Cryoprobe assembly with integrated needle tip sleeve

Abstract

A cryoprobe assembly for cryobiopsy can include a sleeve and a cryoprobe. The sleeve can include a distal end with a sharp tip configured to pierce a portion of tissue. The cryoprobe can be configured to be disposed at least partially within the sleeve. The cryoprobe and the sleeve can be longitudinally slidable relative to each other between a plurality of positions including at least a first position wherein a distal tip of the cryoprobe is retracted within the sleeve and a second position wherein the distal tip of the cryoprobe extends distally beyond the distal end of the sleeve. The sleeve and the cryoprobe can be flexible and configured for insertion into a patient to reach the portion of tissue through a working channel of another device.

Description

CRYOPROBE ASSEMBLY WITH INTEGRATED NEEDLE TIP SLEEVECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 710,138, filed October 22, 2024, which is hereby incorporated by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure relates to cry oprobes used in bronchoscopy for tissue biopsies and diagnosis, as well as for staging and classification of lung cancer.BACKGROUND

[0003] A cryoprobe used in bronchoscopy is a medical device that can apply extreme cold (cryotherapy) to targeted tissues within bronchial airways of a patient. It can be primarily used for both diagnostic and therapeutic purposes during a bronchoscopy procedure. For example, a cryoprobe can be used in bronchoscopy for obtaining a tissue biopsy by exploiting the effects of cryoadhesion to cause tissue to adhere to the tip of the cry oprobe. Existing cry oprobes can be used to obtain large and high-quality tissue samples from tissue within the airways for diagnostic purposes, particularly in the case of lung cancer or other lung diseases. The cold freezes the tissue, which allows for better preservation of the sample's structure. Existing cry oprobes include blunt or round tips which are not designed to penetrate tissue and, therefore, such cry oprobes are ill-suited for obtaining biopsy samples of and / or applying therapy to target tissues which exist beyond the airway wall.SUMMARY

[0004] A cryoprobe assembly can include a cryoprobe and a sleeve. The sleeve can include a needle tip. The cryoprobe can be sheathed within the sleeve or unsheathed from the sleeve to expose the cryoprobe distal end or tip. The needle tip can be integrated with the sleeve. The cryoprobe can be slidablyinserted into or out of the sleeve. The cryoprobe assembly can be used to perform cryoextraction or tissue biopsy of target tissue existing beyond a lumen wall (e.g., airway wall, colon lining, etc.) of a patient. In particular, the cry oprobe may be retracted into the sleeve such that the tip of the cry oprobe is located within the sleeve, and the needle tip of the sleeve may facilitate delivery of the cry oprobe assembly through a lumen wall and into a target tissue located beyond the lumen wall. In some instances, the cry oprobe assembly may need to penetrate through some amount of healthy tissue before reaching the target tissue, and in such instances the cry oprobe may serve to plug the sleeve to prevent coring of the healthy tissue into the sleeve. Then, once the cryoprobe assembly has reached the target tissue the cry oprobe tip may be extended from the sleeve and activate to cause cryoadhesion to occur for obtaining a biopsy sample.

[0005] The sleeve can provide a protective covering for the cry oprobe during insertion in tissue of the patient. The needle tip of the sleeve can allow for penetration of the target tissue. The needle tip can be formed at the distal end of the sleeve. The needle tip can be used to facilitate penetration of the target tissue while keeping the cryoprobe shrouded within the sleeve. The sleeve can be retractable, allowing a user of the cryobiopsy device to expose a distal end of the cryoprobe when extraction of tissue is desired. A retraction mechanism can be used to move the cry oprobe or the sleeve with respect to the other such as to expose the cryoprobe from within the sleeve. Retraction of the sleeve in a proximal direction from the distal end of the sleeve can cause a distal end of the cry oprobe to be exposed such as to contact the target tissue and obtain the biopsy. The cryoprobe can use cryo-adhesion to obtain tissue samples from targets that may be located beyond a tissue wall, such as a Solitary Pulmonary Nodules (SPN) adjacent to an airway.

[0006] The cryobiopsy device's configuration can allow for a two-step process of penetration of the target tissue and obtaining a biopsy from the target tissue. For example, the cryobiopsy device can be sized, shaped, and otherwise configured to penetrate the target tissue safely. Further, once inside the target tissue, the user can retract the needle tip sleeve, exposing the cryoprobe tip. In this way, the needle tip of the sleeve can be inserted into the target tissue. The cryoprobe can be exposed either by retracting the sleeve to expose the cry oprobeor extending the cryoprobe distally into the target tissue, or both of these. The exposed needle tip can then perform cryoextraction or tissue biopsy. This approach provides a solution for obtaining tissue samples from locations that may be challenging to access with other biopsy tools, potentially improving diagnostic capabilities for certain medical conditions. This approach also allows for deployment of a cryobiopsy device that may be inserted into the target tissue as a unit and not individually or separately inserted into the target tissue.

[0007] Further, an ultrasound or other acoustic biopsy device can include an ultrasound transducer, a sleeve that encloses or sheathes a cryoprobe, and a working channel through which the sleeve and the cryoprobe passes to extend outward toward the target tissue. The ultrasound transducer can be located within a distal tip of the ultrasound biopsy device. The same or different ultrasound transducers can be used to generate or receive ultrasound waves, or both, which can be used to create real-time images of the target tissue and surrounding structures. This can allow for precise localization of the area of interest of the tissue. The working channel can serve as a conduit for the delivery of the cryoprobe. This working channel can allow for the controlled advancement and retraction of the cry oprobe within the ultrasound biopsy device. In some embodiments, the working channel extends from a handle portion of having an instrument actuator which can be manipulated by an operator to controllably extend the cryobiopsy device out of a side exit ramp located within the distal tip. Upon extension of the cryobiopsy device (e.g., the combination of cryoprobe and sleeve) via the side exit ramp, the cryobiopsy device may extend distally at an acute or oblique angle relative to the transducer and into a field of view of the transducer. Such embodiments may enable realtime (e.g., live) visualization of the cryobiopsy device within a target tissue during cryobiopsy collection.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Various examples are illustrated in the figures of the accompanying drawings. Such examples are demonstrative and not intended to be exhaustive or exclusive examples of the present subject matter.

[0009] FIG. 1 illustrates a schematic diagram of an example of a medical device system.

[0010] FIG. 2 illustrates a schematic diagram of an example of an imaging and control system of a medical device system.

[0011] FIGS. 3A-3B each illustrate an example cryobiopsy device including a cry oprobe and a sleeve including a needle tip.

[0012] FIG. 4 illustrates an example of a cryoprobe with integrate needle tip sleeve alongside a portion of tissue.

