Patent Grant
9931162
Technical Field
The present invention generally relates to systems, apparatuses, and methods for treating tissue, and more particularly, the invention relates to systems or treatment systems with delivery devices having coolable energy emitting assemblies for eliciting a desired response.
Description of the Related Art
Pulmonary diseases may cause a wide range of problems that adversely affect performance of the lungs. Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (“COPD”), may lead to increased airflow resistance in the lungs. Mortality, health-related costs, and the size of the population having adverse effects due to pulmonary diseases are all substantial. These diseases often adversely affect quality of life. Symptoms are varied but often include cough; breathlessness; and wheeze. In COPD, for example, breathlessness may be noticed when performing somewhat strenuous activities, such as running, jogging, brisk walking, etc. As the disease progresses, breathlessness may be noticed when performing non-strenuous activities, such as walking Over time, symptoms of COPD may occur with less and less effort until they are present all of the time, thereby severely limiting a person's ability to accomplish normal tasks.
Pulmonary diseases are often characterized by airway obstruction associated with blockage of an airway lumen, thickening of an airway wall, alteration of structures within or around the airway wall, or combinations thereof. Airway obstruction can significantly decrease the amount of gas exchanged in the lungs resulting in breathlessness. Blockage of an airway lumen can be caused by excessive intraluminal mucus or edema fluid, or both. Thickening of the airway wall may be attributable to excessive contraction of the airway smooth muscle, airway smooth muscle hypertrophy, mucous glands hypertrophy, inflammation, edema, or combinations thereof. Alteration of structures around the airway, such as destruction of the lung tissue itself, can lead to a loss of radial traction on the airway wall and subsequent narrowing of the airway.
Asthma can be characterized by contraction of airway smooth muscle, smooth muscle hypertrophy, excessive mucus production, mucous gland hypertrophy, and/or inflammation and swelling of airways. These abnormalities are the result of a complex interplay of local inflammatory cytokines (chemicals released locally by immune cells located in or near the airway wall), inhaled irritants (e.g., cold air, smoke, allergens, or other chemicals), systemic hormones (chemicals in the blood such as the anti-inflammatory cortisol and the stimulant epinephrine), local nervous system input (nerve cells contained completely within the airway wall that can produce local reflex stimulation of smooth muscle cells and mucous glands), and the central nervous system input (nervous system signals from the brain to smooth muscle cells and mucous glands carried through the vagus nerve). These conditions often cause widespread temporary tissue alterations and initially reversible airflow obstruction that may ultimately lead to permanent tissue alteration and permanent airflow obstruction that make it difficult for the asthma sufferer to breathe. Asthma can further include acute episodes or attacks of additional airway narrowing via contraction of hyper-responsive airway smooth muscle that significantly increases airflow resistance. Asthma symptoms include recurrent episodes of breathlessness (e.g., shortness of breath or dyspnea), wheezing, chest tightness, and cough.
Emphysema is a type of COPD often characterized by the alteration of lung tissue surrounding or adjacent to the airways in the lungs. Emphysema can involve destruction of lung tissue (e.g., alveoli tissue such as the alveolar sacs) that leads to reduced gas exchange and reduced radial traction applied to the airway wall by the surrounding lung tissue. The destruction of alveoli tissue leaves areas of emphysematous lung with overly large airspaces that are devoid of alveolar walls and alveolar capillaries and are thereby ineffective at gas exchange. Air becomes “trapped” in these larger airspaces. This “trapped” air may cause over-inflation of the lung, and in the confines of the chest restricts the in-flow of oxygen rich air and the proper function of healthier tissue. This results in significant breathlessness and may lead to low oxygen levels and high carbon dioxide levels in the blood. This type of lung tissue destruction occurs as part of the normal aging process, even in healthy individuals. Unfortunately, exposure to chemicals or other substances (e.g., tobacco smoke) may significantly accelerate the rate of tissue damage or destruction. Breathlessness may be further increased by airway obstruction. The reduction of radial traction may cause the airway walls to become “floppy” such that the airway walls partially or fully collapse during exhalation. An individual with emphysema may be unable to deliver air out of their lungs due to this airway collapse and airway obstructions during exhalation.
Chronic bronchitis is a type of COPD that can be characterized by contraction of the airway smooth muscle, smooth muscle hypertrophy, excessive mucus production, mucous gland hypertrophy, and inflammation of airway walls. Like asthma, these abnormalities are the result of a complex interplay of local inflammatory cytokines, inhaled irritants, systemic hormones, local nervous system, and the central nervous system. Unlike asthma where respiratory obstruction may be largely reversible, the airway obstruction in chronic bronchitis is primarily chronic and permanent. It is often difficult for a chronic bronchitis sufferer to breathe because of chronic symptoms of shortness of breath, wheezing, and chest tightness, as well as a mucus producing cough.
Different techniques can be used to assess the severity and progression of pulmonary diseases. For example, pulmonary function tests, exercise capacity, and quality of life questionnaires are often used to evaluate subjects. Pulmonary function tests involve objective and reproducible measures of basic physiologic lung parameters, such as total airflow, lung volume, and gas exchange. Indices of pulmonary function tests used for the assessment of obstructive pulmonary diseases include the forced expiratory volume in 1 second (FEV1), the forced vital capacity (FVC), the ratio of the FEV1 to FVC, the total lung capacity (TLC), airway resistance and the testing of arterial blood gases. The FEV1 is the volume of air a patient can exhale during the first second of a forceful exhalation which starts with the lungs completely filled with air. The FEV1 is also the average flow that occurs during the first second of a forceful exhalation. This parameter may be used to evaluate and determine the presence and impact of any airway obstruction. The FVC is the total volume of air a patient can exhale during a forceful exhalation that starts with the lungs completely filled with air. The FEV1/FVC is the fraction of all the air that can be exhaled during a forceful exhalation during the first second. A FEV1/FVC ratio less than 0.7 after the administration of at least one bronchodilator defines the presence of COPD. The TLC is the total amount of air within the lungs when the lungs are completely filled and may increase when air becomes trapped within the lungs of patients with obstructive lung disease. Airway resistance is defined as the pressure gradient between the alveoli and the mouth to the rate of air flow between the alveoli and the mouth. Similarly, resistance of a given airway would be defined as the ratio of the pressure gradient across the given airway to the flow through the airway. Arterial blood gases tests measure the amount of oxygen and the amount of carbon dioxide in the blood and are the most direct method for assessing the ability of the lungs and respiratory system to bring oxygen from the air into the blood and to get carbon dioxide from the blood out of the body.
Exercise capacity tests are objective and reproducible measures of a patient's ability to perform activities. A six minute walk test (6 MWT) is an exercise capacity test in which a patient walks as far as possible over a flat surface in 6 minutes. Another exercise capacity test involves measuring the maximum exercise capacity of a patient. For example, a physician can measure the amount of power the patient can produce while on a cycle ergometer. The patient can breathe 30 percent oxygen and the work load can increase by 5-10 watts every 3 minutes.
Quality of life questionnaires assess a patient's overall health and well being. The St. George's Respiratory Questionnaire is a quality of life questionnaire that includes 75 questions designed to measure the impact of obstructive lung disease on overall health, daily life, and perceived well-being. The efficacy of a treatment for pulmonary diseases can be evaluated using pulmonary function tests, exercise capacity tests, and/or questionnaires. A treatment program can be modified based on the results from these tests and/or questionnaires.
Treatments, such as bronchial thermoplasty, involve destroying smooth muscle tone by ablating the airway wall in a multitude of bronchial branches within the lung thereby eliminating both smooth muscles and nerves in the airway walls of the lung. The treated airways are unable to respond favorably to inhaled irritants, systemic hormones, and both local and central nervous system input. Unfortunately, this destruction of smooth muscle tone and nerves in the airway wall may therefore adversely affect lung performance. For example, inhaled irritants, such as smoke or other noxious substances, normally stimulate lung irritant receptors to produce coughing and contracting of airway smooth muscle. Elimination of nerves in the airway walls removes both local nerve function and central nervous input, thereby eliminating the lung's ability to expel noxious substances with a forceful cough. Elimination of airway smooth muscle tone may eliminate the airways' ability to constrict, thereby allowing deeper penetration of unwanted substances, such as noxious substances, into the lung.
Both asthma and COPD are serious diseases with growing numbers of sufferers. Current management techniques, which include prescription drugs, are neither completely successful nor free from side effects. Additionally, many patients do not comply with their drug prescription dosage regiment. Accordingly, it would be desirable to provide a treatment which improves resistance to airflow without the need for patient compliance.
In some embodiments, a treatment system can be navigated through airways, such as the right and left main bronchi of the lung root, as well as more distal airways within the lungs, to treat a wide range of pulmonary symptoms, conditions, and/or diseases, including, without limitation, asthma, COPD, obstructive lung diseases, or other diseases that lead to an increased resistance to airflow in the lungs. A collapsible ablation assembly can be conveniently passed through airways. An energy emitter assembly of the ablation assembly can treat one or more target sites without treating non-targeted sites. Even if targeted anatomical features (e.g., nerves, glands, membranes, and the like) of main bronchi, lobar bronchi, segmental bronchi or subsegmental bronchi are treated, non-targeted anatomical features can be substantially unaltered. For example, the treatment system can destroy nerve tissue at target sites without destroying to any significant extent non-targeted tissue that can remain functional after performing treatment. The energy emitter assembly is coolable to avoid or limit destruction of non-targeted tissue.
In some embodiments, a system for treating a subject includes a delivery device configured to move along a lumen of an airway of a bronchial tree. The delivery device can form lesions to attenuate signals transmitted by nerve tissue, such as nerve tissue of nerve trunks, while not irreversibly damaging to any significant extent non-targeted features, such as an inner surface or smooth muscle of the airway. The delivery device can include a distal tip with at least one ablation assembly.
The ablation assembly, in some embodiments, can be moved from a low-profile configuration for delivery to a deployed configuration for treating tissue at a target region. Ablation elements can be activated to ablate tissue. Each ablation element can include one or more electrodes operable to output ultrasound, electrical energy, and/or radiofrequency (RF) energy. In certain embodiments, each electrode is a fluid coolable electrode.
In other embodiments, a delivery device is a catheter with a collapsible energy emitter assembly. An expandable element, or other biasing feature, presses the energy emitter assembly against an airway wall. The energy emitter assembly delivers energy to targeted tissue. In certain embodiments, the energy emitter assembly and the expandable element are expanded simultaneously. In other embodiments, the expandable element is expanded before or after the energy emitter assembly is deployed.
In some embodiments, a method comprises damaging nerve tissue of a first main bronchus to substantially prevent nervous system signals from traveling to substantially all distal bronchial branches connected to the first main bronchus. In some embodiments, most or all of the bronchial branches distal to the first main bronchus are treated. The damaged nerve tissue, in certain embodiments, is positioned between a trachea and the lung through which the bronchial branches extend. The method can further include damaging nerve tissue of a second main bronchus to substantially prevent nervous system signals from traveling to substantially all distal bronchial branches connected to the second main bronchus.
At least some embodiments can denervate the lung bronchus by creating lesions using radiofrequency ablation. Ablating nerve trunks which traverse along the outside of both the right and left main bronchi effectively disconnects airway smooth muscle which lines the inside of the lung airways and mucus producing glands located with the airways from the vagus nerve and central nervous system. When this occurs, airway smooth muscle relaxes and mucus production is decreased. These changes reduce airway obstruction under states of disease, such as COPD and asthma. Reduced airway obstruction makes breathing easier which can improve patient quality of life and health status.
The lesions can be shaped or modified using differential temperature control. Differential temperature control can involve independent cooling of different features of a delivery device, such as an ablation assembly, an expandable element, or an energy emitter assembly. Differential cooling is used to increase or maximize lesion depth. In some procedures, nerve tissue and other structures (e.g., adjacent tissue structures, organs or diseased tissue such as cancerous or non-cancerous tumors, etc.) are part of the target region. Additionally or alternatively, differential cooling can be used to control (e.g., limit or minimize) or eliminate shallow or surface tissue damage.
Lesions can be formed at target regions. Target regions can include, without limitation, nerve tissue (e.g., tissue of the vagus nerves, nerve trunks, etc.), fibrous tissue, diseased or abnormal tissues (e.g., cancerous tissue, inflamed tissue, and the like), cardiac tissue, muscle tissue, blood, blood vessels, anatomical features (e.g., membranes, glands, cilia, and the like), or other sites of interest. In RF ablation, heat is generated due to the tissue resistance as RF electrical current travels through the tissue. The tissue resistance results in power dissipation that is equal to the current flow squared times the tissue resistance. To ablate deep tissues, tissue between an RF electrode and the deep tissue can become heated if active cooling is not employed. Electrode cooling can be used to keep tissue near the electrode below a temperature that results in cell death or damage, thereby protecting tissue. For example, cooling can prevent or limit overheating at the electrode-tissue interface. Overheating (e.g., tissue at temperatures above 95° C. to about 110° C.) can lead to the formation of coagulum, tissue desiccation, tissue charring, and explosive outgassing of steam. These effects can result in increased tissue resistance and reduced RF energy transfer into the tissue, thereby limiting the effective RF ablation lesion depth. Active cooling can be used to produce significantly deeper tissue lesions. The temperature of coolant for active cooling can be about 0° C. to about 24° C. In some embodiments, the coolant and electrode produce a lesion at a therapeutic depth of at least about 3 mm. In some embodiments, the lesions can be formed at a depth of about 3 mm to about 5 mm to damage nerve tissue.
Sensors, in some embodiments, are used to monitor temperatures, inflation pressures, coolant flow rates, tissue impedance, or other parameters of interest. Feedback from the sensors can be used to modulate the power delivered to electrode(s). Outputted energy can be adjusted to account for local variations in tissue that alters the local impedance, thus avoiding excess heating which can lead to unwanted hot spots. Lesions can also be formed independent of regional tissue characteristics.
In some embodiments, a delivery device comprises an ablation assembly and a deployable element including a deployable element movable from a collapsed state to an expanded state to bring the tissue-contacting portion of the energy emitter assembly ablation assembly into contact with tissue, such as an airway wall, cardiac tissue or the like.
The energy emitter assembly, in some embodiments, is configured to output energy to ablate targeted tissue of a bronchial tree and through which a coolant is capable of flowing so as to cool a tissue-contacting portion of the energy emitter assembly. A cooling section is configured to contain the coolant and is movable into contact with the airway wall so as to cool tissue adjacent to the tissue-contacting portion of the energy emitter assembly when energy is being outputted therefrom. The deployable element is configured to contain the coolant such that the coolant cools the energy emitter assembly and the deployable element when the deployable element is in the expanded state and the ablation assembly is in contact with the airway wall to limit or prevent damage to tissue between the ablation assembly and the targeted tissue. An elongate shaft is coupled to the ablation assembly and provides coolant flow to the ablation assembly and receives coolant from the ablation assembly.
A controller can be communicatively coupled to a fluid delivery system and communicatively coupled to a sensor of the ablation assembly. The controller is configured to command the fluid delivery system based on at least one signal from the sensor. The controller is configured to execute at least one differential cooling program to deliver the first fluid at a significantly different temperature from the temperature of the second fluid. The temperature difference can be at least about 5, 10, 20, or 30 degrees C.
In certain embodiments, a delivery device includes an ablation assembly including an energy emitter assembly configured to output energy to ablate targeted tissue of a bronchial tree and through which a coolant is capable of flowing so as to cool a tissue-contacting portion of the energy emitter assembly and a deployable element movable from a collapsed state to an expanded state to bring the tissue-contacting portion of the energy emitter assembly into contact with an airway wall of the bronchial tree. A cooling section is configured to contain the coolant and movable into contact with the airway wall so as to cool tissue adjacent to the tissue-contacting portion of the energy emitter assembly when energy is being outputted therefrom. An elongate shaft is coupled to the ablation assembly. Coolant can flow through the shaft to the ablation assembly.
In some embodiments, a delivery device includes an ablation assembly including an electrode configured to output energy to ablate targeted tissue of an airway. The electrode is movable between a first orientation in which the electrode extends axially along the airway and a second orientation in which the entire electrode is disposed in a space between adjacent cartilage rings of the airway.
A delivery device, in some embodiments, includes a deployable element movable between a collapsed state and an expanded state. An intercartilaginous energy emitter assembly surrounds at least a portion of the deployable element. At least a portion of the energy emitter assembly is moveable with respect to the deployable element in the expanded state to urge an electrode of the energy emitter assembly between adjacent cartilage rings of an airway wall of a bronchial tree.
In yet other embodiments, a delivery device includes an ablation assembly including an energy emitter assembly and an inflatable cooling balloon. The energy emitter assembly includes a cooling channel. The inflatable cooling balloon includes a cooling chamber. An elongate shaft is configured to independently deliver a first fluid to the cooling channel and a second fluid to the cooling chamber.
A delivery device includes an elongate shaft and ablation assembly coupled to the elongate shaft. The ablation assembly, in some embodiments, includes an electrode capable of emitting ablation energy and having a first end, a second end, and a main body between the first end and the second end. At least one of the first end and the second end is covered by an ablation energy insulator, which can be a shield.
A treatment system includes a delivery device configured to deliver energy to a first tissue surface proximate the delivery device to damage a target region of tissue such that a portion of the target region defining a maximum cross-sectional width of the target region is separated from the first tissue surface.
A method of treating a subject including moves a cooling element of a delivery device through a receiving-opening of an energy emitter assembly located in an airway of the subject. The cooling element is expanded to position at least a portion of the energy emitter assembly between the cooling element and a wall of the airway. Energy is delivered from the energy emitter assembly to ablate tissue in the wall of the airway while coolant flows through the expanded cooling element and the energy emitter assembly.
A method of treating a subject includes moving an ablation assembly into an airway of a bronchial tree. The ablation assembly includes a cooling element and an energy emitter assembly. The cooling element is expanded to contact a wall of the airway with the cooling element. Energy is delivered from the energy emitter assembly to damage nerve tissue of a nerve trunk extending along the airway. Coolant flows into contact with at least a portion of the energy emitter assembly while delivering the energy to cool a wall of the airway to limit or prevent cell death in tissue located between the damaged nerve tissue and the ablation assembly.
A method of treating a subject includes positioning an ablation assembly of a delivery device within an airway. Energy is from an electrode of the ablation assembly to damage nerve tissue of a nerve trunk such that nervous system signals transmitted to a portion of the bronchial tree are attenuated. Coolant is delivered through a channel of the electrode of the ablation assembly.
A method of treating tissue includes delivering energy to the tissue from a delivery device positioned near a first surface of the tissue. The energy damages a target region such that a portion of the target region defining a maximum cross-sectional width of the target region is separated from the first surface.
A method of delivering energy includes delivering energy from an electrode with a substantially uniform voltage across the electrode surface in contact with the tissue without contacting the tissue with edges of the electrode. The electrode can comprise a plurality of sub-electrodes that can be independently operated in a desired sequence.
In the Figures, identical reference numbers identify similar elements or acts.
The left and right vagus nerves 41, 42 originate in the brainstem, pass through the neck, and descend through the chest on either side of the trachea 20. The vagus nerves 41, 42 spread out into nerve trunks 45 that include the anterior and posterior pulmonary plexuses that wrap around the trachea 20, the left main bronchus 21, and the right main bronchus 22. The nerve trunks 45 also extend along and outside of the branching airways of the bronchial tree 27. Nerve trunks 45 are the main stem of a nerve, comprising a bundle of nerve fibers bound together by a tough sheath of connective tissue.
