the distal end of the curved cannula is deformable so as to be delivered in a straight configuration through the trocar and deployed in a curved configuration outward from the distal opening at an angle with respect to the central axis. In various embodiments, the proximal end of the trocar comprises a handle having a proximal recess in communication with the central channel of the trocar to allow reciprocation of the curved cannula within the central channel and a lateral slot in communication with the proximal recess. In one embodiment, the lateral slot extends radially outward from the proximal recess at a proximal surface of the handle. The slot may be configured to allow insertion of the curved cannula such that a central axis of the straight tubular body is at an angle with respect to the central axis of the trocar when the curved distal end of the curved cannula is inserted into the proximal recess. In one embodiment, the curved cannula can be inserted within the trocar without requiring a straightening sleeve or other structure to straighten the curved cannula prior to insertion.
In one embodiment, the lateral slot comprises a curvilinear bottom surface configured to allow the curved distal end of the curved cannula to be slideably advanced into the proximal recess and the central channel, thereby facilitating ease of insertion of a curved instrument into a straight channel. In one embodiment, the curvilinear bottom surface of the lateral slot comprises a radius substantially matching the radius of the curved distal end of the curved cannula.
In several embodiments, the system comprises a curved stylet comprising a straight proximal body and a preformed curved distal end. In one embodiment, the curved cannula comprises a cannula channel configured to allow delivery of a treatment device to the location beyond the curved path. The proximal end of the curved cannula may comprise a cannula handle having a central recess in communication with the cannula channel to allow reciprocation of the curved stylet within the cannula channel and a lateral cannula slot in communication with the central recess. In one embodiment, the cannula slot extends radially outward from the central recess at a proximal surface of the cannula handle such that the lateral cannula slot is configured to allow insertion of the curved stylet in a manner such that a central axis of the straight proximal body is at an angle with respect to a central axis of the cannula channel when the preformed curved distal end of the curved stylet is inserted into the central recess.
In some embodiments, the lateral cannula slot comprises a curvilinear bottom surface configured to allow the preformed curved distal end of the curved stylet to be slideably advanced into the central recess and cannula channel. The curvilinear bottom surface of the cannula handle may comprise a radius substantially matching the radius of the preformed curved distal end of the curved stylet. In some embodiments, the curved cannula comprises a stop nut threaded about a threaded portion distal to the cannula handle and proximal to the straight proximal body. In one embodiment, the stop nut is configured to have a first position on the threaded portion. The stop nut may be configured to restrain advancement of the curved cannula within the trocar such that the curved distal end of the cannula does not extend past the distal end of the trocar when the stop nut is in the first position. In one embodiment, the stop nut comprises a second position on the threaded portion configured to allow further translation of the curved cannula with respect to the trocar. The stop nut may be rotated or otherwise translated to the second position prior to extending the curved distal end of the curved cannula laterally outward from the distal opening of the trocar. In some embodiments, the system comprises a treatment probe (e.g., an RF energy delivery probe) configured to be delivered through the central passageway to a location at or beyond the curved path.
In accordance with several embodiments, a method for channeling a path into a vertebral body of a patient using the trocar, curved cannula and/or curved stylet described above is provided. The method comprises inserting a trocar into the vertebral body. The trocar may have any of the structural features of the trocars described herein (e.g., slotted handle) to facilitate insertion of a curved instrument without requiring straightening of the curved instrument prior to insertion, thereby reducing the number of steps and/or instruments in a spine therapy system. In some embodiments, the method comprises inserting the curved distal end of a curved cannula into a proximal recess of a trocar handle through a lateral slot of the trocar handle and such that a central axis of the straight tubular body of the curved cannula is at an angle with respect to the central axis of the trocar. In some embodiments, the method comprises advancing the curved cannula into the proximal recess of the trocar, thereby straightening the curved distal end of the curved cannula. In one embodiment, the method comprises advancing the curved cannula within the central channel of the trocar from the proximal end toward the distal opening of the trocar and extending the curved distal end of the curved cannula laterally outward from the distal opening of the trocar to generate a curved path radially outward from the trocar. In one embodiment, the method comprises delivering a treatment probe through the curved cannula to a location beyond the curved path.
In some embodiments, the method comprises retracting the curved stylet from the curved cannula and delivering a straight stylet into the curved cannula to generate a straight path beyond the curved path radially outward from the trocar. In some embodiments, the method comprises retracting the straight stylet from the curved cannula and delivering the treatment probe through the curved cannula to a location beyond the curved path.
In accordance with several embodiments, a system for delivering a self-guided treatment device into bone is provided. The system may comprise a trocar comprising a proximal end, a distal end and a central channel. In one embodiment, the central channel is disposed along a central axis of the trocar and extends from the proximal end toward the distal end and the trocar comprises a distal opening at or near the distal end of the trocar, the distal opening being in communication with the central channel. The system may also comprise a treatment probe sized to be received in the central channel and delivered from the proximal end toward the distal opening of the trocar. In one embodiment, the treatment probe comprises a stylet comprising a straight proximal end and a curved distal end. In one embodiment, the curved distal end is deformable so as to be delivered in a straight configuration through the trocar and deployed in a curved configuration outward from the distal opening at an angle with respect to the central axis of the trocar. In some embodiments, the curved distal end comprises a treatment device configured to deliver a therapeutic dose of energy to a treatment location.
In some embodiments, the curved distal end of the treatment probe comprises a sharpened distal tip configured to channel through a cancellous bone region of a vertebral body. In some embodiments, the therapeutic dose of energy delivered by the treatment device is configured to denervate a basivertebral nerve associated with the vertebral body. In one embodiment, the proximal end of the trocar comprises a handle comprising a proximal recess in communication with the central channel to allow reciprocation of the curved cannula within the central channel and a lateral slot in communication with the proximal recess. In one embodiment, the lateral slot extends radially outward from the proximal recess at a proximal surface of the handle of the trocar such that the lateral slot is configured to allow insertion of the treatment probe such that a central axis of the straight proximal end of the stylet is at an angle with respect to the central axis of the trocar when the curved distal end of the treatment probe is inserted into the proximal recess of the trocar. The lateral slot may comprise a curvilinear bottom surface configured to allow the curved distal end of the treatment probe to be slideably advanced into the proximal recess and the central channel of the trocar. In one embodiment, the curvilinear bottom surface comprises a radius substantially matching the radius of the curved distal end of the treatment probe.
In several embodiments, the system comprises a straight stylet comprising a straight proximal body and a sharpened distal end. The stylet may be configured to protrude from the distal opening of the trocar when installed in the trocar. In one embodiment, the stylet comprises a striking surface for advancing the trocar through a cortical bone region of the vertebral body. In one embodiment, the treatment probe comprises a handle having a striking surface for advancing the treatment probe through the cancellous bone region of the vertebral body.
In one embodiment, the distal end of the treatment probe comprises a plurality of circumferentially relieved sections. In one embodiment, the distal end of the treatment probe comprises a pair of ring electrodes forming a bipolar RF treatment device. In some embodiments, the stylet of the treatment probe comprises a longitudinal channel extending from the curved distal end to the straight proximal end, the channel configured to house a flexible lead coupled to the pair of ring electrodes. In one embodiment, the probe handle comprises a connector for coupling a power source to the flexible lead.
In accordance with several embodiments, a method for delivering a self-guided treatment device into bone is provided. The method may comprise inserting a trocar into bone. The trocar may comprise any of the structural features of the trocars described herein (e.g., slotted handle) to facilitate insertion of a curved instrument without requiring straightening of the curved instrument prior to insertion, thereby reducing the number of steps and/or instruments in a treatment system. In one embodiment, the method comprise inserting a curved distal end of a treatment probe (such as the treatment probes described above) into a proximal recess of the trocar through a lateral slot and such that a central axis of a straight tubular body of the treatment probe is at an angle with respect to the central axis of the trocar. The method may comprise advancing the treatment probe into the proximal recess of the trocar, thereby straightening the curved distal end of the treatment probe upon insertion rather than prior to insertion (e.g., with a sleeve or other constraint). In one embodiment, the method comprises advancing the treatment probe within the central channel of the trocar from the proximal end toward the distal opening of the trocar and extending the curved distal end of the treatment probe laterally outward from the distal opening of the trocar to generate a curved path radially outward from the trocar. In one embodiment, the method comprises delivering a therapeutic dose of energy to a treatment location within the bone. In some embodiments, the therapeutic dose of energy is configured to denervate a basivertebral nerve associated with the vertebral body. In one embodiment, delivering a therapeutic dose of energy to the treatment location comprises delivering RF energy to denervate the basivertebral nerve.
In several embodiments, the system may comprise a curved stylet comprising a straight proximal body and a curved distal end. The curved stylet may further comprise an inner core and an outer layer. In several embodiments, the inner core comprises an elastic metal alloy. In several embodiments, the outer layer comprises a polymer. In some embodiments, the diameter of the inner core is constant along the length of the inner core. In accordance with several embodiments, during manufacturing, the stiffness of the curved stylet can be altered by manipulating the diameter of the inner core, the wall thickness of the outer layer, or a combination thereof. The curved stylet may be configured to protrude from the distal opening of the trocar when installed in the trocar.
In accordance with several embodiments, a method for manufacturing a curved stylet is provided. The method may comprise providing an inner core, and in some embodiments, providing an inner core of a constant diameter. The method may comprise encasing at least a portion of the inner core with an outer layer. In several embodiments, the inner core comprises an elastic metal alloy. In several embodiments, the outer layer comprises a polymer. In some embodiment, the method may comprise manipulating the diameter of the inner core, the wall thickness of the outer layer, or a combination thereof in order to achieve desired stiffness.
The methods summarized above and set forth in further detail below describe certain actions taken by a practitioner; however, it should be understood that they can also include the instruction of those actions by another party. Thus, actions such as “delivering a therapeutic dose of energy” include “instructing the delivery of a therapeutic dose of energy.” Further aspects of embodiments of the invention will be discussed in the following portions of the specification. With respect to the drawings, elements from one figure may be combined with elements from the other figures.
Several embodiments of the invention will be more fully understood by reference to the following drawings which are for illustrative purposes only:
Several embodiments of the invention are directed to systems and methods to deploy and navigate a treatment instrument, such as a neuromodulation device (e.g., a radiofrequency (RF) bipolar energy delivery device, a microwave energy delivery device, or a fluid or agent delivery device) within bone. Although the systems and methods described herein are primarily directed to navigating through the bone of a vertebral member of the spine, and particularly to treat the basivertebral nerve (BVN) of a vertebral member, the treatment may be applied to any nerve and/or to any tissue segment of the body.
In accordance with several embodiments, the systems and methods of treating back pain or facilitating neuromodulation of intraosseous nerves described herein can be performed without surgical resection, without general anesthesia, and/or with virtually no blood loss. In some embodiments, the systems and methods of treating back pain or facilitating neuromodulation of intraosseous nerves described herein facilitate easy retreat if necessary. In accordance with several embodiments of the invention, successful treatment can be performed in challenging or difficult-to-access locations and access can be varied depending on bone structure. One or more of these advantages also apply to treatment of tissue outside of the spine (e.g., other orthopedic applications or other tissue).
The surgical devices and surgical systems described may be used to deliver numerous types of treatment devices to varying regions of the body. Although embodiments of the devices and systems are particularly useful in navigating through bone, in one embodiment they may also be used to navigate through soft tissue, or through channels or lumens in the body, particularly where one lumen may branch from another lumen.
The following examples illustrate embodiments of the system 10 applied to generating a curved bone path in the vertebral body, and more particularly for creating a bone path via a transpedicular approach to access targeted regions in the spine. In particular, the system 10 may be used to deliver a treatment device to treat or ablate intraosseous nerves, and in particular that basivertebral nerve. Although the system and methods provide significant benefit in accessing the basivertebral nerve, in accordance with several embodiments, the system 10 may similarly be used to create a bone path in any part of the body (such as the humerus, femur, pelvis, fibula, tibia, ulna, radius, etc.)
In accordance with several embodiments, the basivertebral nerves are at, or in close proximity to, the exit point 142. In some embodiments, the exit point 142 is the location along the basivertebral nerve where the basivertebral nerve exits the vertebra. Thus, the target region of the basivertebral nerve 122 is located within the cancellous portion 124 of the bone (i.e., to the interior of the outer cortical bone region 128), and proximal to the junction J of the basivertebral nerve 122 having a plurality of branches 130. Treatment in this target region is advantageous because only a single portion of the basivertebral nerve 122 need be effectively treated to modulate (e.g., denervate or otherwise affect the entire basivertebral nerve system). Treatment, in accordance with one embodiment, can be effectuated by focusing in the region of the vertebral body located between 60% (point A) and 90% (point B) of the distance between the anterior and posterior ends of the vertebral body. In some embodiments, treatment is located at or proximate (e.g., posterior to) the junction J. In some embodiments, treatment of the basivertebral nerve 122 in locations more downstream than the junction J requires the denervation of each branch 130. The target region may be identified or determined by pre-operative imaging, such as from MRI or CT images. In various embodiments, treatment can be effectuated by focusing in the region of the vertebral body located at a region that is more than 1 cm from the outer cortical wall of the vertebral body, within a region that is centered at or about 50% of the distance from the posterior outer wall of the vertebral body to the anterior outer wall, and/or within a region that is between 10% and 90% (e.g., between about 10% and about 60%, between about 20% and about 80%, between about 35% and about 65%, between about 5% and about 65%, between about 10% and about 55%, or overlapping ranges thereof) of the distance from the posterior outer wall of the vertebral body to the anterior outer wall.
In various embodiments, the junction J is located at a location of the terminus of the vertebral foramen, at the junction between a main trunk of the basivertebral nerve 122 and the initial downstream branches, at a location corresponding to a junction between at least one of the initial downstream branches and its respective sub-branches, or other locations along the basivertebral nerve 122.
In accordance with several embodiments, one approach for accessing the basivertebral nerve involves penetrating the patient's skin with a surgical instrument, which is then used to access the desired basivertebral nerves, e.g., percutaneously. In one embodiment, a transpedicular approach is used for penetrating the vertebral cortex to access the basivertebral nerve 122. A passageway 140 is created between the transverse process 134 and spinous process 136 through the pedicle 138 into the cancellous bone region 124 of the vertebral body 126 to access a region at or near the base of the nerve 122. In one embodiment, a postereolateral approach (not shown) may also be used for accessing the nerve. The transpedicular approach, postereolateral approach, basivertebral foramen approach, and other approaches are described in more detail in U.S. Pat. No. 6,699,242, herein incorporated by reference in its entirety.
Referring now to
In some embodiments, after the proper depth is achieved, the straight stylet 80 is removed from the trocar 20, while the trocar 20 remains stationary within the vertebra 120. The straightening stylet 40 can then be inserted into proximal aperture 52 (see
As shown in
Referring to
Once the stylet 60 is fully seated and aligned with the curved cannula 50, the tip of the curved stylet 60 may protrude from the tip of the curved cannula 50 by about 1/16 to 3/16 inches. This protrusion can help to drive the curve in the direction of its orientation during deployment.
Referring now to
In accordance with several embodiments,
Referring now to
Referring now to
With the trocar 20 and curved cannula 50 still in place, a treatment device (e.g. treatment probe 100 shown in
In one embodiment, the active element 102 is delivered to the treatment site and activated to deliver therapeutic treatment energy. In various embodiments, the treatment device comprises a probe, catheter, antenna, wire, tube, needle, cannula, sleeve, or conduit. The treatment device may comprise an RF delivery probe having bipolar electrodes 106 and 108 that deliver a therapeutic level of heating (e.g., thermal dose) to modulate (e.g., stimulate or ablate) at least a portion of the nerve 122.
In some embodiments, the treatment device comprises a microwave energy delivery device comprising one or more antennas. In some embodiments, the treatment device comprises a chemical ablation or cryoablation device comprising a fluid conduit for delivery (e.g., injection) of fluids, chemicals or agents (e.g., neurolytic agents) capable of ablating, stimulating, denervating, blocking, disrupting, or otherwise modulating nerves. In some embodiments, the treatment device comprises an ultrasound delivery device having one or more transducers or a laser energy delivery device comprising one or more light delivery elements (e.g., lasers, such as fiber optic lasers or vertical cavity surface emitting lasers (VCSELs), or light emitting diodes (LEDs)).
According to several embodiments of the invention, many treatment modalities can be delivered to the treatment site for modulation of nerves or other tissue (e.g., neuromodulation, ablation, temporary or permanent denervation, stimulation, inhibition, blocking, disruption, or monitoring). For example, treatment may be affected by monopolar or tripolar RF, ultrasound, radiation, steam, microwave, laser, or other heating means. These modalities may be delivered to the treatment site through one or more of the embodiments of systems and/or methods disclosed herein, and treatment applied such that the nerve is heated to the desired level for the desired duration (e.g., a sufficient thermal dose is applied) to affect stimulation, denervation, ablation or the desired therapeutic effect.
For example, the ultrasonic energy can be controlled by dosing, pulsing or frequency selection to achieve the desired heating level for the desired duration. Similarly, microwave treatment may be applied using a microwave energy delivery catheter and/or one or more antennas. Microwaves may be produced with a frequency in the range of 300 GHz to 300 MHz, between 1 GHz and 5 GHz, between 2 GHz and 10 GHz, between 10 GHZ and 100 GHz, 100 GHz and 300 GHz, between 50 GHz and 200 GHz, between 200 GHz and 300 GHz, or overlapping ranges thereof. Pulses of between 1-5 seconds, between 2-3 seconds, between 0.5 seconds-2 seconds, between 4-5 seconds, between 5-10 seconds, between 10-30 seconds, or overlapping ranges between, in duration may be generated. In some embodiments, a single pulse, 1-3 pulses, 2-4 pulses, 3-8 pulses, 8-20 pulses, or overlapping ranges between, may be generated.
Radiation therapy may use radiation sources comprising any one of a number of different types, such as, but not limited to, particle beam (proton beam therapy), cobalt-60 based (photon or gamma-ray source such as that found in the GammaKnife), or linear accelerator based (e.g., linac source). The dose of radiation delivered to the patient will typically range between 10 Gy and 70 Gy. However, because the treatment region is contained within the large bony mass of the vertebral body, higher doses may be contemplated, as there is little risk to surrounding tissues that are more vulnerable. The dose may be varied based on the treatment volume, or other variables such as treatment time and dose concentration. A prescription of 35 instances of a 2 Gy dose might be replaced by 15 instances of a 3 Gy dose, a technique known as “hypofractionation.” Taken to its logical extreme, this might be replaced with a single 45 Gy dose if the dosage delivered to healthy tissue can be reduced significantly. An identification dose may in some embodiments be used prior to the treatment dose, for example, to elicit some response form the patient relating to the patient's pain. The identification dose is generally a much smaller dose than treatment dose TD, so as not to damage healthy tissue. Doses may range from 0.5 Gy to 5 Gy. However, this range may also change based on considerations such as anatomy, patient, etc.
Additionally or alternatively, the treatment device may comprise a fluid or agent delivery catheter that deposits an agent or fluid, e.g. bone cement, phenol, alcohol, neurotoxin, inhibitory or stimulatory drug, chemical, or medicament, for neuroablation or permanent or temporary denervation, or other therapeutic agent, to the treatment site or location T. Growth factors, stem cells, gene therapy or other biological therapeutic agents may also be delivered.
In some embodiments, cryogenic cooling may be delivered for localized treatment of the basivertebral nerve or an intraosseous nerve using, for example, liquid nitrogen, liquid nitrous oxide, liquid air, or argon gas. Cryotherapy may be delivered in one or more freeze cycles. In several embodiments, two freeze-thaw cycles are used. In some embodiments, 3-5 freeze-thaw cycles are used. In some embodiments, a single freeze-thaw cycle is used In some embodiments, a desired temperature of the tissue is −40° C. to −50° C., −20° C. to −40° C., −35° C. to −45° C., −50° C. to −80° C., or overlapping ranges thereof. The desired temperature may be maintained for 5-20 minutes, 10-15 minutes, or greater than 10 minutes, depending on the temperature and thermal dose desired. Furthermore, treatment may be effected by any mechanical destruction and or removal means capable of severing or denervating the basivertebral nerve. For example, a cutting blade, bur, electrocautery knife or mechanically actuated cutter may be used to effect denervation of the basivertebral nerve.
In addition to or separate from treating (e.g., modulating) the basivertebral nerve or an intraosseous nerve, a sensor may be delivered to the region to preoperatively or postoperatively measure nerve conduction at the treatment region. In this configuration, the sensor may be delivered on a distal tip of a flexible probe that may or may not have treatment elements as well.
In accordance with several embodiments, the goal of the treatment may be ablation, or necrosis of the target nerve or tissue, or some lesser degree of treatment to denervate the basivertebral nerve. For example, the treatment energy or frequency may be just sufficient to stimulate the nerve to block the nerve from transmitting signals (e.g. signals indicating pain) without ablation or necrosis of the nerve. The modulation may be temporary or permanent.
In accordance with several embodiments, the therapeutic modalities described herein (including energy or agent delivery) modulates neurotransmission (e.g., neurotransmitter synthesis, release, degradation and/or receptor function, etc.). In some embodiments, signals of nociception are affected. Effects on neurokinin A, neuropeptide Y, substance P, serotonin and/or other signaling pathways are provided in some embodiments. Calcium and/or sodium channel effects are provided in one embodiment. In some embodiments, G-protein coupled receptors are affected.
Once the treatment is complete, the probe 100 may be withdrawn. The curved cannula 50 may then be withdrawn into the needle trocar 20. The needle trocar 20 with the curved cannula 50 may then be removed and the access site may be closed as prescribed by the physician or other medical professional.
In the above system 10, in accordance with several embodiments, the design of the curves 56 and 66 of the curved cannula 50 and curved stylet 60 is such that a flexible element (e.g., distal portion of the treatment device) can navigate through the angular range of deployment of the curved cannula 50 (e.g., Nitinol or other material tube). The curved cannula 50 allows the flexible element to navigate through a curve within bone without veering off towards an unintended direction. Cancellous bone density varies from person to person. Therefore, creating a curved channel within varying density cancellous bone 124 will generally not predictably or accurately support and contain the treatment device as it tries to navigate the curved channel.
With the system 10, the treatment device 100 may be deployed into the bone through the curved cannula 50 (e.g., Nitinol tube), which supports the flexible element (e.g., distal portion of the treatment device) as it traverses through the curve. When it departs from the tube, it will do so in a linear direction along path 146 towards the target zone. In accordance with several embodiments, this advantageously allows the user to predictably and accurately deploy the treatment device towards the target zone or location T regardless of the density of the cancellous bone.
In some embodiments, a radius of curvature that is smaller than that which can be achieved with a large diameter Nitinol tube may be advantageous. To achieve this, the curved portion of the curved cannula 50 may take one of several forms. In one embodiment, the curved cannula 50 is formed from a rigid polymer (e.g., formed PEEK) that can be heat set in a particular curve. If the polymer was unable to hold the desired curve, an additional stylet (e.g. curved stylet 60) of Nitinol, flexible stainless steel, shape memory material, metallic or metallic-based material, or other appropriate material, may also be used in conjunction with the polymer tube to achieve the desired curve. In some embodiments, the stylet comprises a braided tube, rod, or wire. In some embodiments, the stylet comprises a non-braided tube, rod, or wire, or combinations thereof. This proposed combination of material may encompass any number or variety of materials in multiple different diameters to achieve the desired curve. These combinations only need to ensure that the final outside element (e.g. trocar 20) be “disengageable” from the internal elements and have an inner diameter sufficient to allow the desired treatment device 100 to pass to the treatment region T. In accordance with several embodiments, the treatment region T is in a posterior section (e.g., posterior to a midline) of the vertebral body. The treatment region T may correspond to an expected location of a terminus of a basivertebral foramen.
