Patent Publication Number: US-2023149001-A1

Title: Cytology sampling system and method of utilizing the same

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/810,997, filed on Mar. 6, 2020, now U.S. Pat. No. 11,559,291, which is a continuation of U.S. Pat. application Ser. No. 14/176,256, filed on Feb. 10, 2014, now U.S. Pat. No. 10,595,830, which claims the benefit of the filing date of provisional U.S. Patent Application No. 61/763,316, filed on Feb. 11, 2013. 
    
    
     INTRODUCTION 
     The present disclosure relates to the collecting of cell specimens for diagnostic purposes and, more specifically, a cytology sampling tool that is positionable through one or more branched luminal networks of a patient for collecting cell specimens. 
     BACKGROUND 
     Cancer can be prevented, treated, and possibly cured if it is detected early enough, preferably in its precancerous or precursor stages. Accordingly, much effort has been directed to developing improvements in early detection devices and of the presence of cancer in its early stages. 
     Samples that contain more cells provide a greater accuracy and greater likelihood of early detection of the presence of cancer. A continuing need exists for devices capable of collecting larger cell samples form tissue of a patient. 
     Endobronchial navigation uses CT image data to create a navigation plan to facilitate advancing a navigation catheter (or other suitable device) through a bronchoscope and a branch of the bronchus of a patient to the nodule. Electromagnetic tracking may also be utilized in conjunction with the CT data to facilitate guiding the navigation catheter through the branch of the bronchus to the nodule. In certain instances, the navigation catheter may be positioned within one of the airways of the branched luminal networks adjacent to or within the nodule or point of interest to provide access for one or more tools. Once the navigation catheter is in position, fluoroscopy may be used to visualize cytology tools, such as, for example, biopsy brushes, needle brushes and biopsy forceps as they are passed through the navigation catheter and into the lung and to the nodule or point of interest. 
     SUMMARY 
     In an aspect of the present disclosure, a cytology tool includes a flexible shaft, a brush, and a position sensor. The flexible shaft defines proximal and distal ends. The brush is coupled to the distal end of the flexible shaft. The brush includes a plurality of brush shafts each having bristles along a portion of a length thereof. The bristles are coupled to and extend radially away from an outer surface of each of the plurality of brush shafts. The position sensor is configured to provide an indication of the location of the position sensor within a luminal structure. The distal ends of each of the plurality of brush shafts may be biased away from the distal ends of each of the other brush shafts. 
     In some embodiments, distal ends of each of the plurality of brush shafts include needle tips for penetrating tissue. In certain embodiments, distal ends of each of the plurality of brush shafts are blunt for atraumatically contacting tissue. 
     In some embodiments, the bristles are helically disposed along a length of each of the brush shafts. The bristles may be disposed along the entire length of each of the brush shafts. 
     In aspects of the present disclosure, a cytology sampling system includes a catheter tube and a cytology tool. The catheter tube includes open proximal and distal ends. The cytology tool may be any of the cytology tools disclosed herein. 
     In some embodiments, the brush has a transport configuration such that the distal ends of each the plurality of brush shafts adjacent one another and a deployed configuration such that the distal ends of each of the plurality of brush shafts are spaced-apart from one another. In the transport configuration, the brush may be disposed within the catheter tube between the proximal and distal ends thereof and in the deployed configuration, the brush may extend from the distal end of the catheter tube. 
     In certain embodiments, the cytology sampling system includes a positioning detection system operatively coupled to the position sensor to determine the location of the position sensor with respect to targeted tissue within a bronchial airway. In particular embodiments, the cytology sampling system may include a locatable guide with a steerable distal tip and a working channel. The steerable distal tip is adapted to position the position sensor adjacent target tissue within a bronchial airway. 
     In some aspects of the present disclosure, a method of sampling tissue includes identifying the location of a target in a luminal structure, generating a pathway plan to the target, traversing a cytology tool through the luminal network while sensing its location, generating a representation of the cytology tool traversing the luminal network to the target, and contacting the target tissue with bristles of the cytology tool. The cytology tool may be any of the cytology tools disclosed herein. The method may further include inserting the cytology tool through a catheter tube. The method may include extending the bristles of the cytology tool from a distal end of the catheter tube such that the brush shafts bias away from one another. Positioning the distal end of the catheter tube may include inserting the catheter tube through a working channel of a positioning assembly positioned adjacent the target. 
