Replaceable and/or easily removable needle systems for dermal and transdermal cryogenic remodeling

[0001] The present invention generally relates to systems in particular for tissue remodeling induced by cooling. Embodiments of the invention include systems for subjecting skin tissues to cryogenic cooling so as to selectively rebuild one or more target tissues along and / or below the exposed skin surface. Embodiments can be used for a variety of cosmetic conditions, optionally by inhibiting undesirable ί / or unsightly effects on the skin (such as lines, wrinkles, or ceilulite folds) or on other surrounding tissues. Other embodiments may find use for a wide range of medical indications. By rebuilding the target tissue, you can achieve the desired change in its behavior or composition.

[0002] There is a widespread desire to transform various features of the human body in order to correct shapelessness or merely improve one's appearance. This is evidenced by the growing number of cosmetic procedures performed each year.

[0003] Many treatments are aimed at changing the appearance of the skin surface by reducing lines and wrinkles. Some of these treatments involve injecting fillers or stimulating collagen production. Recently, wrinkle alleviation therapies and other cosmetic applications based on pharmacological agents have gained popularity.

[0004] An example of pharmacological-based therapy used for cosmetic applications is Botulinum toxin type A (ΒΟΤΟΧ®). It is usually injected into the facial muscles to block muscle spasm, which results in temporary weakness or paralysis of the muscle. When the muscle is incapacitated, then the movement contributing to the formation of an unwanted wrinkle is temporarily eliminated, another example of a cosmetic cosmetic procedure is mesotherapy, under which a cocktail of a homeopathic medicine, vitamins and / or tablets approved for other indications for treatment or injection is injected under the skin. correction of a specific area of ​​the body. Various cocktails are used to model your body and reduce cellulite by dissolving fat, or to regenerate your skin through collagen enrichment. The development of non-pharmacological cosmetic procedures is also ongoing. For example, endermology is a mechanical therapy that uses vacuum suction to stretch or relax fibrous connective tissues that are responsible for the folded appearance of cellulite.

[0005] Although ΒΟΤΟΧ® and / or different types of mesotherapy may temporarily reduce lines and wrinkles, reduce body fat or provide other cosmetic benefits, they have their disadvantages, including the risks associated with injecting a substance known as toxic to the body patient, potential risks associated with injecting unknown and / or untested cocktails and the like. In addition, although the effects of endermology are not thought to be potentially dangerous, they are short-lived and only slightly effective.

[0006] In view of the above, it is desirable to develop improved medical devices, systems and methods, in particular for wrinkle, fat, cellulite and other cosmetic defects reduction treatments. It is particularly desirable that such new techniques provide an alternative mechanism to improve the visual appearance that could replace and / or complement known bioactive and other cosmetic therapies, preferably enabling injection reduction or elimination for patients

ΕΡ 2 111 172 Bl toxins and harmful cocktails, while providing similar or better cosmetic results. It is also desirable that such techniques be performed transdermally, without anesthesia or with only local anesthesia and without incision of the skin or with minimal incision, without having to close the wound by suturing or other means, without extensive bandaging and without bruising or with limited bruising. or other factors contributing to long-term recovery, i.e. the patient's return to normal life. It is also desirable to provide new devices, systems and methods for the treatment of other cosmetic and / or dermatological conditions (and potentially also other target tissues), especially in cases where treatments can be carried out with greater accuracy and control, with less damage to surrounding tissue and / or pain and with increased ease of use.

[0007] US 2005/0228288 describes an echogenic needle for vaginal ultrasound-guided reduction of uterine fibroids and the associated method. The echogenic needle has an echogenic surface near its tip that allows the physician to visualize its position using ultrasound imaging. In one embodiment, the needle has an active electrode at its distal end. The active electrode supplies radio frequency energy to the fibroids, causing necrosis of the target myoma or destroying the blood supply to the myoma. In a second embodiment, the needle has a tube for supplying the cryogenic agent and a supply of cryogenic agent to destroy the fibroid tissue by freezing it or its blood supply when the tissue comes into contact with the frozen distal end of the needle.

[0008] WO 2006/127467 describes a subcutaneous cryogenic reconstruction system that includes an independent probe handle with a proximal end and a distal end. The handle housing is of a size and shape suitable for being held by a surgeon or other system operator. The casing contains a supply of cryogenic coolant and a source of electricity, as well as a circuit including a processor for regulating cooling used by the independent system. A tissue piercing cryogenic cooling probe extends beyond the distal end of the housing, which is thermally coupled to the coolant flow path leaving the coolant source.

BRIEF SUMMARY OF THE INVENTION [0009] The present invention is defined in the appended claims. This document describes improved medical devices, systems and methods. Embodiments may be particularly suitable for the treatment of dermatological and / or cosmetic defects, and alternative embodiments may be adapted to perform treatments on a wide range of target tissues. In some embodiments, cooling is utilized with at least one skin piercing probe, which probe typically comprises a needle of a size suitable for being inserted through the exposed surface of the patient's skin without leaving a visible scar. Cooling enables the reconstruction of one or more target tissues to cause a desired change in the composition of the target tissue and / or a change in its behavior. Unlike existing large format cryogenic cooling systems, small needle probes for cryogenic cooling may become blunt or damaged when introduced. Embodiments use interchangeable needle probes held by the probe body holder, with small needle probes typically being replaced during the treatment of one patient. Careful adjustment of the cryogenic coolant supply to the needle probe allows you to control the length of active cooling by exhausting the evaporating cryogenic coolant. Therefore, even needles with similar structures

ΕΡ 2 111 172 Bl external can provide various lengths of effective reconstruction along the axis of the needle. Unexpectedly, small cryogenic cooling needles and / or other cryogenic cooling probes having a lubricity coating allow the probe to be safely removed from the treatment area while at least some of the tissue remains frozen, which significantly reduces the total treatment time involving multiple insertion / freezing / removal cycles.

[0010] This document describes a method of performing surgery on patient tissue. The method includes inserting a first needle through a first entry point into the first tissue target area by manipulating the handle. The handle holds the first needle through the needle coupling. The first target area is cooled by the first needle, after which it is removed from the patient's body. The first needle is replaced in the needle coupling by the second needle. A second needle is inserted through the second insertion point into the second tissue target area by manipulating the handle. The second target area is cooled by the second needle.

