Patent Publication Number: US-2022233227-A1

Title: Cryo-ablation catheter

Description:
RELATED APPLICATIONS 
     This application claims the benefit of priority under 35 USC § 119(e) of U.S. Provisional Patent Application No. 62/854,335 filed May 30, 2019; the contents of which are incorporated herein by reference in their entirety. 
    
    
     FIELD AND BACKGROUND OF THE INVENTION 
     The present invention, in some embodiments thereof, relates to the field of tissue ablation; and more particularly, but not exclusively, to cryoablation of tissue from within the lumenal space of an organ. 
     Currently, ablation is a gold standard therapy for patients who suffer from atrial fibrillation. While traditionally the ablation was done using RF means, an increasing segment of physicians uses a cryoballoon to achieve ablation. Similar to ablation by RF means, the cryoballoon catheter is inserted via an endovascular approach through the septum (i.e. trans-septally). The physician inflates the cryoballoon individually inside each of the four pulmonary veins, aiming to achieve an ablation in a ring-like geometry, along the connection of the pulmonary vein with the left atrium. The procedure may be repeated for each vein one or more times. 
     SUMMARY OF THE INVENTION 
     There is provided, in accordance with some embodiments of the present disclosure, a cooling frame of a cryoablation catheter comprising: a proximal side; a distal connector, sized to fit within an overtube of a catheter; tubing defining at least one extent of cooling tube configured to be chilled by a cooling flowing therein, and extending between the proximal side and the distal connector region; and a tensioning strut, extending between the proximal side and the distal connector. 
     In some embodiments, the cooling frame comprises at least a second extent of cooling tube extending between the proximal side and the distal connector region. 
     In some embodiments, the cooling frame is configured to self-expand from a collapsed configuration sized to fit within the catheter overtube to an expanded configuration. 
     In some embodiments, the cooling frame comprises at least a second extent of cooling tube extending distally from the distal connector region in the collapsed configuration, and, in a deployed configuration, recurving from the distal connector in a proximal direction back to the proximal side of the cooling frame. 
     In some embodiments, a deployment length of the tensioning strut is configured to be advanced relative to the catheter overtube separately from the cooling tubing while remaining connected to the cooling tubing at the distal connector. 
     In some embodiments, the at least two extents of cooling tubing deploy by assuming a curvature that defines an ablation line configured to be brought into contact with a targeted isolation region. 
     In some embodiments, the ablation line is a loop. 
     In some embodiments, a main curve of the tensioning strut deploys by radial expansion away from a central proximal-to-distal axis of the cooling frame in a direction away from the ablation line. 
     In some embodiments, the cooling frame is sized to deploy within a left atrium lumen, with a region of lumenal wall comprising the pulmonary vein ostia located between contacts of the two extents of cooling tubing with lumenal tissue of the left atrium, and the tensioning strut positioned radially opposite the region of lumenal wall comprising the pulmonary vein ostia. 
     In some embodiments, the main curve of the tensioning strut has an anisotropic cross-section at least 1.5× longer in a first direction than in a direction perpendicular to the first direction. 
     In some embodiments, the cross-section is rectangular. 
     In some embodiments, the cross-section is oval. 
     In some embodiments, the main curve expands to lie within a plane. 
     In some embodiments, the tensioning strut comprises a secondary curve, curving in a direction opposite the main curve. 
     In some embodiments, the secondary curve and the main curve lie substantially within a single plane. 
     In some embodiments, the main curve extends at least 70% of the way between the proximal side and the distal connector, when the cooling frame is deployed, and the secondary curve extends the remainder of the way to the distal tip. 
     In some embodiments, the wherein each of the at least one extents and the tensioning strut connect to a proximal side of the distal tip. 
     In some embodiments, the distal connector is a distal tip of the cooling frame. 
     In some embodiments, the tubing comprises nitinol tubing. 
     In some embodiments, the tensioning strut comprises a nitinol alloy. 
     In some embodiments, the cooling frame comprises at least one coolant delivery tube, positioned in fluid communication with a lumen of the tubing, and configured to deliver coolant to the lumen. 
     In some embodiments, a supply port of the coolant delivery tube is configured to move within the lumen of the tubing. 
     In some embodiments, the at least one coolant delivery tube comprises a plurality of supply ports configured to delivery coolant to the lumen. 
     In some embodiments, the cooling frame is configured with a lumenal region between the coolant deliver tube and the cooling tube, allowing return of coolant proximally past the coolant delivery tube, thereby creating a counter-cooling effect. 
     In some embodiments, the distal connector comprises a swivel joint. 
     In some embodiments, the swivel joint is configured to allow rotation of a distal portion of the cooling tube relative to the tensioning strut within a plane of a first rotational axis, whereby the cooling tube assumes a curved shape upon deployment. 
     In some embodiments, the swivel joint is configured to allow rotation of a distal portion of the cooling tube relative to the tensioning strut around a second rotational axis, whereby the curved shape of the cooling tube is rotatable to a plurality of positions while the tensioning strut remains in place. 
     In some embodiments, the cooling frame comprises a plurality of tensioning struts extending between the proximal side and the distal connector. 
     In some embodiments, in the collapsed configuration, the tensioning strut extends distally from the distal connector, and upon expansion to a deployed state, re-curves proximally to the proximal side. 
     In some embodiments, the tensioning strut is joined to the proximal side by a shaping member which can be shortened to secure the tensioning strut at the proximal side. 
     In some embodiments, the at least two extents of tubing comprise a plurality of tubing pieces, each terminating distally at the distal connector, and the distal connector is a distal tip. 
     In some embodiments, the distal connector connects lumens of the tubing pieces through an interconnecting lumen of the distal connector. 
     In some embodiments, the distal tip comprises a cap covered by a hollow tip, and the interconnecting lumen is defined within the cap and the hollow tip. 
     In some embodiments, the distal connector comprises mutually attached connecting tubes, into which the tubing and tensioning strut are inserted. 
     In some embodiments, the tubing and tensioning strut connect to the distal connector through a proximal side. 
     There is provided, in accordance with some embodiments of the present disclosure, a method of manufacturing a hollow distal tip of a cooling frame of a cryoablation catheter, the method comprising: inserting distal ends of at least one tubing section into a sleeve assembly; inserting the sleeve assembly into a cap; and placing a hollow tip over the cap; wherein the tubing sections are attached to the sleeve assembly by crimping, and the sleeve assembly is attached to the cap by an adhesive. 
     There is provided, in accordance with some embodiments of the present disclosure, a hollow distal tip of a cooling frame of a cryoablation catheter, comprising: a sleeve assembly, sized to accept a distal end of at one tubing section; a cap into which the sleeve assembly is inserted; and a hollow tip over the cap; wherein sleeve assembly attaches to the distal end by crimping, and to the cap by an adhesive. 
     There is provided, in accordance with some embodiments of the present disclosure, a method of cryoablation, comprising: deploying a tube of a cryoablation frame from a catheter; curving the tube elastically to contact and conform to a lumenal surface of a heart left atrium, while a strut of the cryoablation frame forces the tube against the lumenal surface; and circulating coolant into the tube while it remains in contact with the lumenal surface, thereby creating an ablation in the lumenal surface that surrounds all the pulmonary ostia of the heart left atrium. 
     There is provided, in accordance with some embodiments of the present disclosure, a method of cryoablation comprising: deploying a cryoablation frame comprising a superelastic metal alloy from a catheter into contact with the lumenal surface of a beating heart left atrium; circulating coolant into tubes of the frame, thereby cooling the superelastic metal alloy enough to reduce its elasticity by at least 50%; and adhering cooled tubes of the frame to the surface of the heart left atrium, by freezing, thereby maintaining thermal contact with the surface. 
     In some embodiments, the superelastic metal alloy comprises nitinol. 
     Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       Some embodiments of the present disclosure are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example, and for purposes of illustrative discussion of embodiments of the present disclosure. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the present disclosure may be practiced. 