     In some embodiments, traversing the luminal network includes steering a distal end of the cytology tool to a location adjacent the target with a steerable distal tip. In certain embodiments, the method includes registering a sensed position of the cytology tool to image data of the luminal network. The method may include registering a sensed position of the cytology tool to image data of the luminal network. The method may also include registering the sensed position of the cytology tool to a 3D model of the luminal network. 
     In certain embodiments, the method includes confirming the placement of the cytology tool using one or more imaging modalities. In particular embodiments, contacting the target tissue includes penetrating the wall of a body lumen with a needle tip of at least one of the plurality of brush shafts to contact the target with bristles of the at least one of the plurality of brush shafts. 
     Further, to the extent consistent, any of the aspects described herein may be used in conjunction with any or all of the other aspects described herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Various embodiments of the present disclosure are described hereinbelow with references to the drawings, wherein: 
         FIG.  1    is a perspective view of a cytology sampling system including a cytology catheter assembly configured for use with the cytology sampling system in accordance with the present disclosure with the brush in a transport configuration; 
         FIG.  2    is a perspective view of the cytology catheter assembly of  FIG.  1    with the brush in a deployed configuration; 
         FIG.  3    is an enlarged view of the detail area  3  shown in  FIG.  2   ; 
         FIG.  4    is a screen shot of a CT based luminal navigation system in accordance with the present disclosure; 
         FIG.  5    is a perspective view of a cytology sampling system and luminal navigation system configured for use the cytology catheter assembly shown in  FIG.  1    in accordance with the present disclosure; 
         FIG.  6    is a side view of a luminal catheter delivery assembly including an extended working channel and locatable guide catheter in accordance with the present disclosure; 
         FIG.  7    is a partial, perspective view of a distal end of the locatable guide catheter shown in  FIG.  6   ; 
         FIG.  8    is a side view of the extended working channel shown in  FIG.  7    with the guided tip extending from a distal end thereof; 
         FIG.  9    is a screen shot of a CT based luminal navigation system in accordance with the present disclosure; 
         FIG.  10 A  is a schematic, plan view of the extended working channel positioned within a bronchoscope prior to being positioned within a trachea of a patient; 
         FIG.  10 B  is a schematic, plan view of the bronchoscope shown in  FIG.  10 A  positioned within the trachea of the patient with the extended working channel extending distally therefrom; 
         FIG.  10 C  is a partial, cutaway view of the extended working channel and locatable guide positioned within the bronchoscope; 
         FIG.  11 A  is a schematic, plan view of the bronchoscope positioned within the trachea of the patient with the extended working channel extending distally therefrom; and 
         FIG.  11 B  is a partial, cutaway view of the extended working channel and the cytology catheter assembly of  FIG.  1    positioned within the bronchoscope. 
     
    
    
     DETAILED DESCRIPTION 
     A sampling tool, such as a cytology-sampling tool that is positionable through one or more branched luminal networks of a patient to sample tissue may prove useful in the surgical arena and the present disclosure is directed to such apparatus, systems, and methods. Access to luminal networks may be percutaneous or through a natural orifice. In the case of a natural orifice, an endobronchial approach may be particularly useful in the treatment of lung disease or the like. Targets, navigation, access, and treatment may be planned pre-procedurally using a combination of imaging and/or planning software. In accordance with these aspects of the present disclosure, the planning software may offer custom guidance using pre-procedure images. Navigation of the luminal network may be accomplished using image-guidance. These image-guidance systems may be separate or integrated with the cytology sampling tool or a separate access tool and may include MM, CT, fluoroscopy, ultrasound, electrical impedance tomography, optical, and device tracking systems. Methodologies for locating the separate or integrated to the sampling device or a separate access tool include EM, IR, echolocation, optical, and others. Tracking systems may be integrated into imaging device, where tracking is done in virtual space or fused with preoperative or live images. In some cases, the sampling target may be directly accessed from within the lumen, such as for the sampling of the endobronchial wall for COPD, Asthma, lung cancer, etc. In other cases, the sampling tool and/or an additional access tool may be required to pierce the lumen and extend into other tissues to reach the target, such as for the sampling of disease within the parenchyma. Final localization and confirmation of sampling tool placement may be performed with imaging or navigational guidance using the modalities listed above. The monitoring of the sampling may be monitored from within the lumen or extracorporeally using the image-guidance modalities described above. 
     Detailed embodiments of the present disclosure are disclosed herein; however, the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure. 
