Ablation probe for drug release in tissue ablation procedures

Tissue ablation probes and methods for treating tissue are provided. The tissue ablation probe comprises an elongated probe shaft, at least one electrode carried by the distal end of the probe shaft, and a pharmaceutical agent carried by the probe shaft. The pharmaceutical agent may be disposed on the electrode(s), the probe shaft, or a releasable portion associated with the electrode or the probe shaft. A method for treating tissue comprises introducing a tissue ablation probe to a tissue site, operating the tissue ablation probe to ablate tissue at the tissue site, and releasing a pharmaceutical agent from the tissue ablation probe at the tissue site.

FIELD OF THE INVENTION

The field of the invention relates to medical devices, and more particularly, to apparatus and methods for delivering therapeutic agents to a site within a body.

BACKGROUND

The delivery of radio frequency (RF) energy to target regions within solid tissue is known for a variety of purposes of particular interest to the present invention. In one particular application, RF energy may be delivered to diseased regions (e.g., tumors) for the purpose of ablating predictable volumes of tissue with minimal patient trauma.

RF ablation of tumors is currently performed using one of two core technologies. The first technology uses a single needle electrode, which when attached to a RF generator, emits RF energy from an exposed, uninsulated portion of the electrode. The second technology utilizes multiple needle electrodes, which have been designed for the treatment and necrosis of tumors in the liver and other solid tissues. U.S. Pat. No. 6,379,353 discloses such a probe, referred to as a LeVeen Needle Electrode™, which comprises a cannula and an electrode deployment member reciprocatably mounted within the delivery cannula to alternately deploy an electrode array from the cannula and retract the electrode array within the cannula. Using either of the two technologies, the energy that is conveyed from the electrode(s) translates into ion agitation, which is converted into heat and induces cellular death via coagulation necrosis. The ablation probes of both technologies are typically designed to be percutaneously introduced into a patient in order to ablate the target tissue.

Following ablation of the target tissue, a transition zone, also described as a hemorrhagic ring, may remain between the dead ablated tissue and live tissue. Over time, the cells in the transition zone may die, or they may continue to live. Should the cells in the transition zone live, there is a risk that the cells carry the same disease as the ablated tissue and thus perpetuate the disease in healthy tissue. Without any preventative treatment, the diseased cells, and any healthy tissue to which the disease spreads, may require one or more follow-up ablation treatments.

To treat any remaining diseased cells, it is known in the art, for example, to follow an ablation procedure with additional treatment in the form of an ingested pharmaceutical agent. These ingested agents, however, circulate the body to locate any remaining diseased tissue, instead of being directly applied to the diseased tissue. This may delay treatment of the diseased tissue, in addition to possibly exposing healthy tissue to the pharmaceutical agent, which may have a toxic effect on the healthy tissue. Additionally, the pharmaceutical agent may be expelled from the body before the cells in the transition zone develop into diseased cells. It is also known in the art to follow an ablation procedure with an additional procedure in which a pharmaceutical agent is directly deposited in the ablated tissue region. However, depositing the pharmaceutical agent into the ablated tissue region would require focusing deposition of the pharmaceutical agent within the hemorrhagic ring, which may be difficult and burdensome to perform without killing healthy tissue. Furthermore, both examples comprise extra procedures in addition to the ablation procedure that may increase patient trauma.

Therefore, there is a need for preventing tissue surrounding an area of ablated tissue from developing into diseased tissue. There is also a need for treating tissue in conjunction with an ablation procedure to minimize the need for further ablation procedures.

SUMMARY OF THE INVENTION

The present inventions are directed to tissue ablation probes and methods for ablating tissue. The tissue ablation probes carry one or more electrodes that can be used to ablate tissue, and one or more pharmaceutical agents that can be released into the tissue. While the present inventions should not be limited in their broadest aspects, the use of a releasable pharmaceutical agent facilitates placement of the pharmaceutical agent at the region where tissue will or has been ablated by the electrode(s).

In accordance with a first aspect of the present inventions, a tissue ablation probe comprises an elongated probe shaft at least one electrode (e.g., a single electrode or an array of electrodes) carried by the distal end of the probe shaft. In an optional embodiment, the tissue ablation probe further comprises a cannula having an elongated cannula shaft and a lumen within the cannula shaft, wherein the probe shaft is slidably disposed within the cannula lumen, such that the at least one electrode is deployable from the cannula lumen.

The tissue ablation probe further comprises a releasable portion detachable from the electrode(s). In one embodiment, the releasable portion is configured to detach from the at least one electrode in response to electrical energy conveyed through the electrode. In this manner, the electrical energy may have the dual function of ablating tissue and detaching the releasable portion. The releasable portion may be attached to the electrode(s) in any one of a variety of manners. For example, the releasable portion is attached to the electrode(s) with a heat-degradable adhesive. As another example, the releasable portion is attached to the electrode(s) via an electrolytically disintegratable link. Other means of attaching releasable portions to electrode(s), such as mechanical activation, shape memory metal or shape memory polymer latches, etc., can be utilized.