[0013] FIGS. 5A-5B each illustrate an example of a cry oprobe with integrated needle tip sleeve being inserted into a portion of tissue where the cry oprobe is sheathed within the sleeve.

[0014] FIGS. 6A-6B each illustrate an example of a cry oprobe with integrated needle tip sleeve being inserted into a portion of tissue where the cry oprobe is unsheathed from the sleeve.

[0015] FIGS. 7A-D each illustrate an example of a cry oprobe with integrated needle tip sleeve being used with real-time imaging.

[0016] FIG. 8 illustrates an example diagram of a method for using a cry oprobe with an integrated needle tip and sleeve for penetrating tissue.

[0017] FIG. 9 shows a schematic diagram of an exemplary computer-based clinical decision support system (CDSS) that can be configured to determine an optical signal parameter(s).DETAILED DESCRIPTION

[0018] Cryoprobes are used to perform cryoextraction in which tissue is cryoadhered to the local area of the cryoprobe tip and removed. In bronchoscopy, cry oprobes are used for tissue biopsies for diagnosis and staging or other classification of lung cancer. Cry oprobes are inserted within bronchial airways, but standard blunt nosed cryoprobes cannot penetrate tissue. Therefore, a tissue penetrating cry oprobe allows for improved targeting and sampling of tissue which lies beyond the airway walls (e.g., eccentric lesions).

[0019] Further, in bronchoscopy, cryoprobes are passed through bronchoscope working channels to obtain biopsies for diagnosis and staging of lung cancer. Radial endobronchial ultrasound probes may not be used concurrently as they also pass through the bronchoscope working channel. Live imaging is therefore either video-based or reliant on imaging technology external to the patient, suchas fluoroscopy. Therefore, there exists a clinical need for a device incorporating the cry oprobe tissue sampling modality with live endobronchial ultrasound.

[0020] To address these and other limitation of other approaches, a cryobiopsy device can be used that includes a cry oprobe slidably inserted into an outer sleeve. The outer sleeve’s distal tip can be shaped into a needle tip. While in its shrouded position, the outer needle tip sleeve can shroud the tip of the cryoprobe. The needle tip sleeve can then penetrate target tissue with the cryoprobe shrouded within. Once inside the target tissue, the needle tip sleeve can be retracted by the user to expose the cry oprobe tip such as for cryoextraction, tissue biopsy, etc.

[0021] Further, to address these and other previous approaches, a device, as described herein, can include an ultrasound transducer located within a distal tip and a working channel for delivery of the cryoprobe. The cryoprobe can exit the device such that the cry oprobe tip is located within the ultrasound’s field of view. The user can advance the device to locate a target tissue in the ultrasound field of view. Then, the physician can advance the cryoprobe endobronchially until the cryoprobe is adjacent to the tissue region of interest. The ultrasound image can facilitate both the location of the tissue to be sampled as well as the positioning of the cryoprobe tip. The cryoprobe can then be activated to freeze the local area of tissue surrounding the tip and removed such as for diagnosis and staging.

[0022] The above discussion is intended to provide an overview of subject matter of the present patent application. It is not intended to provide an exclusive or exhaustive explanation of the invention. The description below is included to provide further information about the present patent application.

[0023] FIG. 1 is a schematic diagram of an endoscopy system 100 that can include a control system 102 and an endobronchial ultrasound biopsy-sampling arrangement including an endoscope 104 and a medical device 108 that is attachable to the endoscope 104 and which includes a distal end 110 that extends from the distal end of the endoscope 104 via a distal working channel port (e.g., working channel port 112). The system of FIG. 1 is an illustrative example of an endoscopy system suitable for use with the systems, devices, and methods described herein.

[0024] The endoscope 104 can be insertable into an anatomical region for imaging or attachment to (e.g., via tethering) one or more sampling devices for biopsies or to one or more therapeutic devices such as for treating a disease or other undesired state associated with the anatomical region. The endoscope 104 can interface with or connect to the control system 102. The endoscope 104 is described in the present example as a bronchoscope, though other endoscopes are contemplated for use with the features and teachings of the present disclosure. The control system 102 can include a control unit 114, a display unit 116, an input unit 118, a light source 120, a fluid source 122, and a suction pump 124.

[0025] The control system 102 can include various ports for coupling with the endoscopy system 100. For example, the control unit 114 can include a data input / output port for receiving data from and communicating data to the endoscope 104. The light source 120 can include an output port for transmitting light to the endoscope 104, such as via a fiber optic link. Additionally, or alternatively, the endoscope 104 can include one or more light sources disposed near the distal end 110 to illuminate an interior anatomy for capturing images (e.g., still images or video streams) thereof. The fluid source 122 can include a port for transmitting fluid to the endoscope 104. The fluid source 122 can include, for example, a pump and a fluid tank or can be connected to an external tank, vessel, or storage unit. The suction pump 124 can include a port to draw a vacuum from the endoscope 104 to generate suction, such as for withdrawing fluid from the anatomical region into which the endoscope 104 is inserted. The display unit 116 and the input unit 118 can be used by an operator of the endoscopy system 100 to control functions of the endoscopy system 100 and view the output of the endoscope 104 such as, for example, a live video stream provided by imaging device 144. The control unit 114 can also generate signals or other outputs from treating the anatomical region where the endoscope 104 is inserted. In examples, the control unit 114 can generate electrical output, acoustic output, fluid output, gas output, or the like such as for treating the anatomical region with, for example, cauterizing, cutting, freezing, or the like. For example, the control unit 114 can include a cryobiopsy controller that controls compressed gas (e.g., compressed CO2 gas) from a gas canister 133 through a supply line 135 to a cryoprobe (e.g., cryoprobe 320 in FIGS. 3A-7D)at a distal end 110 of a medical device 108. The gas canister 133 may be coupled to the coupler section 134, which is connected to the control unit 114.

[0026] The endoscope 104 can include an insertion section 126, a functional section 128, and a handle section 130, which can be coupled to a cable section 132 and a coupler section 134. The insertion section 126 can extend distally from the handle section 130, and the cable section 132 can extend proximally from the handle section 130. The insertion section 126 can be elongated and include a bending section and a distal end to which the functional section 128 can be attached. The bending section can be controllable (e.g., by a steering control 136 on the handle section 130) to maneuver the distal end through tortuous anatomical passageways (e.g., stomach, duodenum, kidney, ureter, trachea, lungs, or the like). The insertion section 126 can also include one or more working channels (e.g., an internal lumen) that can be elongate and can support the insertion of one or more therapeutic tools of the functional section 128, such as a bronchoscope. The working channel can extend between the handle section 130 and the functional section 128. Additional functionalities, such as fluid passages, guide wires, and pull wires, can also be provided by the insertion section 126 (e.g., via suction or irrigation passageways, or the like).

