Patent Description:
Cryoablation is a surgical technique for ablating tissue by cooling or freezing the tissue to a lethal degree. Cryoablation has the benefit of minimizing permanent collateral tissue damage and has applicability to a wide range of therapies including the treatment of cancer and heart disease.

A shortcoming with certain cryosurgical systems, however, arises from the process of evaporation. The process of evaporation of a liquefied gas results in enormous expansion as the liquid converts to a gas; the volume expansion is on the order of a factor of <NUM>. In a small-diameter system, this degree of expansion consistently results in a phenomenon known in the art as "vapor lock. " The phenomenon is exemplified by the flow of a cryogen in a thin-diameter tube. The formation of a relatively massive volume of expanding gas impedes the forward flow of the liquid cryogen through the tubes.

Traditional techniques that have been used to avoid vapor lock have included restrictions on the diameter of the tube, requiring that it be sufficiently large to accommodate the evaporative effects that lead to vapor lock. Other complex cryo-apparatus and tubing configurations have been used to "vent" N<NUM> gas as it is formed along transport tubing. These designs also contributed to limiting the cost efficacy and tube diameter.

There is accordingly a need for improved systems for providing minimally invasive, safe and efficient cryogenic cooling of tissues.

<CIT> discloses methods and system for cryogenic cooling.

<CIT> describes a cryoablation system comprising a cryogen supply for providing a cryogenic fluid, a cooler for the cryogenic fluid, a medical device comprising a distal treatment section, a fluid path and a controller to control cooling power delivered from the distal treatment section by modulating a pressure from a first fluid pressure to a second fluid pressure less than the first fluid pressure.

Aspects of the invention are recited in the independent claim and preferred features are recited in the dependent claims.

In examples, the pressure is modulated based on the temperature of the catheter. When the temperature of the catheter reaches a target temperature, the pressure is reduced.

The description, objects and advantages of the present invention will become apparent from the detailed description to follow, together with the accompanying drawings.

The exemplary methods, which are not part of the claimed invention, recited herein may be carried out in any order of the recited events which is logically possible, as well as the recited order of events. Furthermore, where a range of values is provided, it is understood that every intervening value, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention.

Embodiments of the invention make use of thermodynamic processes using cryogens that provide cooling without encountering the phenomenon of vapor lock.

This application uses phase diagrams to illustrate and compare various thermodynamic processes. An example phase diagram is shown in <FIG>. The axes of the diagram correspond to pressure P and temperature T, and includes a phase line <NUM> that delineates the locus of all (P, T) points where liquid and gas coexist. For (P, T) values to the left of the phase line <NUM>, the cryogen is in a liquid state, generally achieved with higher pressures and lower temperatures, while (P, T) values to the right of the phase line <NUM> define regions where the cryogen is in a gaseous state, generally achieved with lower pressures and higher temperatures. The phase line <NUM> ends abruptly in a single point known as the critical point <NUM>. In the case of nitrogen N<NUM>, the critical point is at Pc=<NUM> MPa and Tc=-<NUM>.

When a fluid has both liquid and gas phases present during a gradual increase in pressure, the system moves up along the liquid-gas phase line <NUM>. In the case of N<NUM>, the liquid at low pressures is up to two hundred times more dense than the gas phase. A continual increase in pressure causes the density of the liquid to decrease and the density of the gas phase to increase, until they are equal only at the critical point <NUM>. The distinction between liquid and gas disappears at the critical point <NUM>. The blockage of forward flow by gas expanding ahead of the liquid cryogen is thus avoided by conditions surrounding the critical point, defined herein as "near-critical conditions. " Factors that allow greater departure from the critical point while maintaining a functional flow include greater speed of cryogen flow, larger diameter of the flow lumen and lower heat load upon the thermal exchanger, or cryo treatment region tip.