The tissue ablation probe further comprises a pharmaceutical agent (e.g., a cancer-fighting drug) carried by the releasable portion. The pharmaceutical agent may be associated with the releasable portion in any one of a variety of manners. For example, the pharmaceutical agent may be disposed on the releasable tip or may even at least partially form the releasable portion.

In accordance with a second aspect of the present inventions, a tissue ablation probe comprises an elongated cannula shaft, a lumen within the cannula shaft, an elongated probe shaft slidably disposed within the cannula lumen, and an electrode array carried by a distal end of the probe shaft, wherein the electrode array is deployable from the cannula lumen. The tissue ablation probe further comprises a pharmaceutical agent (e.g., a cancer-fighting drug) carried by the electrode array. The pharmaceutical agent may be carried by the electrode in any one of a variety of manners. For example, the tissue ablation probe may further comprise a releasable portion detachable from at least one electrode of the electrode array, in which case, the pharmaceutical agent may be carried by the releasable portion. Or, the pharmaceutical agent may simply be disposed on the electrode(s).

In accordance with a third aspect of the present inventions, a tissue ablation probe comprises an elongated probe shaft and an electrode array carried by the distal end of the probe shaft. In an optional embodiment, the tissue ablation probe further comprises a cannula having an elongated cannula shaft and a lumen within the cannula shaft, wherein the probe shaft is slidably disposed within the cannula lumen, such that the electrode array is deployable from the cannula lumen. A releasable portion of the electrode array including substantially an entire electrode tine or tines of the array is configured to detach from a distal end of the probe shaft. In one embodiment, the releasable portion of the electrode array is configured to detach from the probe shaft in response to electrical energy conveyed through the electrode array. The releasable portion of the electrode array may be attached to the probe shaft in any one of a variety of manners. For example, the releasable portion of the electrode array may be coupled to the distal end of the probe shaft via a heat-degradable adhesive. As another example, the releasable portion of the electrode array may be coupled to the distal end of the probe shaft via one or more electrolytically disintegratable links. Other means for attaching releasable portions to the distal end of the probe shaft, such as mechanical activation, shape memory metal or shape memory polymer latches, etc., can be utilized. The tissue ablation probe further comprises a pharmaceutical agent (e.g., a cancer-fighting drug) carried by the releasable portion of the electrode array.

In accordance with a fourth aspect of the present inventions, a tissue ablation probe comprises an elongated probe shaft, at least one electrode carried by a distal end of the probe shaft, a releasable portion detachable from the distal end of the probe shaft, and a pharmaceutical agent (e.g., a cancer-fighting drug) carried by the releasable portion. In an optional embodiment, the at least one electrode comprises an array of electrodes, and the tissue ablation probe further comprises a cannula having an elongated cannula shaft and a lumen within the cannula shaft, wherein the probe shaft is slidably disposed within the cannula lumen, such that the electrode array is deployable from the cannula lumen. In this case, the releasable portion may be a tissue piercing tip directly attached to a distal end of the cannula shaft, and another pharmaceutical agent is carried by the electrode array.

In one embodiment, the releasable portion is configured to detach from the distal end of the probe shaft in response to electrical energy conveyed through the electrode. The releasable portion may be coupled to the distal end of the probe shaft in any one of a variety of manners. For example, the releasable portion is coupled to the distal end of the probe shaft via a heat-degradable adhesive. As another example, the releasable portion is coupled to the distal end of the probe shaft via an electrolytically disintegratable link. Other means of attaching releasable portions to probe shafts, such as mechanical activation, shape memory metal or shape memory polymer latches, etc., can be utilized. The pharmaceutical agent may be associated with the releasable portion in any one of a variety of manners. For example, the pharmaceutical agent may be disposed on the releasable portion or may even at least partially form the releasable portion.

In accordance with a fifth aspect of the present inventions, a method of treating tissue comprises introducing any one of the above-described tissue ablation probes to a tissue site, operating the tissue ablation probe to ablate tissue at the tissue site, and releasing or detaching the pharmaceutical agent, or the releasable portion at the tissue site.

DETAILED DESCRIPTION OF THE INVENTION

Referring toFIG. 1, a tissue ablation system10constructed in accordance with one embodiment of the present inventions, will now be described. The tissue ablation system10generally comprises an ablation probe12configured for introduction into the body of a patient for ablative treatment of target tissue, a source of ablation energy, and in particular a radio frequency (RF) generator14, and a cable16electrically connecting the ablation probe12to the RF generator14.

The RF generator14may be a conventional general purpose electrosurgical power supply operating at a frequency in the range from 300 kHz to 9.5 MHz, with a conventional sinusoidal or non-sinusoidal wave form. Such power supplies are available from many commercial suppliers, such as Valleylab, Aspen, Bovie, and Ellman. Most general purpose electrosurgical power supplies, however, are constant current, variable voltage devices and operate at higher voltages and powers than would normally be necessary or suitable. Thus, such power supplies will usually be operated initially at the lower ends of their voltage and power capabilities, with voltage then being increased as necessary to maintain current flow. More suitable power supplies will be capable of supplying an ablation current at a relatively low fixed voltage, typically below 200 V (peak-to-peak). Such low voltage operation permits use of a power supply that will significantly and passively reduce output in response to impedance changes in the target tissue. The output will usually be from 5 W to 300 W, usually having a sinusoidal wave form, but other wave forms would also be acceptable. Power supplies capable of operating within these ranges are available from commercial vendors, such as Boston Scientific Corporation. Preferred power supplies are models RF-2000 and RF-3000, available from Boston Scientific Corporation.

