Cryotherapy device flow control

Abstract

To provide a cryotherapy system.SOLUTION: An elongate cryo therapy device having a proximal end and a distal end shaped and sized for placement within a body lumen, the cryo therapy device including a cryogenic inflow path fluidly coupling a cryogenic fluid source to a distal end 1113 of the cryo therapy device, the cryogenic inflow path configured to allow cryogenic flow from the cryogenic fluid source into the body lumen, an optics assembly configured to visualize a field of view between the distal end and a target region within the body lumen, and an irrigation inflow path fluidly coupling an irrigation fluid source to at least one irrigation aperture, the irrigation inflow path configured to direct irrigation fluid toward the optics assembly and / or the field of view within the distal end.SELECTED DRAWING: Figure 20

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 62 / 454,753, filed February 4, 2017, the entire contents of which are incorporated herein by reference.

[0002] In some embodiments of the present invention, the present invention relates to ablation, including cryoablation, cryosurgery, or cryotherapy devices, and more particularly, but not exclusively, to cryotherapy of disease within body cavities. [Background technology]

[0003] Cryoablation, cryosurgery, or cryotherapy is a technique that destroys or ablates a target site, which may contain unwanted symptoms, lesions, or free nerve endings, by freezing. Tissue destruction by freezing includes direct damage to cells caused by the formation of ice crystals, as well as delayed damage that may be caused by apoptosis (controlled cell death) and / or vascular effects. Cryotherapy is performed by utilizing pressurized coolants (such as CO2, LN2, and / or nitrous oxide) to spray cryogenic fluid directly onto the treated tissue and / or to allow for the indirect Joule-Thomson effect (using coolants such as argon, nitrogen, and / or krypton).

[0004] The use of cryosurgery to remove tumors is expanding, primarily due to its technical ease and low morbidity. A potential secondary benefit of in situ freezing of malignant disease is the generation of a cryoimmunological response, i.e., an antitumor immune response induced by the natural resorption of malignant tissue. Clinical reports suggest that cryoablation can induce a systemic antitumor immune response, and this has also been confirmed in animal models.

[0005] Body cavities include the bladder, uterus, etc. Bladder cancer is one of the most common cancers. When diagnosed early, the majority of patients diagnosed with bladder cancer have superficial disease and are low-grade in nature, while others are diagnosed at later stages, where the cancer is more invasive and aggressive, and therefore surgical intervention (including cystectomy) may be utilized. Bladder cancer has a high rate of recurrence, and therefore treatment and follow-up management are essential to prevent recurrence and progression. The use of cryotherapy has been proposed to improve treatment of bladder lesions, reduce recurrence, and potentially increase bladder preservation rates.

[0006] An additional example of a bladder condition is interstitial cystitis (IC), also known as bladder pain syndrome, which is a chronic condition of bladder and / or pelvic pain ranging from mild discomfort to severe pain. While there is no definitive cure for IC, medications and other therapies are used to reduce pain. For example, intravesical Botox injections are thought to block the sensory nerves in the bladder that transmit pain. To improve treatment for IC and similar conditions and increase patient comfort over a longer period of time, cryotherapy has been proposed to ablate / injure free nerve endings.

[0007] For uterine diseases and lesions, hysteroscopic procedures may be utilized to avoid major surgical interventions such as hysterectomy or myomectomy. Uterine lesions include submucosal fibroids, large polyps, or menorrhagia with normal endometrium. Additional uterine-related conditions include thin endometrium and / or Ascherman's syndrome (AS), both of which impede conception. The use of cryotherapy has been proposed to improve treatment for uterine diseases and lesions, thus facilitating treatment and potentially increasing uterine preservation rates. Overall, cryotherapy can aid in endometrial recovery and therefore increase the chances of successful conception.

[0008] There are no known cryotherapy devices inserted into a body lumen through the working channel of an endoscope. On the other hand, catheter devices inserted through an endoscope and used to treat the gastrointestinal (GI) tract are known in the art. The key differences between current GI devices and devices needed to treat body lumens are the size of the required insertion cavity (the esophagus or colon have significantly larger diameters), the need for sensing and closed-loop pressure control to keep the lumen open while avoiding overpressure, and the need to address moisture and even residual fluid, which can interfere with the efficacy of ablation and further significantly complicate visualization. For example, some cryotherapy devices involve the use of a cryogenic fluid jet, whereby the cryogenic fluid or coolant exits the nozzle and is applied directly onto the tissue in the form of a spray. In some cryotherapy devices utilizing a spray, an additional suction channel is required to evacuate the expanding fluid of the spray, thus preventing undesired lumen distension or tissue perforation. Known suction channels lack sensing means and appropriate control mechanisms, and therefore lack the ability to control the volume or pressure of the lumen. Additionally, the distance of the nozzle from the target site is not clear, and as a result, treatment results are unpredictable and may make it difficult for the physician to follow the cryosurgery protocol.

[0009] The use of cryotherapy devices in combination with immunomodulatory therapy within a body lumen, with or without an endoscope, is unknown. Summary of the Invention [Problem to be solved by the invention]

[0010] Therefore, there is a need for an improved endoscopic cryotherapy device that allows for tissue ablation within a body lumen, has the ability to control pressure and / or volume, and further has the ability to operate in the presence of moisture or even liquid. There is also a need for an improved cryotherapy device that has the ability to eject a coolant expansion fluid through a body lumen inlet of a limited size. There is also a need for a device that specifically defines the distance between the cryogenic spray and the treated tissue. There is also a need for improved cryoimmunotherapy methods adapted for cryoablation within a body lumen. [Means for solving the problem]

[0011] Below are some examples of some embodiments of the present invention.

[0012] Example 1. A method for treating a vascular disease comprising: providing an elongated cryotherapy device having a proximal end and a distal end shaped and sized for placement within a body lumen; said cryotherapy device comprising: a cryogenic inlet pathway fluidly connecting a cryogenic fluid source to the distal end of the cryotherapy device, the cryogenic inlet pathway configured to allow cryogenic flow from the cryogenic fluid source into the body lumen; an optical system assembly configured to visualize a field of view between the distal end and a target area within the body lumen; an irrigation inlet path fluidly connecting an irrigation fluid source to at least one irrigation opening configured to direct irrigation fluid toward the optical assembly and / or the field of view in the distal end, the irrigation inlet path configured to introduce irrigation fluid from the irrigation fluid source through the irrigation inlet path and the opening toward the optical assembly, thereby enabling cleaning of the optical assembly; Cryotherapy system.

[0013] Example 2. At least one cryogenic flow regulator located on the cryogenic inlet pathway and configured to control the flow of the cryogenic fluid through the cryogenic inlet pathway and into the body lumen; a control unit connected to the cryotherapy device, the control unit comprising: a control circuit connected to the at least one cryogenic flow regulator and configured to control the cryogenic fluid flow into the body lumen by sending a signal to the at least one cryogenic flow regulator. The system described in Example 1.

[0014] Example 3. The system of Example 2, including at least one wash flow regulator located on the wash inlet path connected to the control circuit, the wash flow regulator controlling flow through the wash inlet path in response to a signal from the control circuit.

[0015] Example 4. The system of Example 3, wherein the control circuit signals the irrigation flow regulator to regulate irrigation flow into the body lumen when the cryogenic flow is stopped.

[0016] Example 5. The system of Example 2, comprising at least one purge flow regulator located on the cryogenic inlet path connected to the control circuit and configured to control low-pressure fluid flow through the cryogenic inlet path when the cryogenic flow from the cryogenic fluid source is stopped.

[0017] Example 6. The device includes at least one outlet path configured to discharge fluid from a distal opening located at the distal end toward a proximal opening of the cryotherapy device; and at least one outflow regulator located on the outflow pathway and configured to control fluid discharge from the body lumen through the at least one outflow pathway.

[0018] Example 7. The system of Example 6, wherein the outflow regulator comprises a check valve configured to open when pressure within the body lumen is above a predetermined value.

[0019] Example 8. The system of Example 6 or 7, wherein the outflow regulator comprises a valve connected to the control circuit, the control circuit opening the valve when pressure in the body lumen is above a predetermined value.

[0020] Example 9. The system of any one of Examples 2-8, further comprising at least one pressure sensor connected to the control circuit and configured to measure body cavity pressure or a change in the body cavity pressure, wherein the control circuit controls flow in the cryogenic inlet path and / or the irrigation inlet path based on the at least one sensor measurement.

[0021] Example 10. The system of any one of Examples 2-9, comprising at least one temperature sensor connected to the control circuit and configured to measure temperature levels and / or temperature changes within the body lumen, wherein the control circuit controls the flow of the cryogenic fluid through the cryogenic inlet path and into the body lumen based on the measured temperature values.

[0022] Example 11. The system of any one of Examples 1-10, wherein the distal end of the cryotherapy device is shaped and sized for introduction into a body lumen, including the bladder.

[0023] Example 12. The system of any one of Examples 1-11, wherein the cryotherapy device comprises an irrigation flow director located at the irrigation opening and configured to direct the irrigation fluid toward the optical assembly and / or the field of view.

[0024] Example 13. The system of Example 12, wherein the wash flow director comprises a nozzle and / or a deflection surface.

[0025] Example 14. The system of any one of Examples 1 to 13, wherein the optical system assembly comprises at least one lens and / or at least one illumination source.

[0026] Example 15. The system of any one of Examples 1-14, wherein the cleaning fluid comprises a warm fluid having a temperature greater than 15 degrees Celsius.

[0027] Example 16. A method for treating a body cavity comprising: providing an elongated cryotherapy device having a proximal end and a distal end shaped and sized for placement within a body lumen; a cryogenic inlet pathway configured to fluidly connect a cryogenic fluid source to a cryogenic flow opening in the distal end of the cryotherapy device and to allow cryogenic fluid flow into the body lumen; at least one cryogenic flow regulator located on the cryogenic inlet path and configured to control cryogenic fluid flow through the cryogenic inlet path and into the body lumen; at least one purge flow regulator located on a purge inlet path that overlaps the cryogenic inlet path and configured to allow low-pressure purge fluid flow through the cryogenic inlet path and into the body lumen when the cryogenic fluid flow is stopped, thereby reducing backflow from the lumen into the cryogenic inlet path; Cryotherapy system.

[0028] Example 17. The cryotherapy device includes an outflow pathway extending from the body cavity to the exterior of the body; and at least one outflow regulator located on the outflow pathway and configured to control fluid flow out of the body lumen.

[0029] Example 18. The system of Example 17, wherein the outflow regulator comprises a check valve configured to open when pressure within the body lumen is above a predetermined value.

[0030] Example 19. A control unit connected to the cryotherapy device, the control unit comprising: a control circuit connected to the at least one cryogenic flow regulator and the at least one purge flow regulator, the control circuit opening the purge flow regulator when the cryogenic flow regulator is closed to allow low pressure fluid flow through the cryogenic inlet path and into the body lumen; The system described in Example 17.

[0031] Example 20. The system of any one of Examples 16-19, comprising at least one sensor connected to the control circuit and configured to measure a pressure level within the body lumen.

[0032] Example 21. The system of Example 19, wherein the outflow regulator is connected to the control circuit and configured to open the outflow pathway by sending a signal to the outflow regulator when pressure in the body lumen is greater than a predetermined pressure value.

[0033] Example 22. The system of Example 20, wherein the control circuit determines whether the pressure level within the body lumen is greater than a predetermined pressure value and, in response to the determination, sends a signal to the cryogenic flow regulator to adjust the cryogenic fluid flow through the cryogenic inlet path.

[0034] Example 23. The system of example 21 or 22, wherein the predetermined pressure value is in the range of 25 to 100 millibars.

[0035] Example 24. The system of any one of Examples 19-23, comprising at least one temperature sensor connected to the control circuit and configured to measure a temperature level within the body lumen or the outflow pathway.

[0036] Example 25. The system of Example 24, wherein the control circuit determines whether the measured temperature within the body lumen is below a predetermined temperature value and, in response to the temperature determination, sends a signal to the cryogenic flow regulator to adjust the cryogenic fluid flow through the cryogenic inlet path and into the body lumen.

[0037] Example 26. The system of Example 25, wherein the control circuit signals the outflow regulator to adjust the fluid flow in response to the temperature determination.

[0038] Example 27. The system of any one of Examples 24-26, wherein the low-pressure fluid comprises warm low-pressure fluid having a temperature greater than 15 degrees Celsius, and wherein the control circuit, in response to the temperature determination, opens the purge flow regulator to allow flow of the warm low-pressure fluid through the cryogenic inlet path and into the body lumen.

[0039] Example 28. The system of any one of Examples 25-27, wherein the predetermined temperature value is 10°C.

[0040] Example 29. The system of any one of Examples 16-28, wherein the cryotherapy device comprises at least one volumetric subdivider configured to define a treatment space within the body lumen between the distal end of the cryotherapy device and a target area within the body lumen.

[0041] Example 30. The system of Example 29, wherein the control circuitry is configured to control temperature and / or humidity levels within the treatment space.

[0042] Example 31. The system of example 29 or 30, wherein the volumetric subdivider comprises a fluid flow surrounding the cryogenic fluid flow opening.

[0043] Example 32. The system of any one of Examples 16-31, wherein the body cavity includes a bladder and the distal end of the cryotherapy device is shaped and sized for introduction into the bladder.

[0044] Example 33. The system of any one of Examples 16-32, wherein the low-pressure purge fluid flow is sufficiently warm to reduce the accumulation of frozen particles in the cryogenic inlet path.

[0045] Example 34. A method for controlling flow within a body lumen, comprising: spraying a cryogenic fluid into the body lumen through a cryogenic inlet path and a cryogenic nozzle of a cryotherapy device at least partially disposed within the body lumen; clearing a treatment space between the cryogenic nozzle and a target area within the body lumen by introducing an irrigation fluid into the treatment space through an irrigation inlet path of the cryotherapy device; and varying the spraying and / or the removal depending on a pressure level within the body lumen.

[0046] Example 35. The method of Example 34, comprising distending the body lumen with a low pressure fluid prior to said spraying.

[0047] Example 36. The method of Example 34 or 35, comprising expelling at least a portion of the cryogenic fluid from the body lumen through an outlet path of the cryotherapy device in response to a pressure level within the body lumen.

[0048] Example 37. The method of any one of Examples 34-36, wherein the altering comprises adjusting the introduction of the cryogenic material if the pressure value is higher than a predetermined value.

[0049] Example 38. The method of Example 37, including withdrawing at least a portion of the cryogenic material from the cryogenic inlet path after the adjustment.

[0050] Example 39. The method of Example 37 or 38, including purging low pressure fluid through the cryogenic inlet path and the cryogenic nozzle to prevent clogging of the cryogenic nozzle after the adjustment.

[0051] Example 40. The method of any one of Examples 34-39, comprising visualizing the treatment space with an optical assembly of the cryotherapy device.

[0052] Example 41. The method of Example 40, wherein the removing comprises cleaning the optical assembly with the cleaning fluid.

[0053] Example 42. The method of Example 40 or 41, wherein the optical assembly comprises one or more of a light source, a lens, a light sensor, and / or a fiber optic bundle.

[0054] Example 43. The method of any one of Examples 36-42, wherein the draining comprises opening a flow regulator in the outlet path if the pressure value is higher than a predetermined pressure value.

[0055] Example 44. The method of any one of Examples 36-43, wherein the evacuating comprises activating a pump to create a negative pressure in the outflow path.

[0056] Example 45. The method of any one of Examples 34-44, comprising determining the distance and / or angle between the distal end of the cryotherapy device and the target area.

[0057] Example 46. The method of Example 45, comprising modifying at least one cryotherapy parameter, including a spray duration and / or pressure of the cryogenic fluid, in response to the determination.

[0058] Example 47. The method of Example 45 or 46, wherein determining the distance and / or angle comprises spraying a fluid stream from the cryotherapy device against the target area and determining the distance and / or angle by visualizing the size and / or shape of a depression formed in the target area by the fluid stream.

[0059] Example 48. An elongated cryotherapy device having a proximal end and a distal end shaped and sized for placement within a body lumen, comprising: a cryogenic inlet pathway fluidly connecting a cryogenic fluid source to the distal end of the cryotherapy device, the cryogenic inlet pathway being shaped and sized to permit spraying of the cryogenic fluid at a selected target area within the body lumen through a cryogenic opening in the distal end; at least one outlet pathway configured to allow fluid flow from a distal opening located at the distal end to a proximal opening disposed outside the body lumen; at least one sensor disposed within the outflow pathway and configured to measure at least one microenvironment parameter; a cryotherapy device comprising: at least one volumetric divider configured to define a treatment space between the distal end and the selected target area by reducing intermixing of fluids between the treatment space and other portions of the lumen; a control unit connected to the cryotherapy device, a control unit comprising: control circuitry coupled to the at least one sensor, the control circuitry determining a level of the at least one microenvironment parameter within the defined treatment space based on signals received from the at least one sensor; A cryotherapy system comprising:

[0060] Example 49. The system of Example 48, wherein the microenvironment parameters include pressure, temperature, and / or humidity levels.

[0061] Example 50. The system of example 48 or 49, wherein the volumetric subdivider comprises a fluid flow surrounding the cryogenic opening.

[0062] Example 51. An elongated cryotherapy device having a proximal end and a distal end shaped and sized for placement within a body lumen, comprising: a cryogenic inlet pathway fluidly connecting a cryogenic fluid source to the distal end of the cryotherapy device; an optical system assembly configured to visualize a field of view between the distal end and a target area within the body lumen; a control unit connected to the cryotherapy device, a control unit comprising: control circuitry coupled to the optical system assembly, the control circuitry configured to determine a geometric relationship between the distal tip and the target area based on signals received from the optical system assembly; A cryotherapy system comprising:

[0063] Example 52. The system of Example 51, wherein the optical system assembly comprises at least one illumination source configured to project a light spot onto the target area, and the control circuitry determines the geometric relationship between the distal end and the target area based on the size and / or shape of the light spot.

[0064] Example 53. The cryotherapy device comprises at least one foldable element positioned within a lumen of the cryotherapy device, extending into the body lumen, and configured to at least partially contact the target area at a contact point; 53. The system of Example 51 or 52, wherein the control circuitry determines the geometric relationship between the distal end and the target area based on visualization of the contact point.

[0065] Example 54. The cryogenic inlet pathway is connected to a low-pressure fluid source configured to release a flow of low-pressure fluid through the cryogenic inlet pathway at the target region with sufficient force to cause a temporary depression in the surface of the target region; 54. The system of any one of Examples 51 to 53, wherein the control circuit determines the geometric relationship between the distal end and the target area based on visualization of the size, shape, and depth of the depression.

[0066] Example 55. The system of any one of Examples 51 to 54, wherein the geometric relationship includes a distance and / or an angle between the distal end and the target area.

[0067] Example 56. A control unit for a cryotherapy device, comprising: a control circuit connected to at least one inlet regulator on an inlet path of the cryotherapy device configured to allow fluid flow into a body lumen and at least one outlet regulator on an outlet path of the cryotherapy device configured to allow fluid evacuation from the body lumen; A control unit, wherein the control circuit controls the inflow regulator and the outflow regulator to regulate the pressure level within the body lumen to a pressure level below a predetermined pressure value.

[0068] Example 57. The control unit of Example 56, wherein the control circuit controls the inflow regulator and the outflow regulator to regulate a temperature level within the body lumen to a temperature level above a predetermined temperature value.

[0069] Example 58. The control unit of Example 56 or 57, wherein the control circuit controls the inflow regulator and the outflow regulator to regulate environmental parameters within the body lumen in response to a signal received from an interface connected to the control circuit.

[0070] An embodiment of the present invention comprises: - at least one inflow channel; - at least one outflow channel; - control means for controlling the evacuation of the expanding cryogenic fluid from the body lumen; - visualization means for visualizing the field of view; The present invention is directed to a cryotherapy device in which a control means receives data from at least one sensor that collects data regarding at least one parameter of the body lumen, and the cryotherapy device is introduced into the body lumen via an endoscope or sheath.

[0071] According to some embodiments, the device further comprises a rolling component, the inflow channel being directed towards the rolling component.

[0072] According to some embodiments, the device further comprises an extension that separates the distal end of the device from the treatment site, at least partially separates the treatment volume from the surrounding volume of the body lumen, or both. According to some embodiments, the distal end of the visualization means, the distal end of the inflow channel, or both, is located within the treatment volume. According to some embodiments, the extension separates between the inflow channel and the outflow channel. According to some embodiments, the sensing means is located within the treatment volume, outside the treatment volume, or both inside and outside the treatment volume.

[0073] According to some embodiments, the extension includes a folded configuration, a partially folded configuration, and an unfolded configuration, and the volume and shape of the treatment volume vary depending on the configuration of the extension. According to some embodiments, the extension includes a support component, an extendable component, a flexible component, a non-flexible component, a semi-flexible component, a flexible component, a non-flexible component, or any combination thereof. According to some embodiments, the extension includes overlapping components, and the degree of overlap between the overlapping components is variable. According to some embodiments, the extension includes any number of vent holes.

[0074] According to some embodiments, the distal end of the device comprises a pivoting component comprising at least one inlet nozzle that pivots with the pivoting component.

[0075] According to some embodiments, the inflow channel and the outflow channel are the same channel. According to some embodiments, the overall diameter of the inflow channel, the outflow channel, and any other channels or devices introduced is 0.8 to 9.0 mm. According to some embodiments, at least one tube or catheter is fed through the at least one channel, and the tube or catheter is at least partially flexible, bendable, kink-resistant, or any combination thereof. According to some embodiments, the at least one inflow channel and the at least one outflow channel are part of a fabricated or extruded tube or catheter having multiple channels. According to some embodiments, the inflow channel, the outflow channel, or both, are at least partially braided, coiled, or both.

[0076] According to some embodiments, the inlet channel is attached to at least one inlet nozzle, any one of which has an inner diameter in the range of 0.05 to 0.3 mm. According to some embodiments, the outlet channel is attached to at least one outlet opening, any one of which has an inner diameter in the range of 0.5 to 4.0 mm.