       In the drawings: 
         FIG. 1A  schematically illustrates a deployed cooling frame of a cryoablation catheter, according to some embodiments of the present disclosure; 
         FIG. 1B  schematically illustrates cooling frame retracted into overtube of a cryoablation catheter, according to some embodiments of the present disclosure; 
         FIG. 1C  is a block diagram schematically illustrating a catheter system for cryoablation using cooling frame, according to some embodiments of the present disclosure; 
         FIG. 2  is a schematic flowchart of a method of operating the cooling frame of  FIGS. 1A-1B , according to some embodiments of the present disclosure; 
         FIGS. 3A-3D  schematically illustrate a deployment sequence of for deployment of cooling frame within a left atrium, according to some embodiments of the present disclosure; 
         FIGS. 4A-4B  schematically illustrate selected phases of the deployment of cooling frame within a left atrium, according to some embodiments of the present disclosure; 
         FIGS. 4C-4D  schematically illustrate expansion states of cooling frame during deployment, corresponding to the in situ states described in relation to  FIGS. 4A and 4B , respectively, according to some embodiments of the present disclosure; 
         FIGS. 5A-5B  schematically illustrate different positions of a coolant supply tube within a cooling tube of cooling frame, according to some embodiments of the present disclosure; 
         FIG. 5C  is a schematic flowchart of a method of delivering coolant to cooling frame, according to some embodiments of the present disclosure; 
         FIG. 5D  schematically illustrates a two-tube arrangement for coolant supply, according to some embodiments of the present disclosure; 
         FIG. 6  is a schematic flowchart of a method of maintaining contact of a cooling frame with a heart during operation, according to some embodiments of the present disclosure; 
         FIG. 7  schematically illustrates a cutaway view of a channeled frame connector at a distal tip of cooling frame, according to some embodiments of the present disclosure; 
         FIGS. 8A-8F  illustrate stages in the manufacture of a frame connector placed at a distal tip of a cooling frame, according to some embodiments of the present disclosure; 
         FIGS. 9A-9E  represent different methods of circulating cooling fluid within a cooling frame, according to some embodiments of the present disclosure; 
         FIG. 10  schematically represents a cooling frame of a cryoablation catheter comprising a redoubling cooling tube, according to some embodiments of the present disclosure; 
         FIG. 11  schematically represents a cooling frame of a cryoablation catheter comprising a redoubling cooling tube and a tensioning member, according to some embodiments of the present disclosure; 
         FIGS. 12A-12B  schematically illustrate a cooling frame comprising a single lumen-spanning arc of a single cooling tube, according to some embodiments of the present disclosure; 
         FIG. 13  schematically illustrates a cooling frame comprising two separate lumen-spanning arcs comprising cooling tubes, respectively, according to some embodiments of the present disclosure; 
         FIG. 14  schematically illustrates a cooling frame comprising two separate lumen-spanning arcs comprising cooling tubes, respectively, each having its own tensioning element, according to some embodiments of the present disclosure; 
         FIGS. 15A-15B  schematically illustrate a cooling frame comprising at least one shaping member, which is operable to pull a free distal end of a cooling tube and/or of an extension of the cooling tube, back toward a proximal region of the cooling frame; and 
         FIGS. 16A-16B, 17A-17C and 18A-18C  schematically illustrate a cooling frame comprising a swiveling distal connection, according to some embodiments of the present disclosure. 
     
    
    
     DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION 
     The present invention, in some embodiments thereof, relates to the field of tissue ablation and more particularly, to cryoablation of tissue from within the lumenal space of an organ. 
     Overview 
     A broad aspect of some embodiments of the present disclosure relates to a cryoablation device configured for ablating tissue along a path from within a body lumen. 
     In some embodiments, the cryoablation device is used for ablation treatment of atrial fibrillation. One ablation pattern considered potentially effective preferably comprises creation of a continuous, substantially unbroken ring of ablated tissue which surrounds the ostia of the pulmonary veins, thereby isolating the rest of the atrium from, e.g., re-entrant electrical conduction from the pulmonary veins. In some embodiments of the present invention, a cooling frame is provided which deploys from a catheter-delivered configuration to a state which is sufficiently expanded, strong, and stable that it potentially ensures contacts with cooling surfaces of the device to allow creating lesions which result in effective treatment. In some embodiments, frame strength and stability is achieved substantially without interfering with blood flow; i.e., without use of a balloon. 
     In some embodiments, the cooling frame combines at least one cooling tube, used to perform cryoablation, and a tensioning device, which helps to ensure that the at least one cooling tube establishes a reliable and reproducible contact with endoluminal surfaces targeted for ablation. Structural and/or cooling components of the frame, in some embodiments, comprises a superelastic material such as nitinol, which potentially gives added reliability for the device to reach and maintain an expanded state without support by pressurized inflation (e.g., of a balloon), potentially to the degree of stretching targeted tissue over the frame for enhanced security of contact. 
     In some embodiments, continuity of the ablation is achieved by ablating from an expanding loop that contacts the whole ablation region simultaneously while cooling it. In some embodiments, continuity of ablation is achieved with stabilization of a portion of the frame by expanding it into place with the targeted body lumen, then moving a cooling tube relative to the rest of the frame in order to ablate at two or more locations in reliably selected relative locations. 
     In some embodiments, the device is delivered over a catheter configured for use in ablating within a left heart atrium. The catheter is provided with the distally deployable cooling frame configured for cryoablation of tissue near and/or surrounding the pulmonary vein ostia; optionally all pulmonary vein ostia at once (typically four in number, and varying in the healthy population between three and five pulmonary veins). 
     For example, the catheter is inserted into the left atrium in a conventional endovascular transseptal approach. Once the cooling frame is placed inside the left atrium, in some embodiments, the physician retracts a catheter-external sleeve (i.e., an overtube). This allows self-deploying of a cooling frame. Additionally or alternatively, the cooling frame is extruded from the catheter into the left atrium. 
     After the cooling frame is placed, the physician activates a coolant flow through the tubes (e.g., a flow of pressurized nitrogen). The cooling frame cools tissue it contacts, ablating it. 
     To end the procedure, the physician retracts the cooling frame into the sheath, collapsing it, and retracts the system through the guiding catheter. 
     Potential advantages of ablating around all pulmonary veins simultaneously include: 
     The shape of ablations formed mimic ablations of an open heart surgery technique (the Maze procedure), known to be very effective, but now relatively disused due to its invasiveness. 
     Ablation of the four pulmonary vessels simultaneously instead of each one individually potentially shortens and/or simplifies the ablation procedure. 
     Ablation within the left atrium is optionally performed without blocking blood flow, e.g., in contrast to the operation of certain balloon ablation devices. 
     Potential problems of ablation using a frame that contacts a lumenal surface over a substantial extent of the surface (e.g., circumscribing the ostia of all pulmonary veins, and/or extending between a septal wall of a left atrium and the left atrial wall opposite the septal wall) include readily obtaining stable and reliable surface contact all around a targeted ablation pathway, using a transcatheter delivered device. 
     An aspect of some embodiments of the invention relates to a cooling frame comprising one or more cooling tubes, and a tensioning member actuatable to press the cooling tube(s) against the inner surface of a body lumen within which cryoablation is being performed. 
     In some embodiments, the cooling tube(s) and/or the tensioning member comprise a shape memory and/or superelastic alloy such as nitinol. Superelasticity comprises an elastic response to applied stress, related to reversible movements during phase transformation of a crystal; e.g., between the austenitic and martensitic phases of the crystal. Shape memory is a related property that allows a deformed alloy to be returned to an original set shape by a change in conditions (e.g., upon heating). 
     The cooling frame, in some embodiments, comprises two main components: 
     One or more cooling tubes, which deploy to conform to a body lumen interior, thereby defining an ablation surface targeted for ablation (e.g., creating a substantially closed-loop geometry sized to surrounding the pulmonary vein ostia). 
     A tensioning member. In some embodiments, the tensioning member comprises a strut that deploys to a curve. The curve may be to an opposite direction from a curve of the cooling tube(s). The curve may be opposite the direction of the lumenal surface targeted for ablation, and/or radially opposite a loop surface or other ablation surface defined by the cooling tube(s) which contacts the lumenal surface targeted for ablation. In some embodiments, the tensioning member comprises a plurality of members which expand in two or more directions to position and stabilize the frame. By pressing against portions of the lumen (e.g., an atrial wall opposite the pulmonary veins), the tensioning member potentially acts to help ensure that the lumenal surface targeted for ablation makes reliable surface contact with the cooling tube(s). 
     In some embodiments, the tensioning member spans the cooling frame between a proximal side and a distal side of the cooling frame. Preferably, the tensioning member is physically coupled to the cooling tubes at a both the proximal side and the distal side in order to stabilize their shape and/or positioning. 
     In some embodiments, reliably establishing and maintaining surface contact is assisted by the use of planar curves to define the cooling frame. Planar curves have the potential advantage of being relatively resistant to the transmission of deformation into out-of-plane directions, particularly if the planarity of the curves is furthermore supported by at least one member having a cross-section which is anisotropic or “ribbon-like”—that is, wider in one direction than in another (e.g., by a factor of at least 1.5, 2, 3, 4 or another factor). Even one such anisotropic member (e.g., the tensioning member) potentially is sufficient to stabilize the whole device against torqueing, since one member that resists twisting acts to resist twisting of the device overall. 
     A potential advantage of the tube(s)-and-tensioning member cooling frame design is simple and reliable control. For example, a cryoballoon&#39; s pressure (one of the factors which can affect its tissue contact) is potentially temperature dependent to a significant degree (e.g., due to thermodynamic laws governing gas volume as a function of temperature). By relying on elastic tension rather than gas pressure, cooling control and contact control are potentially decoupled. 