The ablation probe12comprises an elongated, rigid probe shaft18having a proximal end20and a distal end22. For the purposes of this specification, a shaft of a probe is rigid if it is generally not suitable to be advanced along a tortuous anatomical conduit of a patient, as contrasted to, e.g., guidewires and intravascular catheters. The probe shaft18has a suitable length, typically in the range from 5 cm to 30 cm, preferably from 10 cm to 25 cm, and an outer diameter consistent with its intended use, typically being from 0.7 mm to 5 mm, usually from 1 mm to 4 mm. In the illustrated embodiment, the probe shaft18is composed of an electrically conductive material, such as stainless steel. Alternatively, the probe shaft18may be composed of an electrically insulative material, such as plastic.

The ablation probe12also comprises an electrically insulative layer32disposed on the probe shaft to impart an insulative property to the shaft18. The insulative layer32comprises any material suited for its purpose, such as polyether ether ketone (PEEK) or fluorinated ethylene-propylene (FEP). Preferably, the insulative layer32is sized to cover most of the probe shaft18, with the exception of a distal tip of the probe shaft18. In this manner, an RF ablation electrode26is formed by the exposed portion of the distal tip. Thus, all of the RF energy is focused at the electrode26where the targeted tissue presumably lies, while the insulative layer32prevents RF energy conducted through the shaft18from damaging healthy tissue surrounding the shaft18. In an alternative embodiment, the electrode26is a discrete element mounted on the distal end22of the probe shaft18via suitable means, such as bonding or welding.

The ablation probe12further comprises a handle28mounted to the proximal end20of the probe shaft18. The handle28is preferably composed of a durable and rigid material, such as medical grade plastic, and is ergonomically molded to allow a physician to more easily manipulate the ablation probe12. The handle28comprises an electrical connector30with which the cable16(shown inFIG. 1) mates. Alternatively, the RF cable16may be hardwired within the handle28. The electrical connector30is electrically coupled to the ablation electrode26via the probe shaft18. Alternatively, if the probe shaft18is electrically insulative, the electrical connector30can be electrically coupled to the ablation electrode26via an internal conductor, such as a wire.

In the illustrated embodiment, the RF current is delivered to the electrode26in a monopolar fashion, which means that current will pass from the electrode26, which is configured to concentrate the energy flux in order to have an injurious effect on the surrounding tissue, and a dispersive electrode (not shown), which is located remotely from the electrode26and has a sufficiently large area (typically 130 cm2for an adult), so that the current density is low and non-injurious to surrounding tissue. The dispersive electrode may be attached externally to the patient, e.g., using a contact pad placed on the patient's flank.

In an alternative embodiment, another electrode (not shown) may be carried on the distal end22of the probe shaft18, along with the electrode26, in a bipolar fashion. Thus, when the RF energy is conveyed to the electrodes, the RF current passes between the electrodes; i.e., between a positive one of the electrodes and a negative one of the electrodes, thereby concentrating the energy flux in order to have an injurious effect on the tissue between the electrodes. In this bipolar arrangement, the electrodes will have to be electrically insulative from each other, in which case, the electrical connector30may be coupled to one or both of the electrodes26via separate wires, instead of through the probe shaft18.

The tissue ablation probe10further comprises a pharmaceutical agent34(best shown inFIG. 2), and in particular a cancer-fighting drug, such as doxorubicin, carried by the distal end22of the probe shaft18. The pharmaceutical agent34is carried by the distal end22such that it is releasable from the distal end22and may be deposited into the ablated tissue region either during or after a tissue ablation procedure. The pharmaceutical agent34remains in the ablated tissue region to treat any surviving diseased tissue, particularly in the hemorrhagic ring.

In one embodiment, the pharmaceutical agent34comprises a compound that is released over time, i.e. a time-releasable compound. This may be beneficial as there may not be any immediate indication after a tissue ablation process of whether any diseased tissue in the hemorrhagic ring has survived. The presence of surviving diseased tissue may only become evident over time, and possibly after the surviving diseased tissue has already spread to a significant portion of otherwise healthy tissue. The pharmaceutical agent34may thus treat any such surviving tissue more effectively if the agent34remains in the ablation region for an extended period. When the pharmaceutical agent34comprises a time-releasable compound, the agent34is less likely to prematurely dissipate or to be immediately absorbed into the surrounding bodily tissue, thus remaining in the ablated tissue region to treat the surviving diseased tissue.