[0011] The second needle may optionally have a size and / or cooling properties similar to the first needle. This needle exchange may be particularly useful when using small needles that may dull after a limited number of introductions into the patient's body. In other embodiments, the size and / or cooling properties of the second needle may differ from the first needle, for example, its length, gauge size, i.e. diameter, length of active cooling, or the like may be different. In some embodiments, a first needle may be included in a first needle assembly that has only one needle, while a second needle is included in a needle assembly having a series of needles. The needles of the second needle assembly can be introduced simultaneously into the target tissue, usually these needles are substantially parallel. The coolant supply tube (and its associated light) may be led away from the common supply of coolant of the needle coupling member, and the lights for evaporating the coolant of each needle may flow to a common outlet with a pressure control, also usually via the needle coupling member. In many embodiments, cooling with a series of needles of the second needle assembly can be carried out so that the cooled tissues are rebuilt in a compact treatment zone. In other embodiments, the spacing between needles and the like can result in a number of distinct remodeling zones.

[0012] Usually, each of the first and second needles has a pointed distal tip and a size 20 by gauge or less. The needles can be thrown away after use to prevent the blunt needle from entering the patient's body, the needles being optionally inserted only once or, alternatively, they are inserted several times (usually less than ten times and in many cases less than five times) through the patient's skin . The system holder may be contained within the probe body, in which the fluid supply and accumulator can also be held and / or accommodated. The probe body can be thrown away, so one of these components or each of them is used to treat only one patient. This design also avoids the requirement to include a cable, power outlet, flexible lead, or the like that would otherwise hinder the manipulation and use of a hand probe. Cooling is usually terminated by closing the coolant shutoff valve located along the coolant supply path between the coolant source and the light. Since the cooling can be carried out by evaporating the liquid coolant in the needle lumen, the volume of the feed path between the valve and the light is preferably quite small (usually less than 0.05 cubic inches, and optionally less than 0.005 cubic inches) so as to allow accurate

EP 2 111 172 Bl controlling the time of surgery. The feed path between the valve and the needle lumen is preferably vented after closing the valve to prevent further cooling by any residual cryogenic liquid within this volume.

[0013] This document describes a method of performing surgery on a patient's target tissue. This method involves introducing the cooling probe towards the distal end through the surrounding tissue and into the target tissue. The cooling probe has a light with a distal segment that is adjacent to the target tissue, and a proximal segment that is adjacent to the surrounding tissue. The coolant is introduced into the distal lumen, and the vaporization of the liquid in the coolant to the gaseous state occurs as the coolant flows toward the proximal end in the distal lumen. This evaporation occurs so as to cool the target tissue sufficiently for the desired remodeling procedure. In addition, evaporation occurs such that when the gas flows through a proximal section of light, the liquid in the coolant is consumed sufficiently to hinder the cooling of surrounding tissue.

[0014] The target tissue along the distal lumen can be cooled to a treatment temperature that is within the first temperature range. The surrounding tissue along the proximal segment is usually cooled to a temperature of the surrounding tissue that is within the second temperature range, higher than the first temperature range. It should be noted that variation in cooling effects between the distal and proximal light sections may occur despite the needle structure having a substantially uniform and / or constant cross section along the proximal and distal sections. Preferably, the length of the distal tissue remodeling section can be selected from a series of alternative values ​​by selecting a probe to be mounted to the probe body. Alternative probes may include different coolant supply routes to introduce different streams of coolant supply with correspondingly different fluid consumption properties. More specifically, the use of probes with structures similar in many respects, but with different coolant supply lines with different internal diameters and / or different lengths, allows the axial length of the tissue undergoing reconstruction to be varied, especially to a large extent the metering of coolant flow resulting from flow resistance through the coolant supply light. Preferably, the treatment temperatures along the distal portion may remain substantially constant as long as a sufficient mixture of cooling liquid and evaporated gas is maintained in the coolant stream. As the liquid from the cooling fluid is depleted in this stream, the temperatures of the stream may increase and / or the heat transfer from the surrounding probe (and tissue) structure may decrease significantly, with the cooling being changed over a relatively short and predictable probe axis.

[0015] A method of remodeling a patient's target tissue is described herein. This method involves introducing the cooling probe towards the distal end into the target tissue. The target tissue is cooled sufficiently to freeze some area. The cooling probe is removed from the target tissue while this area remains frozen.

[0016] In many embodiments, the cooling probe can be removed less than 15 seconds from the end of cooling, and usually the probe is removed less than 10 seconds from the end of cooling (and even less than 5 seconds from the end of cooling) . Such counterintuitive removal of the cryogenic cooling probe from the still frozen treatment area can be safely carried out, for example, when cooling is carried out with a cooling probe with a cross-sectional size equal to the needle

1112 111 172 Bl size 20 by gauge or less, the needle usually being size 25 by gauge or less, and preferably 30 by gauge. A thawed zone can form relatively quickly between such a probe and the frozen tissue that surrounds it, which facilitates safe removal of the probe even though the area remains frozen. Therefore, not all initially frozen tissue remains frozen when removed, although in many embodiments most of the tissue that has been frozen can remain frozen.

[0017] Many embodiments may facilitate removal of the cryogenic probe from the still frozen tissue area by cooling the target tissue through the probe lubricating coating. Although the thermal conductivity of the lubricating coating is usually much lower than the thermal conductivity of the probe material underneath it (the probe material usually contains a thin stainless steel tube or the like for small needle probes), complete heat transfer from the target tissue can be facilitated by using a lubricating coating with a much smaller thickness than the probe material. In addition, the temperature inside the vaporization chamber of the cryogenic fluid, i.e. light, can be selected to give the desired cooling properties, despite the heat insulation of the lubricating coating. Nevertheless, the overall treatment time is much shorter, especially when a large number of insertion / freezing / removal cycles are used and / or when the total cooling time is relatively short compared to the time required for complete defrosting of frozen tissue.

[0018] A document for treating patient tissue is described herein. This system includes a first needle with a first end, a distal end for tissue piercing, a lumen between these ends, and a coolant supply light extending toward the distal end to the connector in the lumen of the needle. The needle is size 20 by gauge or less. The other needle has a proximal end, a distal end for tissue piercing, and the light between these ends. To the connection in the lumen of the second needle, which also has a size of 20 by gauge or less, a coolant supply light runs towards the distal end. The probe body has a handle holding a source of coolant and a needle coupling element for receiving the first and second needles in turn. Light evaporation of the needle sediment cools the tissue when the needle is inserted and the coolant is supplied through the connection from a coolant source.

[0019] This document describes a system for performing surgery on a target tissue of a patient's body. In the vicinity of the patient's target tissue, surrounding tissue is present, and the system includes a probe with a proximal end and a distal end. The distal end is introduced through the surrounding tissue into the target tissue. The inserted probe has light with a proximal segment adjacent to the target tissue and a distal segment adjacent to the surrounding tissue when the distal end is inserted. A coolant source is in fluid communication with the distal lumen. The source is configured such that when fluid flows from the source to (and towards the proximal end along) the light of the introduced probe, the coolant liquid evaporates to a gaseous state within the distal lumen of light such that evaporation cools the intraocular tissue sufficiently for the procedure. In addition, the liquid is consumed sufficiently when the coolant passes through a proximal section of light to hinder the cooling of surrounding tissue.