     Referring to  FIGS.  1 - 3   , a cytology sampling system  10  is provided in accordance with the present disclosure including a cytology catheter assembly  12 . The cytology catheter assembly  12  includes a cytology tool  14  and a catheter tube  43  configured to house the cytology tool  14 . A proximal end  43   a  of the catheter tube  43  is open and may include a cuff  49 . A distal end  43   b  of the catheter tube  43  is open. The catheter tube  43  may have an outer diameter in a range of about 1.5 mm to about 2.5 mm, e.g., about 1.92 mm. 
     The cytology tool  14  includes a handle  40 , a flexible shaft  42 , and a brush  44 . The handle  40  includes a distal handle surface  41  configured to abut the proximal end  43   a  of the catheter tube  43 . A working length of the flexible shaft  42  distally extends from the distal handle surface  41  to the brush  44  and is insertable through the catheter tube  43  as detailed below. The working length of the flexible shaft  42  may be in a range of about 60 cm to about 180 cm, e.g., about 120 cm. The brush  44  is coupled to a distal end  42   b  of the flexible shaft  42 . As shown in  FIG.  2   , brush  44  includes three brush tips  45 ; however, it is contemplated that brush  44  may include a fewer or a greater number of brush tips  45 . The inclusion of additional brush tips has been shown to increase the number of cells collected from targeted tissue during a sampling procedure. 
     With particular reference to  FIG.  3   , each brush tip  45  includes a brush shaft  46 , bristles  47 , and a tip  48 . The brush shaft  46  is flexible and biased away from a longitudinal axis defined by the flexible shaft  42 . The bristles  47  cover a portion of the brush shaft  46 . In embodiments, the bristles  47  are disposed along an entire length L of the brush shaft  46 . In some embodiments, the bristles  47  are helically disposed about a portion of the length L of the brush shaft  46 . The bristles  47  are configured to capture tissue, i.e., cells, from targeted tissue. The tip  48  may be a needle tip configured to penetrate tissue. In certain embodiments, the tip  48  may be blunt to atraumatically contact tissue. The brush shaft  46  defines the length L from a proximal end  46   a  to a distal end  46   b  thereof. The length L may be in a range of about 10 mm to about  25  mm, e.g., about 15 mm. It is also contemplated that the length L may be less than 10 mm or greater than 25 mm. Each brush shaft  46  may have an outer diameter in a range of about 0.5 mm to about b 1 mm, e.g., about 0.75 mm. The bristles  47  may be constructed of nylon extending in a range of about 0.25 mm to about 1.0 mm, e.g., about 0.85 mm, from the brush shaft  46 . 
     The brush  44  has a transport or insertion configuration ( FIG.  1   ) and a deployed configuration ( FIG.  2   ). In the transport configuration each brush shaft  46  is substantially aligned with the other brush shafts  46  with the distal ends  46   b  of the brush shafts  46  adjacent one another as shown in  FIG.  1   . The brush  44  is disposed within the catheter tube  43  such that catheter tube  43  urges each brush shaft  46  into substantial alignment with the longitudinal axis defined by the flexible shaft  42  to substantially align the brush shafts  46  in the transport configuration. In the deployed configuration, the distal ends  46   b  of the brush shafts  46  are spaced-apart from one another in cooperation with the biasing of the brush shafts  46  as shown in  FIG.  2   . The brush  44  is disposed outside of the catheter tube  43  permitting the brush shafts  46  to spread-apart into the deployed configuration. 
     In use, the distal end  43   b  of the catheter tube  43  is positioned adjacent targeted tissue with the brush  44  in the transport configuration and the distal handle surface  41  of the handle  40  spaced-apart from the proximal end  43   a  of the catheter tube  43  as shown in  FIG.  1   . A method for positioning the distal end  43   b  of the catheter tube  43  adjacent targeted tissue is described in detail below. When the distal end  43   b  is positioned adjacent the targeted tissue, the distal handle surface  41  of the handle  40  is moved towards the proximal end  43   a  of the catheter tube  43  to extend the brush  44  from the distal end  43   b  of the catheter tube  43  as shown in  FIG.  2   . When the brush  44  extends from the distal end  43   b  of the catheter tube  43 , the brush shafts  46  bias the brush  44  to the deployed configuration. In the deployed configuration, the bristles  47  contact targeted tissue to capturing cell samples from the targeted tissue. When the bristles  47  have captured cell samples, the distal handle surface  41  of the handle  40  is retracted away from the proximal end  43   a  of the catheter tube  43  to withdraw the brush  44  into the distal end  43   b  of the catheter tube  43  transitioning the brush  44  into the transport configuration. The cell samples are retained on the bristles  47  of the brush  44  when the brush  44  is withdrawn into the catheter tube  43 . The cell samples may be removed from the bristles  47  and examined to determine if the targeted tissue is diseased. It is also contemplated that the catheter tube  43  may be used to aspirate cells adjacent the distal end thereof to retain cell samples . 