As the critical point is approached from below, the vapor phase density increases and the liquid phase density decreases until right at the critical point, where the densities of these two phases are exactly equal. Above the critical point, the distinction of liquid and vapor phases vanishes, leaving only a single, supercritical phase. All gases obey quite well the following van der Waals equation of state:
<MAT>
where p = P/Pc, v= V/Vc, and t=T/Tc, and Pc, Vc, and Tc are the critical pressure, critical molar volume, and the critical temperature respectively.

The variables v, p, and t are often referred to as the "reduced molar volume," the "reduced pressure," and the "reduced temperature," respectively. Hence, any two substances with the same values of p, v, and t are in the same thermodynamic state of fluid near its critical point. Eq. <NUM> is thus referred to as embodying the "Law of Corresponding States. " This is described more fully in <NPL>).

In examples, the reduced pressure p is fixed at a constant value of approximately one, and hence at a fixed physical pressure near the critical pressure, while the reduced temperature t varies with the heat load applied to the device. If the reduced pressure p is a constant set by the engineering of the system, then the reduced molar volume v is an exact function of the reduced temperature t.

In other examples, the operating pressure p may be adjusted so that over the course of variations in the temperature t of the device, v is maintained below some maximum value at which the vapor lock condition will result. It is generally desirable to maintain p at the lowest value at which this is true since boosting the pressure to achieve higher values of p may involve use of a more complex and more expensive compressor, resulting in more expensive procurement and maintenance of the entire apparatus support system and lower overall cooling efficiency.

The conditions that need to be placed on v depend in a complex and non-analytic way on the volume flow rate dV/dt, the heat capacity of the liquid and vapor phases, and the transport properties such as the thermal conductivity, viscosity, etc., in both the liquid and the vapor. This exact relationship is not derived here in closed form algebraically, but may be determined numerically by integrating the model equations that describe mass and heat transport within the device. Conceptually, vapor lock occurs when the rate of heating of the needle (or other device structure for transporting the cryogen and cooling the tissue) produces the vapor phase. The cooling power of this vapor phase, which is proportional to the flow rate of the vapor times its heat capacity divided by its molar volume, is not able to keep up with the rate of heating to the needle. When this occurs, more and more of the vapor phase is formed in order to absorb the excess heat through the conversion of the liquid phase to vapor in the cryogen flow. This creates a runaway condition where the liquid converts into vapor phase to fill the needle, and effectively all cryogen flow stops due to the large pressure that results in this vapor phase as the heat flow into the needle increases its temperature and pressure rapidly. This condition is called "vapor lock.

In accordance with the present invention, the liquid and vapor phases are identical in their molar volume. The cooling power is at the critical point, and the cooling system avoids vapor lock. Additionally, at conditions below the critical point, the apparatus may avoid vapor lock as well.

<FIG> provides a schematic illustration of a structural arrangement for a cryogenic system, and <FIG> provides a phase diagram that illustrates a thermodynamic path taken by the cryogen when the system of <FIG> is operated. The circled numerical identifiers in the two figures correspond so that a physical position is indicated in <FIG> where operating points identified along the thermodynamic path are achieved. The following description thus sometimes makes simultaneous reference to both the structural drawing of <FIG> and to the phase diagram of <FIG> in describing physical and thermodynamic aspects of the cooling flow.

For purposes of illustration, both <FIG> and <FIG> make specific reference to a nitrogen cryogen, but this is not intended to be limiting. The invention may more generally be used with any suitable cryogen such as, for example, argon, neon, helium, hydrogen, and oxygen.

In <FIG>, the liquid-gas phase line is identified with reference label <NUM> and the thermodynamic path followed by the cryogen is identified with reference label <NUM>.

A cryogenic generator <NUM> is used to supply the cryogen at a pressure that exceeds the critical-point pressure Pc for the cryogen at its outlet, referenced in <FIG> and <FIG> by label ①. The cooling cycle may generally begin at any point in the phase diagram having a pressure above or slightly below Pc, although it is advantageous for the pressure to be near the critical-point pressure Pc. The cooling efficiency of the process described herein is generally greater when the initial pressure is near the critical-point pressure Pc so that at higher pressures there may be increased energy requirements to achieve the desired flow. Thus, examples may sometimes incorporate various higher upper boundary pressure but generally begin near the critical point, such as between <NUM> and <NUM> times Pc, and in one embodiment at about <NUM> times Pc.