[0020] This document describes a system for remodeling a patient's target tissue. This system includes a cooling probe introduced toward the distal end into the target tissue. The cooling probe has a cooling surface to cool the target tissue sufficiently to freeze

ΕΡ 2 111 172 BI a certain area. A lubricity coating is provided on the probe cooling surface to facilitate removal of the cooling probe from the target tissue while the area remains frozen.

[0021] Examples of lubricating and / or hydrophobic coatings include polymers such as Teflon ™ (PTFE) polymers, silicone or the like. Typical coating thicknesses are from about 0.00005 inches to about 0.001 inches, with an exemplary PTFE polymer coating having a thickness of 0.0005 inches, and exemplary silicone coatings being even thinner. In some embodiments, a portion of the probe (such as its distal end or small area near the distal end) may not have a coating to allow the uncoated area to be used as an electrode or the like.

BRIEF DESCRIPTION OF THE DRAWINGS [0022] Fig. 1A is a perspective view of an independent subcutaneous probe and cryogenic remodeling system.

[0023] Fig. 1B shows the independent probe of Fig. 1A in a partially transparent perspective view, which shows the internal components of the cryogenic remodeling system and schematically shows the spare treatment needles intended for use with a disposable probe.

[0024] Fig. 2 schematically shows components that may be included in the system for performing the procedure.

[0025] Fig. 3 shows an embodiment of the distal part of the probe and system of Fig. 1B in a schematic cross-sectional view in which the replaceable needle and safety valve with limited outlet volume are shown.

[0026] Fig. 3A shows a coolant supply tube made of fused silica and intended for use in the exchangeable needle of Fig. 3.

[0027] Fig. 4 is a more detailed view of an interchangeable needle assembly for use in the system of Figs. 1A and 1B.

[0028] Figs. 5A-5C show an exemplary delivery valve for use in the probe and system of Figs. 1A and 1B.

[0029] Figs. 6-8 show skin contact surfaces that respectively selectively reduce the length of the actually inserted needle section, exert pain suppression pressure, and subject the skin to cooling inhibiting inflammation prior to surgery and / or during surgery on the target tissue.

[0030] Figs. 9, 9A and 9B schematically show a needle with an elongated cross-sectional shape to increase the volume of tissue to be treated.

[0031] Fig. 10 schematically shows a thermal model of a micrometer needle for cryogenic cooling. [0032] Figures 10A-10C graphically illustrate aspects of cryogenic cooling with nitrous oxide in microneedle needles described herein.

[0033] Figs. 11A and 11B schematically show, in cross-sectional views, cooling with a single needle system and a multi-needle system.

[0034] Fig. 12 graphically illustrates uneven cooling, which may be due to lack of space for evaporation in a small needle probe for cryogenic cooling.

[0035] Figures 13A-13D graphically illustrate the effect of changes in outlet volume on the cooling response of a small needle probe for cryogenic cooling.

1112 111 172 Bl [0036] Fig. 14 schematically shows a microchip needle system for cryogenic cooling used to perform a dermatological procedure.

[0037] Fig. 15 is a block diagram schematically showing how to perform a procedure using a disposable cryogenic probe and the system of Fig. 1B.

[0038] Fig. 16 is a schematic cross-sectional view showing an alternative example of a needle engagement member as well as adjacent structures of the needle assembly and the probe body.

[0039] Figs. 17A and 17B schematically show, in partial sections, removal of the probe needle for cryogenic cooling while at least part of the tissue remains frozen.

[0040] Figs. 18A and 18B schematically show, in partial cross-sections, a manner in which fluid depletion from an evaporating cryogenic cooling fluid can be used to limit the effective length of treatment on a portion of the cryogenic probe.

DETAILED DESCRIPTION OF THE INVENTION [0041] Improved medical devices, systems and methods are described herein. Embodiments facilitate the remodeling of tissues located in and below the skin optionally for the treatment of a cosmetic defect, lesion, disease state and / or to change the shape of the covering skin surface.

[0042] Among the most direct applications may be the alleviation of lines and wrinkles, in particular by inhibiting muscle spasms that are associated with these cosmetic defects to improve the patient's appearance. Instead of relying solely on a pharmacological toxin or the like to incapacitate muscles, to cause temporary paralysis, in many embodiments, at least some cold is used to immobilize the muscles. Advantageously, nerves, muscles and associated tissues can be temporarily immobilized with moderately low temperatures of 10 ° C to -5 ° C without permanently damaging tissue structures. Using an approach similar to that used to recognize structures associated with atrial fibrillation, a needle probe or other device for surgery can be used to recognize the target tissue structure diagnostically at such moderate temperatures, and the same probe (or other probe) can also be used for ensuring long-term or permanent treatment, optionally by ablation of the target tissue zone and / or induction of apoptosis at temperatures from about -5 ° C to about -50 ° C. In some embodiments, apoptosis can be induced by treatment temperatures from about -1 ° C to about -15 ° C or from about -1 ° C to about -19 ° C, optionally to provide a permanent treatment that limits or inhibits the condition inflammation and mobilization of skeletal muscle satellite repair cells. Therefore, the period of effectiveness of such subcutaneous cryogenic procedures can be selected and controlled, with the duration of such surgery determined by lower temperatures, longer treatment periods and / or larger volumes or selected target tissue designs. An additional description of cryogenic cooling for the treatment of cosmetic and other defects can be found in US Patent Application No. 11/295 204, pending December 5, 2005 and entitled "Subcutaneous cryogenic remodeling of muscles, nerves, connective tissue and / or adipose tissue" ("Su bd er mai Cryogenic Remodeling of Muscle, Nerves, Connective Tissue, and / or Adipose Tissue (Fat) "), the full disclosure of which is incorporated herein by reference.

[0043] In addition to cosmetic procedures for reducing lines, wrinkles and the like, embodiments may also find use in treatments for reducing subcutaneous fat, treating benign (pre-malignant) lesions, malignant lesions, acne, and a wide range of other conditions

ΕΡ2 111 172 Bl dermatological (including dermatological diseases for which cryogenic procedures and other dermatological diseases were proposed) and the like. Embodiments may also find use in alleviating pain, including pain associated with muscle spasms. Accordingly, various embodiments are envisaged.