     In embodiments, that the bristles  47  capture tissue between the brush shafts  46  as the brush  44  transitions from the deployed configuration to the transport configuration. For example, the distal ends  46   b  of the brush shafts  46  may pierce targeted tissue and the catheter tube  43  may be advanced over the brush  44  to transition the brush  44  to the transport configuration such that a portion of the tissue between the brush shafts  46  (i.e., the tissue pierced by the brush shafts  46 ) is retained between the brush shafts  46  and drawn into the catheter tube  43 . 
     The cytology catheter assembly  12 , depicted in  FIG.  1    is configured to collect cell samples from targeted tissue, and as further set forth in  FIG.  4    enables a method of identifying targeted tissue (hereinafter simply referred to as “a target”) utilizing computed tomographic (CT) images, and once identified further enables the use of a navigation or guidance system to position the distal end  43   b  of the catheter tube  43  adjacent the target. CT data facilitates the planning of a pathway to an identified target as well as providing the ability to navigate through the body to the target location, this includes a preoperative and an operative component (i.e., pathway planning and pathway navigation). As detailed below, the cytology catheter assembly  12  is guided through the lungs of a patient; however, it is contemplated that the cytology catheter assembly  12  may be guided through other tubular structures of a patient; e.g., gastro-intestinal tract, lymphatic system, venous, billiary, etc. 
     The pathway planning phase is generally described below. First, planning a pathway involves using software for generating and viewing a three-dimensional (3D) model of the bronchial airway tree (“BT”) and viewing the CT data to identify targets. Next, the software is used to select a pathway on the BT, either automatically, semi-automatically, or manually, if desired. It is to be understood that the airways are being used herein as an example of a branched luminal network. Hence, the term “BT” is being used in a general sense to represent any such luminal network (e.g., the circulatory system, or the gastro-intestional tract, etc.) 
     Using a software graphical interface  64  as shown in  FIG.  4   , generating and viewing a BT, starts with importing CT scan images of a patient&#39;s lungs into the software. The software processes the CT scans and assembles them into a three-dimensional CT volume by arranging the scans in the order they were taken and spacing them apart according to the setting on the CT when they were taken. The software uses the newly-constructed CT volume to generate a three-dimensional map, or BT, of the airways. The software then displays a representation of the three-dimensional map  66  on the software graphical interface  64 . A user may be presented with various views to identify masses or tumors that the medical professional would like to biopsy or treat, and to which the medical professional would like to use the cytology sampling system  10  to navigate. 
     Next, the software selects a pathway to a target, e.g., target  68  identified by a medical professional. In one embodiment, the software includes an algorithm that does this by beginning at the selected target and following lumina back to the entry point. The software then selects a point in the airways nearest the target. The pathway to the target may be determined using airway diameter. Alternatively, the user rotates the generated volume to identify a convenient entry into the luminal network and the software generates a pathway back to the starting point. 
     After the pathway has been determined, or concurrently with the pathway determination, the suggested pathway is displayed for user review. This pathway is the path from the trachea to the target that the software has determined the medical professional is to follow for treating the patient. This pathway may be accepted, rejected, or altered by the medical professional. Having identified a pathway in the BT connecting the trachea in a CT image with a target, the pathway is exported for use by cytology sampling system  10  to place a catheter and tools at the target for biopsy of the target and eventually treatment if necessary. Additional methods of determining a pathway from CT images are described in commonly assigned U.S. patent application Ser. No. 13/838,805 entitled “Pathway Planning System and Method” the entirety of which is incorporated herein by reference. 
