Patent Application
20060178662
The present invention pertains generally to systems and methods for effectively cryoablating target tissue. More particularly, the present invention pertains to methods for cryoablating tissue using specific freezing/thawing regimens. The present invention is particularly, but not exclusively, useful as a method for cryoablating tissue using a relatively fast cooling rate followed by a controlled relatively slow warming rate to minimize the probability of tissue cell survival.
It is well known that some (if not all) types of tissue cells can remain viable after being frozen and subsequently thawed. Indeed, tissue cells are often frozen to preserve the cells and research is ongoing with the ultimate goal that someday, whole organs may be completely and effectively preserved by freezing. Such an achievement would, hopefully, increase the transplant success rate and prolong the storage life of major organs prior to transplantation.
On the other hand, when the aim is to destroy diseased tissue, for example by using cryoablation techniques, cell survivability poses a serious obstacle. In fact, for almost all cryoablation procedures, the objective is complete ablation (i.e. destruction) of the targeted tissue. For example, it is often desirable to cryoablate internal tissue in a relatively non-invasive procedure. For this purpose, cryocatheters have been developed, such as the cryocatheter and associated refrigeration system that is disclosed in co-pending U.S. patent application Ser. No. 10/243,997, entitled “A Refrigeration Source for a Cryoablation Catheter.” Co-pending U.S. application Ser. No. 10/243,997 was filed on Sep. 12, 2002, is assigned to the same assignee as the present invention, and is hereby incorporated by reference herein. In one exemplary application of a cryocatheter, conduction blocks can be created that are particularly effective for curing heart arrhythmias, such as atrial fibrillation.
In a typical cryocatheter procedure, a cryoelement located at the distal end of the applicator is positioned near or in contact with the tissue requiring ablation (i.e. the target tissue). Next, a fluid refrigerant is expanded within the cryoelement, cooling the cryoelement to a cryogenic temperature to thereby cryoablate the target tissue. Heretofore, the standard practice has been to continue the expansion of refrigerant in the cryoelement to maintain the tissue in a frozen state for a predetermined residence time (e.g. 5 minutes). At the completion of the residence time, the standard practice has been to discontinue the expansion of refrigerant inside the cryoelement, allowing the tissue to passively warm and thaw at a rate dictated by the absorption rate of surrounding body heat by the affected tissue. Since little attention has been directed toward controlling the cooling or warming rates, the goal of complete target tissue destruction has not always been obtained.
In addition to cryocatheters, exposed tissue can be also destroyed using a cryoprobe. For example, a suitable cryoprobe and associated refrigeration system for destroying exposed tissue is disclosed in co-pending U.S. patent application Ser. No. 10/646,486, entitled “Reshapeable Tip for a Cryoprobe.” Co-pending U.S. application Ser. No. 10/646,486 was filed on Aug. 22, 2003, is assigned to the same assignee as the present invention, and is hereby incorporated by reference herein.
Experiment has shown that there are effectively at least three mechanisms, operable during cooling, which are responsible for causing cell death when tissue is frozen. The two main mechanisms are referred to, hereinafter, respectively, as “solution effects” and “intracellular freezing”. For most cell types, the percentage of cells which survive the cooling step is dependent on the cooling rate used to freeze the tissue and the lowest tissue temperature obtained during cooling. Moreover, some tissue cells exhibit a maximum cell survivability percentage at a certain cooling rate. As detailed further below, a portion of cells that survive the cooling step may be subsequently killed when the surviving cell is warmed to its original temperature.
The so-called “solution effects” result from four identifiable phenomena that occur simultaneously during freezing. These phenomena are: 1) a dehydration of the cell; 2) the concentration of solutes; 3) a decrease in cell size; and 4) the precipitation of solutes. On the other hand, as the name implies, “intracellular freezing” results in the freezing of water inside a tissue cell. Although water will freeze inside a tissue cell in both instances, it has been observed that if the “solution effects” predominate, there will be less water inside the cell to be frozen. This is due to dehydration and diminished cell size during freezing.
As a general proposition, it can be said that “solution effects” will predominate when the freezing velocity (i.e. the cooling rate) of tissue cells is relatively slow, and the cell permeability to water is high. On the other hand, “intracellular freezing” will predominate when the cooling rate is relatively fast, and the cell permeability to water is low. Moreover, it has also been observed that when the cooling rate is relatively fast and “intracellular freezing” predominates, relatively small ice crystals will form in the frozen water. This factor becomes important when the warming of the frozen tissue cells is considered.
During the warming of frozen tissue cells, it can happen that smaller ice crystals tend to experience a grain growth phenomenon referred to as “recrystallization”. This phenomenon occurs due to the high surface free energies of the small ice crystals, and results in the creation of larger crystals. Importantly for the present invention, it has been observed that recrystallization is most pronounced when tissue cells are warmed relatively slowly. It has been further observed that there is a higher probability the tissue cells will not survive when significant recrystallization is allowed to occur than when recrystallization is minimal or absent.
In light of the above, it is an object of the present invention to provide systems and methods suitable for the purposes of effectively cryoablating target tissue. It is another object of the present invention to provide systems and methods for cryoablating target tissue using specific freezing/thawing regimens which minimize the probability of tissue cell survival. It is yet another object of the present invention to provide systems and methods for controlling a cryocatheter to effectuate a pre-selected regimen of tissue cooling and warming rates. Yet another object of the present invention is to provide systems and methods for cryoablating target tissue which are easy to use, relatively simple to implement, and comparatively cost effective.
