Patent Application
20190046289
Embodiments of the present disclosure relate generally to the field of medical devices, and in particular, to apparatuses, methods, and devices for identifying and treating portions of the body. In particular, certain embodiments of the present disclosure are related to the identification and treatment of diseased and/or cancerous regions in a lung, and in particular lung nodules.
Lung cancer has a high incidence of morbidity and mortality in patients. There is presently an extensive effort to develop diagnostic methods for early identification of areas of the lung, for example pulmonary nodules, which may be precursors of cancer. Pulmonary or lung nodules are small masses of tissue in the lung that may range in size between 0.5-30 mm. Pulmonary nodules often require careful evaluation by a medical professional, especially in patients that have risk factors such as tobacco use or a family history of cancer. Imaging methods are evolving to produce more accurate identification of pulmonary nodules to determine whether these may be cancerous or otherwise diseased.
Management of pulmonary nodules has varied from simple observation and follow up at given time intervals to immediate biopsy and surgery. Needle biopsies are often an important step in the management of pulmonary nodules as well as for bigger tumors and/or lung masses. A positive identification of cancer is typically an indication for pulmonary surgery, i.e., lobectomy. Unfortunately, a negative biopsy does not entirely eliminate the risk of cancer at a particular location, and may require further follow up and surgical biopsy.
Although advances in diagnostic methods are in some cases improving the early identification and follow up to lung nodules, the methods for their removal are lagging in development. Biopsy surgery typically consists of a mini-thoracotomy or the use of thoracoscopic or endoscopic methods to access the thoracic cavity and lung tissue. A bronchial blockade is sometimes needed to isolate and deflate the lung segment or lobe where the biopsy will take place. With lung deflation, the anatomy of the lung becomes distorted, making the imaging and anatomical correlations needed to locate the appropriate lung area imprecise, vague, and in some cases useless.
Once the surgeon accesses the deflated lung portion thought to contain the nodule, visual identification is typically used to find the nodule. This task is far easier if the lung area is superficial and accessible. In the case of an isolated lung area, such as a nodule that is small and located deeply within the parenchyma, visual identification may be difficult or impossible, and the surgeon may be forced, for example, to use his or her fingers to palpate the suspected area. The palpation process may thus require performing a mini-thoracotomy (or extending an existing incision) to permit the surgeon's fingers to reach the targeted lung area. Even with palpation, nodules may be difficult to identify.
After the lung area or nodule has been located and identified, surgical removal of the affected area typically follows. Removal may comprise at least a wedge resection of the affected area. If a lung nodule, tumor, or mass is cancerous, current knowledge and recommendations include performing a lobectomy.
It is therefore a goal of the embodiments described herein to provide new devices, systems, and methods for the identification and treatment of tissue, in particular lung tissue and lung nodules.
A system for locating a region of tissue can comprise: a traceable marker configured to be implanted and retained in the region of tissue, wherein the traceable marker comprises one or more localization attributes; and, a sensor configured to detect one or more localization attributes. In some embodiments, the system further comprises an insertion instrument configured to implant the traceable marker in the region of tissue. According to some configurations, the localization attribute is magnetic, radioactive, and/or radioopaque. The sensor can further comprises a navigational aid. In some embodiments, the navigation aid comprises a gauge and/or a graphical readout. The sensor can be configured to be inserted through a patient's thoracic cavity and/or into a patient's airway. In some embodiments, the system further comprises a resection device. According to some configurations, the sensor is integrated into the resection device. The resection device can comprise a receptacle configured to aspirate and receive a portion of tissue. In some embodiments, the resection device comprises an elongated, hollow cylindrical body with an aperture at a distal end of the hollow cylindrical body and a conduit connected to a proximal end of the hollow cylindrical body, the conduit being configured to be connected to a source of vacuum. According to some variants, the system further comprises a treatment device. In some embodiments, the traceable marker comprises an auxiliary power lead. The auxiliary power lead can be configured to be selectively connected to a catheter. In some embodiments, the auxiliary power lead is configured to be connected to a secondary module. The secondary module can comprise a power storage module. In some embodiments, the power storage module is configured to be charged wirelessly. The treatment device can be configured to heat the traceable marker electrically. In some embodiments, the treatment device is configured to cause the traceable marker to release an agent from the traceable marker. In some embodiments, the treatment device is configured to heat the traceable marker using magnetic coupling. According to some variants, the treatment device comprises a magnetic probe. The magnetic probe can be attached to a catheter inserted into a patient's airway. In some embodiments, the treatment device is an MRI device. According to some variants, the traceable marker comprises a power source. The power source can comprise a battery and/or a capacitor. In some embodiments, the system further comprises a second traceable marker.