[0027] A coupler section 134 can be connected to the control unit 114 to connect the endoscope 104 to multiple features of the control unit 114, such as the input unit 118, the light source 120, the fluid source 122, the suction pump 124, and a gas (e.g., CO2 gas) canister 133.

[0028] The handle section 130 can include a steering control 136 and a cable attachment portion 138, which may include a stress relief boot to shield the endoscope cable from mechanical stress (e.g., bending and / or twisting). The steering control 136 can be a knob, lever, or other actuation mechanism or the like, which can be used to navigate or control advancement of the endoscope 104 within the patient (e.g., by articulating a bending portion near the distal end of the insertion section 126). The steering control 136 can be connected to a pull wire or other actuation mechanism, extending through the insertion section 126. The endoscope 104 may further include a proximal working channel port 140 configured to facilitate delivery of components into the proximal working channel port 140 and through a working channel that extends through the insertion section 126 and out of the distal working channel port 112. Asillustrated in FIGS. 1 and 2, the proximal working channel port 140 may be configured to facilitate attachment of the medical device 108 to the handle section 130 of the endoscope 104, thereby facilitating delivery of a cry oprobe into a patient’s anatomy.

[0029] According to examples, the control system 102 can be provided on a mobile platform (e.g., a cart 142) with shelves housing the light source 120, the suction pump 124, an image processing unit 202 (FIG. 2), or the like.Alternatively, components of the control system 102, shown in FIG. 1 and FIG.2, can be provided directly on the endoscope 104 to make the endoscope “self-contained.”

[0030] The functional section 128 can include components for treating and diagnosing the anatomy of a patient. The functional section 128 can include an imaging device 144 (e.g., a complementary metal oxide semiconductor (CMOS) based, Chip-on-the-Tip image sensors), an illumination device 146 (e.g., a light emitting diode), and the working channel port 112 at a distal face of the functional section 128.

[0031] As shown in FIG. 1, a distal end 110 of the medical device 108 can extend from the working channel port 112 at the distal face of the functional section 128 of the endoscope 104. The medical device 108 can be configured to be attached to the working channel port 140 (of the endoscope 104) such that the medical device 108 extends through a working channel (e.g., extending through the insertion section 126 to the working channel port 112) of the endoscope 104 and out the distal end of the endoscope 104. The medical device 108 can include a sheath extension mechanism 148 for advancing or retracting a flexible sheath of the medical device 108 within the working channel so as to control how far distally from the working channel port 112 the distal end of the medical device 108 extends, an instrument actuator 150 (e.g., for actuating, from a side exit port of the medical device 108, a flexible cry oprobe that is enshrouded within a sheath with a needle tip as described herein), and a distal end 110. For example, the instrument actuator 150 can controllably advance and retract a medical instrument (e.g., the cryobiopsy device 300) within a lumen of the medical device 108, where the lumen extends from the medical device 108 handle through the lumen of the medical device 108 to the side exit port at or near the distal end. Manipulation of the instrument actuator 150 can control advancementor retraction of the cryobiopsy device 300 from the side exit port of the medical device 108 while the distal end 110 of the medical device 108 is extended beyond the distal end of the endoscope 104, thereby facilitating treatment or biopsy of target anatomy within a patient beyond the distal end of the endoscope 104. The sheath extension mechanism 148 can be configured to extend the medical device 108 beyond a distal end of the endoscope 104, such as to navigate the medical device 108 toward the target area within the patient. The sheath extension mechanism 148 can slide along a housing 152 of the medical device 108. The housing 152 can include one or more indicia, which indicates an amount of extension of the medical device 108 beyond a distal end of the endoscope 104 (e.g., extension beyond the working channel port 112 indicated in inches, centimeters, or other suitable linear distance units). The instrument actuator 150 can be configured to extend an instrument from the medical device 108 to obtain a tissue sample from the patient. A distal end 110 of the medical device 108 can include a transducer (or other viewing or imaging device) and a side exit port having a roof liner configured to minimize the effects of friction and / or scraping against the instrument as it is extended or retraction from the side exit port. The side exit port can be located proximal from the transducer and configured to deflect the instrument at an acute or oblique angle with respect to a longitudinal axis of the distal end 110 of the medical device 108 such that a tissue sample can be obtained from the patient while the instrument and tissue sample are within the field of view of the transducer. Stated alternatively, the configuration of the side exit port with respect to the transducer can facilitate real time visualization of the instrument within the target anatomy (e.g., visualization of a biopsy needle and target nodule being biopsied in real-time). The medical device 108 will be discussed in more detail herein.

[0032] FIG. 2 is a schematic diagram of the endoscopy system 100 of FIG. 1 including the control system 102 and the endobronchial ultrasound arrangement, which includes an endoscope 104 and a medical device 108 extendable via a distal working channel port of the endoscope 104. FIG. 2 schematically illustrates components of the control system 102 coupled to the endoscope 104 and the medical device 108. The control system 102 can include the control unit 114, which can include or be coupled to an image processing unit 202, a treatment generator 204, and a drive unit 206, as well as the light source 120, theinput unit 118, and the display unit 116. The control unit 114 can include, or can be in communication with, an endoscope, a surgical instrument, and an endoscopy system, which can include a device configured to engage tissue and collect and store a portion of that tissue and through which imaging equipment (e.g., a camera) can view target tissue via the inclusion of optically enhanced materials and components. The control unit 114can include controls for the cryoprobe 320, as described below. For example, the control unit 114 can cause the cry oprobe 320 to be exposed or extended out of the sleeve 310, as is described below in FIGS. 3 A-7D, or sheathed within the sleeve 310. The control unit 114 can activate a camera (e.g., imaging device 144) to view target tissues distal of the endoscopy system. Likewise, the control unit 114 can activate the light source 120 to illuminate an area surrounding the distal end of the endoscope 104 to facilitate capturing images via the camera (e.g., imaging device 144), which in the context of the endobronchial ultrasound arrangement depicted enables a user to visualize in real-time the internal anatomy of a patient as the distal end of the endoscope 104 is advanced and can further enable the user to visualize a distal end of the medical device 108 upon extension via a distal working channel port of the endoscope 104. As the outer profile or diameter of the medical device 108 may be less than that of the endoscope 104 (e.g., since it fits within a working channel of the endoscope 104), advancement of the medical device 108 beyond the endoscope 104 can enable tissue treatment or sampling in anatomical regions (e.g., airways) that are too small for the endoscope 104 to be advanced through. Further, the cryobiopsy device 300 may deploy a sleeve containing a cry oprobe that can sample tissue beyond the airways of the patient, as will be described below.