In one embodiment, the curved cannula 50 may comprise a Nitinol, shape memory material, stainless steel or other metallic tube having a pattern of reliefs or cuts (not shown) in the wall of the tube (particularly on the outer radius of the bend). The pattern of cuts or reliefs could allow the tube to bend into a radius tighter than a solid tube could without compromising the integrity of the tubing wall. The curved portion of the curved cannula 50 may comprise a different material than the main body of the curved cannula or the same material.
In an embodiment of the method, the straightening stylet 40 is inserted into the curved cannula 50 and secured. In this embodiment, the straightening stylet 40 has a sharp tip 46 designed to penetrate bone. Once the straightening stylet 40 is secure and the curved cannula 50 is straight, they are inserted into the needle trocar 20 and secured. In tone embodiment, the curved cannula 50 and straightening stylet 40 are inserted into the shaft 28 of the trocar 20 only as far as to have sharp tip 46 of the straightening stylet 40 protrude from the distal end 22 of the trocar 20. Proper alignment is maintained by aligning a flat on the upper portion of the curved cannula 50 with a pin secured perpendicularly into the needle trocar 20 handle. Other alignment elements may also be used (e.g., visual indicia such as lines, text, shapes, orientations, or coloring).
Referring now to
In accordance with several embodiments, after the proper depth is achieved, the straightening stylet 40 may be removed. The curved stylet 60 may then be straightened out by sliding the small tube 68 on its shaft towards the distal tip 64. In some embodiments, the curved distal tip 66 is straightened out and fully retracted inside the small tube 68, and then the curved stylet 60 is inserted into the curved cannula 50, which still resides inside the needle trocar 20. Once the curved stylet 60 is inserted into the curved cannula 50, the small tube 68 may be met by a stop 55 as illustrated in
In several embodiments, to create a maximum force, the curves of the two parts (50 & 60) may be aligned. To ensure alignment, the cap on the curved stylet 60 may have an alignment pin, which engages with a notch on the top of the curved cannula 50. Other alignment elements may also be used (e.g., visual indicia such as lines, text, shapes, orientations, or coloring).
In one embodiment, when the stylet 60 is fully seated and aligned with the curved cannula 50, the tip of the curved stylet 60 may protrude from the tip of the curved cannula 50 by about 1/16 to 3/16 inches. This protrusion can help to drive the curved cannula 50 in the direction of its orientation during deployment. Once the curved stylet 60 and the curved cannula 50 are engaged, the lock nut at the top of the curved cannula 50 may be rotated counter clockwise to allow the cannula 50 and stylet 60 to be advanced with relation to the needle trocar 20, as illustrated in
In accordance with several embodiments, the curved stylet 60 may then be removed and replaced by the channeling stylet 90. In some embodiments, the channeling stylet 90 is advanced beyond the end of the curved cannula 50, as illustrated in
Once the treatment is complete, the treatment device 100 can be withdrawn. In some embodiments, the curved cannula 50 is then withdrawn into the needle trocar 20. The needle trocar 20 with the curved cannula 50 can then be removed and the access site can be closed as prescribed by the physician or other medical professional.
In accordance with several embodiments,
As shown in
In the example illustrated in
Any of the embodiments described herein may be provided as a kit of instruments to treat different regions of the body. For example, the location, orientation and angle of the treatment device with respect to the trocar 20 may be varied by providing a set of instruments at varying increments. This may be achieved by varying the curvature (56, 66) in the curved cannula 50 and curved stylet 60. The curvature may be varied by varying the radius of curvature r, the insertion depth (shaft length LS and tip length LT, and/or the final exit angle ⋅ with respect to the trocar 20 central bore. Thus, the physician or other clinician may select a different kit for treating a lumber spine segment as opposed to a cervical spine segment, as the anatomy will dictate the path that needs to be channeled.
Thus in accordance with several embodiments, when treating different spine segments, a set out of the kit may be selected to match the vertebra (or other region being treated). For example, delivering the treatment device at or near the basivertebral nerve junction or terminus for a lumbar vertebra may have a different angle than for a sacral or cervical vertebra, and may vary from patient to patient. The set may be selected from the kit intraoperatively, or from a pre-surgery diagnostic evaluation (e.g. radiographic imaging of the target region).
The elongate delivery tube 204 comprises a laterally positioned radial opening or window 212 disposed just proximal or at the distal tip 208. The window 212 provides radial access from the central channel 218 of tube 204 so that an instrument or probe (e.g. probe 250 distal end) may be delivered at an angle (e.g. non-axial) with respect to the tube axis or central channel 218.
In one embodiment, the proximal end 206 of trocar housing 202 comprises a centrally-located, counter-bore or recess 216 that is in communication with trocar channel 218. Trocar recess 216 allows placement and reciprocation of curveable cannula 230 within the trocar recess 216 and trocar central channel 218. The curveable cannula 230 may be held in place at a specified location within the trocar recess 216 via a stop nut 240 that is threaded about proximal body 246 of the curveable cannula 230. The curveable cannula 230 also comprises a central recess 268 within proximal body 246 that is centrally aligned with cannula channel 245. Central recess 268 and cannula channel 245 are configured to receive and allow reciprocation of probe 250, which is threaded into drive nut 270. In several embodiments, the drive nut 270 comprises a hardened proximal surface suitable for applying an impact force to advance one or more of the trocar, curveable cannula, or probe through bone.
During insertion of the trocar 210, in accordance with several embodiments, the stop nut 240 may be threaded distally along external threads 248 of the proximal body 246 of the curveable cannula 230 to restrict motion of the cannula 230 distally down trocar recess 216. This restrained motion may keep the distal end 232 of the cannula 230 from prematurely deploying while the trocar 210 is being delivered.
In accordance with several embodiments, the distal end of the curveable cannula is deformable so as to be delivered in a straight configuration through the trocar and deployed in a curved configuration outward from the radial opening at an angle with respect to the central axis. As shown in
In one embodiment, the mating links 234 are held together with a cord 242 that runs from the proximal body 246 of the curveable cannula 230, and terminates at an aperture 236 in the distal link 232. In some embodiments, the distal end of cord 242 terminates at a ball 238 that is disposed in a counter-bore, countersink, or like retaining surface of the aperture 236 to retain the cord within the distal link 232.
Referring now to
In accordance with several embodiments, the proximal body 246 of curveable cannula 230 may then be deployed downward within trocar recess 216, as shown in
In some embodiments, a pull cord 242 is coupled to the distal tip of the curveable cannula 230, the pull cord extending to the proximal end of the trocar 210. In addition to the ramp 209, the curved path of the distal tip 233 is facilitated by tension provided by cord 242, which forces the mating links 232, 234 to arch upon the applied tension. The pull cord may be configured to apply a tensile force to the distal end of the curveable cannula to bias the curveable cannula into a curved configuration. In some embodiments, the cord 242 is coupled to male-threaded dial 212 (see
In an alternative embodiment, cord 242 may comprise a memory material such as a Nitinol wire that fastens the tube 244 and links 232, 234 in a preformed curved-shape. The cord 246 in this configuration stretches to allow the curveable cannula 230 to be delivered into and stowed in a linear form within channel 218, and retracts when not restrained in channel 218 to drive a curved path when exiting window 212.
As shown in
As shown in
Furthermore, the proximal end 254 of the probe 250 may comprise a plurality of vertical grooves 264, at least one of which interfaces with key 266 of the curveable cannula 230. This interface, in one embodiment, only allows axial motion of the proximal body 264 with the curveable cannula 230, and restricts rotation of the proximal body 264 with the curveable cannula 230. Thus, rotation of the drive nut 270 may only result in proximal translation of the drive nut 270. As seen in
Referring now to
In one embodiment, a channeling stylet (such as stylet 90 shown in kit 10 of
Once the distal tip 274 of the probe 250 is positioned at the desired location, treatment of the target tissue may be performed. As shown in
Cap 290 may further be configured to include (e.g. a self-contained unit) a power source (e.g. battery) and receptacles (not shown) to couple to the probe 250, thereby supplying the energy to deliver a therapeutic level of energy to the tissue. In this configuration, the cap 290 may have sufficient power to deliver one or more metered doses of energy specifically measured to modulate (e.g., denervate) at least a portion of the basivertebral nerve of a vertebral body.
In accordance with several embodiments, the cap 290 may be threaded (or otherwise releasable coupled) into drive nut 270 to be interchangeable depending on the application or step of the procedure. For example, a cap 290 having a reinforced/hardened surface 292 used for driving the system 201 into the bone may be replaced by another cap having couplings (not shown) for probe 250, an internal power supply (not shown), or couplings for an external power supply/controller (not shown) for delivering energy for treatment and/or diagnosis of a region of tissue. For embodiments wherein a fluid and/or agent is delivered to the target tissue, the cap 290 may be configured to facilitate delivery of the fluid through a probe having one or more fluid delivery channels. In some embodiments, the interchangeable cap 290 is configured to provide access to the probe 250 for providing a therapeutic energy.
In one embodiment, a curveable cannula 322 is positioned in the trocar 302, the curveable cannula 322 having a distal end 324 coupled via linkage 326 to a pivotable arm 310. The proximal end (not shown) of the curveable cannula may comprise a portion or all of any of the previously described proximal ends for devices 10, 200, or 201 disclosed herein. The pivotable arm 310 has a first end pivotably coupled at joint 314 at a location at or near the distal tip 334 of the trocar 334. In a stowed configuration (illustrated in
As shown in
In one embodiment, system 400 further comprises a straight stylet 450 having an elongate shaft 454 configured to be received in trocar channel 418 of slotted needle trocar 410. Elongate shaft 454 has a sharp-tipped distal end 456 that, when installed fully within the slotted needle trocar 410, extends slightly beyond the distal end 416 of the trocar tube 410 (see
In one embodiment, cannula stylet 450 comprises a pair of key protrusions 458 that are orthogonally oriented with respect to the length of the stylet handle 452. The key protrusions are configured to lock with key slots 426 on the trocar handle 412 via rotation of the stylet handle 452 after full insertion in the trocar 410. When the stylet handle 452 is fully rotated to the orientation shown in
With the stylet 450 locked into place with respect to the trocar handle 412, the stylet 450 and slotted needle trocar 410 may be configured to be inserted in unison into the patient's tissue. In accordance with several embodiments, this step may be performed prior to insertion into the patient or after insertion into the patient.
In one embodiment, the stylet handle 452 comprises a raised striking surface 460 made of a hard, rigid material (e.g. stainless steel or similar metallic or plastic material) to allow the trocar 410 to be tapped into place with a mallet or the like, particularly when piercing the hard cortical shell of the vertebral body.
In accordance with several embodiments,
In one embodiment, system 400 further comprises a curved cannula 430 that is used to create and/or maintain a curved path within the bone and/or tissue when extended past the distal end 416 of trocar 410. Curved cannula 430 may comprise a slotted handle 432 that is proximal to a threaded tube 446 and elongate straight tubular body 434 section and a preformed, curved distal end 436. In accordance with several embodiments, the curved distal end 436 of tubular body 434 is made of a shape memory material (e.g., Nitinol) that allows the curved distal end to be bent into a straight configuration, and retain its curved shape upon release of a restraint.
Referring to
In one embodiment, the curved cannula 430 is held in place at a specified location within the trocar recess 420 and trocar channel 418 via a stop nut 440 that is threaded about proximal body 446 of the curved cannula 430. With the stop nut 440 in the position shown in
In accordance with several embodiments,
As shown in
In one embodiment, the curvilinear bottom surface 424 comprises a radius substantially matching the natural radius of curved distal end 436. The curvilinear bottom surface 424 having such a matching radius may advantageously promote an evenly distributed loading along the curved distal end 436 while the curved distal end 436 is advanced into the tapered section 428 and straightened into trocar channel 418.
In order to ensure proper trajectory of the curved cannula 430, the indicia arrows 404 of the curved cannula handle 432 (see
Referring now to
Referring to
Referring to
In one embodiment, the curved cannula 430 comprises a central recess 448 within cannula handle 432 that is in communication with and centrally aligned with cannula channel 438. Central recess 448 and cannula channel 438 may be configured to receive and allow reciprocation of curved stylet 470 (and a treatment probe that may be deployed subsequently). Similar to the trocar handle 412, the cannula handle 432 may comprise a lateral slot 433 that is in communication with the central recess 448. In one embodiment, lateral slot 433 comprises a curved lower surface 435 that facilitates insertion of the curved tip 476 of the stylet body 474 into the central recess 448 and cannula channel 438 (e.g., similar to the illustration in
In accordance with several embodiments, to facilitate proper orientation of the curved end 476 of stylet 450 with the curved distal end 436 of the curved cannula 430, arrow indicia 406 (see
With the curved stylet 470 installed into the curved cannula 430, the lock nut 440 may be raised along proximal body 446 of curved cannula 430, and the curved stylet 470 and curved cannula 430 assembly may be further extended down trocar central channel 418 so that the curved distal end 476 generates a curved path beyond the distal end 416 of the trocar 410.
In accordance with several embodiments, when the curved path is created, the curved stylet 470 is removed. A treatment probe (such as the treatment probes described herein) may then be delivered through the curved cannula 430 to the treatment site.
In some embodiments, a channeling stylet 490 is used to create a working channel beyond the end of the curved path created by the curveable cannula 430 prior to deploying a treatment probe for a diagnostic device. In one embodiment, the elongate body 494 of the channeling stylet 490 is inserted in the recess 448 of the cannula handle 432 and delivered through the cannula channel 438 so that the distal end 496 of the channeling stylet 490 extends beyond the curved distal end 436 of the curved cannula 430 a specified distance, creating a hybrid curved and straight channel through the cancellous bone. The channeling stylet 490 may then be removed, and a treatment probe may be installed in its place to deliver therapeutic treatment to the target treatment site.
Several embodiments of the invention are shown in
In accordance with several embodiments, surgical devices and surgical systems described herein may be used to deliver numerous types of treatment modalities to varying regions of the body. In addition to the particular usefulness of several embodiments in navigating through bone. The systems and methods may also be used to navigate through soft tissue, or through channels or lumens in the body, particularly where one lumen may branch from another lumen.
The following examples illustrate several embodiments of a system 510 for generating a curve bone path in the vertebral body, and more particularly, for creating a bone path via a transpedicular approach to access targeted regions in the spine. In particular, the system 510 may be used to deliver a treatment device to treat or modulate (e.g., ablate) intraosseous nerves, and in particular the basivertebral nerve. In accordance with several embodiments, in addition to the system and methods providing significant benefit in accessing the basivertebral nerve, the systems and methods may similarly be used to create a bone path in any part of the body.
Referring to
Referring to
In one embodiment, in communication with the trocar recess 534 is a lateral slot 530 running through the handle 522 generally orthogonally to the axis of the trocar recess 534 and trocar channel 528. The lateral slot comprises a curvilinear lower surface 532 that may be configured to allow the curved distal end 560 of the treatment probe 550 to be inserted in the trocar 520 without having to pre-straighten the curved distal end 560 of the treatment probe 550. Indicia 540 may be positioned on the top of the handle 522 to guide proper orientation of the treatment probe 550.
In accordance with several embodiments,
As shown in
In one embodiment, the curvilinear bottom surface 532 may comprise a radius significantly matching the natural radius of curved distal end 560 of the treatment probe 560. The curvilinear bottom surface 532 having such a matching radius may advantageously promote an evenly distributed loading along the curved distal end 650 while the curved distal end 560 is advanced into and straightened into trocar channel 528.
To ensure proper trajectory of the probe 550 in one embodiment, the indicia arrows (not shown) of the probe handle 552 may be lined up in the same direction as indicia arrows 540 (
Referring now to
Referring to
The distal end 560 of stylet 558 may be pre-curved to create an angular range of approximately 0° to approximately 180° (e.g., from approximately 45° to approximately 110°, or from approximately 75° to approximately 100°), when fully deployed from the trocar 520.
In several embodiments, the curved distal end 560 comprises a plurality of circumferentially relieved sections 578 separated by a plurality of bosses 566. The bosses 566 have an outside diameter that corresponds closely to the inside diameter of the trocar channel 528 of hypotube 524 (e.g., the diameter of each boss 566 will be approximately 0.025″ to 0.060″ smaller than the diameter of the trocar channel 528). The circumferentially relieved sections 578 may allow for the curved distal end 560 to conform to the straight confines of the trocar channel 528, while promoting retention of the curved distal end 560 to its preformed curved state. In one embodiment, the stylet 552 is machined with groove 574 and recesses 578, 582 prior to heat setting the curve 560.
In accordance with several embodiments, the basivertebral nerves are at, or in close proximity to, the exit point 642. Thus, the target region of the basivertebral nerve 622 is located within the cancellous portion 624 of the bone (i.e., to the interior of the outer cortical bone region 628), and proximal to the junction J of the basivertebral nerve 622 having a plurality of branches 630 (e.g. between points A and B along nerve 622). Treatment in this region may be advantageous because only a single portion of the basivertebral nerve 622 need be effectively treated to denervate or affect the entire system. Typically, treatment in accordance with this embodiment can be effectuated by focusing in the region of the vertebral body located between 60%, 643, and 90%, 644, of the distance between the anterior and posterior ends of the vertebral body. In contrast, treatment of the basivertebral nerve 622 in locations more downstream than the junction J may require the denervation of each branch 630.
In accordance with several embodiments for accessing the basivertebral nerve, the patient's skin is penetrated with a surgical instrument which is then used to access the desired basivertebral nerves, i.e., percutaneously. In one embodiment, a transpedicular approach is used for penetrating the vertebral cortex to access the basivertebral nerve 622. A passageway 640 is created between the transverse process 634 and spinous process 636 through the pedicle 638 into the cancellous bone region 124 of the vertebral body 626 to access a region at or near the base of the nerve 622. It is appreciated that a postereolateral approach (not shown) may also be used for accessing the nerve.
In accordance with several embodiments,
As shown in
Referring now to
In an alternative embodiment, the tip 562 of probe may be used as the stylet for piercing the cortical shell 628 and generating path 640 through vertebra 620. In this configuration, the probe tip 662 is only advanced slightly from distal end 526 of trocar hypotube 524 to act as stylet for advancement of trocar. A releasable collar (not shown) may be used between probe handle 552 and trocar handle 522 to restrict advancement of the curved distal end 560 past distal opening 526 of the trocar body 524. In one embodiment the trocar 520 is then driven to the proper location within the vertebral body 626 with striking surface 554 to generate passageway 640 between the transverse process 634 and spinous process 636 through the pedicle 638 into the cancellous bone region 624 of the vertebral body 626.
Referring now to
In accordance with several embodiments, treatment energy may then be delivered via bipolar electrodes 564 to the target treatment location T at the basivertebral nerve 622 to perform a localized treatment via delivery of a therapeutic level of heating to stimulate or ablate the basivertebral nerve 622.
In one embodiment, the RF energy is delivered to the treatment site via electrodes 564, and activated to deliver therapeutic treatment energy. In one embodiment, the treatment probe comprises an RF delivery probe having bipolar electrodes.
In accordance with several embodiments, any number of treatment modalities may be delivered to the treatment site for therapeutic treatment. For example, treatment may be affected by monopolar, tripolar or sesquipolar RF, ultrasound, radiation, steam, microwave, laser, or other heating means. In one embodiment, the treatment device comprises a fluid delivery catheter that deposits an agent (e.g., bone cement, or other therapeutic agent) to the treatment site T.
In accordance with several embodiments, cryogenic cooling (not shown) may be delivered for localized treatment of the basivertebral nerve. Furthermore, treatment may be affected by any mechanical destruction and or removal means capable of severing or denervating the basivertebral nerve. For example, a cutting blade, bur or mechanically actuated cutter (not shown) typically used in the art of orthoscopic surgery may be used to affect denervation of the basivertebral nerve.
In addition to or separate from treating the basivertebral nerve, a sensor (not shown) may be delivered to the region to preoperatively or postoperatively measure nerve conduction at the treatment region. In this configuration, the sensor may be delivered on a distal tip of a flexible probe that may or may not have treatment elements as well.
In other embodiments, the goal of the treatment may be ablation, or necrosis of the target nerve or tissue, or some lesser degree of treatment to denervate the basivertebral nerve. For example, the treatment energy or frequency may be just sufficient to stimulate the nerve to block the nerve from transmitting signal (e.g. signals indicating pain).
Once the treatment is complete, the curved probe 550 may be withdrawn into the cannula. The needle trocar 550 with the curved cannula 550 is then removed and the access site is closed as prescribed by the physician.
In accordance with several embodiments, the above systems 10, 200, 201, 300, 400, and 510 may be provided as a kit of instruments to treat different regions of the body. As one example, the varying of location, orientation, and angle may be achieved by varying the curvature in the curved or curveable cannula (e.g., 230, 322, 430, or 550). The curvature may be varied by varying the radius of curvature, the insertion depth (shaft length and tip length), and/or the final exit angle with respect to the trocar channel 528. Thus, the physician may select a different kit for treating a lumber spine segment as opposed to a cervical spine segment, as the anatomy may dictate the path that needs to be channeled.
In accordance with several embodiments, each of the components in the systems 10, 200, 201, 300, 400 and 510 may have any length, shape, or diameter desired or required to provide access to the treatment and/or diagnostic region (e.g. intraosseous nerve or basivertebral nerve trunk) thereby facilitating effective treatment and/or diagnostic of the target region. For example, the size of the intraosseous nerve to be treated, the size of the passageway in the bone (e.g. pedicle 138 or 638) for accessing the intraosseous nerve, and the location of the bone (and thus the intraosseous nerve) are factors that that may assist in determining the desired size and shape of the individual instruments. In several embodiments, the treatment device (e.g., RF probe) has a diameter between 1 mm and 5 mm (e.g., between 1 mm and 3 mm, between 2 mm and 4 mm, between 3 mm and 5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, or any diameter between the recited ranges).
In accordance with several embodiments, the systems 10, 200, 201, 300, 400, and 510 described above may be used with a number of different treatment modalities for therapeutic treatment of the target region, which may be spinal or non-spinal. For example, in one embodiment, it is desirable to operate the treatment devices or probes in system 10, 200, 201, 300, 400, and 510 in a manner that ablates the tissue of the target region (e.g. basivertebral nerve) to produce heat as described in U.S. Pat. No. 6,699,242, herein incorporated by reference in its entirety.
In another embodiment, the treatment device is configured to deliver therapeutic treatment that is targeted to block nerve conduction without ablating the nerve, i.e. thermal treatment is delivered to the nerve (e.g. via thermal therapy, agent or the like) that results in denervation of the basivertebral nerve without necrosis of tissue. This may be achieved via delivery of a lesser amount of energy or agent to the tissue site (either in the form of less exposure time, concentration, intensity, thermal dose etc.) than is required for ablation, but an amount sufficient to achieve some amount of temporary or permanent denervation.
In accordance with several embodiments, the probe described herein may comprise non-therapy devices, such as diagnostic devises (e.g. ultrasound, cameras, or the like) to diagnose a region of tissue independent of or in connection with treatment of the region of tissue.
In several embodiments, individual elements of any of the systems 10, 200, 201, 300, 400, and 510 detailed above may be used interchangeably where applicable. For example, the curved stylet 60 shown in systems 10 and 200 may be temporarily implemented in place of the probe of systems 201 and 300 to provide additional curving bias to the curveable cannula (230, 320) while the cannula is being driven into the bone. Furthermore, the channeling stylet 90 may be used to further generate a channel beyond the curved path provided by the curveable cannula (230, 320).