According to some variants, a system for the treatment of a region of tissue can comprise a catheter configured to be inserted within a patient's airway, wherein the catheter comprises an antenna at a distal end of the catheter; a microwave generator configured to be connected to the catheter so as to emit microwave radiation from the antenna. In some embodiments, the system can further comprise a bronchoscope, wherein the catheter is configured for insertion into a working channel of the bronchoscope. The antenna tip can be configured to circumscribe an exterior perimeter of a lung nodule. In some embodiments, the antenna tip is configured to be inserted into a lung nodule. According to some variants, the system further comprises a second antenna tip at the distal end of the catheter.
A method of repeatedly locating a position m a lung can comprise: navigating to the position within the lung; implanting a traceable marker into the position, wherein the traceable marker comprises at least one localization attribute; locating the traceable marker based on the at least one localization attribute. In some embodiments, the method further comprises implanting a second traceable marker near the position within the lung. According to some variants, the step of navigating comprises using a bronchoscope. In some embodiments, the traceable marker is implanted via a catheter or needle inserted into a working channel in the bronchoscope. The method can further comprise biopsying a tissue sample at or near the position in the lung. In some embodiments, the at least one localization attribute is selected from the group consisting of: radioopacity localization, magnetism localization, radioactivity localization, and visual localization. The step of locating the traceable marker can comprise using a localization device. According to some variants, the localization device comprises a magnetic sensor. In some embodiments, the method further comprises applying treatment to the position in the lung. In some embodiments, the treatment is repeatedly applied to the position in the lung by repeatedly locating the traceable marker. The treatment can comprise resecting lung tissue near or at the position in the lung. According to some variants, the step of resecting lung tissue comprises positioning a receptacle in fluid communication with a source of vacuum near the position in the lung, activating the source of vacuum, suctioning lung tissue into the receptacle, and severing the tissue within the receptacle from the remainder of the lung. The treatment can comprise applying microwave radiation. In some embodiments, the microwave radiation is applied via an antenna tip connected to a source of microwave radiation, the antenna tip being inserted into a catheter. According to some variants, the treatment comprises applying heat. The heating can be applied using a magnetic field acting upon the traceable marker. In some embodiments, the magnetic field is applied via a probe positioned near the traceable marker. The magnetic field can be applied using an MRI device. According to some variants, the treatment comprises applying electrical treatment. In some embodiments, the traceable marker comprises a treatment modality. The traceable marker can be configured to release one or more therapeutic agents. In some embodiments, the traceable marker comprises a power source. The power source can a battery attached to the traceable marker. In some embodiments, the power source is attached to the traceable marker via a wire.
According to some variants, a traceable marker is configured to be implanted into a site in a lung and the marker can comprise at least one localization attribute. The marker can comprise a battery. In some embodiments, the marker comprises an auxiliary power lead. The auxiliary power lead may be attached to a source of power. In some embodiments, the auxiliary power lead functions as a wireless charging lead. According to some variants, the marker comprises a radioactive material. The marker can be constructed at least in part from a magnetically-active material.
Various embodiments are depicted in the accompanying drawings for illustrative purposes, and the drawings should in no way be interpreted as limiting the scope of the embodiments. In addition, various features of one or more disclosed embodiments can be combined to form additional embodiments, which are part of this disclosure.
Embodiments of an apparatus, system, and method for identification and treatment of regions of the lung, and in particular, pulmonary nodules, tumors and/or lesions will be described with reference to the accompanying figures of one or more embodiments. The terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive manner. Rather, the terminology is simply being utilized in conjunction with a detailed description of embodiments of the systems, methods and related components. Furthermore, embodiments may comprise several novel features, no single one of which is solely responsible for its desirable attributes or is believed to be essential to practicing the inventions herein described.