As used herein, the term "near critical" is meant to refer to near the liquid-vapor critical point. Use of this term is equivalent to "near a critical point" and it is the region where the liquid-vapor system is adequately close to the critical point, where the dynamic viscosity of the fluid is close to that of a normal gas and much less than that of the liquid; yet, at the same time its density is close to that of a normal liquid state. The thermal capacity of the near critical fluid is even greater than that of its liquid phase. The combination of gas-like viscosity, liquid-like density and very large thermal capacity makes it a very efficient cooling agent. Reference to a near critical point refers to the region where the liquid-vapor system is adequately close to the critical point so that the fluctuations of the liquid and vapor phases are large enough to create a large enhancement of the heat capacity over its background value. The near critical temperature is a temperature within ±<NUM>% of the critical point temperature. The near critical pressure is between <NUM> and <NUM> times the critical point pressure.

Referring again to <FIG>, the cryogen is flowed through a tube, at least part of which is surrounded by a reservoir <NUM> of the cryogen in a liquid state, reducing its temperature without substantially changing its pressure. In <FIG>, reservoir is shown as liquid N<NUM>, with a heat exchanger <NUM> provided within the reservoir <NUM> to extract heat from the flowing cryogen. Outside the reservoir <NUM>, thermal insulation may be provided around the tube to prevent unwanted warming of the cryogen as it is flowed from the cryogen generator <NUM>. At point ②, after being cooled by being brought into thermal contact with the liquid cryogen, the cryogen has a lower temperature but is at substantially the initial pressure. In some instances, there may be a pressure change, as is indicated in <FIG> in the form of a slight pressure decrease, provided that the pressure does not drop substantially below the critical-point pressure Pc, i.e. does not drop below the determined minimum pressure. In the example shown in <FIG>, the temperature drop as a result of flowing through the liquid cryogen is about <NUM>° C.

The cryogen is then provided to a device for use in cryogenic applications. In the example shown in <FIG>, the cryogen is provided to an inlet <NUM> of a catheter <NUM>, such as may be used in medical cryogenic endovascular applications, but this is not a requirement.

Indeed, the form of the medical device may vary widely and include without limitation: instruments, appliances, catheters, devices, tools, apparatus', and probes regardless of whether such probe is short and rigid, or long and flexible, and regardless of whether it is intended for open, minimal, non-invasive, manual or robotic surgeries.

The cryogen may be introduced through a proximal portion of a catheter, continue along a flexible intermediate section of the catheter, and into the distal treatment section of the catheter. As the cryogen is transported through the catheter, and across the cryoablation treatment region <NUM>, between labels ② and ③ in <FIG> and <FIG>, there may be a slight change in pressure and/or temperature of the cryogen as it moves through the interface with the device, e.g. cryoablation region <NUM> in <FIG>. Such changes may typically show a slight increase in temperature and a slight decrease in pressure. Provided the cryogen pressure remains above the determined minimum pressure (and associated conditions), slight increases in temperature do not significantly affect performance because the cryogen simply moves back towards the critical point without encountering the liquid-gas phase line <NUM>, thereby avoiding vapor lock.

Thermal insulation along the shaft of the cryotherapy catheter (or apparatus, appliance, needle, probe, etc.) and along the support system that delivers near-critical freeze capability to these needles may use a vacuum.