[0077] A further embodiment of the present invention is a method of treating tissue in a body lumen, comprising: - introducing a cryotherapy device equipped with visualization means into a body lumen via an endoscope or sheath; - visualizing the field of view by a visualization means; - injecting a cryogenic fluid directly or indirectly into the body lumen through at least one inlet channel of the cryotherapy device, such that the cryogenic fluid expands directly or indirectly within the body lumen, thereby freezing at least a portion of the treatment tissue; - discharging the expanding cryogenic fluid from the body lumen, directly or indirectly, through at least one outlet channel of the cryotherapy device; The present invention is directed to a method in which the discharge of the cryogenic fluid is controlled by a control means that receives data from at least one sensor that collects data regarding at least one parameter of the body lumen.

[0078] According to some embodiments, - Cryogenic fluid is injected into the field of view, - The treatment area or volume is within the field of view, - Cryogenic fluid is ejected from the field of view, or any combination of these.

[0079] According to some embodiments, the method further includes injecting at least one additional fluid directly or indirectly into the body lumen through at least one inlet channel of the cryotherapy device, the additional fluid maintaining the body lumen above a defined pressure, desiccating at least a portion of the treatment volume or site, or any combination thereof. According to some embodiments, the defined pressure is 10-20 mbar. According to some embodiments, the additional fluid is selected from CO2, air, argon, N2, a lower pressure gas, and / or a warm gas.

[0080] According to some embodiments, the cryotherapy device includes a rolling component, and the method further comprises: - injecting a cryogenic fluid into or onto the rolling components; - rolling the rolling component over at least a portion of the treatment tissue within the body lumen.

[0081] According to some embodiments, the cryotherapy device includes an extension, the extension comprising: - the distance between the distal end of the cryotherapy device and the treated tissue; a treatment volume that is at least partially separated from the surrounding volume of the body lumen, or - forming both, said method comprising: - injecting a cryogenic fluid into the treatment volume; - visualizing the treatment volume with a visualization means, wherein a distal end of the visualization means is inside or outside the treatment volume; - optionally injecting additional fluid into the treatment volume, where the additional fluid reduces humidity within the treatment volume, maintains the pressure of the body lumen or treatment volume above the defined pressure, or both.

[0082] According to some embodiments, the device comprises additional sensing means, the distal end of each of the sensing means being within the treatment volume, outside the treatment volume, or both. According to some embodiments, the configuration of the extensions is changed during cryotherapy, such that the extensions are folded, partially folded, unfolded, or any combination thereof during cryotherapy, thereby changing the volume and shape of the treatment volume.

[0083] According to some embodiments, the distal end of the cryotherapy device includes a swirling component with at least one inlet nozzle, and the cryogenic fluid is injected through the inlet nozzle, which swivels with the swirling component, thereby facilitating coverage of the area or volume with the cryogenic fluid.

[0084] According to some embodiments, the at least one inlet channel and the at least one outlet channel are the same channel, and the direction of flow through these channels is controlled by the control means.

[0085] According to some embodiments, the at least one inflow channel and the at least one outflow channel are part of a fabricated or extruded tube or catheter having multiple channels. According to some embodiments, sharp angular movements of the endoscope or sheath do not cause kinks in the inflow or outflow channels. According to some embodiments, the inflow and outflow channels are at least partially bendable, flexible, or kink-resistant. According to some embodiments, the inflow channel, the outflow channel, or both, are at least partially braided, coiled, or both.

[0086] According to some embodiments, the body lumen is the bladder, cervix, prostate, urethra, ureter, stomach, or uterus. According to some embodiments, bodily fluid is drained from the body lumen through at least one outflow channel. According to some embodiments, the control means receives parameters related to an internal pressure within the body lumen to be treated, a temperature within the body lumen to be treated, a flow rate, a flow time, or any combination thereof.

[0087] According to some embodiments, the cryogenic fluid is indirectly injected into the body lumen and injected into the collapsed component. According to some embodiments, the collapsed component is a cryogenic balloon. According to some embodiments, the cryogenic fluid is injected into a catheter, which does not have an opening into the body lumen but is inserted into the body lumen, and the expanding cryogenic fluid is expelled from within the catheter.

[0088] According to some embodiments, the cryogenic fluid is infused with at least one additional active ingredient. According to some embodiments, the active ingredient is a biological, immunological, chemical, nanoparticle, or chemotherapeutic entity. According to some embodiments, the active ingredient is selected from mitomycin C, doxorubicin, and dendritic cells.

[0089] According to some embodiments, the cryogenic fluid is selected from liquid nitrogen, carbon dioxide (CO2), nitrous oxide (N2O), or any combination thereof.

[0090] A further embodiment of the present invention is a cryotherapy device for treating at least one target area within a body lumen, the cryotherapy device being passed through an endoscope or sheath, the cryotherapy device comprising: - a folded ablation cryogenic balloon; - a means for introducing the folded cryogenic balloon into a body lumen through an endoscope or sheath; - means for expanding the cryogenic balloon within the body lumen; - visualization means for visualizing a field of view that includes at least a portion of the expanded cryogenic balloon and at least a portion of the target area.

[0091] According to some embodiments, the cryogenic balloon has regions with different degrees of compliance, and the regions of the cryogenic balloon that are active in transferring the low temperature to the target region contact the target region by inflation of the balloon, by movement of the balloon, or by both inflation and movement of the balloon. According to some embodiments, the cryogenic balloon includes at least one non-compliant support region and at least one flexible or semi-compliant active region, and the visualization means visualizes a field of view that includes the support region, a portion of the active region, or both.

[0092] According to some embodiments, the means for expanding the cryogenic balloon within the body lumen includes a cryogenic fluid jet, an additional fluid jet, or any combination thereof, any of which jets are provided by any number of nozzles, and optionally any of which nozzles are rotated about an axis by any number of degrees. According to some embodiments, the cryogenic balloon is flexible, semi-compliant, non-compliant, or any combination thereof. According to some embodiments, the diameter or average diameter of the cryogenic balloon when folded is less than 2.5 mm.

[0093] A further embodiment of the present invention is a cryotherapy device for treating at least one treatment site within a body lumen, the cryotherapy device being passed through an endoscope or sheath, the cryotherapy device comprising: - a rolling element; - a means for introducing the rolling component through an endoscope or sheath into a body lumen; - means for injecting a cryogenic fluid into the rolling components.

[0094] 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 this invention 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 invention, exemplary methods and / or materials are described below. In case of conflict, the present patent specification, including definitions, will control. Additionally, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0095] As will be appreciated by those skilled in the art, some embodiments of the present invention may be embodied as a system, a method, or a computer program product. Accordingly, some embodiments of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.), or an embodiment combining software and hardware aspects, all of which may be generally referred to herein as a "circuit," "module," or "system." Furthermore, some embodiments of the present invention may take the form of a computer program product embodied in one or more computer-readable medium(s) having computer-readable program code embodied therein. Implementation of the method and / or system of some embodiments of the present invention may involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Furthermore, depending on the actual apparatus and equipment of some embodiments of the method and / or system of the present invention, some selected tasks may be performed by hardware, software, or firmware, and / or a combination thereof, e.g., using an operating system.

[0096] For example, hardware performing selected tasks according to some embodiments of the present invention may be implemented as a chip or circuit. As software, selected tasks according to some embodiments of the present invention may be implemented as a plurality of software instructions executed by a computer using any suitable operating system. In exemplary embodiments of the present invention, one or more tasks according to some exemplary embodiments of the methods and / or systems described herein are performed by a data processor, such as a computing platform, executing a plurality of instructions. Optionally, the data processor includes volatile memory for storing instructions and / or data, and / or non-volatile storage, e.g., a magnetic hard disk, and / or removable media for storing instructions and / or data. Optionally, a network connection is provided as well. Optionally, a display and / or a user input device, such as a keyboard or mouse, is provided as well.

[0097] Any combination of one or more computer-readable media may be utilized for some embodiments of the present invention. The computer-readable medium may be a computer-readable signal medium or a computer-readable storage medium. The computer-readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the above. More specific examples (non-exclusive list) of computer-readable storage media include an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. In the context of this document, a computer-readable storage medium may be any tangible medium capable of containing or storing a program for use by or in connection with an instruction execution system, apparatus, or device.

[0098] A computer-readable signal medium may include a propagated data signal in which computer-readable program code is embodied, for example in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including but not limited to, electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium may be any computer-readable medium, other than a computer-readable storage medium, that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0099] The program code embodied on the computer readable medium and / or data used thereby may be transmitted using any suitable medium, including but not limited to wireless, wired, fiber optic cable, RF, etc., or any suitable combination of the above.

[0100] Computer program code implementing operations for some embodiments of the present invention may be written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Java, Smalltalk, C++, and conventional procedural programming languages ​​such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partially on the user's computer, as a stand-alone software package, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be to an external computer (e.g., via the Internet using an Internet Service Provider).

[0101] Some embodiments of the present invention may be described below with reference to flowcharts and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the present invention. It will be understood that each block of the flowcharts and / or block diagrams, and combinations of blocks in the flowcharts and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, or other programmable data processing apparatus to create a machine, such that the instructions, executed by the processor of the computer or other programmable data processing apparatus, provide means for implementing the functions / acts specified in one or more blocks of the flowcharts and / or block diagrams.

[0102] These computer program instructions may also be stored in a computer-readable medium and may instruct a computer, other programmable data processing apparatus, or other device to function in a particular manner, such that the instructions stored in the computer-readable medium create an article of manufacture including instructions that implement the functions / acts specified in one or more blocks of the flowcharts and / or block diagrams.

[0103] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device and a series of operational steps executed on the computer, other programmable apparatus, or other device to create a computer-implemented process, such that the instructions executing on the computer or other programmable apparatus provide a process that implements the functions / operations specified in one or more blocks of the flowcharts and / or block diagrams.

[0104] Some of the methods described herein are generally designed for use solely by a computer and are not feasible or practical for purely manual execution by a professional. A professional wishing to manually perform a similar task, such as monitoring pressure and / or temperature during cryotherapy, may anticipate using an entirely different method that is significantly more efficient than manually performing the method steps described herein, e.g., using the expertise and / or pattern recognition capabilities of the human brain.

[0105] Certain embodiments of the present invention are described herein, by way of example only, with reference to the accompanying drawings. It is emphasized that the details shown below, with particular reference to the drawings, are for the purposes of illustration and for the purpose of providing a detailed description of embodiments of the present invention. Similarly, from viewing the description in conjunction with the drawings, it will become apparent to those skilled in the art how embodiments of the present invention may be practiced. [Brief explanation of the drawings]

[0106] [Figure 1-1]FIG. 1A is a block diagram of a cryotherapy system according to some embodiments of the present invention. [Figure 1-2] FIG. 1B is a flow chart of a schematic cryotherapy process according to some embodiments of the present invention. [Figure 1-3] 1C and 1D are schematic longitudinal cross-sectional views of a cryotherapy device during a cryotherapy procedure introduced into a treatment lumen via an endoscope according to some embodiments of the present invention. [Figure 1-4] 1E and 1F are schematic longitudinal cross-sectional views of a cryotherapy device during a cryotherapy procedure introduced into a treatment lumen via an endoscope according to some embodiments of the present invention. [Figure 2] 2A-2C are schematic cross-sectional views of a cryotherapy system illustrating the means by which fluid can be advanced into and out of a treatment area according to some embodiments of the present invention. [Figure 3] FIG. 3 is a schematic longitudinal cross-sectional view of a cryotherapy system illustrating the means by which the distal end of the device is positioned and secured, according to some embodiments of the present invention. [Figure 4-1] 4A-4D are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device according to some embodiments of the present invention. [Figure 4-2] FIG. 4E is a schematic longitudinal cross-sectional view of a distal end of a cryotherapy device according to some embodiments of the present invention, and FIGS. 4F-4H are schematic transverse cross-sectional views of the distal end. [Figure 5] 5A-5D are schematic longitudinal cross-sectional views of a cryotherapy device introduced through an endoscope during an acute angle formation scenario according to some embodiments of the present invention. [Figure 6-1] 6A-6C are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device including unique nozzles providing different types of spray according to some embodiments of the present invention. [Figure 6-2] 6D and 6E are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device including unique nozzles providing different types of spray according to some embodiments of the present invention. [Figure 7]7A and 7B are schematic longitudinal cross-sectional views of a cryotherapy device introduced through an endoscope, in particular using the inflow and outflow channels of the endoscope, according to some embodiments of the present invention. [Figure 8-1] Figures 8A and 8B are schematic longitudinal cross-sectional views of a cryotherapy device introduced via an endoscope into a treatment cavity during an ablation procedure in accordance with some embodiments of the present invention, and Figures 8C and 8D are schematic longitudinal cross-sectional views of an expanded cryotherapy device introduced via an endoscope into a treatment cavity during an ablation procedure in accordance with some embodiments of the present invention. [Figure 8-2] 8E-8G are schematic longitudinal cross-sectional views of an expanded cryotherapy device introduced into a lumen during an ablation procedure according to some embodiments of the present invention. [Figure 9] 9A and 9B are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device, specifically depicting a cryogenic balloon according to some embodiments of the present invention. [Figure 10-1] 10A and 10B are schematic longitudinal cross-sectional views of a cryotherapy device introduced into a treatment lumen via an endoscope or sheath during a cryotherapy procedure according to an additional embodiment of the present invention. [Figure 10-2] 10C and 10D are schematic longitudinal cross-sectional views of a cryotherapy device introduced into a treatment lumen via an endoscope or sheath during a cryotherapy procedure according to an additional embodiment of the present invention. [Figure 11] FIG. 11 is a schematic longitudinal cross-sectional view of a cryotherapy system illustrating the flow paths and means by which fluids can be advanced into and out of the treatment lumen, according to some embodiments of the present invention. [Figure 12] 12A and 12B are schematic longitudinal cross-sectional views of a rolling cryotherapy device having rollers according to some embodiments of the present invention. [Figure 13] FIG. 13 is a schematic longitudinal cross-sectional view of a distal end of a cryotherapy device including an extension according to some embodiments of the present invention. [Figure 14] FIG. 14 is a schematic longitudinal cross-sectional view of a distal end of a cryotherapy device including a rotating nozzle according to some embodiments of the present invention. [Figure 15] 15A and 15B are schematic longitudinal cross-sectional views of a cryotherapy device introduced via an endoscope, including the use of inflow and outflow channels of the endoscope, according to some embodiments of the present invention. [Figure 16] 16A-16C are schematic longitudinal cross-sectional views of an expanded cryotherapy device including an extension during an ablation procedure according to some embodiments of the present invention, and FIGS. 16D and 16E are schematic top views of the distal end of a cryotherapy device including an extension according to some embodiments of the present invention. [Figure 17-1] 17A-17C are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device including an extension according to some embodiments of the present invention. [Figure 17-2] 17D-17F are schematic longitudinal cross-sectional views of the distal end of a cryotherapy device including an extension according to some embodiments of the present invention. [Figure 18] 18A-18C are schematic cross-sectional views of the distal end of a cryotherapy device including an endoscopic visualization means and extension according to some embodiments of the present invention. [Figure 19] 19A-19C are schematic cross-sectional views of the distal end of a cryotherapy device including an extension according to some embodiments of the present invention. [Figure 20] 20A and 20B are schematic cross-sectional views of a distal end of a cryotherapy device including an inflow pathway according to some embodiments of the present invention. [Figure 21A] FIG. 21A is a flow chart of coolant flow and low pressure flow through a cryotherapy device according to some embodiments of the present invention. [Figure 21B] FIG. 21B is a flowchart of a process for flow and / or purge control according to some embodiments of the present invention. [Figure 22A] FIG. 22A is a graph illustrating pressure changes in a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 22B] FIG. 22B is a graph illustrating pressure changes within a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 22C] FIG. 22C is a graph illustrating pressure changes within a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 22D] FIG. 22D is a graph illustrating pressure changes within a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 22E] FIG. 22E is a graph illustrating pressure changes within a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 22F] FIG. 22F is a graph illustrating pressure changes within a body lumen as a function of flow and time according to some embodiments of the present invention. [Figure 23-1] 23A and 23B are schematic illustrations of the distal end of a cryotherapy device having different distance and angle measurement means according to some embodiments of the present invention. [Figure 23-2] FIG. 23C is a schematic illustration of a distal end of a cryotherapy device having different distance and angle measurement means according to some embodiments of the present invention. [Figure 23-3] Figure 23D is a schematic diagram of the distal end of a cryotherapy device with different distance and angle measurement means according to some embodiments of the present invention, and Figure 23E is a schematic top view of the target area after projection of the light beam or low pressure flow. [Figure 23-4] Figure 23F is a schematic diagram of the distal end of a cryotherapy device with different distance and angle measurement means according to some embodiments of the present invention, and Figure 23G is a schematic top view of the target area after projection of the light beam or low pressure flow. DETAILED DESCRIPTION OF THE INVENTION

[0107] It will be understood that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Furthermore, where considered appropriate, reference numerals may be repeated among the figures to refer to corresponding or analogous elements.

[0108] The present invention, in some embodiments thereof, relates to ablation, including cryoablation, cryosurgery, or cryotherapy devices, and more particularly, but not exclusively, to cryotherapy of disease within body lumens.

[0109] An aspect of some embodiments relates to performing cryotherapy while controlling at least one microenvironment parameter within a body lumen. In some embodiments, the parameter is controlled within a defined treatment space, such as the treatment space between a cryotherapy device and a target region. In some embodiments, the parameter is controlled to allow for better visualization of the treatment region.

[0110] According to some embodiments, the parameter is controlled by controlling flow into the treatment space through at least one inlet path of the cryotherapy device. Alternatively or additionally, the at least one parameter is controlled by controlling evacuation of material from the treatment space, optionally through at least one outlet path of the cryotherapy device. In some embodiments, the flow within the treatment space is controlled to increase the efficacy of cryotherapy, for example, to allow better engagement with the target tissue. Alternatively or additionally, the flow within the treatment space is controlled to increase the safety of cryotherapy, for example, to avoid exceeding maximum pressure and / or temperature values ​​that may result in tissue damage.

[0111] According to some embodiments, flow into the treatment space is controlled to, for example, allow for cleaning of the optical assembly (e.g., lenses and / or light source). Alternatively or additionally, flow is controlled to, for example, allow for removal of vapor, cryogenic mist, and / or liquid droplets from the treatment space that obstruct the field of view between the optical assembly and the target site. In some embodiments, removing vapor, cryogenic mist, and / or liquid droplets from the treatment space allows for, for example, improved and / or optimized cryotherapy and visualization of the treatment site within the body lumen. In some embodiments, flow into the treatment space is controlled to, for example, allow for expansion of the body lumen prior to and / or during the cryotherapy process. Alternatively or additionally, flow through a nozzle used to spray the cryogenic fluid is controlled to prevent clogging of the nozzle with liquid droplets or frozen particles.

[0112] According to some embodiments, the treatment space is defined by adjusting geometric parameters of the treatment space. In some embodiments, a treatment site and / or volume between the cryotherapy device and the target region is demarcated by a volume subdivider, which is optionally configured to define the treatment space within the body lumen, e.g., to better control microenvironmental parameters affecting cryotherapy within the lumen. The volume subdivider is configured to define the treatment space between the distal end and the selected target region by reducing fluid mixing between the treatment space and other parts of the lumen. In some embodiments, the volume subdivider comprises a geometric element. In some embodiments, the geometric element, e.g., an extension, cone, or dress, optionally extends from the distal end of the cryotherapy device disposed within the body lumen. Alternatively or additionally, the volume subdivider includes a surrounding fluid flow within the distal end of the cryotherapy device around the distal end or cryogenic inlet opening of the cryotherapy device. In some embodiments, the surrounding fluid flow, e.g., a surrounding air or gas flow, generates a virtual cone around the distal end or cryogenic inlet opening that defines the treatment space within the body lumen. Optionally, the surrounding fluid flow is generated using a focused flow of gas, optionally low pressure gas, around the cryogenic flow, for example within the body lumen.

[0113] According to some embodiments, the geometric elements allow for better control of, for example, vapors and / or humidity that interfere with visualization within the lumen, e.g., by confining a controlled volume within the lumen during and / or between cryoablation cycles. In some embodiments, the deployed geometric elements allow for the creation of distinct microenvironments within the body lumen, optionally with different, lower or higher humidity, pressure, and / or temperature.

[0114] According to some embodiments, pressure within the body lumen increases during cryotherapy. In some embodiments, the pressure is increased by inflation of the body lumen with low-pressure gas, e.g., to allow better visualization and / or access to a selected target region. Alternatively or additionally, the pressure within the body lumen is increased by expansion of a cryogenic fluid within the body lumen. In some embodiments, the control unit regulates flow into the body lumen through at least one inlet path to reduce the pressure level, e.g., so as not to exceed a maximum allowable pressure value. In some embodiments, flow into the body lumen is stopped and / or at least partially diverted to a flow path outside the body. Alternatively, at least one flow regulator coupled to the outlet path is opened to expel a portion of the material within the body lumen. In some embodiments, the flow regulator is opened passively. Alternatively, the flow regulator is opened actively, e.g., by an electrical signal. In some embodiments, the flow regulator comprises a valve, e.g., a check valve, and / or a pump, e.g., a vacuum pump. In some embodiments, the flow regulator is used to control the pressure within the body lumen.

[0115] According to some embodiments, the maximum pressure value is determined based on the tissue type and / or duration of the pressure. In some embodiments, pressure values ​​during cryotherapy lasting 30-70 minutes in a body cavity, such as the bladder, include normal distending pressures in the range of 10-30 mbar, higher pressure values ​​in the range of 20-50 mbar during 10-30 second cryotherapy cycles, and allow peaks in the range of 50-150 mbar for periods of 1 second or less. In some embodiments, the maximum pressure value during a cryotherapy session lasting 30-70 minutes in a body cavity, such as the bladder, is about 80 mbar, e.g., 50 mbar, 60 mbar, 70 mbar, or any intermediate value, smaller or larger.