[0044] Referring now to Figures 1A and 1B, the cryogenic remodeling system in this case includes an independent probe handle generally with a proximal end 12 and a distal end 14. The handle body, or housing 16, has a size and shape suitable for holding in hand. by a surgeon or other system operator. As can be clearly seen in fig. 1B, the housing 16 has a supply of 18 cryogenic coolant and electrical power source 20, as well as a circuit 22 comprising a processor for regulating the cooling used by the independent system 10 in response to the input 24 activation. Some embodiments may at least partially be turned on manually for example by using a manual feed valve and / or the like, whereby processors, power supply and the like may be absent.

[0045] A tissue piercing probe 26 for cryogenic cooling extends beyond the distal end 14 of the housing 16. The probe 26 is heat coupled to a coolant flow path extending from the coolant source 18, the exemplary probe comprising a tubular body receiving at least a portion of the coolant from a coolant source therein. Exemplary probe 26 includes a 30 g needle with a pointed point that is axially sealed. The axial length of probe 26 between the distal end 14 of the housing 16 and the distal end of the needle may be between about 1/2 mm and about 5 cm, and preferably this length is from about 1 cm to about 3 cm. Such needles may include a stainless steel tube with an inner diameter of about 0.006 inches and an outer diameter of about 0.012 inches, while alternative probes may be constructions with outer diameters (or other transverse cross-sectional dimensions) from about 0.006 inches to about 100 inches. Typically, the needle probe 26 contains a 16 g or smaller needle, usually a 20 g or smaller needle, and usually a 26 g or smaller needle.

[0046] Referring to some of the components in the housing 16, an exemplary coolant supply 18 includes a reservoir containing a pressurized liquid whose boiling point is less than 37 ° C. When the fluid is heat-coupled to the skin piercing probe 26 and the probe is positioned in the patient's body such that the outer surface of the probe adjacent the target tissue, the heat of the target tissue evaporates at least some of the liquid, and the enthalpy of evaporation cools the target tissue. Along the coolant flow path, between the reservoir 18 and probe 26, or along the coolant flow path, a valve (not shown) may be located downstream of the probe so as to limit temperature, time, temperature change rate or other cooling properties. The valve is usually electrically powered by power source 20 as directed by processor 22, although it may at least partially be manually operated. An exemplary power source 20 is a rechargeable battery or disposable battery.

[0047] An exemplary coolant supply 18 is a disposable reservoir. Advantageously, the reservoir and the coolant contained therein can be stored and / or used at room temperature (and even above it). The reservoirs may have a frangible seal or may be refillable, the example reservoir containing liquid N₂A. A variety of alternative coolants can also be used, for example fluids

112 111172 Bl cooling agents include fluorocarbon coolants and / or carbon dioxide. The amount of coolant that is contained in the reservoir 18 is usually sufficient to treat at least a significant area of ​​the patient's body, but is usually not sufficient to treat two or more patients. An example of a liquid container N₂O may contain, for example, an amount of liquid in the range of from about 7 g to about 30 g.

[0048] Processor 22 typically is a programmable electronic microprocessor that executes computer code or machine-readable program instructions to perform one or more of the treatment methods described herein. A microprocessor usually includes or is connected to a memory (e.g., non-volatile flash memory, read-only memory ("ROM"), random access memory ("RAM") or the like) that stores computer code and data to be used by it, and / or information media (which includes magnetic media such as a hard disk, floppy disk or the like; or optical optical media such as a CD or DVD) may be present. Suitable interface devices (such as digital-to-analogue or analog-to-digital converters or the like) and input / output devices (such as USB or serial I / O ports, wireless communication cards, graphics cards and the like) may also be present. In various embodiments, a variety of commercially available or specialized processor designs may be used, with appropriate processors may use a variety of different combinations of hardware and / or combinations of hardware / software. For example, processor 22 may be integrated on a single processor board and may execute a single program or may use multiple boards and execute a variety of different program modules in a wide variety of alternative distributed data or code architectures.

[0049] Referring now to Fig. 2, the flow of cryogenic coolant from the fluid supply 18 is regulated by the supply valve 32. The supply valve may be an electrically controlled solenoid valve or the like that acts in response to control signals sent by controller 22 I / or it can be a manual valve. Exemplary supply valves may be constructions suitable for two-position valve operation and may provide venting of the coolant flow path downstream of the valve after stopping the coolant flow so as to limit cooling due to evaporation of cryogenic fluid residues. In other embodiments, more complex valve constructions may also be used to regulate flow.

[0050] The coolant exiting the valve 32 flows through the lumen 34 of the coolant supply tube 36. The inlet tube 36 is at least partially inserted into the lumen 38 of the needle 26, the inlet tube extending from the proximal end 40 of the needle towards the distal end 42. An example of the inlet tube 36 is a fused silica tubular structure 36a having a polymer coating 36b (see Fig. 3A) and enters the needle 38 into the cantilever. The delivery tube 36 may have an internal light with an operating inside diameter 36c of less than about 200 pm, with the inside diameter generally being less than about 100 pm, and usually less than about 40 pm. Embodiments of the delivery tube 36 typically have internal lights between about 15 and 50 pm, for example about 30 pm. The outer diameter, i.e. the size 36d of the delivery tube 36 is usually less than about 1000 pm, and usually less than about 800 pm, in embodiments it is between about 60 pm and 150 pm, for example about 90 pm or 105 pm. The size tolerance of the inside diameter of the lumen of the delivery tube 36 is preferably relatively narrow, typically about +/- 10 pm or less, usually +/- 5 pm or less, and preferably

1112 111 172 Bl +/- 3 pm or less, because the small diameter supply tube can provide most (or even substantially all) of the coolant flow to the needle 26.

[0051] Although the supply tubes 36 with outer polyimide sheaths (or other suitable polymer materials) can bend in the light of the surrounding needle 38, the supply tube should be strong enough to prevent breakage or excessive backflow when injecting coolant into the coolant the inside of the needle. In addition, polyimide coatings can provide durability during assembly and use, and fused silica / polymer structures can withstand pressures up to 100 kpsi. The relatively thin wall of the tube and the small external dimensions of the recommended delivery tubes give enough space for the evaporation of nitrous oxide or other coolant in the annular space between the delivery tube 36 and the lumen 38 of the surrounding needle. The lack of space for evaporation could otherwise result in liquid accumulation in this annular space and an unstable temperature, as shown in Fig. 12. Exemplary structures for use as supply tube 36 may include fused silica capillary tube sold by Polymicro Technologies, LLC, based in Phoenix, Arizona, under the model names TSP, TSG, and TSU, optionally including model numbers TSP 020090, TSP 040105 and / or other.