Several embodiments of a steerable devices or systems (e.g., including a distal treatment probe and a proximal handle) for actuating curvature/steering of the distal probe are shown in
As shown in
In one embodiment, not shown, an actuation knob is spring loaded to restrain/retain the knob in respective slots at given increments (e.g., in an “escalating ladder” embodiment). The handle 9910 may have a stationary rail and a spring retainer that slides along the stationary rail. As the knob is moved toward the 90 degree marking, the pull wire may be retracted to allow the distal end to bend upon actuation of the pull wire. This escalating ladder embodiment may allow the knob to come to rest at certain preset locations on the handle 9910. In one embodiment, the steerable probe 9900 comprises curved slots 9932.
In one embodiment, during operation, the treatment probe 9220 is configured to be disposed within the steerable sleeve 9240 so that the spherical tip of the electrode 9261 protrudes out of the distal end of the central channel of the sleeve 9240, and acts as a stylet while the probe 9220 and sleeve 9240 are guided in a curved path to the treatment site. Prior to delivery of the treatment probe 9220, a sharp stylet (not shown) may be inserted in the sleeve 9240 for piercing the outer cortical shell of the vertebral body. The stylet may then be removed and the treatment probe 9220 may be inserted for delivery to the treatment site via a steered, curved path. Upon reaching the treatment site, the sleeve 9240 may be retracted (or probe 9220 advanced) to expose the second of two bipolar electrodes for treatment.
In general, it may be desirable to operate embodiments of the invention in a manner that produce a peak temperature in the target tissue of between about 80° C. and 95° C. When the peak temperature is below 80° C., the off-peak temperatures may quickly fall below about 45° C. When the peak temperature is above about 95° C., the bone tissue exposed to that peak temperature may experience necrosis and produce charring. This charring reduces the electrical conductivity of the charred tissue, thereby making it more difficult to pass RF current through the target tissue beyond the char and to resistively heat the target tissue beyond the char. In some embodiments, the peak temperature is between 86° C. and 94° C., between 80° C. and 90° C., 85° C., overlapping ranges thereof, or any temperature value between 80° C. and 95° C.
It may be desirable to heat the volume of target tissue to a minimum temperature of at least 42° C., in accordance with several embodiments. When the tissue experiences a temperature above 42° C., nerves within the target tissue may be desirably damaged. However, it is believed that denervation is a function of the total quantum of energy delivered to the target tissue; i.e., both exposure temperature and exposure time determine the total dose of energy delivered.
Typically, the period of time that an intraosseous nerve is exposed to therapeutic temperatures is in general related to the length of time in which the electrodes are activated. In some embodiments, the electrodes, when the peak temperature is between 80° C. and 95° C., may be activated between 10 and 20 minutes, between 10 and 15 minutes, 12 minutes, 15 minutes, less than 10 minutes, greater than 20 minutes, or any duration of time between 10 and 20 minutes, to achieve the minimum target tissue temperature such that the nerve tissue is modulated (e.g., denervated). However, since it has been observed that the total heating zone remains relatively hot even after power has been turned off (and the electric field eliminated), the exposure time can include a period of time in which current is not running through the electrodes.
In general, the farther apart the electrodes, the greater the likelihood that the ION will be contained within the total heating zone. Therefore, in some embodiments the electrodes are placed at least 5 mm apart or at least 10 mm apart. However, if the electrodes are spaced too far apart, the electric field takes on an undesirably extreme dumbbell shape. Therefore, in many embodiments, the electrodes are placed apart a distance of between 1 mm and 25 mm, between 5 mm and 15 mm, between 10 mm and 15 mm between 3 mm and 10 mm, between 8 mm and 13 mm, between 10 mm and 18 mm, between 12 mm and 20 mm between 20 and 25 mm, between 1 mm and 3 mm, or any integer or value between 1 mm and 25 mm.
In some embodiments, it is desirable to heat the target tissue so that at least about 1 cc of bone tissue experiences the minimum temperature. This volume corresponds to a sphere having a radius of about 0.6 cm. Alternatively stated, it is desirable to heat the target tissue so the minimum temperature is achieved by every portion of the bone within 0.6 cm of the point experiencing the peak temperature.
In accordance with several embodiments, it is desirable to heat the target tissue so that at least about 3 cc of bone experiences the minimum temperature. This volume corresponds to a sphere having a radius of about 1 cm (e.g., 0.7 cm, 0.8 cm. 0.9 cm, 1.0 cm, 1.1 cm, 1.2 cm, 1.3 cm, 1.4 cm).
Some embodiments provide a steady-state heated zone having a peak temperature of between 80° C. and 95° C. (e.g., between 86° C. and 94° C., between 80° C. and 90° C., or overlapping ranges thereof), and heat at least 1 cc of bone (e.g., at least 2 cc of bone, at least 3 cc of bone, at least 4 cc of bone, at least 5 cc of bone) to a temperature of at least 50° C. (e.g., 60° C.).
In accordance with several embodiments, a method of therapeutically treating a vertebral body having a basivertebral nerve comprises providing an energy device having an active and a return electrode, inserting the active electrode into the vertebral body, inserting the return electrode into the vertebral body, and applying a sufficiently high frequency voltage difference between the active and return electrodes to generate a current therebetween to produce a total heating zone having a diameter of at least 0.5 cm and a steady state temperature of at least 50° C.
As noted above, a peak temperature below about 100° C. or below about 105° C. is desirable in order to prevent charring of the adjacent tissue, steam formation and tissue popping. In some embodiments, this is accomplished by providing the power supply with a feedback means that allows the peak temperature within the heating zone to be maintained at a desired target temperature, such as 90° C. In some embodiments, the peak temperature is in the range of 85° C. to 95° C. In other embodiments, the peak temperature is between about 70° C. and 90° C.
In some embodiments, between about 24 watts and 30 watts of power is first supplied to the device in order to rapidly heat the relatively cool bone, with maximum amperage being obtained within about 10-15 seconds. In other embodiments, between about 28 watts and 32 watts of power, between about 20 watts and 26 watts of power, between 30 watts and 40 watts of power, between 15 watts and 24 watts of power, overlapping ranges thereof, or any power level within the ranges, is first supplied to the device. In some embodiments, the maximum amperage may be obtained within 5-10 seconds, within about 15-25 seconds, within about 7-12 seconds, within about 13-18 seconds, overlapping ranges thereof, or any duration within the recited ranges. As the bone is further heated to the target temperature, the feedback means gradually reduces the power input to the device to between about 6-10 watts. In some embodiments, the power input is reduced to between 4-7 watts, about 8-12 watts, between 2-6 watts, between about 7-15 watts, or overlapping ranges thereto.
Cooling may be employed for any of the neuromodulation devices (e.g., energy delivery devices) described herein. In several embodiments, a cooling balloon or other cooling device or fluid (e.g., heat removal elements, heat sinks, cooling fluid circulating through one or more lumens of the neuromodulation device) is used for cooling the treatment zone or location or the area surrounding the treatment zone or location.
If the active electrode has no active cooling means, it may become subject to conductive heating by the heated tissue, and the resultant increased temperature in the electrode may adversely affect performance by charring the adjacent bone tissue. Accordingly, in some embodiments, a cool tip active electrode may be employed. The cooled electrode helps maintain the temperature of the electrode at a desired temperature. Cooled tip active electrodes are known in the art. Alternatively, the power supply may be designed to provide a pulsed energy input. It has been found that pulsing the current favorably allows heat to dissipate from the electrode tip, and so the active electrode stays relatively cooler.
In various embodiments, the neuromodulation device comprises an electrosurgical probe having a shaft with a proximal end, a distal end, and at least one active electrode at or near the distal end. A connector may be provided at or near the proximal end of the shaft for electrically coupling the active electrode to a high frequency voltage source. In some embodiments, a return electrode coupled to the voltage source is spaced a sufficient distance from the active electrode to substantially avoid or minimize current shorting therebetween. The return electrode may be provided integral with the shaft of the probe or it may be separate from the shaft
In some embodiments, the electrosurgical probe or catheter comprises a shaft or a handpiece having a proximal end and a distal end which supports one or more electrode terminal(s). The shaft or handpiece may assume a wide variety of configurations, with the primary purpose being to mechanically support the active electrode and permit the treating physician to manipulate the electrode from a proximal end of the shaft. The shaft may be rigid or flexible, with flexible shafts optionally being combined with a generally rigid external tube for mechanical support. Flexible shafts may be combined with pull wires, shape memory actuators, and other known mechanisms for effecting selective deflection of the distal end of the shaft to facilitate positioning of the electrode array. The shaft will usually include a plurality of wires or other conductive elements running axially therethrough to permit connection of the electrode array to a connector at the proximal end of the shaft.
In several embodiments, the shaft is a rigid needle that is introduced through a percutaneous penetration in the patient. However, for endoscopic procedures within the spine, the shaft may have a suitable diameter and length to allow the surgeon to reach the target site (e.g., a disc) by delivering the shaft through the thoracic cavity, the abdomen or the like. Thus, the shaft may have a length in the range of about 5.0 to 30.0 cm (e.g., about 5-10, 10-15, 10-20, or 10-30 cm, or overlapping ranges thereof), and a diameter in the range of about 0.2 mm to about 10 mm (e.g., about 0.2-1, 1-2, 2-4, 2-6, 6-8, or 5-10 mm, or overlapping ranges thereof). In any of these embodiments, the shaft may also be introduced through rigid or flexible endoscopes.
The probe may include one or more active electrode(s) for applying electrical energy to tissues within the spine. The probe may include one or more return electrode(s), or the return electrode may be positioned on the patient's back, as a dispersive pad. In either embodiment, sufficient electrical energy is applied through the probe to the active electrode(s) to either necrose the blood supply or nerves within the vertebral body.
The electrosurgical instrument may also be a catheter that is delivered percutaneously and/or endoluminally into the patient by insertion through a conventional or specialized guide catheter, or the invention may include a catheter having an active electrode or electrode array integral with its distal end. The catheter shaft may be rigid or flexible, with flexible shafts optionally being combined with a generally rigid external tube for mechanical support. Flexible shafts may be combined with pull wires, shape memory actuators, and other known mechanisms for effecting selective deflection of the distal end of the shaft to facilitate positioning of the electrode or electrode array. The catheter shaft may include a plurality of wires or other conductive elements running axially therethrough to permit connection of the electrode or electrode array and the return electrode to a connector at the proximal end of the catheter shaft. The catheter shaft may include a guide wire for guiding the catheter to the target site, or the catheter may comprise a steerable guide catheter. The catheter may also include a substantially rigid distal end portion to increase the torque control of the distal end portion as the catheter is advanced further into the patient's body. Specific deployment means will be described in detail in connection with the figures hereinafter.
In some embodiments, the electrically conductive wires may run freely inside the catheter bore in an unconstrained made, or within multiple lumens within the catheter bore.
The tip region of the instrument may comprise many independent electrode terminals designed to deliver electrical energy in the vicinity of the tip. The selective application of electrical energy is achieved by connecting each individual electrode terminal and the return electrode to a power source having independently controlled or current limited channels. The return electrode(s) may comprise a single tubular member of conductive material proximal to the electrode array. Alternatively, the instrument may comprise an array of return electrodes at the distal tip of the instrument (together with the active electrodes) to maintain the electric current at the tip. The application of high frequency voltage between the return electrode(s) and the electrode array results in the generation of high electric field intensities at the distal tips of the electrode terminals with conduction of high frequency current from each individual electrode terminal to the return electrode. The current flow from each individual electrode terminal to the return electrode(s) is controlled by either active or passive means, or a combination thereof, to deliver electrical energy to the surrounding conductive fluid while minimizing or preventing energy delivery to surrounding (non-target) tissue, such as the spinal cord.
Temperature probes associated with the apparatus may be disposed on or within the electrode carrier; between the electrodes (may be preferred in bipolar embodiments); or within the electrodes (may be preferred for monopolar embodiments). In some embodiments wherein the electrodes are placed on either side of the ION, a temperature probe is disposed between the electrodes or in the electrodes. In alternate embodiments, the deployable portion of the temperature probe comprises a memory metal.
The electrode terminal(s) may be supported within or by an inorganic insulating support positioned near the distal end of the instrument shaft. The return electrode may be located on the instrument shaft, on another instrument or on the external surface of the patient (i.e., a dispersive pad). In some embodiments, the close proximity of the dual needle design to the intraosseous nerve makes a bipolar design more preferable because this minimizes the current flow through non-target tissue and surrounding nerves. Accordingly, the return electrode may be either integrated with the instrument body, or another instrument located in close proximity thereto. The proximal end of the instrument(s) may include the appropriate electrical connections for coupling the return electrode(s) and the electrode terminal(s) to a high frequency power supply, such as an electrosurgical generator.
In some embodiments, the active electrode(s) have an active portion or surface with surface geometries shaped to promote the electric field intensity and associated current density along the leading edges of the electrodes. Suitable surface geometries may be obtained by creating electrode shapes that include sharp edges, or by creating asperities or other surface roughness on the active surface(s) of the electrodes. Electrode shapes can include the use of formed wire (e.g., by drawing round wire through a shaping die) to form electrodes with a variety of cross-sectional shapes, such as square, rectangular, L or V shaped, or the like. The electrodes may be tip electrodes, ring electrodes, plate electrodes, cylindrical electrodes, frustoconical electrodes, or any other shape electrodes. Electrode edges may also be created by removing a portion of the elongate metal electrode to reshape the cross-section. For example, material can be ground along the length of a round or hollow wire electrode to form D or C shaped wires, respectively, with edges facing in ⋅ the cutting direction. Alternatively, material can be removed at closely spaced intervals along the electrode length to form transverse grooves, slots, threads or the like along the electrodes. In other embodiments, the probe can be sectored so that a given circumference comprises an electrode region and an inactive region. In some embodiments, the inactive region is masked.
The return electrode is, in several embodiments, spaced proximally from the active electrode(s) a suitable distance. In most of the embodiments described herein, the distal edge of the exposed surface of the return electrode is spaced about 1 to 25 mm (or any distance therebetween) from the proximal edge of the exposed surface of the active electrode(s), in dual needle insertions. Of course, this distance may vary with different voltage ranges, the electrode geometry and depend on the proximity of tissue structures to active and return electrodes. In several embodiments, the return electrode has an exposed length in the range of about 1 to 20 mm, about 2 to 6 mm, about 3 to 5 mm, about 1 to 8 mm, about 4 to 12 mm, about 6 to 16 mm, about 10 to 20 mm, 4 mm, 5 mm, 10 mm, or any length between 1 and 20 mm. The application of a high frequency voltage between the return electrode(s) and the electrode terminal(s) for appropriate time intervals effects modifying the target tissue. In several embodiments, the electrodes have an outer diameter of between 1 and 2 mm (e.g., between 1 and 1.5 mm, between 1.2 and 1.8 mm, between 1.5 and 1.7 mm, between 1.6 and 2 mm, 1.65 mm, or any outer diameter between the recited ranges). In several embodiments, the electrodes have an inner diameter of between 0.5 and 1.5 mm (e.g., between 0.5 and 0.8 mm, between 0.75 and 0.9 mm, between 0.8 and 1 mm, between 1 mm and 1.5 mm, 0.85 mm, or any inner diameter between the recited ranges).
Embodiments may use a single active electrode terminal or an array of electrode terminals spaced around the distal surface of a catheter or probe. In the latter embodiment, the electrode array usually includes a plurality of independently current limited and/or power-controlled electrode terminals to apply electrical energy selectively to the target tissue while limiting the unwanted application of electrical energy to the surrounding tissue and environment resulting from power dissipation into surrounding electrically conductive fluids, such as blood, normal saline, and the like. The electrode terminals may be independently current-limited by isolating the terminals from each other and connecting each terminal to a separate power source that is isolated from the other electrode terminals. Alternatively, the electrode terminals may be connected to each other at either the proximal or distal ends of the catheter to form a single wire that couples to a power source.
In one configuration, each individual electrode terminal in the electrode array is electrically insulated from all other electrode terminals in the array within said instrument and is connected to a power source which is isolated from each of the other. electrode terminals in the array or to circuitry which limits or interrupts current flow to the electrode terminal when low resistivity material (e.g., blood) causes a lower impedance path between the return electrode and the individual electrode terminal. The isolated power sources for each individual electrode terminal may be separate power supply circuits having internal impedance characteristics which limit power to the associated electrode terminal when a low impedance return path is encountered. By way of example, the isolated power source may be a user selectable constant current source. In one embodiment, lower impedance paths may automatically result in lower resistive heating levels since the heating is proportional to the square of the operating current times the impedance. Alternatively, a single power source may be connected to each of the electrode terminals through independently actuatable switches, or by independent current limiting elements, such as inductors, capacitors, resistors and/or combinations thereof. The current limiting elements may be provided in the instrument, connectors, cable, controller, or along the conductive path from the controller to the distal tip of the instrument. Alternatively, the resistance and/or capacitance may occur on the surface of the active electrode terminal(s) due to oxide layers which form selected electrode terminals (e.g., titanium or a resistive coating on the surface of me till, such as platinum).
In one embodiment of the invention, the active electrode comprises an electrode array having a plurality of electrically isolated electrode terminals disposed over a contact surface, which may be a planar or non-planar surface and which may be located at the distal tip or over a lateral surface of the shaft, or over both the tip and lateral surface(s). The electrode array may include at least two or more electrode terminals and may further comprise a temperature sensor. In one embodiment, each electrode terminal may be connected to the proximal connector by an electrically isolated conductor disposed within the shaft. The conductors permit independent electrical coupling of the electrode terminals to a high frequency power supply and control system with optional temperature monitor for operation of the probe. The control system may advantageously incorporate active and/or passive current limiting structures, which are designed to limit current flow when the associated electrode terminal is in contact with a low resistance return path back to the return electrode.
In one embodiment, the use of such electrode arrays in electrosurgical procedures may be particularly advantageous as it has been found to limit the depth of tissue necrosis without substantially reducing power delivery. The voltage applied to each electrode terminal causes electrical energy to be imparted to any body structure which is contacted by, or comes into close proximity with, the electrode terminal, where a current flow through all low electrical impedance paths may be limited. Since some of the needles are hollow, a conductive fluid could be added through the needle and into the bone structure for the purposes of lowering the electrical impedance and fill the spaces in the cancellous bone to make them better conductors to the needle.
It should be clearly understood that embodiments of the invention are not limited to electrically isolated electrode terminals, or even to a plurality of electrode terminals. For example, the array of active electrode terminals may be connected to a single lead that extends through the catheter shaft to a power source of high frequency current. Alternatively, the instrument may incorporate a single electrode that extends directly through the catheter shaft or is connected to a single lead that extends to the power source. The active electrode(s) may have ball shapes, twizzle shapes, spring shapes, twisted metal shapes, cone shapes, annular or solid tube shapes or the like. Alternatively, the electrode(s) may comprise a plurality of filaments, rigid or flexible brush electrode(s), side-effect brush electrode(s) on a lateral surface of the shaft, coiled electrode(s) or the like.
The voltage difference applied between the return electrode(s) and the electrode terminal(s) can be at high or radio frequency (e.g., between about 50 kHz and 20 MHz, between about 100 kHz and 2.5 MHz, between about 400 kHz and 1000 kHz, less than 600 kHz, between about 400 kHz and 600 kHz, overlapping ranges thereof, 500 kHz, or any frequency within the recited ranges. The RMS (root mean square) voltage applied may be in the range from about 5 volts to 1000 volts, in the range from about 10 volts to 200 volts, between about 20 to 100 volts, between about 40 to 60 volts, depending on the electrode terminal size, the operating frequency and the operation mode of the particular procedure. Lower peak-to-peak voltages may be used for tissue coagulation, thermal heating of tissue, or collagen contraction and may be in the range from 50 to 1500, from 100 to 1000, from 120 to 400 volts, from 100 to 250 volts, from 200 to 600 volts, from 150 to 350 volts peak-to-peak, overlapping ranges thereof, or any voltage within the recited ranges. As discussed above, the voltage may be delivered continuously with a sufficiently high frequency (e.g., on the order of 50 kHz to 20 MHz) (as compared with e.g., lasers claiming small depths of necrosis, which are generally pulsed about 10 to 20 Hz). In addition, the sine wave duty cycle (i.e., cumulative time in anyone-second interval that energy is applied) may be on the order of about 100%, as compared with pulsed lasers which typically have a duty cycle of about 0.0001%. In various embodiments, the current ranges from 50 to 300 mA (e.g., from 50 to 150 mA, from 100 to 200 mA, from 150 to 300 mA, overlapping ranges thereof, or any current level within the recited ranges).
A power source may deliver a high frequency current selectable to generate average power levels ranging from several milliwatts to tens of watts per electrode, depending on the volume of target tissue being heated, and/or the maximum allowed temperature selected for the instrument, tip. The power source allows the user to select the power level according to the specific requirements of a particular procedure.
The power source may be current limited or otherwise controlled so that undesired heating of the target tissue or surrounding (non-target) tissue does not occur. In one embodiment, current limiting inductors are placed in series with each independent electrode terminal, where the inductance of the inductor is in the range of 10 uH to 50,000 uH, depending on the electrical properties of the target tissue, the desired tissue heating rate and the operating frequency. Alternatively, capacitor-inductor (LC) circuit structures may be employed, as described previously in U.S. Pat. No. 5,697,909. Additionally, current limiting resistors may be selected. In several embodiments, microprocessors are employed to monitor the measured current and control the output to limit the current.
The area of the tissue treatment surface can vary widely, and the tissue treatment surface can assume a variety of geometries, with particular areas and geometries being selected for specific applications. The geometries can be planar, concave, convex, hemispherical, conical, linear “in-line” array or virtually any other regular or irregular shape. Most commonly, the active electrode(s) or electrode terminal(s) can be formed at the distal tip of the electrosurgical instrument shaft, frequently being planar, disk-shaped, ring-shaped, or hemispherical surfaces for use in reshaping procedures or being linear arrays for use in cutting. Alternatively or additionally, the active electrode(s) may be formed on lateral surfaces of the electrosurgical instrument shaft (e.g., in the manner of a spatula), facilitating access to certain body structures in endoscopic procedures.
The devices may be suitably used for insertion into any hard tissue in the human body. In some embodiments, the hard tissue is bone. In other embodiments, the hard tissue is cartilage. In some embodiments when bone is selected as the tissue of choice, the bone is a vertebral body. In several embodiments, devices are adapted to puncture the hard cortical shell of the bone and penetrate at least a portion of the underlying cancellous bone. In some embodiments, the probe advances into the bone to a distance of at least ⅓ of the cross-section of the bone defined by the advance of the probe. Some method embodiments are practiced in vertebral bodies substantially free of tumors. In others, method embodiments are practiced in vertebral bodies having tumors and may be used in conjunction with treatment of tumors.
The following Example illustrates some embodiments of the invention and is not intended in any way to limit the scope of the disclosure. Moreover, the methods and procedures described in the following examples, and in the above disclosure, need not be performed in the sequence presented.
A pilot human clinical study was performed to determine efficacy of a minimally invasive technique involving ablation of the basivertebral nerve in providing relief to patients with chronic lower back pain.
In the present study, a radiofrequency device was used to ablate the nerves within the vertebral bone that transmit pain signals. The study involved treatment of 16 human patients with chronic (greater than 6 months) isolated lower back pain who were unresponsive to at least 3 months of nonsurgical conservative care. The patients treated and observed in the study were an average of 47.6 years old and had undergone an average of 32.4 months of conservative treatment. The patients all had Oswestry Disability Index (ODI) scores greater than 30 and either pathologic changes or positive provocative discography at the targeted degenerated disc level.