The terms “lung region,” “lung area,” “tissue,” “tumor,” “mass,” and “nodule” as used herein are broad interchangeable terms and, unless otherwise indicated, the terms can include within their meaning, and without limitation, other organs or regions of tissue in a human or animal body, including diseased, cancerous, and/or pre-cancerous tissue, lesions, tumors, masses, or other areas of interest within the body. In general, nodules can be grouped into three or more types. For example, nodules located in the lung parenchyma outside of an airway passage and are not invading or compressing airways (e.g., see nodule 402 of
The traceable marker 104 preferably comprises at least one localization attribute that permits it to be detected with a localization device. The localization attribute refers to any attribute that permits the traceable marker 104 to be identified (e.g., after implantation), and may comprise distinguishable visual, radioopaque, magnetic, and/or radioactive markings or attributes, or any combination thereof. In a preferred embodiment, the traceable marker 104 is constructed at least in part of a metal such as, for example but without limitation, iron oxide or stainless steel, and can be localized at least via visual, tactile, radiographic, and magnetic means. The traceable marker 104 may also be covered or coated at least in part with a biocompatible coating, or may be constructed of an inherently biocompatible material (e.g., polished stainless steel, titanium, polymethylmethacrylate, polytetrafluoroethylene) that minimizes or substantially eliminates immunological and other adverse reactions. This may be of particular interest for a traceable marker configured for long term implantation.
The various traceable markers (e.g., traceable marker 104) described herein may be provided with agents that may cause a beneficial, therapeutic, or diagnostic effect in the body and particularly when implanted into or near a lung nodule, for example as a coating or as a part of the traceable marker. Various types of drugs may be incorporated into the traceable marker. Certain chemicals may also be used to provide, for example, a heating effect. Here, a heating effect could be provided by using an air-activated iron-based exothermic reaction typically used in hand-warmers. The agents referred to herein may include chemicals, drugs, or other agents, either alone or in combination, that cause a beneficial, therapeutic, or diagnostic effect with regard to the nodule 102 and/or tissue surrounding the nodule 102, and may comprise anticancer agents (including chemotherapy agents), anti-inflammatory agents, antimicrobial agents, antiviral agents, contrast-enhancing agents (including MRI contrast agents), tissue growth enhancers (including stem cells), tissue growth inhibitors, radioprotective agents, radioactive materials and agents, and other such agents.
In use, an operator may navigate the sensor 110 in proximity of the nodule 102 by means of a navigation aid 112. For example, the sensor 110 may be configured to identify the marker I 04 by magnetic means, and the sensor 110 may comprise a magnetic induction loop or other such magnetic localization functionality, and the navigation aid 112 may then comprise a gauge illustrating graphically how the magnetic field increases in relation to the proximity and orientation of the sensor 110 with respect to the marker 104. In a preferred embodiment, the navigation aid 112 indicates the direction of the marker I 04 with respect to the location of the sensor 110. Of course, the sensor 110 may be configured to detect any other localization attributes, and could, in the case of the marker I 04 being constructed at least in part from a radioactive material, incorporate a Geiger counter or other sensor responsive to radioactivity. The navigation aid 112 is not necessarily a gauge, and could include, for example, a graphical or numerical readout (e.g., on a computer screen), or could include any one or more of visual, audible, or tactile (e.g., vibrational) feedback responsive to the localization attribute.
Here, the receptacle 306, with the aid of the sensor 310, is navigated near the marker 304. The marker 304 may, as described above, be provided with one or more localization attributes that permit the sensor 310 to locate it. As discussed above in
Once the marker 304 has been located, the aperture 309 is positioned in close proximity to the marker 304, and the vacuum source 314 is activated or placed in fluidic communication with the receptacle 306 so as to suction the marker 304 and the tissue surrounding it (which should include the nodule 302) into the receptacle 306. The potion of tissue within the receptacle 306 may then be resected, for example by cutting the tissue flush with the aperture 309. In some embodiments, a cutting apparatus (not illustrated) integrated with the device 301 may be provided to re sect the tissue within the receptacle 306.
The proximal end 410 of the delivery catheter 403 may be attached to an energy source 412, and the distal tip 408 of the catheter 403 comprises an antenna or other emitter. Examples of antenna tips that may be suitable for use with the system 401 are discussed below in relation to
The distal tip 408 is placed in close proximity to the nodule 402 such that energy (e.g., microwaves) emitted from the antenna may be used to irradiate, heat, or otherwise treat the nodule 402. Microwaves in some cases may be advantageous in the treatment of lung nodules because they are able to preferentially heat the denser nodule tissue while minimally heating the less-dense surrounding tissue. Thus, a preferred method of treatment may comprise navigating the delivery catheter 403 such that the distal tip 408 is in close proximity to the nodule 402. Activation of the energy source 412, configured here to generate microwaves, then permits the antenna to irradiate the nodule 402 with microwaves. In some embodiments, the distal tip 408, and in particular the antenna, may comprise a protective sheath or covering. In some embodiments, openings may be provided on at least a portion of the antenna, and these may be configured so that the energy emitted by the antenna may pass in a cross-hatch pattern into the nodule 402.