Flow of the cryogen from the cryogen generator <NUM> through the catheter <NUM> or other device may be controlled in the illustrated embodiment with an assembly that includes a check valve <NUM>, a flow impedance, and/or a flow controller. The catheter <NUM> itself may comprise a vacuum insulation <NUM> (e.g., a cover or jacket) along its length and may have a cold cryoablation region <NUM> that is used for the cryogenic applications. Unlike a Joule-Thomson probe, where the pressure of the working cryogen changes significantly at the probe tip, these embodiments of the invention provide relatively little change in pressure throughout the apparatus. Thus, at point ④, the temperature of the cryogen has increased approximately to ambient temperature, but the pressure remains elevated. By maintaining the pressure above or near the critical-point pressure Pc as the cryogen is transported through the catheter, the liquid-gas phase line <NUM> and vapor lock are avoided.

The cryogen pressure returns to ambient pressure at point ⑤. The cryogen may then be vented through vent <NUM> at substantially ambient conditions.

Examples of near critical fluid cryoablation systems, their components, and various arrangements are described in <CIT> which issued as <CIT>; <CIT> which issued as <CIT>; <CIT> which issued as <CIT> and <CIT>.

An exemplary method for cooling a target tissue in which the cryogen follows a thermodynamic path similar to that shown in <FIG> is illustrated with the flow diagram of <FIG>. At block <NUM>, the cryogen is generated with a pressure that exceeds the critical-point pressure and is near the critical-point temperature. The temperature of the generated cryogen is lowered at block <NUM> through heat exchange with a substance having a lower temperature. In some instances, this may conveniently be performed by using heat exchange with an ambient-pressure liquid state of the cryogen, although the heat exchange may be performed under other conditions in different embodiments. For instance, a different cryogen might be used in some embodiments, such as by providing heat exchange with liquid nitrogen when the working fluid is argon. Also, in other alternative embodiments, heat exchange may be performed with a cryogen that is at a pressure that differs from ambient pressure, such as by providing the cryogen at lower pressure to create a colder ambient.

The further cooled cryogen is provided at block <NUM> to a cryogenic-application device, which may be used for a cooling application at block <NUM>. The cooling application may comprise chilling and/or freezing, depending on whether an object is frozen with the cooling application. The temperature of the cryogen is increased as a result of the cryogen application, and the heated cryogen is flowed to a control console at block <NUM>. While there may be some variation, the cryogen pressure is generally maintained greater than the critical-point pressure throughout blocks <NUM>-<NUM>; the principal change in thermodynamic properties of the cryogen at these stages is its temperature. At block <NUM>, the pressure of the heated cryogen is then allowed to drop to ambient pressure so that the cryogen may be vented, or recycled, at block <NUM>. In other embodiments, the remaining pressurized cryogen at block <NUM> may also return along a path to block <NUM> to recycle rather than vent the cryogen at ambient pressure.

<FIG> is a flow diagram <NUM> illustrating another example.

Step <NUM> recites to generate cryogen at or near critical pressure and temperature. Step <NUM> may be carried out, for example, as described above with reference to <FIG>.

Step <NUM> recites to lower the cryogen temperature. Step <NUM> may also be carried out, for example, as described above with reference to <FIG>.

Step <NUM> recites to determine whether the catheter temperature is below a threshold value. Temperature measurement may be performed using thermocouples placed on the end of the treatment section, or within the transport channels or otherwise along the flow path so as to measure temperature of the apparatus itself, the cryogen, and/or the tissue. Indeed a plurality of temperature sensors may be placed throughout the tip, treatment section, the inlet flowpath, the return flowpath, and preferably, in direct contact with the cryogen to obtain an accurate measurement of real time temperature, temperature change over time, and temperature difference of the incoming cryogen versus the outgoing cryogen.

If the temperature is not below a threshold value, the pressure is not reduced.

If the temperature is below a threshold value, then the pressure is decreased to a pre-set value as indicated by step <NUM>. In embodiments, after the cryo apparatus treatment section is placed adjacent the target tissue to be cooled, and the temperature is confirmed to be below a threshold value, the pressure is substantially reduced from the first relatively high (near critical) pressure to a second lower pressure once the apparatus tip or tissue reaches a target temperature.