     An aspect of some embodiments of the invention relates to continued stabilization of device-tissue contact as the superelasticity of the cooling tube(s) reduces during cryoablation. 
     In some embodiments, a method of cryoablation comprises expanding a frame comprising a plurality of tubes and/or struts to press against a cryoablation target, and cooling one or more of the tubes and/or struts to a temperature at which their elasticity is reduced (for example, reduced by at least 50%), while at least one tube and/or strut remains uncooled, with elasticity maintained (for example, maintained to at least 95% of its original elasticity). In some embodiments, the uncooled tube and/or strut is provided with an anisotropic cross-section (e.g., at least 1.5, 2, 3 or more times wider in one direction than in an orthogonal direction). 
     A potential advantage of providing a tensioning member separate from the cooling tube(s) is to protect against changes in elasticity (e.g., reduction of superelasticity) as a function of temperature. In some embodiments, the superelasticity and/or planar stability of the tensioning member is sufficient to stabilize the cooling frame even as superelasticity of the cooling tube(s) is reduced as they near cryoablation temperatures. In some embodiments, at least a portion of stability reduction due to loss of superelasticity at cryotemperatures is compensated for (and potentially even improved upon) by freeze-adherence of the cooling tube(s) to contacted tissue. 
     An aspect of some embodiments of the invention relates to the construction of a distal connector (e.g., a distal tip) of the cooling frame. The distal connector has at least two important functions: 
     It allows the tensioning member to recontact the cooling tubes(s) at a distal position, so that it can provide support at both distal and proximal sides of the frame; 
     Before deployment, it joins tensioning member and cooling tube(s) in a way which can be collapsed to a small-diameter package without stressing any element to the point of breaking. 
     A third function, in some embodiments—especially when the distal connector is also a distal tip—is to join the tensioning member to the cooling tube(s) in a structure which is atraumatic to the extent that it will not cause injury to the lumen in which it deploys by poking, cutting, or scraping. 
     In some embodiments, the cooling frame comprises three or more tube and/or strut members, each of which extends from a proximal side of the frame to connect with a distal tip of the cooling frame, and each connecting to the cooling frame from a same proximal side of the distal tip. In some embodiments, a segment of the cooling tube projects past the distal connector, curving in a new direction (e.g., recurving proximally again) to form a second ablation segment of the cooling frame. 
     In some embodiments, the cooling frame is configured to reversibly convert between a collapsed state and an expanded state. In the collapsed state, each of the tube and/or strut members extend substantially parallel to one another, optionally connecting to the distal tip without creating a region of side protrusion (e.g., a region extending beyond the perimeter of the tip cross-section relative to a longitudinal axis of the collapsed cooling frame). 
     In some embodiments, in the expanded state, a midline of each of the tube and/or strut members extends through a different plane (optionally a best-fitting plane) than any of the other tube and/or strut members. 
     In some embodiments, the tip is re-oriented by expansion of the cooling frame so that it points substantially sideways (or optionally even partially proximally), relative to the initial direction of distal extension of the device. This potentially helps to ensure that the tip does not interfere with contact of cooling tube(s) of the cooling with targeted ablation surfaces. 
     The deployed three strut and/or tube members, in some embodiments, are arrayed at least partially in opposition around the cooling frame perimeter, while the tip comes to occupy a sideways orientation—and, optionally, all these members nevertheless connect to the tip on its proximal side. Correspondingly, in some embodiments, at least one of the strut and/or tube members has a deployed main curve that in some region extends proximally (points backwards) relative to the (sideways-deployed) distal tip in order to reach the proximal side of the distal tip where it is connected. To finally connect, a secondary curve is optionally provided to this member that turns the member back to extend in the tip-relative distal direction. 
     In some embodiments, the secondary curve is provided to a strut that acts as a tensioning member. In some embodiments, the secondary curve provides an additional function in taking up any excess extent of the tensioning member, beyond that needed to press the cooling frame fully into place. This provides a potential safety mechanism by preventing advance of the tensioning member from stretching the lumenal tissue (e.g., of the left atrium) to the point of rupture or other damage. In some embodiments, both the main curve and the secondary curve lie substantially in a same plane through which centerlines of the curve extend. 
     Before explaining at least one embodiment of the present disclosure in detail, it is to be understood that the present disclosure is not necessarily limited in its application to the details of construction and the arrangement of the components and/or methods set forth in the following description and/or illustrated in the drawings. Features described in the current disclosure, including features of the invention, are capable of other embodiments or of being practiced or carried out in various ways. 
     Exemplary Embodiment of a Cooling Frame 
     Reference is now made to  FIG. 1A , which schematically illustrates a deployed cooling frame  101  of a cryoablation catheter  100 , according to some embodiments of the present disclosure. Reference is also made to  FIG. 1B , which schematically illustrates cooling frame  101  retracted into overtube  110  of a cryoablation catheter  100 , according to some embodiments of the present disclosure. Further reference is made to  FIG. 1C , which is a block diagram schematically illustrating a catheter system for cryoablation using cooling frame  101 , according to some embodiments of the present disclosure. 
     In some embodiments, a cryoablation catheter  100  comprises an overtube  110 , within which ( FIG. 1A ) a cooling frame  101  is deliverable, e.g., via blood vessels, to a target organ lumen such as a heart left atrium. Upon reaching its target, cooling frame  101  is deployable to an expanded state ( FIG. 1A ) used for the ablation itself. 
     In some embodiments, the cooling frame  101  of cryoablation catheter  100  comprises at least one cooling tube  102 A,  102 B, optionally arranged, upon expansion, to define a contact surface (e.g., extending underneath the dotted line of loop  130 ), shaped to be pressed into contact with tissue of the curved interior surface of the target organ lumen. In some embodiments, the line of contact comprises a substantially loop-shaped region of contact that surrounds a region which is to be isolated (e.g., electrically isolated) from the rest of the lumen by cryoablation. Herein this region is referred to as a targeted isolation region. 
     Optionally, upon circulation of cooling fluid through cooling tubes  102 A,  102 B, contacted tissue is ablated by cooling to temperatures that result in cellular death. In some embodiments, the size of loop  130  is large enough to encompass a plurality of left pulmonary vein ostia, for example as discussed herein in relation to in situ deployment of the cooling frame  101  and  FIGS. 3A-3D . In some embodiments, cooling tubes  102 A,  102 B exit overtube  110  closely enough to one another, and/or meet closely enough at tip  106 , that the spread of the cryogenic ablating zone from each tube (e.g., to a range of about ±5 mm, or another distance) results in closure of loop  130 . In some embodiments, tip  106  itself becomes cryogenically cold sufficiently during operation of the device that it also acts as an ablating surface. For example, it cools due to contact with cooling tubes  102 A,  102 B, and/or itself comprises a passageway for cryogenic coolant. 
     In some embodiments, cooling tubes  102 A,  102 B comprise a plurality of tubes which are joined together proximally at base  111 , and distally at tip  106 . In some embodiments, tip  106  includes a lumen that joins tubes  102 A,  102 B so that coolant fluid is allowed to circulate between cooling tubes  102 A,  102 B. Alternatively, in some embodiments, tubes  102 A,  102 B terminate blindly at tip  106 , and are cooled separately. In some embodiments, cooling tubes  102 A,  102 B together comprise a single extent of tubing with a sharp bend at it distal end in the region of tip  106 . However, tight curvature constraints in the region of tip  106  (e.g., to allow retraction of cooling frame  101  into overtube  110 ) make manufacture of a one-piece tube design potentially more difficult, so that joining separate tubes  102 A,  102 B at a distal tip  106  has potential advantages. 
     In some embodiments, cooling tubes  102 A,  102 B have an outer diameter of about 0.8-2 mm, and a wall thickness of about 100 μm. Alternatively, a non-circular cross-section is used, for example, oval and/or a flat sided cross section (e.g., square, triangular, or another cross-section). A potential advantage of a non-circular cross-section is to increase tissue contact along a flat or flattened side of cooling tubes  102 A,  102 B. 
     In some embodiments, overtube  110  comprise a polymer, e.g., PTFE and/or nylon. In some embodiments, coolant supply tubing (described as coolant supply tube  120  in relation, for example, to  FIGS. 5A-5B ) is provided which is positioned and/or positionable inside cooling tubes  102 A,  102 B; for example as described in relation to  FIGS. 5A-5D and/or 9A-9E , herein. Coolant is supplied, e.g., from a pressurized coolant supply  132 , optionally via a pre-cooling chamber  132  which reduces the temperature of supplied coolant before it passes through overtube  110  along coolant supply tube  120  and into cooling frame  101 . In some embodiments, one or more of pressurized coolant supply  132 , overtube  110 , and cooling frame  101  comprises one or more sensors. Sensors optionally comprise, for example: 
     A pressure sensor configured to detect coolant pressure, and to provide pressure data optionally as a basis for controlling coolant flow and/or verifying safe operation. 