The present invention is directed to systems and methods for cryoablating tissue cells. More specifically, the invention is directed to the cryoablation of tissue cells that can be characterized by a relationship of cooling rate versus cell survivability percentage that exhibits a maximum cell survivability percentage at a cooling rate, RMAX.
While it is not necessarily intended that all aspects of the present invention be limited by any one theory or mechanism of cryoablation, for tissue cells exhibiting a maximum cell survivability percentage at a cooling rate, RMAx, the invention recognizes that effective cell cryoablation can be achieved using a regimen of selected cooling and warming rates. Specifically, for the invention, cells are typically ablated by first cooling the cells at a relatively fast cooling rate (e.g. greater than 200° C. per minute delivered to the tissue) and subsequently allowing the cells to warm at a controlled, relatively slow warming rate (e.g. less than 100° C. per minute). In general, this warming rate is slower than the rate of passive warming as might occur when cooling is abruptly removed.
During cooling, the temperature of the cells is reduced to below the minimum temperature (e.g. minus 10-15° C.) required to cause the cells to freeze. More typically, the cells are cooled to a temperature (e.g. minus 70° C. to minus 80° C. at the tissue surface) that is substantially below the minimum freezing temperature. In one aspect of the invention, the cells are cooled at a rate greater than the rate, RMAX, (where the maximum cell survivability percentage occurs) causing intracellular freezing of the tissue cells and the formation of relatively small ice crystals. Subsequently, during warming at a relatively slow warming rate, the small ice crystals recrystallize and grow, causing a relatively high rate of cell destruction. The result is an effective way to cryoablate the tissue cells with a relatively low probability of cell survival. Moreover, the cooling/warming cycle can be repeated, as desired, to further decrease the probability of cell survival.
Operationally, the methods of the invention are typically performed using an applicator, such as a probe or catheter, having a cryoelement positioned at the applicator's distal end. Typically, the cryoelement is formed with an expansion chamber to allow a fluid refrigerant to expand therein and cool the cryoelement. Supply and return lines are placed in fluid communication with the expansion chamber to respectively deliver a fluid refrigerant to the chamber for expansion therein and exhaust the expanded refrigerant therefrom.
In use, the cryoelement is first positioned proximate the target tissue (i.e. in contact with or close enough to the target tissue to cause a significant, measurable change in target tissue temperature in response to a change in cryoelement temperature). Once the cryoelement is proximate the target tissue, refrigerant is delivered to and expanded in the expansion chamber to cool the cryoelement and target tissue. Refrigerant then flows out of the chamber through the return line. In one implementation, the flow of coolant through the chamber is varied to achieve the cooling and warming rates described above. For example, a control valve operable on the supply line can be selectively adjusted to vary the flow of coolant through the chamber. Typically, during the cooling stage, a pre-selected, substantially constant flow of coolant is maintained. On the other hand, during the warming stage, the flow of coolant is slowly reduced until the tissue cells have warmed to a pre-selected temperature.
The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which:
Referring initially to
Turning now to
Continuing now with reference to
Continuing with cross reference to
In one embodiment of the present invention, a fluid refrigerant is used that transitions from a liquid state to a gaseous state as it expands into the expansion chamber 44 of the cryoelement 40. A suitable refrigerant supply unit 32 for delivering a refrigerant in a liquid state to the distal end of the restriction tube 50 for transition to a gaseous state in the expansion chamber 44 is disclosed in co-pending, co-owned U.S. patent application Ser. No. 10/243,997, entitled “A Refrigeration Source for a Cryoablation Catheter” and filed on Sep. 12, 2002. Co-pending U.S. patent application Ser. No. 10/243,997 was previously incorporated by reference herein. Heat absorbed by the refrigerant during the liquid to gas phase transition (i.e. latent heat) cools the cryoelement 40. After expansion, the gaseous fluid refrigerant passes through the return line 52 and exits at the proximal end 26 of the cryocatheter 24. In one implementation, nitrous oxide is used as the refrigerant with suction applied to the return line 52 allowing the cryoelement 40 to be cooled to a temperature of approximately −85 degrees Celsius. For the system 20, the cryoelement 40 is made of a thermally conductive material (e.g. metal) to allow heat to flow easily between the chamber 44 and the target tissue.
As best seen by cross-referencing
For the present methods, effective cell cryoablation is achieved using a regimen of selected cooling and warming rates. Specifically, as shown in
After intracellular freezing, the cells are warmed at a relatively slow warming rate, causing the small ice crystals to recrystallize and grow. This process leads to a relatively high rate of cell destruction. The result is an effective way to cryoablate the tissue cells with a relatively low probability of cell survival. In a typical implementation, cells are ablated by first cooling the cells at a relatively fast cooling rate (e.g. greater than 200° C. per minute at the tissue surface) and subsequently allowing the cooled cells to warm at a controlled, relatively slow warming rate (e.g. less than 100° C. per minute). In some applications, a warming rate of less than 50° C. per minute is used, while other applications are performed using a warming rate between 10-50° C. per minute. In certain cases, some tissue cells are destroyed by thrombosis of the included microcirculation (i.e. starvation or suffocation).
One way to effectuate the cooling/warming regimen described above is to vary the flow of fluid refrigerant in the supply line using the valve 58. Once the cryoelement 40 is proximate the target tissue as shown in
While the particular Warming Gradient Control For A Cryoablation Applicator and corresponding methods of use as herein shown and disclosed in detail are fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that they are merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.