Subsequent to determining whether the temperature is below a pre-set value and whether to reduce the pressure, step <NUM> recites to provide cryogen to a catheter. Step <NUM> may also be carried out, for example, as described above with reference to <FIG>.

Without being bound by theory, once the catheter freezing element or tissue temperature is lowered to a target cold temperature (for example, -<NUM> degrees C), the above mentioned problem associated with vapor lock is minimized because the tissue surrounding the apparatus' treatment section is lowered (namely, frozen). The chilled tissue does not act as a heat sink (and warm) the flowing cryogen in the same way that the tissue initially acted as a heat sink to warm the cryogen. The cryogen shall not have a tendency to transform from a liquid phase to vapor phase within the apparatus. The cryogen is anticipated to remain as a liquid, and the gas molar volume does not increase during the flow cycle. Consequently, the embodiment described in <FIG> provides an initial (or first) high pressure phase of cryogen operation, and a second low-pressure treatment phase. Exemplary pressures during the low pressure treatment phase range from <NUM> MPa to <NUM> MPa (<NUM> to <NUM> psi) and temperatures in the range of -<NUM> to -<NUM> degrees C. Additionally, the time period for the initial high pressure and lower treatment phases range from <NUM> seconds to <NUM> minute, and <NUM> seconds to <NUM> minutes respectively.

A wide variety of systems may be employed to modulate the pressure between the high (near critical) pressure to a relatively low pressure. <FIG> are schematic diagrams illustrating various cryoablation systems having pressure modulation or adjustment components.

With reference to <FIG>, a cryoablation system <NUM> comprises a first cryogen flow path including a high pressure cryogen supply or generator <NUM>, a cooling means <NUM>, a cryoablation catheter <NUM>, and a high pressure check valve <NUM>. Check valve <NUM> may operate to open at pressures ranging from, e.g., <NUM> MPa to <NUM> MPa (<NUM> to <NUM> psi). The first flow path transports the cryogen for a first or initial phase to the treatment section of the catheter preferably under a near critical pressure. Vapor lock is avoided.

After an initial phase, or at which point in time the measured temperature reaches a threshold temperature indicating that the adjacent tissue is substantially cooled, and that the risk of vapor lock is minimized, valve <NUM> is opened. The cryogen flows to low pressure valve <NUM>, which opens at a second substantially lower pressure than check valve <NUM>. The second low pressure valve may be programmed to open at a pressure ranging from <NUM> MPa to <NUM> MPa (<NUM> to <NUM> psi), and more preferably less than or equal to <NUM> Mpa (<NUM> psi). The cryogen may then be further processed, or released to the environment.

The valves described herein may be operated manually or, in embodiments, by using more sophisticated equipment such as a controller. The controller would operate to send signals to the valves and other system components to perform a cryoablation treatment.

The pressure modulated system described herein has both practical and safety advantages over a steady state near critical based cryoablation system. Lower pressure cryogen is easier to work with because there is less energy required to reach the operating pressure, the risk of a leak is less likely at low pressure, the consequences or damage arising from leaks is less with use of a cryogen under a lower pressure. In particular, a leak of a low pressure cryogen would have less impact on equipment, patient safety, and the operator than a leak of high pressure cryogen. Additionally, a low pressure cryogen may be vented directly to the atmosphere.

<FIG> illustrates a cryoablation system <NUM> capable of modulating the pressure according to the claimed invention. Similar to the system described above, cryoablation system <NUM> comprises a high pressure cryogen supply or generator <NUM>, a cooling means <NUM>, a cryoablation catheter <NUM>, and a first check valve <NUM>. A first flow path transports the cryogen for a first or initial phase to the treatment section of the catheter preferably under a near critical pressure. Vapor lock is avoided.