     A temperature sensor, configured to detect temperature at or near cooling frame  101 , and to provide temperature data optionally as a basis for controlling coolant flow, coolant supply tube position, and/or verifying safe and/or effective operation. 
     An electrode, configured to deploy within the region 
     One or more electrical sensors (electrodes, for example), configured, e.g., to verify tissue contact, for example by using impedance measurements. 
     One or more electrodes which deploy between cooling tubes  102 A,  102 B at positions suitable for sensing of myocardial electrical activity, e.g., electrical activity transmitted from outside of loop  130 . Such electrodes are optionally used in the verification of ablation effectiveness. 
     In some embodiments, cooling tubes  102 A,  102 B divide the cooling section of cooling frame  101  into a respective plurality of separate arc-shaped regions (one for each tube). Mechanically, this has potential advantages for helping to ensure good lumen surface contact along all or most of loop  130 . These advantages may be understood, without commitment to a particular theory of operation, as comprising two main factors. 
     First, corresponding ends (distal ends and proximal ends being understood to correspond) of each of cooling tubes  102 A,  102 B proceed from almost the same place—one where they separate from each other at base  111  (which can be positioned near the exit from overtube  110 ); and one where they rejoin at tip  106 . Assuming these two positions can be reliably defined at positions in contact with the lumenal wall (this is further described, for example, in relation to  FIGS. 3A-3D , herein); then the problem of ensuring good contact along the whole of each tube  102 A,  102 B is reduced, in some embodiments, to the problem of ensuring good contact along a single planar arc in between two well-defined contact points. 
     Second, insofar as the two arcs are substantially planar and/or lack an interconnecting gradual curvature, there is potentially an advantage for stiffness. For example, a likelihood is potentially reduced that pushing in one direction will lead to the transmission of frame distortions by torqueing, and/or “sliding” through the curvature into the orthogonal direction. 
     Stiffness provides a potential advantage, insofar as it provides the arcs of the cooling tubes  102 A,  102 B with mechanical strength to “stretch out” tissue of the lumen to conform to its arc when pressed against it, in increased preference to relieving force by cooling tube deformation. 
     There is also a potential advantage, in some embodiments, for activating cooling of the cooling tubes  102 A,  102 B separately, optionally at different times. For example, this may help to resist instability of the frame due to loss of superelasticity at cryogenic temperatures. Optionally, cooling tubes  102 A,  102 B are composed of a superelastic alloy. Nitinol, for example, is optionally used; a material well-known for its superelasticity (as well as shape memory) properties. 
     Shape memory provides a potential advantage for delivery and deployment, allowing flattened (collapsed) delivery packaging of tubes  102 A,  102 B, and then recovery of a curved shape, without introducing permanent deformation that could interfere with the shape to which they deploy. Superelasticity furthermore potentially assists in deployment of cooling frame  101  to exert force on the lumen in which it is deployed in a way that results in a region of continuous contact. 
     It should be understood, however, that for any given alloy composition (particularly when restricted to alloys well-accepted for their biocompatibility), superelasticity properties are typically exhibited in relatively narrow temperature ranges. The range can be varied according to the formation of the alloy, but not necessarily with full superelasticity and/or biocompatibility available for all temperatures. 
     Thus, nitinol alloys capable of exhibiting superelasticity at body temperature are potentially substantially inelastic (in particular, soft and easily deformed) at typical cryoablation temperatures (e.g., temperatures typically well below −20° C.), though the shape memory effect allows them to recover their shapes upon re-warming. Even if some low-temperature superelasticity is retained, there may still be loss of structural strength. This raises a potential problem—particularly in a beating heart chamber—for maintaining cryoablation contact at low temperatures, as superelasticity is lost. While some nitinol alloys exhibit superelasticity at nearer to cryotemperatures, they are potentially more expensive and/or difficult to use in manufacturing. 
     Accordingly, there arises a potential problem wherein cooling sufficient to cause tissue ablation also impairs superelastic properties of the cooling tubes  102 A,  102 B which initially help to ensure adequate stability and surface contact with the lumen tissue targeted for ablation. In some embodiments, this problem is addressed in part, through a use of an auxiliary tensioning member  104 . 
     In some embodiments, pressing contact between the cooling tubes  102 A,  102 B and the interior surface of the target organ lumen is assisted by tensioning member  104 , also optionally made of a superelastic material such as nitinol. Tensioning member  104  is not subject to cryoablation temperatures during operation. Optionally, tensioning member  104  is shaped (e.g., shape set during manufacture at a temperature of several hundred ° C.) to deploy as a curving wire. Upon deployment, tensioning member  104  extends distally from the position where cooling frame  101  exits overtube  110  to connect at a distal tip  106  which also is connected with cooling tubes  102 A,  102 B. 
     By means of tensioning member  104  (which does not circulate coolant), it is potentially ensured that distal tip  106  remains pressed against the lumenal wall even as cooling tubes  102 A,  102 B potentially lose superelasticity as a result of reaching cryotemperatures. In some embodiments, loss of superelasticity is compensated for in part by freeze-attachment of the cooling tubes  102 A,  102 B to tissue as they reach cryotemperatures. In some embodiments, the exchange of contact-maintenance mechanisms occur while the cooling tubes  102 A,  102 B remain substantially self-supporting. Optionally, exchange of contact-maintenance mechanisms is potentially assisted by the force exerted by tensioning member  104  to keep distal tip  106  pressed against the lumenal wall. 
     Optionally, control of the position of coolant supply (e.g., by movement of coolant supply tubes within cooling tubes  102 A,  102 B) assists in managing where and when superelasticity is lost, so that a reliable exchange between tension-based and attachment-based surface contact mechanisms is achieved, for example as described in relation to  FIGS. 5A-5D . 
     In some embodiments, tensioning member  104  comprises a main curve  105 A. During deployment, distal advance of tensioning member  104  is controllable separately from cooling tubes  102 A,  102 B. As more of tensioning member  104  is extruded from overtube  110 , main curve  105 A assumes an increasingly large bulge, expanding in a radial direction away from a central proximal-to-distal axis of the frame, and reaching a size that causes it contact and exert force against a wall of the target organ lumen that potentially helps press cooling tubes  102 A,  102 B against another wall section of the target organ lumen (e.g., an opposite wall section). In some embodiments, the unconstrained curvature of main curve  105 A has a significantly larger radius of curvature than it will assume in the deployed (and lumen-restricted) form it assumes within a target body lumen (e.g., at least a 50% larger radius of curvature, or larger). In some embodiments, a minimal unconstrained curvature (e.g., 10 mm or less of bending over its whole length) is set on the main curve: just enough to ensure that it will bend in the correct direction upon deployment. This potentially helps to ensure that the main curve will be exerting a higher pressing force when deployed within the constraints of a target lumen. 
     In some embodiments, main curve  105 A comprises a cross section which is wider in one direction that another (e.g., rectangular or oval). This potentially helps to ensure that tensioning member  104  bends within a predetermined plane (e.g., a plane perpendicular to the wider direction of the cross-section). 
     Optionally, tensioning member  104  also comprises a secondary curve  105 . A role of secondary curve  105 , in some embodiments, is to re-orient the direction of tensioning member  104  after passing through secondary curve  105 A so that it enters distal tip  106  in a direction parallel to (and from the same side as) cooling tubes  102 A,  102 B. When collapsed, it is a potential advantage for each of tension member  104  and cooling tubes  102 A,  102 B enter to distal tip  106  from a same (proximal) side, allowing a smaller device diameter in the collapsed state. Optionally, secondary curve  105  comprises the same cross-section as main curve  105 A, and optionally secondary curve  105  bends within the same plane as main curve  105 A. 
     In some embodiments, secondary curve  105  is shaped to accept deformation as expanding tensioning member  104  encounters expansion resistance (e.g., due to wall contacts made by cooling frame  101 ), thereby acting as a strain relief on main curve  105 A. This potentially increases the reliable range of advance with which tensioning member  104  can be distally deployed. For example, strain relief from secondary curve  105  potentially reduces a risk of damage to the lumenal wall, and/or a risk of uncontrolled buckling of the device. 
     Optionally, secondary curve  105  is narrower that main curve  105 A (e.g., comprises a region in which tensioning member  104  has a radius of curvature narrower than in main curve  105 A, for example, by a factor of 1.5, 2, 3, 4, or another factor). In some embodiments, main curve  105 A extends (when deployed) at least 70% or 80% of the distance between a proximal side of the cooling frame  101  and a distal tip  106 . 
     In some embodiments, tensioning member  104  is configured so that main curve  105 A extends approximately within a plane that bisects the loop  130  defined by cooling tubes  102 A,  102 B at about equal distances from each cooling tube  102 A,  102 B. In some embodiments, this comprises orienting a longer side of a cross-section of tensioning member  104  (e.g., at positions where it is joined to the cooling frame  101 ) to be substantially perpendicular to the bisecting plane. 