[0052] Referring now to Figs. 2 and 3, the coolant injected into the lumen 38 of needle 26 usually includes liquid, although some gas may also be injected. At least some of the liquid evaporates inside the needle 26, and the enthalpy of evaporation cools the tissue in contact with the needle. Adjusting the pressure of the gas / liquid mixture inside the needle 26 essentially regulates the lumen temperature 38, and thus the temperature range of tissue correction. A relatively simple mechanical safety valve 46 can be used to adjust the needle lumen, the exemplary valve includes valve body 48 (in this case in the form of a ball bearing) pressed against the valve seat 50 by a setting spring 52. [0053] When starting the cooling cycle, a large volume along the coolant flow path between the outlet of the supply tube and the outlet of the safety valve 46 may contribute to excessive transients. In particular, a large volume in this area can result in significantly lower initial temperatures than the target temperature and / or steady state temperature as shown in Fig. 13D. This can be a problem, especially in the case (for example) when the target temperature is only slightly higher than the temperature causing the undesirable phenomena, for example when remodeling is carried out by apoptosis or the like and at the same time trying to avoid necrosis. In order to limit such transients, the safety valve 46 can be integrated with the housing 54 holding the needle 26, and then the valve spring 52 is outside the valve seat (and thus the output for regulating the pressure of the safety valve 46). In addition, in the case where the needle 26 is included in the replaceable needle assembly 26A, the safety valve 46 is also located adjacent to the element engaging the needle assembly with the probe handle housing 54. To hold the needle assembly detachably in place, a spring latch may be engaged in the latch 56, and components of the needle assembly 26A (such as a brass or other metal housing, polyimide tube 58, needle 26 and the like) may be attached to each other using a binder. Alternatively, as shown in Figures 1B and 4, the needle assembly and handle housing may have matching threads for assembling and replacing the needle assembly. The coolant flow path is sealed by O-ring washers 60.

ΕΡ 2 111172 Bl [0054] Figs. 13A-13C show additional details regarding the effect of outlet volume on cooling transients. In each case, a graph of temperature over time is provided for the ambient temperature of a 30 g in vivo cooling needle for which the target temperature is about -12 ° C. The device has been designed to have different outlet volumes, with the volume of more than 0.009 in the embodiment according to Fig. 13A³. The outlet volumes of the embodiments of Figures 13B and 13C are approximately 0.009 in³ and about 0.0025 in³The speed of data collection is about 0.7 seconds. for the embodiment according to Fig. 13A, while for both embodiments according to Figures 13B and 13C, the data collection rate is about 0.1 sec, so the actual lowest temperature point for the embodiment according to Fig. 13A may actually be much lower than shown. Regardless, the outlet volume is preferably less than about 0.05 in³, usually less than about 0.01 in³ and / or 0.009 in³, and preferably less than about 0.005 in³.

[0055] Alternative methods may be used to prevent excessively low transient temperatures at the beginning of the cooling cycle instead of or in combination with limiting the outlet volume. For example, the supply valve can be cyclically moved between the closed and open positions, usually by the controller 22, in a time sequence that limits the flow rate of the coolant so that only the vaporized gas enters the needle light (or so much liquid that it avoids excessive drop in temperature in the needle). This cyclical adjustment can be completed when the pressure in the outlet volume is so high that the cooling temperature is within the desired limits during steady flow.

[0056] Further aspects of exemplary delivery valve 32 can be understood with reference to Figs. 2, 3 and 5A-5C. In Fig. 3, the valve is shown in an open configuration, with the O-ring sealing washers 60 sealing the fluid flow path and the coolant fluid that flows around the displaced valve member from both sides. In fig. 5A-5C, the coolant flows through the passage 64, which extends axially along the alternative valve body 32 'when the valve is in the open configuration (shown in Fig. 5B), with sealing washers of type o being placed between the depressions in the movable body of the valve. -ring to allow valve operation regardless of the body's rotational orientation around its axis. In both embodiments, the coolant flow path downstream of the valve is vented when the valve is in a closed configuration (in the embodiment of Fig. 3, through channel 66, and in the embodiment of Figs. 5A-5C, through the flow of evaporating coolant through the annular the space between the valve body and the adjacent housing 54 so as to keep the coolant in the displaceable valve body).

[0057] Draining the coolant from the coolant supply tube 36 when the coolant flow is stopped by the supply valve 32, 32 'is advantageous to ensure rapid cooling of the needle 26. For example, a 30 g needle with a 2.5 cm length cooled to an ambient temperature of -15 ° C can only use about 0.003 g / s nitrous oxide when it approaches or reaches a steady state (for example, 10 seconds after cooling starts) ). If the total volume along the coolant flow path from the inlet valve to the distal end or outlet of the inlet tube 36 is approximately 0.1 cm³, then the minimum flow time of all the evaporating liquid through the delivery tube can be calculated as follows:

0.1 cm³ * (0.7 g / cm³ ) = 0.07 g of liquid nitrous oxide, 11

ΕΡ2 111 172 BI

0.07g / (0.003 g / s) = 23 s

These calculations assume a fused silica tube sized to allow minimal nitrous oxide to flow when the fluid reservoir pressure is about 900 psi. When the delivery valve closes, the needle side pressure of the delivery valve disappears, resulting in an extension of the actual residue delivery period and only partial cooling near the distal tip of the needle 16. Regardless, it is desirable to limit the flow rate of the coolant to the needle to aibo almost to the level where it evaporates into the needle, so as to facilitate the use of a simple disposable coolant supply reservoir 18. The analytical models that can be used to determine such coolant flows are shown in Fig. 10, which can be used in conjunction with the coolant properties (such as the graph of nitrous oxide versus pressure and enthalpy shown in Fig. 10A) and the thermal properties of the tissue shown in Table I, to determine the theoretical minimum coolant flow rates (see Figure 10B), theoretical minimum amounts of coolant (see Figure 10C) and the like.

Table and

<td>Property</td><td>units</td><td>Value</td>

<td>Freezing temperature upper limit (T₂)</td><td>° C</td><td> -1</td>

<td>Phase transition peak temperature (T₃)</td><td>° C</td><td> -3</td>

<td>Freezing point lower limit (TO</td><td>° C</td><td> -8</td>

<td>Thermal conductivity in a non-frozen area (k_at)</td><td>W / (mm - ° C)</td><td> 0,00063</td>

<td>Thermal conductivity in a frozen area (k_f)</td><td>W / (mm - ° C)</td><td> 0,00151</td>

<td>Specific volume heat in a non-frozen area ({paK)</td><td>J / mm³ - ° C</td><td> 0,00316</td>

<td>Specific volume heat in a frozen area ({ptCjf)</td><td>J / mm³ - ° C</td><td> 0,00193</td>

<td>Latent heat of solidification (HF)</td><td>J / mm³</td><td> 0,300</td>

[0058] Referring now to Figs. 3 and 4, a variety of alternative embodiments and improvements are envisaged. The fluid supply 18 may be pre-opened for use by piercing the frangible reservoir seal with a piercing blade 70 (e.g., by tightening the threaded reservoir carrier coupled to the housing 54), wherein the nitrogen tie is filtered through the filter 72 before being sent along the coolant flow path. Suitable filters can have pores ranging from about 6 to about 25 pm and are commercially available from Porex based in Georgia (or from various other suppliers) or they can be a dense stainless steel mesh (such as those whose size the mesh is approximately 635, the wire thickness is 0.0009 inches, and the wire edge spacing is approximately 0.0006 inches) or the like. A variety of different epoxy or other binders 74 can be used, and the replaceable needle housing 24A and other structural components may contain a variety of different metals or polymers, including brass or the like.