With reference to <FIG>, after the initial time period ti, according to the invention, pressure regulator <NUM> is activated to cause a reduction in the pressure to a second low pressure Pt. Consequently, a low pressure cryogen is transported through the cryoablation catheter <NUM> for treating an adjacent tissue. Vapor lock is avoided despite the reduction in pressure to a pressure substantially below near critical pressure because the instrument end section, and surrounding tissue is cold, and does not cause the cryogen fluid to change phase despite the decrease in pressure.

The pressure regulator and valves may be operated manually or, according to the invention, using more sophisticated equipment such as a controller which sends signals to the valves and other system components to perform a cryoablation treatment as described herein.

<FIG> illustrates another cryoablation system <NUM> capable of modulating the pressure falling within the scope of the claims. Cryoablation system <NUM> comprises a cryogen supply <NUM>, one way valve <NUM>, a cooling means <NUM>, a cryoablation catheter <NUM>, and a check valve <NUM>.

Additionally, the system shown in <FIG> includes a piston <NUM> downstream of the one way valve <NUM>. The piston is activated to increase the pressure of the cryogen downstream of the one way valve <NUM> to a high pressure at or above near critical pressure. Preferably piston is a fast activating member which can increase pressure instantaneously and maintain the desired high pressure for a selected time period. For example, the pressure P may be increased to near critical pressure Pc periodically as shown in plot 9B. As such, the pressure time curve may be defined as a waveform having an amplitude and frequency. The instrument and tissue decrease in temperature towards a lower steady state lethal target temperature. Time period (tt) is representative of a second treatment phase during which the instrument ablation is maintained at the low pressure Pt.

Alternatively, the pressure may be modulated in steps as shown in <FIG>. The steps may decrease in equal increments, or non-linearly.

Still in another example, the pressure may be decreased at a continuous rate as shown in <FIG>. Although <FIG> illustrates a straight profile, the profile may be curved or otherwise ramped towards the low treatment pressure Pt.

With reference again to <FIG>. after the initial phase, piston <NUM> is deactivated, and valves <NUM> and <NUM> are opened. Consequently, a low pressure cryogen is transported through the cryoablation catheter <NUM> for treating an adjacent tissue. Vapor lock is avoided despite the reduction in pressure to a pressure substantially below near critical pressure because the instrument end section, and surrounding tissue is cold, and does not cause the cryogen fluid to change phase despite the decrease in pressure.

As described further herein, the system components (including without limitation the piston, valves, pumps, switches, and regulators) may be activated manually or in other embodiments via a controller. A workstation or console as shown in <FIG> and described in the corresponding text may be provided to allow an operator to conveniently operate the cryoablation instrument.

The cryoablation apparatus may have a wide variety of configurations. For example, one example is a flexible catheter <NUM> as shown in <FIG>. The catheter <NUM> includes a proximally disposed housing or connector <NUM> adapted to fluidly connect to a fluid source (not shown).

A plurality of fluid transfer tubes <NUM> are shown extending from the connector <NUM>. These tubes include a set of inlet fluid transfer tubes <NUM> for receiving the inlet flow from the connector and a set of outlet fluid transfer tubes <NUM> for discharging the outlet flow to the connector <NUM>. In examples each of the fluid transfer tubes <NUM>,<NUM> is formed of material that maintains flexibility in a full range of temperatures from -<NUM>° C to ambient temperature. In examples each fluid transfer tube has an inside diameter in a range of between about <NUM> and <NUM> (preferably between about <NUM> and <NUM>). Each fluid transfer tube may have a wall thickness in a range of between about <NUM> and <NUM> (preferably between about <NUM> and <NUM>).

An end cap <NUM> is positioned at the ends of the fluid transfer tubes <NUM>, <NUM> to provide fluid transfer from the inlet fluid transfer tubes <NUM> to the outlet fluid transfer tubes <NUM>. The endcap is shown having an atraumatic tip. The endcap <NUM> may be any suitable element for providing fluid transfer from the inlet fluid transfer tubes <NUM> to the outlet fluid transfer tubes <NUM>. For example, endcap <NUM> may define an internal chamber, cavity, or passage serving to fluidly connect tubes <NUM>,<NUM>.