[0033] The coupler section 134 can be connected to the control unit 114 to connect to the endoscope 104 to multiple features of the control unit 114, such as the image processing unit 202, the treatment generator 204, or the like. The coupler section 134 can connect the gas canister 133 to a gas supply line 135, as illustrated in FIG. 1, that supplies compressed gas (e.g., compressed CChgas) to a cry oprobe. In examples, the port 138 can be used to insert another instrument or device, such as a daughter scope or auxiliary scope, or a sampling needle, biopsy needle, ablation instrument, scalpel, or the like, into the endoscope 104. Such instruments and devices can be independently connected to the control unit114 via the cable section 132. In examples, the port 140 can be used to connect the coupler section 134 to various inputs and outputs, such as video, air, light, and electricity.

[0034] The image processing unit 202, the ultrasound image processing unit 208, and the light source 120 can each interface with the endoscope 104 (e.g., at the functional section 128) or the medical device 108 such as by wired or wireless electrical connections. The control system 102 can accordingly illuminate an anatomical region, collect one or more signals representing the anatomical region, process signals representing the anatomical region, and display images representing the anatomical region on the display unit 116. The ultrasound image processing unit 208 can be configured to receive ultrasonic signals from either of the endoscope 104 or the medical device 108, which can be converted into ultrasonic images and transmitted to the display unit 116 or any other component of the endoscopy system 100. The control system 102 can include the light source 120 to illuminate the anatomical region using light of a desired spectrum (e.g., broadband white light, narrow-band imaging using electromagnetic wavelengths, and the like). The control system 102 can connect (e.g., via an endoscope connector) to the endoscope 104 for signal transmission (e.g., light output from the light source, video signals from the imaging system in the distal end, diagnostic and sensor signals from a diagnostic device, or the like).

[0035] The fluid source 122 (shown in FIG. 1) can be in communication with the control unit 114 and can include one or more sources of air, saline, or other fluids, as well as associated fluid pathways (e.g., air channels, irrigation channels, suction channels, and the like) and connectors (barb fittings, fluid seals, valves, or the like). The control system 102 can also include a drive unit 206, which can include a motorized drive for advancing a distal section of endoscope 104.

[0036] FIGS. 3A-3B each illustrate an example cryobiopsy device 300 including a cry oprobe 320 and a sleeve 310 including a needle tip 314. FIG. 3 A shows a side view of the cryobiopsy device 300 where the cry oprobe 320 is sheathed within the sleeve 310. The needle tip 314 can be integrated with the sleeve 310. FIG. 3B shows a side view of the cryobiopsy device 300 in which the cryoprobe device 300 is unsheathed from the sleeve 310. The cut at thedistal end of the needle tip 314 can be referred to as a beveled tip. This design can allow the needle tip 314 to cut into tissue effectively. There can be different types of needle tips or biopsy needles with specific tip designs, such as the Menghini needle, which has a sharp, beveled convex tip, or the Franseen needle, which features a serrated sawtooth tip, among other needle tip types not listed. The cryoprobe 320 can be slidably inserted into the sleeve 310. The cryoprobe 320 can be used to perform cryoextraction or tissue biopsy once exposed to target tissue of a patient.

[0037] The sleeve 310 can include a distal end 312 with a sharp needle tip 314 configured to pierce a portion of tissue (such as tissue 330 in FIGS. 4-7 A). The cry oprobe 320 can be configured to be disposed at least partially within the sleeve 310. The cryoprobe 320 and the sleeve 310 can be longitudinally slidable relative to each other between a plurality of positions including at least a first position (shown in FIGS. 3A and 4-5B), wherein a distal end 322 of the cry oprobe 320 is retracted within the sleeve 310 and a second position (shown in FIGS. 3B and 6A-6B) wherein the distal end 322 of the cryoprobe 320 extends distally beyond the distal end 312 of the sleeve 310. The sleeve 310 and the cry oprobe 320 can be flexible and configured for insertion into a patient to reach the portion of tissue (e.g., 330) through a working channel of another device, such as working channel 352 in FIG. 7 A described below. The needle tip of the sleeve 310 may gain its flexibility, for example, due to spiral laser cuts in the needle wall. Further, the needle tip could be shrink-wrapped to add integrity and seal the lumen.

[0038] The sleeve 310 can sheath the cryoprobe 320, as shown in FIG. 3 A. The sleeve 310 can have a needle tip 314 at a distal end 312 of the sleeve 310. The sleeve 310 can provide a protective covering for the cry oprobe 320 during insertion in tissue of the patient. The needle tip 314 can allow for penetration of the target tissue, as shown in FIGS. 5A-5B. The needle tip 314 can be formed at the distal end 312 of the sleeve 310. The needle tip can be used to facilitate penetration of the target tissue while keeping the cry oprobe 320 shrouded within the sleeve 310. The sleeve 310 can be retractable, from the position shown in FIG. 3 A to the position shown in FIG. 3B, allowing a user of the cryobiopsy device 300 to expose a distal end 322 of the cry oprobe 320 when extraction of tissue is desired, as shown in association with FIGS. 6A-6B. A retractionmechanism can be used to move the cry oprobe 320 or the sleeve 310 with respect to the other such as to expose the cry oprobe 320 from within the sleeve 310, as shown in FIG. 3B. Retraction of the sleeve 310 in a proximal direction from the distal end 312 of the sleeve 310 can cause a distal end 322 of the cry oprobe 320 to be exposed in order to penetrate the target tissue and obtain the biopsy. The cryoprobe 320 can use cryo-adhesion to obtain tissue samples from targets that may be located beyond a tissue wall, such as a Solitary Pulmonary Nodules (SPN) adjacent to an airway. The distal end 322 of the cry oprobe 320 can include a diffuser 323 that uses the Joule-Thomson effect to obtain the biopsy. The Joule-Thomson effect refers to a phenomenon where the temperature of a gas changes when it passes through a throttling element due to a pressure drop, deviating from ideal gas behavior.