In accordance with several embodiments, the intraosseous course of the basivertebral foramen for the targeted vertebral bodies was visualized and mapped using MRI imaging (e.g., anteroposterior and lateral still images). CT or other imaging techniques can also be used. In the study, treatment was performed using intraoperative fluoroscopy and a transpedicular approach; however, other visualization and approach techniques can be used. The treatment device used during the study was a bipolar radiofrequency probe with a curved obturator. In the study, the bipolar RF probe was inserted through a bone biopsy needle and guided to the target treatment location under fluoroscopy. The bipolar RF probe was then used to ablate the basivertebral nerve in a controlled manner. The RF energy delivered in the study had a frequency of 500 kHz, the temperature at the electrodes was 85° C., and the duration of treatment varied between 5 and 15 minutes. In accordance with several embodiments, the RF energy delivered may be between 400 and 600 kHz (e.g., 450 kHz, 500 kHz, 550 kHz), the temperature at the electrodes may be between 80° C. and 100° C. (e.g., 85° C., 90° C., 95° C.), and the duration of treatment may be between 4 and 20 minutes (e.g., 6 minutes, 8 minutes, 10 minutes, 12 minutes, 15 minutes).
In accordance with several embodiments, the treatment was limited to the L3, L4, L5 and Si vertebrae. Two-level and three-level intraosseous ablation treatments were performed on various patients. The multiple levels treated during the study were at adjacent levels. Twelve patients were treated at the L4 and L5 levels, two patients were treated at L3 through L5 levels, and two patients were treated at the L5 and Si levels.
Radiographs found no factures during the follow-up period, and no remodeling of bone was observed. Thirteen of the sixteen patients reported “profound and immediate relief.” The treatment procedure resulted in improved ODI scores and Visual Analogue Pain Scale (VAS) values, which were sustained at one year. ODI scores were significantly improved at six weeks, three months, six months, and twelve months. The mean decrease in ODI scores at 1 year was 31 points. VAS values decreased from a preoperative average of 61.1 to an average of 45.6 at the 1-year follow-up. No device-related serious adverse events were reported. Accordingly, in one embodiment, basivertebral nerve ablation is a safe, simple procedure that is applicable during the early stages of treatment for patients with disabling back pain.
Conditional language, for example, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and/or steps.
Although certain embodiments and examples have been described herein, aspects of the methods and devices shown and described in the present disclosure may be differently combined and/or modified to form still further embodiments. Additionally, the methods described herein may be practiced using any device suitable for performing the recited steps. Some embodiments have been described in connection with the accompanying drawings. However, it should be understood that the figures are not drawn to scale. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and/or rearranged. Further, the disclosure (including the figures) herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with various embodiments can be used in all other embodiments set forth herein.
For purposes of this disclosure, certain aspects, advantages, and novel features of the inventions are described herein. Embodiments embodied or carried out in a manner may achieve one advantage or group of advantages as taught herein without necessarily achieving other advantages. The headings used herein are merely provided to enhance readability and are not intended to limit the scope of the embodiments disclosed in a particular section to the features or elements disclosed in that section. The features or elements from one embodiment of the disclosure can be employed by other embodiments of the disclosure. For example, features described in one figure may be used in conjunction with embodiments illustrated in other figures.
While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “delivering a therapeutic dose of energy” include “instructing the delivery of a therapeutic dose of energy.”
Various embodiments of the invention have been presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. The ranges disclosed herein encompass any and all overlap, sub-ranges, and combinations thereof, as well as individual numerical values within that range. For example, description of a range such as from about 5 to about 30 minutes should be considered to have specifically disclosed subranges such as from 5 to 10 degrees, from 10 to 20 minutes, from 5 to 25 minutes, from 15 to 30 minutes etc., as well as individual numbers within that range, for example, 5, 10, 15, 20, 25, 12, 15.5 and any whole and partial increments therebetween. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers. For example, “about 10%” includes “10%.” For example, the terms “approximately”, “about”, and “substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result.
| Number | Name | Date | Kind |
|---|---|---|---|
| 3054881 | Metz et al. | Sep 1962 | A |
| 3062876 | Pons, Jr. et al. | Nov 1962 | A |
| 3565062 | Kuris | Feb 1971 | A |
| 3822708 | Zilber | Jul 1974 | A |
| 3845771 | Vise | Nov 1974 | A |
| 3920021 | Hiltebrandt | Nov 1975 | A |
| 3938502 | Bom | Feb 1976 | A |
| 3977408 | MacKew | Aug 1976 | A |
| 4044774 | Corgin et al. | Aug 1977 | A |
| 4116198 | Roos | Sep 1978 | A |
| 4311154 | Sterzer et al. | Jan 1982 | A |
| 4312364 | Convert et al. | Jan 1982 | A |
| 4378806 | Henley-Cohn | Apr 1983 | A |
| 4448198 | Turner | May 1984 | A |
| 4449528 | Auth et al. | May 1984 | A |
| 4462408 | Silverstein et al. | Jul 1984 | A |
| 4528979 | Marchenko et al. | Jul 1985 | A |
| 4530360 | Duarte | Jul 1985 | A |
| 4541423 | Barber | Sep 1985 | A |
| 4569351 | Tang | Feb 1986 | A |
| 4573448 | Kambin | Mar 1986 | A |
| 4586512 | Do-huu | May 1986 | A |
| 4601296 | Yerushalmi | Jul 1986 | A |
| 4612940 | Kasevich et al. | Sep 1986 | A |
| 4657017 | Sorochenko | Apr 1987 | A |
| 4662383 | Sogawa et al. | May 1987 | A |
| 4671293 | Shaulov | Jun 1987 | A |
| 4676258 | Inokuchi et al. | Jun 1987 | A |
| 4679561 | Doss | Jul 1987 | A |
| 4681122 | Winters et al. | Jul 1987 | A |
| 4750499 | Hoffer | Jun 1988 | A |
| 4754757 | Feucht | Jul 1988 | A |
| 4757820 | Itoh | Jul 1988 | A |
| 4774967 | Zanakis et al. | Oct 1988 | A |
| 4800899 | Elliott | Jan 1989 | A |
| 4813429 | Eshel et al. | Mar 1989 | A |
| 4841977 | Griffith et al. | Jun 1989 | A |
| 4907589 | Cosman | Mar 1990 | A |
| 4924863 | Sterzer | May 1990 | A |
| 4936281 | Stasz | Jun 1990 | A |
| 4941466 | Romano | Jul 1990 | A |
| 4950267 | Ishihara et al. | Aug 1990 | A |
| 4951677 | Crowley et al. | Aug 1990 | A |
| 4955377 | Lennox et al. | Sep 1990 | A |
| 4959063 | Kojima | Sep 1990 | A |
| 4961435 | Kitagawa et al. | Oct 1990 | A |
| 4963142 | Loertscher | Oct 1990 | A |
| 4966144 | Rochkind et al. | Oct 1990 | A |
| 4967765 | Turner et al. | Nov 1990 | A |
| 4976711 | Parins et al. | Dec 1990 | A |
| 4977902 | Sekino et al. | Dec 1990 | A |
| 5000185 | Yock | Mar 1991 | A |
| 5002058 | Marinelli | Mar 1991 | A |
| 5002059 | Crowley et al. | Mar 1991 | A |
| 5007437 | Sterzer | Apr 1991 | A |
| 5025778 | Silverstein et al. | Jun 1991 | A |
| 5031618 | Mullet | Jul 1991 | A |
| 5061266 | Hakky | Oct 1991 | A |
| 5070879 | Herres | Dec 1991 | A |
| RE33791 | Carr | Jan 1992 | E |
| 5078736 | Behl | Jan 1992 | A |
| 5080660 | Buelna | Jan 1992 | A |
| 5084043 | Hertzmann et al. | Jan 1992 | A |
| 5090414 | Takano | Feb 1992 | A |
| 5098431 | Rydell | Mar 1992 | A |
| 5106376 | Mononen et al. | Apr 1992 | A |
| 5108404 | Scholten et al. | Apr 1992 | A |
| 5131397 | Crowley | Jul 1992 | A |
| 5147355 | Cravalho et al. | Sep 1992 | A |
| 5156157 | Nappholz et al. | Oct 1992 | A |
| 5158536 | Sekins et al. | Oct 1992 | A |
| 5161533 | Prass et al. | Nov 1992 | A |
| 5167231 | Matsui | Dec 1992 | A |
| 5186177 | O'Donnell et al. | Feb 1993 | A |
| 5190540 | Lee | Mar 1993 | A |
| 5190546 | Jervis | Mar 1993 | A |
| 5201729 | Hertzmann et al. | Apr 1993 | A |
| 5207672 | Martinelli et al. | May 1993 | A |
| 5209748 | Daikuzono | May 1993 | A |
| 5222953 | Dowlatshahi | Jun 1993 | A |
| 5226430 | Bourgelais et al. | Jul 1993 | A |
| 5242439 | Larsen et al. | Sep 1993 | A |
| 5255679 | Imran | Oct 1993 | A |
| 5271408 | Breyer et al. | Dec 1993 | A |
| 5273026 | Wilk | Dec 1993 | A |
| 5281213 | Milder et al. | Jan 1994 | A |
| 5281215 | Milder | Jan 1994 | A |
| 5282468 | Klepinski | Feb 1994 | A |
| 5292321 | Lee | Mar 1994 | A |
| 5295484 | Hynynen et al. | Mar 1994 | A |
| 5300085 | Yock | Apr 1994 | A |
| 5304214 | DeFord et al. | Apr 1994 | A |
| 5305756 | Entrekin et al. | Apr 1994 | A |
| 5314463 | Camps et al. | May 1994 | A |
| 5320617 | Leach | Jun 1994 | A |
| 5324255 | Gesswein et al. | Jun 1994 | A |
| 5325860 | Seward et al. | Jul 1994 | A |
| 5342292 | Nita et al. | Aug 1994 | A |
| 5342357 | Nardella | Aug 1994 | A |
| 5342409 | Mullett | Aug 1994 | A |
| 5344435 | Schaefermeyer et al. | Sep 1994 | A |
| 5345940 | Seward et al. | Sep 1994 | A |
| 5348554 | Imran et al. | Sep 1994 | A |
| 5350377 | Winston et al. | Sep 1994 | A |
| 5351691 | Brommersma | Oct 1994 | A |
| 5366443 | Eggers et al. | Nov 1994 | A |
| 5366490 | Edwards et al. | Nov 1994 | A |
| 5368031 | Cline et al. | Nov 1994 | A |
| 5368035 | Crowley et al. | Nov 1994 | A |
| 5368557 | Mills et al. | Nov 1994 | A |
| 5368558 | Nita | Nov 1994 | A |
| 5370675 | Edwards et al. | Dec 1994 | A |
| 5370678 | Edwards et al. | Dec 1994 | A |
| 5372138 | Abele et al. | Dec 1994 | A |
| 5374265 | Sand | Dec 1994 | A |
| 5383876 | Nardella | Jan 1995 | A |
| 5385148 | Jackson et al. | Jan 1995 | A |
| 5385544 | Edwards et al. | Jan 1995 | A |
| 5391197 | Burdette et al. | Feb 1995 | A |
| 5391199 | Ben-Haim | Feb 1995 | A |
| 5405376 | Mulier et al. | Apr 1995 | A |
| 5411527 | Alt | May 1995 | A |
| 5417719 | Hull et al. | May 1995 | A |
| 5419767 | Eggers et al. | May 1995 | A |
| 5421338 | Crowley et al. | Jun 1995 | A |
| 5423811 | Imran et al. | Jun 1995 | A |
| 5431649 | Mulier et al. | Jul 1995 | A |
| 5433739 | Sluijter et al. | Jul 1995 | A |
| D361555 | Bettin et al. | Aug 1995 | S |
| 5437661 | Rieser | Aug 1995 | A |
| 5441499 | Fritzsch | Aug 1995 | A |
| 5441527 | Erickson et al. | Aug 1995 | A |
| 5443463 | Stern et al. | Aug 1995 | A |
| 5447509 | Mills et al. | Sep 1995 | A |
| 5449380 | Chin | Sep 1995 | A |
| 5454373 | Crowley | Oct 1995 | A |
| 5458596 | Lax et al. | Oct 1995 | A |
| 5458597 | Edwards et al. | Oct 1995 | A |
| 5471988 | Fujio et al. | Dec 1995 | A |
| 5472441 | Edwards et al. | Dec 1995 | A |
| 5474530 | Gesswein et al. | Dec 1995 | A |
| 5484432 | Sand | Jan 1996 | A |
| 5486170 | Winston et al. | Jan 1996 | A |
| 5501703 | Holsheirner et al. | Mar 1996 | A |
| 5505730 | Edwards | Apr 1996 | A |
| 5514130 | Baker | May 1996 | A |
| 5524624 | Tepper et al. | Jun 1996 | A |
| 5526815 | Granz et al. | Jun 1996 | A |
| 5529580 | Hagino et al. | Jun 1996 | A |
| 5540679 | Berns et al. | Jul 1996 | A |
| 5540681 | Strul et al. | Jul 1996 | A |
| 5540684 | Hassler, Jr. | Jul 1996 | A |
| 5545161 | Imran | Aug 1996 | A |
| 5560362 | Curley et al. | Oct 1996 | A |
| 5565005 | Bettin et al. | Oct 1996 | A |
| 5569242 | Lax et al. | Oct 1996 | A |
| 5571088 | Beaudet et al. | Nov 1996 | A |
| 5571147 | Sluijter et al. | Nov 1996 | A |
| 5575772 | Lennox | Nov 1996 | A |
| 5575788 | Baker et al. | Nov 1996 | A |
| 5588432 | Crowley | Dec 1996 | A |
| 5596988 | Markle et al. | Jan 1997 | A |
| 5601526 | Blanc et al. | Feb 1997 | A |
| 5606974 | Castellano et al. | Mar 1997 | A |
| 5609151 | Mulier et al. | Mar 1997 | A |
| 5620479 | Diederich | Apr 1997 | A |
| 5628317 | Starkebaum et al. | May 1997 | A |
| 5630426 | Shmulewitz et al. | May 1997 | A |
| 5630837 | Crowley | May 1997 | A |
| 5643319 | Green et al. | Jul 1997 | A |
| 5643330 | Holsheimer et al. | Jul 1997 | A |
| 5647361 | Damadian | Jul 1997 | A |
| 5647871 | Levine et al. | Jul 1997 | A |
| 5658278 | Imran et al. | Aug 1997 | A |
| 5672173 | Gough et al. | Sep 1997 | A |
| 5681282 | Eggers et al. | Oct 1997 | A |
| 5683366 | Eggers et al. | Nov 1997 | A |
| 5685839 | Baker et al. | Nov 1997 | A |
| 5687729 | Schaetzle | Nov 1997 | A |
| 5688267 | Panescu | Nov 1997 | A |
| 5693052 | Weaver | Dec 1997 | A |
| 5697281 | Eggers et al. | Dec 1997 | A |
| 5697536 | Eggers et al. | Dec 1997 | A |
| 5697882 | Eggers | Dec 1997 | A |
| 5697909 | Eggers et al. | Dec 1997 | A |
| 5697927 | Imran et al. | Dec 1997 | A |
| 5700262 | Acosta et al. | Dec 1997 | A |
| 5718231 | Chen et al. | Feb 1998 | A |
| 5720286 | Blanc et al. | Feb 1998 | A |
| 5720287 | Chapelon et al. | Feb 1998 | A |
| 5722403 | McGee et al. | Mar 1998 | A |
| 5725494 | Brisken | Mar 1998 | A |
| 5728062 | Brisken | Mar 1998 | A |
| 5730706 | Garnies | Mar 1998 | A |
| 5733315 | Burdette et al. | Mar 1998 | A |
| 5735280 | Sherman et al. | Apr 1998 | A |
| 5735811 | Brisken | Apr 1998 | A |
| 5735846 | Fleischman et al. | Apr 1998 | A |
| 5735847 | Gough et al. | Apr 1998 | A |
| 5738680 | Mueller et al. | Apr 1998 | A |
| 5741249 | Moss et al. | Apr 1998 | A |
| 5743904 | Edwards | Apr 1998 | A |
| 5746737 | Saadat | May 1998 | A |
| 5752969 | Cunci et al. | May 1998 | A |
| 5755663 | Johnson et al. | May 1998 | A |
| 5762066 | Law et al. | Jun 1998 | A |
| 5762616 | Talish | Jun 1998 | A |
| 5766153 | Eggers et al. | Jun 1998 | A |
| 5766231 | Bettin | Jun 1998 | A |
| 5776092 | Farin et al. | Jul 1998 | A |
| 5785705 | Baker | Jul 1998 | A |
| 5800378 | Edwards et al. | Sep 1998 | A |
| 5800429 | Edwards | Sep 1998 | A |
| 5800432 | Swanson | Sep 1998 | A |
| 5807237 | Tindel | Sep 1998 | A |
| 5807391 | Cornelius et al. | Sep 1998 | A |
| 5807392 | Eggers | Sep 1998 | A |
| 5807395 | Mulier et al. | Sep 1998 | A |
| 5810764 | Eggers et al. | Sep 1998 | A |
| 5817021 | Reichenberger | Oct 1998 | A |
| 5824021 | Rise | Oct 1998 | A |
| 5840031 | Crowley | Nov 1998 | A |
| 5843019 | Eggers et al. | Dec 1998 | A |
| 5843021 | Edwards et al. | Dec 1998 | A |
| 5844092 | Presta et al. | Dec 1998 | A |
| 5846218 | Brisken et al. | Dec 1998 | A |
| 5849011 | Jones | Dec 1998 | A |
| 5855576 | LeVeen et al. | Jan 1999 | A |
| 5860951 | Eggers et al. | Jan 1999 | A |
| 5865788 | Edwards et al. | Feb 1999 | A |
| 5865801 | Houser | Feb 1999 | A |
| 5868740 | LeVeen et al. | Feb 1999 | A |
| 5871469 | Eggers et al. | Feb 1999 | A |
| 5871470 | McWha | Feb 1999 | A |
| 5871481 | Kannenberg et al. | Feb 1999 | A |
| 5873855 | Eggers et al. | Feb 1999 | A |
| 5873877 | McGaffigan et al. | Feb 1999 | A |
| 5876398 | Mulier et al. | Mar 1999 | A |
| 5888198 | Eggers et al. | Mar 1999 | A |
| 5891095 | Eggers et al. | Apr 1999 | A |
| 5895370 | Edwards et al. | Apr 1999 | A |
| 5902272 | Eggers et al. | May 1999 | A |
| 5902308 | Murphy | May 1999 | A |
| 5904681 | West, Jr. | May 1999 | A |
| 5906613 | Mulier et al. | May 1999 | A |
| 5916213 | Haissaguerre et al. | Jun 1999 | A |
| 5916214 | Cosio | Jun 1999 | A |
| 5919188 | Shearon et al. | Jul 1999 | A |
| 5931805 | Brisken | Aug 1999 | A |
| 5935123 | Edwards et al. | Aug 1999 | A |
| 5938582 | Ciamacco et al. | Aug 1999 | A |
| 5941722 | Chen | Aug 1999 | A |
| 5941876 | Nardella et al. | Aug 1999 | A |
| 5944715 | Goble et al. | Aug 1999 | A |
| 5948007 | Starkebaum et al. | Sep 1999 | A |
| 5948008 | Daikuzono | Sep 1999 | A |
| 5954716 | Sharkey et al. | Sep 1999 | A |
| 5964727 | Edwards et al. | Oct 1999 | A |
| 5967988 | Briscoe et al. | Oct 1999 | A |
| 5972015 | Scribner et al. | Oct 1999 | A |
| 5976105 | Casson et al. | Nov 1999 | A |
| 5983141 | Sluijter et al. | Nov 1999 | A |
| 5997497 | Nita et al. | Dec 1999 | A |
| 6001095 | de la Rama et al. | Dec 1999 | A |
| 6007533 | Casscells et al. | Dec 1999 | A |
| 6007570 | Sharkey et al. | Dec 1999 | A |
| 6012457 | Lesh | Jan 2000 | A |
| 6014588 | Fitz | Jan 2000 | A |
| 6016452 | Kasevich | Jan 2000 | A |
| 6016809 | Mulier et al. | Jan 2000 | A |
| 6017356 | Frederick et al. | Jan 2000 | A |
| 6019776 | Preissman et al. | Feb 2000 | A |
| 6022334 | Edwards et al. | Feb 2000 | A |
| 6024733 | Eggers et al. | Feb 2000 | A |
| 6024740 | Lesh et al. | Feb 2000 | A |
| 6030374 | McDaniel | Feb 2000 | A |
| 6030402 | Thompson et al. | Feb 2000 | A |
| 6032673 | Alden et al. | Mar 2000 | A |
| 6032674 | Eggers et al. | Mar 2000 | A |
| 6033411 | Preissman et al. | Mar 2000 | A |
| 6035238 | Ingle et al. | Mar 2000 | A |
| 6045532 | Eggers et al. | Apr 2000 | A |
| 6046187 | Berde et al. | Apr 2000 | A |
| 6047214 | Gyurcsik et al. | Apr 2000 | A |
| 6050995 | Durgin | Apr 2000 | A |
| 6053172 | Hovda et al. | Apr 2000 | A |
| 6053909 | Shadduck | Apr 2000 | A |
| 6038480 | Hrdlicka et al. | May 2000 | A |