The primary function of the lungs 10 is to exchange oxygen from air into the blood and to exchange carbon dioxide from the blood to the air. The process of gas exchange begins when oxygen rich air is pulled into the lungs 10. Contraction of the diaphragm and intercostal chest wall muscles cooperate to decrease the pressure within the chest to cause the oxygen rich air to flow through the airways of the lungs 10. For example, air passes through the mouth and nose, the trachea 20, then through the bronchial tree 27. The air is ultimately delivered to the alveolar air sacs for the gas exchange process.
Oxygen poor blood is pumped from the right side of the heart through the pulmonary artery 30 and is ultimately delivered to alveolar capillaries. This oxygen poor blood is rich in carbon dioxide waste. Thin semi-permeable membranes separate the oxygen poor blood in capillaries from the oxygen rich air in the alveoli. These capillaries wrap around and extend between the alveoli. Oxygen from the air diffuses through the membranes into the blood, and carbon dioxide from the blood diffuses through the membranes to the air in the alveoli. The newly oxygen enriched blood then flows from the alveolar capillaries through the branching blood vessels of the pulmonary venous system to the heart. The heart pumps the oxygen rich blood throughout the body. The oxygen spent air in the lung is exhaled when the diaphragm and intercostal muscles relax and the lungs and chest wall elastically return to the normal relaxed states. In this manner, air can flow through the branching bronchioles, the bronchi 21, 22, and the trachea 20 and is ultimately expelled through the mouth and nose.
Any number of procedures can be performed on one or more of these nerve trunks 45 to affect the portion of the lung associated with those nerve trunks. Because some of the nerve tissue in the network of nerve trunks 45 coalesce into other nerves (e.g., nerves connected to the esophagus, nerves though the chest and into the abdomen, and the like), the treatment system 200 can treat specific sites to minimize, limit, or substantially eliminate unwanted damage of those other nerves. Some fibers of anterior and posterior pulmonary plexuses coalesce into small nerve trunks which extend along the outer surfaces of the trachea 20 and the branching bronchi and bronchioles as they travel outward into the lungs 10. Along the branching bronchi, these small nerve trunks continually ramify with each other and send fibers into the walls of the airways, as discussed in connection with
The treatment system 200 can affect specific nerve tissue, such as vagus nerve tissue, associated with particular sites of interest. Vagus nerve tissue includes efferent fibers and afferent fibers oriented parallel to one another within a nerve branch. The efferent nerve tissue transmits signals from the brain to airway effector cells, mostly airway smooth muscle cells and mucus producing cells. The afferent nerve tissue transmits signals from airway sensory receptors, which respond to irritants, and stretch to the brain. While efferent nerve tissue innervates smooth muscle cells all the way from the trachea 20 to the terminal bronchioles, the afferent fiber innervation is largely limited to the trachea 20 and larger bronchi. There is a constant, baseline tonic activity of the efferent vagus nerve tissues to the airways which causes a baseline level of smooth muscle contraction and mucous secretion. The treatment system 200 can affect the efferent and/or the afferent tissues to control airway smooth muscle (e.g., innervate smooth muscle), mucous secretion, nervous mediated inflammation, and tissue fluid content (e.g., edema). The contraction of airway smooth muscle, excess mucous secretion, inflammation, and airway wall edema associated with pulmonary diseases often results in relatively high air flow resistance causing reduced gas exchange and decreased lung performance.
In certain procedures, the treatment system 200 can be used to attenuate the transmission of signals traveling along the vagus nerves 41, 42 that cause or mediate muscle contractions, mucus production, inflammation, edema, and the like. Attenuation can include, without limitation, hindering, limiting, blocking, and/or interrupting the transmission of signals. For example, the attenuation can include decreasing signal amplitude of nerve signals or weakening the transmission of nerve signals. Decreasing or stopping nervous system input to distal airways can alter airway smooth muscle tone, airway mucus production, airway inflammation, and the like, thereby controlling airflow into and out of the lungs 10. Decreasing or stopping sensory input from the airways and lungs to local effector cells or to the central nervous system can also decrease reflex bronchoconstriction, reflex mucous production, release of inflammatory mediators, and nervous system input to other cells in the lungs or organs in the body that may cause airway wall edema. In some embodiments, the nervous system input can be decreased to correspondingly decrease airway smooth muscle tone. In some embodiments, the airway mucus production can be decreased a sufficient amount to cause a substantial decrease in coughing and/or in airflow resistance. In some embodiments, the airway inflammation can be decreased a sufficient amount to cause a substantial decrease in airflow resistance and ongoing inflammatory injury to the airway wall. Signal attenuation may allow the smooth muscles to relax, prevent, limit, or substantially eliminate mucus production by mucous producing cells, and decrease inflammation. In this manner, healthy and/or diseased airways can be altered to adjust lung function. After treatment, various types of questionnaires or tests can be used to assess the subject's response to the treatment. If needed or desired, additional procedures can be performed to reduce the frequency of coughing, decrease breathlessness, decrease wheezing, and the like.
Main bronchi 21, 22 (i.e., airway generation 1) of
Each segmental bronchus may be treated by delivering energy to a single treatment site along each segmental bronchus. For example, the catheter system 204 can deliver energy to each segmental bronchus of the right lung. In some procedures, ten applications of energy can treat most of or substantially all of the right lung. In some procedures, most or substantially all of both lungs are treated using less than thirty-six different applications of energy. Depending on the anatomical structure of the bronchial tree, segmental bronchi can often be denervated using one or two applications of energy.
Function of other tissue or anatomical features, such as the mucous glands, cilia, smooth muscle, body vessels (e.g., blood vessels), and the like can be maintained when nerve tissue is ablated. Nerve tissue includes nerve cells, nerve fibers, dendrites, and supporting tissue, such as neuroglia. Nerve cells transmit electrical impulses, and nerve fibers are prolonged axons that conduct the impulses. The electrical impulses are converted to chemical signals to communicate with effector cells or other nerve cells. By way of example, a portion of an airway of the bronchial tree 27 can be denervated to attenuate one or more nervous system signals transmitted by nerve tissue. Denervating can include damaging all of the nerve tissue of a section of a nerve trunk along an airway to stop substantially all the signals from traveling through the damaged section of the nerve trunk to more distal locations along the bronchial tree or from the bronchial tree more proximally to the central nervous system. Additionally, signals that travel along nerve fibers that go directly from sensory receptors (e.g., cough and irritant receptors) in the airway to nearby effector cells (e.g., postganglionic nerve cells, smooth muscle cells, mucous cells, inflammatory cells, and vascular cells) will also be stopped. If a plurality of nerve trunks extends along the airway, each nerve trunk can be damaged. As such, the nerve supply along a section of the bronchial tree can be cut off. When the signals are cut off, the distal airway smooth muscle can relax leading to airway dilation, mucous cells decrease mucous production, or inflammatory cells stop producing airway wall swelling and edema. These changes reduce airflow resistance so as to increase gas exchange in the lungs 10, thereby reducing, limiting, or substantially eliminating one or more symptoms, such as breathlessness, wheezing, chest tightness, and the like. Tissue surrounding or adjacent to the targeted nerve tissue may be affected but not permanently damaged. In some embodiments, for example, the bronchial blood vessels along the treated airway can deliver a similar amount of blood to bronchial wall tissues and the pulmonary blood vessels along the treated airway can deliver a similar amount of blood to the alveolar sacs at the distal regions of the bronchial tree 27 before and after treatment. These blood vessels can continue to transport blood to maintain sufficient gas exchange. In some embodiments, airway smooth muscle is not damaged to a significant extent. For example, a relatively small section of smooth muscle in an airway wall which does not appreciably impact respiratory function may be reversibly altered. If energy is used to destroy the nerve tissue outside of the airways, a therapeutically effective amount of energy does not reach a significant portion of the non-targeted smooth muscle tissue.
In some embodiments, one of the left and right main bronchi 21, 22 is treated to treat one side of the bronchial tree 27. The other main bronchus 21, 22 can be treated based on the effectiveness of the first treatment. For example, the left main bronchus 21 can be treated to treat the left lung 11. The right main bronchus 22 can be treated to treat the right lung 12. In some embodiments, a single treatment system can damage the nerve tissue of one of the bronchi 21, 22 and can damage the nerve tissue of the other main bronchus 21, 22 without removing the treatment system from the trachea 20. Nerve tissue positioned along the main bronchi 21, 22 can thus be damaged without removing the treatment system from the trachea 20. In some embodiments, a single procedure can be performed to conveniently treat substantially all, or at least a significant portion (e.g., at least 50%, 70%, 80%, 90% of the bronchial airways), of the patient's bronchial tree. In other procedures, the treatment system can be removed from the patient after treating one of the lungs 11, 12. If needed, the other lung 11, 12 can be treated in a subsequent procedure.
Cilia can be damaged, excited, or otherwise altered to elicit a desired response along the epithelium 110 in order to control (e.g., increase or decrease) mucociliary transport. Many particles are inhaled as a person breathes, and the airways function as a filter to remove the particles from the air. The mucociliary transport system functions as a self-cleaning mechanism for all the airways throughout the lungs 10. The mucociliary transport is a primary method for mucus clearance from distal portions of the lungs 10, thereby serving as a primary immune barrier for the lungs 10. For example, the inner surface 102 of
The ablation assembly 208 can selectively treat target regions inside of the airway wall 103 (e.g., anatomical features in the stromas 112a, 112b). For example, the mucous glands 116 can be damaged to reduce mucus production a sufficient amount to prevent the accumulation of mucus that causes increased air flow resistance while preserving enough mucus production to maintain effective mucociliary transport, if needed or desired. Nerve branches/fibers passing through the airway wall 103 or other anatomical features in the airway wall 103 can also be destroyed.
If an ablation element is an RF electrode 214, the electrode 214 can be brought into contact with or proximate to the inner surface 102. The RF electrode 214 can output RF energy which travels through the tissue and is converted into heat. The heat causes formation of a lesion. The RF energy can be directed radially outward towards the nerve truck 45 and between the cartilage plates 118. The nerve trunk 45 can be damaged without causing appreciable damage to the adjacent cartilage plates 118. Damage to other non-targeted regions (e.g., the epithelium) can also be kept at or below an acceptable level.
Natural body functions can help prevent, reduce, or limit damage to tissue. Blood within the blood vessels 130 can absorb thermal energy and can then carry the thermal energy away from the heated section of the branches 130. In this manner, blood can mitigate or avoid damage to the blood vessels 130. After the treatment is performed, the bronchial artery branches 130 can continue to maintain the health of lung tissue. In some embodiments, a sufficient amount of RF energy is delivered to the nerve trunk 45 to destroy an entire longitudinal section of the nerve trunk 45 while keeping the amount of energy that reaches the blood vessels 130 below an amount that causes tissue destruction of the vessel 130. Thus, therapies can be performed without damaging to any significant extent other regions of the airway 100, even regions that are adjacent to the treatment site.
Treatment efficacy can be evaluated based at least in part on one or more airway attributes, pulmonary function tests, exercise capacity tests, and/or questionnaires. Patients can be evaluated to track and monitor their progress. If needed or desired, additional procedures can be performed until desired responses are achieved. Different types of instruments for evaluating airway attributes may be used. During ablation, feedback from an instrument can indicate whether the targeted tissue has been ablated. Once targeted tissue is ablated, therapy can be discontinued to minimize or limit collateral damage, if any, to healthy untargeted tissue.
Different attributes of airways can be evaluated to determine procedures to be performed. Such airway attributes include, without limitation, physical properties of airways (e.g., airway compliance, contractile properties, etc.), airway resistance, dimensions of airway lumens (e.g., shapes of airways, diameters of airways, etc.), responsiveness of airways (e.g., responsiveness to stimulation), muscle characteristics (e.g., muscle tone, muscle tension, etc.), inflammatory cells, inflammatory cytokines, or the like. In some embodiments, changes of airway muscle characteristics can be monitored by measuring pressure changes in the ablation assembly 208, which is inflated to a known pressure. Based on pressure changes, a physician determines the effects, if any, of the treatment, including, without limitation, whether targeted tissue has been stimulated, ablated, or the like.
Energy can be used to damage target regions. As used herein, the term “energy” is broadly construed to include, without limitation, thermal energy, cryogenic energy (e.g., cooling energy), electrical energy, acoustic energy (e.g., ultrasonic energy), radio frequency energy, pulsed high voltage energy, mechanical energy, ionizing radiation, optical energy (e.g., light energy), and combinations thereof, as well as other types of energy suitable for treating tissue. In some embodiments, the catheter system 204 delivers energy and one or more substances (e.g., radioactive seeds, radioactive materials, etc.), treatment agents, and the like. Exemplary non-limiting treatment agents include, without limitation, one or more antibiotics, anti-inflammatory agents, pharmaceutically active substances, bronchoconstrictors, bronchodilators (e.g., beta-adrenergic agonists, anticholinergics, etc.), nerve blocking drugs, photoreactive agents, or combinations thereof. For example, long acting or short acting nerve blocking drugs (e.g., anticholinergics) can be delivered to the nerve tissue to temporarily or permanently attenuate signal transmission. Substances can also be delivered directly to the nerves 122 or the nerve trunks 45, or both, to chemically damage the nerve tissue.
Curve A shown in
If active cooling is employed, the temperature drops to a much lower level, for example, about 35° C. as represented by the curve A1 at the electrode-tissue interface at 0 millimeters in distance. Since this temperature is below 50° C., cell death will not begin to occur until a distance of d2 at the point where the curve A2 crosses the cell death line at 50° C., for example, a depth of 3 millimeters from the surface. Cell death will occur at depths from 3 millimeters to 5 millimeters as represented by the distance d3. Such a cooled ablation procedure is advantageous because it permits cell death and tissue destruction to occur at a distance (or a range of distances) from the electrode-tissue interface without destroying the epithelium and the tissue immediately underlying the same. In some embodiments, the nerve tissues running along the outside of the airway can be ablated without damaging the epithelium or underlying structures, such as the stroma and smooth muscle cells.
The curve B represents what occurs with and without cooling of the electrode at a higher power level, for example, 20 watts of RF energy. Segment B2 of curve B represents a continuation of the exponential curve of the segment B3 without cooling. As can be seen, the temperature at the electrode-tissue interface approaches 100° C. which may be undesirable because that is a temperature at which boiling of tissue fluid and coagulation and charring of tissue at the tissue-electrode interface will occur, thus making significantly increasing the tissue impedance and compromising the ability to deliver additional RF energy into the airway wall. By providing active cooling, the curve B1 shows that the temperature at the electrode-tissue interface drops to approximately 40° C. and that cell death occurs at depths of two millimeters as represented by d4 to a depth of approximately 8 millimeters where the curve B3 crosses the 50° C. tissue cell death boundary. Thus, it can be seen that it is possible to provide a much deeper and larger region of cell death using the higher power level without reaching an undesirable high temperature (e.g., a temperature that would result in coagulation and charring of tissue at the electrode-tissue interface). The systems can be used to achieve cell death below the epithelial surface of the airway so that the surface need not be destroyed, thus facilitating early recovery by the patient from a treatment.
The curve C represents a still higher power level, for example, 40 watts of RF energy. The curve C includes segments C1, C2, and C3. The broken line segment C2 is a continuation of the exponential curve C3. Segment C2 shows that the temperature at the electrode-tissue interface far exceeds 100° C. and would be unsuitable without active cooling. With active cooling, the temperature at the electrode-tissue interface approaches 80° C. and gradually increases and approaches 95° C. and then drops off exponentially to cross the 50° C. cell death line 216 at a distance of about 15 millimeters from the electrode-tissue interface at the epithelial surface of the airway represented by the distance d6. Because the starting temperature is above the 50° C. cell death line 216, tissue cell death will occur from the epithelial surface to a depth of about 15 millimeters to provide large and deep regions of tissue destruction.
In
By adjusting the rate of power delivery to the electrode 214, the rate at which coolant (e.g., saline solution) is passed into the balloon 212, the temperature of the saline solution, and the size of the balloon 212, and the exact contour and temperature of the individual isotherms can be modified. For example, by selecting the proper temperature and flow rate of saline and the rate of power delivery to the electrode, it is possible to achieve temperatures in which isotherm A=60° C., B=55° C., C=50° C., D=45° C., E=40° C., and F=37° C. Further adjustments make it possible to achieve temperatures where isotherm A=50° C., B=47.5° C., C=45° C., D=42.5° C., E=40° C., and F=37° C. Only those areas contained within the 50° C. isotherm will be heated enough to induce cell death. In some procedures, tissue at a depth of about 2 mm to about 8 mm in the airway wall can be ablated while other non-targeted tissues at a depth less than 2 mm in the airway wall are kept at a temperature below at temperature that would cause cell death. The coolant 218 can absorb energy to cool the tissue-contacting portion 215 of the energy emitter assembly 220 while the balloon 212 holds the energy emitter assembly 220 against the airway 100.
Referring to
The control module 210 generally includes a controller 244 and a fluid delivery system 246. The controller 244 includes, without limitation, one or more processors, microprocessors, digital signal processors (DSPs), field programmable gate arrays (FPGA), and/or application-specific integrated circuits (ASICs), memory devices, buses, power sources, and the like. For example, the controller 244 can include a processor in communication with one or more memory devices. Buses can link an internal or external power supply to the processor. The memories may take a variety of forms, including, for example, one or more buffers, registers, random access memories (RAMs), and/or read only memories (ROMs). The controller 244 may also include a display 245, such as a screen, and an input device 250. The input device 250 can include a keyboard, touchpad, or the like and can be operated by a user to control the catheter 207.
The controller 244 can store different programs. A user can select a program that accounts for the characteristics of the tissue and desired target region. For example, an air-filled lung can have relatively high impedance, lymph nodes have medium impedance, and blood vessels have relatively low impedance. The controller 244 can determine an appropriate program based on the impedance. A differential cooling program can be executed to deliver different temperature coolants through the balloon 212 and the energy emitter assembly 220. The temperature difference can be at least 10° C. Performance can be optimized based on feedback from sensors that detect temperatures, tissue impedance, or the like. For example, the controller 244 can control operation of the ablation assembly 208 based on a surface temperature of the tissue to which energy is delivered. If the surface temperature becomes excessively hot, cooling can be increased and/or electrode power decreased in order to produce deep lesions while protecting surface tissues.
An internal power supply 248 (illustrated in dashed line in
The fluid delivery system 246 includes a fluid source 260 coupled to a supply line 268 and a fluid receptacle 262 coupled to a return line 272. The fluid source 260 can include a container (e.g., a bottle, a canister, a tank, or other type of vessel for holding fluid) held in a housing unit 264. In pressurizable embodiments, the fluid source 260 includes one or more pressurization devices (e.g., one or more pumps, compressors, or the like) that pressurize coolant. Temperature control devices (e.g., Peltier devices, heat exchangers, or the like) can cool or recondition the fluid. The fluid can be a coolant comprising saline, de-ionized water, refrigerant, cryogenic fluid, gas, or the like. In other embodiments, the fluid source 260 can be an insulated container that holds and delivers a chilled coolant to the supply line 268. The coolant flows distally through the elongate shaft 230 into the ablation assembly 208. Coolant in the ablation assembly 208 flows proximally through the elongate shaft 230 to the return line 272. The coolant proceeds along the return line 272 and ultimately flows into the fluid receptacle 262.