     This potentially allows main curve  105 A to act simultaneously to press both cooling tubes  102 A,  102 B about equally against an organ&#39;s internal lumenal wall. Additionally or alternatively, in some embodiments, secondary curve  105  is positioned so that upon deployment it also presses against portions of the body organ lumen in which it is deployed. For example, secondary curve  105  presses with a surface outer to its curve against portions of the atrium above a mitral valve  14  (e.g., as shown in  FIGS. 4B and 4D , herein). This potentially contributes to tensioning forces. 
     Optionally, secondary curve  105  is oppositely curved to main curve  1045 A, e.g., so that tensioning member  104  forms an “S” shaped curve (albeit with one curve of the “S” potentially being smaller than the other). Optionally, secondary curve  105  is located on a distal side of tensioning member  104 , for example as shown in  FIG. 1A . In some embodiments, secondary curve  105  is located on a proximal side of tensioning member  104 . Optionally, one or more secondary curves  105  are superimposed on the main curve  105 A, e.g., forming a sinusoidal or other repeating pattern superimposed on the longer (higher radius) curvature of main curve  105 A. In some embodiments, main curve  105 A and secondary curve  105  are within a same plane. In some embodiments, they form arcs within separate planes. In some embodiments, one or both of the curves are themselves non-planar. 
     Optionally, additional tensioning members  104  are provided, for example, extending alongside and/or attached at intervals inside the curves of cooling tubes  102 A,  102 B. These provide a potential advantage of additional—and optionally more direct—support of cooling tubes  102 A,  102 B, particularly during periods of cooling below their superelasticity temperature. Constraints on the size of collapsed delivery size of cooling frame  101 , however, potentially limit the amount of auxiliary support which can practically be provided. The three-member frame design (two cooling tubes  102 A,  102 B, and one tensioning member  104 ) is potentially sufficient. 
     In some embodiments, base  111  comprises an aperture  111 A, sized for passing a guidewire therethrough. 
     Deployment and Operation of a Cooling Frame 
     Reference is now made to  FIG. 2 , which is a schematic flowchart of a method of operating the cooling frame  101  of  FIGS. 1A-1B , according to some embodiments of the present disclosure. Further reference is made to  FIGS. 3A-3D , which schematically illustrate a deployment sequence of for deployment of cooling frame  101  within a left atrium  10 , according to some embodiments of the present disclosure. 
     In some embodiments, reaching the body lumen is performed with the assistance of a guidewire  120 , for example as shown in  FIG. 3A . Optionally, access to the left atrium is transseptal. In case another access is used, the orientation of the members of cooling frame relative to overtube  110  is optionally adjusted. Transseptal access provides a potential advantage by creating a device  100  axis extending across left atrium  10  with the distal side of cooling frame  101  in contact with one wall (distal wall  15 ), and the proximal side of cooling frame  101  readily placed in proximity to the septal wall  16 . 
     Also shown in  FIG. 3A  are dorsal left atrial wall  11 , which optionally includes the ostia of four pulmonary veins  12 A,  12 B,  12 C,  12 D (depending on details of patient anatomy, details of the number and arrangement of pulmonary vein ostia may be different). The general location of ventral left atrial wall  13  is indicated with dotted lines; it has been cut away in  FIGS. 3A-3D  in order to allow viewing of details of device deployment. Mitral valve  14  is schematically indicated as the floor of left atrium  10 . 
     At block  210  ( FIG. 2 ), in some embodiments, a cooling frame  101  is deployed into the body lumen from within which a cryoablation procedure is to be performed, e.g., left atrium  10 . For example ( FIG. 3B ), the overtube  110  is inserted over the guidewire across septal wall  16  and advanced to distal wall  15 . Then, optionally, overtube  110  is withdrawn, allowing cooling frame  101  to expand. Optionally, cooling frame  101  is extruded into left atrium  10  from the distal end of overtube  110  from a more proximal position in the left atrium. The advance-then-withdraw sequence illustrated has a potential advantage of avoiding a chance for the expanding frame to become entangled (e.g., with the leaflets of mitral valve  14 ) during unprotected movement across the proximal-distal extent of the lumen of the left atrium. Advance of the device from the septum provides a potential advantage for reducing a chance of inadvertent puncture of the distal-side atrial wall while advancing overtube  110 . 
       FIGS. 3C-3D  shows the partially deployed cooling frame  101  from two different orientations. Cooling tube  102 A is oriented generally to extend across the roof of the left atrium  10  (opposite the mitral valve  14 ). Cooling tube  102 B extends across the dorsal wall of mitral valve  10 . On dorsal wall  11 , in positions within a loop area defined by the two cooling tubes  102 A,  102 B lie the ostia of the pulmonary veins  12 A,  12 B,  12 C,  12 D. Tensioning member  104  is partially deployed, but not fully activated to create pressure against ventral wall  13 . 
     At block  212 , in some embodiments, the deployed cooling frame  101  is pressed against the wall of the body organ lumen in which it is deployed. This is now explained further with respect to  FIGS. 4A-4D . 
     Reference is now made to  FIGS. 4A-4B , which schematically illustrate selected phases of the deployment of cooling frame  101  within a left atrium  10 , according to some embodiments of the present disclosure. Further reference is made to  FIGS. 4C-4D , which schematically illustrate expansion states of cooling frame  101  during deployment, corresponding to the in situ states described in relation to  FIGS. 4A and 4B , respectively, according to some embodiments of the present disclosure. 
       FIGS. 4A and 4C  represent the stage of deployment also shown in  FIGS. 3C-3D . Main curve  105 A of tensioning member  104  is deployed and awaiting further actuation to press the cooling tubes  102 A,  102 B of cooling frame  101  into position. 
       FIGS. 4B and 4D  show the configuration of tensioning member  104  after it has been further extended out of overtube  110 . The bulge of main curve  105 A is increased, to the point where it contacts, and potentially stretches ventral wall  13 . Secondary curve  105  optionally takes up some of the force, to avoid buckling of members of the cooling frame  101 , and/or protect against damage to the walls of the atrium  10 . The force of contact between main curve  105 A and ventral wall  13  potentially acts to force cooling tubes  102 A,  102 B into position in substantially continuous contact with dorsal wall  11 , surrounding (e.g., bracketing) the ostia of the pulmonary veins  12 A,  12 B,  12 C,  12 D. 
     Optionally, secondary curve  105  also performs a positioning function, e.g., by interaction with peripheral portions of mitral valve  14 . This may help to force cooling frame  101  (and, e.g., cooling tube  102 A in particular) upward against the roof of left atrium  10 . 
     At block  214 , in some embodiments, the deployed cooling frame  101  is activated to perform ablation. This is now explained further with respect to  FIGS. 5A-5D . 
     Reference is now made to  FIGS. 5A-5B , which schematically illustrate different positions of a coolant supply tube  120  within a cooling tube  120 A of cooling frame  101 , according to some embodiments of the present disclosure. 
     In some embodiments, cryoablation begins with coolant supply tube  120  located within cooling tube  102 A, with its distal end  121  positioned in the vicinity of distal tip  106 . Distal end,  121 , in some embodiments, comprises an opening which acts as a supply port for coolant entry into the containment area of cooling tube  102 A,  102 B. Optionally, one or more supply ports are provided at other positions along cooling tube  102 A,  102 B; for example, at the distal end, proximal end, and/or near the middle of cooling tube  102 A,  102 B. For purposes of discussion, examples are presented in which distal end  121  acts as a supply port; however, other supply port positions and/or patterns (i.e., of two or more supply ports) along cooling tube  120  are optionally used. 
     Optionally, coolant discharges from distal end  121  to flow into both of cooling tubes  102 A,  102 B, e.g., back across its own longitudinal extent where it passes through cooling tube  102 A, and across a lumen of tip  106  to flow back through cooling tube  102 B. Additionally or alternatively, a coolant supply tube  120  is located within cooling tube  102 B. If, for example, there is a coolant supply tube  120  feeding each of cooling tubes  102 A,  102 B, the two tubes optionally are not in fluid communication with each other. 
     The coolant delivered may be, for example, nitrogen. In some embodiments, another coolant is optionally used, for example, nitrox and/or argon. Delivery pressure is, optionally between 40-90 Bars (e.g., when using a liquid evaporation method of cooling), or a higher pressure (e.g., 150-400 Bars when using Joule-Thompson cooling). Coolant delivery tube  120  is optionally, e.g., about 300 μm in outer diameter, with a wall thickness of about 50 μm. 
     Coolant fluid leaving tube coolant supply tube  120  can create cooling according to one or more different mechanisms. 