| 6063078 | Wittkampf | May 2000 | A |
| 6063079 | Hovda et al. | May 2000 | A |
| 6066134 | Eggers et al. | May 2000 | A |
| 6066139 | Ryan et al. | May 2000 | A |
| 6068642 | Johnson et al. | May 2000 | A |
| 6071279 | Fleishman et al. | Jun 2000 | A |
| 6073051 | Sharkey et al. | Jun 2000 | A |
| 6074352 | Foldes et al. | Jun 2000 | A |
| 6086585 | Hovda et al. | Jul 2000 | A |
| 6090105 | Zepeda et al. | Jul 2000 | A |
| 6095149 | Sharkey et al. | Aug 2000 | A |
| 6099499 | Ciamacco | Aug 2000 | A |
| 6099514 | Sharkey et al. | Aug 2000 | A |
| 6099524 | Lipson et al. | Aug 2000 | A |
| 6102046 | Weinstein et al. | Aug 2000 | A |
| 6104957 | Alo et al. | Aug 2000 | A |
| 6105581 | Eggers et al. | Aug 2000 | A |
| 6106454 | Berg et al. | Aug 2000 | A |
| 6109268 | Thapliyal et al. | Aug 2000 | A |
| 6112122 | Schwardt et al. | Aug 2000 | A |
| 6113597 | Eggers et al. | Sep 2000 | A |
| 6117101 | Diederich et al. | Sep 2000 | A |
| 6117109 | Eggers et al. | Sep 2000 | A |
| 6117128 | Gregory | Sep 2000 | A |
| 6120467 | Schallhorn | Sep 2000 | A |
| 6120502 | Michelson | Sep 2000 | A |
| 6122549 | Sharkey et al. | Sep 2000 | A |
| 6126682 | Ashley et al. | Oct 2000 | A |
| 6137209 | Dahlberg et al. | Oct 2000 | A |
| 6139545 | Utley et al. | Oct 2000 | A |
| 6142992 | Cheng et al. | Nov 2000 | A |
| 6143019 | Motamedi et al. | Nov 2000 | A |
| 6146380 | Racz et al. | Nov 2000 | A |
| 6149620 | Baker et al. | Nov 2000 | A |
| 6159194 | Eggers et al. | Dec 2000 | A |
| 6159208 | Hovda et al. | Dec 2000 | A |
| 6161048 | Sluijter et al. | Dec 2000 | A |
| 6164283 | Lesh | Dec 2000 | A |
| 6165172 | Farley et al. | Dec 2000 | A |
| 6168593 | Sharkey et al. | Jan 2001 | B1 |
| 6169924 | Meloy et al. | Jan 2001 | B1 |
| 6171239 | Humphrey | Jan 2001 | B1 |
| 6176857 | Ashley | Jan 2001 | B1 |
| 6179824 | Eggers et al. | Jan 2001 | B1 |
| 6179836 | Eggers et al. | Jan 2001 | B1 |
| 6179858 | Squire et al. | Jan 2001 | B1 |
| 6183469 | Thapliyal et al. | Feb 2001 | B1 |
| 6190381 | Olsen et al. | Feb 2001 | B1 |
| 6190383 | Schmaltz et al. | Feb 2001 | B1 |
| 6193715 | Wrublewski et al. | Feb 2001 | B1 |
| 6203542 | Elisberry et al. | Mar 2001 | B1 |
| 6206842 | Tu et al. | Mar 2001 | B1 |
| 6270498 | Michelson | Mar 2001 | B1 |
| 6210393 | Brisken | Apr 2001 | B1 |
| 6210402 | Olsen et al. | Apr 2001 | B1 |
| 6210415 | Bester | Apr 2001 | B1 |
| 6216704 | Ingle et al. | Apr 2001 | B1 |
| 6221038 | Brisken | Apr 2001 | B1 |
| 6224592 | Eggers et al. | May 2001 | B1 |
| 6228046 | Brisken | May 2001 | B1 |
| 6228078 | Eggers et al. | May 2001 | B1 |
| 6228082 | Baker et al. | May 2001 | B1 |
| 6231516 | Keilman et al. | May 2001 | B1 |
| 6231528 | Kaufman et al. | May 2001 | B1 |
| 6231571 | Ellman et al. | May 2001 | B1 |
| 6231615 | Preissman | May 2001 | B1 |
| 6233488 | Hess | May 2001 | B1 |
| 6235020 | Cheng et al. | May 2001 | B1 |
| 6235024 | Tu | May 2001 | B1 |
| 6237604 | Burnside et al. | May 2001 | B1 |
| 6238391 | Olsen et al. | May 2001 | B1 |
| 6238393 | Muller et al. | May 2001 | B1 |
| 6241665 | Negus et al. | Jun 2001 | B1 |
| 6241725 | Cosman | Jun 2001 | B1 |
| 6241734 | Scribner et al. | Jun 2001 | B1 |
| 6245064 | Lesh | Jun 2001 | B1 |
| 6246912 | Siuijter et al. | Jun 2001 | B1 |
| 6248110 | Reiley et al. | Jun 2001 | B1 |
| 6248345 | Goldenheim et al. | Jun 2001 | B1 |
| 6254553 | Lidgren et al. | Jul 2001 | B1 |
| 6254599 | Lesh et al. | Jul 2001 | B1 |
| 6254600 | Willink et al. | Jul 2001 | B1 |
| 6258086 | Ashley et al. | Jul 2001 | B1 |
| 6259952 | Sluijter et al. | Jul 2001 | B1 |
| 6261311 | Sharkey et al. | Jul 2001 | B1 |
| 6264650 | Hovda et al. | Jul 2001 | B1 |
| 6264651 | Underwood et al. | Jul 2001 | B1 |
| 6264652 | Eggers et al. | Jul 2001 | B1 |
| 6264659 | Ross et al. | Jul 2001 | B1 |
| 6267770 | Truwit | Jul 2001 | B1 |
| 6277112 | Underwood et al. | Aug 2001 | B1 |
| 6277122 | McGahan et al. | Aug 2001 | B1 |
| 6280441 | Ryan | Aug 2001 | B1 |
| 6280456 | Scribner et al. | Aug 2001 | B1 |
| 6237272 | Brisken et al. | Sep 2001 | B1 |
| 6283961 | Underwood et al. | Sep 2001 | B1 |
| 6287114 | Meller et al. | Sep 2001 | B1 |
| 6287304 | Eggers et al. | Sep 2001 | B1 |
| 6290715 | Sharkey et al. | Sep 2001 | B1 |
| 6292699 | Simon et al. | Sep 2001 | B1 |
| 6296619 | Brisken et al. | Oct 2001 | B1 |
| 6296636 | Cheng et al. | Oct 2001 | B1 |
| 6296638 | Davison et al. | Oct 2001 | B1 |
| 6305378 | Lesh et al. | Oct 2001 | B1 |
| 6309387 | Eggers et al. | Oct 2001 | B1 |
| 6309420 | Preissman | Oct 2001 | B1 |
| 6312408 | Eggers et al. | Nov 2001 | B1 |
| 6312425 | Simpson et al. | Nov 2001 | B1 |
| 6312426 | Goldberg et al. | Nov 2001 | B1 |
| 6319241 | King et al. | Nov 2001 | B1 |
| 6322549 | Eggers et al. | Nov 2001 | B1 |
| 6348055 | Preissman | Feb 2002 | B1 |
| 6355032 | Hovda et al. | Mar 2002 | B1 |
| 6356790 | Maguire et al. | Mar 2002 | B1 |
| 6361531 | Hissong | Mar 2002 | B1 |
| 6363937 | Hovda et al. | Apr 2002 | B1 |
| 6368292 | Ogden et al. | Apr 2002 | B1 |
| 6379351 | Thapliyal et al. | Apr 2002 | B1 |
| 6383190 | Preissman | May 2002 | B1 |
| 6391025 | Weinstein et al. | May 2002 | B1 |
| 6398782 | Pecor et al. | Jun 2002 | B1 |
| 6416507 | Eggers et al. | Jul 2002 | B1 |
| 6416508 | Eggers et al. | Jul 2002 | B1 |
| 6423057 | He et al. | Jul 2002 | B1 |
| 6423059 | Hanson et al. | Jul 2002 | B1 |
| 6425887 | McGuckin et al. | Jul 2002 | B1 |
| 6426339 | Berde et al. | Jul 2002 | B1 |
| 6428491 | Weiss | Aug 2002 | B1 |
| 6432103 | Ellsberry et al. | Aug 2002 | B1 |
| 6436060 | Talish | Aug 2002 | B1 |
| 6436098 | Michelson | Aug 2002 | B1 |
| 6440138 | Reiley et al. | Aug 2002 | B1 |
| 6447448 | Ishikawa et al. | Sep 2002 | B1 |
| 6451013 | Bays et al. | Sep 2002 | B1 |
| 6454727 | Bubank et al. | Sep 2002 | B1 |
| 6461350 | Underwood et al. | Oct 2002 | B1 |
| 6461354 | Olsen et al. | Oct 2002 | B1 |
| 6464695 | Hovda et al. | Oct 2002 | B2 |
| 6468270 | Hovda et al. | Oct 2002 | B1 |
| 6468274 | Alleyne et al. | Oct 2002 | B1 |
| 6470220 | Kraus et al. | Oct 2002 | B1 |
| 6478793 | Cosman et al. | Nov 2002 | B1 |
| 6482201 | Olsen et al. | Nov 2002 | B1 |
| 6485271 | Tack | Nov 2002 | B1 |
| 6487446 | Hill et al. | Nov 2002 | B1 |
| 6491893 | Babich | Dec 2002 | B1 |
| 6493592 | Leonard et al. | Dec 2002 | B1 |
| 6494902 | Hoey et al. | Dec 2002 | B2 |
| 6500173 | Underwood et al. | Dec 2002 | B2 |
| 6503839 | Lambrecht et al. | Jan 2003 | B2 |
| 6505075 | Weiner | Jan 2003 | B1 |
| 6524261 | Talish et al. | Feb 2003 | B2 |
| 6527759 | Tachibana et al. | Mar 2003 | B1 |
| 6537306 | Burdette et al. | Mar 2003 | B1 |
| 6540741 | Underwood et al. | Apr 2003 | B1 |
| 6544261 | Ellsberry et al. | Apr 2003 | B2 |
| 6553385 | McClurken et al. | Apr 2003 | B2 |
| 6557559 | Eggers et al. | May 2003 | B1 |
| 6558390 | Cragg | May 2003 | B2 |
| 6560486 | Osorio et al. | May 2003 | B1 |
| 6562033 | Shah et al. | May 2003 | B2 |
| 6575919 | Reiley et al. | Jun 2003 | B1 |
| 6575968 | Eggers et al. | Jun 2003 | B1 |
| 6575969 | Rittman et al. | Jun 2003 | B1 |
| 6575979 | Cragg | Jun 2003 | B1 |
| 6578579 | Burnside et al. | Jun 2003 | B2 |
| 6582423 | Thapliyal et al. | Jun 2003 | B1 |
| 6535656 | Masters | Jul 2003 | B1 |
| 6589237 | Woloszko et al. | Jul 2003 | B2 |
| 6592559 | Pakter et al. | Jul 2003 | B1 |
| 6595990 | Weinstein et al. | Jul 2003 | B1 |
| 6599283 | Maguire et al. | Jul 2003 | B1 |
| 6602248 | Sharps et al. | Aug 2003 | B1 |
| 6604003 | Fredricks et al. | Aug 2003 | B2 |
| 6607502 | Maguire et al. | Aug 2003 | B1 |
| 6607529 | Jones et al. | Aug 2003 | B1 |
| 6608502 | Aoki et al. | Aug 2003 | B2 |
| 6622731 | Daniel et al. | Sep 2003 | B2 |
| 6623505 | Scribner et al. | Sep 2003 | B2 |
| 6632193 | Davison et al. | Oct 2003 | B1 |
| 6632220 | Eggers et al. | Oct 2003 | B1 |
| 6645202 | Pless et al. | Nov 2003 | B1 |
| 6648883 | Francischelli et al. | Nov 2003 | B2 |
| 6651669 | Burnside | Nov 2003 | B1 |
| 6659106 | Hovda et al. | Dec 2003 | B1 |
| 6663627 | Francischelli et al. | Dec 2003 | B2 |
| 6663647 | Reiley et al. | Dec 2003 | B2 |
| 6673063 | Brett | Jan 2004 | B2 |
| 6689086 | Nita et al. | Feb 2004 | B1 |
| 6689125 | Keith et al. | Feb 2004 | B1 |
| 6692450 | Coleman | Feb 2004 | B1 |
| 6699240 | Francischelli | Mar 2004 | B2 |
| 6699242 | Heggeness | Mar 2004 | B2 |
| 6709432 | Ferek-Patric | Mar 2004 | B2 |
| 6718208 | Hill et al. | Apr 2004 | B2 |
| 6719761 | Reiley et al. | Apr 2004 | B1 |
| 6723087 | O'Neill et al. | Apr 2004 | B2 |
| 6723094 | Desinger | Apr 2004 | B1 |
| 6726684 | Woloszko et al. | Apr 2004 | B1 |
| 6736810 | Hoey et al. | May 2004 | B2 |
| 6736835 | Pellegrino et al. | May 2004 | B2 |
| 6745079 | King | Jun 2004 | B2 |
| 6746447 | Davison et al. | Jun 2004 | B2 |
| 6746451 | Middleton et al. | Jun 2004 | B2 |
| 6749604 | Eggers et al. | Jun 2004 | B1 |
| 6758846 | Goble et al. | Jul 2004 | B2 |
| 6770071 | Woloszko et al. | Aug 2004 | B2 |
| 6772012 | Ricart et al. | Aug 2004 | B2 |
| 6773431 | Eggers et al. | Aug 2004 | B2 |
| 6795737 | Gielen et al. | Sep 2004 | B2 |
| 6805697 | Helm et al. | Oct 2004 | B1 |
| 6827715 | Francischelli et al. | Dec 2004 | B2 |
| 6827716 | Ryan et al. | Dec 2004 | B2 |
| 6832996 | Woloszko et al. | Dec 2004 | B2 |
| 6837887 | Woloszko et al. | Jan 2005 | B2 |
| 6837888 | Ciarrocca et al. | Jan 2005 | B2 |
| 6852091 | Edwards et al. | Feb 2005 | B2 |
| 6863672 | Reiley et al. | Mar 2005 | B2 |
| 6875219 | Arramon et al. | Apr 2005 | B2 |
| 6881214 | Cosman et al. | Apr 2005 | B2 |
| 6896674 | Woloszko et al. | May 2005 | B1 |
| 6896675 | Leung et al. | May 2005 | B2 |
| 6907884 | Pellegrino et al. | Jun 2005 | B2 |
| 6915806 | Pacek et al. | Jul 2005 | B2 |
| 6922579 | Taimisto et al. | Jul 2005 | B2 |
| 6923813 | Phillips et al. | Aug 2005 | B2 |
| 6936046 | Hissong et al. | Aug 2005 | B2 |
| 6955674 | Eick et al. | Oct 2005 | B2 |
| 6960204 | Eggers et al. | Nov 2005 | B2 |
| 6962589 | Mulier et al. | Nov 2005 | B2 |
| 6974453 | Woloszko et al. | Dec 2005 | B2 |
| 6980849 | Sasso | Dec 2005 | B2 |
| 6981981 | Reiley et al. | Jan 2006 | B2 |
| 6989010 | Francischelli et al. | Jan 2006 | B2 |
| 6997941 | Sharkey et al. | Feb 2006 | B2 |
| 7001383 | Keidar | Feb 2006 | B2 |
| 7041096 | Malis et al. | May 2006 | B2 |
| 7044954 | Reiley et al. | May 2006 | B2 |
| 7048743 | Miller et al. | May 2006 | B2 |
| 7065408 | Herman et al. | Jun 2006 | B2 |
| 7081122 | Reiley et al. | Jul 2006 | B1 |
| 7090672 | Underwood et al. | Aug 2006 | B2 |
| 7104989 | Skarda | Sep 2006 | B2 |
| 7118574 | Patel et al. | Oct 2006 | B2 |
| 7131969 | Hovda et al. | Nov 2006 | B1 |
| 7153307 | Scribner et al. | Dec 2006 | B2 |
| 7163536 | Godara | Jan 2007 | B2 |
| 7177678 | Osorio et al. | Feb 2007 | B1 |
| 7179255 | Lettice et al. | Feb 2007 | B2 |
| 7186234 | Dahla et al. | Mar 2007 | B2 |
| 7192428 | Eggers et al. | Mar 2007 | B2 |
| 7201731 | Lundquist et al. | Apr 2007 | B1 |
| 7201750 | Eggers et al. | Apr 2007 | B1 |
| 7211055 | Diederich et al. | May 2007 | B2 |
| 7217268 | Eggers et al. | May 2007 | B2 |
| 7238184 | Megerman et al. | Jul 2007 | B2 |
| 7241297 | Shaolian et al. | Jul 2007 | B2 |
| 7250048 | Francischelli et al. | Jul 2007 | B2 |
| 7258690 | Sutton et al. | Aug 2007 | B2 |
| 7270659 | Ricart et al. | Sep 2007 | B2 |
| 7270661 | Dahla et al. | Sep 2007 | B2 |
| 7276063 | Davison et al. | Oct 2007 | B2 |
| 7294127 | Leung et al. | Nov 2007 | B2 |
| 7305264 | Larson et al. | Dec 2007 | B2 |
| 7306596 | Hillier et al. | Dec 2007 | B2 |
| 7306598 | Truckai et al. | Dec 2007 | B2 |
| 7318823 | Sharps et al. | Jan 2008 | B2 |
| 7318826 | Teitelbaum et al. | Jan 2008 | B2 |
| 7326203 | Papineau et al. | Feb 2008 | B2 |
| 7331956 | Hovda et al. | Feb 2008 | B2 |
| 7331957 | Woloszko et al. | Feb 2008 | B2 |
| RE40156 | Sharps et al. | Mar 2008 | E |
| 7346391 | Osorio et al. | Mar 2008 | B1 |
| 7386350 | Vilims | Jun 2008 | B2 |
| 7387625 | Hovda et al. | Jun 2008 | B2 |
| 7393351 | Woloszko et al. | Jul 2008 | B2 |
| 7399306 | Reiley et al. | Jul 2008 | B2 |
| 7422585 | Eggers et al. | Sep 2008 | B1 |
| 7429262 | Woloszko et al. | Sep 2008 | B2 |
| 7435247 | Woloszko et al. | Oct 2008 | B2 |
| 7435250 | Francischelli et al. | Oct 2008 | B2 |
| 7442191 | Hovda et al. | Oct 2008 | B2 |
| 7468059 | Eggers et al. | Dec 2008 | B2 |
| 7480533 | Cosman et al. | Jan 2009 | B2 |
| 7502652 | Gaunt et al. | Mar 2009 | B2 |
| 7503920 | Siegal | Mar 2009 | B2 |
| 7503921 | Siegal | Mar 2009 | B2 |
| 7507236 | Eggers et al. | Mar 2009 | B2 |
| 7546164 | King | Jun 2009 | B2 |
| 7553307 | Bleich et al. | Jun 2009 | B2 |
| 7553309 | Buysse et al. | Jun 2009 | B2 |
| 7555343 | Bleich | Jun 2009 | B2 |
| 7559932 | Truckai et al. | Jul 2009 | B2 |
| 7569626 | Truckai | Aug 2009 | B2 |
| 7574257 | Rittman, III | Aug 2009 | B2 |
| 7585300 | Cha | Sep 2009 | B2 |
| 7593778 | Chandran et al. | Sep 2009 | B2 |
| 7594913 | Ormsby et al. | Sep 2009 | B2 |
| 7604636 | Walters et al. | Oct 2009 | B1 |
| 7621952 | Truckai et al. | Nov 2009 | B2 |
| 7645277 | McClurken et al. | Jan 2010 | B2 |
| 7678111 | Mulier et al. | Mar 2010 | B2 |
| 7678116 | Truckai et al. | Mar 2010 | B2 |
| 7682378 | Truckai et al. | Mar 2010 | B2 |
| 7708733 | Sanders et al. | May 2010 | B2 |
| 7722620 | Truckai et al. | May 2010 | B2 |
| 7731720 | Truckai et al. | Jun 2010 | B2 |
| 7738968 | Bleich | Jun 2010 | B2 |
| 7740631 | Bleich et al. | Jun 2010 | B2 |
| 7749218 | Pellegrino et al. | Jul 2010 | B2 |
| 7749220 | Schmaltz et al. | Jul 2010 | B2 |
| 7780733 | Carver et al. | Aug 2010 | B2 |
| 7792588 | Harding | Sep 2010 | B2 |
| 7799021 | Leung et al. | Sep 2010 | B2 |
| 7819826 | Diederich et al. | Oct 2010 | B2 |
| 7819869 | Godara et al. | Oct 2010 | B2 |
| 7824398 | Woloszko et al. | Nov 2010 | B2 |
| 7824404 | Godara et al. | Nov 2010 | B2 |
| 7828804 | Li et al. | Nov 2010 | B2 |
| 7846156 | Malis et al. | Dec 2010 | B2 |
| 7850685 | Kunis et al. | Dec 2010 | B2 |
| 7853326 | Rittman, III | Dec 2010 | B2 |
| 7857813 | Schmitz et al. | Dec 2010 | B2 |
| 7879032 | Garito et al. | Feb 2011 | B1 |
| 7887543 | Sand et al. | Feb 2011 | B2 |
| 7892235 | Ellis | Feb 2011 | B2 |
| 7896870 | Arless et al. | Mar 2011 | B2 |
| 7896909 | Sharkey et al. | Mar 2011 | B2 |
| 7901403 | Woloszko et al. | Mar 2011 | B2 |
| 7909827 | Reiley et al. | Mar 2011 | B2 |
| 7909873 | Tan-Melecki et al. | Mar 2011 | B2 |
| 7914526 | Lehmann et al. | Mar 2011 | B2 |
| 7914535 | Assell et al. | Mar 2011 | B2 |
| 7917222 | Osorio et al. | Mar 2011 | B1 |
| 7918849 | Bleich et al. | Apr 2011 | B2 |
| 7918874 | Siegal | Apr 2011 | B2 |
| 7938835 | Boucher et al. | May 2011 | B2 |
| 7945331 | Vilims | May 2011 | B2 |
| 7951140 | Arless et al. | May 2011 | B2 |
| 7959634 | Sennett | Jun 2011 | B2 |
| 7963915 | Bleich | Jun 2011 | B2 |
| 7967827 | Osorio et al. | Jun 2011 | B2 |
| 7972340 | Sand et al. | Jul 2011 | B2 |
| 8000785 | Rittman, III | Aug 2011 | B2 |
| 8021401 | Carl et al. | Sep 2011 | B2 |
| 8025688 | Diederich et al. | Sep 2011 | B2 |
| 8034052 | Podhajsky | Oct 2011 | B2 |
| 8034071 | Scribner et al. | Oct 2011 | B2 |
| 8043287 | Conquergood et al. | Oct 2011 | B2 |
| 8048030 | Conquergood et al. | Nov 2011 | B2 |
| 8048071 | Youssef et al. | Nov 2011 | B2 |
| 8048083 | Shadduck et al. | Nov 2011 | B2 |
| 8052661 | McGuckin, Jr. et al. | Nov 2011 | B2 |
| 8062290 | Buysse et al. | Nov 2011 | B2 |
| 8066702 | Rittman, III et al. | Nov 2011 | B2 |
| 8066712 | Truckai et al. | Nov 2011 | B2 |
| 8070753 | Truckai et al. | Dec 2011 | B2 |
| 8082043 | Sharkey et al. | Dec 2011 | B2 |
| 8083736 | McClurken et al. | Dec 2011 | B2 |
| 8096957 | Conquergood et al. | Jan 2012 | B2 |
| 8100896 | Podhajsky | Jan 2012 | B2 |
| 8109933 | Truckai et al. | Feb 2012 | B2 |
| 8123750 | Norton et al. | Feb 2012 | B2 |
| 8123756 | Miller et al. | Feb 2012 | B2 |
| 8128619 | Sharkey et al. | Mar 2012 | B2 |
| 8128633 | Linderman et al. | Mar 2012 | B2 |
| 8162933 | Francischelli et al. | Apr 2012 | B2 |
| 8163031 | Truckai et al. | Apr 2012 | B2 |
| 8172846 | Brunnett et al. | May 2012 | B2 |
| 8182477 | Orszulak et al. | May 2012 | B2 |
| 8187312 | Sharkey et al. | May 2012 | B2 |
| 8192424 | Woloszko et al. | Jun 2012 | B2 |
| 8192435 | Bleich et al. | Jun 2012 | B2 |
| 8216223 | Wham et al. | Jul 2012 | B2 |
| 8226697 | Sharkey et al. | Jul 2012 | B2 |
| 8231616 | McPherson et al. | Jul 2012 | B2 |
| 8241335 | Truckai et al. | Aug 2012 | B2 |
| 8246627 | Vanleeuwen et al. | Aug 2012 | B2 |
| 8265747 | Rittman, III et al. | Sep 2012 | B2 |
| 8282628 | Paul et al. | Oct 2012 | B2 |
| 8292882 | Danek et al. | Oct 2012 | B2 |
| 8292887 | Woloszko et al. | Oct 2012 | B2 |
| 8323277 | Vilims | Dec 2012 | B2 |
| 8323279 | Dahla et al. | Dec 2012 | B2 |
| 8343146 | Godara | Jan 2013 | B2 |
| 8348946 | McClurken et al. | Jan 2013 | B2 |
| 8348955 | Truckai et al. | Jan 2013 | B2 |
| 8355799 | Marion et al. | Jan 2013 | B2 |
| 8361063 | Godara | Jan 2013 | B2 |
| 8361067 | Pellegrino et al. | Jan 2013 | B2 |
| 8406886 | Gaunt et al. | Mar 2013 | B2 |
| 8409289 | Truckai et al. | Apr 2013 | B2 |