[0039] The cryobiopsy device 349 can allow for a two-step process of penetration of the target tissue and obtaining a biopsy from the target tissue 330. The target tissue 330 can represent a target nodule (e.g., a Solitary Pulmonary Nodule “SPN” that is suspected of being cancerous). As shown in FIG. 4 with the cryoprobe 320 sheathed within the sleeve 310, the cryobiopsy device 300 can allow the device to penetrate the target tissue safely. As illustrated, in some instances the cryobiopsy device 349 may penetrate through an airway wall 364 and some distance of tissue beyond the airway wall prior to reaching and penetrating the target tissue 330. In such instances, the cry oprobe 320 may be positioned within the sleeve 310 such that the distal end of the cry oprobe 320 is located substantially at the distal end of the sleeve 310 so as to prevent coring of tissue into the sleeve 310. For example, as shown in FIG. 7B the distal end 322 of the cry oprobe 320 may be located within the beveled tip which forms the needle tip of the sleeve 310. Further, once inside the target tissue 330, as shown in FIGS. 5A-5B, the user can retract the needle tip sleeve, exposing the cry oprobe tip, as shown in FIGS. 6A-6B. FIG. 5 A illustrates the outer circumference of the sleeve 310 while sheathing the cry oprobe 320, and FIG. 5B shows a transparent view of the sleeve 310 to reveal the position of the cryoprobe 320 within the sleeve 310 while sheathed. FIG. 6A illustrates the outer circumference of the sleeve 310 while the cry oprobe 320 is exposed and at least a portion of the cryoprobe 320 is unsheathed toward the distal end 322, andFIG. 6B illustrates a transparent view of the sleeve 310 to reveal the position of the cry oprobe 320 within the sleave while at least a portion is unsheathed.

[0040] In this way, the needle tip 314 of the sleeve 310 can be inserted into the target tissue 330 (shown in FIGS. 5A-5B). The cryoprobe 320 can be exposed either by retracting the sleeve 310 to expose the cry oprobe 320 or extending the cryoprobe 320 distally into the target tissue 330. The exposed needle tip 314 can then perform cryoextraction or tissue biopsy. This approach provides a solution for obtaining tissue samples from locations that may be challenging to access with conventional biopsy tools, potentially improving diagnostic capabilities for certain medical conditions. This approach also allows for deployment of a cryobiopsy device 300 that may be inserted into the target tissue 330 as a unit and not individually or separately into the target tissue 330.

[0041] FIGS. 7A-D each illustrate an example of a schematic diagram showing a view of an ultrasound-guided cryoprobe device. FIGS. 7B-7C are cutout views 342-1, 342-2 showing a zoomed-in view of a distal end of the distal end 312 of the sleeve and a distal end 322 of the cry oprobe where the cry oprobe is sheathed within the sleeve (FIG. 7B) and where the cryoprobe is exposed and the distal end 322 is outside the sleeve (FIG. 7C).

[0042] As illustrated in FIG. 7A, the schematic diagram shows a cross-sectional view of an ultrasound biopsy device 349 that includes an ultrasound transducer 356, a sleeve 310 that encloses or sheathes the cryoprobe 320, and a working channel 352 that the sleeve 310 and cry oprobe 320 passes through to extend outward toward the target tissue 330. As illustrated in FIG. 7A, the ultrasound biopsy device 349 can be positioned within an airway 361 of a patient between walls 362, 364, of the airway 361. The cryobiopsy device 349 can have a device catheter 353 that is in contact with the walls 362, 364 of the airway 361 and within which are the other components of the cryobiopsy device 349. The ultrasound transducer 356 can be located within a distal end 358 of the ultrasound biopsy device 349. The ultrasound transducer 346 can be used to generate and receive ultrasound waves, which are used to create real-time images of the target tissue 330 and surrounding structures. This can allow for precise localization of the area of interest of the tissue. The working channel 352 can serve as a conduit for the delivery of the cry oprobe 320. This workingchannel 352 can allow for the controlled advancement and retraction of the cryoprobe 320 within the ultrasound biopsy device 349.

[0043] The ultrasound biopsy device 349 can include an elongate body 350 that includes an instrument lumen 354 that connects to the distal end 358 that houses the ultrasound transducer 356. The elongate body 350 can include an opening, or exit port, 351 spaced proximally from the location of the ultrasound transducer. The cryoprobe can be configured to extend through the opening within a field of view of the ultrasound transducer 356. The exit port 351 can be a side exit port that is proximal from the ultrasound transducer 356. The exit port 351 includes an offset angle which causes the sleeve 310 and cryoprobe 320 to advance into the field of view 347 of the ultrasound transducer 356.

[0044] The cry oprobe 320 can be advanced through the working channel 352 and exit the ultrasound biopsy device 349 at an exit port 351 of an instrument lumen 354 of the ultrasound biopsy device 349 in a manner that positions its tip within the ultrasound's field of view (FOV) 347. The cryoprobe 320 can be used to freeze the local area of tissue surrounding its distal end 322 for diagnostic and staging purposes. The instrument lumen 354 can serve as the exit point, at the exit port 351, for the cry oprobe 320. This design can allow for the integration of imaging and interventional capabilities in a single device. The ultrasound field of view (FOV) 347 can be an area acoustically “visualized” by the ultrasound transducer 356. The ultrasound biopsy device 349 can be configured such that the distal end 322 of the cryoprobe 320 is located within this field of view 347, enabling real-time visualization of both the target tissue 330 and the position of the cryoprob e tip.

[0045] The ultrasound biopsy device 349 can be configured to work synergistically, with the ultrasound transducer 346 providing imaging guidance for the precise placement of the cryoprobe 320. The user can advance the sleeve 310 and the cry oprobe 320 within the sleeve 310 to locate the target tissue 330 in the ultrasound field of view 347, then advance the cryoprobe 320 endobronchially until it is adjacent to the target tissue 330. The ultrasound image can facilitate both the location of the tissue to be sampled and the positioning of the cryoprobe distal end 322. Once in position, the cryoprobe 320 can be activated to freeze the local area of tissue for subsequent removal and analysis. In some embodiments, the ultrasound biopsy device 349 may be the medicaldevice 108 shown and described in relation to FIGS. 1 and 2. Specifically, the ultrasound biopsy device 349 may be configured to be delivered into the patient’s anatomy adjacent to the target tissue 330 via a working channel of an endoscope 104 (e.g., a bronchoscope, gastroscope, etc.).

[0046] FIG. 7D shows a side view of the schematic diagram of the cryobiopsy device 349. FIG. 7D shows the outer wall of the sleeve 310 where the cry oprobe 320 is hidden within as it does not show a cross-section where the sheathed cryoprobe 320 is revealed, as in FIG. 7A.

[0047] FIG. 8 illustrates an example diagram of a method 400 for using a cry oprobe with an integrated needle tip and sleeve for penetrating tissue. The method 400 may include or comprise a number of Operations or Steps (472, 474, 476, 478). These Operations are exemplary, and the executed method can omit one or more of the listed Operations, can repeat Operations, can include other Operations, or can execute the Operations concurrently, substantially simultaneously, or in any order, as appropriate or desired.

[0048] At 472, the method 400 can include providing a sampling device such as, for example, the ultrasound biopsy device 349 described above in relation to FIGS. 7A-7C. The sampling device can include an ultrasound transducer configured to generate signal data corresponding to a field of view. The processing of the signal data by an image processing unit can facilitate generation of a real-time ultrasound image of the field of view. The sampling device can further include an instrument lumen that extends to an exit port configured to direct an instrument into the field of view. The ultrasound transducer can be configured to use either linear or radial imaging odalities.