The balloon 212 optionally has a sensor 247 (illustrated in dashed line) that is communicatively coupled to the controller 244. The controller 244 can command the catheter 207 based on signals from the sensor 247 (e.g., a pressure sensor, a temperature sensor, a thermocouple, a pressure sensor, a contact sensor, or the like). Sensors can also be positioned on energy emitter assembly 220, along the elongate shaft 230 or at any other location. The controller 244 can be a closed loop system or an open loop system. For example, in a closed loop system, the electrical energy is delivered to the electrode 214 based upon feedback signals from one or more sensors configured to transmit (or send) one or more signals indicative of one or more tissue characteristics, energy distribution, tissue temperatures, or any other measurable parameters of interest. Based on those readings, the controller 244 adjusts operation of the electrode 214. Alternatively, in an open loop system, the operation of the electrode 214 is set by user input. For example, the user can observe tissue temperature or impedance readings and manually adjust the power level delivered to the electrode 214. Alternatively, the power can be set to a fixed power mode. In yet other embodiments, a user can repeatedly switch between a closed loop system and an open loop system.
To effectively cool the electrode 214, a conduit 234 coupled to the electrode 214 is fluidly coupled to a coolant delivery lumen within the shaft 230 to receive coolant therefrom. Alternatively, flow diverters within the balloon 212 can direct some or all of the coolant in the balloon 212 towards the electrode 214 or a balloon sidewall and may provide a separate cooling channel for the electrode 214. In some embodiments, one or more cooling channels extend through the electrode 214 (e.g., electrode 214 may be tubular so that coolant can flow through it). In other embodiments, the coolant flows around or adjacent the electrode 214. For example, an outer member, illustrated as a conduit 234 in
Referring to
Referring to
The conduit 234 includes a proximal section 286, a distal section 288, and a non-linear section 300. The proximal section 286 functions as an inlet and extends distally from the elongate shaft 230. The non-linear section 300 extends circumferentially about the balloon 212 and has an arc length in a range of about 180 degrees to 450 degrees. As shown in
When deflated (i.e., when not pressurized with coolant), the conduit 234 can be highly flexible to conform about the elongate shaft 230 and can be made, in whole or in part, of a material that assumes a preset shape when pressurized or activated. Such materials include, without limitation, thermoformed polymers (e.g., polyethylene terephthalate, polyethylene, or polyurethanes), shape memory materials, or combinations thereof. When the conduit 234 is inflated, it assumes a preset shape configured to position electrode 214 in the desired transverse orientation with respect to longitudinal axis 310.
The balloon 212 can be made, in whole or in part, of polymers, plastics, silicon, rubber, polyethylene, polyvinyl chloride, chemically inert materials, non-toxic materials, electrically insulating materials, combinations thereof, or the like. To enhance heat transfer, the balloon sidewall can comprise one or more conductive materials with a high thermal conductivity. For example, conductive strips (e.g., metal strips) can extend along the balloon 212 to help conduct thermal energy away from hot spots, if any. The balloon 212 can conform to irregularities on the airway surface (e.g., cartilaginous rings, side branches, etc.) and can be made, in whole or in part, of a distensible material, such as polyurethane (e.g., low durometer polyurethane) or other type of highly conformable material that may be transparent, semi-transparent, or opaque. The balloon 212 can have different inflated shapes, including a hot dog shape, an ovoid shape, a cylindrical shape, or the like.
As shown in
In multilayer embodiments, the electrode main body 350 can include at least one tube (e.g., a non-metal tube, a plastic tube, etc.) with one or more films or coatings. The films or coatings can be made of metal, conductive polymers, or other suitable materials formed by a deposition process (e.g., a metal deposition process), coating process, etc., and can comprise, in whole or in part, silver ink, silver epoxy, combinations thereof, or the like.
Radio-opaque markers or other types of visualization features can be used to position the main body 350. To increase visibility of the electrode 214 itself, the electrode 214 may be made, in whole or in part, of radiographically opaque material.
When the delivery apparatus 206 of
With continued reference to
The balloon 212 can be inflated to move the energy emitter assembly 220 near (e.g., proximate to or in contact with) the airway 100. The angle β can be increased between 70 degrees and about 110 degrees when the balloon 212 is fully inflated.
As the balloon 212 inflates, the electrode 214 moves (e.g., pivots, rotates, displaces, etc.) from a first orientation of
To deploy the energy emitting assembly 208, coolant from the elongate shaft 230 flows through the energy emitter assembly 220 and into the balloon 212. The electrode 214 can output a sufficient amount of energy to ablate a target region. The coolant absorbs thermal energy from electrode 214 and the airway wall 100.
The diameter DE of the electrode 214 and conduit 234 can be in a range of about 1.5 mm to about 2.5 mm when pressurized with coolant. Such embodiments are well suited to treat tissue outside the lung along the main bronchi. In certain embodiments, the diameter DE is about 2 mm. In yet other embodiments, the diameter DE can be in a range of about 0.1 mm to about 3 mm. The diameter DE of the deflated conduit 234 and electrode 214 can be about 0.1 mm to about 1 mm.
To treat a bronchial tree of a human, the diameter of the inflated balloon 212 can be in a range of about 12 mm to about 18 mm. For enhanced treatment flexibility, the inflated balloon diameter may be in a range of about 7 mm to about 25 mm. Of course, the balloon 212 can be other sizes to treat other organs or tissue of other animals.
The ablation assembly 208 provides differential cooling because the coolant in the energy emitter assembly 220 is at a lower temperature and higher velocity than the coolant in the balloon 212. Coolant, represented by arrows, flows out of the elongate shaft 230 and into the energy emitter assembly 220. The coolant proceeds through the energy emitter assembly 220 and the coolant channel 340 (
The coolant flows through a port 430, a lumen 432, and a throttle 434. The throttles 420, 434 can cooperate to maintain a desired pressure. The throttle 420 is configured to maintain a first flow rate of the coolant through the energy emitting assembly 220 and a second flow rate of the coolant through the cooling section 209. The first flow rate can be significantly different from the second flow rate.
The conduit 234 can assume a preset shape when pressurized. The valves 420, 434 can cooperate to maintain the desired pressure within the balloon 212 within a range of about 5 psig to about 15 psig. Such pressures are well suited to help push the electrode 214 between cartilaginous rings. Other pressures can be selected based on the treatment to be performed. The valves 420, 434 can be throttle valves, butterfly valves, check valves, duck bill valves, one-way valves, or other suitable valves.
When RF energy is transmitted to the electrode 214, the electrode 214 outputs RF energy that travels through tissue. The RF energy can heat tissue (e.g., superficial and deep tissue) of the airway wall while the coolant cools the tissue (e.g., superficial tissues). The net effect of this superficial and deep heating by RF energy and superficial cooling by the circulating coolant is the concentration of heat in the outer layers of the airway wall 100, as discussed in connection with
Heat can be concentrated in one or more of the internal layers (e.g., the stroma) of the airway wall or in the inner lining (e.g., the epithelium) of the airway wall. Furthermore, one or more of the vessels of the bronchial artery branches may be within the lesion. The heat generated using the electrode 214 can be controlled such that blood flowing through the bronchial artery branches protects those branches from thermal injury while nerve trunk tissue is damaged, even if the nerve tissue is next to the artery branches. The catheter 207 can produce relatively small regions of cell death. For example, a 2 mm to 3 mm section of tissue in the middle of the airway wall 100 or along the outer surface of the airway wall 100 can be destroyed. By the appropriate application of power and the appropriate cooling, lesions can be created at any desired depth.
A circumferential lesion can be formed around all or most of the circumference of the airway wall 100 by ablating tissue while slowly rotating the ablation assembly 208 or by positioning the ablation assembly 208 in a series of rotational positions at each of which energy is delivered for a desired time period. Some procedures form adjacent lesions that become contiguous and form a circumferential band all the way around the airway wall 100. In some embodiments, the entire loop 221 (
If the user wants the coolant in the balloon 212 to be at a lower temperature than the coolant in the energy emitter assembly 220, chilled coolant can be delivered into the balloon 212 and then into the energy emitter assembly 220.
Airway cartilage rings or cartilage layers typically have a significantly larger electrical resistance than airway soft tissue (e.g., smooth muscle or connective tissue). Airway cartilage impedes energy flow (e.g., electrical radiofrequency current flow) and makes the formation of therapeutic lesions with radiofrequency electrical energy to affect airway nerve trunk(s) challenging when the electrode is next to cartilage.
Positioners can facilitate positioning of the electrodes. Such positioners include, without limitation, bumps, bulges, protrusions, ribs or other features that help preferentially seat the electrode 214 at a desired location, thus making it easy to perform the treatment or to verify correct positioning.
The plurality of electrodes 214 can reduce both treatment time and procedure complexity as compared to a catheter with a single electrode. This is because the multi-electrode catheter may have to be positioned a smaller number of times within a bronchial tree (or other hollow organ) as compared to single electrode catheters to produce a number of lesions of a desired therapeutic size. Multi-electrode catheters can thus precisely and accurately treat a user's respiratory system.
Referring to
When the balloon 554 is partially inflated (shown in
The catheter 704 has a proximal section 732 configured for differential cooling. A proximal end 741 of an inflow line 742 has an inline valve 743 and is in fluid communication with an inflow lumen 750 of
A proximal end 744 of an inflow line 745 of
The ablation assemblies 780 may be spaced apart to allow each of the ablation assemblies 780 to be positioned between cartilaginous rings. For example, the distance D in
Fluids at different temperatures can be delivered to the ablation assemblies 780 and the balloon 720. In some embodiments, the coolant is delivered through cooling channels of the energy emitting assemblies 780 and then into the balloon 720 if the therapeutic goal is to produce lesions with the maximum depth. The balloon 720 and the energy emitting assemblies 780 can also be coupled to a common source (or sink) path. This allows for unique coolant flow in each path. This also may reduce the overall diameter of the expanded ablation assembly 710 as compared to using completely separate coolant paths. Electrodes 790a, 790b may be independently controlled so that energy may be delivered simultaneously or separately, and at the same or different power levels.
One of shafts 817, 819 is adapted to deliver coolant through loop 823 while the other received coolant from the loop and returns it to the proximal end of the device. In
The energy emitter assembly 820 can be moveable between a straightened and collapsed configuration for delivery and the illustrated deployed configuration. For example, in the preshaped embodiment described above, the distal loop 823 on energy emitter assembly 820 can be straightened and collapsed inwardly so as to be positionable in a constraining sheath during introduction. Upon removal from the sheath, distal loop 823 will return to its unbiased deployed orientation, lying in a plane generally perpendicular to the longitudinal axes of shafts 817, 819. In alternative embodiments, the distal loop 823 may be flaccid and collapsible when unpressurized, and will assume the desired deployed shape when coolant is introduced through shafts 817, 819. To manufacture distal loop 823, a polymer tube may be heat treated to assume a desired shape when pressurized.
By decoupling the energy emitter apparatus 820 from the deployment catheter 811 they may be introduced separately from each other, allowing the apparatus to be introduced through very small-diameter passageways. This is particularly useful to allow the ablation assembly to be inserted through a working channel of a bronchoscope. First, the energy emitter assembly 820 may be collapsed and introduced through the working channel (with or without a sheath), then the deployment catheter 811 may be introduced. The combined apparatus may then be assembled within the airway.
As shown in
One or move valves can provide for different flow rates through the balloon 810 and the energy emitter assembly 820. For example, a valve system (e.g., one or more valves, throttles, etc.) can provide a first flow rate of coolant through the energy emitting assembly 220 and a second flow rate of coolant through the balloon 810. The first flow rate can be significantly different from the second flow rate. For example, the first flow rate can be significantly greater than the second flow rate. In yet other embodiments, the first flow rate can be generally the same as the second flow rate.
Referring to
The ventilation passageway 890 is configured to allow expiratory airflow, represented by arrows 892 in
As in the embodiment of
The coiled section 946 can be formed of a hollow tubular member and has seven coil turns. The number of coil turns can be increased or decreased to increase or decrease the axial length of the coiled section 946. Each coil turn can be connected to an adjacent coil turn to prevent separation. Alternatively, adjacent coil turns may not be physically coupled together to allow the ablation assembly 910 to uncoil for delivery through airways.
The ablation assembly 910 can be inflated to assume the coiled configuration and can be made, in whole or in part, of a pre-formed material, such as PET or other thermoformed material. Alternatively, the ablation assembly 910 can be formed of shape memory material that assumes different configurations when thermally activated or when released from a constrained configuration.
To help facilitate contact between the electrode 940 and tissue, the electrode 940 can protrude outwardly. The electrode 940 can be a surface mounted plate. In other embodiments, the electrode 940 is a conductive coating.
As shown in
With reference to
With reference to
Electrodes can include one or more heat transfer elements for enhancing heat transfer.
If electrodes have sharp edges at one or both ends, electrons have a tendency to accumulate near those sharp edges and other irregularities. The voltage near the edges is often higher than in other regions of the electrode.
The shielding portions 1484a, 1484b can be cooling conduits. Coolant can flow through the shielding portions 1484 and through a cooling channel of the electrode 1480. In other embodiments, a Peltier device is used to cool the electrode 1480. It will be understood that any of the electrode embodiments of
Lesion shapes can be controlled by adjusting the temperature of the coolant, coolant flow rates, heat carrying capacity of coolants, thermal characteristics of the balloon (e.g., the heat transfer properties of the balloon), or the amount of delivered power.
Chilled coolant can be delivered through the balloon 1510 to reduce the cross-sectional width of the lesion at the tissue surface 1525.
The lesion can have a generally elliptical shape. In some embodiments, including the illustrated embodiment of
The DWidth Max can be selected based on the location of the target region. To damage nerve tissue, the DWidth Max can be at least about 2 mm to ensure that the lesion includes the nerve tissue. The depth D can be at least about 2 mm to mitigate or avoid a significant amount of damage to smooth muscle tissue. Such embodiments are well suited for treating an airway wall because the smooth muscle tissue is typically not below a depth of 2 mm. In this manner, the cross-sectional width of the target region can be maximized at a depth deeper than the smooth muscle tissue. The majority, and in some embodiments substantially all, of the lesion will be in tissue which is not smooth muscle tissue, typically lying deeper in the airway wall than the region of smooth muscle tissue. Further, any damage to smooth muscle cells in the airway wall can be less than the amount of damage that, in the absence of damaging nerve tissue, would be required to substantially alter the responsiveness or constriction of the airway, e.g. as a result of asthma, COPD, or other pulmonary disease.
The lesion can be separated from the tissue surface by a protected region in which a significant amount of the tissue is not permanently damaged.
It will be understood that the term “lesion” as used herein is intended to mean tissue which is permanently damaged, i.e. to the point of cell death. In some cases, the delivery of energy will cause temporary or non-lethal damage to cells outside the region referred to as the “lesion.” For example, epithelial or smooth muscle cells may be temporarily damaged or altered by the energy delivery described herein. However, advantageously, through the use of differential cooling, these cells can recover and remain functional, thus are not considered part of the “lesion” created. By contrast, the catheter 207 can impart permanent damage to nerve tissues lying deep in the airway wall or on the outside of the airway wall, thus attenuating nerve signals that are the cause of certain pulmonary diseases.
The catheter 207 of
If external liquid (e.g., blood, urine, mucous, etc.) flows about the delivery device 1600, the balloon 1620 can block liquid flow along the tissue 1650. The electrode 1610 can deliver energy to the tissue 1650 without an appreciable amount of heat being absorbed by the external fluid flow. For example, if the tissue 1650 is cardiac tissue, the balloon 1620 can prevent a significant amount of blood flow between the balloon 1620 and the tissue 1650, thus preventing tissue near the electrode 1610 from being cooled due to blood flow. Additionally, the balloon 1620 can cool the tissue 1650 to shape lesions, if needed or desired.
The distally ablating delivery devices of
The balloon 1620 can be inflated with a gas (e.g., ambient air) or other fluid that does not absorb a significant amount of thermal energy. The balloon 1620 blocks blood flow and allows ablation of the tissue adjacent to the balloon-tissue interface 2042. As shown in
Chilled coolant can be passed through both the electrode 1610 and the balloon 1620 to form lesions spaced apart from the delivery device-tissue interface.
Other types of structures can block fluid or blood flow. For example, shields, masks, umbrella structures, or the like can be placed against tissue to prevent the flow of natural bodily fluids along the tissue and, thus, promote shallow lesion formation.
The coolant can be chilled saline or chilled water, which mixes with bodily fluids (e.g., blood). If the delivery device 2100 is used in organs containing air or other gas, the coolant can be a gas.
A high pressure gas P1 of
T1-T2=μ(P1-P2)
where
The Joule-Thomson coefficient (μ) is specific for each gas or combination of gasses. Standard temperature values for μ are:
These coefficients indicate that for a given pressure drop, CO2 will cause a 5 times greater drop in temperature than a similar drop in pressure experienced by air.
The use of air in the lungs can be desirable. Carbon dioxide can be used if the flow rates of coolant gas are sufficiently low so as to not overwhelm the patient's ability to ventilate this additional carbon dioxide out of the lungs. The cooling effect can be enhanced if the coolant in the coolant conduit is a high pressure liquid, such as liquid air or liquid CO2. The high pressure liquid passes through the pressure reducing element 2032 (e.g., a throttle) and undergoes an endothermal phase change from a high pressure liquid to a high pressure gas, which causes the temperature of the gas to be lower than that of the high pressure liquid. It then goes through a Joule-Thomson expansion from P1 to P2 which causes a further drop in temperature, before being vented out of the electrode via the vents 2033.
It will be understood that in any of the embodiments of energy emitter assemblies disclosed herein, the electrodes and/or the tissue adjacent to the electrodes may be cooled by fluids undergoing Joule-Thomson expansion as described above. For example, a pressurized fluid may be passed through a pressure reducing element in any of these energy emitting assemblies such that the fluid undergoes a phase change to gas, which may be vented directly toward the electrodes to be cooled, and/or toward the airway wall tissues adjacent to the area of contact by the electrodes.
The deployed section 2230 can have an arcuate shape for conforming to the inner surface of an airway or other vessel. The arcuate deployed section 2230 can have an axis of curvature which is generally coplanar with a longitudinal axis of the elongate body 2212. A biasing element such as a wire or push rod extending through elongate body 2212 can adjust the configuration of the delivery device 2200. If the biasing element is a wire, the wire can be pulled to move the deployed section 2230 into the arcuate shape. Alternatively, a sleeve 2210 can be slid distally over the distal section 1230 to cover the deployed section 2230 and constrain it in a straightened configuration during delivery. When the sleeve is removed the deployed section 2230 will resiliently return to the arcuate shape. In other embodiments, when a coolant is delivered through the distal section 2230, the pressure of the coolant can cause the distal section 2230 to assume the curved shape (e.g., a spiral configuration, a coiled configuration, or a helical configuration).
The visual indicator or marking 2310a can be colored, reflective, or otherwise readily visible through a bronchoscope. In some embodiments, the visual indicator 2310a can be a longitudinally-extending stripe or mark. In other embodiments, the visual indicator 2310a can be one or more light sources. If the ablation assembly 2320 includes a plurality of electrodes, different visual indicators can correspond to the positions of different electrodes. Visual indicators can be located on the elongate shaft 2350, the balloon 2330, electrode 2340, or other suitable location.