| 8414509 | Diederich et al. | Apr 2013 | B2 |
| 8414571 | Pellegrino et al. | Apr 2013 | B2 |
| 8419730 | Pellegrino et al. | Apr 2013 | B2 |
| 8419731 | Pellegrino et al. | Apr 2013 | B2 |
| 8425507 | Pellegrino et al. | Apr 2013 | B2 |
| 8430887 | Truckai et al. | Apr 2013 | B2 |
| 8444636 | Shadduck et al. | May 2013 | B2 |
| 8444640 | Demarais et al. | May 2013 | B2 |
| 8454594 | Demarais et al. | Jun 2013 | B2 |
| 8460382 | Helm et al. | Jun 2013 | B2 |
| 8475449 | Werneth et al. | Jul 2013 | B2 |
| 8486063 | Werneth et al. | Jul 2013 | B2 |
| 8487021 | Truckai et al. | Jul 2013 | B2 |
| 8504147 | Deem et al. | Aug 2013 | B2 |
| 8505545 | Conquergood et al. | Aug 2013 | B2 |
| 8518036 | Leung et al. | Aug 2013 | B2 |
| 8523871 | Truckai et al. | Sep 2013 | B2 |
| 8535309 | Pellegrino et al. | Sep 2013 | B2 |
| 8540723 | Shadduck | Sep 2013 | B2 |
| 8556910 | Truckai et al. | Oct 2013 | B2 |
| 8556911 | Mehta et al. | Oct 2013 | B2 |
| 8560062 | Rittman, III et al. | Oct 2013 | B2 |
| 8562598 | Falkenstein et al. | Oct 2013 | B2 |
| 8562607 | Truckai et al. | Oct 2013 | B2 |
| 8562620 | Truckai et al. | Oct 2013 | B2 |
| 8579903 | Carl | Nov 2013 | B2 |
| 8585694 | Amoah et al. | Nov 2013 | B2 |
| 8591507 | Kramer et al. | Nov 2013 | B2 |
| 8597301 | Mitchell | Dec 2013 | B2 |
| 8603088 | Stern et al. | Dec 2013 | B2 |
| 8613744 | Pellegrino et al. | Dec 2013 | B2 |
| 8617156 | Werneth et al. | Dec 2013 | B2 |
| 8623014 | Pellegrino et al. | Jan 2014 | B2 |
| 8623025 | Tan-Malecki et al. | Jan 2014 | B2 |
| 8628528 | Pellegrino et al. | Jan 2014 | B2 |
| 8636736 | Yates et al. | Jan 2014 | B2 |
| 8644941 | Rooney et al. | Feb 2014 | B2 |
| 8657814 | Werneth et al. | Feb 2014 | B2 |
| 8663266 | Obsuth | Mar 2014 | B1 |
| 8672934 | Benamou et al. | Mar 2014 | B2 |
| 8676309 | Deem et al. | Mar 2014 | B2 |
| 8679023 | Kobayashi et al. | Mar 2014 | B2 |
| 8690884 | Linderman et al. | Apr 2014 | B2 |
| 8696679 | Shadduck et al. | Apr 2014 | B2 |
| RE44883 | Cha | May 2014 | E |
| 8740897 | Leung et al. | Jun 2014 | B2 |
| 8747359 | Pakter et al. | Jun 2014 | B2 |
| 8747398 | Behnke | Jun 2014 | B2 |
| 8758349 | Germain et al. | Jun 2014 | B2 |
| 8764761 | Truckai et al. | Jul 2014 | B2 |
| 8771265 | Truckai | Jul 2014 | B2 |
| 8771276 | Linderman | Jul 2014 | B2 |
| 8774913 | Demarais et al. | Jul 2014 | B2 |
| 8774924 | Weiner | Jul 2014 | B2 |
| 8777479 | Kwan et al. | Jul 2014 | B2 |
| 8784411 | Leuthardt et al. | Jul 2014 | B2 |
| 8795270 | Drake | Aug 2014 | B2 |
| 8808161 | Gregg et al. | Aug 2014 | B2 |
| 8808284 | Pellegrino et al. | Aug 2014 | B2 |
| 8814873 | Schaller et al. | Aug 2014 | B2 |
| 8818503 | Rittman, III | Aug 2014 | B2 |
| 8821488 | Stewart et al. | Sep 2014 | B2 |
| 8845631 | Werneth et al. | Sep 2014 | B2 |
| 8864759 | Godara et al. | Oct 2014 | B2 |
| 8864760 | Kramer et al. | Oct 2014 | B2 |
| 8864777 | Harrison et al. | Oct 2014 | B2 |
| 8882755 | Leung et al. | Nov 2014 | B2 |
| 8882759 | Manley et al. | Nov 2014 | B2 |
| 8882764 | Pellegrino et al. | Nov 2014 | B2 |
| 8894658 | Linderman et al. | Nov 2014 | B2 |
| 8911497 | Chavatte et al. | Dec 2014 | B2 |
| 8915949 | Diederich et al. | Dec 2014 | B2 |
| 8926620 | Chasmawala et al. | Jan 2015 | B2 |
| 8932300 | Shadduck et al. | Jan 2015 | B2 |
| 8939969 | Temelli et al. | Jan 2015 | B2 |
| 8968288 | Brannan | Mar 2015 | B2 |
| 8989859 | Deem et al. | Mar 2015 | B2 |
| 8992522 | Pellegrino et al. | Mar 2015 | B2 |
| 8992523 | Pellegrino et al. | Mar 2015 | B2 |
| 9005210 | Truckai et al. | Apr 2015 | B2 |
| 9008793 | Cosman, Sr. et al. | Apr 2015 | B1 |
| 9017325 | Pellegrino et al. | Apr 2015 | B2 |
| 9023038 | Pellegrino et al. | May 2015 | B2 |
| 9028488 | Goshayeshgar | May 2015 | B2 |
| 9028538 | Paul et al. | May 2015 | B2 |
| 9039701 | Pellegrino et al. | May 2015 | B2 |
| 9044245 | Condie et al. | Jun 2015 | B2 |
| 9044254 | Ladtkow et al. | Jun 2015 | B2 |
| 9044575 | Beasley et al. | Jun 2015 | B2 |
| 9066769 | Truckai et al. | Jun 2015 | B2 |
| 9078761 | Godara et al. | Jul 2015 | B2 |
| 9095359 | Robert et al. | Aug 2015 | B2 |
| 9113896 | Mulier et al. | Aug 2015 | B2 |
| 9113911 | Sherman | Aug 2015 | B2 |
| 9113925 | Smith et al. | Aug 2015 | B2 |
| 9113950 | Schultz et al. | Aug 2015 | B2 |
| 9113974 | Germain | Aug 2015 | B2 |
| 9119639 | Kuntz | Sep 2015 | B2 |
| 9119647 | Brannan | Sep 2015 | B2 |
| 9119650 | Brannan et al. | Sep 2015 | B2 |
| 9125671 | Germain et al. | Sep 2015 | B2 |
| 9131597 | Taft et al. | Sep 2015 | B2 |
| 9149652 | Wenz et al. | Oct 2015 | B2 |
| 9151680 | Brannan | Oct 2015 | B2 |
| 9155895 | Wacnik et al. | Oct 2015 | B2 |
| 9161735 | Bradford et al. | Oct 2015 | B2 |
| 9161797 | Truckai et al. | Oct 2015 | B2 |
| 9161798 | Truckai et al. | Oct 2015 | B2 |
| 9161805 | Isenberg | Oct 2015 | B2 |
| 9161809 | Germain et al. | Oct 2015 | B2 |
| 9161814 | Brannan et al. | Oct 2015 | B2 |
| 9168054 | Turner et al. | Oct 2015 | B2 |
| 9168078 | Linderman et al. | Oct 2015 | B2 |
| 9168085 | Juzkiw | Oct 2015 | B2 |
| 9173676 | Pellegrino et al. | Nov 2015 | B2 |
| 9173700 | Godara et al. | Nov 2015 | B2 |
| 9179970 | Utley et al. | Nov 2015 | B2 |
| 9179972 | Olson | Nov 2015 | B2 |
| 9180416 | Phan et al. | Nov 2015 | B2 |
| 9186197 | McKay | Nov 2015 | B2 |
| 9192308 | Brannan et al. | Nov 2015 | B2 |
| 9192397 | Sennett et al. | Nov 2015 | B2 |
| 9198684 | Arthur et al. | Dec 2015 | B2 |
| 9216053 | Godara et al. | Dec 2015 | B2 |
| 9226756 | Teisen et al. | Jan 2016 | B2 |
| 9232954 | Steiner et al. | Jan 2016 | B2 |
| 9237916 | Crainich et al. | Jan 2016 | B2 |
| 9238139 | Degiorgio et al. | Jan 2016 | B2 |
| 9241057 | Van Wyk et al. | Jan 2016 | B2 |
| 9241729 | Juntz et al. | Jan 2016 | B2 |
| 9241760 | Godara et al. | Jan 2016 | B2 |
| 9247970 | Teisen | Feb 2016 | B2 |
| 9247992 | Ladtkow et al. | Feb 2016 | B2 |
| 9247993 | Ladtkow et al. | Feb 2016 | B2 |
| 9248278 | Crosby et al. | Feb 2016 | B2 |
| 9248289 | Bennett et al. | Feb 2016 | B2 |
| 9254168 | Palanker | Feb 2016 | B2 |
| 9254386 | Lee et al. | Feb 2016 | B2 |
| 9259241 | Pellegrino et al. | Feb 2016 | B2 |
| 9259248 | Leuthardt et al. | Feb 2016 | B2 |
| 9259269 | Ladtkow et al. | Feb 2016 | B2 |
| 9259569 | Brounstein et al. | Feb 2016 | B2 |
| 9259577 | Kaula et al. | Feb 2016 | B2 |
| 9265522 | Pellegrino et al. | Feb 2016 | B2 |
| 9265557 | Sherman et al. | Feb 2016 | B2 |
| 9277969 | Brannan et al. | Mar 2016 | B2 |
| 9282979 | O'Neil et al. | Mar 2016 | B2 |
| 9282988 | Goshayeshgar | Mar 2016 | B2 |
| 9283015 | Tan-Malecki et al. | Mar 2016 | B2 |
| 9289607 | Su et al. | Mar 2016 | B2 |
| 9295517 | Peyman et al. | Mar 2016 | B2 |
| 9295841 | Fang et al. | Mar 2016 | B2 |
| 9301723 | Brannan et al. | Apr 2016 | B2 |
| 9301804 | Bonn | Apr 2016 | B2 |
| 9302117 | De Vincentiis | Apr 2016 | B2 |
| 9308036 | Robinson | Apr 2016 | B2 |
| 9308045 | Kim et al. | Apr 2016 | B2 |
| 9314252 | Schaller et al. | Apr 2016 | B2 |
| 9314613 | Mashiach | Apr 2016 | B2 |
| 9314618 | Imran et al. | Apr 2016 | B2 |
| 9333033 | Gliner | May 2016 | B2 |
| 9333144 | Baxter et al. | May 2016 | B2 |
| 9333339 | Weiner | May 2016 | B2 |
| 9333361 | Li et al. | May 2016 | B2 |
| 9333373 | Imran | May 2016 | B2 |
| 9339655 | Carbunaru | May 2016 | B2 |
| 9345530 | Ballakur et al. | May 2016 | B2 |
| 9345537 | Harrison et al. | May 2016 | B2 |
| 9345538 | Deem et al. | May 2016 | B2 |
| 9351739 | Mahoney et al. | May 2016 | B2 |
| 9358059 | Linderman et al. | Jun 2016 | B2 |
| 9358067 | Lee et al. | Jun 2016 | B2 |
| 9358396 | Holley | Jun 2016 | B2 |
| 9364242 | Tornier et al. | Jun 2016 | B2 |
| 9364286 | Werneth et al. | Jun 2016 | B2 |
| 9370348 | Tally et al. | Jun 2016 | B2 |
| 9370392 | Sharonov | Jun 2016 | B2 |
| 9370398 | Ladtkow et al. | Jun 2016 | B2 |
| 9375274 | Reid | Jun 2016 | B2 |
| 9375275 | Lee et al. | Jun 2016 | B2 |
| 9375278 | Robert et al. | Jun 2016 | B2 |
| 9375279 | Brannan | Jun 2016 | B2 |
| 9375283 | Arts et al. | Jun 2016 | B2 |
| 9381024 | Globerman et al. | Jul 2016 | B2 |
| 9381045 | Donner et al. | Jul 2016 | B2 |
| 9381050 | Lee et al. | Jul 2016 | B2 |
| 9381359 | Parramon et al. | Jul 2016 | B2 |
| 9387094 | Manrique et al. | Jul 2016 | B2 |
| 9393416 | Rooney et al. | Jul 2016 | B2 |
| 9398931 | Wittenberger et al. | Jul 2016 | B2 |
| 9399144 | Howard | Jul 2016 | B2 |
| 9403038 | Tyler | Aug 2016 | B2 |
| 9409023 | Burdick et al. | Aug 2016 | B2 |
| 9414884 | Faehndrich et al. | Aug 2016 | B2 |
| 9421064 | Pellegrino et al. | Aug 2016 | B2 |
| 9421123 | Lee et al. | Aug 2016 | B2 |
| 9421371 | Pless et al. | Aug 2016 | B2 |
| 9421378 | Lian et al. | Aug 2016 | B2 |
| 9439693 | Childs et al. | Sep 2016 | B2 |
| 9439721 | Werneth et al. | Sep 2016 | B2 |
| 9445859 | Pageard | Sep 2016 | B2 |
| 9446229 | Omar-Pasha | Sep 2016 | B2 |
| 9446235 | Su et al. | Sep 2016 | B2 |
| 9452286 | Cowan et al. | Sep 2016 | B2 |
| 9456836 | Boling et al. | Oct 2016 | B2 |
| 9457182 | Koop | Oct 2016 | B2 |
| 9468485 | Wittenberger et al. | Oct 2016 | B2 |
| 9468495 | Kunis et al. | Oct 2016 | B2 |
| 9474565 | Shikhman et al. | Oct 2016 | B2 |
| 9474906 | Sachs et al. | Oct 2016 | B2 |
| 9480485 | Aho et al. | Nov 2016 | B2 |
| 9486279 | Pellegrino et al. | Nov 2016 | B2 |
| 9486447 | Peterson et al. | Nov 2016 | B2 |
| 9486621 | Howard et al. | Nov 2016 | B2 |
| 9492657 | Gerber | Nov 2016 | B2 |
| 9492664 | Peterson | Nov 2016 | B2 |
| 9504372 | Kim | Nov 2016 | B2 |
| 9504481 | Germain et al. | Nov 2016 | B2 |
| 9504506 | Crainich et al. | Nov 2016 | B2 |
| 9504518 | Condie et al. | Nov 2016 | B2 |
| 9504530 | Hartmann et al. | Nov 2016 | B2 |
| 9504818 | Moffitt et al. | Nov 2016 | B2 |
| 9511229 | Bradley | Dec 2016 | B2 |
| 9511231 | Kent et al. | Dec 2016 | B1 |
| 9513761 | Shikhman et al. | Dec 2016 | B2 |
| 9517077 | Blain et al. | Dec 2016 | B2 |
| 9517200 | Bleier | Dec 2016 | B2 |
| 9526507 | Germain | Dec 2016 | B2 |
| 9526551 | Linderman | Dec 2016 | B2 |
| 9526559 | Benamou et al. | Dec 2016 | B2 |
| 9532828 | Condie et al. | Jan 2017 | B2 |
| 9549772 | Carl | Jan 2017 | B2 |
| 9550041 | Bedell | Jan 2017 | B2 |
| 9555037 | Podhajsky | Jan 2017 | B2 |
| 9556101 | Robertson et al. | Jan 2017 | B2 |
| 9556449 | Basu et al. | Jan 2017 | B2 |
| 9566449 | Perryman et al. | Feb 2017 | B2 |
| 9572976 | Howard et al. | Feb 2017 | B2 |
| 9572986 | Moffitt | Feb 2017 | B2 |
| 9579127 | Kostuik et al. | Feb 2017 | B2 |
| 9579518 | Gertner | Feb 2017 | B2 |
| 9597091 | Bromer | Mar 2017 | B2 |
| 9597148 | Olson | Mar 2017 | B2 |
| RE46356 | Pellegrino et al. | Apr 2017 | E |
| 9610083 | Kuntz | Apr 2017 | B2 |
| 9610117 | Germain | Apr 2017 | B2 |
| 9636175 | Stern et al. | May 2017 | B2 |
| 9642629 | Griffiths et al. | May 2017 | B2 |
| 9649116 | Germain | May 2017 | B2 |
| 9681889 | Greenhalgh et al. | Jun 2017 | B1 |
| 9687255 | Sennett et al. | Jun 2017 | B2 |
| 9724107 | Pellegrino et al. | Aug 2017 | B2 |
| 9724151 | Edidin | Aug 2017 | B2 |
| 9730707 | Sasaki et al. | Aug 2017 | B2 |
| 9743854 | Stewart et al. | Aug 2017 | B2 |
| 9743938 | Germain et al. | Aug 2017 | B2 |
| 9750560 | Ballakur et al. | Sep 2017 | B2 |
| 9757193 | Zarins et al. | Sep 2017 | B2 |
| 9770280 | Diederich et al. | Sep 2017 | B2 |
| 9775627 | Patel et al. | Oct 2017 | B2 |
| 9782221 | Srinivasan | Oct 2017 | B2 |
| 9795802 | Mohamed et al. | Oct 2017 | B2 |
| 9814514 | Shelton, IV et al. | Nov 2017 | B2 |
| 9844406 | Edwards et al. | Dec 2017 | B2 |
| 9848944 | Sutton et al. | Dec 2017 | B2 |
| 9872687 | Tornier et al. | Jan 2018 | B2 |
| 9872691 | Griffiths et al. | Jan 2018 | B2 |
| 9877707 | Godara et al. | Jan 2018 | B2 |
| 9913675 | Germain | Mar 2018 | B2 |
| 10028753 | Pellegrino et al. | Jul 2018 | B2 |
| 10028784 | Kramer et al. | Jul 2018 | B2 |
| 10052152 | Tegg et al. | Aug 2018 | B2 |
| 10111674 | Crainich et al. | Oct 2018 | B2 |
| 10111704 | Pellegrino et al. | Oct 2018 | B2 |
| 10123809 | Germain | Nov 2018 | B2 |
| 10245092 | Germain | Apr 2019 | B2 |
| 10265099 | Pellegrino et al. | Apr 2019 | B2 |
| 10272271 | Diederich et al. | Apr 2019 | B2 |
| 10292716 | Aho et al. | May 2019 | B2 |
| 10292719 | Burger et al. | May 2019 | B2 |
| 10299805 | Germain et al. | May 2019 | B2 |
| 10327841 | Germain | Jun 2019 | B2 |
| 10357258 | Patel et al. | Jul 2019 | B2 |
| 10383641 | LeRoy et al. | Aug 2019 | B2 |
| 10390877 | Heggeness et al. | Aug 2019 | B2 |
| 10441295 | Brockman et al. | Oct 2019 | B2 |
| 10448995 | Olson | Oct 2019 | B2 |
| 10456187 | Edidin | Oct 2019 | B2 |
| 10463380 | Purdy et al. | Nov 2019 | B2 |
| 10463423 | Sutton et al. | Nov 2019 | B2 |
| 10470781 | Purdy et al. | Nov 2019 | B2 |
| 10478241 | Purdy et al. | Nov 2019 | B2 |
| 10478246 | Pellegrino et al. | Nov 2019 | B2 |
| 10493247 | Goshayeshgar | Dec 2019 | B2 |
| 10499960 | Sinnott et al. | Dec 2019 | B2 |
| 10517611 | Patel et al. | Dec 2019 | B2 |
| 10524805 | Zilberman et al. | Jan 2020 | B2 |
| 10588691 | Pellegrino et al. | Mar 2020 | B2 |
| 10589131 | Diederich et al. | Mar 2020 | B2 |
| 10603522 | Diederich et al. | Mar 2020 | B2 |
| 10624652 | Germain et al. | Apr 2020 | B2 |
| 10660656 | Purdy et al. | May 2020 | B2 |
| 10898254 | Diederich et al. | Jan 2021 | B2 |
| 10905440 | Pellegrino et al. | Feb 2021 | B2 |
| RE48460 | Pellegrino et al. | Mar 2021 | E |
| 11007010 | Donovan et al. | May 2021 | B2 |
| 11026734 | Truckai et al. | Jun 2021 | B2 |
| 11026744 | Purdy et al. | Jun 2021 | B2 |
| 11052267 | Diederich et al. | Jul 2021 | B2 |
| 11065046 | Edidin | Jul 2021 | B2 |
| 11123103 | Donovan et al. | Sep 2021 | B2 |
| 11160563 | Patel et al. | Nov 2021 | B2 |
| 20010001314 | Davison et al. | May 2001 | A1 |
| 20010001811 | Burney et al. | May 2001 | A1 |
| 20010020167 | Woloszko et al. | Sep 2001 | A1 |
| 20010023348 | Ashley et al. | Sep 2001 | A1 |
| 20010025176 | Ellsberry et al. | Sep 2001 | A1 |
| 20010025177 | Woloszko et al. | Sep 2001 | A1 |
| 20010027295 | Dulak et al. | Oct 2001 | A1 |
| 20010029370 | Hovda et al. | Oct 2001 | A1 |
| 20010029373 | Baker et al. | Oct 2001 | A1 |
| 20010029393 | Tierney et al. | Oct 2001 | A1 |
| 20010032001 | Ricart et al. | Oct 2001 | A1 |
| 20010047167 | Heggeness | Nov 2001 | A1 |
| 20010049522 | Eggers et al. | Dec 2001 | A1 |
| 20010049527 | Cragg | Dec 2001 | A1 |
| 20010051802 | Woloszko et al. | Dec 2001 | A1 |
| 20010053885 | Gielen et al. | Dec 2001 | A1 |
| 20010056280 | Underwood et al. | Dec 2001 | A1 |
| 20020016583 | Cragg | Feb 2002 | A1 |
| 20020016600 | Cosman | Feb 2002 | A1 |
| 20020019626 | Sharkey et al. | Feb 2002 | A1 |
| 20020026186 | Woloszko et al. | Feb 2002 | A1 |
| 20020049438 | Sharkey et al. | Apr 2002 | A1 |
| 20020052600 | Davison et al. | May 2002 | A1 |
| 20020068930 | Tasto et al. | Jun 2002 | A1 |
| 20020095144 | Carl | Jul 2002 | A1 |
| 20020095151 | Dahla et al. | Jul 2002 | A1 |
| 20020095152 | Ciarrocca et al. | Jul 2002 | A1 |
| 20020099366 | Dahla et al. | Jul 2002 | A1 |
| 20020111661 | Cross et al. | Aug 2002 | A1 |
| 20020115945 | D'Luzansky et al. | Aug 2002 | A1 |
| 20020120259 | Lettice et al. | Aug 2002 | A1 |
| 20020133148 | Daniel et al. | Sep 2002 | A1 |
| 20020147444 | Shah et al. | Oct 2002 | A1 |
| 20020151885 | Underwood et al. | Oct 2002 | A1 |
| 20020165532 | Hill et al. | Nov 2002 | A1 |
| 20020183758 | Middleton | Dec 2002 | A1 |
| 20020188284 | To et al. | Dec 2002 | A1 |
| 20020188290 | Sharkey et al. | Dec 2002 | A1 |
| 20020193708 | Horzewski et al. | Dec 2002 | A1 |
| 20020193789 | Underwood et al. | Dec 2002 | A1 |
| 20030009164 | Woloszko et al. | Jan 2003 | A1 |
| 20030014047 | Woloszko et al. | Jan 2003 | A1 |
| 20030014088 | Fang et al. | Jan 2003 | A1 |
| 20030028147 | Aves et al. | Feb 2003 | A1 |
| 20030028189 | Woloszko et al. | Feb 2003 | A1 |
| 20030040742 | Underwood et al. | Feb 2003 | A1 |
| 20030055418 | Tasto et al. | Mar 2003 | A1 |
| 20030069569 | Burdette et al. | Apr 2003 | A1 |
| 20030083592 | Faciszewski | May 2003 | A1 |
| 20030084907 | Pacek et al. | May 2003 | A1 |
| 20030097126 | Woloszko et al. | May 2003 | A1 |
| 20030097129 | Davison et al. | May 2003 | A1 |
| 20030130655 | Woloszko et al. | Jul 2003 | A1 |
| 20030139652 | Kang et al. | Jul 2003 | A1 |
| 20030158545 | Hovda et al. | Aug 2003 | A1 |
| 20030181963 | Pellegrino et al. | Sep 2003 | A1 |
| 20030208194 | Hovda et al. | Nov 2003 | A1 |
| 20030216725 | Woloszko et al. | Nov 2003 | A1 |
| 20030216726 | Eggers et al. | Nov 2003 | A1 |
| 20030225364 | Kraft | Dec 2003 | A1 |
| 20040006339 | Underwood et al. | Jan 2004 | A1 |
| 20040015163 | Buysse et al. | Jan 2004 | A1 |
| 20040024399 | Sharps et al. | Feb 2004 | A1 |
| 20040054366 | Davison et al. | Mar 2004 | A1 |
| 20040064023 | Thomas et al. | Apr 2004 | A1 |
| 20040064136 | Crombie et al. | Apr 2004 | A1 |
| 20040064137 | Pellegrino et al. | Apr 2004 | A1 |
| 20040068242 | McGuckin, Jr. | Apr 2004 | A1 |
| 20040082942 | Katzman | Apr 2004 | A1 |
| 20040082946 | Malis et al. | Apr 2004 | A1 |
| 20040087937 | Eggers et al. | May 2004 | A1 |
| 20040111087 | Stern et al. | Jun 2004 | A1 |