[0049] At 474, the method 400 can include providing or obtaining a cryoprobe assembly comprising a cryoprobe. The cryoprobe assembly can include an elongate body and the ultrasound transducer can be located at a distal end of the elongate body. The instrument lumen can be part of an elongate body of the sampling device. The elongate body can include an opening spaced proximally from the location of the ultrasound transducer. A cryoprobe can be configured to extend through the opening within a field of view of the ultrasound transducer.

[0050] At 476, the method 400 can include locating a tissue region of interest within the field of view of the ultrasound transducer. The cryoprobe can beadvanced within a field of view of the ultrasound transducer to locate the tissue region of interest.

[0051] At 478, the method 400 can include advancing the cryoprobe from the exit port and into the field of view of the ultrasound transducer until a distal tip of the cry oprobe is within or adjacent the tissue region of interest. The ciyoprobe can be advanced endobronchially using at least one ultrasound image generated by the ultrasound transducer. The cry oprobe can be retracted within a sleeve and a sharp tip of the sleeve can be used to pierce tissue while advancing the cry oprobe to be adjacent the tissue region of interest. The method can include retracting the sleeve to expose a distal portion of the cry oprobe to the tissue region of interest.

[0052] In some examples, the method 400 can include activating the cry oprobe to freeze a local area of tissue surrounding the distal tip. Activating the cry oprobe can include modulating a flow of pressurized gas from a proximal end to a diffuser 323 located adjacent to the distal tip of the cry oprobe The cry oprobe can be activated in response to advancement of the cry oprobe into the field of view. The method 400 can include removing, after the freezing and using cryoadhesion, the local area of tissue surrounding the distal tip.

[0053] FIG. 9 shows a schematic diagram of an exemplary computer-based clinical decision support system (CDSS) 660 that is configured to determine a location of the cry oprobe within a field of view of an ultrasound transducer and / or other location identifying outputs and information. In various embodiments, the CDSS 660 includes an input interface 664 through which the ultrasound information and / or associated parameter(s) which are specific to patient tissue identified in the field of view of the ultrasound transducer are provided as input features to an artificial intelligence (Al) model 666, a processor 602 which performs an inference operation in which the ultrasound information is applied to the Al model to generate the location of the tissue that the cry oprobe is in contact with, and a user interface (UI) through which the location of the tissue is communicated to a user, e.g., a clinician.

[0054] In some embodiments, the input interface 664 may be a direct data link between the CDSS 660 and one or more medical devices that generate at least some of the input features. For example, the input interface 664 may transmit the ultrasound information directly to the CDSS 660 during a therapeutic and / ordiagnostic medical procedure. Additionally, or alternatively, the input interface 664 may be a classical user interface that facilitates interaction between a user and the CDSS 660. For example, the input interface 664 may facilitate a user interface through which the user may manually enter data associated with the ultrasound information and / or other imaging information, or a combination of both. Additionally, or alternatively, the input interface 664 may provide the CDSS 660 with access to an electronic patient record from which one or more input features may be extracted. In any of these cases, the input interface 664 is configured to collect one or more of the following input features in association with a specific patient on or before a time at which the CDSS 660 is used to assess the location of the cryoprobe within the tissue:[first location of the cry oprobe or other elements within the tissue] [Nth location of the cryoprobe or other elements within the tissue]

[0055] Based on one or more of the above input features, a processor can perform an inference operation using the Al model 666 to generate the location of the cry oprobe within the tissue. For example, input interface 664 may deliver the ultrasound information into an input layer of the Al model 666 which propagates these input features through the Al model 666 to an output layer that is transferred to an output interface 668. The Al model 666 can provide a computer system the ability to perform tasks, without explicitly being programmed, by making inferences based on patterns found in the analysis of data. Al model 666 explores the study and construction of algorithms (e.g., machine-learning algorithms) that may learn from existing data and make predictions about new data. Such algorithms operate by building an Al model 666 from example training data in order to make data-driven predictions or decisions expressed as outputs or assessments.

[0056] There are two common modes for machine learning (ML): supervised ML and unsupervised ML. Supervised ML uses prior knowledge (e.g., examples that correlate inputs to outputs or outcomes) to learn the relationships between the inputs and the outputs. The goal of supervised ML is to learn a function that, given some training data, best approximates the relationship between the training inputs and outputs so that the ML model can implement the same relationships when given inputs to generate the corresponding outputs. Unsupervised ML is the training of an ML algorithm using information that is neither classified norlabeled and allowing the algorithm to act on that information without guidance. Unsupervised ML is useful in exploratory analysis because it can automatically identify structure in data.

[0057] Common tasks for supervised ML are classification problems and regression problems. Classification problems, also referred to as categorization problems, aim at classifying items into one of several category values (for example, is this object an apple or an orange?). Regression algorithms aim at quantifying some items (for example, by providing a score to the value of some input). Some examples of commonly used supervised-ML algorithms are Logistic Regression (LR), Naive-Bayes, Random Forest (RF), neural networks (NN), deep neural networks (DNN), matrix factorization, and Support Vector Machines (SVM).

[0058] Some common tasks for unsupervised ML include clustering, representation learning, and density estimation. Some examples of commonly used unsupervised-ML algorithms are K-means clustering, principal component analysis, and autoencoders.

[0059] Another type of ML is federated learning (also known as collaborative learning) that trains an algorithm across multiple decentralized devices holding local data, without exchanging the data. This approach stands in contrast to traditional centralized machine-learning techniques where all the local datasets are uploaded to one server, as well as to more classical decentralized approaches which often assume that local data samples are identically distributed. Federated learning enables multiple actors to build a common, robust machine learning model without sharing data, thus allowing to address critical issues such as data privacy, data security, data access rights and access to heterogeneous data.

[0060] In some examples, the Al model 666 may be trained continuously or periodically prior to performance of the inference operation by the processor-. Then, during the inference operation, the patient specific input features provided to the Al model 666 may be propagated from an input layer, through one or more hidden layers, and ultimately to an output layer that is transferred to the output interface 668 and corresponds to the location(s) of the cry oprobe within the tissue. For example, the ultrasound information may be used to locate the cry oprobe within the tissue and activate the cryoadhesion or freezing of the tissue at that specific location to obtain a biopsy at the specific location.