[0116] According to some embodiments, the temperature within the body lumen is reduced during cryotherapy, e.g., by expansion of a cryogenic coolant. In some embodiments, the temperature within the body lumen is controlled, e.g., by controlling the flow of coolant into the body lumen. Alternatively or additionally, the temperature is controlled by opening an outflow path to expel a portion of material from within the body lumen. In some embodiments, a warmed irrigation fluid, e.g., a warmed gas, is forced into the body lumen, e.g., to increase the temperature level within the treatment space. Additionally or alternatively, the warmed gas is forced toward lenses of the optical assembly, e.g., to maintain the lenses at a constant temperature and / or prevent condensation of water droplets on the lens surfaces.

[0117] An aspect of some embodiments relates to performing cryotherapy in a body lumen by adjusting geometric parameters related to the treatment. In some embodiments, a geometric relationship, such as a distance and / or an angle, between a distal end of a cryotherapy device disposed in the body lumen and a target site within the body lumen is determined. Optionally, at least one cryotherapy parameter, such as a duration of cryogenic fluid spraying, a time between spray sessions, and / or a pressure of the cryogenic fluid, is determined and / or adjusted depending on the determined distance and / or angle.

[0118] According to some embodiments, the distance and / or angle is determined based on the placement of at least one geometric element, such as an extension, cone, or dress, optionally extending from a distal end of the cryotherapy device portion disposed within the body lumen.

[0119] According to some embodiments, the geometric element allows for determining, for example, the distance and / or angle between a cryogenic nozzle of a cryotherapy device positioned within a body lumen and a selected target region. In some embodiments, the placement of the geometric element, optionally with a known size and / or shape, allows for determining, for example, the distance to a selected target region and / or the angle between the cryogenic nozzle and the target region by visualizing the contact point between the geometric element and the inner surface of the lumen. Alternatively or additionally, the distance to the target region is determined by receiving a signal when the geometric element contacts the inner surface.

[0120] According to some embodiments, a focused stream of gas, e.g., low-pressure gas, from the cryo-nozzle allows for determining the distance between the cryo-nozzle and a selected target region and / or the angle between the cryo-nozzle and the target region. In some embodiments, the distance and / or angle is determined by visualizing the contact point of the gas with the inner surface of the lumen. Optionally, the focused gas stream is delivered through the cryo-nozzle during a cryo-ablation session. In some embodiments, the focused gas stream partially deforms the shape of the inner surface of the lumen, e.g., by forming a depression (or elliptical deformation) at the contact point with the inner surface. In some embodiments, visualizing the size and / or shape of the depression allows for determining, e.g., the distance to the target region and / or the angle between the cryo-nozzle and the target region.

[0121] According to some exemplary embodiments, the distance and / or angle are determined by visualizing a projected light spot on the surface of the target area. In some embodiments, the distance and / or angle are determined based on changes in the shape and / or size and / or color of the light spot. In some embodiments, the light spot is generated by a light beam from a light source disposed at the distal end of a cryotherapy device disposed within a body lumen. Optionally, the light source is generated by a laser light source or any other light source capable of generating a focused light source. In some embodiments, the distance and / or angle between the cryotherapy device and the target area are determined by visualizing the target area, optionally together with at least a portion of the cryotherapy device, and processing the image with one or more image processing algorithms.

[0122] An aspect of some embodiments relates to performing cryotherapy while adding an irrigation fluid, also referred to herein as a sweep material, into a body lumen. In some embodiments, the irrigation fluid, e.g., gas, optionally low-pressure gas, is introduced into the body lumen while a coolant is being sprayed onto the target area. Alternatively or additionally, the irrigation fluid is introduced into the body lumen between spray cycles. In some embodiments, the irrigation fluid is forced into the body lumen through at least one opening at or near the distal end of the cryotherapy device.

[0123] According to some embodiments, irrigation fluid is forced into the body lumen to expand the lumen. In some embodiments, the lumen is expanded to allow for better visualization of the cryotherapy target area. Alternatively or additionally, the lumen is expanded to allow for better manipulation of the distal end of the cryotherapy device to the selected target area.

[0124] According to some embodiments, a rinsing fluid is introduced into a body lumen to clean an optical assembly, e.g., a lens, of a cryotherapy device. In some embodiments, the rinsing gas cleans the lens, e.g., from moisture and / or dirt that may coat the lens. Alternatively or additionally, the rinsing fluid is introduced into a body lumen to clear a field of view (FOV) between the optical assembly and the target area. In some embodiments, the rinsing fluid is used to flush cold, humid gas, e.g., mist, from the optical assembly. In some embodiments, the rinsing gas clears mist and / or frozen droplets from the FOV, which are formed by the interaction of expanding cryogenic gas with liquid particles within the humidified space of the lumen.

[0125] According to some embodiments, the cleaning fluid, optionally warm cleaning fluid, creates a dynamic buffer ("optics cleaning fluid") around the lens surface, e.g., to prevent mist remnants (or expelled mist) from flowing toward the lens. In some embodiments, the cleaning fluid pushes mist and / or frozen particles away from the optical assembly. Alternatively or additionally, the warm cleaning fluid keeps the optical assembly, e.g., the lenses of the optical assembly, at a constant warm temperature to prevent the formation of mist or droplets on the lens surface.

[0126] According to some embodiments, the irrigation fluid is used for pressure measurement. In some embodiments, pressure changes within the lumen can be measured closer to the irrigation pressure source (upstream, e.g., in a control unit) so that the pressure within the lumen can be measured / approximated (e.g., used for control and / or safety measures) as a result of the pressure changes within the lumen.

[0127] According to some embodiments, as described above, the irrigation fluid is optionally used simultaneously for two or more of cleaning the optical assembly, clearing mist from the FOV, optionally expanding the body lumen during the cryotherapy process, and measuring the body lumen pressure level. In some embodiments, a control unit of the cryotherapy device controls the flow distribution of the irrigation fluid between the flow toward the optical assembly and the flow clearing mist from the FOV. Alternatively or additionally, the control unit controls the flow and timing of the irrigation fluid flow relative to the spraying of cryogenic coolant, for example, to ensure that a maximum pressure value in the body lumen is not exceeded. In some embodiments, the control unit controls the flow of irrigation fluid into the body lumen alone or in combination with a cryogenic coolant flow or a purge flow, e.g., a low-pressure flow, through the nozzle, for example, to ensure that the expansion level of the body lumen is above a minimum pressure value.

[0128] An aspect of some embodiments relates to preventing blockage of a cryogenic nozzle in a cryogenic inlet path by controlling flow through the nozzle. In some embodiments, flow through the cryogenic nozzle is controlled to prevent blockage when the cryogenic coolant flow is stopped. In some embodiments, a purge flow through the cryogenic nozzle is initiated when the coolant flow is stopped. In some embodiments, the purge flow is a flow of non-cryogenic gas, optionally a low-pressure gas. In some embodiments, when the cryogenic coolant fluid is stopped, a vent is opened, optionally for a predetermined period of time, to release residual cryogenic fluid trapped in the inlet path. Alternatively, the vent is opened for a period of time adjusted depending on the amount of residual cryogenic coolant trapped in the cryogenic inlet path.

[0129] According to some embodiments, the cryogenic fluid described herein comprises a cryogenic compressed fluid, liquid CO2, at a pressure level of about 50-80 bar in the cryogenic source. Alternatively, the cryogenic fluid comprises a fluid, e.g., nitrogen gas, at a pressure of about 200 bar in the cryogenic fluid source. In some embodiments, the cryogenic fluid exists as a liquid at a pressure of a few bars, e.g., 1-10 bar, and the liquid expands to a gas, e.g., LN2, optionally at a liquid:gas ratio of about 1:1000. In some embodiments, without being bound by any theory, expansion of the high-pressure fluid within a body lumen reduces the pressure of the fluid, resulting in a cryogenic effect, e.g., the Joule-Thomson effect.

[0130] According to some embodiments, the irrigation fluid comprises a low-pressure gas having a pressure of 1-4 bar at its source and optionally expanding into the bladder to a pressure of tens of millibars. In some embodiments, any low-pressure gas can be used for irrigating and / or distending the body lumen. Optionally, stored high-pressure gas is used after pressure reduction, e.g., within the lumen of a cryotherapy device, before release into the body lumen. A possible advantage of using the same type of gas for both irrigation and cryoablation is that separate sources for both cryoablation and irrigation are not required. A possible advantage of using air as the irrigation fluid is that the need for additional cylinders / canisters for connection / replacement / space / cost, etc. is reduced. In some embodiments, the irrigation fluid is warmed and / or dried, e.g., to reduce mist in the treatment space and / or to clean the optical assembly. In some embodiments, when the irrigation gas is stored in a cylinder / canister, its moisture content (measured in parts per million (PPM)) is much lower than that of regular air.

[0131] According to some embodiments, the irrigation fluid is introduced into the body lumen at a rate of at least 4 liters per minute (air), e.g., 5 liters per minute (air), 7 liters per minute (air), 10 liters per minute (air), or any smaller or greater intermediate value. In some embodiments, a low pressure fluid, e.g., a low pressure gas purge, is introduced into the body lumen at a rate of up to 1 liter / minute (air), e.g., 1 liter / minute (air), 0.7 liter / minute (air), 0.5 liter / minute (air), or any smaller or greater intermediate value. In some embodiments, the cryogenic fluid is introduced into the body lumen at a flow rate of at least 5 liters / minute, e.g., 5 liters / minute, 7 liters / minute, 10 liters / minute, or any smaller or greater intermediate value.

[0132] An aspect of some embodiments relates to applying cryotherapy to large target areas or large treatment volumes with a movable cryogenic inlet opening. In some embodiments, the cryotherapy device includes a cryogenic inlet path with a movable nozzle, e.g., a nozzle that rotates in a selected direction and / or at a selected angle to enable coverage of large target areas, e.g., within a body lumen. In some embodiments, the nozzle rotates about an axis. Alternatively or additionally, the cryotherapy device includes a swivel element in combination with the cryogenic nozzle. In some embodiments, the cryogenic fluid is sprayed through a nozzle that can swivel with the swivel element, thereby assisting in coverage of areas or volumes within a body lumen.

[0133] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components are not described in detail so as not to obscure the present invention.

[0134] It should be noted that, as used herein, terms such as "body lumen," "treatment lumen," "target lumen," etc. are interchangeable unless specifically stated otherwise. Similarly, terms such as "treatment tissue," "treatment site," "target tissue," "target site," "target region," "treatment region," etc. are interchangeable unless specifically stated otherwise. Furthermore, references to elements at the distal end of the sensing means are intended to refer to the portion of the sensing means that senses the required parameter, even if a specific sensing element is not specifically located at the distal end of the sensing means.

[0135] Embodiments of the present invention are directed to devices and systems for cryotherapy that can be introduced into a body lumen via an endoscope or any other suitable means (e.g., direct insertion of a catheter into the lumen without visualization or external imaging means such as ultrasound, CT, etc.). The present invention is further directed to cryotherapy within a body lumen. According to some embodiments, cryotherapy involves a cryoimmunological process.

[0136] It should be noted that, as used herein, the term "endoscope" is intended to include any type of known endoscope, as well as any type of sheath, catheter, tube, etc., that can be inserted into the body so that any necessary working channels, visualization means, etc. can be positioned within a body lumen. Thus, an endoscope can include its own visualization means, etc., which can be inserted through any type of sheath, etc., such that the visualization means can be changed during a procedure, i.e., several different types of visualization means can be used throughout a procedure. It should be noted that, as used herein, the term "visualization means," or any other equivalent term, is intended to include optical means, ultrasound, MRI, X-ray, etc. Any other sensors can also be inherent within the endoscope or can be inserted into a body lumen via the endoscope. It should be noted that, as used herein, the term "working channel," or any other equivalent term, can refer to an integral passageway through an endoscope or a passageway available by any means, such as a sheath, catheter, tube, etc., by which any device, such as a visualization means, and / or sensor, can be inserted into a body lumen.

[0137] According to some embodiments, a cryotherapy device includes two or more channels, tubes, catheters, etc., that allow both the infusion of pressurized fluid and the evacuation of expansion fluid, with the pressurized fluid being infused into a lumen through at least one channel and the expansion fluid being evacuation from the lumen through at least one second channel. It should be noted that the terms catheter, tube, etc. are used interchangeably herein unless specifically stated otherwise. According to some embodiments, at least one infusion channel and at least one evacuation channel are inserted into a body lumen via an endoscope. According to some embodiments, any channel can pass through or be fed through any one of the other channels. According to other embodiments, the same channel can be used for both infusion and evacuation, using any suitable type of sensor and / or individual algorithm to control flow direction, relative amount, and timing. While pressurized and expansion fluids have been described above, it should be noted that any type of fluid can be introduced / released from the system according to any one of the above embodiments. It should be noted that, as known in the art, the term "fluid" includes both gases and liquids.

[0138] Embodiments of the present invention further include cryotherapy devices comprising at least one evacuation means and a control means for controlling the evacuation of the inflation fluid and, optionally, the injection of the pressurized fluid. The control means can be automatic, predefined, electronic, manual, etc. The cryotherapy device can further include any number or type of sensors, with the control means receiving data from these sensors and controlling the evacuation and / or injection according to predefined values, manual decisions, values ​​that can be changed during the process, etc. Without such control means, evacuation may be insufficient, causing pressure to build up within the target organ and possibly even causing rupture. Furthermore, it may be necessary to control the internal pressure of the target lumen so that it does not fall below a specific, possibly predefined, value. In particular, if the pressure is too low (e.g., below 10 millibars), it may become difficult or even impossible to operate within the lumen and / or visually see inside the lumen, as the lumen may collapse at low pressure. Thus, the control means can ensure that the pressure does not become too high, causing damage to the lumen, or too low, causing the lumen to collapse. Additionally, bodily fluids may be present within the body lumen being treated (e.g., urine in the bladder). Such bodily fluids may be frozen by the cryotherapy process and may potentially prevent the evacuation of the expanding cryogenic fluid; therefore, it is important to include a sensor within the system, and the control means responds by controlling the evacuation, and possibly the injection, so as to avoid damaging the treatment lumen. According to some embodiments, any number of sensors are inserted into the body lumen. According to some embodiments, any number of external sensors, such as ultrasound, x-ray, etc., may be used in addition to, or possibly instead of, the internal sensors.

[0139] According to some embodiments, the inflow can be stopped when the pressure in the lumen exceeds about 30-100 mbar. According to some embodiments, the outflow can continue to be discharged until the pressure in the lumen falls below about 20-10 mbar. According to some embodiments, the inflow can be stopped when the temperature in the lumen falls below about 5-10°C. According to some embodiments, the inflow can be started when the temperature in the lumen exceeds about 15-20°C. According to some embodiments, both temperature and pressure, as well as any other suitable parameters, can be used to control the system.

[0140] Thus, according to the present invention, lumens such as the uterus, stomach, bladder, renal pelvis, urethra, and ureters can be treated even when gas cannot be safely expelled therefrom naturally. According to some embodiments, the dynamics of the system, including both the injection and evacuation of cryogenic fluid, prevent liquid or vapor within the lumen from freezing, thus preventing blockages and the like, while monitoring and controlling both the injection and evacuation throughout the process. According to some embodiments, in addition to the injection of cryogenic fluid, the system includes an additional flow injection source that introduces non-cryogenic fluid into the lumen when desired. For example, fluid can be injected into the lumen to potentially visualize the interior of the lumen, while leaving a certain volume of the lumen to allow the user to perform necessary actions. This may be necessary, particularly between any two freeze cycles or after the final freeze cycle. Additionally, fluid can be injected into the lumen to desiccate the lumen or a region therein. According to some embodiments, the lumen can be desiccated with dry and / or warm gas, and the pressure within the lumen can be maintained above a predefined value, e.g., 10 mbar, using gases such as CO2, air, argon, or N2. The combined infusion, evacuation, and control provide the dynamics necessary for the system to operate properly. Furthermore, the relatively small diameter of the infusion and evacuation tubes (approximately 0.8-4 mm overall diameter for all tubes combined, or approximately 4.0-9.0 mm overall diameter for all tubes, especially when visualization tools are included) allows treatment of lumens with small diameter entrances, such as the ureter. Furthermore, since each additional tube increases the overall diameter, one or two adjacent tubes can be used to further limit the diameter. Note that the small diameter, e.g., approximately 0.8-9.0 mm overall diameter, can include not only the infusion and evacuation channels but also any other channels, devices, sensors, etc., introduced into the body lumen, such as visualization tools. According to some embodiments, the overall diameter of the inflow and outflow channels is about 0.8 to 4.0 mm.The diameter of the outer sheath can be about 5.0 to 9.0 mm, and the outer diameter of the visualization means is about 3.0 to 5.0 mm.

[0141] According to some embodiments, bladder, cervix, stomach, prostate, urethra, ureter, or uterine conditions are treated. According to further embodiments, bladder, cervix, stomach, prostate, urethra, ureter, or uterine cancer is treated. Benign tumors can be treated as well. Pain symptoms within the bladder, stomach, cervix, prostate, or uterus can also be treated. According to further embodiments, any type of urinary tract condition can be treated, including upper urinary tract cancer, interstitial cystitis, bladder pain syndrome, overactive bladder (OAB), etc.

[0142] The distal end of the cryotherapy device can include any number of holes, nozzles, gaps, etc., through which fluid can be injected / introduced / released into the body lumen. According to some embodiments, the fluid can be injected into the lumen along with any additional materials, such as chemotherapy, immunotherapy, and / or other chemical or biological agents. The additional materials can be introduced simultaneously with, before, and / or after cryotherapy for optimal results. Herein, the introduced fluid is also referred to as a "coolant," "cryogenic fluid," etc. Note that the coolant can ablate / freeze any desired treatment area. According to some embodiments, the distal end of the cryotherapy device includes a nozzle designed to spray fluid directly onto and / or around the target site. The distal end of the cryotherapy device can further include an exhaust means for exhausting the expansion fluid from the body lumen. According to some embodiments, the cryogenic fluid is selected from liquid nitrogen, carbon dioxide (CO), nitrous oxide (N2O), or any combination thereof. According to some embodiments, the cryogenic fluid is selected from argon, nitrogen, krypton, or any combination thereof, which may be important when the cryogenic fluid does not directly contact bodily tissue. According to other embodiments, the cryogenic fluid may further include any additional materials, such as chemotherapy, immunotherapy, and / or other therapies, such as chemical or biological agents. According to some embodiments, the additional materials are introduced into the bodily lumen before, during, and / or after cryotherapy.

[0143] It should be noted that the terms "target region," "target site," "treatment region," "treatment site," "treatment cavity," "target cavity," etc. are used interchangeably and are intended to include any type of condition that can be cryotreated, such as lesions (including cancerous and benign tumors, cysts, polyps, etc.), nerves / nerve endings, and various conditions, even when the specific cause is not fully understood.

[0144] According to other embodiments, the coolant remains and expands within the infusion channel (e.g., catheter, tubing, etc.), resulting in the cold temperature being transmitted into the tissue by the intervening distal section of the cryotherapy device. According to such embodiments, since the coolant remains within the infusion channel, there is no need to evacuate the coolant from the body lumen.

[0145] According to some embodiments, the medial distal section of the cryotherapy device is a cryoballoon, which is introduced into the treatment lumen via an endoscope. The cryoballoon can be inflexible and therefore can withstand high pressures. If the balloon is inflexible, the size of the balloon is selected depending on the size of the lumen into which the balloon is inserted or the shape of the treatment site. According to other embodiments, the balloon can be semi-flexible or flexible. According to further embodiments, different sections of the cryoballoon can have different degrees of flexibility. Different parameters of the balloon, including the flexibility of various sections of the balloon, the shape of the cryoballoon, and the size of the cryoballoon, can vary depending on the treatment lumen, the target site within the lumen, etc. The balloon can be round, elliptical, tubular, or have any flat or partially flat surface. The balloon can also be wide in certain areas and narrow in other areas depending on the intended application. When inflated or partially inflated, the balloon can only locally contact the treatment site, rather than the entire lumen in which the balloon is used. According to other embodiments, inflation of a cryogenic balloon, for example within the urethra or ureter, can cause the balloon or portions of the balloon to contact the entire circumference of the treatment site. According to some embodiments, an external force, for example movement by a user of the device, can cause at least a portion of the cryogenic balloon to contact the treatment site, possibly in conjunction with inflation.

[0146] According to some embodiments, the diameter or average diameter of the cryogenic balloon when folded (when inserted through an endoscope or working channel) is less than 2.5 mm. According to some embodiments, the diameter or average diameter of the cryogenic balloon when folded (when inserted through an endoscope or working channel) is less than 2.0 mm. According to some embodiments, the diameter or average diameter of the balloon when folded (when inserted through an endoscope or working channel) is less than 1.5 mm.

[0147] Additionally, the balloon can be brought into contact with the target site by balloon inflation, partial balloon inflation, and / or balloon movement, which can be controlled externally by the user and / or any suitable mechanical and / or electronic means. The balloon inflation and / or movement can be further controlled in response to data received from any internal or external sensors.

[0148] It should be noted that, herein, the infusion and evacuation channels are also referred to as catheters, tubes, and the like.

[0149] According to some embodiments, the cryotherapy device can include a flexible or kink-resistant catheter, such as a braided or coiled tube, that can allow for sharp angular movements, thus allowing for easy targeting of the target site regardless of its location within the body.

[0150] According to some embodiments, the cryotherapy device includes a single nozzle at the distal end of the device, allowing the operator to perform treatment within the field of view of the endoscope. According to other embodiments, the device includes at least two nozzles, and any two nozzles can be positioned in the same or different orientation relative to each other. For example, one of the nozzles can be pointed downward in a distal direction, while the other nozzle can be pointed laterally at any desired angle and distance from the distal end of the device, thereby enabling multidirectional treatment, such as treating different portions of the same target area or treating several target sites at once. According to some embodiments, one or more of the nozzles have an open / close configuration. Furthermore, any one of the nozzles can be partially open or closed for any period of time required. According to some embodiments, any number of nozzles can be electronically controlled, allowing the practitioner using the device to use any number of existing nozzles at any time depending on the desired treatment. According to some embodiments, the user predefines the specific nozzle to be used. According to other embodiments, any one of the nozzles can be opened, partially opened, or closed at any time during the procedure, as desired, by any suitable means, including separate sensors, computerized applications, user commands, etc.