| 20040116922 | Hovda et al. | Jun 2004 | A1 |
| 20040120668 | Loeb | Jun 2004 | A1 |
| 20040120891 | Hili et al. | Jun 2004 | A1 |
| 20040133124 | Bates et al. | Jul 2004 | A1 |
| 20040162559 | Arramon | Aug 2004 | A1 |
| 20040186544 | King | Sep 2004 | A1 |
| 20040193151 | To et al. | Sep 2004 | A1 |
| 20040220577 | Cragg et al. | Nov 2004 | A1 |
| 20040225228 | Ferree | Nov 2004 | A1 |
| 20040230190 | Dahla et al. | Nov 2004 | A1 |
| 20040267269 | Middleton et al. | Dec 2004 | A1 |
| 20050004634 | Ricart et al. | Jan 2005 | A1 |
| 20050010095 | Stewart et al. | Jan 2005 | A1 |
| 20050010203 | Edwards et al. | Jan 2005 | A1 |
| 20050010205 | Hovda et al. | Jan 2005 | A1 |
| 20050043737 | Reiley et al. | Feb 2005 | A1 |
| 20050055096 | Serhan et al. | Mar 2005 | A1 |
| 20050124989 | Suddaby | Jun 2005 | A1 |
| 20050177209 | Leung et al. | Aug 2005 | A1 |
| 20050177210 | Leung et al. | Aug 2005 | A1 |
| 20050177211 | Leung et al. | Aug 2005 | A1 |
| 20050182417 | Pagano | Aug 2005 | A1 |
| 20050192564 | Cosman et al. | Sep 2005 | A1 |
| 20050209610 | Carrison | Sep 2005 | A1 |
| 20050209659 | Pellegrino et al. | Sep 2005 | A1 |
| 20050216018 | Sennett | Sep 2005 | A1 |
| 20050234445 | Conquergood et al. | Oct 2005 | A1 |
| 20050261754 | Woloszko | Nov 2005 | A1 |
| 20050267552 | Conquergood et al. | Dec 2005 | A1 |
| 20050278007 | Godara | Dec 2005 | A1 |
| 20050283148 | Janssen et al. | Dec 2005 | A1 |
| 20060004369 | Patel et al. | Jan 2006 | A1 |
| 20060036264 | Selover et al. | Feb 2006 | A1 |
| 20060052743 | Reynolds | Mar 2006 | A1 |
| 20060064101 | Arramon | Mar 2006 | A1 |
| 20060095026 | Ricart et al. | May 2006 | A1 |
| 20060095028 | Bleich | May 2006 | A1 |
| 20060106375 | Werneth et al. | May 2006 | A1 |
| 20060106376 | Godara et al. | May 2006 | A1 |
| 20060122458 | Bleich | Jun 2006 | A1 |
| 20060129101 | MoGuckin | Jun 2006 | A1 |
| 20060178670 | Woloszko et al. | Aug 2006 | A1 |
| 20060200121 | Mowery | Sep 2006 | A1 |
| 20060206128 | Conquergood et al. | Sep 2006 | A1 |
| 20060206129 | Conquergood et al. | Sep 2006 | A1 |
| 20060206130 | Conquergood et al. | Sep 2006 | A1 |
| 20060206132 | Conquergood et al. | Sep 2006 | A1 |
| 20060206133 | Conquergood et al. | Sep 2006 | A1 |
| 20060206134 | Conquergood et al. | Sep 2006 | A1 |
| 20060206166 | Weiner | Sep 2006 | A1 |
| 20060217736 | Kaneko et al. | Sep 2006 | A1 |
| 20060229625 | Truckai et al. | Oct 2006 | A1 |
| 20060247746 | Danek et al. | Nov 2006 | A1 |
| 20060253117 | Hovda et al. | Nov 2006 | A1 |
| 20060259026 | Godara et al. | Nov 2006 | A1 |
| 20060264957 | Cragg et al. | Nov 2006 | A1 |
| 20060264965 | Shadduck et al. | Nov 2006 | A1 |
| 20060265014 | Demarais et al. | Nov 2006 | A1 |
| 20060276749 | Selmon et al. | Dec 2006 | A1 |
| 20060287649 | Ormsby et al. | Dec 2006 | A1 |
| 20070027449 | Godara et al. | Feb 2007 | A1 |
| 20070055316 | Godara et al. | Mar 2007 | A1 |
| 20070066987 | Scanlan, Jr. et al. | Mar 2007 | A1 |
| 20070074719 | Danek et al. | Apr 2007 | A1 |
| 20070118142 | Krueger et al. | May 2007 | A1 |
| 20070129715 | Eggers et al. | Jun 2007 | A1 |
| 20070142791 | Yeung | Jun 2007 | A1 |
| 20070142842 | Krueger et al. | Jun 2007 | A1 |
| 20070149966 | Dahla et al. | Jun 2007 | A1 |
| 20070179497 | Eggers et al. | Aug 2007 | A1 |
| 20070185231 | Liu et al. | Aug 2007 | A1 |
| 20070213584 | Kim et al. | Sep 2007 | A1 |
| 20070213735 | Saadat et al. | Sep 2007 | A1 |
| 20070260237 | Sutton et al. | Nov 2007 | A1 |
| 20080004621 | Dahla et al. | Jan 2008 | A1 |
| 20080004675 | King et al. | Jan 2008 | A1 |
| 20080009847 | Ricart et al. | Jan 2008 | A1 |
| 20080021447 | Davison et al. | Jan 2008 | A1 |
| 20080021463 | Georgy | Jan 2008 | A1 |
| 20080058707 | Ashley et al. | Mar 2008 | A1 |
| 20080065062 | Leung et al. | Mar 2008 | A1 |
| 20080091207 | Truckai et al. | Apr 2008 | A1 |
| 20080114364 | Goldin et al. | May 2008 | A1 |
| 20080119844 | Woloszko et al. | May 2008 | A1 |
| 20080119846 | Rioux | May 2008 | A1 |
| 20080132890 | Woloszko et al. | Jun 2008 | A1 |
| 20080161804 | Rioux et al. | Jul 2008 | A1 |
| 20080275458 | Bieich et al. | Nov 2008 | A1 |
| 20080281322 | Sherman et al. | Nov 2008 | A1 |
| 20080294166 | Goldin et al. | Nov 2008 | A1 |
| 20080294167 | Schumacher et al. | Nov 2008 | A1 |
| 20090030308 | Bradford et al. | Jan 2009 | A1 |
| 20090054951 | Leuthardt et al. | Feb 2009 | A1 |
| 20090069807 | Eggers et al. | Mar 2009 | A1 |
| 20090076520 | Choi | Mar 2009 | A1 |
| 20090105775 | Mitchell et al. | Apr 2009 | A1 |
| 20090112278 | Wingeier et al. | Apr 2009 | A1 |
| 20090118731 | Young et al. | May 2009 | A1 |
| 20090131867 | Liu et al. | May 2009 | A1 |
| 20090131886 | Liu et al. | May 2009 | A1 |
| 20090149878 | Truckai et al. | Jun 2009 | A1 |
| 20090204192 | Carlton et al. | Aug 2009 | A1 |
| 20090222053 | Gaunt et al. | Sep 2009 | A1 |
| 20090312764 | Marino | Dec 2009 | A1 |
| 20100010392 | Skelton et al. | Jan 2010 | A1 |
| 20100016929 | Prochazka | Jan 2010 | A1 |
| 20100023006 | Ellman | Jan 2010 | A1 |
| 20100023065 | Welch et al. | Jan 2010 | A1 |
| 20100082033 | Germain | Apr 2010 | A1 |
| 20100094269 | Pellegrino et al. | Apr 2010 | A1 |
| 20100114098 | Carl | May 2010 | A1 |
| 20100145424 | Podhajsky et al. | Jun 2010 | A1 |
| 20100179556 | Scribner et al. | Jul 2010 | A1 |
| 20100185082 | Chandran et al. | Jul 2010 | A1 |
| 20100185161 | Pellegrino et al. | Jul 2010 | A1 |
| 20100211076 | Germain et al. | Aug 2010 | A1 |
| 20100222777 | Sutton et al. | Sep 2010 | A1 |
| 20100261989 | Boseck et al. | Oct 2010 | A1 |
| 20100261990 | Gillis et al. | Oct 2010 | A1 |
| 20100298737 | Koehler | Nov 2010 | A1 |
| 20100298832 | Lau et al. | Nov 2010 | A1 |
| 20100324506 | Pellegrino | Dec 2010 | A1 |
| 20110022133 | Diederich et al. | Jan 2011 | A1 |
| 20110034884 | Pellegrino et al. | Feb 2011 | A9 |
| 20110040362 | Godara et al. | Feb 2011 | A1 |
| 20110077628 | Hoey et al. | Mar 2011 | A1 |
| 20110087314 | Diederich et al. | Apr 2011 | A1 |
| 20110118735 | Abou-Marie et al. | May 2011 | A1 |
| 20110130751 | Malis et al. | Jun 2011 | A1 |
| 20110144524 | Fish et al. | Jun 2011 | A1 |
| 20110196361 | Vilims | Aug 2011 | A1 |
| 20110206260 | Bergmans et al. | Aug 2011 | A1 |
| 20110264098 | Cobbs | Oct 2011 | A1 |
| 20110276001 | Schultz et al. | Nov 2011 | A1 |
| 20110295261 | Germain | Dec 2011 | A1 |
| 20110319765 | Gertner et al. | Dec 2011 | A1 |
| 20120029420 | Vilims | Feb 2012 | A1 |
| 20120116266 | House et al. | May 2012 | A1 |
| 20120123427 | McGuckin, Jr | May 2012 | A1 |
| 20120136346 | Condie et al. | May 2012 | A1 |
| 20120136348 | Condie et al. | May 2012 | A1 |
| 20120143090 | Hay et al. | Jun 2012 | A1 |
| 20120172858 | Harrison et al. | Jul 2012 | A1 |
| 20120172859 | Condie et al. | Jul 2012 | A1 |
| 20120191095 | Burger et al. | Jul 2012 | A1 |
| 20120196251 | Taft et al. | Aug 2012 | A1 |
| 20120197344 | Taft et al. | Aug 2012 | A1 |
| 20120203219 | Evans et al. | Aug 2012 | A1 |
| 20120226273 | Nguyen et al. | Sep 2012 | A1 |
| 20120239050 | Linderman | Sep 2012 | A1 |
| 20120265186 | Burger et al. | Oct 2012 | A1 |
| 20120330180 | Pellegrino et al. | Dec 2012 | A1 |
| 20120330300 | Pellegrino et al. | Dec 2012 | A1 |
| 20120339301 | Pellegrino et al. | Dec 2012 | |
| 20130006232 | Pellegrino et al. | Jan 2013 | A1 |
| 20130006233 | Pellegrino et al. | Jan 2013 | A1 |
| 20130012933 | Pellegrino et al. | Jan 2013 | A1 |
| 20130012935 | Pellegrino et al. | Jan 2013 | A1 |
| 20130012936 | Pellegrino et al. | Jan 2013 | A1 |
| 20130012951 | Linderman | Jan 2013 | A1 |
| 20130060244 | Godara et al. | Mar 2013 | A1 |
| 20130079810 | Isenberg | Mar 2013 | A1 |
| 20130197508 | Shikhman et al. | Aug 2013 | A1 |
| 20130231654 | Germain | Sep 2013 | A1 |
| 20130237979 | Shikhman et al. | Sep 2013 | A1 |
| 20130103022 | Sutton et al. | Oct 2013 | A1 |
| 20130261507 | Diederich et al. | Oct 2013 | A1 |
| 20130274784 | Lenker et al. | Oct 2013 | A1 |
| 20130296767 | Zarins et al. | Nov 2013 | A1 |
| 20130324993 | McCarthey et al. | Dec 2013 | A1 |
| 20130324994 | Pellegrino et al. | Dec 2013 | A1 |
| 20130324996 | Pellegrino et al. | Dec 2013 | A1 |
| 20130324997 | Pellegrino et al. | Dec 2013 | A1 |
| 20130331840 | Teisen et al. | Dec 2013 | A1 |
| 20130345765 | Brockman et al. | Dec 2013 | A1 |
| 20140005614 | Abousleiman | Jan 2014 | A1 |
| 20140031715 | Sherar et al. | Jan 2014 | A1 |
| 20140039500 | Pellegrino et al. | Feb 2014 | A1 |
| 20140046245 | Cornacchia | Feb 2014 | A1 |
| 20140046328 | Schumacher et al. | Feb 2014 | A1 |
| 20140066913 | Sherman | Mar 2014 | A1 |
| 20140088575 | Loeb | Mar 2014 | A1 |
| 20140148801 | Asher et al. | May 2014 | A1 |
| 20140148805 | Stewart et al. | May 2014 | A1 |
| 20140171942 | Werneth et al. | Jun 2014 | A1 |
| 20140194887 | Shenoy | Jul 2014 | A1 |
| 20140221967 | Childs et al. | Aug 2014 | A1 |
| 20140236137 | Tran et al. | Aug 2014 | A1 |
| 20140236144 | Krueger et al. | Aug 2014 | A1 |
| 20140243823 | Godara et al. | Aug 2014 | A1 |
| 20140243943 | Rao et al. | Aug 2014 | A1 |
| 20140257265 | Godara et al. | Sep 2014 | A1 |
| 20140257296 | Morgenstern Lopez | Sep 2014 | A1 |
| 20140271717 | Goshayeshgar et al. | Sep 2014 | A1 |
| 20140276728 | Goshayeshgar et al. | Sep 2014 | A1 |
| 20140276744 | Arthur et al. | Sep 2014 | A1 |
| 20140288544 | Diederich et al. | Sep 2014 | A1 |
| 20140288546 | Sherman et al. | Sep 2014 | A1 |
| 20140296850 | Condie et al. | Oct 2014 | A1 |
| 20140303610 | McCarthy et al. | Oct 2014 | A1 |
| 20140303614 | McCarthy et al. | Oct 2014 | A1 |
| 20140316405 | Pellegrino et al. | Oct 2014 | A1 |
| 20140316413 | Burger et al. | Oct 2014 | A1 |
| 20140324051 | Pellegrino et al. | Oct 2014 | A1 |
| 20140330332 | Danek et al. | Nov 2014 | A1 |
| 20140336630 | Woloszko et al. | Nov 2014 | A1 |
| 20140336667 | Pellegrino et al. | Nov 2014 | A1 |
| 20140364842 | Werneth et al. | Dec 2014 | A1 |
| 20140371740 | Germain et al. | Dec 2014 | A1 |
| 20150005767 | Werneth et al. | Jan 2015 | A1 |
| 20150045783 | Edidin | Feb 2015 | A1 |
| 20150057658 | Sutton et al. | Feb 2015 | A1 |
| 20150065945 | Zarins et al. | Mar 2015 | A1 |
| 20150073515 | Turovskiy et al. | Mar 2015 | A1 |
| 20150105701 | Mayer et al. | Apr 2015 | A1 |
| 20150141876 | Diederich et al. | May 2015 | A1 |
| 20150157402 | Kunis et al. | Jun 2015 | A1 |
| 20150164546 | Pellegrino et al. | Jun 2015 | A1 |
| 20150196358 | Goshayeshgar | Jul 2015 | A1 |
| 20150216588 | Deem et al. | Aug 2015 | A1 |
| 20150231417 | Metcalf et al. | Aug 2015 | A1 |
| 20150272655 | Condie et al. | Oct 2015 | A1 |
| 20150273208 | Hamilton | Oct 2015 | A1 |
| 20150297246 | Patel et al. | Oct 2015 | A1 |
| 20150297282 | Cadouri | Oct 2015 | A1 |
| 20150320480 | Cosman, Jr. et al. | Nov 2015 | A1 |
| 20150335349 | Pellegrino et al. | Nov 2015 | A1 |
| 20150335382 | Pellegrino et al. | Nov 2015 | A1 |
| 20150342619 | Weitzman | Dec 2015 | A1 |
| 20150342660 | Nash | Dec 2015 | A1 |
| 20150342670 | Pellegrino et al. | Dec 2015 | A1 |
| 20150359586 | Heggeness | Dec 2015 | A1 |
| 20150374432 | Godara et al. | Dec 2015 | A1 |
| 20150374992 | Crosby et al. | Dec 2015 | A1 |
| 20150374995 | Foreman et al. | Dec 2015 | A1 |
| 20160000601 | Burger et al. | Jan 2016 | A1 |
| 20160001096 | Mishelevich | Jan 2016 | A1 |
| 20160002627 | Bennett et al. | Jan 2016 | A1 |
| 20160008593 | Cairns | Jan 2016 | A1 |
| 20160008618 | Omar-Pasha | Jan 2016 | A1 |
| 20160008628 | Morries et al. | Jan 2016 | A1 |
| 20160016012 | Youn et al. | Jan 2016 | A1 |
| 20160022988 | Thieme et al. | Jan 2016 | A1 |
| 20160022994 | Moffitt et al. | Jan 2016 | A1 |
| 20160024208 | MacDonald et al. | Jan 2016 | A1 |
| 20160029930 | Plumley et al. | Feb 2016 | A1 |
| 20160030276 | Spanyer | Feb 2016 | A1 |
| 20160030408 | Levin | Feb 2016 | A1 |
| 20160030748 | Edgerton et al. | Feb 2016 | A1 |
| 20160030765 | Towne et al. | Feb 2016 | A1 |
| 20160045207 | Kovacs et al. | Feb 2016 | A1 |
| 20160045256 | Godara et al. | Feb 2016 | A1 |
| 20160051831 | Lundmark et al. | Feb 2016 | A1 |
| 20160059007 | Koop | Mar 2016 | A1 |
| 20160074068 | Patwardhan | Mar 2016 | A1 |
| 20160074133 | Shikhman et al. | Mar 2016 | A1 |
| 20160074279 | Shin | Mar 2016 | A1 |
| 20160074661 | Lipani | Mar 2016 | A1 |
| 20160081716 | Boling et al. | Mar 2016 | A1 |
| 20160081810 | Reiley et al. | Mar 2016 | A1 |
| 20160095721 | Schell et al. | Apr 2016 | A1 |
| 20160106443 | Kuntz et al. | Apr 2016 | A1 |
| 20160106985 | Zhu | Apr 2016 | A1 |
| 20160106994 | Crosby et al. | Apr 2016 | A1 |
| 20160113704 | Godara et al. | Apr 2016 | A1 |
| 20160115173 | Bois et al. | Apr 2016 | A1 |
| 20160136310 | Bradford et al. | May 2016 | A1 |
| 20160144182 | Bennett et al. | May 2016 | A1 |
| 20160144187 | Caparso et al. | May 2016 | A1 |
| 20160158551 | Kent et al. | Jun 2016 | A1 |
| 20160166302 | Tan-Malecki et al. | Jun 2016 | A1 |
| 20160166835 | De Ridder | Jun 2016 | A1 |
| 20160175586 | Edgerton et al. | Jun 2016 | A1 |
| 20160199097 | Linderman et al. | Jul 2016 | A1 |
| 20160199117 | Druma | Jul 2016 | A1 |
| 20160213927 | McGee et al. | Jul 2016 | A1 |
| 20160220317 | Shikhman et al. | Aug 2016 | A1 |
| 20160220393 | Slivka et al. | Aug 2016 | A1 |
| 20160220638 | Dony et al. | Aug 2016 | A1 |
| 20160220672 | Chalasani et al. | Aug 2016 | A1 |
| 20160228131 | Brockman et al. | Aug 2016 | A1 |
| 20160228696 | Imran et al. | Aug 2016 | A1 |
| 20160235471 | Godara et al. | Aug 2016 | A1 |
| 20160235474 | Prisco et al. | Aug 2016 | A1 |
| 20160243353 | Ahmed | Aug 2016 | A1 |
| 20160246944 | Jain et al. | Aug 2016 | A1 |
| 20160250469 | Kim et al. | Sep 2016 | A1 |
| 20160250472 | Carbunaru | Sep 2016 | A1 |
| 20160262830 | Werneth et al. | Sep 2016 | A1 |
| 20160262904 | Schaller et al. | Sep 2016 | A1 |
| 20160271405 | Angara et al. | Sep 2016 | A1 |
| 20160278791 | Pellegrino et al. | Sep 2016 | A1 |
| 20160278846 | Harrison et al. | Sep 2016 | A1 |
| 20160278861 | Ko | Sep 2016 | A1 |
| 20160279190 | Watts et al. | Sep 2016 | A1 |
| 20160279408 | Grigsby et al. | Sep 2016 | A1 |
| 20160279411 | Rooney et al. | Sep 2016 | A1 |
| 20160279441 | Imran | Sep 2016 | A1 |
| 20160302925 | Keogh et al. | Oct 2016 | A1 |
| 20160302936 | Billon et al. | Oct 2016 | A1 |
| 20160310739 | Burdick et al. | Oct 2016 | A1 |
| 20160317053 | Srivastava | Nov 2016 | A1 |
| 20160317211 | Harrison et al. | Nov 2016 | A1 |
| 20160317621 | Bright | Nov 2016 | A1 |
| 20160324541 | Pellegrino et al. | Nov 2016 | A1 |
| 20160324677 | Hyde et al. | Nov 2016 | A1 |
| 20160325100 | Lian et al. | Nov 2016 | A1 |
| 20160339251 | Kent et al. | Nov 2016 | A1 |
| 20160354093 | Pellegrino et al. | Nov 2016 | A1 |
| 20160354233 | Sansone et al. | Dec 2016 | A1 |
| 20160367797 | Eckermann | Dec 2016 | A1 |
| 20160367823 | Cowan et al. | Dec 2016 | A1 |
| 20160375259 | Davis et al. | Dec 2016 | A1 |
| 20170000501 | Aho et al. | Jan 2017 | A1 |
| 20170001026 | Schwarz et al. | Jan 2017 | A1 |
| 20170007277 | Drapeau et al. | Jan 2017 | A1 |
| 20170014169 | Dean et al. | Jan 2017 | A1 |
| 20170027618 | Lee et al. | Feb 2017 | A1 |
| 20170028201 | Howard | Feb 2017 | A1 |
| 20170035483 | Crainich et al. | Feb 2017 | A1 |
| 20170036009 | Hughes et al. | Feb 2017 | A1 |
| 20170036025 | Sachs et al. | Feb 2017 | A1 |
| 20170036033 | Perryman et al. | Feb 2017 | A9 |
| 20170042834 | Westphal et al. | Feb 2017 | A1 |
| 20170049500 | Shikhman et al. | Feb 2017 | A1 |
| 20170049503 | Cosman | Feb 2017 | A1 |
| 20170049507 | Cosman | Feb 2017 | A1 |
| 20170049513 | Cosman | Feb 2017 | A1 |
| 20170050017 | Cosman | Feb 2017 | A1 |
| 20170050021 | Cosman | Feb 2017 | A1 |
| 20170050024 | Bhadra et al. | Feb 2017 | A1 |
| 20170628198 | Degiorgio et al. | Feb 2017 | |
| 20170056028 | Germain et al. | Mar 2017 | A1 |
| 20170065329 | Benamou et al. | Mar 2017 | A1 |
| 20170112507 | Crainich et al. | Apr 2017 | A1 |
| 20170119461 | Godara et al. | May 2017 | A1 |
| 20170128080 | Torrie | May 2017 | A1 |
| 20170128112 | Germain | May 2017 | A1 |
| 20170135742 | Lee et al. | May 2017 | A1 |
| 20170164998 | Klimovitch | Jun 2017 | A1 |
| 20170172650 | Germain | Jun 2017 | A1 |
| 20170181788 | Dastjerdi et al. | Jun 2017 | A1 |
| 20170202613 | Pellegrino et al. | Jul 2017 | A1 |
| 20170238943 | Sennett et al. | Aug 2017 | A1 |
| 20170266419 | Goshayeshgar | Sep 2017 | A1 |
| 20170303983 | Linderman et al. | Oct 2017 | A1 |
| 20170312007 | Harlev et al. | Nov 2017 | A1 |
| 20170333052 | Ding et al. | Nov 2017 | A1 |
| 20180021048 | Pellegrino et al. | Jan 2018 | A1 |
| 20180042656 | Edidin | Feb 2018 | A1 |
| 20180055539 | Pellegrino | Mar 2018 | A1 |
| 20180103964 | Patel et al. | Apr 2018 | A1 |
| 20180153604 | Ayvazyan et al. | Jun 2018 | A1 |
| 20180161047 | Purdy et al. | Jun 2018 | A1 |
| 20180193088 | Sutton et al. | Jul 2018 | A1 |
| 20190029698 | Pellegrino et al. | Jan 2019 | A1 |
| 20190038296 | Pellegrino | Feb 2019 | A1 |
| 20190038343 | Sutton et al. | Feb 2019 | A1 |
| 20190038344 | Pellegrino | Feb 2019 | A1 |
| 20190038345 | Pellegrino | Feb 2019 | A1 |