       FIG.  5    shows a patient “P” lying on an operating table  70  and connected to a positioning detection system  60  enabling navigation along the determined pathway within the luminal network to achieve access to the identified target. The positioning detection system  60  includes a bronchoscope  72 , monitoring equipment  74 , and a tracking module  80 . The bronchoscope  72  is inserted into the patient&#39;s lungs. The bronchoscope  72  is connected to the monitoring equipment  74  and the tracking module  80 , and typically includes a source of illumination and a video imaging system. In certain cases, the devices of the present disclosure may be used without a bronchoscope, as will be detailed below. The tracking module  80  receives sensor data from a variety of sensors enabling the position of the patient “P”, the location of the cytology catheter assembly  12 , and the image data to be registered to one another thereby permitting navigation of the luminal network using the CT image data and real-time detection of location. Specifically, tracking module  80  utilizes a six DOF (degrees of freedom) electromagnetic position measuring system according to the teachings of U.S. Pat. No. 6,188,355 and published PCT Application Nos. WO 00/10456 and WO 01/67035, which are incorporated herein by reference. An electromagnetic field transmitter  76  is implemented as a board or mat positioned beneath patient “P.” A plurality of reference sensors  78  are placed on the patient “P” and their location within the electromagnetic field generated by the electromagnetic field transmitter  76  can be detected. The location of each sensor  78  is determined in six DOF and their six coordinates sent to tracking module  80  and computer  82 . One of skill in the art will recognize that the tracking module  80  may be incorporated into computer  82  as a software component and need not be a separate component as depicted in  FIG.  5   . 
       FIG.  6    depicts a positioning assembly  84 , constructed and operative according to the teachings of the present disclosure. The positioning assembly  84  includes a locatable guide  86  which has a steerable distal tip  88 , an extended working channel  90 , and, at its proximal end, a control handle  92 . 
     There are several methods of steering the locatable guide  86 , and therewith the extended working channel  90 . In a first method, a single direction of deflection may be employed. Alternatively, a multi-directional steering mechanism with a manual direction selector may be employed to allow selection of a steering direction by the practitioner without necessitating rotation of the catheter body. With multi-directional steering four elongated tensioning elements (“steering wires”)  98   a  are implemented as pairs of wires formed from a single long wire extending from handle  92  to steerable distal tip  88 . Steering wires  98   a  are bent over part of a base  98   b  and return to handle  92 . Steering wires  98   a  are deployed such that tension on each wire individually will steer the steerable distal tip  88  towards a predefined lateral direction. In the case of four steering wires  98   a , the directions are chosen to be opposite directions along two perpendicular axes. In other words, the four steering wires  98   a  are deployed such that each wire, when actuated alone, causes deflection of the steerable distal tip  88  in a different one of four predefined directions separated substantially by multiples of  90 °. 
     Locatable guide  86  is inserted into the extended working channel  90  within which it is locked in position by a locking mechanism  94 . A position sensor element  96  is integrated with the steerable distal tip  88  of the locatable guide  86  and allows monitoring of the tip position and orientation (six DOF) as the sensor element  96  traverses the electromagnetic field generated by the electromagnetic field transmitter  76 . 
     In embodiments, extended working channel  90  may have a curved or hooked tip configuration  91  as shown in  FIG.  8   . This alternative is currently marketed by Covidien LP under the name EDGE®. Differing amounts of pre-curve implemented in the extended working channel  90  can be used, however, common curvatures include  45 ,  90 , and  180  degrees. The  180  degree extending working channel  90  has been found particular useful for directing the locatable guide  86  to posterior portions of the upper lobe of the lung which can be particularly difficult to navigate. The locatable guide  86  is inserted into the extended working channel  90  such that the position sensor  96  projects from the extended working channel  90 . The extended working channel  90  and the locatable guide  86  are locked together such that they are advanced together into the lung passages of the patient “P.” Optionally, the locatable guide  86  or the extended working channel  90  may include a steering mechanism similar to the one described above. As can be appreciated, certain modifications may need to be made to the extended working channel  90  in order for the extended working channel to function as intended. 
     In embodiments, an integrated radial ultrasound probe “US” ( FIG.  8   ) may be provided on the extended working channel  90 , the locatable guide  86 , and/or the cytology catheter assembly  12 . For illustrative purposes, the ultrasound probe “US” is shown disposed on the extended working channel  90  and the locatable guide  86 . The ultrasound probe “US” may be configured to provide ultrasound feedback to one or more modules of the cytology sampling system  10  during navigation and insertion of the cytology tool  14  to facilitate positioning the distal end  43   b  of the catheter tube  43  adjacent target tissue. As will be appreciated a US probe may also be used without the extended working channel but in conjunction with an endoscope for imaging central lesions that would be accessible to the endoscope. Furthermore, the US probe may be used to conduct ultrasound interrogation of tissue. Alternatively, fluoroscopy or other imaging modalities may be used to confirm the placement of the locatable guide and therewith the extended working channel  90  and the brush  44 . 