[0151] According to some embodiments, a folded component, such as a cryogenic balloon, can be attached to any portion of the distal end of the cryotherapy device. Thus, the injected cryogenic fluid, optionally in conjunction with any other suitable pressure source, inflates the balloon, which freezes at least a portion of the treatment tissue. According to some embodiments, prior to injection of the cryogenic fluid, the balloon is inflated by any other suitable pressure source to prepare the balloon for cryotherapy, inspect or test the system or specific parameters of the system, etc. As detailed above with respect to injection through the nozzles, the inflation of the balloon can be controlled by any number of sensors, including inflation rate, size, etc. Additionally, any one of the nozzles can be attached to the cryogenic balloon outside the nozzle, such that as the cryogenic fluid exits the nozzle, it inflates the balloon attached outside the nozzle.

[0152] Thus, according to some embodiments, the cryogenic fluid is injected directly into the body lumen, i.e., directly contacts at least a portion of the tissue in the body lumen. According to such embodiments, the cryogenic fluid is injected directly into the body lumen through any number of nozzles, holes, gaps, and / or valves, as detailed herein. Furthermore, if the cryogenic fluid is injected directly into the body lumen, the cryogenic fluid can also be directly expelled from the body lumen by any of the means detailed herein. According to other embodiments, the cryogenic fluid can be introduced indirectly into the body lumen, so that rather than directly contacting the tissue in the body lumen, the cryogenic fluid is injected into any suitable component disposed within the body lumen that does not include an opening into the body lumen, such as a catheter, cryogenic balloon, tube, etc. The cryogenic fluid expands within the component, thereby cooling at least a portion of the treated tissue. The cryogenic fluid can then be expelled indirectly from the body lumen, i.e., expelled from the component into which the cryogenic fluid was injected. The cryogenic fluid can be expelled by active or passive means.

[0153] According to some embodiments, the folded component is a cryogenic balloon that is inflated and / or filled with a coolant within the lumen to treat the desired site.

[0154] According to other embodiments of the present invention, any one of the endoscope's existing "inflow" and "outflow" channels can be used to introduce or evacuate material from a body lumen (e.g., to evacuate cryotherapy inflation fluid).

[0155] According to some embodiments, the cryotherapy treatment is performed in combination with any other type of treatment, including intracavitary chemotherapy and / or immunotherapy agents. It should be noted that the cryogenic fluid can be injected with any other active ingredient. As mentioned above, additional active ingredients can be introduced simultaneously with, before, and / or after cryotherapy.

[0156] Tissue cells frozen by cryotherapy are removed from the body, particularly through the lymphatic system, and can elicit an immunological response that can affect such cells anywhere in the body, not just the area being treated by cryotherapy. According to some embodiments, the introduction of additional active ingredients into the body lumen before or during cryotherapy can cause the treated tissue to react differently to the cryotherapy, and the cells, together with the additional active ingredients, can elicit an enhanced immune response when introduced into the lymphatic system.

[0157] The additional active ingredient can be any immunological, chemical, chemotherapeutic, biological, or nanoparticulate entity, including, but not limited to, mitomycin C, doxorubicin, dendritic cells, and the like.

[0158] Before describing at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of elements and / or methods set forth in the following description and / or illustrated in the drawings and / or examples. The invention is capable of other embodiments and of being practiced or carried out in various ways.

[0159] Exemplary Cryotherapy System According to some exemplary embodiments, a cryotherapy system includes a cryotherapy probe configured to be at least partially inserted into a body lumen and a control unit connected to the cryotherapy device. In some embodiments, the control unit is located outside the body. Reference is now made to FIG. 1A, which illustrates a cryotherapy system according to some exemplary embodiments of the present invention.

[0160] According to some exemplary embodiments, a cryotherapy system 1000 includes a cryotherapy probe, e.g., a cryotherapy device 1002, and a control unit 1004 connected to the cryotherapy device 1002. In some embodiments, the cryotherapy device 1002 is an elongated probe having a distal end 1021 shaped and sized to be optionally introduceable into a body lumen and to face a target area within the interior surface of the lumen, and a proximal end 1025 optionally positioned outside the body lumen. In some embodiments, the cryotherapy device 1002 is cylindrical, and the diameter of the cryotherapy device and surrounding sheath at the distal end 1021 is in the range of 3-15 mm, e.g., 3 mm, 5 mm, 7 mm, 9 mm, or any smaller or larger intermediate value. In some embodiments, the diameter of the cryotherapy device without the sheath is in the range of 0.3-5 mm, e.g., 0.5 mm, 1 mm, 2 mm, or any smaller or larger intermediate value. In some embodiments, the cryotherapy device 1002 is shaped and sized to be introduced into a body lumen through a working channel of an endoscope. Alternatively, the cryotherapy device 1002 is introduced into a body lumen through a sheath 1024.

[0161] According to some exemplary embodiments, the cryotherapy device 1002 comprises at least one flow path, e.g., a channel, passing through the lumen of the cryotherapy device from the proximal end 1025 to the distal end 1021. In some embodiments, the at least one flow path is used both as an inflow path into the body lumen toward the distal end 1021 and as an outflow path from the body lumen toward the proximal end 1025. In some embodiments, the cryotherapy device 1002 comprises at least one inflow path, e.g., inflow channel 1006, for delivering fluid or gas into the body lumen. Additionally or optionally, the cryotherapy device 1002 comprises at least one outflow path, e.g., outflow channel 1010, for evacuating fluid, particles, and / or gas from the body lumen.

[0162] According to some exemplary embodiments, the outflow pathway, e.g., outflow channel 1010, includes at least one outflow regulator, e.g., valve 1023, for controlling the passage of a substance, e.g., a gas or fluid, through the outflow pathway. In some embodiments, the at least one valve comprises at least one check valve configured to optionally passively open when pressure within the body lumen exceeds a predetermined value. Optionally, the outflow regulator is located near a proximal end 1025 of the cryotherapy device 1002 located outside the body.

[0163] According to some exemplary embodiments, the inlet channel 1006 includes at least one forward-facing cryogenic nozzle configured to spray a cryogenic fluid, e.g., a cryogenic gas and / or a cryogenic liquid, toward a selected target area within the interior surface of the lumen. Optionally, the cryogenic fluid is stored at high pressure. In some embodiments, without being bound by any theory, expansion of the high-pressure cryogenic fluid within the body lumen rapidly reduces the pressure of the fluid, resulting in a cryogenic effect, e.g., the Joule-Thomson effect, within the body lumen.

[0164] According to some exemplary embodiments, the cryogenic nozzle is an adjustable cryogenic nozzle configured to spray the cryogenic fluid at an angle less than or greater than 90 degrees relative to the target area. Alternatively, the cryogenic nozzle is a fixed angle cryogenic nozzle that is fixed at an angle different from 90 degrees, such as 15 degrees, 30 degrees, 45 degrees, 55 degrees, or any intermediate angle less than or greater than 90 degrees. In some embodiments, the adjustable cryogenic nozzle is configured to control the amount of cryogenic fluid sprayed and released through the nozzle into the lumen, for example, by adjusting the opening diameter of the cryogenic nozzle.

[0165] According to some exemplary embodiments, the cryotherapy device 1002 comprises at least one optical assembly, e.g., an optical path, optionally an optical channel 1018, which delivers images and / or visual signals of tissue facing the distal end 1021 of the cryotherapy device 1002 to an optical sensor located outside the body, e.g., an optical sensor in the control unit 1004, or to an external optical assembly, e.g., an optical assembly of a different control unit. Alternatively, the optical assembly comprises at least one optical sensor, e.g., optical sensor 1022, at the distal end 1021 of the cryotherapy device 1002, configured to sense images and / or visual signals of tissue facing the distal end 1021 of the cryotherapy device 1002, e.g., a target area in a body lumen. Alternatively, the optical assembly comprises a sensor, optionally an ultrasound (US) sensor or a magnetic resonance (MR) sensor. In some embodiments, the cryotherapy device 1002 comprises at least one irradiation source, e.g., irradiation source 1019. In some embodiments, the irradiation source 1019 is disposed at the distal end 1021 of the cryotherapy device, optionally facing the tissue of the body lumen. Alternatively, the at least one light source is disposed in a channel within the cryotherapy device, such as the optical channel 1018. In some embodiments, the optical channel 1018 is or comprises an optical fiber, a group of optical fibers, or an optical fiber cable. In some embodiments, when the optical channel 1018 is or comprises an optical fiber, a group of optical fibers, or an optical cable, the light source is disposed outside the body, and optionally the optical sensor is also disposed outside the body.

[0166] According to some exemplary embodiments, the cryotherapy device 1002 comprises at least one flow path, e.g., irrigation channel 1014, for inserting a irrigation gas, optionally a low-pressure gas, into the body lumen. In some embodiments, the irrigation gas is used to distend the body lumen, e.g., to allow better visualization of the inner surface of the lumen and / or better access to a desired area within the body lumen, optionally an area selected for cryotherapy. Additionally or alternatively, the irrigation gas is sprayed through an irrigation gas nozzle into the treatment area, e.g., to blow away condensation particles and / or multiple condensation particles formed by interaction of the cryogenic gas with the humidified environment within the body lumen.

[0167] According to some exemplary embodiments, the irrigation channel 1014 includes at least one forward-facing irrigation nozzle at the distal end of the cryotherapy device, facing the tissue. Optionally, the forward-facing irrigation nozzle is configured to spray gas, e.g., low-pressure gas, into the space between the cryotherapy device 1002 and the target area. In some embodiments, the forward-facing nozzle is an adjustable irrigation nozzle, e.g., allowing the irrigation gas to be sprayed laterally or at an angle relative to the target area. In some embodiments, the forward-facing irrigation nozzle sprays the irrigation gas into the FOV of the optical sensor 1022 or the field of view of the optics channel 1018.

[0168] According to some exemplary embodiments, the irrigation channel 1014 comprises at least one opening, e.g., a front irrigation opening and / or a side irrigation opening, optionally located near the distal end 1021 of the cryotherapy device 1002. In some embodiments, the cryotherapy device comprises at least one irrigation director, e.g., a nozzle and / or a deflecting surface, at the irrigation opening configured to direct irrigation fluid toward the optical assembly, e.g., the lens, and / or into the FOV of the optical sensor 1022 or the FOV of the optics channel 1018. Optionally, the at least one irrigation director is an adjustable irrigation director, e.g., configured to allow irrigation gas to be sprayed at an angle relative to the FOV.

[0169] According to some exemplary embodiments, at least one irrigation flow regulator on the irrigation inlet path is configured to adjust the amount of irrigation fluid released through the irrigation opening, optionally in response to a signal received from the control unit.

[0170] According to some exemplary embodiments, the cryotherapy device 1002 includes at least one foldable element, e.g., foldable elements 1001 and 1003. In some embodiments, the at least one foldable element is configured to be folded within an inner lumen of the cryotherapy device 1002 and optionally unfolded near the distal end 1021 of the cryotherapy device 1002. In some embodiments, the at least one foldable element is unfolded into a space between the distal end 1021 of the cryotherapy device 1002 and the target area. In some embodiments, this space is referred to as the treatment space. In some embodiments, the foldable element comprises an extension, a cone, or a dress. In some embodiments, the foldable element is unfolded within the treatment space, e.g., to determine the distance or angle between the distal end of the cryotherapy device and the target area. Alternatively, the folded element is unfolded within the treatment space, e.g., to determine the distance and / or angle between a cryogenic nozzle and the target area. In some embodiments, at least two foldable elements or one conical foldable element are unfolded to narrow the treatment space, for example, by creating a microenvironment within the inner space formed by the unfolded foldable elements.

[0171] According to some demonstrative embodiments, the control unit 1004 comprises at least one control circuit, e.g., control circuit 1026. In some embodiments, the control circuit controls the flow of the cryogenic fluid through an inlet pathway, e.g., inlet channel 1006. In some embodiments, the control circuit 1026 controls the flow of the cryogenic fluid by controlling at least one cryogenic flow regulator, e.g., a valve disposed in the inlet pathway, and / or at least one valve between the cryogenic source 1034 and the inlet channel 1006, e.g., at least one valve in a tube connecting the cryogenic source 1006 to the control unit 1004, and / or at least one valve in a tube connecting the cryogenic source and the inlet pathway. Alternatively or additionally, the control unit 1004 controls at least one valve of the cryogenic source, e.g., an outlet valve of the cryogenic source.

[0172] According to some exemplary embodiments, the control circuit 1026 controls the flow of the cleaning fluid through a cleaning inlet path, e.g., the cleaning channel 1014. In some embodiments, the control circuit 1026 controls the flow of the cleaning fluid by controlling at least one cleaning flow regulator, e.g., a valve disposed on the cleaning inlet path, e.g., the cleaning channel 1014. Alternatively or additionally, the control circuit 1026 controls the flow of the cleaning fluid by controlling at least one flow regulator between the cleaning source 1008 and the cleaning channel 1014, e.g., at least one valve in a tube connecting the cleaning source 1008 to the control unit 1004 and / or at least one valve in a tube connecting the cleaning source 1008 and the cleaning channel 1014. Alternatively or additionally, the control circuit 1026 controls at least one valve of the cleaning source, e.g., an outlet valve of the cleaning source 1008.

[0173] According to some exemplary embodiments, the control circuit 1026 controls the flow of fluid, e.g., gas and / or liquid, out of the body lumen through an outlet pathway, e.g., the outlet channel 1010. In some embodiments, the control circuit controls the flow through the outlet channel 1010 by controlling an outlet regulator, e.g., an outlet valve, e.g., valve 1023, in or near the proximal end of the outlet channel. Alternatively or additionally, the control circuit 1026 controls the activation of an evacuation pump 1007, e.g., a vacuum pump coupled to the outlet channel. In some embodiments, the evacuation pump 1007 is used to actively evacuate fluid, e.g., liquid or gas, from the body lumen through the outlet pathway of the cryotherapy device. Optionally, the control circuit 1026 controls at least one evacuation flow regulator, e.g., an evacuation valve on a tube connecting the evacuation pump 1007 and the outlet channel.

[0174] According to some exemplary embodiments, the control circuitry controls an optical sensor, e.g., optical sensor 1022, located on the optical assembly, e.g., cryotherapy device 1002. Alternatively or additionally, the control circuitry 1026 controls at least one optical sensor in the control unit 1002. In some embodiments, the control circuitry 1026 controls the opening or closing of the optical system channel 1018, optionally by controlling an aperture in the optical system channel 1018. In some embodiments, the control circuitry controls the activation of the optical system 1010, e.g., a visualization means.

[0175] According to some exemplary embodiments, the cryotherapy device 1002 includes at least one sensor 1011 located at the distal end 1021 to sense at least one environmental parameter, for example, of the body lumen. In some embodiments, the environmental parameter includes temperature, pressure, and / or humidity level, or any other environmental parameter. Alternatively or additionally, the cryotherapy device 1002 includes at least one sensor, for example, sensor 1005, disposed at least partially within the outflow path to sense the environmental parameter.

[0176] According to some exemplary embodiments, the sensor 1011 and / or the sensor 1005 are electrically connected to the control circuit 1026. Alternatively or additionally, the control circuit 1026 is electrically connected to one or more sensors located inside or outside the body. In some embodiments, the one or more sensors are located near or at a distance from the cryoablation target region. Alternatively, in some embodiments, at least one of the sensors transmits measured environmental parameter values ​​to the control circuit 1026. In some embodiments, the control circuit stores these measurements in the memory 1028. In some embodiments, the memory 1028 includes a predetermined value of at least one environmental parameter, such as a maximum pressure value, a maximum temperature value, or any other predetermined environmental parameter value, or a representation thereof. In some embodiments, the memory 1028 includes at least one cryotherapy protocol, a value of at least one cryotherapy parameter, or a representation thereof. In some embodiments, the memory includes log files related to the operation of the cryotherapy device 1002 or the operation of the cryotherapy system 1000.

[0177] According to some exemplary embodiments, the control unit 1002 comprises at least one interface 1030 electrically connected to the control circuitry 1026. In some embodiments, the interface 1030 comprises an audio source and / or a display. In some embodiments, the control circuitry 1026 signals the interface 1030 to generate at least one indication, e.g., a human-detectable indication, for a user of the cryotherapy device or system. In some embodiments, the control circuitry 1026 signals the interface 1030 to generate an alarm, e.g., when an environmental parameter value measured within the body lumen exceeds a predetermined value.

[0178] According to some exemplary embodiments, the control circuit 1026 is electrically connected to at least one cryogenic flow regulator, e.g., a valve, on the cryogenic inlet pathway. In some embodiments, the control circuit regulates the flow through the cryogenic inlet pathway, e.g., by delivering a signal to the cryogenic flow regulator, e.g., to reduce the flow in the inlet pathway, e.g., to stop the flow in the inlet pathway, and / or to increase the flow in the inlet pathway. In some embodiments, the control circuit regulates the cryogenic fluid flow in the cryogenic inlet pathway, e.g., when the pressure in the body lumen is above a predetermined pressure value. Alternatively, the control circuit regulates the cryogenic fluid flow in the cryogenic inlet pathway, e.g., when the temperature in the body lumen is below a predetermined temperature value.

[0179] According to some exemplary embodiments, the control circuit 1026 controls at least one purge flow regulator on the cryogenic inlet path. In some embodiments, the purge flow regulator is configured to control the flow of low-pressure fluid through the cryogenic inlet path and optionally the cryogenic nozzle into the body lumen, for example, when the cryogenic fluid flow is stopped, reduced, or adjusted by the control circuit.

[0180] According to some exemplary embodiments, the control circuit 1026 is connected to an outflow regulator, e.g., a valve. In some embodiments, the control circuit adjusts the outflow regulator, e.g., by opening the outflow path, e.g., when the pressure in the body lumen is higher than a predetermined value and / or the temperature is lower than a predetermined temperature value. According to some exemplary embodiments, the control unit 1004 comprises a power source, e.g., power source 1032. Alternatively, the control unit 1004 is connected to an external power source by electrical wiring. In some embodiments, the power source comprises a battery, optionally a rechargeable battery.

[0181] According to some exemplary embodiments, a control unit, e.g., control unit 1004, is connected to at least one inlet pathway of the cryotherapy device configured to allow fluid flow from a fluid flow source into the body lumen. Optionally, the control unit is connected to at least one inlet flow regulator on the inlet pathway configured to regulate fluid flow through the inlet pathway into the body lumen.

[0182] In some embodiments, a control unit, e.g., control unit 1004, is connected to at least one outlet pathway of a cryotherapy device configured to allow evacuation of fluid from a body lumen. Optionally, the control unit is connected to at least one outlet regulator, e.g., a valve or check valve, on the outlet pathway configured to regulate evacuation of fluid from the body lumen through the outlet pathway.

[0183] In some embodiments, the control unit 1004 controls the inflow regulator and the outflow regulator to regulate the pressure level within the body lumen to reach a pressure level below a predetermined value. Alternatively or additionally, the control unit 1004 controls the inflow regulator and the outflow regulator to regulate the temperature level within the body lumen to a temperature level above a predetermined temperature value.

[0184] According to some exemplary embodiments, the cleaning source 1008 comprises a fluid container, such as a gas container or a liquid container. In some embodiments, the cryogenic source 1006 comprises a container of a cryogenic fluid, such as liquid nitrogen, liquid carbon dioxide, or any other cryogenic compound, that can be stored as a liquid or gas at high or low pressure at room temperature.

[0185] According to some exemplary embodiments, at least one of the irrigation source 1008, the optics 1036, the cryogenic source 1006, and / or the evacuation pump 1007 are part of the cryotherapy system. Alternatively, the irrigation source 1008, the optics 1010, the cryogenic source 1006, and / or the evacuation pump 1007 are external elements and are optionally connected to the system 1000.

[0186] Exemplary Cryotherapy Process According to some exemplary embodiments, a cryotherapy process is used to ablate material, e.g., tissue, lesions, tumors, from the lining of a body lumen, e.g., the bladder. In some embodiments, some of the cells or portions of the tissue within the lining of the bladder are ablated during cryoablation, also referred to in some embodiments herein as cryoablation, for example, if the cells or tissue are cancerous or tumorigenic. In some embodiments, the expanded coolant material kills some of the cells and / or portions of the tissue within the lining of the body lumen in a rapid ablation effect, e.g., immediate necrosis, or in a slower ablation process, e.g., by being broken down by biological processes as apoptosis.

[0187] Reference is now made to FIG. 1B, which illustrates a cryotherapy process according to some exemplary embodiments of the present invention.

[0188] According to some exemplary embodiments, at least a portion of a cryotherapy device is introduced into a body lumen at 1050. In some embodiments, a cryotherapy device of the cryotherapy system 1000 shown in FIG. 1A, such as cryotherapy device 1002, is inserted into the body lumen through a working channel of an endoscope. Alternatively, the cryotherapy device is introduced into the body lumen through a sheath, such as an endoscope sheath or a separate sheath for the cryotherapy device.

[0189] According to some exemplary embodiments, the body lumen is inflated at 1052. In some embodiments, a device is at least partially inserted into the body lumen to enable inflation of the lumen. In some embodiments, the body lumen is inflated to enable better inspection of the interior surface of the body lumen, for example, by an optical sensor of the cryotherapy device, optionally a camera, or an optical sensor of a different device. Alternatively or additionally, the body lumen is inflated to enable better access to different regions or selected target regions within the body lumen. In some embodiments, the body lumen is inflated by introducing an irrigation fluid, optionally a low-pressure gas, into the body lumen. In some embodiments, during inflation of the body lumen, the pressure within the body lumen is monitored by at least one sensor located within the body lumen or an outflow channel of the cryotherapy device, for example, outflow channel 1010. Alternatively or additionally, the pressure is monitored by measuring the pressure or pressure change in the irrigation flow path by a pressure sensor, optionally located within the irrigation flow path. In some embodiments, the pressure is monitored by at least one sensor, for example, a pressure sensor located outside the body. In some embodiments, the inflation of the body lumen is controlled by a control circuit, e.g., control circuit 1026, optionally based on signals received from at least one sensor. In some embodiments, the body lumen is inflated to a desired or selected degree of inflation.