     In adiabatic (Joule-Thompson) cooling, expansion of, e.g., nitrogen in a pressurized and/or liquid (but not necessarily cooled) state does work on its surroundings, causing it to lose heat energy and cool. If the coolant is delivered in liquid form, there may also be release of heat energy into expansion causing cooling as the coolant undergoes a phase change between liquid and gas. In either case, the larger internal diameter of cooling tubes  102 A,  102 B compared to coolant supply tube  120  will tend to allow significant expansion to occur at distal end  121 , where coolant exits delivery tube  120 . 
     Moreover, in some embodiments (particularly but not exclusively embodiments using Joule-Thompson effect cooling), the expansion-cooled fluid is passed back along the extent of coolant supply tube  120 . This allows a certain amount of heat exchange cooling to take place, creating a feedback cycle. Gas travelling distally to be expanded exchanges heat with the already expansion-chilled return gas, cooling it. Then, when it reaches distal end  121  of the coolant supply tube  120 , expansion cools it still further. This further lowers the temperature of the gas that passes back along coolant supply tube  120  and increases the amount of pre-chilling, until eventually a steady state of maximal cooling is potentially reached. Optionally, exchange surface area is increased, e.g., by coiling one or more of the return conduit and the coolant supply tube. 
     Cooling frame  101  is also used, in some embodiments, with an alternative arrangement for the delivery, distribution, and/or flow of coolant within cooling tubes  102 A,  102 B. Examples of such arrangements are discussed in relation to  FIGS. 9A-9E , herein. 
     Optionally, coolant is delivered completely or to some extent pre-chilled from outside the device (e.g., below ambient temperature). Optionally, pre-chilled coolant is used for non-expansion cooling. However, as there is a relatively great distance to travel along overtube  110  before reaching cooling frame  101 , and restrictions within a catheter on insulation thickness along that distance, this is potentially insufficient to establish cryoablation conditions on its own. 
     Further reference is made to  FIG. 5C , which is a schematic flowchart of a method of delivering coolant to cooling frame  101 , according to some embodiments of the present disclosure. 
     The flowchart of  FIG. 5C  begins with the cooling frame  101  already in position for cryoablation, for example as described in relation to  FIG. 4B . 
     At block  610 , in some embodiments, coolant is supplied through the coolant supply tube  120  into one or more of the cooling tubes  102 A,  102 B. 
     At block  612 , in some embodiments, supply tube  120  slides (e.g., is advanced and/or retracted) through the one or more of the cooling tubes  102 A,  102 B, so that a delivery port for the cooling fluid (e.g., distal aperture  121 ) is moved to a new location. 
     In the embodiments illustrated by  FIGS. 5A-5B , coolant supply tube  120  is optionally configured to be proximally withdrawn during cooling. This provides a potential advantage by allowing cooling frame  101  to be operated in a manner which focuses the coldest coolant first at a distal position on the cooling frame (near tip  106 ), and later in progressively more proximal regions (and/or conversely, focusing cooling first proximally then moving distally). It is a potential advantage to being cooling at an end (distal or proximal) of the device, since the ends also receive substantial mechanical support from, e.g., overtube  10  and/or tensioning member  104 , and there may be a period of weakening support as the metal cools past the temperature range of its superelasticity. There is also a potential advantage for managing, e.g., by a rate of movement of coolant supply tube  120  the transition between the warmer, superelastic state of cooling tubes  102 A,  102 B and the cryogenically chilled, potentially non-superelastic state of cooling tubes  102 A,  102 B. 
     Optionally, movement of the distal end of coolant supply tube  120  includes passage through a channel region of distal tip  106 , e.g., cooling in one cooling tube  102 A proceeds from a proximal to a distal direction, then in the second cooling tube  102 B from a distal to a proximal direction, as coolant supply tube  120  is withdrawn. 
     Reference is made to  FIG. 5D , which schematically illustrates a two-tube arrangement for coolant supply, according to some embodiments of the present disclosure. In some embodiments, a separate coolant supply tube  120  is provided for each of cooling tubes  102 A,  102 B. An example is shown schematically in  FIG. 5D , wherein cap  107  is constructed without a channel allowing fluid communication between the cooling tubes  102 A,  102 B. Distal ends of coolant deliver tubes  120  are shown superimposed in several positions  121 A,  121 B,  121 C,  121 D,  121 E,  121 F, illustrating how cooling can be focused at different positions along cooling tubes  102 A,  102 B. In some embodiments, cooling tube  120  has ports at a plurality of these locations; optionally, the ports can be moved, e.g., so that each port slides across a different portion of cooling tube  102 A,  102 B. 
     Returning to the discussion of  FIG. 5C : it is a potential advantage, during cooling, that loss of structural strength associated with reductions in superelasticity be replaced by having the cooling tubes  102 A,  120 B frozen into place against (freezingly adhere to) the tissue they contact. There is potentially a period of vulnerability of good contact during the change in temperature—e.g., a period while superelasticity is weakened, but before frozen adherence has been established. It is a potential advantage to reduce the duration of this vulnerable period (e.g., by ensuring that regions transition quickly from warm to cold). In some embodiments, the shape memory transition temperature of the alloy used to make at least one of the cooling tubes (e.g., the temperature at which transformation completes, typically notated as A f ) is set to be near or below the freezing point of water and/or blood (about 0° C. or below), which potentially helps to minimize the chances that loss of strength will result in loss of good thermal contact with the lumenal wall. 
     It is noted that the progressive cooling method provides a potential advantage by focusing cooling power on relatively short lengths of tubing, allowing them to quickly transition from maintaining tissue contact by superelastic tension to maintaining tissue contact by frozen adherence. Furthermore, this is potentially achieved while other portions of a cooling tube  102 A,  102 B remain at least to some extent superelastic, potentially helping to maintain device stability. 
     In some embodiments, cooling is intensified particularly at one or more regions along a cooling tube  102 A,  102 B, for example by increasing cryogenic fluid flow and/or increasing dwell time for a delivery port of coolant supply tube  120  to gain a greater spread of. 
     The flowchart of  FIG. 5C  includes aspects and variations of coolant supply tube  120  and/or its movement; for example as described in relation to  FIGS. 5A-5B and 5D , and/or  FIGS. 9A-9E , herein. 
     Reference is now made to  FIG. 6 , which is a schematic flowchart of a method of maintaining contact of a cooling frame with a heart during operation, according to some embodiments of the present disclosure. 
     The flowchart begin with the cooling frame  101  already in position for cryoablation, for example as described in relation to  FIG. 4B . In particular, cooling tubes  102 A,  102 B are in surface contact with an internal surface of an organ lumen; for example, a left atrium, along a path which substantially surrounds one or more pulmonary vein ostia. 
     At block  710 , in some embodiments, coolant is supplied through the coolant supply tube  120  into one or more of the cooling tubes  102 A,  102 B (cooling tubes  102 A,  102 B correspond to the cooling containment tubes mentioned in the block diagram text of  FIG. 6 ). Cooling tubes  102 A,  102 B, in some embodiments, comprise a superelastic alloy which loses some or all of its superelastic properties as it reaches cryoablation temperatures. 
     At block  712 , in some embodiments, one or more of cooling tubes  102 A,  102 B reaches a temperature cold enough to freeze surrounding water-containing liquid into ice, and potentially much lower (e.g., −40° or lower). At sufficiently low temperatures, ice formation (and consequently, freeze-adherence) may occur within seconds even in the presence of blood flow. 
     Optionally, the freezing occurs first at a position along cooling tube  102 A,  102 B which is radially outside the position of a supply port of coolant supply tube  120  (e.g., radially outside the position of distal end  121 ). This potentially helps to ensure that the first-softening region of coolant tube  102 A,  102 B is also be the first freeze-adhering portion of coolant tube  102 A,  102 B. This provides a potential advantage for shortening or eliminating the period during which neither contact-promoting mechanism is functioning effectively in that local region. 
     Distal Tips of a Cooling Frame 
     Reference is now made to  FIG. 7 , which schematically illustrates a cutaway view of a channeled frame connector  107  at a distal tip  106  of cooling frame  101 , according to some embodiments of the present disclosure. 
     In some embodiments, cooling tubes  102 A,  102 B are fluidly interconnected with one another at distal tip  106  via a channel  502  in cap  107 . In some embodiments, cap  107  comprises a tapered end  506  (optionally blunted; or sharp as shown.) Cap  107  is optionally made, for example, of metallic and/or polymeric material, for example, polyether block amide. Cap  107  is optionally comprised of metal coated with polymeric material, for example, stainless steel coated with polytetrafluoroethylene (PTFE). Tensioning member  104  is optionally attached, e.g., to a third lumen of frame connector  107 , or embedded during molding of frame connector  107 . Optionally, tensioning member  104  is attached directly to one or more of cooling tubes  102 A,  102 B at a location proximal to frame connector  107 . 