Certain embodiments may use a traceable marker, for example those described above in relation to
The treatment of nodules 402 or other areas of cancerous or diseased tissue may require expanding a zone of treatment beyond the immediate zone of cancerous or diseased tissue, such that sufficient margins are provided around the area to encompass tissue that may not necessarily be showing indicia of disease or cancer. Such margins may encompass tissue that while not necessarily necrotic or cancerous, may, for example, show signs of inflammation. In some embodiments, as illustrated in
The markers 404 can be implanted into the nodule 402 (e.g., inter-nodule markers 404a), into the airway 400 (e.g., intra-airway markers 404b), and/or into tissue outside of the airway 400 and outside the nodule 402 (e.g., intermediary nodules 404c). In some embodiments, each of the markers 404 can be positioned outside of the nodule 402. Placing all of the markers 404 outside the nodule 402 can, in some embodiments, allow for treatment of a nodule 402 without direct physical contact (e.g., piercing) interaction with the nodule 402. In some embodiments, treatment of a nodule 402 without direct physical contact with the nodule can reduce or eliminate the likelihood of release of contents of the nodule 402 (e.g., cancerous cells, infection) to the tissue surrounding the nodule 402. Each of the markers 404 can have an effective zone 414 surrounding the respective markers 404. The effective zones 414 can generally define the extent to which the respective markers 404 effect treatment (e.g., heating, energy application) to the tissue surrounding the markers 404. The effective zones can 414 can have a generally spherical shape (e.g., for generally spherical markers 404). In some embodiments, the effective zones 414 have oblong or other shapes. According to some variants, the effective zone 414 of a given marker 404 generally follows the shape of that marker 404. The size of an effective zone 414 of a given marker 404 can vary depending on a one or more parameters. For example, in some embodiments, the size of an effective zone 414a can depend, in part, on the size of the associated marker 404. In some embodiments, the size of an effective zone 4 I 4a can depend on the amount of power emit by or into the associated marker 404. In some embodiments, the size of an effective zone 414a can depend on the nature of the tissue into which the marker 404 is deployed (e.g., the effective zone 414a can vary depending on the density and/or resistivity of the tissue into which the marker 404 is deployed).
The treatment efficacy (e.g., the extent to which the marker heats or otherwise treats the surrounding tissue) of each marker 404 within the effective zones 414 at points in the zones 414 can, in some embodiments, diminish at distances further from the markers 404 (e.g., radially-outward points in the effective zones 414 in the case of spherical zones 414). The markers 404 can be distributed such that their respective effective zones 414 overlap in overlap zones 414a in the tissue being treated. In some embodiments, the overlap zones 414a can realize higher treatment efficacy (e.g., greater heating, higher energy application) than the equivalent points in the treatment zones would realize without overlap.
In some embodiments, the treatment efficacy of each individual marker 404 can be low enough such that one or more of the individual markers 404 would not, themselves, effect treatment of the tissue surrounding the marker 404. For example, one or more of the individual markers 404 can be configured to emit heat or other energy to the surrounding tissue at a level that would not, per individual marker 404, damage or otherwise effect change in the surrounding tissue. In some such embodiments, the overlap zones 4 I 4a can realize cumulative treatment efficacy that is high enough to effect treatment of the tissue within the overlap zones 414a. For example, as illustrated in 4B, two or more markers 404 can be positioned into or near a nodule 402 such that the overlap zone 4 I 4a created by the two or more markers 404 completely envelopes the nodule 402.
In some embodiments, application of energy such as, for example, microwave or radiofrequency energy, could selectively heat or thermoablate a zone of treatment that is equal to or greater than the margins around the nodule 402 that encompass tissue that is either diseased or cancerous, or likely to become diseased or cancerous. In some embodiments, the use of multiple markers 404 can facilitate the creation of a customized zone of treatment that more closely maps to the margins around the nodule 402 that encompass tissue that requires treatment.