ΕΡ2 111 172 Bl

Ribs 76 may be present to assist in the evaporation of excess coolant moving towards the proximal end of the insertion portion of the needle 26.

[0059] Usually, very thin needles are used to provide coolant to and / or under the skin surface. Such needles may relatively easily be damaged if they hit the bone, or may otherwise be damaged or deformed before or during use. Thin needles help prevent damage to the skin during insertion, although they may not be suitable for multiple insertions to perform surgery on multiple treatment sites or pathological changes of a given patient, or sequential surgery over a large area of ​​the patient's body. Accordingly, the designs shown in Figures 1B, 3 and 4 allow the use of probe bodies 16, 54 with a plurality of needles exchanged successively. O-ring washers 60 help isolate the flow of coolant (which can be pressurized up to about 900 psi) from the exhaust gas (which can be pressurized between about 50 and 400 psi, depending on the desired temperature). Exemplary O-ring sealing washers may be O-rings of hydrogenated synthetic Buna-N rubber or the like.

[0060] It may be beneficial to increase the volume of tissue to be treated in a single treatment cycle. Because it is generally desirable to increase the size of the needle excessively, as well as select needles of different lengths, needle assemblies with different needle numbers in the needle system may also be selected and mounted on the probe body. Other embodiments may use a single needle system permanently mounted to the probe body or multiple sets of replaceable needles, all of which contain the same number of needles. Regardless, the supply of coolant to a series of needles can be provided, for example, by inserting and connecting multiple fused silica supply tubes to a 0.010 polyimide tube 58 or head in a needle assembly, and by inserting the distal end of each supply tube into the lumen of the associated needle 26. The needles may be vented to a common outlet space coaxially around the polyimide tube 58 in a manner similar to the one-needle construction shown. In this way, the amount of tissue to be treated can be increased in the vicinity of the needles and / or between them, which can be seen by comparing the theoretical 15-second interactions of one needle and two needles with a probe surface temperature of -15 ° C, as shown in Fig. 11A and 11B.

[0061] Referring now to Fig. 6, it may be desirable to allow the system user to select the depth of surgery and / or subject the skin surface to a temperature similar to that applied to the underlying target tissue along the needle 26. The distal end face 82 held by the probe body 54 and the adjacent and / or surrounding proximal end of the needles can be configured to limit heat exchange with the skin when the needle 26 is introduced, whereby the surface 82 contacts the skin and the coolant flows into the needle. Exemplary heat-limiting surfaces may be formed, for example, by a small pad or body 84 of rigid foam. Closed-cell polyethylene foam or expanded polystyrene ™ bodies can be used. As shown in Fig. 6, body kits alternatively selected from the set may also have different thicknesses between the skin contact surface 82 and the surface 86 that contact the distal portion of the probe body. The user can then select the length of the inserted needle section by selecting the appropriate probe body 84, 84a, 84b and mounting the selected probe body on the needles. The skin contact surface 82 of bodies 84, 84a and 84b (or some other skin contact surface adjacent the distal end of the needle) is used to apply pressure to the skin, changing

1112 111 172 Bl pathological and / or target tissue during surgery. Alternative solutions are also envisaged to vary the length of the inserted needle section, including those that include threaded or other articulated structures that maintain skin contact surface 82 relative to the adjacent probe body 54 or the like.

[0062] Referring now to Fig. 7, applying pressure before, during and / or after cooling may assist in suppressing or otherwise suppressing acute pain. Such pain may otherwise result from skin piercing, cooling or thawing of target and / or surrounding tissue. It may also be beneficial to obstruct the patient's view of the cooling needles and / or cover the needles when they are not used to prevent accidental needle sticks and potential transmission of diseases. To this end, the skin contact surface 82 can be held by an articulated support structure with a first configuration (shown in solid line in Fig. 7) and a second configuration (shown in broken line in Fig. 7). A simple spring mechanism is used to apply the desired force between the skin contact surface 82 and the patient's body before insertion and during cooling. More advanced solutions may also be employed in which the needle is pushed toward the distal end and then towards the proximal end relative to the skin contact surface, at appropriate times after applying adequate pressure to the patient's skin, and the like.

[0063] Referring now to Figure 8, other alternative examples are also envisaged, in this case for subjecting the patient's body to different cooling temperatures and / or for cooling the skin surface and the target tissue adjacent to the needle 26. For example, in the case of acne two target chilling temperatures may be desirable, namely chilling temperature on the skin surface to inhibit inflammation (e.g. to about -10 ° C) and (see Fig. 14) the temperature of cooling the TT cylinder of the target tissue around the needle 26 sufficiently to kill germs in the sebaceous gland and the enlarged opening of the hair follicle (e.g. to about -20 ° C). The two-temperature tact procedure can be particularly beneficial for severe acne, including cysts or nodules. To cool the tissue contact surface 82, this surface may be heat coupled to chamber 88. Cooling fluid can be sent to chamber 88 through the outlet of the coolant supply tube 36, and the pressure in chamber 88 (and thus the temperature in the chamber) can optionally be regulated by a dedicated additional safety valve 46a. Because the pressure in chamber 88 may be different from the pressure in the needle, different treatment temperatures may be used. The constructions described in this document can also be combined with each other, e.g. 8 for treatment using two different temperatures for the skin / needle surface is compatible with the replacement needle systems of Figures 1B, 3 and / or 4. Systems and methods for skin surface / needle treatments using two different temperatures may also be compatible example, with articulated support elements according to fig. 7 to the surface of the skin so as to exert pressure on the skin while cooling it prior to insertion and / or when inserting the needle with a fluid delivery tube or the like.