[0190] According to some exemplary embodiments, the body lumen is inflated by a flushing fluid directed to the optical assembly, e.g., to keep the optical assembly, e.g., lens, clean and / or dry and / or at a particular temperature. Alternatively or additionally, the body lumen is inflated by a purge flow of low-pressure fluid entering the body lumen through a cryogenic nozzle.

[0191] According to some exemplary embodiments, the interior surface of the body lumen is visualized at 1054. In some embodiments, the interior surface is visualized by at least an optical sensor of the cryotherapy device, e.g., optical sensor 1022, which is optionally a camera. Alternatively, the interior surface of the body is visualized by at least one optical sensor located outside the body lumen that receives an optical signal via an optical system channel in the cryotherapy device, e.g., optical system channel 1018. In some embodiments, the optical signal is received by an optical system unit, e.g., optical system 1018, optionally located outside the body. In some embodiments, when the body lumen is visualized, at least one light source is activated, e.g., a light source located within the body lumen on the cryotherapy device or a light source located outside the body.

[0192] According to some exemplary embodiments, a target region for cryotherapy is determined at 1056. In some embodiments, the target region is determined based on an analysis of an image showing the interior surface of the body lumen. Optionally, the target region is determined based on imaging results and / or other clinical data.

[0193] According to some exemplary embodiments, at 1058, the cryotherapy device or the distal end of the cryotherapy device, e.g., distal end 1021, is navigated to a selected distance from the determined target region, e.g., up to 50 mm from the target region, e.g., 5 mm, 10 mm, 15 mm, 20 mm, 25 mm from the target region, or any intermediate distance, smaller or larger. Additionally or alternatively, the cryotherapy device or distal end is navigated at a selected angle relative to the determined target region. In some embodiments, the distal end of the cryotherapy device is passively navigated by turning the distal end of the endoscope to the selected angle. Alternatively or additionally, at least a portion of the cryotherapy device is actively navigated to the desired target region and / or to the desired angle between the opening of the cryogenic inflow pathway and the tissue in the selected target region.

[0194] According to some exemplary embodiments, at 1060, a distance to the target area is determined. In some embodiments, the distance between the distal end of the cryotherapy device and the target area is determined by unfolding a ruler or an accessory of known length, such as a wire, to contact the target area within the interior surface of the body lumen. In some embodiments, the distance is determined optically with a light beam, such as a laser light beam. Optionally, the distance is measured with an optical distance meter, such as a laser light meter, connected to the cryotherapy device, optionally the distal end of the cryotherapy device.

[0195] According to some exemplary embodiments, the distance between the cryotherapy device, e.g., the distal end of the cryotherapy device, and the target region is determined by directing a jet of air or gas from an inflow path, e.g., the irrigation channel 1014 or a cryogenic nozzle, of the cryotherapy device toward the target region and visualizing the effect of the air or gas jet on the tissue. In some embodiments, the air or gas jet forms a depression at the site of contact with the interior surface of the body lumen. Optionally, the distance from the site of contact and / or the angle between the cryotherapy device and the target region is determined by visualizing the depth, size, and / or shape of the depression. In some embodiments, at least one parameter value of the cryotherapy process is determined based on the distance and / or angle, e.g., the duration of cryotherapy and / or the pressure and / or volume of cryogenic fluid required to reach a desired outcome of the treatment.

[0196] According to some exemplary embodiments, a treatment space is established at 1062. In some embodiments, the treatment space is established by unfolding at least one foldable element, such as a cone or dress, that seals the treatment space between the cryotherapy device and the target region within the body lumen. In some embodiments, the treatment space is established to reduce damage to tissue surrounding the target region due to release of cryogenic fluid. Alternatively and / or additionally, the treatment space is established to allow for better control over microenvironment parameters within the limited volume of the treatment space.

[0197] According to some exemplary embodiments, a cryotherapy device is directed toward the target area at 1064. In some embodiments, a distal end of the cryotherapy device is directed toward the target area. Alternatively or additionally, a nozzle, optionally an adjustable nozzle, configured to spray the cryogenic fluid is directed toward the target area.

[0198] According to some exemplary embodiments, at 1066, a cryogenic fluid is applied. In some embodiments, the cryogenic fluid is applied, e.g., sprayed, through a nozzle at the target area. In some embodiments, the cryogenic fluid is applied while the body lumen is expanded, optionally with air or gas entering the body lumen through a different inlet channel. Alternatively, when the cryogenic fluid is applied, the body lumen is expanded solely by the application of the cryogenic fluid and, optionally, by the expansion of the cryogenic fluid within the lumen. Alternatively, the body lumen is expanded solely by an irrigation fluid, which optionally keeps the optics dry and / or at a substantially constant temperature.

[0199] According to some exemplary embodiments, a cryogenic irrigation fluid and / or an optics irrigation fluid is applied at 1068. In some embodiments, an irrigation fluid, e.g., a gas, optionally a low-pressure gas, is applied between cryogenic fluid spray sessions. Alternatively, an irrigation fluid is applied during cryogenic fluid spray. Optionally, an irrigation fluid is used to distend the body lumen. In some embodiments, an irrigation fluid is applied through an irrigation inlet path, e.g., irrigation channel 1014 of FIG. 1A . In some embodiments, an irrigation fluid is applied into the space in front of the distal opening of optics channel 1018 and / or the space in front of optical sensor 1022 and / or light source 1019, e.g., to sweep and / or displace particles formed by the cryogenic fluid within the body lumen. Alternatively or additionally, an irrigation fluid is applied to the space between the cryogenic nozzle and the target area to sweep away particles. In some embodiments, these particles are swept away to allow better visualization of the application of the cryogenic fluid on the target area at 1066. In some embodiments, the irrigation fluid comprises a warm gas or warm fluid having a temperature greater than 15 degrees Celsius, for example, 15 degrees Celsius, 20 degrees Celsius, 25 degrees Celsius, or any intermediate temperature value less or greater. In some embodiments, the warm fluid is used to increase the temperature and optionally reduce humidity, for example, within the body lumen.

[0200] According to some exemplary embodiments, material is evacuated from within the body lumen at 1070. In some embodiments, material, e.g., a portion of a liquid, particles, or gas, is evacuated from the body lumen through an outflow channel in the cryotherapy device, e.g., outflow channel 1010 shown in FIG. 1A . In some embodiments, material is evacuated passively when pressure within the body lumen exceeds a predetermined value, e.g., by opening a valve, e.g., a check valve, in the outflow path. Alternatively or additionally, material is purged actively by actively creating a negative pressure in the outflow path, optionally by activating a vacuum pump. In some embodiments, material is evacuated between or during spraying of the cryogenic fluid at 1066. In some embodiments, material is evacuated when pressure exceeds a predetermined pressure value. Alternatively, material is evacuated when the temperature within the body lumen is below a predetermined value.

[0201] According to some exemplary embodiments, the target area is visualized at 1072. In some embodiments, the target area is visualized after spraying of the cryogenic fluid, for example, to determine the effect of the cryogenic fluid on the target area. Optionally, the target area is visualized to determine the success of the cryotherapy session. In some embodiments, if the treatment was ineffective, the device is optionally aimed at a different target area and / or positioned at a different angle and / or distance relative to the target area.

[0202] According to some exemplary embodiments, the cryotherapy device is retracted from the body lumen at 1074. In some embodiments, the cryotherapy device is retracted once the cryotherapy session has reached a desired goal, e.g., cryoablation of the target area. Optionally, the device is retracted to allow re-navigation to a different area within the body lumen.

[0203] Exemplary cryotherapy device within a body lumen 1C-1F, which illustrate schematic longitudinal cross-sectional views of an embodiment of a cryotherapy device according to some exemplary embodiments of the present invention, such as a cryotherapy device 10, delivered through an endoscope 16 to a treatment lumen 11 during a cryotherapy treatment.

[0204] According to some exemplary embodiments, even when the specific cause is unknown, as shown for example in FIG. 1C , a jet 13, which may include an expanded, high-pressure (or compressed) cryogenic fluid, is sprayed from the distal end 14 of the device 10 and directed toward a treatment area 12, which may be a benign or cancerous tumor, cyst, polyp, free nerve ending, or an area experiencing a particular symptom (such as pain), and optionally freezes and thereby treats or ablates the treatment area 12.

[0205] According to some exemplary embodiments, body lumen 11 can include two or more target regions, e.g., regions 12a, 12b, and 12c, as shown in FIG. 1D . Thus, in some embodiments, distal end 14 of device 10 can include two or more nozzles (not shown), with jets 13a, 13b, and 13c emerging from each nozzle directed toward a respective target region. According to some exemplary embodiments, distal end 14 includes multiple nozzles, each of which can have an open and closed configuration. These nozzles can be utilized, or opened, depending on their relative position with respect to the target region, such that the nozzles pointing toward the target region are open, thereby spraying the cryogenic fluid exiting those nozzles directly onto the target region.

[0206] According to some exemplary embodiments, as presented in, for example, FIG. 1E, device 10 includes both an inflow 133 that provides jet 13 (or any number of jets, as presented in FIG. 1B) and an outflow 177 that expels, for example, inflation fluid 17 from lumen 11. In some embodiments, the expanding portion of device 10 illustrates that a tube for inflow 133 can be disposed within a tube for outflow 177, although according to different embodiments, these can be disposed in any relationship relative to one another. Additionally, there can be any number of outflow and inflow tubes.

[0207] According to some exemplary embodiments, as shown, for example, in FIG. 1F, the endoscope 16 can be used at an acute angle so that the jet 13 reaches the treatment area 12 regardless of where the treatment area 12 is located within the body lumen 11.

[0208] Exemplary Cryotherapy System with Inflow and Outflow Means Reference is now made to Figures 2A, 2B, and 2C, which show schematic longitudinal cross-sectional views of cryotherapy systems according to some exemplary embodiments of the present invention, specifically illustrating the means by which fluid flows into and out of a treatment area. According to some exemplary embodiments, a cryotherapy system, such as cryotherapy system 20, includes a pressurized coolant source 201 and an evacuation means 202. In some embodiments, the evacuation means 202 can be separate from the cryotherapy system 20, a general evacuation means, an outlet to the surrounding atmosphere, or any other suitable means by which a substance, such as expansion fluid, can be evacuated from the system. According to some embodiments, the evacuation means 202 includes suction provided by any suitable pump, vacuum, or the like. According to some embodiments, the evacuation means 202 can be attached to the proximal end of the cryotherapy device 10. According to some embodiments, the evacuation means 202 is attached to the cryotherapy device 10 via a joint 28.

[0209] According to some exemplary embodiments, as shown in, for example, FIGS. 2A and 2B , a cryotherapy catheter 224 is inserted into the endoscope 16 so that the distal end 24 of the catheter 224 reaches the distal end of the endoscope 16, while the proximal end 25 of the cryotherapy catheter remains outside the proximal end of the endoscope 16. According to some embodiments, the proximal end 25 is coupled to a junction 28, as described in detail herein. According to some embodiments of the present invention, simultaneous inflow 133 and outflow 177 are permitted ( FIG. 2B ). In some embodiments, a seal 28 a can prevent potential mixing between the two flows. In some embodiments, this may be necessary when the two flows are directed coaxially within the endoscope, thus eliminating the need to separate the flows outside the endoscope. An optional suction trap 203 can collect the evacuation fluid and protect the evacuation means 202 from contamination.

[0210] According to some embodiments, as shown in, for example, FIG. 2C , junction 28 includes valve 28b that controls inflow 133 and outflow 177 to prevent simultaneous flow, and valve 28b determines whether inflow 133 or outflow 177 is activated. In some embodiments, valve 28b may be operated according to any suitable means, including predefined settings, electronic means, manual operation, etc. In some embodiments, the control of valve 28b may take into account pressure, time, target area response, etc.

[0211] According to some embodiments, the inflow can be stopped when the pressure in the lumen exceeds about 30-100 mbar. According to some embodiments, the outflow can continue to be discharged until the pressure in the lumen falls below about 20-10 mbar. According to some embodiments, the inflow can be stopped when the temperature in the lumen falls below about 5-10°C. According to some embodiments, the inflow can be started when the temperature in the lumen exceeds about 15-20°C. According to some embodiments, both temperature and pressure, as well as any other suitable parameters, can be used to control the system.

[0212] According to some embodiments, the cryotherapy system may include a control mechanism, such as the control unit 1004 shown in FIG. 1A, that controls the injection of coolant and / or the ejection of expansion fluid. In some embodiments, the control mechanism may include predetermined parameters (e.g., cyclical) and / or parameters defined by feedback on data collected from the system by any suitable sensors, such as distal pressure, distal temperature, proximal pressure, proximal temperature, inlet flow vs. outlet flow, operating time, and other optional measured parameters. In some embodiments, when such feedback-related control is implemented, the associated sensing and control means are part of the embodiment (e.g., CPU, firmware, flow sensor, pressure sensor, clock, etc.).

[0213] Reference is now made to Figure 3, which shows a schematic longitudinal cross-sectional view of one embodiment of a cryotherapy system, specifically illustrating the positioning and possible fixation of the distal end of the device according to some exemplary embodiments of the present invention. According to some embodiments, a cryotherapy system, e.g., cryotherapy system 20, includes a pressurized coolant source 201 and an evacuation means 202, which are optionally interconnected at junction 28 to the proximal end 35 of the cryotherapy device 10. In some embodiments, an optional suction trap 203 can collect evacuated fluids as needed.

[0214] Exemplary Definition of the Distance Between the Distal End of the Catheter and the Distal End of the Endoscope According to some embodiments, a fixation mechanism is implemented to define the distance between the distal end of the cryotherapy device, e.g., the distal end of the catheter 24, and the distal end of the endoscope 16. In some embodiments, the fixation mechanism can be attached to the proximal end 35 of the cryotherapy device 10. In some embodiments, notches 35a provide a specific distance between the distal end of the catheter 24 and the distal end of the endoscope 16, and the limiter 35b can be moved and / or fixed in accordance with each specific notch or scale within a range defined by the operator to define the desired distance. The desired distance can be predefined, controlled by any suitable electronic means, manually controlled, etc. The desired distance can be changed during device operation or can be constant throughout the cryotherapy procedure. The limiter 35b can be fixed within a particular notch 35a by any suitable fixation mechanism, such as a clip, screw, elastic band, etc.

[0215] Distal End of an Exemplary Cryotherapy Device Reference is now made to FIGS. 4A-4D , which illustrate schematic longitudinal cross-sectional views of the distal end of a cryotherapy device according to some embodiments of the present invention. According to some exemplary embodiments, any number of tubes / catheters can be used for both inflow and outflow into and out of the system, respectively. It is further noted that according to some exemplary embodiments, any suitable configuration of the tubes / catheters relative to one another is possible, such as one within the other, two tubes adjacent to one another, etc. Some embodiments include tubes / catheters with several paths through which fluid can flow in any defined direction. According to some embodiments, the distal end 24 includes paths for the simultaneous flow of pressurized coolant inflow 133, which is sprayed through the nozzle 49, and expansion fluid outflow 177, which is discharged.

[0216] According to some embodiments, as presented in FIG. 4A, the distal end 24 has an inlet nozzle 49 and an outlet opening 407 in adjacent or similar planes.

[0217] According to other embodiments, as shown in Figure 4B, the inlet nozzle 49 and the outlet opening 407 are positioned in different planes of the distal end 24. In some embodiments, when in different planes, the inlet and outlet do not interfere with each other, thereby optimizing the freezing effectiveness of the inlet 133 and the drainage of the outlet 177.

[0218] According to other embodiments, as shown in FIG. 4C , the outlet opening 407 is positioned at a varying distance from the inlet nozzle 49, e.g., has a sloped cross-section. In some embodiments, this can also provide for inflow and outflow that do not interfere with each other. In some embodiments, by having a varying distance between the inlet nozzle 49 and the outlet opening 407, while still at least partially in close proximity to the nozzle 49, the exhaust fluid passing through the outlet opening 407 should not interfere with the inflow 133, thus allowing for efficient exhaust / suction of the outflow 177 through the outlet opening.

[0219] According to another embodiment, as shown in FIG. 4D , the distal end 24 includes several side outlet openings 407. In some embodiments, the side outlet openings 407 can be circumferential or partially circumferential. Utilizing such side openings separates the outlet 177 and the inlet 133 from each other, thus preventing them from interfering with each other. Furthermore, the presence of several outlet openings 407 allows for efficient drainage of fluid, even though the outlet openings 407 are located on the sides of the distal end 24.

[0220] Reference is now made to FIG. 4E, which illustrates a schematic longitudinal cross-section of the distal end 24 of a cryotherapy device according to another embodiment of the present invention. According to some embodiments, the distal end 24 does not include any openings leading to the treatment lumen, so the coolant remains and expands within the distal end 24. According to such embodiments, the transfer of cold temperature into the tissue is mediated by the intervening region 44 of the distal end 24. Therefore, pressure does not build up within the body lumen being treated. According to some embodiments, to further optimize the temperature reduction, i.e., freezing of the treatment site, a feedback coil 409 can be used to pre-cool the pressurized coolant inflow 133 by the already-cooled expansion fluid of the outflow 177.

[0221] According to some embodiments, the intermediary region 44 is prepared from a rigid material, such as stainless steel, copper, or brass. According to other embodiments, the intermediary region 44 can be prepared at least in part from an expandable or distensible material, such as a balloon, which allows the distal end 24 to assume the geometry of the treatment lumen, thereby optimizing the treatment. According to further embodiments, the distensible / expandable portion of the intermediary region 44 can be inflated / expanded to assume a shape that can touch or surround the target area but does not necessarily fill the treatment lumen. According to some embodiments, the distensible / expandable portion of the intermediary region 44 can be inflated / expanded automatically or manually, according to predefined parameters, according to signals received from any appropriate sensor. Furthermore, the rate and size of inflation / expansion can vary throughout the cryotherapy treatment. As detailed above, the intervening region can be made of a flexible material (15-200%, e.g., prepared from polyurethane, nylon elastomers, and other thermoplastic elastomers), a non-compliant material (0-8%, e.g., prepared from PET, nylon, etc.), or a semi-compliant material (5-15%, e.g., prepared from polyamides, and processed nylons (Pebax®) as polyether block amides, and PET and polyurethane), can be of any suitable size and shape, and can be contacted with the treatment area by expansion and / or movement of the intervening region, optionally externally by a user. In some embodiments, expansion and / or movement can be controlled by any suitable means and can further be controlled in response to data gathered by any internal or external sensors.

[0222] Reference is now made to FIGS. 4F-4H, which show schematic cross-sectional views of a cryotherapy device. According to some embodiments, inflow 133 flows through tube / catheter 33, which is disposed within tube / catheter 77, through which outflow 177 flows. According to some embodiments, tube / catheter 33 and 77 can be separate from one another and, if desired, can be disposed during or before the cryotherapy treatment. According to other embodiments, tube / catheter 33 and 77 are integrated together, so that there is essentially only one such tube / catheter containing passages for both outflow 177 and inflow 133. Thus, two tubes can be used to fabricate the desired shape, or alternatively, one tube can be extruded with appropriate channels. Note that while the embodiment presented in FIG. 4F shows tube 33 within tube 77, according to other embodiments, tube 77 can be disposed within or beside tube 33. This is equally true for the embodiments shown in FIGS. 4G and 4H, where the position of either of the tubes can be changed depending on the system / user requirements. Additionally, according to some embodiments, the outer tube, shown as tube 77, can be the working channel of the endoscope through which tube 33 passes (or vice versa).

[0223] According to further embodiments, as shown in FIGS. 4G and 4H, the cross section of the distal end 24 has several openings, with the outflow 177 passing through some of these openings and the inflow 133 passing through other openings. Any one of these openings can serve as an inflow, outflow, or sensing passageway, depending on the system / user requirements. A sensing passageway is a passageway through which at least one sensor passes, and data collected from that sensor can be used to control the system and its use. Furthermore, any one of these passageways can function electronically or manually, depending on predefined conditions, parameters defined in response to data received from any suitable sensor, for outflow or inflow at different times during a cryotherapy treatment. While FIGS. 4A-4H present specific embodiments of the distal end of the device, it should be noted that any other embodiment can be implemented, including any number or location of inflow / outflow tubes. It should also be noted that any such tubes can be prepared from a combination of several tubes, fabricated, and / or extruded.

[0224] According to other embodiments, any number of paths / tubes / catheters may be used through the endoscope 16 for sensing means that may be needed to control the pressure or temperature of the body lumen, such as pressure and / or temperature sensing, or any other sensors that may be needed. Additional sensing means may include sensors that calculate the volume of the lumen (e.g., the internal volume and changes in volume due to inflow and outflow), sensors that sense the wall thickness of the lumen (e.g., with ultrasound or laser light), etc.

[0225] Exemplary Angulation of Cryotherapy Devices Reference is now made to FIGS. 5A-5D, which illustrate schematic longitudinal cross-sectional views of a cryotherapy device delivered into a body lumen via an endoscope during an angulation scenario according to some embodiments of the present invention. According to some embodiments, a cryotherapy device, e.g., cryotherapy device 10, as shown in FIG. 5A, is inserted into a working channel of an endoscope 16, such that a distal end 24 of the cryotherapy device 10 reaches the distal end of the endoscope 16. In some embodiments, when angulation of the endoscope 16, including angulation, is required to navigate a particular passageway and / or target a treatment area, it is necessary to avoid the formation of kinks in the cryotherapy device 10. In some embodiments, such kinks, e.g., kink 505a, as shown in FIG. 5A, may interfere with the inflow and outflow of fluids through the cryotherapy device 10. Thus, the cryotherapy device 10 can include a flexible, flexible, and / or kink-resistant tube / catheter, such as a braided tube 505b (FIG. 5B) or a coiled tube 505c (FIG. 5C), to aid in angulation, including sharp angulation, that allows for targeting of any treatment area throughout the treatment lumen and passage through any necessary passages to reach the body lumen. According to some embodiments, the cryotherapy device 10 includes a tube / catheter, where only certain sections of the tube / catheter are flexible, flexible, and / or kink-resistant. According to other embodiments, the cryotherapy device 10 includes a tube / catheter that is flexible, flexible, and / or kink-resistant throughout its length.