The delivery apparatus 2410 is a bronchoscope with camera optics 2440. A distal end 2470 of the camera optics 2440 is optically coupled to the balloon wall. The distal end 2470 can be pressed against the conformable balloon's proximal surface to provide optical coupling. During use, the user may view the electrode or other components or anatomical features through the wall of the balloon and the fluid within the balloon.
In other embodiments, the delivery apparatus 2410 can be a sheath with fiber optics 2440 having lenses, light sources, cameras, or the like. In certain embodiments, the optical element 2440 is integrated or coupled to the balloon 2460. This prevents mucous or other unwanted substances from obscuring the user's view. The balloon geometry, specifically the angle of the proximal balloon wall, may be selected to optimize optical coupling with the camera optics 2440. The proximal balloon wall can have a section which can be aligned with the camera optics 2440 and which is substantially flat, smooth, transparent, and which is parallel to the plane of the distal end 2470 of the camera optics 2440, preferably in some embodiments being disposed at an angle of about 75 degrees to about 105 degrees relative to the longitudinal axis of the elongate body 2420. The material of the proximal balloon wall may be selected to optimize visibility and transparency, e.g. with a refractive index which is compatible with the camera optics 2440 and/or fluid within the balloon.
As shown in
To inflate the ablation assembly 2600, a fluid can flow through and inflate the conduit 2618. An internal throttle valve can control the relative pressure between the conduit 2618 and the balloon 2630.
A delivery conduit 2754 of
To position the electrode 2830 near tissue, the expandable element 2810 can be inflated to move the arms 2834a, 2834b outwardly. In some embodiments, the arms 2834a, 2834b are self-expanding. As the ablation assembly 2800 moves out of a working lumen of a delivery assembly, the arms 2834a, 2834b can assume an expanded configuration. In other embodiments, the arm 2834a, 2834b are made of a shape memory material and can be activated to assume the expanded configuration. The arms themselves may be made of a conductive material such as Nitinol to conduct energy to the electrode 2830.
The delivery devices disclosed herein can treat the digestive system, nervous system, vascular system, or other systems. For example, the elongate assemblies, intra-luminal catheters, and delivery devices disclosed herein can be delivered through blood vessels to treat the vascular system. The treatment systems and its components disclosed herein can used as an adjunct during another medical procedure, such as minimally invasive procedures, open procedures, semi-open procedures, or other surgical procedures (e.g., lung volume reduction surgery) that provide access to a desired target site. Various surgical procedures on the chest may provide access to lung tissue. Access techniques and procedures used to provide access to a target region can be performed by a surgeon and/or a robotic system. Those skilled in the art recognize that there are many different ways that a target region can be accessed.
The delivery devices disclosed herein can be used with guidewires, delivery sheaths, optical instruments, introducers, trocars, biopsy needles, or other suitable medical equipment. If the target treatment site is at a distant location in the patient (e.g., a treatment site near the lung root 24 of
Semi-rigid or rigid elongated assemblies can be delivered using trocars, access ports, rigid delivery sheaths using semi-open procedures, open procedures, or other delivery tools/procedures that provide a somewhat straight delivery path. Advantageously, the semi-rigid or rigid elongated assemblies can be sufficiently rigid to access and treat remote tissue, such as the vagus nerve, nerve branches, nerve fibers, and/or nerve trunks along the airways, without delivering the elongated assemblies through the airways. The embodiments and techniques disclosed herein can be used with other procedures, such as bronchial thermoplasty.
Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including but not limited to.”
The various embodiments described above can be combined to provide further embodiments. These and other changes can be made to the embodiments in light of the above-detailed description. The embodiments, features, systems, devices, materials, methods and techniques described herein may, in some embodiments, be similar to any one or more of the embodiments, features, systems, devices, materials, methods and techniques described in of application Ser. No. 12/463,304 filed on May 8, 2009; U.S. Provisional Patent Application No. 61/255,367 filed Oct. 27, 2009; and U.S. Provisional Patent Application No. 61/260,348 filed Nov. 11, 2009. Each of these applications is incorporated herein by reference in its entirety. In addition, the embodiments, features, systems, devices, materials, methods and techniques described herein may, in certain embodiments, be applied to or used in connection with any one or more of the embodiments, features, systems, devices, materials, methods and techniques disclosed in the above-mentioned U.S. patent application Ser. No. 12/463,304. For example, the apparatuses of disclosed in U.S. patent application Ser. No. 12/463,304 may incorporate the electrodes or other features disclosed herein.
In addition, the embodiments, features, systems, delivery devices, materials, methods and techniques described herein may, in certain embodiments, be applied to or used in connection with any one or more of the embodiments, features, systems, devices, materials, methods and techniques disclosed in the above-mentioned of application Ser. No. 12/463,304 filed on May 8, 2009; U.S. Provisional Patent Application No. 61/255,367 filed Oct. 27, 2009; and U.S. Provisional Patent Application No. 61/260,348 filed Nov. 11, 2009.
In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.
This application is a continuation of application Ser. No. 12/913,702 filed Oct. 27, 2010, which claims the benefit of U.S. Provisional Application No. 61/255,367 filed Oct. 27, 2009 and U.S. Provisional Application No. 61/260,348 filed Nov. 11, 2009 each of which is herein fully incorporated by reference in its entirety.
| Number | Name | Date | Kind |
|---|---|---|---|
| 612724 | Hamilton | Oct 1898 | A |
| 1155169 | Starkweather | Sep 1915 | A |
| 1207479 | Bisgaard | Dec 1916 | A |
| 1216183 | Swingle | Feb 1917 | A |
| 1695107 | Kahl | Dec 1928 | A |
| 2072346 | Smith | Mar 1937 | A |
| 2279714 | Meyerhof et al. | Apr 1942 | A |
| 3320957 | Sokolik | May 1967 | A |
| 3568659 | Karnegis | Mar 1971 | A |
| 3667476 | Muller | Jun 1972 | A |
| 3692029 | Adair | Sep 1972 | A |
| 3918449 | Pistor | Nov 1975 | A |
| 3946745 | Hsiang-Lai et al. | Mar 1976 | A |
| 3949743 | Shanbrom | Apr 1976 | A |
| 3995617 | Watkins et al. | Dec 1976 | A |
| 4078864 | Howell | Mar 1978 | A |
| 4095602 | Leveen | Jun 1978 | A |
| 4116589 | Rishton | Sep 1978 | A |
| 4129129 | Amrine | Dec 1978 | A |
| 4154246 | Leveen | May 1979 | A |
| 4277168 | Oku | Jul 1981 | A |
| 4305402 | Katims | Dec 1981 | A |
| 4351330 | Scarberry | Sep 1982 | A |
| 4461283 | Doi | Jul 1984 | A |
| 4502490 | Evans et al. | Mar 1985 | A |
| 4503855 | Maslanka | Mar 1985 | A |
| 4503863 | Katims | Mar 1985 | A |
| 4512762 | Spears | Apr 1985 | A |
| 4522212 | Gelinas | Jun 1985 | A |
| 4557272 | Carr | Dec 1985 | A |
| 4565200 | Cosman | Jan 1986 | A |
| 4567882 | Heller | Feb 1986 | A |
| 4573481 | Bullara | Mar 1986 | A |
| 4584998 | McGrail | Apr 1986 | A |
| 4612934 | Borkan | Sep 1986 | A |
| 4621642 | Chen | Nov 1986 | A |
| 4621882 | Krumme | Nov 1986 | A |
| 4625712 | Wampler | Dec 1986 | A |
| 4643186 | Rosen et al. | Feb 1987 | A |
| 4646737 | Hussein et al. | Mar 1987 | A |
| 4649924 | Taccardi | Mar 1987 | A |
| 4649935 | Charmillot et al. | Mar 1987 | A |
| 4658836 | Turner | Apr 1987 | A |
| 4674497 | Ogasawara | Jun 1987 | A |
| 4683890 | Hewson | Aug 1987 | A |
| 4704121 | Moise | Nov 1987 | A |
| 4706688 | Don Michael et al. | Nov 1987 | A |
| 4709698 | Johnston et al. | Dec 1987 | A |
| 4739759 | Rexroth et al. | Apr 1988 | A |
| 4754065 | Levenson et al. | Jun 1988 | A |
| 4754752 | Ginsburg et al. | Jul 1988 | A |
| 4765322 | Charmillot et al. | Aug 1988 | A |
| 4765959 | Fukasawa | Aug 1988 | A |
| 4767402 | Kost et al. | Aug 1988 | A |
| 4772112 | Zider et al. | Sep 1988 | A |
| 4773899 | Spears | Sep 1988 | A |
| 4779614 | Moise | Oct 1988 | A |
| 4784135 | Blum et al. | Nov 1988 | A |
| 4790305 | Zoltan et al. | Dec 1988 | A |
| 4799479 | Spears | Jan 1989 | A |
| 4802492 | Grunstein | Feb 1989 | A |
| 4808164 | Hess | Feb 1989 | A |
| 4817586 | Wampler | Apr 1989 | A |
| 4825871 | Cansell | May 1989 | A |
| 4827935 | Geddes et al. | May 1989 | A |
| 4846152 | Wampler et al. | Jul 1989 | A |
| 4862886 | Clarke et al. | Sep 1989 | A |
| 4881542 | Schmidt et al. | Nov 1989 | A |
| 4895557 | Moise et al. | Jan 1990 | A |
| 4902129 | Siegmund et al. | Feb 1990 | A |
| 4904472 | Belardinelli et al. | Feb 1990 | A |
| 4906229 | Wampler | Mar 1990 | A |
| 4907589 | Cosman | Mar 1990 | A |
| 4908012 | Moise et al. | Mar 1990 | A |
| 4920978 | Colvin | May 1990 | A |
| 4944722 | Carriker et al. | Jul 1990 | A |
| 4945910 | Budyko et al. | Aug 1990 | A |
| 4955377 | Lennox et al. | Sep 1990 | A |
| 4967765 | Turner et al. | Nov 1990 | A |
| 4969865 | Hwang et al. | Nov 1990 | A |
| 4976709 | Sand | Dec 1990 | A |
| 4985014 | Orejola | Jan 1991 | A |
| 4989604 | Fang | Feb 1991 | A |
| 4991603 | Cohen et al. | Feb 1991 | A |
| 4992474 | Skidmore et al. | Feb 1991 | A |
| 5005559 | Blanco et al. | Apr 1991 | A |
| 5007908 | Rydell | Apr 1991 | A |
| 5009636 | Wortley et al. | Apr 1991 | A |
| 5009936 | Yamanaka et al. | Apr 1991 | A |
| 5010892 | Colvin et al. | Apr 1991 | A |
| 5019075 | Spears et al. | May 1991 | A |
| 5027829 | Larsen | Jul 1991 | A |
| 5030645 | Kollonitsch | Jul 1991 | A |
| 5036848 | Hewson | Aug 1991 | A |
| 5053033 | Clarke | Oct 1991 | A |
| 5054486 | Yamada | Oct 1991 | A |
| 5056519 | Vince | Oct 1991 | A |
| 5056529 | de Groot | Oct 1991 | A |
| 5057107 | Parins et al. | Oct 1991 | A |
| 5074860 | Gregory et al. | Dec 1991 | A |
| 5078716 | Doll | Jan 1992 | A |
| 5084044 | Quint | Jan 1992 | A |
| 5096916 | Skupin | Mar 1992 | A |
| 5100388 | Behl et al. | Mar 1992 | A |
| 5100423 | Fearnot | Mar 1992 | A |
| 5103804 | Abele et al. | Apr 1992 | A |
| 5105826 | Smits et al. | Apr 1992 | A |
| 5106360 | Ishiwara et al. | Apr 1992 | A |
| 5107830 | Younes | Apr 1992 | A |
| 5107835 | Thomas | Apr 1992 | A |
| 5109846 | Thomas | May 1992 | A |
| 5114423 | Kasprzyk et al. | May 1992 | A |
| 5116864 | March et al. | May 1992 | A |
| 5117828 | Metzger et al. | Jun 1992 | A |
| 5123413 | Hasegawa et al. | Jun 1992 | A |
| 5126375 | Skidmore et al. | Jun 1992 | A |
| 5135480 | Bannon et al. | Aug 1992 | A |
| 5135517 | McCoy | Aug 1992 | A |
| 5139029 | Fishman et al. | Aug 1992 | A |
| 5151100 | Abele et al. | Sep 1992 | A |
| 5152286 | Sitko et al. | Oct 1992 | A |
| 5165420 | Strickland | Nov 1992 | A |
| 5167223 | Koros et al. | Dec 1992 | A |
| 5170802 | Mehra | Dec 1992 | A |
| 5170803 | Hewson et al. | Dec 1992 | A |
| 5174288 | Bardy et al. | Dec 1992 | A |
| 5188602 | Nichols | Feb 1993 | A |
| 5190540 | Lee | Mar 1993 | A |
| 5191883 | Lennox et al. | Mar 1993 | A |
| 5213576 | Abiuso et al. | May 1993 | A |
| 5215103 | Desai | Jun 1993 | A |
| 5224491 | Mehra | Jul 1993 | A |
| 5225445 | Skidmore et al. | Jul 1993 | A |
| 5231996 | Bardy et al. | Aug 1993 | A |
| 5232444 | Rust et al. | Aug 1993 | A |
| 5234456 | Silvestrini | Aug 1993 | A |
| 5239982 | Trauthen | Aug 1993 | A |
| 5254088 | Lundquist | Oct 1993 | A |
| 5255678 | Deslauriers et al. | Oct 1993 | A |
| 5255679 | Imran | Oct 1993 | A |
| 5265604 | Vince | Nov 1993 | A |
| 5269758 | Taheri | Dec 1993 | A |
| 5281218 | Imran | Jan 1994 | A |
| 5286254 | Shapland et al. | Feb 1994 | A |
| 5292331 | Boneau | Mar 1994 | A |
| 5293869 | Edwards et al. | Mar 1994 | A |
| 5309910 | Edwards et al. | May 1994 | A |
| 5311866 | Kagan et al. | May 1994 | A |
| 5313943 | Houser et al. | May 1994 | A |
| 5324255 | Passafaro et al. | Jun 1994 | A |
| 5324284 | Imran | Jun 1994 | A |
| 5343936 | Beatenbough et al. | Sep 1994 | A |
| 5344398 | Hara | Sep 1994 | A |
| 5345936 | Pomeranz et al. | Sep 1994 | A |
| 5348554 | Imran et al. | Sep 1994 | A |
| 5366443 | Eggers et al. | Nov 1994 | A |
| 5368591 | Lennox et al. | Nov 1994 | A |
| 5370644 | Langberg | Dec 1994 | A |
| 5370675 | Edwards et al. | Dec 1994 | A |
| 5370679 | Atlee, III | Dec 1994 | A |
| 5372603 | Acker et al. | Dec 1994 | A |
| 5374287 | Rubin | Dec 1994 | A |
| 5379765 | Kajiwara et al. | Jan 1995 | A |
| 5383917 | Desai et al. | Jan 1995 | A |
| 5393207 | Maher et al. | Feb 1995 | A |
| 5394880 | Atlee, III | Mar 1995 | A |
| 5396887 | Imran | Mar 1995 | A |
| 5400778 | Jonson et al. | Mar 1995 | A |
| 5400783 | Pomeranz et al. | Mar 1995 | A |
| 5405362 | Kramer et al. | Apr 1995 | A |
| 5405366 | Fox et al. | Apr 1995 | A |
| 5411025 | Webster, Jr. | May 1995 | A |
| 5415166 | Imran | May 1995 | A |
| 5415656 | Tihon et al. | May 1995 | A |
| 5417687 | Nardella et al. | May 1995 | A |
| 5422362 | Vincent et al. | Jun 1995 | A |
| 5423744 | Gencheff et al. | Jun 1995 | A |