[0064] Still other alternatives are envisaged, which include systems that cause rapid cooling to promote the necrosis of malignant lesions or the like. High cooling rates limit osmosis in the target tissue. Slow cooling tends to promote ice formation between cells rather than inside cells due to osmosis. Although such slow cooling may be provided in cases where necrosis is undesirable (for example, by using a proportional delivery valve to regulate flow,

ΕΡ 2 111 172 Bl generated by the processor's opening / closing cycle during initial cooling or the like), the needle probes described herein are generally well suited to cause rapid cooling of the target tissue by evaporating the coolant in close thermal and spatial proximity of this target tissue. Accordingly, in cases where cell necrosis is desired due to intracellular ice formation, cooling rates of about 25 ° C / s or more, and even about 50 ° C / s or more are provided.

[0065] Referring now to Figs. 9, 9A and 9B, generally circular cross-sectional needles may be used, although they may not always provide the desired surface area for the cross-sectional area of ​​the needle. The increased surface area can reduce the amount of time the needle is inserted to cool a specific volume of tissue to a temperature within the target range. In this regard, a needle with an elongated outer cross-sectional shape, such as an elliptical needle 90 may be desirable. A distal cutting edge 92 at the distal tip facilitates insertion, and a circular cross-section 94 near the proximal end limits cooling in the vicinity of the skin, while tissue cooling target between these parts is increased by elliptical cross section 96.

[0066] Referring now to Fig. 15, method 100 facilitates patient cure by means of a cryogenic cooling system having an independent disposable handle and replaceable needles, such as shown in Fig. 1B. Method 100 usually begins with determining in block 110 the desired tissue remodeling and results, such as alleviating specific facial wrinkles, suppressing pain at a particular site, alleviating unsightly skin lesions or cosmetic defects on the face, or the like. Appropriate target tissues for the procedure are identified in block 112 (for example, subcutaneous muscles that cause wrinkles, tissue that sends a pain signal, or infected tissues that cause pathological changes), which allows to determine the target depth of the procedure in block 114, the target treatment temperature profile or the like. Then, a suitable needle assembly can be mounted to the handle 116 in the block 116, wherein the length of the needle, the skin surface cooling chamber, the needle assembly and / or other components of the needle assembly are optionally suitable for surgery on target tissues. Simpler systems may include only one type of needle and / or first needle assembly mounted on the handle.

[0067] As described above, the skin may be subjected to pressure, cooling or both in block 118 adjacent to the needle insertion site before, during and / or after insertion in block 120 and after cryogenic cooling in the needle block 122 and associated tissue target, the needle can then be withdrawn from block 124 from the target tissue. If the procedure is not completed, block 126 and the needle is not yet blunt, block 128, then the next location of needle insertion may be subjected to pressure and / or cooling in block 118 and the procedure may be performed on additional target tissue. However, due to the risk of dulling thin needles after only a few insertions through the skin, any needles that have become dull (or otherwise have been deemed to be worn to the extent that they just need to be replaced, regardless of whether they occurred after one insertion, 5 introductions) or the like) during surgery may be replaced with a new needle in block 116, before the next pressure / cooling application in block 118, insertion of the needle in block 120 and / or the like. After complete treatment on target tissues or when the coolant supply in the cartridge contained in the independent handle is depleted, the used handle and needles can be discarded in block 130.

ΕΡ 2 111 172 Bl [0068] Different target tissues may be used for different target temperatures, periods and cycles of the procedure to achieve the desired remodeling. For example (as described more fully in Patent Application 11/295204, which was previously incorporated herein by reference), the desired temperature ranges for temporarily and / or permanently disabling the muscle, as well as for protecting the skin and surrounding tissues, are indicated in the Table II below:

Table II

<td>Temperature</td><td colspan="2">Skin</td><td>Muscle / fat</td>

<td>37 ° C</td><td>initial state</td><td></td><td></td>

<td>25 ° C</td><td>feeling cold</td><td></td><td></td>

<td>18 ° C</td><td>reflex extension</td><td>deep</td><td></td>

<td></td><td>blood vessels</td><td></td><td></td>

<td>15 ° C</td><td>painful feeling of cold</td><td></td><td></td>

<td>12 ° C</td><td>reduction of spasticity</td><td></td><td></td>

<td>10 ° C</td><td>strong cold feeling</td><td>reduction</td><td></td>

<td></td><td colspan="2">chronic edema, Hunting reaction</td><td></td>

<td>5 ° C</td><td>feeling of pain</td><td></td><td></td>

<td>for C</td><td>temperature of solidification</td><td></td><td></td>

<td>-1 ° C</td><td></td><td></td><td>Start of phase change</td>

<td>-2 ° C</td><td></td><td></td><td>minimal apoptosis</td>

<td>-3 ° C</td><td></td><td></td><td>Phase change peak</td>

<td>-5 ° C</td><td>tissue damage</td><td></td><td>Moderate apoptosis</td>

<td>-8 ° C</td><td></td><td></td><td>Completion of phase change</td>

<td>-10 ° C</td><td></td><td></td><td>Significant apoptosis</td>

<td>-15 ° C</td><td></td><td></td><td>Extensive apoptosis, mild</td>

<td></td><td></td><td></td><td>moderate necrosis</td>

<td>-19 ° C</td><td></td><td></td><td>Apoptosis of certain muscle tissues skeletal</td>

<td>-40 ° C</td><td></td><td></td><td>Extensive necrosis</td>

[0069] To ensure the desired or selected period of tissue remodeling effectiveness, tissue treatment temperatures according to Table III below may be used:

Table III

<td>Temperature range, cooling</td><td>Period of effectiveness</td><td>Goal</td>

<td>&gt; 0 ° C</td><td>The procedure only lasts as long as the needle is placed in tissue target.</td><td>Can be used for tissue recognition target.</td>

<td>from 0^QC to -5 ° C</td><td>It usually lasts days or weeks and target tissue can fix itself.</td><td>Temporary treatment. May be used for evaluation the effectiveness of the procedure</td>

ΕΡ2 111172 Bl

<td></td><td>Examples of implementation last hours or days.</td><td>reconstruction on a shape skin surface or ago like.</td>

<td>from -5 ° C to -15 ° C</td><td>It usually lasts for months or years; can be permanent. Limited muscle repair. Examples of implementation can last weeks or months.</td><td>Long lasting, potentially permanent cosmetic benefits. Maybe be used in limited doses by a certain period of time in order obtaining a stage operation, in result control and avoidance negative result. May be used as a treatment standard.</td>

<td>from -15 ° C to -25 ° C</td><td>It usually lasts for weeks or months. The muscle can repair itself by mobilizing satellite cells. Examples of implementation can last patch.</td><td>May result medium term benefits cosmetics and can be used where permanent effects are undesirable or to evaluate the results potentially persistent dosing. Examples implementation can provide permanent treatments.</td>

[0070] There is a temperature range at which apoptosis can be induced. The phenomenon of apoptosis can be temporary, long-lasting (lasting at least weeks, months or years) and even permanent. Although the effects of necrosis can be long-lasting or even permanent, apoptosis may actually provide more long-lasting cosmetic benefits than necrosis. Apoptosis may show non-inflammatory cell death. Without inflammation, normal muscle recovery can be inhibited. After many muscle injuries (including many injuries involving necrosis), skeletal muscle satellite cells can be mobilized by inflammation. Without inflammation, such mobilization can be limited or can be completely avoided. Apoptotic cell death may reduce muscle mass and / or may break the collagen and elastin combined chain. Temperature ranges that produce a mixture of such phenomena of apoptosis and necrosis may also provide long-term or lasting benefits. For fat reduction, a lasting effect may be beneficial. Surprisingly, both apoptosis and necrosis can produce long-lasting and even lasting fat tissue reduction results because fat cells are regenerated in a different way than muscle cells.