[0061] During and / or after the inference operation, the location(s) of the cry oprobe within the tissue may be communicated to the user via the user interface (UI) and / or automatically cause the cryoprobe to be exposed and a biopsy of the tissue obtained. For example, the CDSS 660 may inform a clinician of the location of the cry oprobe within the tissue in order to indicate where the biopsy is obtained from or which part or location of the patient the biopsy will provide treatment or identification information for diagnosis or treatment information.ADDITIONAL NOTES AND EXAMPLES:

[0062] In Example 1, a cry oprobe system can comprise: an ultrasound transducer having a field of view, the ultrasound transducer being configured to generate signal data that corresponds to a real-time ultrasound image of the field of view, the ultrasound transducer being positionable such that the field of view includes a tissue region of interest; an instrument lumen that extends to an exit port; and a cry oprobe configured to be advanced from the exit port into the field of view of the ultrasound transducer until a distal tip of the cry oprobe is within or adjacent to the tissue region of interest.

[0063] In Example 2, the cry oprobe system of Example 1 can optionally be configured such that: the cry oprobe is activatable to freeze a local area of tissue surrounding the distal tip; and the cry oprobe is activatable by modulating a flow of pressurized gas from a proximal end of the cry oprobe to a diffuser located adjacent to the distal tip of the cry oprobe.

[0064] In Example 3, the cry oprobe system of any one of Examples 1-2 can optionally be configured such that, after the cryoprobe freezes the local area of tissue, the cryoprobe is configured to remove the local area of tissue using cryoadhesion.

[0065] In Example 4, the cry oprobe system of any one of Examples 1-3 can optionally be configured such that the cry oprobe is configured to advance endobronchially using at least one ultrasound image generated by the ultrasound transducer.

[0066] In Example 5, the cry oprobe system of any one of Examples 1-4 can optionally be configured such that the cry oprobe is configured to advance withinthe field of view of the ultrasound transducer to locate the tissue region of interest.

[0067] In Example 6, the cry oprobe system of any one of Examples 1-5 can optionally further comprise: a sleeve comprising a distal end with a sharp tip configured to pierce a portion of tissue, the cry oprobe being retractable within the sleeve.

[0068] In Example 7, the cry oprobe system of any one of Examples 1-6 can optionally be configured such that: the cry oprobe is configured to be disposed at least partially within the sleeve; the cry oprobe and the sleeve are longitudinally slidable relative to each other between positions of a plurality of positions; the plurality of positions includes a first position at which a distal tip of the cryoprobe is retracted within the sleeve; the plurality of positions includes a second position at which the distal tip of the cry oprobe extends distally beyond the distal end of the sleeve; the sleeve and the cryoprobe are flexible; and the sleeve and the cry oprobe are configured for insertion into a patient to reach the portion of tissue through a working channel of another device.

[0069] In Example 8, the cry oprobe system of any one of Examples 1-7 can optionally be configured such that the sleeve includes a sharp tip that is configured to pierce the portion of tissue while the cry oprobe advances to be adjacent to the tissue region of interest.

[0070] In Example 9, the cry oprobe system of any one of Examples 1-8 can optionally be configured such that the sleeve is retractable to expose a distal portion of the cry oprobe to the tissue region of interest.

[0071] In Example 10, the cry oprobe system of any one of Examples 1-9 can optionally be configured such that the distal end of the sleeve defines an opening in communication with an inner lumen of the sleeve to allow the distal tip of the cry oprobe to extend beyond the distal end of the sleeve.

[0072] In Example 11, the cry oprobe system of any one of Examples 1-10 can optionally be configured such that: the distal end of the sleeve with the sharp tip comprises an oval opening; the oval opening defines a cross-section at an oblique angle with a longitudinal axis of the sleeve; and the sharp tip is at a distal portion of the oval opening.

[0073] In Example 12, the cry oprobe system of any one of Examples 1-11 can optionally be configured such that: the cryoprobe comprises an elongate body; and the ultrasound transducer is located at a distal end of the elongate body.

[0074] In Example 13, the cry oprobe system of any one of Examples 1-12 can optionally be configured such that the elongate body comprises an opening spaced proximally from a location of the ultrasound transducer.

[0075] In Example 14, the cry oprobe system of any one of Examples 1-13 can optionally be configured such that the cry oprobe is configured to extend through the opening within the field of view of the ultrasound transducer.

[0076] In Example 15, the cryoprobe system of any one of Examples 1-14 can optionally be configured such that the ultrasound transducer is configured to use one of a linear imaging modality or a radial imaging modality.

[0077] In Example 16, a method for operating a cry oprobe assembly can comprise: providing a sampling device including: an ultrasound transducer configured to generate signal data corresponding to a field of view, wherein processing of the signal data by an image processing unit facilitates generation of a real-time ultrasound image of the field of view, and an instrument lumen that extends to an exit port configured to direct an instrument into the field of view; providing or obtaining a cryoprobe assembly comprising a cryoprobe; locating a tissue region of interest within the field of view of the ultrasound transducer; and advancing the cry oprobe from the exit port and into the field of view of the ultrasound transducer until a distal tip of the cry oprobe is within or adjacent the tissue region of interest.

[0078] In Example 17, the method of Example 16 can optionally further comprise: activating the cry oprobe to freeze a local area of tissue surrounding the distal tip, wherein activating the cryoprobe includes modulating a flow of pressurized gas from a proximal end to a diffuser located adjacent to the distal tip of the cry oprobe; and after the local area of tissue is frozen, removing the local area of tissue surrounding the distal tip using cryoadhesion.

[0079] In Example 18, a cry oprobe system can comprise: a sleeve comprising a distal end having a sharp tip configured to pierce a portion of tissue of a patient; a cry oprobe configured to be disposed at least partially within the sleeve, the cry oprobe and the sleeve being longitudinally slidable relative to each other between positions of a plurality of positions, the plurality of positions includinga first position at which a distal tip of the cry oprobe is retracted within the sleeve, the plurality of positions including a second position at which the distal tip of the cryoprobe extends distally beyond the distal end of the sleeve, the sleeve and the cry oprobe being flexible and being configured for insertion into the patient to reach the portion of tissue through a working channel of another device; and a sampling device including: an ultrasound transducer configured to generate signal data corresponding to a field of view within a portion of tissue that includes a tissue region of interest, the sleeve and the cry oprobe being maneuverable within the tissue region of interest; and an instrument lumen that extends to an exit port configured to direct an instrument into the field of view.

[0080] In Example 19, the cry oprobe system of Example 18 can optionally further comprise a cylindrical cryoprobe housing coupled to the ultrasound transducer, the cry oprobe housing including an exit opening for passage of the cryoprobe, the sleeve shrouding the cryoprobe, the cylindrical cryoprobe housing defining a channel in communication with the exit opening, the channel being configured to slidably receive the sleeve.