An outer sheath <NUM> is also shown in <FIG> surrounding the tube bundle <NUM>. The outer sheath serves to hold the tubes in a tubular arrangement, and protect the construct from being penetrated or disrupted by foreign objects and obstacles.

A temperature sensor <NUM> is shown on the surface of the distal section. Temperature sensor may be a thermocouple to sense a temperature corresponding to the adjacent tissue, and sends the signal back through a wire in the tube bundle to the console for processing. Temperature sensor may be placed elsewhere along the shaft or within one or more of the fluid transport tubes to determine a temperature difference between inflow and outflow.

In examples, the fluid transfer tubes <NUM> are formed of annealed stainless steel or a polymer such as polyimide. In such configurations, the material may maintain flexibility at near critical temperature. In other examples, the transfer tube is shape-forming, deflectable, or steerable to make continuous firm contact with various anatomies. Other suitable device designs including deflectable designs are described in international patent application <CIT>, entitled Endovascular Near Critical Fluid Based Cryoablation Catheter Having Plurality of Preformed Treatment Shapes, published as <CIT>.

There are many configurations for tube arrangements. In examples the fluid transfer tubes are formed of a circular array, wherein the set of inlet fluid transfer tubes comprises at least one inlet fluid transfer tube defining a central region of a circle and wherein the set of outlet fluid transfer tubes comprises a plurality of outlet fluid transfer tubes spaced about the central region in a circular pattern. In the configuration shown in <FIG>, the fluid transfer tubes <NUM>,<NUM> fall within this class of embodiments.

During operation, the cryogen fluid arrives at the catheter through a supply line from a suitable cryogen source at a temperature close to -<NUM>. The cryogen is circulated through the multi-tubular freezing zone provided by the exposed fluid transfer tubes, and returns to the connector.

In examples, the nitrogen flow does not form gaseous bubbles inside the small diameter tubes under any heat load, so as to not create a vapor lock that limits the flow and the cooling power. By operating at the near critical condition for at least an initial period of energy application, the vapor lock is eliminated as the distinction between the liquid and gaseous phases disappears.

A multi-tubular design may be preferably to a single tube design because the additional tubes can provide a substantial increase in the heat exchange area between the cryogen and tissue. Depending on the number of tubes used, cryo instruments can increase the contact area several times over previous designs having similarly sized diameters with single shafts.

<FIG> illustrates a cryoablation system <NUM> having a cart or console <NUM> and a cryoablation catheter <NUM> detachably connected to the console via a flexible elongate tube <NUM>. The cryoablation catheter <NUM>, which shall be described in more detail below in connection with <FIG>, contains one or more fluid transport tubes to remove heat from the tissue.

The console <NUM> may include or house a variety of components (not shown) such as, for example, a generator, controller, tank, valve, pump, etc. A computer <NUM> and display <NUM> are shown in <FIG> positioned on top of cart for convenient user operation. Computer may include a controller, timer, or communicate with an external controller to drive components of the cryoablation systems such as a pump, valve or generator. Input devices such as a mouse <NUM> and a keyboard <NUM> may be provided to allow the user to input data and control the cryoablation devices.

In examples computer <NUM> is configured or programmed to control cryogen flowrate, pressure, and temperatures as described herein. Target values and real time measurement may be sent to, and shown, on the display <NUM>.

<FIG> shows an enlarged view of distal section of cryoablation apparatus <NUM>. The distal section <NUM> is similar in designs described above except that treatment region <NUM> includes a flexible protective cover <NUM>. The cover serves to contain leaks of the cryogen in the event one of the fluid transport tubes is breached. Although a leak is not expected or anticipated in any of the fluid delivery transport tubes, the protective cover provides an extra or redundant barrier that the cryogen would have to penetrate in order to escape the catheter during a procedure. In examples the protective cover may be formed of metal.