| 20190090933 | Pellegrino et al. | Mar 2019 | A1 |
| 20190110833 | Pellegrino et al. | Apr 2019 | A1 |
| 20190118003 | Diederich et al. | Apr 2019 | A1 |
| 20190118004 | Diederich et al. | Apr 2019 | A1 |
| 20190118005 | Diederich et al. | Apr 2019 | A1 |
| 20190175252 | Heggeness | Jun 2019 | A1 |
| 20190282268 | Pellegrino et al. | Sep 2019 | A1 |
| 20190290296 | Patel et al. | Sep 2019 | A1 |
| 20190298392 | Capote et al. | Oct 2019 | A1 |
| 20190365416 | Brockman et al. | Dec 2019 | A1 |
| 20200000480 | Alambeigi et al. | Jan 2020 | A1 |
| 20200022709 | Burger et al. | Jan 2020 | A1 |
| 20200030601 | Molnar et al. | Jan 2020 | A1 |
| 20200060695 | Purdy et al. | Feb 2020 | A1 |
| 20200060747 | Edidin | Feb 2020 | A1 |
| 20200069920 | Goshayeshgar | Mar 2020 | A1 |
| 20200078083 | Sprinkle et al. | Mar 2020 | A1 |
| 20200138454 | Patel et al. | May 2020 | A1 |
| 20200146743 | Defosset et al. | May 2020 | A1 |
| 20200146744 | Defosset et al. | May 2020 | A1 |
| 20200214762 | Pellegrino et al. | Jul 2020 | A1 |
| 20200281646 | Pellegrino et al. | Sep 2020 | A1 |
| 20210113238 | Donovan et al. | Apr 2021 | A1 |
| 20210177502 | Wright et al. | Jun 2021 | A1 |
| Number | Date | Country |
|---|---|---|
| 0040658 | Dec 1981 | EP |
| 0584959 | Mar 1994 | EP |
| 0597463 | May 1994 | EP |
| 0880938 | Dec 1998 | EP |
| 1013228 | Jun 2000 | EP |
| 1059067 | Dec 2000 | EP |
| 1059087 | Dec 2000 | EP |
| 1294323 | Apr 2007 | EP |
| 1938765 | Jul 2008 | EP |
| 1471836 | Apr 2010 | EP |
| 1471836 | Apr 2010 | EP |
| 2785260 | Aug 2015 | EP |
| 2965782 | Jan 2016 | EP |
| 2508225 | Sep 2016 | EP |
| 3078395 | Oct 2016 | EP |
| 2205313 | Nov 2016 | EP |
| 3097946 | Nov 2016 | EP |
| 2913081 | Jan 2017 | EP |
| 53-139791 | Nov 1978 | JP |
| 6-47058 | Feb 1994 | JP |
| 10-290806 | Nov 1998 | JP |
| 2001-037760 | Feb 2001 | JP |
| 2005-169012 | Jun 2005 | JP |
| WO9636289 | Nov 1996 | WO |
| WO9827876 | Jul 1998 | WO |
| WO9834550 | Aug 1998 | WO |
| WO9919025 | Apr 1999 | WO |
| WO9944519 | Sep 1999 | WO |
| WO9948621 | Sep 1999 | WO |
| WO0021448 | Apr 2000 | WO |
| WO0033909 | Jun 2000 | WO |
| WO0049978 | Aug 2000 | WO |
| WO0056237 | Sep 2000 | WO |
| WO0067648 | Nov 2000 | WO |
| WO0067656 | Nov 2000 | WO |
| WO0101877 | Jan 2001 | WO |
| WO0145579 | Jun 2001 | WO |
| WO0157655 | Aug 2001 | WO |
| WO0205699 | Jan 2002 | WO |
| WO0205897 | Jan 2002 | WO |
| WO0228302 | Apr 2002 | WO |
| WO2002026319 | Apr 2002 | WO |
| WO02054941 | Jul 2002 | WO |
| WO02067797 | Sep 2002 | WO |
| WO02096304 | Dec 2002 | WO |
| WO 2006044794 | Apr 2006 | WO |
| WO 2007001981 | Jan 2007 | WO |
| WO 2007008954 | Jan 2007 | WO |
| WO07031264 | Mar 2007 | WO |
| WO08001385 | Jan 2008 | WO |
| WO08008522 | Jan 2008 | WO |
| WO 2008076330 | Jun 2008 | WO |
| WO 2008076357 | Jun 2008 | WO |
| WO08121259 | Oct 2008 | WO |
| WO 2008121259 | Oct 2008 | WO |
| WO2008140519 | Nov 2008 | WO |
| WO 2008141104 | Nov 2008 | WO |
| WO 2008144709 | Nov 2008 | WO |
| WO 2009042172 | Apr 2009 | WO |
| WO 2009076461 | Jun 2009 | WO |
| WO 2009124192 | Oct 2009 | WO |
| WO 2009155319 | Dec 2009 | WO |
| WO 2010111246 | Sep 2010 | WO |
| WO 2010135606 | Nov 2010 | WO |
| WO 2011041038 | Apr 2011 | WO |
| WO 2012024162 | Feb 2012 | WO |
| WO 2012065753 | Mar 2012 | WO |
| WO 2012074932 | Jun 2012 | WO |
| WO 2013009516 | Jan 2013 | WO |
| WO 2013134452 | Sep 2013 | WO |
| WO 2013168006 | Nov 2013 | WO |
| WO 2013180947 | Dec 2013 | WO |
| WO 2014004051 | Jan 2014 | WO |
| WO 2014130231 | Aug 2014 | WO |
| WO 2014141207 | Sep 2014 | WO |
| WO 2014165194 | Oct 2014 | WO |
| WO 2014176141 | Oct 2014 | WO |
| WO 2015038317 | Mar 2015 | WO |
| WO 2015047817 | Apr 2015 | WO |
| WO 2015066295 | May 2015 | WO |
| WO 2015066303 | May 2015 | WO |
| WO 2015079319 | Jun 2015 | WO |
| WO 2015148105 | Oct 2015 | WO |
| WO 2014145222 | Jan 2016 | WO |
| WO 2014145659 | Jan 2016 | WO |
| WO 2014146029 | Jan 2016 | WO |
| WO 2016033380 | Mar 2016 | WO |
| WO 2016048965 | Mar 2016 | WO |
| WO 2014197596 | Apr 2016 | WO |
| WO 2014210373 | May 2016 | WO |
| WO 2016069157 | May 2016 | WO |
| WO 2016075544 | May 2016 | WO |
| WO 2015024013 | Jun 2016 | WO |
| WO 2016090420 | Jun 2016 | WO |
| WO 2016105448 | Jun 2016 | WO |
| WO 2016105449 | Jun 2016 | WO |
| WO 2015044945 | Aug 2016 | WO |
| WO 2015057696 | Aug 2016 | WO |
| WO 2015060927 | Aug 2016 | WO |
| WO 2016127130 | Aug 2016 | WO |
| WO 2016130686 | Aug 2016 | WO |
| WO 2016134273 | Aug 2016 | WO |
| WO 2011157714 | Sep 2016 | WO |
| WO 2016148954 | Sep 2016 | WO |
| WO 2016154091 | Sep 2016 | WO |
| WO 2016168381 | Oct 2016 | WO |
| WO 2016209632 | Dec 2016 | WO |
| WO 2017009472 | Jan 2017 | WO |
| WO 2017010930 | Jan 2017 | WO |
| WO 2017019363 | Feb 2017 | WO |
| WO 2017027703 | Feb 2017 | WO |
| WO 2017027809 | Feb 2017 | WO |
| WO 2018116273 | Jun 2018 | WO |
| WO 2020198150 | Oct 2020 | WO |
| Entry |
|---|
| A Novel Approach for Treating Chronic Lower Back Pain Abstract for Presentation at North American Spine Society 26th Annual Meeting in Chicago IL on Nov. 4, 2011. |
| Antonacci M. Darryl et al.; Innervation of the Human Vertebral Body: A Histologic Study; Journal of Spinal Disorder vol. 11 No. 6 pp. 526-531 1998 Lippincott Wiliams & Wilkins Philadelphia. |
| Arnoldi Carl C.; Intraosseous Hypertension—A Possible Cause of Low Back Pain?; Clinical Orthopedics and Related Research No. 115 Mar.-Apr. 1976. |
| Bailey, Jeannie F., “Innervation Patterns of PGP 9.5—Positive Nerve Fibers within the Human Lumbar Vertebra,” Journal of Anatomy, (2011) 218, pp. 263-270, San Francisco, California. |
| Becker, Stephan, et al., “Ablation of the basivertebral nerve tor treatment of back pain: a clinical study,” The Spine Journal, vol. 17, pp. 218-223 (Feb. 2017). |
| Bergeron et al. “Fluoroscopic-guided radiofrequency ablation of the basivertebral nerve: application and analysis with multiple imaging modalities in an ovine model” Thermal Treatment of Tissue: Energy Delivery and Assessment III edited by Thomas P. Ryan Proceedings of SPIE vol. 5698 (SPIE Bellingham WA 2005) pp. 156-167. |
| Bogduk N. The anatomy of the lumbar intervertebral disc syndrome Med J. Aust. 1976 vol. 1 No. 23 pp. 878-881. |
| Bogduk Nikolai et al.; Technical Limitations to the efficacy of Radiofrequency Neurotomy for Spinal Pain; Neurosurgery vol. 20 No. 4 1987. |
| Caragee, EG et al.; “Discographic, MRI and psychosocial determinants of low back pain disability and remission: A prospective study in subjects with benign persistent back pain”, The Spine Journal: The Official Journal of the North American Spine Society, vol. 5(1), pp. 24-35 (2005). |
| Choy Daniel SS.J. et al.; Percutaneous Laser Disc Decompression A New Therapeutic Modality; Spine vol. 17 No. 8 1992. |
| Cosman E.R. et al. Theoretical Aspects of Radiofrequency Lesions in the Dorsal Root Entry Zone. Neurosurgery vol. 1 No. 6 1984 pp. 945-950. |
| Deardorff Dana L. et al.; Ultrasound applicators with internal cooling for interstitial thermal therapy; SPIE vol. 3594 1999. |
| Deramond H. et al. Temperature Elevation Caused by Bone Cement Polymerization During Vertebroplasty Bone Aug. 1999 pp. 17S-21S vol. 25 No. 2 Supplement. |
| Diederich C. J. et al. “IDTT Therapy in Cadaveric Lumbar Spine: Temperature and thermal dose distributions Thermal Treatment of Tissue: Energy Delivery and Assessment” Thomas P. Ryan Editor Proceedings of SPIE vol. 4247:104-108 (2001). |
| Diederich Chris J. et al.; Ultrasound Catheters for Circumferential Cardiac Ablation; SPIE vol. 3594 (1999). |
| Dupuy D.E. et al. Radiofrequency ablation of spinal tumors: Temperature distribution in the spinal canal AJR vol. 175 pp. 1263-1266 Nov. 2000. |
| Dupuy Damian E.; Radiofrequency Ablation: An Outpatient Percutaneous Treatment; Medicine and Health/Rhode Island vol. 82 No. 6 Jun. 1999. |
| Esses Stephen I. et al.; Intraosseous Vertebral Body Pressures; Spine vol. 17 No. 6 Supplement 1992. |
| FDA Response to 510(k) Submission by Relievant Medsystems Inc. submitted on Sep. 27, 2007 (date stamped on Oct. 5, 2007) and associated documents. |
| Fras M.D. Christian et al. “Substance P-containing Nerves within the Human Vertebral Body: An Immunohistochemical Study of the Basivertebral Nerve” The Spine Journal 3 2003 pp. 63-67RE. |
| Fields, AJ et al; “Innervation of pathologies in the lumbar vertebral endplate and intervertebral disc”, The Spine Journal: Official Journal of the North American Spine Society, vol. 14(3), pp. 513-521 (2014). |
| Fields, Aaron J. et al.; “Cartilage endplate damage strongly associates with chronic low back pain, independent of modic changes”, Abstract form Oral Presentation at the ISSLS Annual Meeting in Banff, Canada (May 14-18, 2018). |
| Fischgrund JS, et al.; “Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain: 2-Year Results from a Prospective Randomized Double-Blind Sham-Controlled Multicenter Study”, International Journal of Spine Surgery, vol. 13 (2), pp. 110-119 (2019). |
| Fras M.D., Christian et al., “Substance P-containing Nerves within the Human Vertebral Body: An Immunohistochemical Study of the Basivertebral Nerve”, The Spine Journal 3, 2003, pp. 63-67. |
| Gehl J. “Electroporation: theory and methods perspectives for drug delivery gene therapy and research” Acta Physiol. Scand. vol. 177 pp. 437-447 (2003). |
| Goldberg S.N. et al. Tissue ablation with radiofrequency: Effect of probe size gauge duration and temperature on lesion volume Acad. Radiol. vol. 2 pp. 399-404 (1995). |
| Gornet, Matthew G et al.; “Magnetic resonance spectroscopy (MRS) can identify painful lumbar discs and may facilitate improved clinical outcomes of lumbar surgeries for discogenic pain”, European Spine Journal, vol. 28, pp. 674-687 (2019). |
| Hanai Kenji et al.; Simultaneous Measurement of Intraosseous and Cerebrospinal Fluid Pressures in the Lumbar Region; Spine vol. 10 No. 1 1985. |
| Heggeness Michael H. et al. The Trabecular Anatomy of Thoracolumbar Vertebrae: Implications for Burst Fractures Journal of Anatomy 1997 pp. 309-312 vol. 191 Great Britain. |
| Heggeness Michael H. et al. Discography Causes End Plate Deflection; Spine vol. 18 No. 8 pp. 1050-1053 1993 J.B. Lippincott Company. |
| Heggeness, M. et al Ablation of the Basivertebral Nerve for the Treatment of Back Pain: A Pilot Clinical Study; The Spine Journal, 2011, vol. 11, Issue 10, Supplement, pp. S65-S66, ISSN 1529-9430. |
| Hoopes et al. “Radiofrequency Ablation of the Basivertebral Nerve as a Potential Treatment of Back Pain: Pathologic Assessment in an Ovine Model” Thermal Treatment of Tissue: Energy Delivery and Assessment III edited by Thomas P. Ryan Proceedings of SPIE vol. 5698 (SPIE Bellingham WA 2005) pp. 168-180. |
| Houpt Jonathan C. et al.; Experimental Study of Temperature Distributions and Thermal Transport During Radiofrequency Current Therapy of the Intervertebral Disc; Spine vol. 21 No. 15 pp. 1808-1813 1996 Lippincott-Raven Publishers. |
| Jourabchi, Natanel et al.; “Irreversible electroporation (NanoKnife) in cancer treatment,” Gastrointestinal Intervention, vol. 3, pp. 8-18 (2014). |
| Khalil, J et al.; “A Prospective, Randomized, Multi-Center Study of Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain”, The Spine Journal (2019), available at https://doi.org/10.1016/jspinee.2019.05.598. |
| Kleinstueck Frank S. et al.; Acute Biomechanical and Histological Effects of Intradiscal Electrothermal Therapy on Human Lumbar Discs; Spine vol. 26 No. 20 pp. 2198-2207; 2001 Lippincott Williams & Wilkins Inc. |
| Kopecky Kenyon K. et al. “Side-Exiting Coaxial Needle for Aspiration Biopsy”—AJR—1996; 167 pp. 661-662. |
| Kuisma M et al.; “Modic changes in endplates of lumbar vertebral bodies: Prevalence and association with low back and sciatic pain among middle-aged male workers”, Spine, vol. 32(10), pp. 1116-1122 (2007). |
| Lehmann Justus F. et al.; Selective Heating Effects of Ultrasound in Human Beings; Archives of Physical Medicine & Rehabilitation Jun. 1966. |
| Letcher Frank S. et al.; The Effect of Radiofrequency Current and Heat on Peripheral Nerve Action Potential in the Cat; U.S. Naval Hospital Philadelphia PA. (1968). |
| Lotz JC, et al.; “The Role of the Vertebral End Plate in Low Back Pain”, Global Spine Journal, vol. 3, pp. 153-164 (2013). |
| Lundskog Jan; Heat and Bone Tissue-/an experimental investigation of the thermal properties of bone tissue and threshold levels for thermal injury; Scandinavian Journal of Plastic and Reconstructive Surgery Supplemental 9 From the Laboratory of Experimental Biology Department of anatomy University of Gothenburg Gothenburg Sweden Goteborg 1972. |
| Martin J.B. et al. Vertebroplasty: Clinical Experience and Follow-up Results Bone Aug. 1999 pp. 11S-15S vol. 25 No. 2 Supplement. |
| Massad Malek M.D. et al.; Endoscopic Thoracic Sympathectomy: Evaluation of Pulsatile Laser Non-Pulsatile Laser and Radiofrequency-Generated Thermocoagulation; Lasers in Surgery and Medicine; 1991; pp. 18-25. |
| Mehta Mark et al.; The treatment of chronic back pain; Anaesthesia 1979 vol. 34 pp. 768-775. |
| Modic MT et al.; “Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging” Radiology vol. 166 pp. 193-199 (1988). |
| Mok, Florence et al.; “Modic changes of the lumbar spine: Prevalence, risk factors, and association with disc degeneration and low back pain in a large-scale population-based cohort”, The Spine Journal: Official Journal of the North American Spine Society, vol. 16(1), pp. 32-41 (2016). |
| Nau William H. Ultrasound interstitial thermal therapy (USITT) in the prostate; SPIE vol. 3594 Jan. 1999. |
| Osteocool Pain Management Brochure, Baylis Medical, copyright 2011. |
| Pang, Henry et al,; The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability, Spine, vol. 42 (Aug. 2017). |
| Radiological Society of North America. “Pulsed radiofrequency relieves acute back pain and sciatica.” ScienceDaily. ScienceDaily, Nov. 27, 2018. <www.sciencedaily.com/releases/2018/11/181127092604.htm>. |
| Rashbaum Ralph F.; Radiofrequency Facet Denervation A Treatment alternative in Refractory Low Back Pain with or without Leg Pain; Orthopedic Clinics of North America—vol. 14 No. 3 Jul. 1983. |
| Rosenthal D.I. Seminars in Musculoskeletal Radiology vol. 1 No. 2. pp. 265-272 (1997). |
| Ryan et al. “Three-Dimensional Finite Element Simulations of Vertebral Body Thermal Treatment” Thermal Treatment of Tissue: Energy Delivery and Assessment III edited by Thomas P. Ryan Proceedings of SPIE vol. 5698 (SPIE Bellingham WA 2005) pp. 137-155. |
| Shealy C. Norman; Percutaneous radiofrequency denervation of spinal facets Treatment for chronic back pain and sciatica; Journal of Neurosurgery/vol. 43/Oct. 1975. |
| Sherman Mary S.; The Nerves of Bone The Journal of Bone and Joint Surgery Apr. 1963 pp. 522-528 vol. 45-A No. 3. |
| Solbiati L. et al. Hepatic metastases: Percutaneous radio-frequency ablation with cooled-tip electrodes. Interventional Radiology vol. 205 No. 2 pp. 367-373 (1997). |
| Stanton Terry “Can Nerve Ablation Reduce Chronic Back Pain ?” AAOS Now Jan. 2012. |
| The AVAmax System—Cardinal Health Special Procedures Lit. No. 25P0459-01—www.cardinal.com (copyright 2007). |
| Tillotson L. et al. Controlled thermal injury of bone: Report of a percutaneous technique using radiofrequency electrode and generator. Investigative Radiology Nov. 1989 pp. 888-892. |
| Troussier B. et al.; Percutaneous Intradiscal Radio-Frequency Thermocoagulation A Cadaveric Study; Spine vol. 20 No. 15 pp. 1713-1718 1995 Lippincott-Raven Publishers. |
| Ullrich Jr. Peter F. “Lumbar Spinal Fusion Surgery” Jan. 9, 2013 Spine-Health (available via wayback machine Internet archive at http://web.archive.org/web/20130109095419/http://www/spine-health.com/treatment/spinal-fusion/lumbar-spinal-fusion-surgery). |
| Weishaupt, D et al.; “Painful Lumbar Disk Derangement: Relevance of Endplate Abnormalities at MR Imaging”, Radiology, vol. 218(2), pp. 420-427 (2001). |
| YouTube Video, “DFINE-STAR Procedure Animation,” dated Sep. 30, 2013, can be viewed at https://www.youtube.com/watch?v=YxtKNyc2e-0. |
| Kim et al., Transforaminal epiduroscopic basivertebral nerve laser ablation for chronic low back pain associated with modic changes: A preliminary open-label study. Pain Research and Management 2018; https://pubmed.ncbi.nlm.nih.gov/30186540. |
| Rahme et al., The modic vertebral endplate and marrow changes: pathologic significance and relation to low back pain and segmental instability of the lumbar spine. American Journal of Neuroradiology 29.5 (2008): 838-842; http://www.ajnr.org/content/29/5/838. |
| Number | Date | Country | |
|---|---|---|---|
| 20220015775 A1 | Jan 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61722750 | Nov 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16717985 | Dec 2019 | US |
| Child | 17488111 | US | |
| Parent | 16370264 | Mar 2019 | US |
| Child | 16717985 | US | |
| Parent | 15722392 | Oct 2017 | US |
| Child | 16370264 | US | |
| Parent | 14440050 | US | |
| Child | 15722392 | US |