| 5423811 | Imran et al. | Jun 1995 | A |
| 5425023 | Haraguchi et al. | Jun 1995 | A |
| 5425703 | Feiring | Jun 1995 | A |
| 5425811 | Mashita | Jun 1995 | A |
| 5431696 | Atlee, III | Jul 1995 | A |
| 5433730 | Alt | Jul 1995 | A |
| 5437665 | Munro | Aug 1995 | A |
| 5443470 | Stern et al. | Aug 1995 | A |
| 5454782 | Perkins | Oct 1995 | A |
| 5454840 | Krakovsky et al. | Oct 1995 | A |
| 5456667 | Ham et al. | Oct 1995 | A |
| 5458596 | Lax et al. | Oct 1995 | A |
| 5465717 | Imran et al. | Nov 1995 | A |
| 5470352 | Rappaport | Nov 1995 | A |
| 5471982 | Edwards et al. | Dec 1995 | A |
| 5474530 | Passafaro et al. | Dec 1995 | A |
| 5478309 | Sweezer et al. | Dec 1995 | A |
| 5478578 | Arnold et al. | Dec 1995 | A |
| 5496271 | Burton et al. | Mar 1996 | A |
| 5496304 | Chasan | Mar 1996 | A |
| 5496311 | Abele et al. | Mar 1996 | A |
| 5496312 | Klicek | Mar 1996 | A |
| 5500011 | Desai | Mar 1996 | A |
| 5505728 | Ellman et al. | Apr 1996 | A |
| 5505730 | Edwards | Apr 1996 | A |
| 5507791 | Sitko | Apr 1996 | A |
| 5509419 | Edwards et al. | Apr 1996 | A |
| 5522862 | Testerman et al. | Jun 1996 | A |
| 5531779 | Dahl et al. | Jul 1996 | A |
| 5540681 | Strul et al. | Jul 1996 | A |
| 5540730 | Terry, Jr. et al. | Jul 1996 | A |
| 5545161 | Imran | Aug 1996 | A |
| 5545193 | Fleischman et al. | Aug 1996 | A |
| 5547469 | Rowland et al. | Aug 1996 | A |
| 5549559 | Eshel | Aug 1996 | A |
| 5549655 | Erickson | Aug 1996 | A |
| 5549661 | Kordis et al. | Aug 1996 | A |
| RE35330 | Malone et al. | Sep 1996 | E |
| 5553611 | Budd et al. | Sep 1996 | A |
| 5558073 | Pomeranz et al. | Sep 1996 | A |
| 5562608 | Sekins et al. | Oct 1996 | A |
| 5571074 | Buckman, Jr. et al. | Nov 1996 | A |
| 5571088 | Lennox et al. | Nov 1996 | A |
| 5574059 | Regunathan et al. | Nov 1996 | A |
| 5578072 | Barone et al. | Nov 1996 | A |
| 5582609 | Swanson et al. | Dec 1996 | A |
| 5588432 | Crowley | Dec 1996 | A |
| 5588812 | Taylor et al. | Dec 1996 | A |
| 5595183 | Swanson et al. | Jan 1997 | A |
| 5598848 | Swanson et al. | Feb 1997 | A |
| 5599345 | Edwards et al. | Feb 1997 | A |
| 5601088 | Swanson et al. | Feb 1997 | A |
| 5605157 | Panescu et al. | Feb 1997 | A |
| 5607419 | Amplatz et al. | Mar 1997 | A |
| 5607462 | Imran | Mar 1997 | A |
| 5620438 | Amplatz et al. | Apr 1997 | A |
| 5620463 | Drolet | Apr 1997 | A |
| 5623940 | Daikuzono | Apr 1997 | A |
| 5624392 | Saab | Apr 1997 | A |
| 5624439 | Edwards et al. | Apr 1997 | A |
| 5626618 | Ward et al. | May 1997 | A |
| 5630425 | Panescu et al. | May 1997 | A |
| 5630794 | Lax et al. | May 1997 | A |
| 5630813 | Kieturakis | May 1997 | A |
| 5634471 | Fairfax et al. | Jun 1997 | A |
| 5641326 | Adams | Jun 1997 | A |
| 5647870 | Kordis et al. | Jul 1997 | A |
| 5658278 | Imran et al. | Aug 1997 | A |
| 5658322 | Fleming | Aug 1997 | A |
| 5658549 | Akehurst et al. | Aug 1997 | A |
| 5660175 | Dayal | Aug 1997 | A |
| 5662108 | Budd et al. | Sep 1997 | A |
| 5669930 | Igarashi | Sep 1997 | A |
| 5669932 | Fischell et al. | Sep 1997 | A |
| 5674472 | Akehurst et al. | Oct 1997 | A |
| 5678535 | DiMarco | Oct 1997 | A |
| 5680860 | Imran | Oct 1997 | A |
| 5681280 | Rusk et al. | Oct 1997 | A |
| 5681308 | Edwards et al. | Oct 1997 | A |
| 5687723 | Avitall | Nov 1997 | A |
| 5688267 | Panescu et al. | Nov 1997 | A |
| 5690692 | Fleming | Nov 1997 | A |
| 5693078 | Desaj et al. | Dec 1997 | A |
| 5694934 | Edelman | Dec 1997 | A |
| 5695471 | Wampler | Dec 1997 | A |
| 5699799 | Xu et al. | Dec 1997 | A |
| 5702386 | Stern et al. | Dec 1997 | A |
| 5707218 | Maher et al. | Jan 1998 | A |
| 5707336 | Rubin | Jan 1998 | A |
| 5707352 | Sekins et al. | Jan 1998 | A |
| 5707400 | Terry, Jr. et al. | Jan 1998 | A |
| 5722401 | Pietroski et al. | Mar 1998 | A |
| 5722403 | McGee et al. | Mar 1998 | A |
| 5722416 | Swanson et al. | Mar 1998 | A |
| 5725525 | Kordis | Mar 1998 | A |
| 5727569 | Benetti et al. | Mar 1998 | A |
| 5728094 | Edwards | Mar 1998 | A |
| 5730128 | Pomeranz et al. | Mar 1998 | A |
| 5730704 | Avitall | Mar 1998 | A |
| 5730726 | Klingenstein | Mar 1998 | A |
| 5730741 | Horzewski et al. | Mar 1998 | A |
| 5733319 | Neilson et al. | Mar 1998 | A |
| 5735846 | Panescu et al. | Apr 1998 | A |
| 5740808 | Panescu et al. | Apr 1998 | A |
| 5741248 | Stern et al. | Apr 1998 | A |
| 5746224 | Edwards | May 1998 | A |
| 5752518 | McGee et al. | May 1998 | A |
| 5755714 | Murphy-Chutorian | May 1998 | A |
| 5755753 | Knowlton | May 1998 | A |
| 5759158 | Swanson | Jun 1998 | A |
| 5765568 | Sweezer, Jr. et al. | Jun 1998 | A |
| 5766605 | Sanders et al. | Jun 1998 | A |
| 5769846 | Edwards et al. | Jun 1998 | A |
| 5772590 | Webster, Jr. | Jun 1998 | A |
| 5779669 | Haissaguerre et al. | Jul 1998 | A |
| 5779698 | Clayman et al. | Jul 1998 | A |
| 5782239 | Webster, Jr. | Jul 1998 | A |
| 5782797 | Schweich, Jr. et al. | Jul 1998 | A |
| 5782827 | Gough et al. | Jul 1998 | A |
| 5782848 | Lennox | Jul 1998 | A |
| 5782899 | Imran | Jul 1998 | A |
| 5792064 | Panescu et al. | Aug 1998 | A |
| 5795303 | Swanson et al. | Aug 1998 | A |
| 5800375 | Sweezer et al. | Sep 1998 | A |
| 5800486 | Thome et al. | Sep 1998 | A |
| 5807306 | Shapland et al. | Sep 1998 | A |
| 5810757 | Sweezer, Jr. et al. | Sep 1998 | A |
| 5810807 | Ganz et al. | Sep 1998 | A |
| 5814078 | Zhou et al. | Sep 1998 | A |
| 5817028 | Anderson | Oct 1998 | A |
| 5817073 | Krespi | Oct 1998 | A |
| 5820554 | Davis et al. | Oct 1998 | A |
| 5820589 | Torgerson et al. | Oct 1998 | A |
| 5823189 | Kordis | Oct 1998 | A |
| 5827277 | Edwards | Oct 1998 | A |
| 5833651 | Donovan et al. | Nov 1998 | A |
| 5836874 | Swanson et al. | Nov 1998 | A |
| 5836905 | Lemelson et al. | Nov 1998 | A |
| 5836947 | Fleischman et al. | Nov 1998 | A |
| 5837001 | Mackey | Nov 1998 | A |
| 5843075 | Taylor | Dec 1998 | A |
| 5843077 | Edwards | Dec 1998 | A |
| 5843088 | Barra et al. | Dec 1998 | A |
| 5846238 | Jackson et al. | Dec 1998 | A |
| 5848969 | Panescu et al. | Dec 1998 | A |
| 5848972 | Triedman et al. | Dec 1998 | A |
| 5849026 | Zhou et al. | Dec 1998 | A |
| 5855577 | Murphy-Chutorian et al. | Jan 1999 | A |
| 5860974 | Abele | Jan 1999 | A |
| 5863291 | Schaer | Jan 1999 | A |
| 5865791 | Whayne et al. | Feb 1999 | A |
| 5868740 | Leveen et al. | Feb 1999 | A |
| 5871443 | Edwards et al. | Feb 1999 | A |
| 5871483 | Jackson et al. | Feb 1999 | A |
| 5871523 | Fleischman et al. | Feb 1999 | A |
| 5873852 | Vigil et al. | Feb 1999 | A |
| 5873865 | Horzewski et al. | Feb 1999 | A |
| 5876340 | Tu et al. | Mar 1999 | A |
| 5876399 | Chia et al. | Mar 1999 | A |
| 5881727 | Edwards | Mar 1999 | A |
| 5882346 | Pomeranz et al. | Mar 1999 | A |
| 5891027 | Tu et al. | Apr 1999 | A |
| 5891135 | Jackson et al. | Apr 1999 | A |
| 5891136 | McGee et al. | Apr 1999 | A |
| 5891138 | Tu et al. | Apr 1999 | A |
| 5891182 | Fleming | Apr 1999 | A |
| 5893847 | Kordis | Apr 1999 | A |
| 5893887 | Jayaraman | Apr 1999 | A |
| 5897554 | Chia et al. | Apr 1999 | A |
| 5899882 | Waksman et al. | May 1999 | A |
| 5902268 | Saab | May 1999 | A |
| 5904651 | Swanson et al. | May 1999 | A |
| 5904711 | Flom et al. | May 1999 | A |
| 5906636 | Casscells, III et al. | May 1999 | A |
| 5908445 | Whayne et al. | Jun 1999 | A |
| 5908446 | Imran | Jun 1999 | A |
| 5908839 | Levitt et al. | Jun 1999 | A |
| 5911218 | DiMarco | Jun 1999 | A |
| 5916235 | Guglielmi | Jun 1999 | A |
| 5919147 | Jain | Jul 1999 | A |
| 5919172 | Golba, Jr. | Jul 1999 | A |
| 5924424 | Stevens et al. | Jul 1999 | A |
| 5928228 | Kordis et al. | Jul 1999 | A |
| 5931806 | Shimada | Aug 1999 | A |
| 5931835 | Mackey | Aug 1999 | A |
| 5935079 | Swanson et al. | Aug 1999 | A |
| 5941869 | Patterson et al. | Aug 1999 | A |
| 5951494 | Wang et al. | Sep 1999 | A |
| 5951546 | Lorentzen | Sep 1999 | A |
| 5954661 | Greenspon et al. | Sep 1999 | A |
| 5954662 | Swanson et al. | Sep 1999 | A |
| 5954717 | Behl et al. | Sep 1999 | A |
| 5956501 | Brown | Sep 1999 | A |
| 5957919 | Laufer | Sep 1999 | A |
| 5957961 | Maguire et al. | Sep 1999 | A |
| 5964223 | Baran | Oct 1999 | A |
| 5964753 | Edwards | Oct 1999 | A |
| 5964796 | Imran | Oct 1999 | A |
| 5971983 | Lesh | Oct 1999 | A |
| 5972026 | Laufer et al. | Oct 1999 | A |
| 5976175 | Hirano et al. | Nov 1999 | A |
| 5976709 | Kageyama et al. | Nov 1999 | A |
| 5979456 | Magovern | Nov 1999 | A |
| 5980563 | Tu et al. | Nov 1999 | A |
| 5984917 | Fleischman et al. | Nov 1999 | A |
| 5984971 | Faccioli et al. | Nov 1999 | A |
| 5989545 | Foster et al. | Nov 1999 | A |
| 5991650 | Swanson et al. | Nov 1999 | A |
| 5992419 | Sterzer et al. | Nov 1999 | A |
| 5993462 | Pomeranz et al. | Nov 1999 | A |
| 5995873 | Rhodes | Nov 1999 | A |
| 5997534 | Tu et al. | Dec 1999 | A |
| 5999855 | DiMarco | Dec 1999 | A |
| 6001054 | Regulla et al. | Dec 1999 | A |
| 6003517 | Sheffield et al. | Dec 1999 | A |
| 6004269 | Crowley et al. | Dec 1999 | A |
| 6006134 | Hill et al. | Dec 1999 | A |
| 6006755 | Edwards | Dec 1999 | A |
| 6008211 | Robinson et al. | Dec 1999 | A |
| 6009877 | Edwards | Jan 2000 | A |
| 6010500 | Sherman et al. | Jan 2000 | A |
| 6014579 | Pomeranz et al. | Jan 2000 | A |
| 6016437 | Tu et al. | Jan 2000 | A |
| 6023638 | Swanson | Feb 2000 | A |
| 6024740 | Lesh et al. | Feb 2000 | A |
| 6029091 | De La Rama et al. | Feb 2000 | A |
| 6033397 | Laufer et al. | Mar 2000 | A |
| 6036687 | Laufer et al. | Mar 2000 | A |
| 6036689 | Tu et al. | Mar 2000 | A |
| 6039731 | Taylor et al. | Mar 2000 | A |
| 6043273 | Duhaylongsod | Mar 2000 | A |
| 6045549 | Smethers et al. | Apr 2000 | A |
| 6045550 | Simpson et al. | Apr 2000 | A |
| 6050992 | Nichols | Apr 2000 | A |
| 6052607 | Edwards et al. | Apr 2000 | A |
| 6053172 | Hovda et al. | Apr 2000 | A |
| 6053909 | Shadduck | Apr 2000 | A |
| 6056744 | Edwards | May 2000 | A |
| 6056745 | Panescu et al. | May 2000 | A |
| 6056769 | Epstein et al. | May 2000 | A |
| 6060454 | Duhaylongsod | May 2000 | A |
| 6063078 | Wittkampf | May 2000 | A |
| 6063768 | First | May 2000 | A |
| 6071280 | Edwards et al. | Jun 2000 | A |
| 6071281 | Burnside et al. | Jun 2000 | A |
| 6071282 | Fleischman | Jun 2000 | A |
| 6081749 | Ingle et al. | Jun 2000 | A |
| 6083249 | Familoni | Jul 2000 | A |
| 6083255 | Laufer et al. | Jul 2000 | A |
| 6087394 | Duhaylongsod | Jul 2000 | A |
| 6090104 | Webster, Jr. | Jul 2000 | A |
| 6091995 | Ingle et al. | Jul 2000 | A |
| 6092528 | Edwards | Jul 2000 | A |
| 6097985 | Kasevich et al. | Aug 2000 | A |
| 6101412 | Duhaylongsod | Aug 2000 | A |
| 6102886 | Lundquist et al. | Aug 2000 | A |
| 6106524 | Eggers et al. | Aug 2000 | A |
| 6117101 | Diedrich et al. | Sep 2000 | A |
| 6123702 | Swanson et al. | Sep 2000 | A |
| 6123703 | Tu et al. | Sep 2000 | A |
| 6123718 | Tu et al. | Sep 2000 | A |
| 6125301 | Capel | Sep 2000 | A |
| 6127410 | Duhaylongsod | Oct 2000 | A |
| 6129726 | Edwards et al. | Oct 2000 | A |
| 6135997 | Laufer et al. | Oct 2000 | A |
| 6139527 | Laufer et al. | Oct 2000 | A |
| 6139571 | Fuller et al. | Oct 2000 | A |
| 6139845 | Donovan | Oct 2000 | A |
| 6141589 | Duhaylongsod | Oct 2000 | A |
| 6142993 | Whayne et al. | Nov 2000 | A |
| 6143013 | Samson et al. | Nov 2000 | A |
| 6143277 | Ashurst et al. | Nov 2000 | A |
| 6149647 | Tu et al. | Nov 2000 | A |
| 6152143 | Edwards | Nov 2000 | A |
| 6152899 | Farley et al. | Nov 2000 | A |
| 6152953 | Hipskind | Nov 2000 | A |
| 6159194 | Eggers et al. | Dec 2000 | A |
| 6163716 | Edwards et al. | Dec 2000 | A |
| 6174323 | Biggs et al. | Jan 2001 | B1 |
| 6179833 | Taylor | Jan 2001 | B1 |
| 6183468 | Swanson et al. | Feb 2001 | B1 |
| 6197013 | Reed et al. | Mar 2001 | B1 |
| 6198970 | Freed et al. | Mar 2001 | B1 |
| 6200311 | Danek et al. | Mar 2001 | B1 |
| 6200332 | Del Giglio | Mar 2001 | B1 |
| 6200333 | Laufer | Mar 2001 | B1 |
| 6203562 | Ohkubo | Mar 2001 | B1 |
| 6210367 | Carr | Apr 2001 | B1 |
| 6212432 | Matsuura | Apr 2001 | B1 |
| 6212433 | Behl | Apr 2001 | B1 |
| 6214002 | Fleischman et al. | Apr 2001 | B1 |
| 6216043 | Swanson et al. | Apr 2001 | B1 |
| 6216044 | Kordis | Apr 2001 | B1 |
| 6216704 | Ingle et al. | Apr 2001 | B1 |
| 6217576 | Tu et al. | Apr 2001 | B1 |
| 6226543 | Gilboa et al. | May 2001 | B1 |
| 6230052 | Wolff et al. | May 2001 | B1 |
| 6231595 | Dobak, III | May 2001 | B1 |
| 6235024 | Tu | May 2001 | B1 |
| 6240307 | Beatty et al. | May 2001 | B1 |
| 6241727 | Tu et al. | Jun 2001 | B1 |
| 6245065 | Panescu et al. | Jun 2001 | B1 |
| 6251368 | Akehurst et al. | Jun 2001 | B1 |
| 6253762 | Britto | Jul 2001 | B1 |
| 6254598 | Edwards et al. | Jul 2001 | B1 |
| 6254599 | Lesh et al. | Jul 2001 | B1 |
| 6258083 | Daniel et al. | Jul 2001 | B1 |
| 6258087 | Edwards et al. | Jul 2001 | B1 |
| 6264653 | Falwell | Jul 2001 | B1 |
| 6265379 | Donovan | Jul 2001 | B1 |
| 6269813 | Fitzgerald et al. | Aug 2001 | B1 |
| 6270476 | Santoianni et al. | Aug 2001 | B1 |
| 6273886 | Edwards et al. | Aug 2001 | B1 |
| 6273907 | Laufer | Aug 2001 | B1 |
| 6283987 | Laird et al. | Sep 2001 | B1 |
| 6283988 | Laufer et al. | Sep 2001 | B1 |
| 6283989 | Laufer et al. | Sep 2001 | B1 |
| 6287304 | Eggers et al. | Sep 2001 | B1 |
| 6296639 | Truckai et al. | Oct 2001 | B1 |
| 6299633 | Laufer | Oct 2001 | B1 |
| 6302870 | Jacobsen et al. | Oct 2001 | B1 |
| 6303509 | Chen et al. | Oct 2001 | B1 |
| 6306423 | Donovan et al. | Oct 2001 | B1 |
| 6315173 | Di Giovanni et al. | Nov 2001 | B1 |
| 6315778 | Gambale et al. | Nov 2001 | B1 |