FIG. SB illustrates another embodiment with dual or multiple antenna tips S08, S09. Here, antenna tips S08, S09 are inserted in proximity to a site of interest such as a nodule S02. The antenna tips S08, S09 may, as illustrated here, be navigated to the nodule S02 via one catheter SOS. Multiple catheters, needles, or other endoscopic apparatuses may also be used alone or in combination to place the antenna tips S08, S09 in proximity to the nodule S02. In a dual or multiple antenna tip arrangement, the respective antenna tips S08, S09 are preferably arranged so as to direct their energy inwards. Accordingly, when these tips S08, S09 are placed in proximity to the nodule S02, energy such as microwave radiation or radiofrequency current may be emitted or directed toward the nodule S02 so as to heat or irradiate it.
In some embodiments using bipolar high frequency (e.g., radiofrequency) current, a system comprising at least two antenna tips S08, S09 functioning as electrodes may be used to treat the nodule S02. Here, positioning the antenna tips S08, S09 on opposite sides of the nodule S02 permits an electric field to flow between the two antenna tips S08, S09, thus causing heating and/or thermoablation of the nodule S02 and intervening tissue. Such a treatment modality may be advantageous if, for example, a nodule S02 is located between two branches of an airway. In such a situation, the antenna tip S08 may be advanced along one airway and positioned in proximity to one side of the nodule S02, and the antenna tip S09 may be advanced along the other airway and positioned similarly along another side of the nodule S02. When activated, the antenna tips S08, S09 would then cause heating of the nodule S02.
FIG. SC illustrates an embodiment of a pinpoint antenna tip S08. As with the preceding figures, the distal tip S06 of a catheter SOS comprises an antenna tip S08. While this embodiment may function in a similar fashion as the other embodiments illustrated in
Although
In some embodiments, it is not necessary to use a probe 608 to induce magnetic heating of the marker 604. For example, the marker 604 may be activated or heated using magnetic coupling via a Magnetic Resonance Imaging (“MRI”) device, which may be advantageous as such devices are present in many hospitals and other patient care settings. In such embodiments, the magnetic field and/or field frequency applied by the MRI device and/or the marker 604 is configured such that the marker 604 activates or heats without significant migration when under the influence of the magnetic field. Without wishing to be bound by theory, it is believed that there is a linear relationship between the magnetic field applied and the resulting heating of the marker 604, and as such the field may be tailored (alone or in combination with other variables) to achieve appropriate heating of the marker 604. In some embodiments, an applied magnetic field in the range of 1.5-3T, and in particular LST, has been found sufficient to induce heating.
In some embodiments, the marker 604 may be made MRI-compatible by having it substantially respond only to magnetic fields stronger than those generated by an MRI device. For example, most MRI devices function in a range between 1.5-3T, and a marker 604 may be designed so as to substantially respond to a magnetic field greater than 4T. The marker 604 may then be used in conjunction with a device capable of generating such a field for magnetic heating of the nodule 602 while still being MRI-compatible.
U.S. patent application Ser. No. 13/778,008, entitled PULMONARY NODULE ACCESS DEVICES AND METHODS OF USING THE SAME, filed Feb. 26, 2013 and hereby incorporated by reference herein in its entirety, and which may be used in conjunction with the embodiments described herein.
Some embodiments may also use an anchoring mechanism positioned along the tail 706, and in particular at its distal end. This anchoring mechanism may be used to secure the tail 706 to tissue (e.g., a portion of an airway). In some embodiments, all or part of the tail 706 is radioopaque, which may be beneficial when used in conjunction with fluoroscopy techniques. Together with embodiments such as those illustrated in
Additional embodiments may use the power supplied to the marker 704 for electrical therapy. The power may also be used to power sensors or other devices integrated into the marker 704. For example, the power may be used to apply an electrical field to a marker 704 comprising a piezoelectric material. In some embodiments, applying an electrical field to a marker 704 comprising a piezoelectric material can cause the marker 704 to emit an ultrasonic wave to the tissue surrounding the marker 704. The ultrasonic wave can be used to treat (e.g., heat) the tissue surrounding the marker 704. In other embodiments, the power supplied to the marker 704 may be used to trigger treatment modalities such as the release of agents on or within the marker 704. The electrical power supplied may also be used to induce electroporation of the cells in the nodule 702 so as to increase their permeability to chemicals or other therapeutic agents. Thus, selective therapy of the nodule 702 may be achieved. In some embodiments, electrical therapy from power supplied to the marker 704 may be used in addition, in combination, or as an alternative to other treatment modalities.