[0226] According to some embodiments, the cryotherapy device can include a non-rigid, flexible, semi-expandable catheter 54a (FIG. 5D) that can be expanded to the geometry of the working channel by one of the device's flows (pressurized or expansion fluid). This is particularly important when the working channel undergoes angulation. According to some embodiments, more rigid components 54b can be found around the distal end of the catheter (FIG. 5D), thus helping to maintain the shape and orientation of the catheter's orifice even when expanded to maintain the desired spray flow 53.

[0227] Exemplary Nozzles Reference is now made to FIGS. 6A-6E, which show schematic longitudinal cross-sectional views of the distal end of a cryotherapy device, specifically illustrating embodiments of nozzles / holes / valves in an inflow tube / catheter and associated cryogenic fluid inflow spraying according to some embodiments of the present invention. A cryotherapy device according to embodiments of the present invention can include a pressurized coolant tube / catheter through which cryogenic fluid can pass before exiting the tube / catheter through a nozzle / hole / valve and thus entering the body lumen to be treated. Such nozzles / holes / valves can be designed in any suitable manner to direct the cryogenic fluid flow into the body lumen and, optionally, to the treatment area. According to one embodiment, as shown in FIG. 6A, for example, an inflow path, e.g., inflow 133, exits tube 60 via hole (nozzle / orifice) 69a, an opening located at the distal end of tube 60. It should be noted that, although not shown, any of the holes / nozzles described herein can include any type of valve or the like.

[0228] According to some embodiments, as presented in Figure 6B, the inflow 133 exits through a hole (nozzle / orifice) 69b that has a reduced diameter relative to the diameter of the tube 60. Such a reduced diameter may provide for cryogenic fluid to be sprayed onto the treatment area at a defined pressure and / or may allow for a more efficient and accurate Joule-Thomson effect.

[0229] According to some embodiments of the invention, as shown in Figures 6A and 6B, the holes / nozzles / orifices 69a or 69b are aligned with the tube 60 to provide a frontal spray of the inflow 133. According to other embodiments of the invention, the holes / nozzles / orifices are directed in any suitable direction, including to the side of the tube 60. According to some embodiments, the direction of the spray exiting any one of the nozzles can be changed by an element within the nozzle that can be directed in any suitable direction, and the direction of this element can be changed automatically, manually, by electronic means, in response to data received from any suitable sensor, etc.

[0230] According to some embodiments, as shown in Figure 6C, there can be any number of holes in the tube 60 that allow the inflow 133 to exit through multiple holes 69c. Additionally, the holes 69c can be arranged in any desired configuration, and each hole 69c can include a valve that can be closed, open, or partially open as needed.

[0231] According to some embodiments, the nozzle is part of the tube 60. According to other embodiments, as shown in FIG. 6D, for example, the nozzle 69d is an additional component attached or connected to the tube 60 by any suitable means. This connection or attachment may result from manufacturing advantages or constraints. According to some embodiments, each nozzle may have a distinct shape or size, such as a tapered nozzle 69e as shown in FIG. 6E. In some embodiments, the size and shape of the nozzles, as well as the number of nozzles, may be optimized for each treatment, e.g., the size or type of treatment area / lesion, the size of the body lumen in which the treatment area / lesion is located, the size and shape of the inflated cryogenic balloon, etc. In some embodiments, additional processes, such as heat treatment or machining, may be required to achieve a distinct shape for the nozzle 69e. In some embodiments, the inner diameter of either the inlet or inlet nozzle may be, on average, in the range of approximately 0.05-0.3 mm, and the inner diameter of either the outlet or outlet nozzle may be in the range of approximately 0.5-4 mm. It should be noted that the cross section of the nozzle may be of any suitable shape, including circular, non-circular, elliptical, slit-shaped, and the like.

[0232] Exemplary Emission Outflow Paths Reference is now made to Figures 7A and 7B, which show schematic cross-sectional views of the distal end of a cryotherapy device within an endoscope having inflow and outflow pathways, e.g., inflow and outflow channels, according to some embodiments of the present invention. According to some embodiments, the distal end 24 of the cryotherapy device directs the inflow 133 of a coolant jet to the target area to be treated. A cryotherapy catheter is inserted from the proximal end of the endoscope through the inflow channel.

[0233] According to some embodiments of the present invention, as shown in detail in FIGS. 1A-6 , the evacuation of the expanded coolant, as well as any other fluids present in the treated organ, is performed through a catheter / tube inserted into the organ via an endoscope, e.g., a cryotherapy device inserted into the organ via the working channel of the endoscope. According to some embodiments, the evacuation can be performed through one or several specific tubes or pathways, which can be part of the endoscope, added to the endoscope, or delivered through the endoscope. For example, some endoscopes (e.g., resectoscopes for cystoscopy and hysteroscopy) have an opening on the posterior side through which the cryotherapy device can be inserted. In such endoscopes, at least a portion of the evacuation can occur at this posterior side (773), and some can occur through the outflow outlet (771) and / or the inflow inlet (772). It is further noted that such openings can be used to control the inflow, outflow, and intraluminal pressures affected by the inflow / outflow.

[0234] According to some embodiments of the present invention, the opening to the exhaust tube / catheter can be adjacent to the inlet 133 or can be located in the same or similar plane as the inlet 133 (see, for example, opening 77a shown in FIG. 7A). According to other embodiments, several circumferential exhaust openings 77b are provided, as shown in FIG. 7B. The location, number, size, diameter, etc. of the exhaust tube can be varied and defined as needed, as detailed herein. Furthermore, any one of these openings can be equipped with a valve that allows the opening to be opened, closed, or partially closed, so that any one of the openings can be used as needed. Operation of the valve can be electronic, manual, automatic, in response to a signal received from any suitable sensor, etc.

[0235] Exemplary Folded Ablation Components Reference is now made to Figures 8A and 8B, which illustrate schematic longitudinal cross-sectional views of a cryotherapy device delivered through an endoscope into a treatment lumen during an ablation procedure according to some embodiments of the present invention. In some embodiments, the individual ablation component 83a shown in Figure 8A or the individual ablation component 83b shown in Figure 8B can be an unfolded cryogenic balloon (partially shown in Figure 4E).

[0236] According to some exemplary embodiments, to treat a target area 82, a cryotherapy device, e.g., an ablation device 80, is inserted into endoscope 16 through its working channel such that a distal end 24 of the device exits the distal end of the endoscope within body lumen 81, while a proximal end 85 of the device remains outside the proximal end of the endoscope and outside the patient being treated, as shown in FIG. 8A. According to some embodiments of the present invention, a separate ablation component 83a is deployed within body lumen 81 to treat target area 82, as shown in FIG. 8A.

[0237] According to another embodiment of the present invention, as shown in Figure 8B, a wider ablation component 83b is deployed within body lumen 81 to simultaneously treat target areas 82 and 82b, and possibly even more areas. Optionally, the entire lumen can be treated if desired.

[0238] Reference is now made to FIGS. 8C and 8D, which illustrate schematic longitudinal cross-sectional views of an expanded cryotherapy device introduced via an endoscope into a treatment lumen during an ablation procedure according to some embodiments of the present invention. In some embodiments, the expanded component can include several regions, each having a different flexibility. In some embodiments, the expanded component can be constructed from an inflexible or semi-flexible portion (0-8%) (see element 83c shown in FIGS. 8C and 8D) and a semi-flexible or flexible portion (5-200%) (see element 83d shown in FIGS. 8C and 8D). According to some embodiments, element 83c can be prepared from any suitable type of metal or plastic. According to some embodiments, element 83c can have a folding or unfolding configuration.

[0239] According to some embodiments, cold energy is delivered to the tissue via flexible / semi-flexible element 83d. According to some embodiments, as shown in these figures, only certain portions of the cryogenic balloon can contact the treatment site, while other areas within the treatment lumen do not directly contact the cryogenic balloon. In some embodiments, element 83d can be an expandable component, and element 83c can be a structured element designed to retain and / or partially define the shape of element 83d. In some embodiments, expanded component 83d can remain expanded while within endoscope 16 (FIG. 8C), such that when expanded (by inflow 133 or other means), element 83d is guided toward the target site and delivers cold energy to the target site.

[0240] Reference is now made to FIGS. 8E-8G, which illustrate schematic longitudinal cross-sectional views of an expanded cryotherapy device introduced into a lumen during an ablation procedure, according to some embodiments of the present invention. FIG. 8E shows an expanded element within the lumen, having an active portion 83d, proximate to a treatment site 82c. FIG. 8F shows an expanded element with a low flexibility (0-8%) active region 83d1, and FIG. 8G shows an expanded element with a high flexibility or semi-flexible (5-200%) active region 83d2. As shown in these figures, the use of a high flexibility or semi-flexible expanded element results in optimal contact between the device and the treatment site, allowing the device to optimally conform to the treatment site.

[0241] Reference is now made to Figures 9A and 9B, which illustrate schematic longitudinal cross-sectional views of the ablation of the device's distal tip 93 according to some embodiments of the present invention. According to some embodiments, the folded distal tip 934a shown in Figure 9A can include support ribs as well as a cryogenic balloon component. According to some embodiments of the present invention, the folded distal tip 934a is inserted into a body lumen through a sheath 99 (which can be the working channel of the endoscope itself) by pushing a catheter or wire 931. When the ablation distal tip 934a is positioned within the body lumen proximate to the target area (see Figures 8A and 8B), a user can manipulate a wand (or lever, valve, faucet, or controller) 933 to unfold the ablation distal tip 934b as shown in Figure 9B and then activate the ablation freeze mechanism.

[0242] Exemplary Cryotherapy Device with Endoscopic Visualization 10A-10D, which show schematic longitudinal cross-sectional views of additional embodiments of a cryotherapy device, such as cryotherapy device 10, during a cryotherapy procedure in which cryotherapy device 10 is introduced into treatment lumen 11 through endoscope 16, relative to the embodiment of FIG.

[0243] According to some embodiments, as shown in FIG. 10A, the endoscope 16 can include a visualization means 18 for visualizing a field of view 19 (FOV), with the jet 13 and / or treatment site 12 within the FOV 19.

[0244] According to other embodiments, as shown in, for example, Figures 10B-10D, the endoscope 16 is a sheath-like device, and devices can be inserted through the sheath into the lumen by various means, for example, using space 188, as shown in, for example, Figure 10D. Thus, the sheath 16 can allow for the insertion of different types of visualization means 18 to view the FOV 19, the cryotherapy device 14, etc. In some embodiments, the outflow 177 can have a separate outflow channel, for example, as shown in, for example, Figure 10D, or can flow through the free space 188 of the endoscope (Figure 10D).

[0245] Exemplary Cryotherapy System with Means for Injecting Fluid Reference is now made to FIG. 11 , which illustrates a schematic longitudinal cross-sectional view of a cryotherapy system similar to the systems illustrated in FIG. 1A or FIG. 2 , but specifically presenting fluid flow paths and means for fluid flow into and out of a treatment lumen according to some embodiments of the present invention, including, for example, means for injecting fluids other than cryogenic fluids. According to some embodiments, cryotherapy system 20 includes pressurized coolant source 201 and exhaust means 202a and 202b. It should be noted that either or both of exhaust means 202a and 202b may be utilized, and any other suitable exhaust means may also be used. In some embodiments, system 20 further includes inlet path 204a for directing fluid into the lumen and outlet path 204b for exhausting fluid from the lumen. It should be noted that any suitable number of inlet and outlet paths may be utilized. In some embodiments, exhaust means 202a and / or 202b may be separate from cryotherapy system 20 and may be any known exhaust means, including an outlet to the ambient atmosphere, or any other suitable means for exhausting a substance, e.g., expansion fluid, from the system. According to some embodiments, the drainage means 202a and / or 202b comprises suction provided by any suitable pump, vacuum, etc. According to some embodiments, the drainage means, e.g., drainage means 202a and / or 202b, can be attached to a proximal end of a cryotherapy device, e.g., cryotherapy device 1002 shown in FIG. 1A, optionally to a proximal end of outlet path 1010 or to outlet path 204b shown in FIG. 11. According to some embodiments, an optional suction trap, e.g., suction trap 203, can collect drained fluid and can protect the drainage means, e.g., drainage means 202a and / or 202b, from contamination.

[0246] According to some embodiments, the inflow and outflow fluids can originate from a combination of sources, such as source 201, as shown in FIG. 11 . Note that any number of sources can be used together or in any order required. According to some embodiments, source 201 can be reduced (e.g., reducing pressure and / or flow rate) by either one or both of reducers 206, thus providing pressurized coolant 205 and / or reduced fluid 207 inflow at different times or simultaneously (e.g., by using path 208, as shown in FIG. 11 ). Note that different sources can be used to provide different pressures and / or flow rates (not shown), or the same source can be used, as will be described in more detail below. According to some embodiments, path 205 can be used to deliver coolant to the target tissue, and path 207 can be used to keep the lumen expanded and / or dehydrate between freezing cycles. Thus, in some embodiments, the pressure of the fluid in each of paths 205, 207, etc. can be the same or different and can even vary over time, as desired. According to other embodiments, path 208 can be used parallel to path 205 and can be used for pressure measurement, for expansion control, and / or as a dehydration means.

[0247] According to other embodiments, instead of using reducer 206, flows 207 and 208 can originate from additional pressure sources (not shown) and can optionally be delivered by separate pumps.

[0248] According to some embodiments, the evacuation means 202a and / or 202b may be utilized at the same time or at different times, for example as shown in Figure 11. In some embodiments, the source 202a may have the capability to handle high pressures and / or high flow rates, etc., and the source 202b may have fine adjustment capabilities that allow for precision and / or enable the system to provide lower pressures, lower flow rates, etc.

[0249] According to some exemplary embodiments, the various pressure and ejection means may be operated according to any suitable means, including predefined settings, electronic means, manual operation, etc. In some embodiments, the control of the different means (205, 206, 207, 208, 202a, 202b) may take into account pressure, time, target area response, etc.

[0250] According to some embodiments, the inflow can be stopped when the pressure in the lumen exceeds about 30-100 mbar. According to some embodiments, the outflow can continue to be discharged until the pressure in the lumen falls below about 20-10 mbar. According to some embodiments, the inflow can be stopped when the temperature in the lumen falls below about 5-10°C. According to some embodiments, the inflow can be started when the temperature in the lumen exceeds about 15-20°C. According to some embodiments, both temperature and pressure, as well as any other suitable parameters, can be used to control the system.

[0251] According to some embodiments, a cryotherapy system can include a control unit, e.g., a control mechanism, that controls the injection of coolant and / or the ejection of expansion fluid. The control mechanism can include predetermined parameters (e.g., cyclical) and / or parameters defined by feedback in response to data collected from the system by any suitable sensors, measured parameters such as distal pressure, distal temperature, proximal pressure, proximal temperature, inlet flow vs. outlet flow, operating time, and other optional measured parameters. In some embodiments, when such feedback-related control is implemented, the associated sensing and control means, such as control circuitry, e.g., CPU, firmware, flow sensors, pressure sensors, clocks, etc., can be included within the device or can operate adjacent to the device.

[0252] Exemplary Rolling Cryotherapy Device Reference is now made to FIGS. 12A and 12B, which illustrate schematic longitudinal cross-sectional views of a rolling cryotherapy device 54 including a rolling component 53 that can be cooled externally (FIG. 12A) or internally (FIG. 12B) according to some embodiments of the present invention. According to some embodiments, the cryotherapy device 54, as shown in FIG. 12A for example, has a rolling component 53 (e.g., made of metal) capable of absorbing cryogenic energy from an external source as jets 13 to cool the treatment tissue 52. According to other embodiments, as shown in FIG. 12B for example, the rolling component 53 can have internal cooling jets 13 extending within the rolling component 53. According to some embodiments, the rolling component 53 is cooled both externally and internally. According to some embodiments, cryotherapy can be performed by positioning the rolling component 53 on the treatment site 52 rather than spraying a coolant directly onto the treatment site 52. According to some embodiments, the rolling component 53 can be replaced with any component capable of transmitting cryogenic energy to the treatment site 52, such as a sliding component or an ironing component.

[0253] Exemplary geometries of the freeze tip Reference is now made to FIG. 13, which shows a schematic longitudinal cross-sectional view of the distal end of a cryotherapy device according to an additional embodiment to that presented in FIG.

[0254] According to some embodiments, for example as presented in Figures 4A-4C, the distal end 24 has an inlet nozzle 49 and an outlet opening 407 in adjacent or similar planes.

[0255] According to other embodiments, as shown in FIG. 13 , the inlet nozzle 49 and the outlet opening 407 are separated by an extension 4100 (e.g., a cone, dress, flap). In some embodiments, due to the separation between the inlet nozzle 49 and the outlet opening 407, when the extension 4100 is used, the inlet and outlet do not interfere with each other, thereby optimizing the freezing effectiveness of the inlet 133 and the drainage of the outlet 177. Additionally, according to some embodiments, the extension 4100 essentially separates at least partially the treatment site from the non-treatment site, isolating the treatment site so that only the treatment site receives cryogenic energy, etc., thereby at least partially controlling the size of the treatment site. According to some embodiments, the extension 4100 separates the distal end of the cryotherapy device from the treatment site. In some embodiments, when the extension 4100 separates the distal end of the cryotherapy device from the treatment site, the extension 4100 may or may not provide separation between the inflow 133 and outflow 177, between the treatment site and a non-treatment site, or between the treatment volume 4200 and the surrounding body lumen volume, as detailed herein. In this regard, in some embodiments, the distal end of the cryotherapy device is intended to include the distal end of any element within the cryotherapy device, including the endoscope / sheath, inflow or outflow channels, optics or visualization means, etc.

[0256] According to some embodiments, the extension 4100 defines a treatment space, e.g., treatment volume 4200, which is essentially the volume formed between the distal end of the cryotherapy device, the treatment site, and the extension 4100. Thus, the treatment volume 4200 is at least partially separated from the surrounding volume of the treatment lumen. It should be noted that the extension 4100 does not necessarily contact the treatment site and therefore does not form an enclosed volume, but rather defines the treatment volume 4200 as the volume that would be formed if the extension 4100 were lengthened to contact the treatment site.

[0257] According to some embodiments, the extension 4100 at least partially isolates the treatment volume from the surrounding lumen volume so as to maintain the hydration level within the treatment volume and the conditions necessary to visualize the treatment site and / or treatment volume 4200. As particularly detailed above, in some embodiments, it is possible to introduce fluids other than cryogenic fluids that can dry or at least reduce humidity within the treatment site and / or treatment volume 4200. In some embodiments, it is also possible to evacuate hydrated gases or even liquids from the treatment volume to enhance visibility. In some embodiments, when the treatment site and / or treatment volume 4200 is at least partially isolated from the surrounding lumen environment by any element, such as the extension 4100, it is optionally easier to control the conditions within the treatment volume and at the treatment site, including its hydration and visibility conditions therein.

[0258] Reference is now made to Figure 14. Figure 14 (related to Figures 6A-6E) shows a schematic longitudinal cross-section of the distal end of a cryotherapy device, specifically illustrating rotating / pivoting or at least partially rotating nozzles / holes / valves in the inflow tube / catheter and associated inflow spray of cryogenic fluid according to some embodiments of the present invention. Note that the outflow tube / catheter may likewise comprise any such rotating element.

[0259] According to some exemplary embodiments, the cryogenic fluid (or any other fluid) jet can be directed in a specific direction (e.g., front, side, etc.), as shown, for example, in Figures 6A-6E. According to other embodiments, a combination of directions (e.g., both front and side) can help cover the area / volume with the spray so that the area / volume is uniformly cooled. In some embodiments, a combination of spray directions can also be used when inflating an inflatable device with a geometric shape that not only inflates the inflatable device but also optionally cools it uniformly (e.g., a flatter shaped balloon).

[0260] According to some embodiments, the nozzle is part of the tube 60 (FIGS. 6A-6C). According to other embodiments, as presented, for example, in FIG. 14, the nozzle 69c is part of an additional component 601 attached or connected to the tube 60 by any suitable means that allows it to at least partially swivel (e.g., about an axis). Note that while only one nozzle 69c is shown, any number of such nozzles may be included and positioned anywhere on the component 601. Note that in some embodiments, the inner diameter of any one of the inlet or outlet nozzles may be in the range of about 0.05-0.3 mm, while the cross-section of the nozzle may be any suitable shape, including circular, non-circular, elliptical, slit-shaped, etc. According to some embodiments, a swivel-shaped nozzle (e.g., 69c, part of 601) may provide spray coverage of an area / volume such that the area / volume is uniformly cooled. In some embodiments, a combination of spray directions can also be used when inflating a geometrically shaped inflatable device to not only inflate the inflatable device but also to uniformly cool it (e.g., a flatter shaped balloon). Note that component 601 can pivot about any suitable axis and can pivot any number of degrees. In some embodiments, the pivoting can be controlled manually, mechanically, automatically, by feedback, by predefined parameters, or by any other suitable means. According to some embodiments, tube 60 and nozzle 69c are not in a straight line, so the force of inflow 133 can cause component 601 to pivot about any suitable axis.

[0261] Exemplary Distal End of Cryotherapy Device with Visualization Means Reference is now made to Figures 15A and 15B, which show schematic cross-sectional views of the distal end of a cryotherapy device within an endoscope having inflow and outflow channels according to additional embodiments to those shown in Figures 7A and 7B. According to some embodiments, the distal end 24 of the cryotherapy device directs the inflow 133 of the coolant jet 13 to the target area to be treated. In some embodiments, a cryotherapy catheter is inserted through the inflow channel from the proximal end of the endoscope. In some embodiments, a visualization means 78 is inserted through the endoscope to allow visualization of the treatment site before, during, and / or after activation of the cryotherapy operation.