The pharmaceutical agent34may be comprised of several materials, many of which may allow the agent to be released over time. In one embodiment, the pharmaceutical agent34comprises a bioabsorbable polymer that it is gradually absorbed by surrounding bodily tissue. In another embodiment, the pharmaceutical agent34may comprise a plurality of embolic particles, such as those described in U.S. Publication No. 2005/0020965, which is fully incorporated by reference herein. These embodiments serve as examples of how the pharmaceutical agent34may be comprised of a cancer-fighting agent or other treatment agent combined with bioabsorbable materials that regulate the rate at which the treatment agent is dissipated in the surrounding tissue region.

In the illustrated embodiment, the pharmaceutical agent34is carried on a releasable portion36detachable from the distal end22of the probe shaft18, as shown inFIG. 2. For example, the releasable portion36may be released from the distal end22, and in particular into the ablated tissue region, during or after operation of the probe12. Then, the releasable portion36may remain in the ablated tissue region to allow the pharmaceutical agent34to dissipate into the surrounding tissue, thus treating the hemorrhagic ring and any other surviving diseased tissue as described above.

In the illustrated embodiment, the releasable portion36has a conical shape with a sharpened point38to puncture skin, thereby allowing the probe12to be percutaneously introduced into a patient. Thus, it may be appreciated that, in this embodiment, the releasable portion36has the dual purpose of puncturing tissue to facilitate entry of the probe12and carrying the pharmaceutical agent34into the ablated tissue region. In alternative embodiments, the releasable portion36may have other shapes suitable for its purpose, such as cylindrical, if a tissue penetrating function is not needed.

As best shown inFIG. 2, the releasable portion36may be attached to the distal end22of the probe shaft18with a heat-degradable adhesive40; that is, the adhesive40forms an intermediary between a distal-facing surface of the distal end22of the probe shaft18and a proximal-facing surface of the releasable portion36. In one embodiment, the releasable portion36and the heat-degradable adhesive40are conductive and thus form a portion of the electrode26. Alternatively, electrical conductivity can be established across electrical connectors left uncovered by the heat-degradable adhesive40.

When the adhesive40is exposed to heat, the adhesive40degrades, allowing the releasable portion36, and likewise the pharmaceutical agent34, to detach from the distal end22of the probe shaft18, as illustrated inFIG. 3. In particular, the adhesive40may degrade from heat generated by electrical energy conducted on the electrode26during a tissue ablation procedure. Thus, electrical energy conducted on the electrode26has the dual effect of ablating target tissue and degrading the adhesive40, so the releasable portion36with the pharmaceutical agent34may be released into the ablated tissue region.

The releasable portion36may comprise a variety of materials suitable for carrying the pharmaceutical agent34. One such material is a biocompatible metal. When the releasable portion36is released from the distal end22of the probe shaft18, the biocompatible metal may remain in bodily tissue without imparting any significant negative effects, even after the pharmaceutical agent34has been fully dissipated into the surrounding bodily tissue.

Alternatively, the releasable portion36may be comprised of a biodegradable polymer or other biocompatible and/or biodegradable materials. It may be desired that such materials are heat-resistant, so that the releasable portion36may remain intact in the presence of heat generated from the electrode26. In yet another embodiment, the pharmaceutical agent34may partially or wholly form the releasable portion36.

The releasable portion36may carry the pharmaceutical agent34in several ways. The pharmaceutical agent34may be disposed on the releasable portion36, for example, by coating the releasable portion36, either wholly, or as shown inFIGS. 1-3, or partially.

In an alternative embodiment, illustrated inFIG. 4, instead of disposing the pharmaceutical agent34over the releasable portion36, the pharmaceutical agent34takes the form of releasable “seeds” distributed over the distal end22of the probe shaft18, and in particular, the electrode26. For example, the seeds34may be attached to the electrode26with heat-degradable adhesive (not shown) that allows the seeds34to be released from the electrode26into the ablated tissue region in the presence of heat. In this embodiment, the distal end22may further comprise indentations (not shown) for housing the seeds34.

Another tissue ablation probe52that can be used in conjunction with the RF generator14to create an alternative tissue ablation system will now be described. As illustrated inFIGS. 5-6, the tissue ablation probe52includes an elongated cannula54and an inner probe55slidably disposed within the cannula54.

The cannula54includes an elongate shaft58having a proximal end60, a distal end62, and a central lumen64(shown inFIG. 7). The cannula shaft58, itself, is composed of an electrically conductive material, such as stainless steel. The material from which the cannula shaft58is composed is preferably a rigid or semi-rigid material, such that the ablation probe52can be introduced through solid tissue to a target tissue site. The distal end62of the cannula shaft58comprises a tissue-penetrating tip68, which allows the ablation probe52to be more easily introduced through tissue, while minimizing tissue trauma. Alternatively, the ablation probe52may be introduced through the tissue with the aid of another cannula and trocar assembly, in which case, the cannula shaft58may be composed of a flexible material, and the distal end62may be blunted. The cannula shaft58has a suitable length, typically in the range from 5 cm to 30 cm, preferably from 10 cm to 25 cm, and an outer diameter consistent with its intended use, typically being from 0.7 mm to 5 mm, usually from 1 mm to 4 mm.