[0081] In Example 20, the cry oprobe system of any one of Examples 18-19 can optionally be configured such that: the sleeve is advanceable within the field of view upon exiting the cylindrical cry oprobe housing to advance the sleeve to the tissue region of interest; the sleeve is configured to be retracted to expose a distal portion of the cryoprobe; and the exposed distal portion of the cryoprobe is configured to freeze and subsequently remove a local area of the tissue within the tissue region of interest.

[0082] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments that can be practiced. These embodiments are also referred to herein as “examples.” Such examples can include elements in addition to those shown or described.However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0083] All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference(s) should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.

[0084] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

Claims

WHAT IS CLAIMED IS:

1. A cryoprobe system comprising:an ultrasound transducer having a field of view, the ultrasound transducer being configured to generate signal data that corresponds to a real-time ultrasound image of the field of view, the ultrasound transducer being positionable such that the field of view includes a tissue region of interest;an instrument lumen that extends to an exit port; anda cry oprobe configured to be advanced from the exit port into the field of view of the ultrasound transducer until a distal tip of the cry oprobe is within or adjacent to the tissue region of interest.

2. The cry oprobe system of claim 1, wherein:the cry oprobe is activatable to freeze a local area of tissue surrounding the distal tip; andthe cry oprobe is activatable by modulating a flow of pressurized gas from a proximal end of the cry oprobe to a diffuser located adjacent to the distal tip of the cry oprobe.

3. The cry oprobe system of claim 2, wherein, after the cry oprobe freezes the local area of tissue, the cryoprobe is configured to remove the local area of tissue using cryoadhesion.

4. The cryoprobe system of any one of claims 1-3, wherein the cryoprobe is configured to advance endobronchially using at least one ultrasound image generated by the ultrasound transducer.

5. The cry oprobe system of any one of claims 1-4, wherein the cry oprobe is configured to advance within the field of view of the ultrasound transducer to locate the tissue region of interest.

6. The cry oprobe system of any one of claims 1-5, further comprising: a sleeve comprising a distal end with a sharp tip configured to pierce a portion of tissue, the cryoprobe being retractable within the sleeve.

7. The cryoprobe of claim 6, wherein:the cry oprobe is configured to be disposed at least partially within the sleeve;the cry oprobe and the sleeve are longitudinally slidable relative to each other between positions of a plurality of positions;the plurality of positions includes a first position at which a distal tip of the cryoprobe is retracted within the sleeve;the plurality of positions includes a second position at which the distal tip of the cry oprobe extends distally beyond the distal end of the sleeve;the sleeve and the cryoprobe are flexible; andthe sleeve and the cry oprobe are configured for insertion into a patient to reach the portion of tissue through a working channel of another device.

8. The cry oprobe system of any one of claims 6-7, wherein the sleeve includes a sharp tip that is configured to pierce the portion of tissue while the cry oprobe advances to be adjacent to the tissue region of interest.

9. The cryoprobe system of any one of claims 6-8, wherein the sleeve is retractable to expose a distal portion of the cry oprobe to the tissue region of interest.

10. The cry oprobe system of any one of claims 6-9, wherein the distal end of the sleeve defines an opening in communication with an inner lumen of the sleeve to allow the distal tip of the cry oprobe to extend beyond the distal end of the sleeve.

11. The cryoprobe system of any one of claims 6-10, wherein:the distal end of the sleeve with the sharp tip comprises an oval opening; the oval opening defines a cross-section at an oblique angle with a longitudinal axis of the sleeve; andthe sharp tip is at a distal portion of the oval opening.

12. The cryoprobe system of any one of claims 1-11, wherein:the cryoprobe comprises an elongate body; andthe ultrasound transducer is located at a distal end of the elongate body.

13. The cryoprobe system of claim 12, wherein the elongate body comprises an opening spaced proximally from a location of the ultrasound transducer.

14. The cryoprobe system of claim 13, wherein the cryoprobe is configured to extend through the opening within the field of view of the ultrasound transducer.

15. The cry oprobe system of any one of claims 1-13, wherein the ultrasound transducer is configured to use one of a linear imaging modality or a radial imaging modality.

16. A method for operating a cry oprobe assembly, the method comprising: providing a sampling device including:an ultrasound transducer configured to generate signal data corresponding to a field of view, wherein processing of the signal data by an image processing unit facilitates generation of a real-time ultrasound image of the field of view, andan instrument lumen that extends to an exit port configured to direct an instrument into the field of view; providing or obtaining a cryoprobe assembly comprising a cryoprobe; locating a tissue region of interest within the field of view of the ultrasound transducer; andadvancing the cry oprobe from the exit port and into the field of view of the ultrasound transducer until a distal tip of the cry oprobe is within or adjacent the tissue region of interest.

17. The method of claim 16, further comprising:activating the cry oprobe to freeze a local area of tissue surrounding the distal tip, wherein activating the cryoprobe includes modulating a flow of pressurized gas from a proximal end to a diffuser located adjacent to the distal tip of the cry oprobe; andafter the local area of tissue is frozen, removing the local area of tissue surrounding the distal tip using cryoadhesion.

18. A cryoprobe system, comprising:a sleeve comprising a distal end having a sharp tip configured to pierce a portion of tissue of a patient;a cry oprobe configured to be disposed at least partially within the sleeve, the cry oprobe and the sleeve being longitudinally slidable relative to each other between positions of a plurality of positions, the plurality of positions including a first position at which a distal tip of the cry oprobe is retracted within the sleeve, the plurality of positions including a second position at which the distal tip of the cryoprobe extends distally beyond the distal end of the sleeve, the sleeve and the cry oprobe being flexible and being configured for insertion into the patient to reach the portion of tissue through a working channel of another device; anda sampling device including:an ultrasound transducer configured to generate signal data corresponding to a field of view within a portion of tissue that includes a tissue region of interest, the sleeve and the cry oprobe being maneuverable within the tissue region of interest; andan instrument lumen that extends to an exit port configured to direct an instrument into the field of view.

19. The cry oprobe system of claim 18, further comprising a cylindrical cryoprobe housing coupled to the ultrasound transducer, the cryoprobe housing including an exit opening for passage of the cry oprobe, the sleeve shrouding the cryoprobe, the cylindrical cryoprobe housing defining a channel in communication with the exit opening, the channel being configured to slidably receive the sleeve.

20. The cry oprobe system of claim 19, wherein:the sleeve is advanceable within the field of view upon exiting the cylindrical cryoprobe housing to advance the sleeve to the tissue region of interest;the sleeve is configured to be retracted to expose a distal portion of the cryoprobe; andthe exposed distal portion of the cryoprobe is configured to freeze and subsequently remove a local area of the tissue within the tissue region of interest.

Images