     As noted above, the present disclosure employs CT data (images) for the route planning phase. CT data is also used for the navigation phase. Specifically, the CT system of coordinates is matched with the collected sensor data; this is commonly known as registration. Manual, semi-automatic, or automatic registration can be utilized with the cytology sampling system  10 . For purposes herein, the cytology sampling system  10  is described in terms of use with automatic registration. Reference is made to commonly assigned U.S. Patent Pub. No. 2011/0085720, which is incorporated herein by reference, for a more detailed description of automatic registration techniques. 
     The automatic registration method includes moving locatable guide  86  containing position sensor  96  within a branched structure of a patient “P.” Data pertaining to locations of the position sensor  96  with respect to the electromagnetic filed generated by the electromagnetic field transmitter  76  is recorded. A shape resulting from the data is compared to an interior geometry of passages of the three-dimensional model of the branched structure. And, a location correlation between the shape and the three-dimensional model based on the comparison is determined. 
     In addition to the foregoing, the software of the cytology sampling system  10  identifies non-tissue space (e.g., air filled cavities) in the three-dimensional model. Thereafter, the software records position data of the position sensor  96  of the locatable guide  86  as the locatable guide  86  is moved through one or more lumens of the branched structure. Further, the software aligns an image representing a location of the locatable guide  86  with an image of the three-dimensional model based on the recorded position data and an assumption that the locatable guide  86  remains located in non-tissue space in the branched structure. 
     Once in place in the patient “P,” a screen  93  will be displayed by the software on the monitoring equipment  74  ( FIG.  9   ). The right image is an actual bronchoscopic image  95  generated by the bronchoscope  72 . Initially there is no image displayed in the left image  97 , this will be a virtual bronchoscopy generated from the CT image data once registration is complete. 
     Starting with the locatable guide  86 , and specifically the position sensor  96  approximately 3-4 cm above the main carina, as viewed through the bronchoscope  72 , the bronchoscope  72  is advanced into both the right and left lungs to, for example, the fourth generation of the lung passages. By traversing these segments of the lungs, sufficient data is collected as described above such that registration can be accomplished. 
     Now that the targets have been identified, the pathway planned, the bronchoscope  72  including locatable guide  86  inserted into the patient “P,” and the virtual bronchoscopy image registered with the image data of the bronchoscope  72 , the cytology sampling system  10  is ready to navigate the position sensor  96  to the target  68  within the patient&#39;s lungs. The computer  82  ( FIG.  5   ) provides a display for identifying the target  68  and depicting the virtual bronchoscopy image  99 . Appearing in each of the images on the display is the pathway from the current location of the position sensor  96  to the target  68 . This is the pathway that was established during the pathway planning phase discussed above. The pathway may be represented, for example, by a colored line. Also appearing in each image is a representation of the steerable distal tip  88  of the locatable guide  86  and position sensor  96 . Once the steerable distal tip  88  traverses the established pathway, a clinician may utilize the cytology catheter assembly  12  to sample the target tissue  68  as detailed below. 
     Operation of the cytology catheter assembly  12  with the positioning assembly  84  to sample target tissue is described with reference to  FIGS.  10 A- 11 B . Once the locatable guide  86  or an additional access tool has successfully been navigated to the target  68  location, the locatable guide  86  or access tool may be removed, leaving the extended working channel  90  in place as a guide channel for the cytology catheter assembly  12  ( FIG.  1   ) to the target  68  location 
     In some cases the target may be directly accessed from within the lumen (such as for the sampling of the endobronchial wall), however in other instances, the target is not within the BT and use of the locatable guide alone does not achieve access to the target. Additional access tools may be required to cross the lumen wall and access the target (such as for the sampling of disease within the parenchyma). 
     Final localization and confirmation of the locatable guide or access tool with extended working channel may be performed with imaging and/or navigational guidance (this may include the same or different combinations of imaging and navigation techniques listed above). 
     The catheter tube  43  is inserted through the working channel  90  such that the distal end  43   b  of the catheter tube  43  is adjacent the target  68 . Alternatively, the catheter tube  43  or the cytology tool  14  may itself include a position sensor  88 , such that the catheter tube  43  is already inserted through the working channel  90  during the positioning of extended working channel. The position sensor  88  may also be disposed on the distal end  43   b  of the catheter tube  43  or on the brush  44 . The cytology tool  14  is inserted through the catheter tube  43  as detailed above to collect cell samples from the target  68 . It is also contemplated that the cytology tool  14  may be inserted directly through working channel  90  without a catheter tube  43 . 
     While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Any combination of the above embodiments is also envisioned and is within the scope of the appended claims. Therefore, the above description should not be construed as limiting, but merely as exemplifications of particular embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.