| 6317615 | KenKnight et al. | Nov 2001 | B1 |
| 6322559 | Daulton | Nov 2001 | B1 |
| 6322584 | Ingle et al. | Nov 2001 | B2 |
| 6325798 | Edwards et al. | Dec 2001 | B1 |
| 6327503 | Familoni | Dec 2001 | B1 |
| 6338727 | Noda et al. | Jan 2002 | B1 |
| 6338836 | Kuth et al. | Jan 2002 | B1 |
| 6341236 | Osorio et al. | Jan 2002 | B1 |
| 6346104 | Daly et al. | Feb 2002 | B2 |
| 6355031 | Edwards et al. | Mar 2002 | B1 |
| 6356786 | Rezai et al. | Mar 2002 | B1 |
| 6356787 | Rezai et al. | Mar 2002 | B1 |
| 6357447 | Swanson et al. | Mar 2002 | B1 |
| 6358245 | Edwards et al. | Mar 2002 | B1 |
| 6358926 | Donovan | Mar 2002 | B2 |
| 6361554 | Brisken | Mar 2002 | B1 |
| 6363937 | Hovda et al. | Apr 2002 | B1 |
| 6366814 | Boveja et al. | Apr 2002 | B1 |
| 6379352 | Reynolds et al. | Apr 2002 | B1 |
| 6383509 | Donovan et al. | May 2002 | B1 |
| 6394956 | Chandrasckaran et al. | May 2002 | B1 |
| 6402744 | Edwards et al. | Jun 2002 | B2 |
| 6405732 | Edwards et al. | Jun 2002 | B1 |
| 6409723 | Edwards | Jun 2002 | B1 |
| 6411852 | Danek et al. | Jun 2002 | B1 |
| 6414018 | Duhaylongsod | Jul 2002 | B1 |
| 6416511 | Lesh et al. | Jul 2002 | B1 |
| 6416740 | Linger | Jul 2002 | B1 |
| 6423058 | Edwards et al. | Jul 2002 | B1 |
| 6423105 | Iijima et al. | Jul 2002 | B1 |
| 6424864 | Matsuura | Jul 2002 | B1 |
| 6425877 | Edwards | Jul 2002 | B1 |
| 6425887 | McGuckin et al. | Jul 2002 | B1 |
| 6425895 | Swanson et al. | Jul 2002 | B1 |
| 6432092 | Miller | Aug 2002 | B2 |
| 6436130 | Philips et al. | Aug 2002 | B1 |
| 6438423 | Rezai et al. | Aug 2002 | B1 |
| 6440128 | Edwards et al. | Aug 2002 | B1 |
| 6440129 | Simpson | Aug 2002 | B1 |
| 6442435 | King et al. | Aug 2002 | B2 |
| 6447505 | McGovern et al. | Sep 2002 | B2 |
| 6447785 | Donovan | Sep 2002 | B1 |
| 6448231 | Graham | Sep 2002 | B2 |
| 6458121 | Rosenstock et al. | Oct 2002 | B1 |
| 6460545 | Kordis | Oct 2002 | B2 |
| 6464680 | Brisken et al. | Oct 2002 | B1 |
| 6464697 | Edwards et al. | Oct 2002 | B1 |
| 6475160 | Sher | Nov 2002 | B1 |
| 6480746 | Ingle et al. | Nov 2002 | B1 |
| 6485416 | Platt et al. | Nov 2002 | B1 |
| 6488673 | Laufer et al. | Dec 2002 | B1 |
| 6488679 | Swanson | Dec 2002 | B1 |
| 6491710 | Satake | Dec 2002 | B2 |
| 6493589 | Medhkour et al. | Dec 2002 | B1 |
| 6494880 | Swanson et al. | Dec 2002 | B1 |
| 6496737 | Rudie et al. | Dec 2002 | B2 |
| 6496738 | Carr | Dec 2002 | B2 |
| 6506399 | Donovan | Jan 2003 | B2 |
| 6510969 | Di Giovanni et al. | Jan 2003 | B2 |
| 6514246 | Swanson et al. | Feb 2003 | B1 |
| 6514290 | Loomas | Feb 2003 | B1 |
| 6519488 | KenKnight et al. | Feb 2003 | B2 |
| 6522913 | Swanson et al. | Feb 2003 | B2 |
| 6524555 | Ashurst et al. | Feb 2003 | B1 |
| 6526320 | Mitchell | Feb 2003 | B2 |
| 6526976 | Baran | Mar 2003 | B1 |
| 6529756 | Phan et al. | Mar 2003 | B1 |
| 6532388 | Hill et al. | Mar 2003 | B1 |
| 6533780 | Laird et al. | Mar 2003 | B1 |
| 6536427 | Davies et al. | Mar 2003 | B2 |
| 6544226 | Gaiser et al. | Apr 2003 | B1 |
| 6544262 | Fleischman | Apr 2003 | B2 |
| 6546928 | Ashurst et al. | Apr 2003 | B1 |
| 6546932 | Nahon et al. | Apr 2003 | B1 |
| 6546934 | Ingle et al. | Apr 2003 | B1 |
| 6547776 | Gaiser et al. | Apr 2003 | B1 |
| 6547788 | Maguire et al. | Apr 2003 | B1 |
| 6549808 | Gisel et al. | Apr 2003 | B1 |
| 6551274 | Heiner | Apr 2003 | B2 |
| 6551310 | Ganz et al. | Apr 2003 | B1 |
| 6558333 | Gilboa et al. | May 2003 | B2 |
| 6558378 | Sherman et al. | May 2003 | B2 |
| 6558381 | Ingle et al. | May 2003 | B2 |
| 6562034 | Edwards et al. | May 2003 | B2 |
| 6572612 | Stewart et al. | Jun 2003 | B2 |
| 6575623 | Werneth | Jun 2003 | B2 |
| 6575969 | Rittman, III et al. | Jun 2003 | B1 |
| 6582427 | Goble et al. | Jun 2003 | B1 |
| 6582430 | Hall | Jun 2003 | B2 |
| 6587718 | Talpade | Jul 2003 | B2 |
| 6587719 | Barrett et al. | Jul 2003 | B1 |
| 6587731 | Ingle et al. | Jul 2003 | B1 |
| 6589235 | Wong et al. | Jul 2003 | B2 |
| 6589238 | Edwards et al. | Jul 2003 | B2 |
| 6593130 | Sen et al. | Jul 2003 | B1 |
| 6599311 | Biggs et al. | Jul 2003 | B1 |
| 6601581 | Babaev | Aug 2003 | B1 |
| 6603996 | Beatty et al. | Aug 2003 | B1 |
| 6610054 | Edwards et al. | Aug 2003 | B1 |
| 6610083 | Keller et al. | Aug 2003 | B2 |
| 6610713 | Tracey | Aug 2003 | B2 |
| 6613002 | Clark et al. | Sep 2003 | B1 |
| 6613045 | Laufer et al. | Sep 2003 | B1 |
| 6620159 | Hegde | Sep 2003 | B2 |
| 6620415 | Donovan | Sep 2003 | B2 |
| 6622047 | Barrett et al. | Sep 2003 | B2 |
| 6623742 | Voet | Sep 2003 | B2 |
| 6626855 | Weng et al. | Sep 2003 | B1 |
| 6626903 | McGuckin, Jr. et al. | Sep 2003 | B2 |
| 6629535 | Ingle et al. | Oct 2003 | B2 |
| 6629951 | Laufer et al. | Oct 2003 | B2 |
| 6632440 | Quinn et al. | Oct 2003 | B1 |
| 6633779 | Schuler et al. | Oct 2003 | B1 |
| 6634363 | Danek et al. | Oct 2003 | B1 |
| 6635054 | Fjield et al. | Oct 2003 | B2 |
| 6635056 | Kadhiresan et al. | Oct 2003 | B2 |
| 6638273 | Farley et al. | Oct 2003 | B1 |
| 6640119 | Budd et al. | Oct 2003 | B1 |
| 6640120 | Swanson et al. | Oct 2003 | B1 |
| 6645200 | Koblish et al. | Nov 2003 | B1 |
| 6645496 | Aoki et al. | Nov 2003 | B2 |
| 6647617 | Beatty et al. | Nov 2003 | B1 |
| 6648881 | KenKnight et al. | Nov 2003 | B2 |
| 6649161 | Donovan | Nov 2003 | B1 |
| 6652517 | Hall et al. | Nov 2003 | B1 |
| 6652548 | Evans et al. | Nov 2003 | B2 |
| 6656960 | Puskas | Dec 2003 | B2 |
| 6658279 | Swanson et al. | Dec 2003 | B2 |
| 6663622 | Foley et al. | Dec 2003 | B1 |
| 6666858 | Lafontaine | Dec 2003 | B2 |
| 6669693 | Friedman | Dec 2003 | B2 |
| 6673068 | Berube | Jan 2004 | B1 |
| 6673070 | Edwards et al. | Jan 2004 | B2 |
| 6675047 | Konoplev et al. | Jan 2004 | B1 |
| 6676686 | Naganuma | Jan 2004 | B2 |
| 6681136 | Schuler et al. | Jan 2004 | B2 |
| 6692492 | Simpson et al. | Feb 2004 | B2 |
| 6692494 | Cooper et al. | Feb 2004 | B1 |
| 6699180 | Kobayashi | Mar 2004 | B2 |
| 6699243 | West et al. | Mar 2004 | B2 |
| 6708064 | Rezai | Mar 2004 | B2 |
| 6711436 | Duhaylongsod | Mar 2004 | B1 |
| 6712074 | Edwards et al. | Mar 2004 | B2 |
| 6712812 | Roschak et al. | Mar 2004 | B2 |
| 6712814 | Edwards et al. | Mar 2004 | B2 |
| 6714822 | King et al. | Mar 2004 | B2 |
| 6719685 | Fujikura et al. | Apr 2004 | B2 |
| 6719694 | Weng et al. | Apr 2004 | B2 |
| 6723053 | Ackerman et al. | Apr 2004 | B2 |
| 6723091 | Goble et al. | Apr 2004 | B2 |
| 6728562 | Budd et al. | Apr 2004 | B1 |
| 6735471 | Hill et al. | May 2004 | B2 |
| 6735475 | Whitehurst et al. | May 2004 | B1 |
| 6740321 | Donovan | May 2004 | B1 |
| 6743197 | Edwards | Jun 2004 | B1 |
| 6743413 | Schultz et al. | Jun 2004 | B1 |
| 6749604 | Eggers et al. | Jun 2004 | B1 |
| 6749606 | Keast et al. | Jun 2004 | B2 |
| 6752765 | Jensen et al. | Jun 2004 | B1 |
| 6755026 | Wallach | Jun 2004 | B2 |
| 6755849 | Gowda et al. | Jun 2004 | B1 |
| 6767347 | Sharkey et al. | Jul 2004 | B2 |
| 6767544 | Brooks et al. | Jul 2004 | B2 |
| 6770070 | Balbierz | Aug 2004 | B1 |
| 6772013 | Ingle et al. | Aug 2004 | B1 |
| 6773711 | Voet et al. | Aug 2004 | B2 |
| 6776991 | Naumann | Aug 2004 | B2 |
| 6777423 | Banholzer et al. | Aug 2004 | B2 |
| 6778854 | Puskas | Aug 2004 | B2 |
| 6780183 | Jimenez et al. | Aug 2004 | B2 |
| 6786889 | Musbach et al. | Sep 2004 | B1 |
| 6802843 | Truckai et al. | Oct 2004 | B2 |
| 6805131 | Kordis | Oct 2004 | B2 |
| 6819956 | DiLorenzo | Nov 2004 | B2 |
| 6826420 | Beatty et al. | Nov 2004 | B1 |
| 6826421 | Beatty et al. | Nov 2004 | B1 |
| 6827931 | Donovan | Dec 2004 | B1 |
| 6836688 | Ingle et al. | Dec 2004 | B2 |
| 6837888 | Ciarrocca et al. | Jan 2005 | B2 |
| 6838429 | Paslin | Jan 2005 | B2 |
| 6838434 | Voet | Jan 2005 | B2 |
| 6838471 | Tracey | Jan 2005 | B2 |
| 6840243 | Deem et al. | Jan 2005 | B2 |
| 6841156 | Aoki et al. | Jan 2005 | B2 |
| 6843998 | Steward et al. | Jan 2005 | B1 |
| 6846312 | Edwards et al. | Jan 2005 | B2 |
| 6847849 | Mamo et al. | Jan 2005 | B2 |
| 6849073 | Hoey et al. | Feb 2005 | B2 |
| 6852091 | Edwards et al. | Feb 2005 | B2 |
| 6852110 | Roy et al. | Feb 2005 | B2 |
| 6861058 | Aoki et al. | Mar 2005 | B2 |
| 6866662 | Fuimaono et al. | Mar 2005 | B2 |
| 6871092 | Piccone | Mar 2005 | B2 |
| 6872206 | Edwards et al. | Mar 2005 | B2 |
| 6872397 | Aoki et al. | Mar 2005 | B2 |
| 6878156 | Noda | Apr 2005 | B1 |
| 6881213 | Ryan et al. | Apr 2005 | B2 |
| 6885888 | Rezai | Apr 2005 | B2 |
| 6890347 | Machold et al. | May 2005 | B2 |
| 6893436 | Woodard et al. | May 2005 | B2 |
| 6893438 | Hall et al. | May 2005 | B2 |
| 6893439 | Fleischman | May 2005 | B2 |
| 6895267 | Panescu et al. | May 2005 | B2 |
| 6904303 | Phan et al. | Jun 2005 | B2 |
| 6908462 | Joye et al. | Jun 2005 | B2 |
| 6908928 | Banholzer et al. | Jun 2005 | B2 |
| 6913616 | Hamilton et al. | Jul 2005 | B2 |
| 6917834 | Koblish et al. | Jul 2005 | B2 |
| 6934583 | Weinberg et al. | Aug 2005 | B2 |
| 6937896 | Kroll | Aug 2005 | B1 |
| 6937903 | Schuler et al. | Aug 2005 | B2 |
| 6939309 | Beatty et al. | Sep 2005 | B1 |
| 6939345 | KenKnight et al. | Sep 2005 | B2 |
| 6939346 | Kannenberg et al. | Sep 2005 | B2 |
| 6947785 | Beatty et al. | Sep 2005 | B1 |
| 6954977 | Maguire et al. | Oct 2005 | B2 |
| 6957106 | Schuler et al. | Oct 2005 | B2 |
| 6961622 | Gilbert | Nov 2005 | B2 |
| 6970742 | Mann et al. | Nov 2005 | B2 |
| RE38912 | Walz et al. | Dec 2005 | E |
| 6971395 | Edwards et al. | Dec 2005 | B2 |
| 6974224 | Thomas-Benedict | Dec 2005 | B2 |
| 6974456 | Edwards et al. | Dec 2005 | B2 |
| 6974578 | Aoki et al. | Dec 2005 | B1 |
| 6978168 | Beatty et al. | Dec 2005 | B2 |
| 6978174 | Gelfand et al. | Dec 2005 | B2 |
| 6990370 | Beatty et al. | Jan 2006 | B1 |
| 6994706 | Chomenky et al. | Feb 2006 | B2 |
| 6997189 | Biggs et al. | Feb 2006 | B2 |
| 7004942 | Laird et al. | Feb 2006 | B2 |
| 7022088 | Keast et al. | Apr 2006 | B2 |
| 7022105 | Edwards | Apr 2006 | B1 |
| 7027869 | Danek et al. | Apr 2006 | B2 |
| 7043307 | Zelickson et al. | May 2006 | B1 |
| 7070800 | Bechtold-Peters et al. | Jul 2006 | B2 |
| 7072720 | Puskas | Jul 2006 | B2 |
| 7083614 | Fjield et al. | Aug 2006 | B2 |
| 7101368 | Lafontaine | Sep 2006 | B2 |
| 7101387 | Garabedian et al. | Sep 2006 | B2 |
| 7104987 | Biggs et al. | Sep 2006 | B2 |
| 7104990 | Jenkins et al. | Sep 2006 | B2 |
| 7112198 | Satake | Sep 2006 | B2 |
| 7118568 | Hassett et al. | Oct 2006 | B2 |
| 7122031 | Edwards et al. | Oct 2006 | B2 |
| 7122033 | Wood | Oct 2006 | B2 |
| 7125407 | Edwards et al. | Oct 2006 | B2 |
| 7131445 | Amoah | Nov 2006 | B2 |
| 7142910 | Puskas | Nov 2006 | B2 |
| 7150745 | Stem et al. | Dec 2006 | B2 |
| 7162303 | Levin et al. | Jan 2007 | B2 |
| 7165551 | Edwards et al. | Jan 2007 | B2 |
| 7167757 | Ingle et al. | Jan 2007 | B2 |
| 7175644 | Cooper et al. | Feb 2007 | B2 |
| 7179257 | West et al. | Feb 2007 | B2 |
| 7186251 | Malecki et al. | Mar 2007 | B2 |
| 7187964 | Khoury | Mar 2007 | B2 |
| 7187973 | Hauck | Mar 2007 | B2 |
| 7189208 | Beatty et al. | Mar 2007 | B1 |
| 7198635 | Danek et al. | Apr 2007 | B2 |
| 7200445 | Dalbec et al. | Apr 2007 | B1 |
| 7229469 | Witzel et al. | Jun 2007 | B1 |
| 7238357 | Barron | Jul 2007 | B2 |
| 7241295 | Maguire | Jul 2007 | B2 |
| 7255693 | Johnston et al. | Aug 2007 | B1 |
| RE39820 | Banholzer et al. | Sep 2007 | E |
| 7264002 | Danek et al. | Sep 2007 | B2 |
| 7266414 | Cornelius et al. | Sep 2007 | B2 |
| 7273055 | Danek et al. | Sep 2007 | B2 |
| 7289843 | Beatty et al. | Oct 2007 | B2 |
| 7291146 | Steinke et al. | Nov 2007 | B2 |
| 7292890 | Whitehurst et al. | Nov 2007 | B2 |
| 7309707 | Bender et al. | Dec 2007 | B2 |
| 7310552 | Puskas | Dec 2007 | B2 |
| RE40045 | Palmer | Feb 2008 | E |
| 7326207 | Edwards | Feb 2008 | B2 |
| 7344535 | Stem et al. | Mar 2008 | B2 |
| 7393330 | Keast et al. | Jul 2008 | B2 |
| 7393350 | Maurice | Jul 2008 | B2 |
| 7394976 | Entenman et al. | Jul 2008 | B2 |
| 7402172 | Chin et al. | Jul 2008 | B2 |
| 7422563 | Roschak et al. | Sep 2008 | B2 |
| 7422584 | Loomas et al. | Sep 2008 | B2 |
| 7425212 | Danek et al. | Sep 2008 | B1 |
| 7430449 | Aldrich et al. | Sep 2008 | B2 |
| 7462162 | Phan et al. | Dec 2008 | B2 |
| 7462179 | Edwards et al. | Dec 2008 | B2 |
| 7473273 | Campbell | Jan 2009 | B2 |
| 7477945 | Rezai et al. | Jan 2009 | B2 |
| 7483755 | Ingle et al. | Jan 2009 | B2 |
| 7493160 | Weber et al. | Feb 2009 | B2 |
| 7494661 | Sanders | Feb 2009 | B2 |
| 7507234 | Utley et al. | Mar 2009 | B2 |
| 7507238 | Edwards et al. | Mar 2009 | B2 |
| 7517320 | Wibowo et al. | Apr 2009 | B2 |
| 7530979 | Ganz et al. | May 2009 | B2 |
| 7532938 | Machado et al. | May 2009 | B2 |
| 7542802 | Danek et al. | Jun 2009 | B2 |
| 7553307 | Bleich et al. | Jun 2009 | B2 |
| 7556624 | Laufer et al. | Jul 2009 | B2 |
| 7559890 | Wallace et al. | Jul 2009 | B2 |
| 7572245 | Herweck et al. | Aug 2009 | B2 |
| 7585296 | Edwards et al. | Sep 2009 | B2 |
| 7588549 | Eccleston | Sep 2009 | B2 |
| 7594925 | Danek et al. | Sep 2009 | B2 |
| 7608275 | Deem et al. | Oct 2009 | B2 |
| 7613515 | Knudson et al. | Nov 2009 | B2 |
| 7617005 | Demarais et al. | Nov 2009 | B2 |
| 7620451 | Demarais et al. | Nov 2009 | B2 |
| 7628789 | Soltesz et al. | Dec 2009 | B2 |
| 7632268 | Edwards et al. | Dec 2009 | B2 |
| 7641632 | Noda et al. | Jan 2010 | B2 |
| 7641633 | Laufer et al. | Jan 2010 | B2 |
| 7648500 | Edwards et al. | Jan 2010 | B2 |
| 7653438 | Deem et al. | Jan 2010 | B2 |
| 7684865 | Aldrich et al. | Mar 2010 | B2 |
| 7689290 | Ingle et al. | Mar 2010 | B2 |