The inner probe55is slidably disposed within the cannula lumen64and includes an elongate shaft56having a proximal end76, a distal end78, and an electrode array80comprising a plurality of tines81carried by the distal end78of the probe shaft56. Like the cannula shaft58, the inner probe shaft56is composed of an electrically conductive material, such as stainless steel. The inner probe shaft56is composed of a suitably rigid material, so that it has the required axial strength to slide within the cannula lumen64.

The ablation probe52further includes a handle assembly82, which includes a handle member84mounted to the proximal end76of the inner probe shaft56, and a handle sleeve86mounted to the proximal end60of the cannula54. The handle member84is slidably engaged with the handle sleeve86(and the cannula54). The handle member84and handle sleeve86can be composed of any suitable rigid material, such as, e.g., metal, plastic, or the like. The handle assembly82also includes an electrical connector88mounted within the handle member84. The electrical connector88is electrically coupled to the electrode array80via the inner probe shaft56. The electrical connector88is configured for mating with the proximal end of the RF cable16(shown inFIG. 1). Alternatively, the RF cable16may be hardwired within the handle member84. Like the previously described ablation probe12, RF current may be delivered to the electrode array80in a monopolar fashion.

It may be readily appreciated that longitudinal translation of the probe shaft56relative to the cannula54in a distal direction90can be achieved by holding the handle sleeve86and displacing the handle member84in the distal direction90, thereby deploying the electrode array80from the distal end62of the cannula shaft58(FIG. 6), and longitudinal translation of the probe shaft56relative to the cannula54in a proximal direction92can be achieved by holding the handle sleeve86and displacing the handle member84in the proximal direction92, thereby retracting the probe shaft56and the electrode array80into the distal end62of the cannula54(FIG. 5). Further details regarding electrode array-type probe arrangements are disclosed in U.S. Pat. No. 6,379,353, which has previously been incorporated herein by reference.

The tissue ablation probe52further comprises the pharmaceutical agent34disposed on a distal portion of the probe52. The pharmaceutical agent34may comprise a time-releasable compound, and may further comprise a bioabsorbable polymer, an embolic particle, or other embodiments, as discussed above.

As illustrated inFIG. 8, the pharmaceutical agent34may be carried on a plurality of releasable portions66that are releasably attached to all or a portion of tines81in the electrode array80. In the embodiment shown inFIG. 8, the releasable portions66include distal tips of the tines81. In one embodiment, the releasable portions66are conductive and thus form a portion of the electrode array80. The releasable portions66may also have sharpened distal tips (not shown) in order to penetrate surrounding tissue.

This embodiment has the benefit of having multiple releasable portions66that can be released into multiple sites in the ablated tissue region. Additionally, the deployment of the electrode array80may cause parts of the releasable portions66to become implanted in the target tissue region, causing the releasable portions66to be more stationary for treating tissue in that region. Furthermore, the electrode array80structure allows the releasable portions66to be released from the array80in an approximate ring formation, as shown inFIG. 9. Thus, the releasable portions66are deposited in a pattern approximating that of the hemorrhagic ring, which may increase the efficiency with which the pharmaceutical agent34treats any surviving diseased cells in the hemorrhagic ring.

As illustrated inFIG. 8, each releasable portion66may be attached to the tines81with a heat-degradable adhesive (not shown), allowing the releasable portions66to be detached when heat generated on the electrode array80causes the adhesive to degrade, as shown inFIG. 9. If the releasable portions66form a portion of the electrode array80, it may be desirable for the adhesive to be electrically conductive, so that RF energy may be conducted to the releasable portions66for ablating a larger region of tissue.

In another embodiment, illustrated inFIG. 10, each of the releasable portions66may be attached to the tines81with an electrolytically disintegratable link83(enlarged for illustration). The link83is severable by electrolysis in an aqueous environment, such as bodily tissue. The link83may be composed of steel, stainless steel, nickel, nickel/titanium alloys, or other materials which will electrolytically dissolve as their ions are transferred, i.e., as electrolytic action occurs in an aqueous fluid medium. As electricity is conveyed to the electrode array80, electrolytic action causes the link83to disintegrate and detach the releasable portion66.

While the above-described embodiments of the releasable portions66may include a variety of forms, it is preferable that when the releasable portion66is releasably attached to the electrode array80, the releasable portion66has a rod-like shape with a gauge approximate to that of the electrode tines81. This is so the electrode array80may be easily deployed from the distal end62of the cannula54. As described above, the releasable portion66may also comprise a variety of materials, such as biocompatible or bioabsorbable metals, polymers, and/or ceramics. Alternatively, the pharmaceutical agent34may partially or wholly form the releasable portion66, as previously described.

Also as previously described, the releasable portions66may carry the pharmaceutical agent34in several ways when the releasable portions66are releasably attached to the electrode array80. For example, the pharmaceutical agent34may be disposed over the releasable portions66by coating the releasable portions66, as described above.

As an alternative to having a releasable portion66, the pharmaceutical agent34may be disposed on and released from the electrode array80. For example, as illustrated inFIG. 11, the pharmaceutical agent34may take the form of seeds distributed over the electrode array80. The seeds34may be releasably attached to the electrode array80with heat-degradable adhesive (not shown), so that the seeds34are released into the ablated tissue region when the adhesive degrades from heat generated on the electrode array80.