[0262] According to some embodiments of the present invention, the opening to the discharge tube / catheter can be adjacent to the jet 13 (shown in FIG. 15A ) or can be located in the same or similar plane as the jet 13. According to other embodiments, as shown in FIG. 15B , the cryotherapy device 76 can include an extension 7100. In some embodiments, the extension 7100 can control conditions within the treatment volume 7200, as well as the treatment site and its conditions, by at least partially isolating the treatment volume 7200 and / or treatment site from the surrounding lumen environment. As detailed above, in some embodiments, isolating the treatment volume 7200 and / or treatment site from the general periphery of the lumen can control dehydration of the treatment volume 7200 and / or treatment site and can provide better visualization (e.g., via visualization means 78) of the treatment volume 7200, treatment site, etc. In some embodiments, compared to the extension 4100 shown in FIG. 13 , both cryotherapy and visualization means can be included within the treatment volume 7200, where in the embodiment presented in FIG. 13 only the cryotherapy means resides within the inner volume of the extension, i.e., treatment volume 4200. In some embodiments, the sensing means 25 can be located outside of the treatment volume 7200, as shown in FIG. 15B , to control the surrounding luminal environment. In some other embodiments, the sensing means can be located within the treatment volume 7200 to control conditions within the treatment volume 7200. According to some embodiments, sensors can be positioned both within and outside of the treatment volume 7200, thereby optionally controlling conditions of both the treatment volume and the surrounding luminal environment.

[0263] According to some embodiments, the extension 7100 separates the distal end of the cryotherapy device from the treatment site. In some embodiments, when the extension 7100 separates the distal end of the cryotherapy device from the treatment site, the extension 7100 may or may not provide separation between the inflow 13 and outflow 17, between the treatment site and a non-treatment site, or between the treatment volume 7200 and the surrounding body lumen volume, as described in detail herein. In this regard, the distal end of the cryotherapy device is intended to include the distal end of any element within the cryotherapy device, including the endoscope / sheath, inflow or outflow channels, optics or visualization means, etc. In some embodiments, such a defined distance, particularly between the cryojet 13 and the target site, can optimize the predictability and potential efficacy of cryoablation results.

[0264] In some embodiments, the defined distance between the cryotherapy device and the target area or tissue within the target area is 5 mm, 10 mm, 15 mm, 20 mm, or any intermediate distance that is smaller or larger. In some embodiments, the minimum distance for spraying the cryogenic fluid is at least 4 mm, e.g., 4 mm, 5 mm, 6 mm, or any intermediate distance that is smaller or larger. In some embodiments, spraying the cryogenic fluid from a distance of less than 4 mm may cause the tip / nozzle to stick to the tissue, e.g., due to cryoadhesive properties. Additionally, when using tapered cryogenic nozzles or freezing tips, getting closer than 4 mm increases the risk of piercing the tissue.

[0265] Exemplary Expansive Cryotherapy Device 16A-16C, which show schematic longitudinal cross-sectional views of an expansile cryotherapy device during an ablation procedure according to some embodiments of the present invention. FIG. 16A shows the expansile component 83 in its collapsed configuration. In some embodiments, while the expansile component 83 is in its collapsed configuration, the distal end 24 of the cryotherapy device can be brought into close proximity with the treatment site 82, such that the visualization means 18 can clearly observe the treatment site 82 and provide a clear field of view, FOV 19.

[0266] 16B shows an unfolded inflatable component 83 having an active area / section / portion / element 83a and a support area / section / portion / element 83b according to some exemplary embodiments. In some embodiments, the support element 83b can be an integral part of the inflatable component 83, e.g., the support element 83b can be a painted area of ​​the inflatable component 83, a surface-treated area of ​​the folded component 83, etc. According to other embodiments, the support element 83b can be an additional or external element, added onto, fused to, or adjacent to the folded component 83. In some embodiments, the support element 83b can have several functions besides providing support to the inflatable component 83. In some embodiments, for example, the support element 83b can absorb the illumination of the visualization means 18, thus overcoming any type of glare and allowing the user to visualize the area around the treatment site 82. Alternatively or additionally, the support element 83b can be painted with an anti-reflective dye and / or its surface can receive any suitable type of surface treatment to make it more light absorbing (diffuse vs. specular). For example, the support element 83b cannot transmit low temperatures (e.g., it can be double-walled in this area or made from an insulating material). Additionally, the support element 83b can provide support so that the active element 83a assumes a relatively flat shape rather than a perfectly round shape; for example, the active element 83a can be cone- or bell-shaped.

[0267] FIG. 16C illustrates the distal end 24 of the device during active cryotherapy according to some exemplary embodiments. In some embodiments, as shown in FIG. 16C, for example, visualization means 18 visualizes support element 83b covering active element 83a while active element 83a is in contact with treatment site 82. This can be useful, as described in more detail below. It is further noted that active element 83a can be equivalent to any one of elements 83d, 83d1, and / or 83d2 detailed in FIGS. 8C-8G, and thus any of the embodiments detailed herein with respect to 83d, 83d1, and / or 83d2 are considered possible embodiments for element 83a of FIGS. 16B-16E.

[0268] Reference is now made to Figures 16D and 16E, which show schematic top views 19 (as viewed through the visualization means 18 of Figure 16C) of the distal end 24 of a cryotherapy device according to some embodiments of the present invention. According to some embodiments, as shown, for example, in Figure 16D, the support element 83b1 can completely block visualization of the active expansion element 83a while still allowing good visualization of the periphery 82 of the treatment tissue. In some embodiments, such blocking may be necessary when the active element 83a causes reflections (gloss, glare) that interfere with the ability to perform the ablation procedure.

[0269] According to other embodiments, as shown in, for example, FIG. 16E , the support element 83b2 can only partially block visualization of the expanding element 83a during activation, while still allowing some visualization of the active element 83a in addition to the surrounding treatment tissue 82. The support element 83b2 can be designed to provide only such partial blocking when the active portion 83a does not cause interfering reflections, and the support element 83b2 functions primarily as a support for forming the expanding active component 83a, e.g., the active component 83a can assume a relatively flat shape due to the support element 83b2.

[0270] According to some embodiments, the expandable component can use a simple front-flow nozzle to cool the expandable volume (from the inside). According to some embodiments, the expandable component is inflated with a cryogenic fluid. According to some embodiments, the inflated component can be inflated with any combination and / or sequence of fluids. According to other embodiments, a special inner nozzle, a swivel jet as shown in FIG. 14 (or a combination of front and side nozzles as shown in FIGS. 6b and 6c) can help distribute the cryogenic fluid within a shaped expandable component (e.g., a flatter balloon as shown in FIGS. 16b-16e).

[0271] Exemplary Cryotherapy Devices with Geometric Extensions Reference is now made to FIGS. 17A-17F, which show schematic longitudinal cross-sectional views of a distal end 90 of a cryotherapy device according to some embodiments of the present invention. According to some embodiments, components of the cryotherapy device can be held within an endoscope or sheath 16 during screening or insertion into a lumen, using input from a visualization means 18 to guide the sheath / endoscope into proximity with the treatment site, as shown, for example, in FIG. 17A. According to some embodiments, components of the cryotherapy device include an extension, a sensing means 25, and a cryotherapy catheter 24, and the extension can have different configurations, including a collapsed configuration 93a (FIG. 17A) and an unfolded configuration 93b (FIG. 17B), as well as any other partially collapsed configuration. In some embodiments, the distal end 90 can further include a separate evacuation means. According to other embodiments, the remaining volume within the working channel or sheath can be used as an evacuation means. According to some embodiments, a user can manipulate a wand (or lever, valve, faucet, or controller) 933 to unfold the distal end components and then activate the ablation mechanism, as shown in, for example, FIG. 17B. In some embodiments, the unfolded extension 93b can comprise support ribs or wires and support components (e.g., flexible polymers), which, similar to extensions 4100 and 7100 (shown in FIGS. 13 and 15B, respectively), can at least partially isolate the treatment site and / or treatment volume 930b from the overall luminal environment, further controlling conditions within the interior volume defined by the extension, i.e., treatment volume 930b. In some embodiments, cryotherapy and visualization means can both be included within the treatment volume 930b. In some embodiments, sensing means 25 can be located outside of the treatment volume 930b, as shown in FIG. 17B, to control the surrounding luminal environment. In some other embodiments, sensing means can also be located within the treatment volume 930b, or both inside and outside the treatment volume 930b, for improved control over one another. FIG. 17C illustrates the activation of cryotherapy within lumen 11 according to some exemplary embodiments of the present invention.In some embodiments, the cryogenic jet 13 treats the treatment site 12 while the exhaust flow 17 is directed and pushed out of the treatment volume 930b defined by the enlarged extension 93b, for example. According to some embodiments, the enlarged extension 93b can also define a distance between the cryogenic jet 13 and the treatment site 12, assuming the enlarged extension 93b is in contact with or in close proximity to the tissue surrounding the treatment site 12, as shown, for example, in FIGS. 17B and 17C . In some embodiments, such a defined distance can help optimize the ablation parameters as well as the results achieved by the treatment.

[0272] According to other embodiments, a user can manipulate a controller (or lever, valve, faucet, or wand) 933 to change the geometry and / or functionality of the extensions (e.g., 903a, 903b, 903c), as shown, for example, in Figures 17D-17F. According to some embodiments, as shown, for example, in Figure 17D, extension 903a can be positioned around visualization means 18 to visualize the lumen and the pathway to the lumen by visualization means 18 without interference from other components (e.g., cryotherapy catheter 24, sensing means 25, etc.) until activation of the ablation procedure when needed.

[0273] According to some embodiments, as shown in FIG. 17E, extension 903b can be used similarly to extension 93b shown in FIGS. 17B and 17C, depending on the operation of controller 933. In some embodiments, similar to extension 93b (FIGS. 17B and 17C), the predefined geometry of extension 903b can define the distance between the cryogenic jet 13 and the treatment site, thus optimizing device performance. According to other embodiments, as shown in FIG. 17F, additional geometries of extension 903c can be used using controller 933 to apply different set points (e.g., tissue separation) or enable ablation under different constraints (e.g., limited space, non-smooth target site, sharp angle formation). Thus, controller 933 can be used to control both the inner volume defined by the extension, i.e., treatment volume 9030c, and the distance of the distal end of the device from the treatment site.

[0274] Exemplary Geometric Extensions Reference is now made to FIGS. 18A-18C, which illustrate schematic cross-sectional views of the distal end of an endoscopic visualization tool and cryotherapy device according to some embodiments of the present invention. According to some embodiments, as shown in FIG. 18A, extension 903a (shown in longitudinal section in FIG. 17D) can be prepared from overlapping slices or materials (e.g., rigid slice 903a1 and flexible slice 903a2). In some embodiments, as shown in FIG. 18B (longitudinal section in FIG. 17E), when extension 903b is unfolded, overlapping slices 903b1 and 903b2 or different materials can optionally form a cone-shaped or dress-like separate extension 903. As shown in FIG. 18B, both visualization tool 18 and cryotherapy catheter 24 are located within the treatment volume (e.g., cone, dress) defined by the unfolded extension, allowing the user to visualize the ablation process.

[0275] According to other embodiments, the extension 93 can be folded within the endoscope or sheath 16 (93a shown in longitudinal cross section in FIG. 17A) before being unfolded for use, as shown, for example, in FIG. 18C. In some embodiments, the extension can then be partially unfolded, for example, by partially extending it from the endoscope / sheath, as shown, for example, in FIGS. 17D, 17F, and 18A. Additionally, the extension can optionally be fully unfolded, for example, as presented in FIGS. 17B, 17C, 17E, and 18B. Note that any portion of the cryotherapy treatment can be performed when the extension is fully folded, partially folded, and / or fully unfolded.

[0276] Reference is now made to FIGS. 19A-19C, which show schematic cross-sectional views of the distal end of a cryotherapy device according to some embodiments of the present invention, specifically illustrating a means for isolating a treatment site / volume. According to some embodiments, as shown in FIG. 19A, the unfolded extension 93b can include vent holes 94 that allow expansion fluid 17 to exit or be removed from the interior volume defined by the extension 93b and flow toward an evacuation means opening (not shown). In some embodiments, the extension 93b (or cone, dress) can be prepared from a support structure (such as Nitinol, wires / ribs of a superelastic material) and a fabric / polymer / folded surface, or by overlapping rigid and flexible laminae (e.g., as shown in FIGS. 18A and 18B).

[0277] According to some embodiments, the unfolded extension 93b can be positioned a particular distance, possibly a predefined distance, from the treatment site 112, thereby allowing the expansion fluid 17 to naturally exit the interior volume defined by the extension 93b. According to other embodiments, as shown, for example in FIG. 19A, the unfolded extension 93b is in close proximity to or in contact with the treatment site 112, and thus the vent 94 allows the expansion fluid 17 to flow toward the evacuation means opening (not shown).

[0278] FIG. 19B illustrates an extension (or cone, dress) 93b1 with a flattened end 94a according to some exemplary embodiments of the present invention. In some embodiments, the extension 93b1 can be used by any suitable means when the extension 93b1 is held a specific distance, possibly a predefined distance, from the treatment site, as shown, for example, in FIG. 19B, or when the tissue is not smooth, or whenever inflation fluid 17 can exit the interior volume defined by the extension 93b1. According to other embodiments, as shown, for example, in FIG. 19C, the unfolded extension 93b2 includes vent holes 94b in the wall of the extension to facilitate the flow of inflation fluid 17 out of the interior volume defined by the extension. In some embodiments, the extension 93b2 can include vent holes of different sizes and positions, as demonstrated, for example, in FIG. 19C.

[0279] Distal end of an exemplary cryotherapy device having an irrigation inlet path According to some exemplary embodiments, the cryotherapy device comprises at least one inlet irrigation pathway, for example, to allow the introduction of an irrigation fluid, e.g., an irrigation liquid or irrigation gas, into the body lumen. In some embodiments, the irrigation fluid is introduced into the body lumen through at least one irrigation opening, e.g., at least one side opening and / or at least one front opening, located at the distal end of the cryotherapy device, optionally near the opening of the inlet pathway used to release the coolant material. In some embodiments, the at least one side opening is positioned at a selected angle to direct the irrigation fluid toward the optical assembly and / or the distal opening of the optical system channel. In some embodiments, the cryotherapy device comprises at least one irrigation flow director, e.g., a nozzle or deflection surface in the at least one irrigation opening. In some embodiments, the at least one flow director is configured to direct the irrigation fluid toward the optical assembly, the FOV between the cryotherapy device and the target area, and / or a selected treatment space within the body lumen.

[0280] Reference is now made to Figures 20A and 20B, which illustrate the distal end of a cryotherapy device having at least one inflow irrigation pathway into a body lumen, according to some exemplary embodiments of the present invention.

[0281] According to some exemplary embodiments, the distal end of the cryotherapy device, e.g., distal tip 1113, is shaped and sized to be inserted into a body lumen, e.g., through a working channel in an endoscope or sheath, optionally a rigid sheath 1116. In some embodiments, distal tip 1113 is navigated toward a target area, e.g., treatment tissue 1104 located on the interior surface of a body lumen.

[0282] According to some exemplary embodiments, the cryotherapy device includes at least one inflow pathway that delivers coolant into a body lumen for cryoablation of treatment tissue. In some embodiments, the coolant is delivered through a cryogenic inflow pathway, e.g., a cryogenic inflow channel. In some embodiments, a cryogenic spray 1106 is sprayed through a nozzle onto treatment tissue in a target area.

[0283] According to some exemplary embodiments, the cryotherapy device comprises at least one optical element, e.g., optical system 1110. In some embodiments, optical system 1110 allows for visualization within FOV 1112, and optionally, for visualization of the effect of the cryogenic spray 1106 on the treatment tissue 1104. In some embodiments, during release of the coolant into the body lumen, condensation particles are formed, optionally due to interaction of the coolant material with droplets in the humidified environment within the body lumen. In some embodiments, the formation of condensation particles creates a group of particles that prevent or limit visualization of the cryogenic spray effect.

[0284] According to some exemplary embodiments, the cryotherapy device comprises at least one irrigation inlet pathway for delivering an irrigation fluid, e.g., a gas, into the body lumen to displace condensation particles from the FOV 1112. In some embodiments, the irrigation fluid is introduced through the inlet irrigation pathway and an opening, e.g., opening 1115 facing the treatment tissue, e.g., to enable cryogenic irrigation 1108. Alternatively or additionally, the inlet irrigation pathway comprises at least one side opening, e.g., side opening 1117, for introducing irrigation fluid near the distal opening of the optics 1110, e.g., to enable optics irrigation 1114.

[0285] According to some exemplary embodiments, as shown in, for example, FIG. 20B , the cryotherapy device includes at least one effluent path that allows, for example, a portion of gas, particles, and / or liquid to be evacuated from the body lumen; such evacuating is also referred to herein as purging. In some embodiments, as shown in, for example, FIG. 20B , the effluent path is a path that surrounds the inflow path and the optics and is optionally enclosed within a sheath, for example, a rigid sheath 1116. In some embodiments, the effluent path is used for returning or evacuating expansion gas 1118. In some embodiments, the effluent path is defined by a space between the inflow path and / or the optics 1110 within the rigid sheath.

[0286] Exemplary Flow Control According to some exemplary embodiments, flow within a body lumen is regulated to avoid damage to tissue due to, for example, high pressure levels and / or low temperature levels, hi some embodiments, flow is regulated to allow for an effective cryotherapy process and / or better visualization of the target area.

[0287] Reference is now made to FIG. 21A, which illustrates a flow control element scheme according to some exemplary embodiments of the present invention.

[0288] According to some exemplary embodiments, the cryogenic coolant is stored in a cryogenic source 1202 and delivered to the nozzle 1208 through at least one input path, e.g., a cryogenic flow path of a cryotherapy device. In some embodiments, a cryogenic flow regulator, e.g., a cryogenic controller 1204, is located in the cryotherapy device shown in FIG. 1A , e.g., cryotherapy device 1002, and / or in a control unit, e.g., control unit 1004. In some embodiments, the cryogenic controller 1204 controls the amount, e.g., rate, of cryogenic fluid, e.g., cryogenic coolant, flowing toward the nozzle 1208 or through the vent 1206, which is configured to allow the cryogenic coolant to be released outside the body. In some embodiments, the cryogenic controller is under the control of the control circuit 1026. In some embodiments, the cryogenic controller comprises a valve, e.g., a solenoid valve, having an internal orifice that is normally closed by a spring and opened by the electrically induced force of the solenoid, which opens the flow path.

[0289] According to some exemplary embodiments, the control circuitry signals the cryogenic control unit to allow 100% passage through the nozzle 1208 and optionally 0% passage through the vent 1206. Alternatively, the control circuitry signals the cryogenic control unit to allow 0% passage through the nozzle 1208 and 100% passage through the vent 1206. In some embodiments, the control circuitry determines the cryogenic coolant flow distribution between the vent 1206 and the nozzle 1208 based on the pressure level and / or temperature within the body lumen or flow path. Alternatively or additionally, the control circuitry determines the cryogenic coolant flow distribution between the vent 1206 and the nozzle 1208 based on the distance from the target region or the angle between the distal end of the cryotherapy device or the cryogenic nozzle and the target region.

[0290] According to some exemplary embodiments, a low-pressure source 1210 is connected through a different inlet path of the cryotherapy device to an irrigation opening 1218, e.g., an irrigation opening. In some embodiments, the irrigation opening comprises a slot or notch. In some embodiments, an adjustment mechanism, e.g., a regulator 1212, adjusts the flow of low-pressure gas through the cryogenic flow path and toward the nozzle 1208. In some embodiments, when the cryogenic coolant flow is stopped and optionally the vent is closed, low-pressure gas is directed by the regulator 1212 toward the cryogenic nozzle 1208, e.g., to "clean" the nozzle and / or prevent moisture from entering while the cryogenic flow is not flowing. Additionally or alternatively, when the distal end of the cryotherapy device is proximate to the target tissue, the low pressure flow through the cryogenic nozzle 1208 marks the tissue, e.g., by a shallow depression, thereby indicating that the distal end of the cryotherapy device or the tip of the cryocatheter is sufficiently close to the tissue, e.g., for optimal freeze initiation and / or to prevent the tip from piercing the lumen wall and / or to prevent tissue adhesion by the cryogenic flow.

[0291] According to some exemplary embodiments, the low pressure flow is directed by an adjustment mechanism 1214 to an irrigation control unit 1216, which determines the amount and pressure of the flow through the irrigation opening 1218. In some embodiments, for example, between or during coolant spray sessions, the low pressure flow is directed toward the optics of the cryotherapy device to irrigate the treatment space and / or to cleanse the field of view of the optics, for example.

[0292] Exemplary control during cryotherapy According to some exemplary embodiments, at least one microenvironment parameter of a cryotherapy treatment space is controlled. In some embodiments, a cryotherapy system determines a treatment space within a body lumen. In some embodiments, the treatment space is determined to control at least one microenvironment parameter within a limited, and optionally more controllable, space.

[0293] In some embodiments, the cryotherapy treatment space is determined based on the distance of the cryotherapy device from the selected target region. Alternatively or additionally, the treatment space is determined based on the angle between the cryotherapy device and the treatment region. Optionally, the treatment space is determined based on the field of view of an imager of the cryotherapy device.

[0294] According to some exemplary embodiments, the efficacy of a cryotherapy process within a body lumen is controlled. In some embodiments, the release of cryogenic coolant material into the body lumen is controlled. Additionally or optionally, the evacuation of cryogenic coolant fluid from the body lumen is controlled. In some embodiments, the effect of the cryogenic coolant material on the internal tissue of the body lumen is controlled, for example, to increase the efficacy of the treatment.