| 7691079 | Gobel | Apr 2010 | B2 |
| RE41334 | Beatty et al. | May 2010 | E |
| 7708712 | Phan et al. | May 2010 | B2 |
| 7708768 | Danek et al. | May 2010 | B2 |
| 7711430 | Errico et al. | May 2010 | B2 |
| 7717948 | Demarais et al. | May 2010 | B2 |
| 7722538 | Khoury | May 2010 | B2 |
| 7725188 | Errico et al. | May 2010 | B2 |
| 7734355 | Cohen et al. | Jun 2010 | B2 |
| 7734535 | Bums | Jun 2010 | B1 |
| 7740017 | Danek et al. | Jun 2010 | B2 |
| 7740631 | Bleich et al. | Jun 2010 | B2 |
| 7742795 | Stone et al. | Jun 2010 | B2 |
| 7747324 | Errico et al. | Jun 2010 | B2 |
| 7756583 | Demarais et al. | Jul 2010 | B2 |
| 7765010 | Chomenky et al. | Jul 2010 | B2 |
| 7770584 | Danek et al. | Aug 2010 | B2 |
| 7783358 | Aldrich et al. | Aug 2010 | B2 |
| 7815590 | Cooper | Oct 2010 | B2 |
| 7826881 | Beatty et al. | Nov 2010 | B1 |
| 7831288 | Beatty et al. | Nov 2010 | B1 |
| 7837676 | Sinelnikov et al. | Nov 2010 | B2 |
| 7837679 | Biggs et al. | Nov 2010 | B2 |
| 7841986 | He et al. | Nov 2010 | B2 |
| 7844338 | Knudson et al. | Nov 2010 | B2 |
| 7853331 | Kaplan et al. | Dec 2010 | B2 |
| 7854734 | Biggs et al. | Dec 2010 | B2 |
| 7854740 | Carney | Dec 2010 | B2 |
| 7869879 | Errico et al. | Jan 2011 | B2 |
| 7869880 | Errico et al. | Jan 2011 | B2 |
| 7873417 | Demarais et al. | Jan 2011 | B2 |
| 7877146 | Rezai et al. | Jan 2011 | B2 |
| 7904159 | Errico et al. | Mar 2011 | B2 |
| 7906124 | Laufer et al. | Mar 2011 | B2 |
| 7914448 | Bob et al. | Mar 2011 | B2 |
| 7921855 | Danek et al. | Apr 2011 | B2 |
| 7930012 | Beatty et al. | Apr 2011 | B2 |
| 7931647 | Wizeman et al. | Apr 2011 | B2 |
| 7937143 | Demarais et al. | May 2011 | B2 |
| 7938123 | Danek et al. | May 2011 | B2 |
| 7949407 | Kaplan et al. | May 2011 | B2 |
| 7967782 | Laufer et al. | Jun 2011 | B2 |
| 7985187 | Wibowo et al. | Jul 2011 | B2 |
| 7992572 | Danek et al. | Aug 2011 | B2 |
| 7993336 | Jackson et al. | Aug 2011 | B2 |
| 8002740 | Willink et al. | Aug 2011 | B2 |
| 8010197 | Errico et al. | Aug 2011 | B2 |
| 8012149 | Jackson et al. | Sep 2011 | B2 |
| 8041428 | Errico et al. | Oct 2011 | B2 |
| 8046085 | Knudson et al. | Oct 2011 | B2 |
| 8052668 | Sih | Nov 2011 | B2 |
| 8088127 | Mayse et al. | Jan 2012 | B2 |
| 8099167 | Errico et al. | Jan 2012 | B1 |
| 8105817 | Deem et al. | Jan 2012 | B2 |
| 8128595 | Walker et al. | Mar 2012 | B2 |
| 8128617 | Bencini et al. | Mar 2012 | B2 |
| 8131371 | Demarais et al. | Mar 2012 | B2 |
| 8152803 | Edwards et al. | Apr 2012 | B2 |
| 8204598 | Errico et al. | Jun 2012 | B2 |
| 8208998 | Beatty et al. | Jun 2012 | B2 |
| 8209034 | Simon et al. | Jun 2012 | B2 |
| 8216216 | Warnking et al. | Jul 2012 | B2 |
| 8226638 | Mayse et al. | Jul 2012 | B2 |
| 8229564 | Rezai | Jul 2012 | B2 |
| 8231621 | Hutchins et al. | Jul 2012 | B2 |
| 8233988 | Errico et al. | Jul 2012 | B2 |
| 8251992 | Utley et al. | Aug 2012 | B2 |
| 8267094 | Danek et al. | Sep 2012 | B2 |
| 8295902 | Salahieh et al. | Oct 2012 | B2 |
| 8303581 | Arts et al. | Nov 2012 | B2 |
| 8313484 | Edwards et al. | Nov 2012 | B2 |
| 8328798 | Witzel et al. | Dec 2012 | B2 |
| 8347891 | Demarais et al. | Jan 2013 | B2 |
| 8357118 | Orr | Jan 2013 | B2 |
| 8364237 | Stone et al. | Jan 2013 | B2 |
| 8371303 | Schaner et al. | Feb 2013 | B2 |
| 8377055 | Jackson et al. | Feb 2013 | B2 |
| 20010020151 | Reed et al. | Sep 2001 | A1 |
| 20010044596 | Jaafar | Nov 2001 | A1 |
| 20020002387 | Naganuma | Jan 2002 | A1 |
| 20020010495 | Freed et al. | Jan 2002 | A1 |
| 20020016344 | Tracey | Feb 2002 | A1 |
| 20020042564 | Cooper et al. | Apr 2002 | A1 |
| 20020042565 | Cooper et al. | Apr 2002 | A1 |
| 20020049370 | Laufer et al. | Apr 2002 | A1 |
| 20020072738 | Edwards et al. | Jun 2002 | A1 |
| 20020082197 | Aoki et al. | Jun 2002 | A1 |
| 20020087153 | Roschak et al. | Jul 2002 | A1 |
| 20020087208 | Koblish | Jul 2002 | A1 |
| 20020091379 | Danek et al. | Jul 2002 | A1 |
| 20020107512 | Edwards | Aug 2002 | A1 |
| 20020107515 | Edwards et al. | Aug 2002 | A1 |
| 20020111386 | Sekins et al. | Aug 2002 | A1 |
| 20020111619 | Keast et al. | Aug 2002 | A1 |
| 20020111620 | Cooper et al. | Aug 2002 | A1 |
| 20020115991 | Edwards | Aug 2002 | A1 |
| 20020116030 | Rezai | Aug 2002 | A1 |
| 20020143302 | Hinchliffe et al. | Oct 2002 | A1 |
| 20020143326 | Foley et al. | Oct 2002 | A1 |
| 20020143373 | Courtnage et al. | Oct 2002 | A1 |
| 20020151888 | Edwards et al. | Oct 2002 | A1 |
| 20020183682 | Darvish et al. | Dec 2002 | A1 |
| 20020198512 | Seward | Dec 2002 | A1 |
| 20020198570 | Puskas | Dec 2002 | A1 |
| 20020198574 | Gumpert | Dec 2002 | A1 |
| 20030018344 | Kaji et al. | Jan 2003 | A1 |
| 20030023287 | Edwards et al. | Jan 2003 | A1 |
| 20030027752 | Steward et al. | Feb 2003 | A1 |
| 20030050591 | McHale | Mar 2003 | A1 |
| 20030050631 | Mody et al. | Mar 2003 | A1 |
| 20030065371 | Satake | Apr 2003 | A1 |
| 20030069570 | Witzel et al. | Apr 2003 | A1 |
| 20030070676 | Cooper et al. | Apr 2003 | A1 |
| 20030074039 | Puskas | Apr 2003 | A1 |
| 20030093128 | Freed et al. | May 2003 | A1 |
| 20030125786 | Gliner et al. | Jul 2003 | A1 |
| 20030130657 | Tom et al. | Jul 2003 | A1 |
| 20030144572 | Oschman et al. | Jul 2003 | A1 |
| 20030153905 | Edwards et al. | Aug 2003 | A1 |
| 20030159700 | Laufer et al. | Aug 2003 | A1 |
| 20030181949 | Whale | Sep 2003 | A1 |
| 20030187430 | Vorisek | Oct 2003 | A1 |
| 20030195593 | Ingle et al. | Oct 2003 | A1 |
| 20030195604 | Ingle et al. | Oct 2003 | A1 |
| 20030202990 | Donovan et al. | Oct 2003 | A1 |
| 20030208103 | Sonnenschein et al. | Nov 2003 | A1 |
| 20030211121 | Donovan | Nov 2003 | A1 |
| 20030216791 | Schuler et al. | Nov 2003 | A1 |
| 20030216792 | Levin et al. | Nov 2003 | A1 |
| 20030216891 | Wegener | Nov 2003 | A1 |
| 20030225443 | Kiran et al. | Dec 2003 | A1 |
| 20030233099 | Danaek et al. | Dec 2003 | A1 |
| 20030236455 | Swanson et al. | Dec 2003 | A1 |
| 20040006268 | Gilboa et al. | Jan 2004 | A1 |
| 20040009180 | Donovan | Jan 2004 | A1 |
| 20040010289 | Biggs et al. | Jan 2004 | A1 |
| 20040010290 | Schroeppel et al. | Jan 2004 | A1 |
| 20040028676 | Klein et al. | Feb 2004 | A1 |
| 20040029849 | Schatzberg et al. | Feb 2004 | A1 |
| 20040030368 | Kemeny et al. | Feb 2004 | A1 |
| 20040031494 | Danek et al. | Feb 2004 | A1 |
| 20040044390 | Szeles | Mar 2004 | A1 |
| 20040059383 | Puskas | Mar 2004 | A1 |
| 20040073201 | Cooper et al. | Apr 2004 | A1 |
| 20040073206 | Foley et al. | Apr 2004 | A1 |
| 20040073278 | Pachys | Apr 2004 | A1 |
| 20040086531 | Barron | May 2004 | A1 |
| 20040087936 | Stem et al. | May 2004 | A1 |
| 20040088030 | Jung, Jr. | May 2004 | A1 |
| 20040088036 | Gilbert | May 2004 | A1 |
| 20040091880 | Wiebusch et al. | May 2004 | A1 |
| 20040106954 | Whitehurst et al. | Jun 2004 | A1 |
| 20040116981 | Mazar | Jun 2004 | A1 |
| 20040122488 | Mazar et al. | Jun 2004 | A1 |
| 20040122489 | Mazar et al. | Jun 2004 | A1 |
| 20040127942 | Yomtov et al. | Jul 2004 | A1 |
| 20040127958 | Mazar et al. | Jul 2004 | A1 |
| 20040142005 | Brooks et al. | Jul 2004 | A1 |
| 20040147921 | Edwards et al. | Jul 2004 | A1 |
| 20040147969 | Mann et al. | Jul 2004 | A1 |
| 20040147988 | Stephens | Jul 2004 | A1 |
| 20040151741 | Borodic | Aug 2004 | A1 |
| 20040153056 | Muller et al. | Aug 2004 | A1 |
| 20040162584 | Hill et al. | Aug 2004 | A1 |
| 20040162597 | Hamilton et al. | Aug 2004 | A1 |
| 20040167509 | Taimisto | Aug 2004 | A1 |
| 20040167580 | Mann et al. | Aug 2004 | A1 |
| 20040172075 | Shafer et al. | Sep 2004 | A1 |
| 20040172080 | Stadler et al. | Sep 2004 | A1 |
| 20040172084 | Knudson et al. | Sep 2004 | A1 |
| 20040175399 | Schiffman | Sep 2004 | A1 |
| 20040176803 | Whelan et al. | Sep 2004 | A1 |
| 20040176805 | Whelan et al. | Sep 2004 | A1 |
| 20040182399 | Danek et al. | Sep 2004 | A1 |
| 20040186435 | Seward | Sep 2004 | A1 |
| 20040204747 | Kemeny et al. | Oct 2004 | A1 |
| 20040213813 | Ackerman | Oct 2004 | A1 |
| 20040213814 | Ackerman | Oct 2004 | A1 |
| 20040215235 | Jackson et al. | Oct 2004 | A1 |
| 20040215289 | Fukui | Oct 2004 | A1 |
| 20040215296 | Ganz et al. | Oct 2004 | A1 |
| 20040220556 | Cooper et al. | Nov 2004 | A1 |
| 20040220621 | Zhou et al. | Nov 2004 | A1 |
| 20040226556 | Deem et al. | Nov 2004 | A1 |
| 20040230251 | Schuler et al. | Nov 2004 | A1 |
| 20040230252 | Kullok et al. | Nov 2004 | A1 |
| 20040243118 | Ayers et al. | Dec 2004 | A1 |
| 20040243182 | Cohen et al. | Dec 2004 | A1 |
| 20040248188 | Sanders | Dec 2004 | A1 |
| 20040249401 | Rabiner et al. | Dec 2004 | A1 |
| 20040249416 | Yun et al. | Dec 2004 | A1 |
| 20040253274 | Voet | Dec 2004 | A1 |
| 20050004609 | Stahmann et al. | Jan 2005 | A1 |
| 20050004631 | Benedict | Jan 2005 | A1 |
| 20050010263 | Schauerte | Jan 2005 | A1 |
| 20050010270 | Laufer | Jan 2005 | A1 |
| 20050015117 | Gerber | Jan 2005 | A1 |
| 20050019346 | Boulis | Jan 2005 | A1 |
| 20050021092 | Yun et al. | Jan 2005 | A1 |
| 20050049615 | Cooper et al. | Mar 2005 | A1 |
| 20050056292 | Cooper | Mar 2005 | A1 |
| 20050059153 | George et al. | Mar 2005 | A1 |
| 20050060041 | Phan et al. | Mar 2005 | A1 |
| 20050060042 | Phan et al. | Mar 2005 | A1 |
| 20050060044 | Roschak et al. | Mar 2005 | A1 |
| 20050065553 | Ben Ezra et al. | Mar 2005 | A1 |
| 20050065562 | Rezai | Mar 2005 | A1 |
| 20050065567 | Lee et al. | Mar 2005 | A1 |
| 20050065573 | Rezai | Mar 2005 | A1 |
| 20050065574 | Rezai | Mar 2005 | A1 |
| 20050065575 | Dobak | Mar 2005 | A1 |
| 20050065584 | Schiff et al. | Mar 2005 | A1 |
| 20050074461 | Donovan | Apr 2005 | A1 |
| 20050076909 | Stahmann et al. | Apr 2005 | A1 |
| 20050080461 | Stahmann et al. | Apr 2005 | A1 |
| 20050085801 | Cooper et al. | Apr 2005 | A1 |
| 20050090722 | Perez | Apr 2005 | A1 |
| 20050096529 | Cooper et al. | May 2005 | A1 |
| 20050096644 | Hall et al. | May 2005 | A1 |
| 20050107783 | Tom et al. | May 2005 | A1 |
| 20050107829 | Edwards et al. | May 2005 | A1 |
| 20050107853 | Krespi et al. | May 2005 | A1 |
| 20050125044 | Tracey | Jun 2005 | A1 |
| 20050137518 | Biggs et al. | Jun 2005 | A1 |
| 20050137611 | Escudero et al. | Jun 2005 | A1 |
| 20050137715 | Phan et al. | Jun 2005 | A1 |
| 20050143788 | Yun et al. | Jun 2005 | A1 |
| 20050149146 | Boveja et al. | Jul 2005 | A1 |
| 20050152924 | Voet | Jul 2005 | A1 |
| 20050153885 | Yun et al. | Jul 2005 | A1 |
| 20050159736 | Danek et al. | Jul 2005 | A9 |
| 20050165456 | Mann et al. | Jul 2005 | A1 |
| 20050171396 | Pankratov et al. | Aug 2005 | A1 |
| 20050177144 | Phan et al. | Aug 2005 | A1 |
| 20050177192 | Rezai et al. | Aug 2005 | A1 |
| 20050182288 | Zabara | Aug 2005 | A1 |
| 20050183732 | Edwards | Aug 2005 | A1 |
| 20050187579 | Danek et al. | Aug 2005 | A1 |
| 20050193279 | Daners | Sep 2005 | A1 |
| 20050203503 | Edwards et al. | Sep 2005 | A1 |
| 20050222628 | Krakousky | Oct 2005 | A1 |
| 20050222635 | Krakovsky | Oct 2005 | A1 |
| 20050222651 | Jung, Jr. | Oct 2005 | A1 |
| 20050228054 | Tatton | Oct 2005 | A1 |
| 20050228459 | Levin et al. | Oct 2005 | A1 |
| 20050228460 | Levin et al. | Oct 2005 | A1 |
| 20050234523 | Levin et al. | Oct 2005 | A1 |
| 20050238693 | Whyte | Oct 2005 | A1 |
| 20050240176 | Oral et al. | Oct 2005 | A1 |
| 20050240241 | Yun et al. | Oct 2005 | A1 |
| 20050245992 | Persen et al. | Nov 2005 | A1 |
| 20050251128 | Amoah | Nov 2005 | A1 |
| 20050251213 | Freeman | Nov 2005 | A1 |
| 20050255317 | Bavaro et al. | Nov 2005 | A1 |
| 20050256028 | Yun et al. | Nov 2005 | A1 |
| 20050261747 | Schuler et al. | Nov 2005 | A1 |
| 20050267536 | Freeman et al. | Dec 2005 | A1 |
| 20050277993 | Mower | Dec 2005 | A1 |
| 20050283197 | Daum et al. | Dec 2005 | A1 |
| 20060015151 | Aldrich | Jan 2006 | A1 |
| 20060058692 | Beatty et al. | Mar 2006 | A1 |
| 20060058693 | Beatty et al. | Mar 2006 | A1 |
| 20060058780 | Edwards et al. | Mar 2006 | A1 |
| 20060062808 | Laufer et al. | Mar 2006 | A1 |
| 20060079887 | Buysse et al. | Apr 2006 | A1 |
| 20060084884 | Beatty et al. | Apr 2006 | A1 |
| 20060084970 | Beatty et al. | Apr 2006 | A1 |
| 20060084971 | Beatty et al. | Apr 2006 | A1 |
| 20060084972 | Beatty et al. | Apr 2006 | A1 |
| 20060089637 | Werneth et al. | Apr 2006 | A1 |
| 20060095032 | Jackson et al. | May 2006 | A1 |
| 20060100666 | Wilkinson et al. | May 2006 | A1 |
| 20060106361 | Muni | May 2006 | A1 |
| 20060111755 | Stone et al. | May 2006 | A1 |
| 20060116749 | Willink et al. | Jun 2006 | A1 |
| 20060135953 | Kania et al. | Jun 2006 | A1 |
| 20060135984 | Kramer et al. | Jun 2006 | A1 |
| 20060135998 | Libbus et al. | Jun 2006 | A1 |
| 20060137698 | Danek et al. | Jun 2006 | A1 |
| 20060142801 | Demarais et al. | Jun 2006 | A1 |
| 20060167498 | DiLorenzo | Jul 2006 | A1 |
| 20060178703 | Huston et al. | Aug 2006 | A1 |
| 20060206150 | Demarais et al. | Sep 2006 | A1 |
| 20060212076 | Demarais et al. | Sep 2006 | A1 |
| 20060212078 | Demarais et al. | Sep 2006 | A1 |
| 20060222667 | Deem et al. | Oct 2006 | A1 |
| 20060225742 | Deem et al. | Oct 2006 | A1 |
| 20060235474 | Demarais | Oct 2006 | A1 |
| 20060241523 | Sinelnikov et al. | Oct 2006 | A1 |
| 20060247617 | Danek et al. | Nov 2006 | A1 |
| 20060247618 | Kaplan et al. | Nov 2006 | A1 |
| 20060247619 | Kaplan et al. | Nov 2006 | A1 |
| 20060247683 | Danck et al. | Nov 2006 | A1 |
| 20060247726 | Biggs et al. | Nov 2006 | A1 |
| 20060247727 | Biggs et al. | Nov 2006 | A1 |
| 20060247746 | Danck et al. | Nov 2006 | A1 |
| 20060254600 | Danek et al. | Nov 2006 | A1 |