Additionally, a thermally conducting liquid may be disposed within spaces or gaps between the transport tubes and the inner surface of the cover to enhance the device's thermal cooling efficiency during treatment. In examples the thermally conductive liquid is water.

Cover <NUM> is shown being tubular or cylindrically shaped and terminates at distal tip <NUM>. As described herein, the cooling region <NUM> contains a plurality of fluid delivery and fluid return tubes to transport a cooling fluid through the treatment region <NUM> causing heat to be transferred/removed from the target tissue. In examples, the fluid is transported through the tube bundle under physical conditions near the fluid's critical point in the phase diagram for a first time period, and then the pressure is reduced for a second time period as described herein. The cover serves to, amongst other things, contain the cooling fluid and prevent it from escaping from the catheter in the event a leak forms in one of the delivery tubes.

Although a cover is shown in <FIG>, the invention is not intended to be so limited except as where recited in the claims. The apparatus may be provided with or without a protective cover and used to cool a target tissue.

The systems described herein may be used in a wide variety of medical applications including, for example, oncology and cardiovascular applications. Candidate tumors to be ablated with cryoenergy include target tissues and tumors in the thorax, and upper and lower GI. The devices described herein may also be applied to destroy or reduce target tissues in the head and neck.

An exemplary cardiovascular application is endovascular-based cardiac ablation to create elongate continuous lesions. As described herein, creating elongate continuous lesions in certain locations of the heart can serve to treat various conditions such as, for example, atrial fibrillation.

The systems described herein serve to create lesions having a length ranging from <NUM>-<NUM>, or <NUM>-<NUM>. , and more preferably between <NUM>-<NUM>. The lesions are preferably continuous and linear, not a series of spots such as in some prior art point-ablation techniques. In accordance with the designs described above, the cryoenergy and heat transfer may be focused on the endocardium, creating a lesion completely through the endocardium (a transmural lesion). Additionally, in embodiments, catheters achieve cooling power without vapor lock by modulating the pressure of the cooling fluid. The cooling fluid is preferably transported near its critical point in the phase diagram for at least a portion of the time of energy activation, and then optionally reduced to a lower pressure.

A cardiac ablation catheter in accordance with the principals of the present invention can be placed in direct contact along the internal lining of the left atrium, thereby avoiding most of the massive heat-sink of flowing blood inside the heart as the ablation proceeds outward.

Additionally, catheter configurations may include substantial bends, or loops which provide both the circumferential, as well as linear, ablations. The catheters described herein may be manipulated to form ring-shaped lesions near or around the pulmonary vessel entries, for example.

Claim 1:
A cryoablation system (<NUM>, <NUM>, <NUM>, <NUM>) for creating a lesion in target tissue, the cryoablation system comprising:
a cryogen supply (<NUM>, <NUM>, <NUM>) for providing a cryogenic fluid having a molar volume of gas and a molar volume of liquid;
a cooler (<NUM>, <NUM>, <NUM>) for cooling the cryogenic fluid;
a medical device (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) comprising a distal treatment section, and a fluid path in fluid communication with the cryogen supply wherein the fluid is transported along the fluid path under pressure; and
a controller operable to control cooling power delivered from the distal treatment section to create the lesion, wherein the controller is configured to activate a pressure regulator (<NUM>) between the cryogen supply (<NUM>, <NUM>, <NUM>) and the distal treatment section to modulate the pressure of the cryogenic fluid in the distal treatment section from a first fluid pressure to a second fluid pressure less than the first fluid pressure, and wherein the first fluid pressure is at a near critical pressure of the cryogenic fluid such that the molar volume of gas and the molar volume of liquid are equivalent, and wherein the second fluid pressure is below the near critical pressure of the cryogenic fluid, and
wherein modulating the pressure from the first fluid pressure to the second fluid pressure is carried out without increasing the molar volume of gas in the fluid, thereby avoiding vapor lock associated with cooling the medical device.