[0295] According to some exemplary embodiments, at least one safety parameter of the cryotherapy process is controlled. In some embodiments, the pressure and / or temperature within the body lumen during the cryotherapy process are controlled. In some embodiments, the introduction of cryogenic fluid into the body lumen is stopped when the pressure within the body lumen is higher than a predetermined pressure value. Alternatively or additionally, the introduction of non-cryogenic gas for purging and / or expanding the body lumen is stopped. In some embodiments, a portion of the fluid, e.g., cryogenic gas or cryogenic liquid, is evacuated through an outflow channel either passively by opening a check valve or actively by activating a pump, e.g., a vacuum pump.

[0296] Exemplary Controls Within a Defined Treatment Space According to some exemplary embodiments, a treatment space is defined by restricting the space between the cryotherapy device and the target area, for example, to allow better visualization of the target area. In some embodiments, the treatment space is defined by at least one extension, e.g., a cone or dress, which is optionally an unfolded and / or elongated element. In some embodiments, the at least one extension is brought into contact with the inner surface of the body lumen, optionally around the selected target site. Alternatively or additionally, the treatment space is defined by a cone-shaped flow formed by the irrigation flow.

[0297] According to some exemplary embodiments, at least one environmental parameter, such as an environmental parameter that affects visualization of the target area, is controlled within the defined treatment space, hi some embodiments, the environmental parameter includes temperature and / or humidity within the treatment space.

[0298] According to some exemplary embodiments, the temperature level within the defined treatment space is controlled by evacuating a portion of the cryogenic fluid from the defined space. Alternatively, warm air is introduced into the defined treatment space through an inlet path of the cryotherapy device. Alternatively, an IR light source irradiates the treatment space to increase the temperature level or to allow visualization through a mist. In some embodiments, the humidity level within the defined treatment space is controlled by introducing a gas to dehydrate the space.

[0299] According to some exemplary embodiments, the mist or formed particles are swept away from the defined treatment area by using an irrigation fluid, for example, to remove humidity from the FOV and allow for better visualization of the target area. Alternatively, a portion of the mist particles are expelled from the defined space through an outlet path within the cryotherapy device.

[0300] Exemplary Flow Control Process According to some exemplary embodiments, at least one microenvironment parameter, such as pressure, temperature, and / or humidity within the body lumen, is monitored before, during, and / or after the cryotherapy process. In some embodiments, the low-pressure flow and / or coolant flow into the body lumen is controlled based on the measurement of the at least one microenvironment parameter, for example, to prevent a maximum pressure value from being exceeded or to prevent the temperature within the body lumen from dropping below a predetermined value. Reference is now made to FIG. 21B, which illustrates a flow control process according to some exemplary embodiments of the present invention.

[0301] According to some exemplary embodiments, at least a portion of the cryotherapy device is introduced into a body lumen, as previously described at 1050.

[0302] According to some exemplary embodiments, the body lumen is inflated at 1220. In some embodiments, the body lumen is inflated by low pressure flow or by a combination of low pressure flow and expanded coolant flow.

[0303] According to some exemplary embodiments, the pressure level within the lumen is determined at 1222. In some embodiments, the pressure level is determined based on a signal received from at least one sensor, e.g., a pressure sensor located within the body lumen, and / or based on at least one sensor located outside the body lumen or within a flow path of the cryotherapy device, e.g., the outflow path. In some embodiments, the pressure level within the lumen is determined by monitoring the pressure level and / or pressure changes within the irrigation inflow path, optionally by a sensor located outside the body. Alternatively, the sensor is located within a portion of the irrigation inflow path located within the body.

[0304] According to some exemplary embodiments, if the pressure determined after inflation is normal and / or within a desired range of values, coolant is introduced into the body lumen for cryoablation of the selected target region at 1224. In some embodiments, the coolant is introduced for a predetermined period of time. Alternatively, if the determined pressure level is too high, at least a portion of the gas within the body lumen is optionally evacuated through an outflow channel at 1226.

[0305] According to some exemplary embodiments, irrigation is activated and introduced into the body lumen at 1228. Alternatively, irrigation fluid is used to distend the body lumen at 1220. In some embodiments, irrigation is introduced through the cryogenic nozzle during purging or through an irrigation inlet channel, for example, to cleanse the treatment space between the optical assembly and / or the distal end of the cryotherapy device and the target area. Alternatively or additionally, irrigation is used around the cryogenic spray, for example, to push the cryogenic spray away from the optical assembly and / or optionally to obtain a virtual cone / dress that defines the microenvironment.

[0306] According to some exemplary embodiments, the pressure and / or temperature within the body lumen is determined at 1230. In some embodiments, the pressure is determined after cryoablation and / or after irrigation to determine whether the pressure within the body lumen exceeds a maximum possible pressure value. Additionally or alternatively, the temperature is determined before, during, and after cryotherapy to determine whether the introduced coolant has reduced the temperature level within the body lumen below a predetermined value. In some embodiments, if the pressure and temperature are within the range of possible values, an optionally continuous cryoablation coolant flow is introduced into the body lumen at 1224.

[0307] According to some exemplary embodiments, if the pressure is within normal values ​​but the temperature is too low, the cryoablation process is stopped at 1238. In some embodiments, at least a portion of the fluid, e.g., gas or liquid, within the body lumen is evacuated at 1240. Alternatively or additionally, warm gas is introduced into the body lumen at 1242, e.g., to increase the temperature within the body lumen. Alternatively, warm gas is introduced into the body lumen through an inflow irrigation channel during cryotherapy, and optionally during expansion of the body lumen. In some embodiments, after some of the gas has been evacuated and / or warm gas has been introduced into the body lumen at 1230, the pressure and / or temperature are determined.

[0308] According to some exemplary embodiments, if the pressure in the body lumen is too high, cryoablation is stopped at 1232 and, optionally, irrigation is stopped at 1234. In some embodiments, some of the gas in the body lumen is evacuated at 1236.

[0309] Exemplary Pressure Monitoring Within the Lumen 22A-22F, which illustrate pressure monitoring within a range of predetermined pressure levels within a body lumen. According to some exemplary embodiments, within pressure graph 1502, the pressure is desirably maintained between a minimum inflation pressure value 1508 and a maximum inflation pressure value 1506. In some embodiments, as shown in graph 1504, when the wash, cryogenic, and purge flows are activated, the pressure level within the body lumen changes accordingly.

[0310] In some embodiments, the pressure within the body lumen is maintained above a minimum distension pressure value, e.g., to allow for better visualization of the target region and / or to allow for better accessibility to the target region. In some embodiments, the minimum pressure within the bladder is at least 10 mbar, e.g., 10 mbar, 12 mbar, 15 mbar, or any intermediate value less or greater. In some embodiments, the pressure within the body lumen is maintained below a maximum pressure value, e.g., to prevent tissue damage. In some embodiments, the maximum pressure within the bladder is about 30 mbar.

[0311] According to some exemplary embodiments, in a freeze activation cycle, as shown, for example, in Figure 22A, when the cleaning and purging flows are applied at 1516, the pressure is within a desired range between a minimum pressure value 1508 and a maximum pressure value 1506. In some embodiments, when the cryogenic flow is activated at 1510, the pressure increases above the maximum possible pressure value, after which the cryogenic flow is stopped at 1512.

[0312] According to some exemplary embodiments, when constant flushing and purging flows are activated within the overall flow 1520 and the exhaust opening is wider, the pressure within the body lumen falls below a minimum pressure value 1508, as shown, for example, in FIG. 22B . In some embodiments, partial or complete collapse of the body lumen due to low inflation pressure may prevent good visualization of the target area and / or limit or prevent navigation of the cryotherapy device within the body lumen, thereby reducing the efficacy of the cryoablation treatment. In some embodiments, when the cryogenic flow is activated at 1510, the overall flow 1518 produces an overall pressure within a desired range during cryoablation.

[0313] According to some exemplary embodiments, when using a valve, e.g., a check valve, fluid evacuation from the body lumen is optionally controlled, with constant flow 1522 causing the pressure to be higher than the minimum pressure required for inflation, e.g., when cryogenic flow is not activated, as shown in Figure 22C. In some embodiments, when freezing is activated, the pressure rises but is still below the maximum pressure value. In some embodiments, this situation is safe and should allow for work within the lumen, e.g., by allowing good visualization and maneuverability within the body lumen.

[0314] According to some exemplary embodiments, active feedback on flow control is used to maintain the pressure in the body lumen below a maximum pressure value, as shown, for example, in FIG. 22D . In some embodiments, at 1510, the cryogenic flow is activated to introduce coolant into the body lumen along with the irrigation flow. In some embodiments, at 1524, the cryogenic flow and irrigation flow increase the pressure level, optionally as measured by a sensor, optionally through an inlet path, e.g., an inlet irrigation path, to a maximum possible pressure value. In some embodiments, when the pressure level reaches the maximum possible pressure level, the active flow control or active flow regulator stops the cryogenic flow. Additionally, if the pressure still increases, the active flow control also stops the irrigation flow.

[0315] According to some exemplary embodiments, the "wash" flow has several purposes, including, for example, to provide a constant expansion of the lumen, e.g., to prevent partial or complete collapse, and optionally to allow good visualization and maneuverability within the lumen. Additionally or alternatively, the wash flow is used to clean the optical assembly, e.g., the optical lens, from moisture and other contaminants, and optionally to maintain the optics of the optical assembly at a relatively constant temperature, e.g., at a temperature level with fluctuations of up to 30%, e.g., 10%, 15%, 20%, or any smaller or larger intermediate fluctuation percentage. In some embodiments, the wash flow is used to flush cold, humid gas (mist) from the optics (the "cryogenic cleaning fluid" forms insulation around the cryogenic spray) and, optionally, to build a dynamic buffer around the lens surface (the "optics cleaning fluid"), making it difficult for mist residue (or expelled mist) to flow toward the lens. Alternatively and / or additionally, the cryogenic cleaning fluid is used for pressure measurements. In some embodiments, the pressure change within the lumen can be measured closer to the source of the irrigation pressure (upstream, e.g., in a control console) so that the pressure within the lumen can be measured / approximated as a result of the pressure change within the lumen and optionally used, e.g., for control and / or safety measures.

[0316] According to some exemplary embodiments, active control of irrigation flow is applied at 1528, e.g., to ensure that the pressure level is between a minimum pressure value required for distension of the body lumen and a lower maximum pressure value, as shown in, e.g., FIG. 22E. Optionally, controlling the irrigation flow allows for conserving irrigation fluid, e.g., during long observation or visualization periods between cryogenic spray sessions. In some embodiments, active irrigation flow control is deactivated when freeze is applied at 1504.

[0317] According to some exemplary embodiments, in addition to active flow control, active control over the evacuation of material from the body lumen is also activated, as shown, for example, in Figure 22F. In some embodiments, when the cryogenic flow is activated at 1510, active evacuation control is activated at 1532, for example, by activating a vacuum pump to evacuate some fluids and / or other material from the body lumen, thereby optionally reducing pressure levels.

[0318] Exemplary Determination of Distance and Angle to Target Area According to some exemplary embodiments, the distance between the distal end of the cryotherapy device and the target region is determined, for example, to allow for better control of the effect of the coolant on the tissue. In some embodiments, spraying the coolant too close to the tissue can damage deeper layers of the tissue that were not selected as the target for cryotherapy. Alternatively, spraying the coolant on the target region from a large distance can result in ineffective treatment, for example, due to mist generation and / or visualization difficulties. Additionally, determining the distance to the target region can allow for adjustment of at least one parameter of the cryotherapy process, for example, coolant pressure and / or duration of coolant spray.

[0319] According to some exemplary embodiments, as shown in, for example, FIG. 23A , a distal tip 1602 of a cryotherapy device is advanced toward a target region 1608. In some embodiments, a low-pressure gas flow 1604 is optionally released toward the target region 1608 from an irrigation channel 1612 and / or through a cryogenic nozzle by a purge flow when the cryogenic fluid flow is stopped. In some embodiments, the pressure of the low-pressure gas creates a depression 1622 in the body lumen surface. In some embodiments, a distance 1610 between the distal tip 1602 and the target region 1608 is determined by visualizing the depth and / or shape of the depression 1622 using an optical system 1614.

[0320] According to some exemplary embodiments, as shown in, for example, Figure 23B, the distal end 1603 of the cryotherapy device comprises at least one irradiation source 1620 configured to project a light beam towards the target region 1608. In some embodiments, the distance 1610 between the distal end 1603 and the target region 1608 is determined by visualizing, for example manually or automatically by image processing, the size and / or shape of the projected point 1621 on the target region 1608. Alternatively or additionally, the cryotherapy device comprises a light meter, optionally a laser light meter, to measure the distance to the target region.

[0321] According to some exemplary embodiments, as shown in, for example, FIG. 23C , the cryotherapy device includes at least one foldable element, e.g., folded element 1626, which is optionally an extension, dress, or cone. Optionally, the folded element has a known length in an unfolded state. In some embodiments, the folded element 1626 is configured to fold within a lumen of the cryotherapy device during navigation to the target region and unfold upon reaching the target region. In some embodiments, the elements contact tissue at or near the target region when unfolded. In some embodiments, visualization of the contact point between the folded element and tissue allows for determining, for example, the distance 1610 between the distal end 1605 and the target region.

[0322] According to some exemplary embodiments, the angle between distal tip 1702 and target area 1711 is determined based on the shape and size of a light spot 1712 projected onto the target area, as shown, for example, in Figures 23D and 23E. In some embodiments, a light beam 1708 is projected by an illumination source onto target area 1711 at a 90-degree angle 1710, as shown, for example, in Figure 23D. In some embodiments, visualizing the shape and / or size of the light spot allows for determining the relative angle between distal tip 1702 and target area 1711. In some embodiments, when projected at a 90-degree angle, light spot 1712 has a smallest size, length, and / or diameter compared to other projection angles. Optionally, when projected at a 90-degree angle, the light spot has a round shape, as shown, for example, in the top view of the target area in Figure 23E.

[0323] According to some exemplary embodiments, light beam 1708 is projected at an angle 1716 greater than 90 degrees, as shown, for example, in FIG. 23F. In some embodiments, when projecting light beam at an angle greater than 90 degrees, light spot 1714 becomes larger and optionally more elliptical as compared to light spot 1712, as shown, for example, in FIG. 23G, which shows a top view of target area 1711. Alternatively or additionally, similar to the illumination effect, the purge flow may result in the same elliptical shape related to the angle, or a larger circle related to a greater distance between the freeze tip and the target tissue being treated.

[0324] According to some exemplary embodiments, at least one parameter of the cryotherapy treatment, such as the pressure of the cryogenic fluid released into the body lumen, the position of the distal end of the cryotherapy device, and / or the duration of the cryospray, is optionally automatically modified or adjusted based on the determined distance and / or angle. In some embodiments, a new treatment space and / or a new FOV is defined based on the determined angle and / or distance. In some embodiments, the direction of the irrigation fluid flow is adjusted or modified, for example, to direct the irrigation fluid toward the newly defined treatment space and / or the newly defined FOV.

[0325] The specific embodiments described above are illustrative of the implementation of the techniques of this disclosure, and it is therefore to be understood that other approaches known to those skilled in the art or disclosed herein may be employed without departing from the scope of the following claims.

[0326] It is expected that many related cryotherapy devices will be developed during the life of the patent expiring from this application. The scope of the term cryotherapy device is intended to include, a priori, all such new articles. As used herein, when referring to a quantity or value, the term "about" means "within ±10%."

[0327] The terms "comprises," "comprising," "includes," "including," "has," "having" and conjugations thereof mean "including but not limited to."

[0328] The term "consisting of" means "including and limited to."

[0329] The term "consisting essentially of" means that a composition, method, or structure may include additional ingredients, steps, and / or moieties, provided that the additional ingredients, steps, and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0330] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, "a compound" or "at least one compound" includes a plurality of compounds, and may also include mixtures thereof.

[0331] Throughout this application, various embodiments of the invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and is not an inflexible limitation on the scope of the invention. Thus, the description of a range should be considered to specifically disclose all of the possible subranges and individual numerical values ​​within that range. For example, description of a range such as 1 to 6 specifically discloses subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the magnitude of the range.

[0332] Whenever a numerical range is given herein (e.g., "10-15," "10 to 15," or a pair of numbers linked as a range designator), it is intended to include any recited number (fractional or integer) within the range indicated. The phrases "ranging between" a first designated number and a second designated number and "ranging from" a first designated number to a second designated number are used interchangeably herein and are intended to include the first designated number and the second designated number, and all fractional and integer numbers therebetween.

[0333] Unless otherwise indicated, numbers used herein and any numerical ranges based thereon are approximations within the accuracy of reasonable measurement and rounding errors, as will be understood by one of ordinary skill in the art.

[0334] As used herein, the term "method" means manner, means, techniques, and procedures for accomplishing a given task, including, but not limited to, those known to practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine, or those that can be readily developed by practitioners from known manners, means, techniques, and procedures.

[0335] The term "treating" as used herein in connection with an abnormal activity, disease, or condition includes arresting, substantially inhibiting, slowing, or reversing the progression of the condition, substantially ameliorating the clinical or cosmetic symptoms of the condition, or substantially preventing the worsening of the clinical or cosmetic symptoms of the condition.

[0336] It will be understood that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in any combination of these features in a single embodiment. Conversely, multiple features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or with respect to other described embodiments as appropriate. A given feature described in the context of various embodiments should not be construed as essential to that embodiment, unless the particular embodiment is inoperable without that element.

[0337] While the present invention has been described in conjunction with specific embodiments thereof, 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.

[0338] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference in their entirety to the same extent as if each individual publication, patent, and patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application should not be construed as an admission that such reference is available as prior art to the present invention. Nor should it be construed as necessarily limiting, to the extent that section headings are used.

Claims

1. 1. A cryotherapy system comprising:

1. An elongated cryotherapy device having a proximal end and a distal end shaped and sized for introduction into and placement within a body lumen, said cryotherapy device comprising: the cryotherapy device comprising a cryogenic inlet pathway fluidly connecting a cryogenic fluid source to at least one cryogenic opening at the distal end of the cryotherapy device, the cryogenic inlet pathway configured to allow a cryogenic flow to flow from the cryogenic fluid source through the at least one cryogenic opening and into the body lumen, and to spray the cryogenic fluid from the distal end through the at least one cryogenic opening onto a target area within the body lumen; a vent opening fluidly connected to the cryogenic inlet pathway, the vent opening configured to release cryogenic fluid located within the cryogenic inlet pathway outside the body; a control unit connected to the elongated cryotherapy device, the control unit comprising a control circuit, the control circuit configured to control the flow of the cryogenic fluid through the cryogenic inlet path and at least one cryogenic opening towards the body lumen and from the cryogenic inlet path through the vent opening to outside the body; 1. A cryotherapy system comprising:

2. 2. The system of claim 1, wherein the control circuit is configured to open the vent opening to release residual cryogenic coolant trapped within the cryogenic inlet path outside the body when the flow of the cryogenic fluid into the body lumen through the cryogenic inlet path stops or decreases.

3. 3. The system of claim 2, wherein the control circuitry opens the vent for a predetermined period of time to release the residual cryogenic coolant outside the body.

4. 10. The system of claim 1, wherein the control circuit determines a distribution between an amount of cryogenic fluid flowing through the at least one cryogenic opening into the body lumen and an amount of cryogenic fluid flowing outside the body through the vent.

5. The system of claim 1 , wherein the control circuit determines a cryogenic fluid flow distribution between the at least one cryogenic opening and the vent opening based on pressure and / or temperature levels in the cryogenic inlet path.

6. 10. The system of claim 1, wherein the control circuit determines a cryogenic fluid flow distribution between the at least one cryogenic opening and the vent opening based on pressure and / or temperature levels within the body lumen.

7. 10. The system of claim 1, further comprising at least one purge flow regulator configured to direct low pressure fluid to the at least one cryogenic opening when the cryogenic fluid flow from the cryogenic fluid source is stopped or reduced and when the vent is at least partially closed.

8. The system of claim 2 , wherein the control circuitry is configured to open the vent for a period of time that is adjusted according to an amount of residual cryogenic coolant trapped within the cryogenic inlet path.

9. The system of claim 1 , comprising at least one cryogenic flow regulator located on the cryogenic inlet pathway and configured to control cryogenic fluid flow through the cryogenic inlet pathway and into the body lumen.

10. The system of claim 1 , wherein the body lumen comprises at least one of a bladder, a cervix, a prostate, a urethra, a ureter, a uterus, or a stomach.

11. 10. The system of claim 1, wherein the elongated cryotherapy device comprises an irrigation inlet pathway fluidly connecting an irrigation fluid source to at least one irrigation outlet in the distal end and configured to direct and release irrigation fluid toward an optical system assembly located within the body lumen and / or toward a field of view (FOV) between the optical system assembly and the target area within the body lumen.

12. 12. The system of claim 11, comprising the optical system assembly located at the distal end of the elongated cryotherapy device, the optical system assembly defining the FOV.

13. 12. The system of claim 11, wherein the at least one irrigation outlet comprises a side irrigation outlet and / or at least one front irrigation outlet at the distal end of the elongated cryotherapy device.

14. The system of claim 12 , wherein the optical assembly comprises at least one lens and / or at least one illumination source.

15. 12. The system of claim 11, wherein the cryotherapy device comprises at least one irrigation flow director located at the irrigation outlet and configured to provide a virtual cone-shaped flow, the at least one irrigation flow director comprising a deflection surface.

16. The system of claim 15 , wherein the at least one wash flow director is an adjustable wash director configured to spray wash fluid at an angle.

17. The device comprises: at least one outlet path configured to drain fluid from the body lumen through a distal outlet opening located at the distal end toward a proximal opening of the cryotherapy device located outside the body lumen; and at least one outflow regulator located on the outflow pathway and configured to control fluid evacuation from the body lumen through the at least one outflow pathway.

18. 20. The system of claim 17, wherein the outflow regulator comprises a check valve configured to open when pressure within the body lumen is above a predetermined pressure value.

19. 20. The system of claim 17, wherein the outflow regulator comprises a valve connected to the control circuit, the control circuit opening the valve when pressure in the body lumen is above a predetermined pressure value.

20. The system of claim 18 or 19, wherein the predetermined pressure value is in the range of 25 to 100 mbar.

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