| 20060259028 | Utley et al. | Nov 2006 | A1 |
| 20060259029 | Utley et al. | Nov 2006 | A1 |
| 20060259030 | Utley et al. | Nov 2006 | A1 |
| 20060265014 | Demarais et al. | Nov 2006 | A1 |
| 20060265015 | Demarais et al. | Nov 2006 | A1 |
| 20060271111 | Demarais et al. | Nov 2006 | A1 |
| 20060276807 | Keast et al. | Dec 2006 | A1 |
| 20060276852 | Demarais et al. | Dec 2006 | A1 |
| 20060278243 | Danek et al. | Dec 2006 | A1 |
| 20060278244 | Danek et al. | Dec 2006 | A1 |
| 20060280772 | Roschak et al. | Dec 2006 | A1 |
| 20060280773 | Roschak et al. | Dec 2006 | A1 |
| 20060282071 | Utley et al. | Dec 2006 | A1 |
| 20060287679 | Stone | Dec 2006 | A1 |
| 20070021803 | Deem et al. | Jan 2007 | A1 |
| 20070025919 | Deem et al. | Feb 2007 | A1 |
| 20070027496 | Pamis et al. | Feb 2007 | A1 |
| 20070032788 | Edwards et al. | Feb 2007 | A1 |
| 20070043342 | Kleinberger | Feb 2007 | A1 |
| 20070055328 | Mayse et al. | Mar 2007 | A1 |
| 20070060954 | Cameron et al. | Mar 2007 | A1 |
| 20070060990 | Satake | Mar 2007 | A1 |
| 20070062545 | Danek et al. | Mar 2007 | A1 |
| 20070066957 | Demarais et al. | Mar 2007 | A1 |
| 20070074719 | Danek et al. | Apr 2007 | A1 |
| 20070083194 | Kunis et al. | Apr 2007 | A1 |
| 20070083197 | Danek et al. | Apr 2007 | A1 |
| 20070083239 | Demarais et al. | Apr 2007 | A1 |
| 20070093802 | Danek et al. | Apr 2007 | A1 |
| 20070093809 | Edwards et al. | Apr 2007 | A1 |
| 20070100390 | Danaek et al. | May 2007 | A1 |
| 20070102011 | Danek et al. | May 2007 | A1 |
| 20070106292 | Kaplan et al. | May 2007 | A1 |
| 20070106296 | Laufer et al. | May 2007 | A1 |
| 20070106337 | Errico et al. | May 2007 | A1 |
| 20070106338 | Ericco | May 2007 | A1 |
| 20070106339 | Errico et al. | May 2007 | A1 |
| 20070106348 | Laufer | May 2007 | A1 |
| 20070112349 | Danek et al. | May 2007 | A1 |
| 20070118184 | Danek et al. | May 2007 | A1 |
| 20070118190 | Danek et al. | May 2007 | A1 |
| 20070123922 | Cooper et al. | May 2007 | A1 |
| 20070123958 | Laufer | May 2007 | A1 |
| 20070123961 | Danek et al. | May 2007 | A1 |
| 20070129720 | Demarais et al. | Jun 2007 | A1 |
| 20070129760 | Demarais et al. | Jun 2007 | A1 |
| 20070129761 | Demarais et al. | Jun 2007 | A1 |
| 20070135875 | Demarais et al. | Jun 2007 | A1 |
| 20070173899 | Levin et al. | Jul 2007 | A1 |
| 20070191902 | Errico et al. | Aug 2007 | A1 |
| 20070197896 | Moll | Aug 2007 | A1 |
| 20070203549 | Demarais et al. | Aug 2007 | A1 |
| 20070225768 | Dobak, III | Sep 2007 | A1 |
| 20070232896 | Gilboa et al. | Oct 2007 | A1 |
| 20070239256 | Weber et al. | Oct 2007 | A1 |
| 20070244479 | Beatty et al. | Oct 2007 | A1 |
| 20070255270 | Carney | Nov 2007 | A1 |
| 20070255304 | Roschak et al. | Nov 2007 | A1 |
| 20070265639 | Danek et al. | Nov 2007 | A1 |
| 20070265687 | Deem et al. | Nov 2007 | A1 |
| 20070267011 | Deem et al. | Nov 2007 | A1 |
| 20080004596 | Yun et al. | Jan 2008 | A1 |
| 20080021274 | Bayer et al. | Jan 2008 | A1 |
| 20080021369 | Deem et al. | Jan 2008 | A1 |
| 20080051839 | Libbus et al. | Feb 2008 | A1 |
| 20080086107 | Roschak | Apr 2008 | A1 |
| 20080097422 | Edwards et al. | Apr 2008 | A1 |
| 20080097424 | Wizeman et al. | Apr 2008 | A1 |
| 20080125772 | Stone et al. | May 2008 | A1 |
| 20080147137 | Cohen et al. | Jun 2008 | A1 |
| 20080154258 | Chang et al. | Jun 2008 | A1 |
| 20080161801 | Steinke et al. | Jul 2008 | A1 |
| 20080183248 | Rezai et al. | Jul 2008 | A1 |
| 20080188912 | Stone et al. | Aug 2008 | A1 |
| 20080188913 | Stone et al. | Aug 2008 | A1 |
| 20080194956 | Aldrich et al. | Aug 2008 | A1 |
| 20080208305 | Rezai et al. | Aug 2008 | A1 |
| 20080213331 | Gelfand et al. | Sep 2008 | A1 |
| 20080234564 | Beatty et al. | Sep 2008 | A1 |
| 20080243112 | DeNeve | Oct 2008 | A1 |
| 20080255449 | Warnking et al. | Oct 2008 | A1 |
| 20080255642 | Zarins et al. | Oct 2008 | A1 |
| 20080262489 | Steinke | Oct 2008 | A1 |
| 20080275445 | Kelly et al. | Nov 2008 | A1 |
| 20080302359 | Loomas et al. | Dec 2008 | A1 |
| 20080306570 | Rezai et al. | Dec 2008 | A1 |
| 20080312543 | Laufer et al. | Dec 2008 | A1 |
| 20080312725 | Penner | Dec 2008 | A1 |
| 20080319350 | Wallace et al. | Dec 2008 | A1 |
| 20090018473 | Aldrich et al. | Jan 2009 | A1 |
| 20090018538 | Webster et al. | Jan 2009 | A1 |
| 20090030477 | Jarrard | Jan 2009 | A1 |
| 20090036948 | Levin et al. | Feb 2009 | A1 |
| 20090043301 | Jarrard | Feb 2009 | A1 |
| 20090043302 | Ford et al. | Feb 2009 | A1 |
| 20090048593 | Ganz et al. | Feb 2009 | A1 |
| 20090060953 | Sandars | Mar 2009 | A1 |
| 20090062873 | Wu et al. | Mar 2009 | A1 |
| 20090069797 | Danek et al. | Mar 2009 | A1 |
| 20090076409 | Wu et al. | Mar 2009 | A1 |
| 20090076491 | Roschak et al. | Mar 2009 | A1 |
| 20090112203 | Danek et al. | Apr 2009 | A1 |
| 20090124883 | Wibowo et al. | May 2009 | A1 |
| 20090131765 | Roschak et al. | May 2009 | A1 |
| 20090131928 | Edwards et al. | May 2009 | A1 |
| 20090131930 | Gelbart et al. | May 2009 | A1 |
| 20090143678 | Keast et al. | Jun 2009 | A1 |
| 20090143705 | Danek et al. | Jun 2009 | A1 |
| 20090143776 | Danek et al. | Jun 2009 | A1 |
| 20090143831 | Huston et al. | Jun 2009 | A1 |
| 20090155336 | Rezai | Jun 2009 | A1 |
| 20090192505 | Askew et al. | Jul 2009 | A1 |
| 20090192508 | Laufer et al. | Jul 2009 | A1 |
| 20090204005 | Keast et al. | Aug 2009 | A1 |
| 20090204119 | Bleich et al. | Aug 2009 | A1 |
| 20090227885 | Lowery et al. | Sep 2009 | A1 |
| 20090227980 | Kangas et al. | Sep 2009 | A1 |
| 20090232850 | Manack et al. | Sep 2009 | A1 |
| 20090248011 | Hlavka et al. | Oct 2009 | A1 |
| 20090254079 | Edwards et al. | Oct 2009 | A1 |
| 20090254142 | Edwards et al. | Oct 2009 | A1 |
| 20090259274 | Simon | Oct 2009 | A1 |
| 20090275840 | Roschak et al. | Nov 2009 | A1 |
| 20090275878 | Cambier et al. | Nov 2009 | A1 |
| 20090281593 | Errico et al. | Nov 2009 | A9 |
| 20090287087 | Gwerder et al. | Nov 2009 | A1 |
| 20090306644 | Mayse et al. | Dec 2009 | A1 |
| 20090318904 | Cooper et al. | Dec 2009 | A9 |
| 20090319002 | Simon | Dec 2009 | A1 |
| 20100003282 | Deem et al. | Jan 2010 | A1 |
| 20100004648 | Edwards et al. | Jan 2010 | A1 |
| 20100010564 | Simon | Jan 2010 | A1 |
| 20100016709 | Gilboa et al. | Jan 2010 | A1 |
| 20100042089 | Soltesz et al. | Feb 2010 | A1 |
| 20100049031 | Fruland et al. | Feb 2010 | A1 |
| 20100049186 | Ingle et al. | Feb 2010 | A1 |
| 20100049188 | Nelson et al. | Feb 2010 | A1 |
| 20100057178 | Simon | Mar 2010 | A1 |
| 20100063495 | Edwards et al. | Mar 2010 | A1 |
| 20100070004 | Hlavka et al. | Mar 2010 | A1 |
| 20100076518 | Hlavka et al. | Mar 2010 | A1 |
| 20100087783 | Weber et al. | Apr 2010 | A1 |
| 20100087809 | Edwards et al. | Apr 2010 | A1 |
| 20100094231 | Bleich et al. | Apr 2010 | A1 |
| 20100114087 | Edwards et al. | May 2010 | A1 |
| 20100116279 | Cooper | May 2010 | A9 |
| 20100125239 | Perry et al. | May 2010 | A1 |
| 20100130892 | Warnking | May 2010 | A1 |
| 20100137860 | Demarais et al. | Jun 2010 | A1 |
| 20100145427 | Gliner et al. | Jun 2010 | A1 |
| 20100152835 | Orr | Jun 2010 | A1 |
| 20100160906 | Jarrard | Jun 2010 | A1 |
| 20100160996 | Simon | Jun 2010 | A1 |
| 20100174340 | Simon | Jul 2010 | A1 |
| 20100179424 | Warnking et al. | Jul 2010 | A1 |
| 20100185190 | Danek et al. | Jul 2010 | A1 |
| 20100191089 | Stebler et al. | Jul 2010 | A1 |
| 20100204689 | Danek et al. | Aug 2010 | A1 |
| 20100222851 | Deem et al. | Sep 2010 | A1 |
| 20100228318 | Errico et al. | Sep 2010 | A1 |
| 20100241188 | Errico et al. | Sep 2010 | A1 |
| 20100249873 | Errico | Sep 2010 | A1 |
| 20100256629 | Wylie et al. | Oct 2010 | A1 |
| 20100256630 | Hamilton et al. | Oct 2010 | A1 |
| 20100268222 | Danek et al. | Oct 2010 | A1 |
| 20100298905 | Simon | Nov 2010 | A1 |
| 20100305463 | Macklem et al. | Dec 2010 | A1 |
| 20100318020 | Atanasoska et al. | Dec 2010 | A1 |
| 20100331776 | Salahieh et al. | Dec 2010 | A1 |
| 20110004148 | Ishii | Jan 2011 | A1 |
| 20110015548 | Aldrich et al. | Jan 2011 | A1 |
| 20110028898 | Clark, III et al. | Feb 2011 | A1 |
| 20110046432 | Simon et al. | Feb 2011 | A1 |
| 20110060380 | Gelfand et al. | Mar 2011 | A1 |
| 20110079230 | Danek et al. | Apr 2011 | A1 |
| 20110093032 | Boggs, II et al. | Apr 2011 | A1 |
| 20110098762 | Rezai | Apr 2011 | A1 |
| 20110112400 | Emery et al. | May 2011 | A1 |
| 20110112521 | DeLonzor et al. | May 2011 | A1 |
| 20110118725 | Mayse et al. | May 2011 | A1 |
| 20110125203 | Simon et al. | May 2011 | A1 |
| 20110125213 | Simon et al. | May 2011 | A1 |
| 20110130708 | Perry et al. | Jun 2011 | A1 |
| 20110137284 | Arora et al. | Jun 2011 | A1 |
| 20110144630 | Loeb | Jun 2011 | A1 |
| 20110146673 | Keast et al. | Jun 2011 | A1 |
| 20110146674 | Roschak | Jun 2011 | A1 |
| 20110152855 | Mayse et al. | Jun 2011 | A1 |
| 20110152967 | Simon et al. | Jun 2011 | A1 |
| 20110152974 | Rezai et al. | Jun 2011 | A1 |
| 20110166499 | Demarais et al. | Jul 2011 | A1 |
| 20110166565 | Wizeman et al. | Jul 2011 | A1 |
| 20110172655 | Biggs et al. | Jul 2011 | A1 |
| 20110172658 | Gelbart et al. | Jul 2011 | A1 |
| 20110178569 | Pamis et al. | Jul 2011 | A1 |
| 20110184330 | Laufer et al. | Jul 2011 | A1 |
| 20110190569 | Simon et al. | Aug 2011 | A1 |
| 20110196288 | Kaplan et al. | Aug 2011 | A1 |
| 20110202098 | Demarais et al. | Aug 2011 | A1 |
| 20110224768 | Edwards | Sep 2011 | A1 |
| 20110230701 | Simon et al. | Sep 2011 | A1 |
| 20110230938 | Simon et al. | Sep 2011 | A1 |
| 20110245756 | Arora et al. | Oct 2011 | A1 |
| 20110251592 | Biggs et al. | Oct 2011 | A1 |
| 20110257622 | Salahieh et al. | Oct 2011 | A1 |
| 20110257647 | Mayse et al. | Oct 2011 | A1 |
| 20110263960 | Mitchell | Oct 2011 | A1 |
| 20110264086 | Ingle | Oct 2011 | A1 |
| 20110270249 | Utley et al. | Nov 2011 | A1 |
| 20110276107 | Simon et al. | Nov 2011 | A1 |
| 20110276112 | Simon et al. | Nov 2011 | A1 |
| 20110282229 | Danek et al. | Nov 2011 | A1 |
| 20110282418 | Saunders et al. | Nov 2011 | A1 |
| 20110301587 | Deem et al. | Dec 2011 | A1 |
| 20110301664 | Rczai | Dec 2011 | A1 |
| 20110301679 | Rezai et al. | Dec 2011 | A1 |
| 20110306851 | Wang | Dec 2011 | A1 |
| 20110306904 | Jacobson et al. | Dec 2011 | A1 |
| 20110306997 | Roschak et al. | Dec 2011 | A9 |
| 20110319958 | Simon et al. | Dec 2011 | A1 |
| 20120004656 | Jackson et al. | Jan 2012 | A1 |
| 20120015019 | Pacetti et al. | Jan 2012 | A1 |
| 20120016256 | Mabary et al. | Jan 2012 | A1 |
| 20120016358 | Mayse et al. | Jan 2012 | A1 |
| 20120016363 | Mayse et al. | Jan 2012 | A1 |
| 20120016364 | Mayse et al. | Jan 2012 | A1 |
| 20120029261 | Deem et al. | Feb 2012 | A1 |
| 20120029500 | Jenson | Feb 2012 | A1 |
| 20120029512 | Willard et al. | Feb 2012 | A1 |
| 20120029591 | Simon et al. | Feb 2012 | A1 |
| 20120029601 | Simon et al. | Feb 2012 | A1 |
| 20120041412 | Roth et al. | Feb 2012 | A1 |
| 20120041509 | Knudson et al. | Feb 2012 | A1 |
| 20120071870 | Saiahieh et al. | Mar 2012 | A1 |
| 20120078096 | Kroiik et al. | Mar 2012 | A1 |
| 20120083734 | Ayres et al. | Apr 2012 | A1 |
| 20120089078 | Deem et al. | Apr 2012 | A1 |
| 20120089138 | Edwards et al. | Apr 2012 | A1 |
| 20120101326 | Simon et al. | Apr 2012 | A1 |
| 20120101413 | Beetei et al. | Apr 2012 | A1 |
| 20120109278 | Sih | May 2012 | A1 |
| 20120143132 | Orlowski | Jun 2012 | A1 |
| 20120143177 | Avitall | Jun 2012 | A1 |
| 20120143179 | Avitall | Jun 2012 | A1 |
| 20120143181 | Demarais et al. | Jun 2012 | A1 |
| 20120157986 | Stone et al. | Jun 2012 | A1 |
| 20120157987 | Steinke et al. | Jun 2012 | A1 |
| 20120157988 | Stone et al. | Jun 2012 | A1 |
| 20120157989 | Stone et al. | Jun 2012 | A1 |
| 20120158101 | Stone et al. | Jun 2012 | A1 |
| 20120165803 | Bencini et al. | Jun 2012 | A1 |
| 20120184801 | Simon et al. | Jul 2012 | A1 |
| 20120185020 | Simon et al. | Jul 2012 | A1 |
| 20120191081 | Markowitz | Jul 2012 | A1 |
| 20120191082 | Markowitz | Jul 2012 | A1 |
| 20120197100 | Razavi et al. | Aug 2012 | A1 |
| 20120197246 | Mauch | Aug 2012 | A1 |
| 20120197251 | Edwards et al. | Aug 2012 | A1 |
| 20120203067 | Higgins et al. | Aug 2012 | A1 |
| 20120203216 | Mayse et al. | Aug 2012 | A1 |
| 20120203222 | Mayse et al. | Aug 2012 | A1 |
| 20120209118 | Warnking | Aug 2012 | A1 |
| 20120209259 | Danek et al. | Aug 2012 | A1 |
| 20120209261 | Mayse et al. | Aug 2012 | A1 |
| 20120221087 | Parnis et al. | Aug 2012 | A1 |
| 20120232436 | Warnking | Sep 2012 | A1 |
| 20120245415 | Emura et al. | Sep 2012 | A1 |
| 20120253442 | Gliner et al. | Oct 2012 | A1 |
| 20120259263 | Celermajer et al. | Oct 2012 | A1 |
| 20120259269 | Meyer | Oct 2012 | A1 |
| 20120259326 | Brannan et al. | Oct 2012 | A1 |
| 20120265280 | Errico et al. | Oct 2012 | A1 |
| 20120289952 | Utley et al. | Nov 2012 | A1 |
| 20120290035 | Levine et al. | Nov 2012 | A1 |
| 20120294424 | Chin et al. | Nov 2012 | A1 |
| 20120296329 | Ng | Nov 2012 | A1 |
| 20120310233 | Dimmer et al. | Dec 2012 | A1 |
| 20120316552 | Mayse et al. | Dec 2012 | A1 |
| 20120330298 | Ganz et al. | Dec 2012 | A1 |
| 20130012844 | Demarais et al. | Jan 2013 | A1 |
| 20130012866 | Deem et al. | Jan 2013 | A1 |
| 20130012867 | Demarais et al. | Jan 2013 | A1 |
| 20130035576 | O'Grady et al. | Feb 2013 | A1 |
| Number | Date | Country | |
|---|---|---|---|
| 20150141985 A1 | May 2015 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61255367 | Oct 2009 | US | |
| 61260348 | Nov 2009 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12913702 | Oct 2010 | US |
| Child | 14601717 | US |