In another embodiment, shown inFIGS. 12A and 12B, the releasable portion66includes substantially an entire tine81or tines81of the electrode array80. In the illustrated embodiment, portions of the tines81remain attached to the distal end78of the probe shaft56, as shown inFIG. 12A. Thus, when the releasable portion66, in this case tines81of the array80, detaches from the probe shaft56as shown inFIG. 12B, the tines81may remain in the ablated tissue region even when the probe shaft56is removed from the patient while the pharmaceutical agent34dissipates. The releasable portion66of the electrode array80may be releasably attached with a heat-degradable adhesive (not shown), which may be electrically conductive, as previously described. Thus, the releasable portion of the electrode array80carrying the pharmaceutical agent34detaches in response to electrical energy conducted through the array80.

In another embodiment, the releasable portion66of the array80may be releasably attached to a stationary portion of the array80with the electrolytically disintegratable link83, similar to that shown inFIG. 10, such that detachment results when the link83disintegrates in response to electricity conducted through the array80. In still another embodiment, the releasable portion66can be mechanically released by coupling the tines81to the remaining portion of the electrode array80via a mechanical connection (e.g., an anchor and hook) that activates when the electrode array80is fully deployed. In this case, ablation can occur when the electrode array80is less than fully deployed, after which, the electrode array80can be fully deployed to detach the releasable portion66from the probe shaft78.

The releasable portion66of the electrode array80may be comprised of, for example, a biocompatible or bioabsorbable metal, polymer, and/or ceramic. Thus, when the releasable portion66of the array80detaches from the distal end78of the probe shaft56to remain in the ablated tissue region, the array80will not impart any significant negative effects on surrounding bodily tissue.

In an alternative embodiment, illustrated inFIG. 13the releasable portion66may include a hollow portion100that carries the pharmaceutical agent34. The hollow portion100may be pre-filled with the pharmaceutical agent34. Alternatively, the hollow portion100may be in fluid communication with an additional lumen (not shown) in the probe shaft56that carries the pharmaceutical agent34, such that during or after the delivery of energy to the electrode array80, the pharmaceutical agent34may be injected from the additional lumen into the hollow portion100. This may be desirable if the pharmaceutical agent34is heat-sensitive to prevent degradation during the ablation process.

Thus, the releasable portion66of the electrode array80carries the pharmaceutical agent34upon disengagement and releases the pharmaceutical agent34from the hollow portion100. This may happen immediately, for example, if the pharmaceutical agent34exits through an opening in the releasable portion66, or over time, if the releasable portion66is porous, bioabsorbable, or biodegradable. In this embodiment, the releasable portion66of the electrode array80is connected to the probe12, for example with the heat-degradable adhesive40, such that there is a continuous channel in fluid communication with the additional lumen, allowing the hollow portion100to receive the pharmaceutical agent34.

In another embodiment, it may also be desirable for the distal end22of the probe12to include an opening (not shown) in fluid communication with the additional lumen, such that the pharmaceutical agent34may be delivered from the additional lumen through the opening to the target tissue site. This may be desirable if the pharmaceutical agent34is heat-sensitive, to ensure there is sufficient pharmaceutical agent34that has not been altered by heat from the RF energy to treat the ablated tissue region.

In an alternative embodiment, instead of the array80being deployed through the distal end62of the cannula54, the array80may be deployed through slots85on sides of the distal end62of the cannula shaft58, as shown inFIG. 14. In this embodiment, a pharmaceutical agent (not shown) may be carried by releasable portions on the array, or on the array80, as described above.

In another embodiment, as shown inFIG. 15, the distal end62of the cannula54may comprise a closed tissue-penetrating tip57. This allows the cannula54to be more easily introduced through tissue, while preventing tissue coring and minimizing tissue trauma. The tissue-penetrating tip57may carry the pharmaceutical agent34and thus be releasably attached to the distal end62of the cannula54with the heat-degradable adhesive40.

In addition, the cannula54further comprises side slots85, similar to those shown inFIG. 14, such that the when the inner probe shaft56is advanced through the cannula54, the electrode array80is deployed through the side slots85. The electrode array80may also have releasable portions66carrying the pharmaceutical agent34, or the array80may carry the pharmaceutical agent34, as described above.

As an alternative to the probes12,52described above, a co-access probe assembly102may also be used, as shown inFIGS. 16 and 17. The co-access probe assembly102comprises a delivery cannula108, a biopsy stylet110, and a tissue ablation probe112. The biopsy stylet110and ablation probe112are configured to be alternately introduced through the delivery cannula108in contact with the tissue to be treated. Additionally, either the biopsy stylet110, the ablation probe112, or a separate trocar (not shown) can be used to facilitate the percutaneous introduction of the delivery cannula108, which has a blunt end.