[0071] Referring now to Fig. 16, it illustrates an exemplary coupling member 160 between the cryogenic cooling probe 162 and the associated probe body structure 164, along with adjacent needle parts, a valve, the probe body and the like. The needle probe 162 is included in the needle assembly having a needle cap 166 with a light comprising a polyimide tube 168 around a fused silica tube for supplying a cooling fluid with its polyamide sheath 170. pads

1112 111 172 The O-ring seal 172 seals the exhaust gas path 174 and the coolant inlet path 176, the inlet path having an outlet 178 to minimize post-cooling, after the valve 180 has shut off the coolant supply, as described generally above . The valve is here driven by the engine 182 and the exhaust gas pressure is regulated by means of an adjustment spring and ball valve 184 as described above. A setting screw 186 with a socket is used for mounting and / or regulating the pressure relief valve, and a thermistor 188 is used to detect the flow of cooling gas.

[0072] Referring now to Figures 17A and 17B, cryogenic cooling probes 196, 198 are introduced into the target tissue TT, and a stream of cryogenic coolant is injected into the needle, as generally described above. The target tissue area 200 TT is cooled sufficiently to freeze and perform the desired remodeling of at least part of the target tissue. Instead of waiting for thawed frozen target tissue, in the embodiment of Fig. 17A, the removal of the needle is facilitated by a lubricity coating 202, while at least some of the frozen tissue remains frozen. The lubricity coating 202 may consist of a material with a much lower thermal conductivity than the thermal conductivity of the probe structure 204 below it. The coating 202 may have a thickness considerably smaller than the probe structure 204 below it, which limits the overall coating insulation effect, and / or the temperature inside the probe 196 may be reduced to provide the desired overall cooling operation. Although cooling the target tissue via a heat-insulating lubricating coating may be counterintuitive, the ability to quickly remove the probe 196 from the patient's body can significantly increase the rate at which treatments can be performed, especially when they involve a large number of cycles and insertion / freezing / removal and / or when the defrost time is equal to at least half the active cooling time (and is usually equally long or even longer).

[0073] It should be noted that the small surface 206 of the probe 196 may not have a lubricity coating 202. In cases where the coated structure 204 of the probe is made of an electrical conductor, such as stainless steel and some alternative metal, the uncoated surface portion 206 may be used as an electrode for neurostimulation when positioning the 196 probe or the like. [0074] In the embodiment according to Fig. 17B, ​​the use of small diameter cryosurgical probes can facilitate removal of the probe without having to wait for the area to completely thaw 200. In this embodiment, the cross-sectional size of the microneedle probe 198 is equal to the needle size 20 gauge and less, preferably it contains a needle size 25 gauge or less and preferably contains a 30 gauge needle. Such small-needle micro-probes have a small heat capacity so they can be heated relatively quickly by heat conduction from adjacent tissues and / or by any warm fluids flowing through them. As a result, although the main portion 208 of the target tissue remains frozen, the layer 210 located between the still frozen area and the probe 198 may facilitate safe removal of the probe from the patient's body. Thawed layer 210 may comprise thawed target tissue, thawed extracellular fluids or the like. Small needles also have small areas of probe contact with the tissue that can limit the total resting friction between the probe and frozen tissue. Regardless of any particular mechanism of action, the use of cryogenic microneedles with small diameters allows you to safely remove the probe from the tissue undergoing treatment in a much shorter time than associated with complete defrosting of the ice ball that has been created. Embodiments using a lubricity coating and / or small diameter probe allow the probe to be removed within about 10 seconds after cooling, optional

ΕΡ2 111172 Bl allow safe removal within about 5 seconds of cooling, and even within about 3 seconds of cooling.

[0075] Referring now to Figs. 18A and 18B, in order to adjust the length of the probe that uses therapeutic cooling, appropriate dosing of the coolant flow to the probe for cryogenic cooling 220, 222 may be used. Probes 220, 222 are interchangeably held by body 224 probes via a needle holder or needle engaging means as generally described above. Each probe includes a light 226 with a coolant supply tube 228 that extends to a distal connection 230. The coolant supply tube 228 can be used to dispense the coolant by appropriately selecting its length and / or the inside diameter of the light in the supply tube. More specifically, as stated above, cooling the target TT tissue along distal portion 232 of probe 228 occurs by evaporating the liquid contained in the cryogenic coolant. As shown in Figure 18A, cooling of the CT surrounding tissue near the target TT tissue may be limited by adjusting the amount of coolant flowing in, whereby the evaporating liquid is exhausted until the stream reaches the proximal portion 234 of the probe. In the embodiment of Fig. 18b, the greater length of probe 222 is cooled by applying a relatively larger amount of coolant fluid (and liquid) from the supply tube 238 to the light through port 230, whereby the liquid remains present for its evaporation over a longer distal portion 232 probe. It should be noted that a difference in length of the cooled portion 232 may exist despite the use of an external probe structure that has a similar cross-section and / or overall length. [0076] Although the proximal portion 234 of the probes 220, 222 may be somewhat cooled (by conduction through the dafa portion of the probe 232, through the flow of gas evaporated from the coolant or the like), the temperature of the tissue surrounding CT may remain above the temperature of the remodeling procedure treatment zone 238 in the target tissue. Therefore, damage to the target tissue can be avoided despite the lack of any additional insulation on the proximal part of the probe. It also facilitates the use of different test zones 238 at different locations for a given patient by selecting needle assemblies having appropriate coolant delivery pathways with the desired differing coolant flow properties.

[0077] Although the embodiments have been described in sufficient detail for the sake of clarity of understanding and by way of example, many modifications, changes and adaptations may be made and / or will be apparent to those skilled in the art. For example, one or more temperature feedback loops can be used to control treatments, wherein tissue temperature is optionally measured using a temperature sensing needle having a temperature sensor located adjacent the outer surface of contact of the needle with the cooled skin. Accordingly, the scope of the present invention is limited only by the independent claims.