     Reference is now made to  FIGS. 8A-8F  which illustrate stages in the manufacture of a frame connector placed at a distal tip  106  of a cooling frame  101 , according to some embodiments of the present disclosure. 
     Nitinol can be a difficult metal to reform into a sealed enclosure, particularly one which is intended to withstand high pressures.  FIG. 8A-8F  explain a method of construction by means of which nitinol cooling tubes  102 A,  102 B are optionally bound into a leak-proof tip enclosure. 
     In some embodiments ( FIG. 8A ), the frame connector comprises a plurality of metal connecting tubes, optionally each attached to the other to form a sleeve assembly  806 . Assembly of sleeve assembly  806  to cooling tubes  102 A,  102 B and tensioning member  104  comprises slipping over them and attaching; attaching is optionally by soldering and/or crimping. In some embodiments, connecting tubes  806  comprise a non-nitinol metal such as stainless steel, cobalt chrome, or another metal. 
     Added over sleeve assembly  806 ,  FIGS. 8B-8C  show cap  807 . Cap  807 , in some embodiments, is welded to sleeve assembly  806 . Cap  807  may be filled, e.g., with epoxy, potentially increasing the stability and fixation of sleeve assembly  806  itself, as well as its connection with cap  807 . It is noted that cooling tube  102 A,  102 B protrude past cap  807 . 
     In some embodiments, hollow tip  809  is placed over cap  807  (e.g. slid over from a distal side;  FIGS. 8D-8F ). Tip  809  is closed on its distal side, and sealingly attaches over cap  806 . Optionally, sealing comprises creation of a continuous laser welding line, and/or use of epoxy (e.g. additional filler material). Optionally, tip  809  terminates in a tapered end  811 . Optionally, hollow tip  809  is comprised of a soft polymer, for example, polyether block amide. 
     In some embodiments, hollow tip  809  encloses a hollow chamber  900 , through which cooling tubes  102 A,  102 B are in fluid communication. Alternatively, in some embodiments, cavity  900  is also filled (e.g., with epoxy), terminating cooling tubes  102 A,  102 B so that they are not in fluid communication with each other. 
     Circulation Patterns of Coolant Within a Cooling Frame 
     Reference is now made to  FIGS. 9A-9E , which represent different methods of circulating cooling fluid within a cooling frame  101 , according to some embodiments of the present disclosure. 
     In  FIG. 9A , coolant supply tube  120  is placed in a cooling tube  102 A, which is in fluid communication with another cooling tube  102 B, interconnected through distal tip  106 . Cooling is optionally achieved by gas expansion and/or liquid evaporation as coolant exits one or more ports of coolant supply tube  120 . Once coolant is delivered, the flow pattern  1000  draws coolant distally through cooling tube  102 A, into tip  106 , and then proximally out through cooling tube  102 B. Optionally, coolant delivery tube  120  is movable within the tubes to change the position at which initial expansion occurs. Optionally, tube  120  is advanceable; optionally, tube  120  begins fully inserted (e.g., all the way forward and then bending around to reach back to a proximal area of cooling tube  102 B), and is withdrawn during cooling to reach all parts of the cooling frame  101 . In some embodiments, tube  120  can be alternately—optionally repeatedly—advanced and withdrawn. This has a potential advantage for increasing temperature uniformity. 
     Optionally, surface portions of cooling tube(s)  102 A,  102 B which are not used for transferring thermal energy from the lumen surface are provided with an insulating coating and/or lining. For example, a partial-circumferential coating  127  is optionally provided, as shown in  FIG. 9A . The portion of the circumference insulated (inside and/or outside) may be about 30%, 50%, or 70%, for example. This potentially helps to increase the efficacy of cryoablation. It should be understood that this lining or coating is optionally applied to any of the cooling tube embodiments described herein. 
       FIG. 9B  illustrates substantially the same configuration (admissible of the same variants), as  FIG. 9A , except that in  FIG. 9B , a portion of the coolant flow pattern  1002  directs coolant back proximally along coolant supply tube  120 . This potentially creates counter-cooling, leading to a feedback cycle that may allow lower temperatures to be reached. Optionally, an insulating polymer lining  125  is provided within and/or over at least the portion of cooling tube  102 A in which counter-cooling occurs. 
       FIG. 9C  illustrates a variant where cap  107  connects but prevents fluid communication between cooling tubes  102 A,  102 B. Each cooling tube  102 A,  102 B has its own coolant supply tube  120 . Circulation pattern  1004  separately extends proximally along the full length of both of cooling tubes  102 A,  102 B, with at least one supply port (e.g., distal end  121 ) located within the distal portion of each cooling tube  102 A,  102 B. 
       FIG. 9D  illustrates a variant of the situation of  FIG. 9B , wherein surface area for counter-cooling is increased by configuring a portion of coolant supply tube  120  in the form of a coil  124 . Alternatively, in some embodiments, a coolant return tube  126  is arranged as a coil around coolant supply tube  120 , for example as shown in  FIG. 9E . In some embodiments, both the return path and the coolant supply tube  120  are arranged in coils, e.g., interdigitated coils. 
     Another arrangement, in some embodiments, is to flow cold fluid directly through the cooling tubes  102 A,  102 B, optionally without additional cooling at the site of the cooling frame  101 . 
     Other Frame Configurations 
     Redoubling Cooling Tube 
     Reference is now made to  FIG. 10 , which schematically represents a cooling frame  1001  of a cryoablation catheter  1000  comprising a redoubling cooling tube  102 C, according to some embodiments of the present disclosure. Reference is also made to  FIG. 11 , which schematically represents a cooling frame  1101  of a cryoablation catheter  1100  comprising a redoubling cooling tube  102 C and a tensioning member  1104 , according to some embodiments of the present disclosure. 
     In some embodiments, a cooling frame  1001 ,  1101  comprises a redoubling cooling tube  102 C. In its constrained and collapsed form (e.g., while still confined within overtube  110 ), cooling tube  102 C extends in a straightened configuration from a proximal to distal direction, terminating in a tube cap  1103 . 
     Cooling tube  102 C, in some embodiments, comprises a superelastic, shape-memory alloy such as nitinol. Upon advancement distally from the overtube  110 , the cooling tube  102 C assumes a redoubled configuration. The redoubled configuration extends distally (e.g., in an arc  1007 , optionally a planar arc) to distal bend  1005 , changes direction at distal bend  1005  and re-curves proximally (e.g., in another arc  1009 , optionally a planar arc); returning to meet itself near its own proximal side  1011 . Optionally, it meets itself at about the place where it exits overtube  110 . The overall deployed shape of cooling frame  1001 ,  1101  defines a contact surface (underneath loop  1030 ), shaped to be pressed into contact with tissue of the curved interior surface of a target organ lumen. The contact surface underneath loop  1030  is, for example, substantially as described, for example, in relation to loop  130  of  FIG. 1A . As also for the contact surface indicated by loop  130 , actual breaks in continuity of contact (for example, at proximal side  1011 ) are potentially overcome by the spread of lesioning during cryoablation, e.g., to a distance of 1-5 mm or more from regions of direct contact. 
     The cooling frame  1001  of  FIG. 10  is shown without a tensioning member. Instead, cooling frame  1001  relies on the intrinsic shape memory and elasticity of cooling tube  102 C to achieve contact with the interior lumenal surface of the target organ lumen. 
     In some embodiments ( FIG. 11 ), tensioning member  1104  is provided. Tensioning member  1104  potentially increases a reliability of surface contact of cooling frame  1101 , compared to cooling frame  1001 . Tensioning member  1104  has a distal extension distance from overtube  110  separately controllable from the distal extension of cooling tube  102 C, for example, similar to the operation to tensioning member  104 . Tensioning member  1104  connects at its distal end to connector  1106 . Connector  1106  is placed near the distal-most position of redoubled cooling tube  102 C, for example, at about the position of distal bend  1005 , e.g., adjoining one side of distal bend  1005 . This position is also near the middle of cooling tube  102 C, for example, when cooling frame  1101  is in its collapsed state. Optionally connector  1106  comprises a plurality of short stainless steel tubes. The tubes may be welded to each other, and, for example, crimped and/or adhered to the cooling tube  102 C and tensioning member  1104 . Optionally, most (e.g., through at least 80% or 90% of its length) of tensioning member  1104  extends through a planar arc. Optionally, tensioning member  1104  connects to connector  1106  from a direction which is on the proximal side of connector  1106 , at least when the cooling frame is in its collapsed (substantially linear) state. This potentially means that tensioning member  1104  does not need to pass through an extremely tight (e.g., 4 mm or less) radius of curvature when packaged. Such a tight radius of curvature would potentially increase a risk of device failure, and/or create difficulties for reliable manufacture. 
     It should be noted that the shape of the redoubled tube is not necessarily limited to the shape shown. For example, the arcs of the redoubled tube are optionally non-planar, undulating, and/or helical or partially helical. 