The delivery cannula108comprises a cannula shaft114having a proximal end116and a distal end118, and a delivery lumen120extending therebetween. The cannula shaft114has a suitable length, and may be rigid, semi-rigid, or flexible, depending upon the designed means for introducing the delivery cannula108to the target tissue. The delivery cannula108further comprises a handle124mounted to the proximal end116of the cannula shaft114.

The biopsy stylet110comprises a solid elongated shaft128with a tissue-penetrating distal tip130and a proximal handle piece132. The biopsy stylet110may be operated in a standard manner to obtain a tissue sample. For example, the biopsy stylet110may comprise a grooved notch (not shown) configured to extract and hold a tissue sample from a patient. Further details regarding the structure and use of biopsy stylets in association with cannulae are disclosed in U.S. Pat. No. 5,989,196, which is expressly incorporated herein by reference. In an alternative embodiment, if no tissue sample is required, a trocar (not shown) may be used in place of the stylet110to penetrate tissue and carry the delivery cannula108to the treatment site.

The tissue ablation probe112is similar to the tissue ablation probe52illustrated inFIGS. 5-7, in that it comprises a cannula134and an inner probe shaft136slidable within the cannula134. A proximal handle assembly138with an electrical connector139can be manipulated to distally advance the inner probe shaft136through the cannula134, thereby deploying an electrode array140from the cannula134, as shown inFIG. 17. In an alternative embodiment, the use of the cannula134is foregone, so that the inner probe shaft136is slidably disposed in direct contact with the cannula shaft114.

Similar to the embodiments described above, the pharmaceutical agent34may be carried on releasable portions66that are releasably attached to tines141of the electrode array140with a heat-degradable adhesive, or the pharmaceutical agent34may comprise seeds34releasably attached to the array140. In another embodiment, the pharmaceutical agent34may be disposed on the array140, wherein at least a portion of the array140is releasable from the probe shaft136, as described above.

Having described the structure of the tissue ablation system10, its operation in treating targeted tissue will now be described. The treatment region may be located anywhere in the body where hyperthermic exposure may be beneficial. Most commonly, the treatment region will comprise a solid tumor within an organ of the body, such as the liver, kidney, pancreas, breast, prostrate (not accessed via the urethra), and the like. The volume to be treated will depend on the size of the tumor or other lesion, typically having a total volume from 1 cm3to 150 cm3, and often from 2 cm3to 35 cm3The peripheral dimensions of the treatment region may be regular, e.g., spherical or ellipsoidal, but will more usually be irregular. The treatment region may be identified using conventional imaging techniques capable of elucidating a target tissue, e.g., tumor tissue, such as ultrasonic scanning, magnetic resonance imaging (MRI), computer-assisted tomography (CAT), fluoroscopy, nuclear scanning (using radiolabeled tumor-specific probes), and the like. Preferred is the use of high resolution ultrasound of the tumor or other lesion being treated, either intraoperatively or externally.

Referring now toFIGS. 18A and 18B, the operation of the tissue ablation system10is described in treating a treatment region TR with tissue T located beneath the skin or an organ surface S of a patient. The ablation probe12is first introduced through the tissue T under the guidance of a conventional ultrasound imaging device, so that the electrode26is located at a target site TS within the treatment region TR, as shown inFIG. 18A. This can be accomplished using any one of a variety of techniques. In the preferred method, a delivery device, such as a probe guide (not shown), is used to guide the ablation probe12towards the target site TS. In particular, the probe guide is affixed and aligned relative to the target site TS, and the ablation probe12is introduced through the probe guide. Facilitated by the sharpened tip38on the releasable tip36, the ablation probe12is percutaneously introduced through the patient's skin until the electrode26is located in the treatment region TR.

Once the ablation probe12is properly positioned, the cable16of the RF generator14(shown in FIG.1)is then connected to the electrical connector30of the ablation probe12, and then operated to transmit RF energy to the electrode26, thereby ablating the treatment region TR, as illustrated inFIG. 18B. As a result, a lesion L will be created, which will eventually expand to include the entire treatment region TR. The ablation also results in the creation of a hemorrhagic ring HR around the lesion L.

Next, the pharmaceutical agent34is released from the ablation probe12into the lesion L and hemorrhagic ring HR area. In the illustrated method, as RF energy is transmitted to the electrode26, the heat generated on the electrode26causes the adhesive40(shown inFIGS. 2 and 3) to degrade, allowing the releasable portion36to be released into the lesion L and hemorrhagic ring HR area, as shown inFIG. 18C. In the embodiment for which the pharmaceutical agent34comprises seeds distributed over the releasable portion36(shown inFIG. 4), the heat generated on the electrode26causes the adhesive that secures the seeds34to the releasable portion36to degrade, allowing the seeds34to be released into the lesion L and hemorrhagic ring HR area, as shown inFIG. 18D.

The pharmaceutical agent34may then remain in the lesion L and hemorrhagic ring HR area to be released over time to treat any surviving diseased tissue. The releasable portion36, if in the embodiment used, may also remain in the ablated tissue region, or it may dissolve or degrade, depending upon the material selected for the releasable portion36.

In an alternative method, the ablation probe52illustrated inFIGS. 5 and 6may be used to ablate tissue by guiding the distal end62of the cannula54to the target site TS, after which the inner probe shaft56can be distally advanced through the cannula54to deploy the electrode array80out from the distal end62of the cannula54, as shown inFIG. 19A. Alternatively, using the embodiment shown inFIG. 14, the array80may be deployed through the side slots85on the distal end62of the cannula54.

As previously discussed, once the ablation probe52is properly positioned, the cable16of the RF generator14(shown inFIG. 1) is then connected to the electrical connector88of the ablation probe52, and then operated to transmit RF energy to the electrode array80, thereby ablating the treatment region TR, as illustrated inFIG. 19B. As a result, lesion L will be created, encircled by hemorrhagic ring HR.

For the embodiment in which the releasable portions66are carried on the electrode array80(shown inFIGS. 8 and 9), the heat generated on the array80by the RF energy causes the adhesive to degrade, allowing the releasable portions66to be released into the ablated tissue region, as shown inFIG. 19C. Alternatively, if the releasable portions66are attached to the tines81of the electrode array80via electrolytic links83(as shown inFIG. 10), the releasable portions66will detach from the tines81when the links83electrolytically dissolve in response to current flowing through the electrode array80.

In the embodiment in which the pharmaceutical agent34comprises seeds disposed on the array80(shown inFIGS. 10 and 11), the heat generated on the array80causes the adhesive that secures the seeds34to the releasable portions66to degrade, allowing the seeds34to be released into the ablated tissue region, as shown inFIG. 19D, where the seeds34remain to treat any remaining diseased tissue.

In the embodiment in which the releasable portion66includes substantially an entire tine81or tines81of the electrode array80, and the pharmaceutical agent34coats the releasable portion66(shown inFIGS. 12 and 13), the heat generated on the array80causes the adhesive to degrade, allowing the tine(s)81to be released into the ablated tissue region, as shown inFIG. 19E. The tine(s)81may remain in the ablated tissue region, while the pharmaceutical agent34dissipates into the ablated tissue region to treat any remaining diseased tissue.

In the embodiment in which the releasable portion66includes the hollow portion100in communication with an additional lumen, the pharmaceutical agent34may be injected from the additional lumen into the hollow portion100during or after the RF energy is delivered to the electrode array80. Alternatively, the pharmaceutical agent34may already be carried within the hollow portion100of the releasable portion66. When the releasable portion66is released into the ablated tissue region, the pharmaceutical agent34is released from the hollow portion100. In an alternative embodiment, the pharmaceutical agent34may be delivered from the additional lumen to the ablated tissue region through the opening at the distal end22of the probe12, to help ensure a sufficient amount of pharmaceutical agent34is distributed to the ablated tissue region.

Referring toFIG. 20, RF energy is transmitted to the electrode array80of the embodiment illustrated inFIG. 15to ablate the tissue region, creating lesion L encircled by hemorrhagic ring HR. Depending on the embodiment used, the heat generated on the array80causes the adhesive40(shown inFIG. 15) to degrade, allowing the tip57of the cannula54to be released into the ablated tissue region.

In another method, the co-access assembly102shown inFIGS. 16 and 17may be used to ablate tissue. In the preferred method, the biopsy stylet110is introduced into the delivery cannula108, and then the cannula108with the stylet110is percutaneously introduced through the patient's skin to the treatment region TR, as shown inFIG. 21A. The biopsy stylet110is manipulated to retrieve a tissue sample from the patient, and then removed from the delivery cannula108, while the delivery cannula108remains in position. Next, the probe112is introduced into the delivery cannula108until a distal end of the inner probe shaft136is located at the target site TS, after which the inner probe shaft116can be distally advanced through the cannula114to deploy the electrode array140, as shown inFIG. 21B.

Alternatively, if a distal end of the inner probe shaft136is sharpened, the probe112may be introduced into the delivery cannula108and then percutaneously introduced through the patient's skin, instead of the stylet110, and advanced to the treatment region TR. Then, the electrode array140may be deployed as described above.

As previously discussed, once the ablation probe112is properly positioned, the cable16of the RF generator14(shown inFIG. 1) is then connected to an electrical connector (not shown) on the ablation probe112, and then operated to transmit RF energy to the electrode array140, thereby ablating the treatment region TR, as illustrated inFIG. 21B. As a result, lesion L will be created, encircled by hemorrhagic ring HR.

For the embodiment in which the releasable portions66are carried on the electrode array140, the heat generated on the array140by the RF energy causes the adhesive40to degrade, allowing the releasable portions66, and thus the pharmaceutical agent34, to be released into the ablated tissue region, as shown inFIG. 21C. There, the releasable portions66and the pharmaceutical agent34may remain to treat any surviving diseased tissue.

In the embodiment in which the electrode array140is releasable from the inner probe shaft136and the pharmaceutical agent34coats the array140, the heat generated on the array140causes the adhesive40to degrade, allowing the tines141to be released into the ablated tissue region, as shown inFIG. 21D. The tines141may remain in the ablated tissue region, while the pharmaceutical agent34dissipates into the ablated tissue region to treat any remaining diseased tissue.