In some embodiments, the marker 704 may be configured to cool and/or heat tissue surrounding the marker 704 through use of the Peltier effect. For example. the marker 704 can be constructed from at least two different materials (e.g., two metals) having a junction through which an electric current is directed. In some embodiments, heat is absorbed on one side of the junction and heat is generated on the other side of the junction. A heat sink (e.g., a conductive wire or other structure) can be coupled to the heat generating side of the junction to dissipate the generated heat. In some embodiments, dissipation of the heat from the heat generating side of the junction and heat absorption from the opposite side of the junction can cool the tissue surrounding the marker 704. In some embodiments, the heat generated from the heat generating side of the marker 704 can be used to heat and/or thermoablate a portion of tissue surrounding the marker 704.
Some embodiments may also provide for injecting or releasing an enhancement substance such as an electrically or thermally conductive fluid or gel in the tissue and space around the marker 704. Such an enhancement substance may for example be released from the marker 704, or be injected (for example, by using a catheter or needle) around the marker 704. The use of an enhancement substance may allow the treatment modality used in conjunction with the marker 704 to affect a greater area of tissue near the marker 704 and specifically the nodule 702. Such an effect may enhance treatment of the tissue margins surrounding the nodule 702, which may be cancerous or pre-cancerous but not yet identifiable as such.
The secondary module 908 may comprise a wireless charging module. In one embodiment, the wireless charging module may comprise a passive coil that is activated when the wand 910 is passed over it. The wand 910 may be connected to a charging mechanism present in the master control unit 912, and which may comprise a RF or high frequency generator that can charge the battery or other power storage module present in the secondary module 908 via the wand 910. In some embodiments, the wand 910 may also be used to activate and/or control the secondary module 908 and/or the marker 904 so as to activate therapy (e.g., heating), transmit data, and so forth.
Although this invention has been disclosed in the context of certain embodiments and examples, those skilled in the art will understand that the present invention extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the invention and obvious modifications and equivalents thereof. In addition, while several variations of the invention have been shown and described in detail, other modifications, which are within the scope of this invention, will be readily apparent to those of skill in the art based upon this disclosure. It is also contemplated that various combinations or sub-combinations of the specific features and aspects of the embodiments may be made and still fall within the scope of the invention. It should be understood that various features and aspects of the disclosed embodiments can be combined with, or substituted for, one another in order to form varying modes or embodiments of the disclosed invention. Thus, it is intended that the scope of the present invention herein disclosed should not be limited by the particular disclosed embodiments described above.
This application claims the benefit under 35 U.S.C. § 120 as a continuation of U.S. patent application Ser. No. 16/024,144, titled APPARATUSES, METHODS, AND SYSTEMS FOR THE IDENTIFICATION AND TREATMENT OF PULMONARY TISSUE, filed Jun. 29, 2018, which claims benefit under 35 U.S.C. § 120 as a continuation of U.S. patent application Ser. No. 14/498,365, titled APPARATUSES, METHODS, AND SYSTEMS FOR THE IDENTIFICATION AND TREATMENT OF PULMONARY TISSUE, filed Sep. 26, 2014, which claims the benefit under 35 U.S.C. § 120 and 35 U.S.C. § 365(c) as a continuation of International Application No. PCT/US2013/031067, designating the United States, with an international filing date of Mar. 13, 2013, titled APPARATUSES, METHODS, AND SYSTEMS FOR THE IDENTIFICATION AND TREATMENT OF PULMONARY TISSUE, which claims the benefit of U.S. Provisional Application No. 61/617,590, titled APPARATUSES, METHODS, AND SYSTEMS FOR THE IDENTIFICATION AND TREATMENT OF PULMONARY TISSUE, filed Mar. 29, 2012, which is hereby incorporated by reference herein in its entirety. Any and all priority claims identified in the Application Data Sheet, or any correction thereto, are hereby incorporated by reference under 37 CFR 1.57.
| Number | Date | Country | |
|---|---|---|---|
| 61617590 | Mar 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16024144 | Jun 2018 | US |
| Child | 16151993 | US | |
| Parent | 14498365 | Sep 2014 | US |
| Child | 16024144 | US | |
| Parent | PCT/US2013/031067 | Mar 2013 | US |
| Child | 14498365 | US |