     Single-Arc Cooling Frame 
     Reference is now made to  FIGS. 12A-12B , which schematically illustrate a cooling frame  1201  comprising a single lumen-spanning arc of a single cooling tube  102 D, according to some embodiments of the present disclosure. 
     In some embodiments, a single-arc cooling frame  1201  is provided. To ablate a whole loop (e.g., of a lumen surface extending substantially along loop  1230 ), the cooling tube  102 D is operated sequentially in two different positions. For example,  FIG. 12A  shows cooling tube  102 D in a first position for cooling, and  FIG. 12B  shows cooling tube  102 D rotated (e.g., around axis  1231 ) and placed in a second position for cooling. In the first and second positions, distal and proximal sides of cooling tube  102 D remain in about the same positions, so that a substantially closed loop is formed by cryoablation. The proximal side, for example, is near an exit from overtube  110 , and the distal side may be near distal cap  1203 . The ablation order for the two positions is optionally first position, then second position; or the reverse. 
     Swiveling, Single-Arc Cooling Frame 
     Reference is now made to  FIGS. 16A-18C , which schematically illustrate a cooling frame  1601  comprising a swiveling distal connection  1610 , according to some embodiments of the present disclosure. 
     In some embodiments, a cooling frame  1601  comprises a tensioning element  1604 A,  1604 B which is connected to a distal end of a cooling tube  102 K. In some embodiments, cooling frame  1601  is a single cooling tube design. 
     Tensioning element  1604 A,  1604 B, in some embodiments, comprises two arcs which expand oppositely upon deployment to anchor substantially around a circumference of a lumen targeted for ablation. Thereby, cooling frame  1601  provides an anchor (the region of swiveling distal connection  1610 ) which remains substantially in place while allowing separate manipulation of cooling tube  102 K. This provides a potential advantage for reliability and/or stability of placement of cooling tube  102 K. For example, cooling tube  102 K can be operated to ablate in a first position, and then in a second position, while assuring that its distal end remains positioned in a same region so that the loop of a cryoablation lesion will be closed. 
       FIG. 16A  shows the cooling frame pre-expansion (e.g., collapsed for delivery, as it would be while confined within an overtube  110 , not shown in this drawing). Upon distal advance of cooling frame  1601  from overtube  110  ( FIG. 16B  and then  FIG. 17A ), tensioning element portions  1604 A,  1604 B expand away from each other to create a loop-shaped anchor. 
     Along with this (although optionally separately controllable), cooling tube  102 K advance distally to take up an arc-shaped configuration. In some embodiments, the components are biased toward their expanded configurations, e.g., by the use of a superelastic and shape memory metal alloy such as nitinol. In some embodiments, advancement from the proximal side while holding the distal end in position forces components to expand. 
     Once the cooling frame  1601  is deployed, cooling tube  102 K can be moved to different positions (e.g., as shown in  FIGS. 17A-17C ) in order to perform cryoablation. In some embodiments, moving to a new position comprises pulling cooling tube  102 K slightly proximally to un-expand it (e.g., after a first cryoablation), rotating cooling tube  102   k  (e.g., by rotation of an external control member), then re-expanding the cooling tube  102 K by pushing it distally again. Once re-positioned, a second cryoablation may be performed. 
     Stability of the position of the proximal end is assured by maintaining a position of the overtube  110 , while stability of the distal end is assured by maintaining a position of the expended tensioning element  1604 A,  1604 B. 
       FIGS. 18A-18C  illustrate details of swiveling distal connection  1610 . In some embodiments, swiveling distal connection  16010  comprises two interlocking loops  1611 ,  1612 . The loop connection allows movements around two different rotational axes. In the first movement, cooling tube  102 K is free to rotate approximately through 90° from a flattened configuration ( FIG. 18A ) to a deployed, arc-shaped configuration ( FIG. 18B ). In the second movement, the deployed cooling tube  102 K is rotatable, e.g., through the positions shown in  FIGS. 17A-17C . The range of movement allowed around for this axis of rotation optionally comprises at least 45° of rotation, and optionally 90° or more of rotation. 
     While uses of a single-arced cryoablation frame using two-position ablation protocol has just been described, it should be noted that the single arc is optionally used for ablation in only one position (e.g., to supplement and/or correct results of another ablation procedure), and/or in three or more positions. 
     Unconnected-Arc Cooling Frames 
     Reference is now made to  FIG. 13 , which schematically illustrates a cooling frame  1301  comprising two separate lumen-spanning arcs comprising cooling tubes  102 E,  102 F, respectively, according to some embodiments of the present disclosure. 
     In some embodiments, cooling tubes  102 E,  102 F extend separately through their arcs from a distal side near where they exit overtube  110  to their respective distal caps  1303 . The cooling tubes  102 E,  102 F again comprise a superelastic and shape memory alloy such as nitinol. When unconnected, there is potentially less certainty of position, continuous lumenal surface contact, and/or loop closure, however tube positioning can be verified and/or adjusted, for example, under fluoroscopic examination. 
     Reference is now made to  FIG. 14 , which schematically illustrates a cooling frame  1401  comprising two separate lumen-spanning arcs comprising cooling tubes  102 G,  102 H, respectively, each having its own tensioning element  1403 ,  1404 , according to some embodiments of the present disclosure. 
     In some embodiments, at least one of cooling tubes  102 G,  102 H is provided with its own tensioning element  1403 ,  1404 . The design of the tensioning element can be adjusted, depending on the relevant geometry of the target lumen. For example, tensioning element  1404  substantially continues the arc of cooling tube  102 G, allowing it to create force by pressing against an opposite wall of the target lumen than that contacted by cooling tube  102 G. Additionally or alternatively, tensioning element  1403  curves to create a blunted end at a position near to the distal wall of the lumen, where it potentially operated by pressing against structures at or near to the distal wall, such as tissues comprising a ring of a mitral valve. 
     Optionally, the tensioning elements  1403 ,  1404  are separately extendable, e.g., slideable over their respective cooling tubes  102 G,  102 H. Optionally, they are of fixed length, and extend along with their respective cooling tube 
     Reference is now made to  FIGS. 15A-15B , which schematically illustrate a cooling frame  1501  comprising at least one shaping member  1510 , which is operable to pull a free distal end  1508  of a cooling tube  1021  and/or of an extension  1504  of the cooling tube, back toward a proximal region of the cooling frame  1501 . Potentially, this helps stabilize deployment of the cooling frame  1501 . The cooling frame, in some embodiments, comprises any configuration having a free end extending beyond the distal side of the cooling frame, for example, the configuration of  FIGS. 10-11  (wherein cooling tube  102 C itself terminates the free distal end), or, as illustrated, the configuration of  FIG. 14  (wherein a tensioning member  1404  terminates the distal free end). 
     In some embodiments, shaping member  1510  comprises a wire. Shaping member  1510  is allowed to be pulled from overtube  110  by extrusion of cooling tube  102 I. To complete deployment, shaping member  1510  is then shortened (pulled proximally) again, drawing free distal end  1508  back toward the proximal side of the cooling frame. 
     General 
     As used herein with reference to quantity or value, the term “about” means “within ±10% of”. 
     The terms “comprises”, “comprising”, “includes”, “including”, “having” and their conjugates mean: “including but not limited to”. 
     The term “consisting of” means: “including and limited to”. 
     The term “consisting essentially of” means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure. 
     As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof. 
     The words “example” and “exemplary” are used herein to mean “serving as an example, instance or illustration”. Any embodiment described as an “example” or “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments. 
     The word “optionally” is used herein to mean “is provided in some embodiments and not provided in other embodiments”. Any particular embodiment of the present disclosure may include a plurality of “optional” features except insofar as such features conflict. 
     As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts. 
     As used herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition. 
     Throughout this application, embodiments may be presented with reference to a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of descriptions of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as “from 1 to 6” should be considered to have specifically disclosed subranges such as “from 1 to 3”, “from 1 to 4”, “from 1 to 5”, “from 2 to 4”, “from 2 to 6”, “from 3 to 6”, etc.; as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range. 
     Whenever a numerical range is indicated herein (for example “10-15”, “10 to 15”, or any pair of numbers linked by these another such range indication), it is meant to include any number (fractional or integral) within the indicated range limits, including the range limits, unless the context clearly dictates otherwise. The phrases “range/ranging/ranges between” a first indicate number and a second indicate number and “range/ranging/ranges from” a first indicate number “to”, “up to”, “until” or “through” (or another such range-indicating term) a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numbers therebetween. 
     Although descriptions of the present disclosure are provided in conjunction with specific embodiments, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. 
     All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present disclosure. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety. 
     It is appreciated that certain features which are, for clarity, described in the present disclosure in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the present disclosure. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements. 
     In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety.