Patent Application
20090281477
1. Field of the Invention
The present application relates generally to devices and methods for tissue treatment using Irreversible Electroporation (IRE). More specifically, the application relates to devices and methods for treatment of tissue through the application of pulsed electric fields that create nonthermal cellular effects and that can be applied at a level of sufficient strength so as to result in ablation of tissue.
2. Description of the Related Art
The application of an electric field to transiently permeabilize cells is a method known as reversible electroporation. In such as a case, membrane defects are created and later reseal, allowing a time when macromolecules can be introduced across the cell membrane. This has been used, for example, to insert genes into cells (electrogenetherapy), and to insert anti-cancer drugs into cells (electrochemotherapy). A primary goal of reversible electroporation is to lead to cellular defects that allow passage of macromolecules awhile still allowing cell survival.
Irreversible electroporation (IRE) is a novel method of applying electrical fields across tissue through a delivery of pulses that effectively result in membrane permeabilization and in cell necrosis. IRE has been discussed in the following publication, which is hereby incorporated by reference: Rubinsky B., Onik G., Mikus P. “Irreversible Electroporation: A New Ablation Modality—Clinical Implications.” Technology in Cancer Research and Treatment. Vol. 6(1):37-48 (2007).
Devices and methods of the present application can be suitable for deliver of gradients of electric fields in a pulsed manner for certain tissue treatments, including but not limited to ablation purposes. For pulsed electric field ablation treatments, a selected ablation voltage threshold with a field strength of 0.25 kV/cm or greater can outline an ablation volume within the electric field gradient, which emanates radially from the voltage delivery regions with decreasing field strengths. During pulsed electric field ablation treatments, tissue at a specific point within the ablation volume can be subjected to an electric field having a field strength equal to or greater than a selected ablation voltage threshold, with tissue points closer to the single probe of the device being subjected to voltages fields of greater strengths.
One embodiment of the device includes a first voltage deliverer member wherein the first voltage delivery member includes a single tissue piercing tip and a first voltage delivery region: a second voltage delivery member extending along the probe, wherein the second voltage delivery member includes a second voltage delivery region; and an electrically insulating region extending along the probe and that separates the first and second voltage delivery regions. The first and second voltage delivery regions and the electrically insulating region in one embodiment have substantially equivalent outer diameters and are configured for electroporative ablation of tissue a tissue volume. In another embodiment the ablation involves a mammalian tissue volume. In yet another embodiment the ablation volume can have a ratio of diameter to length being 1:2 or greater.
One example method of tissue treatment includes: utilizing the device disclosed herein, positioning the first and second voltage delivery regions within or adjacent to a selected volume of tissue, and energizing the device to deliver pulsed electric fields to the selected volume of tissue.
An additional method of tissue treatment includes: utilizing a device with a probe having two or more coaxially arranged voltage delivery regions, positioning the two or more voltage delivery regions within or adjacent to a selected volume of tissue, and energizing the device to deliver pulsed electric fields to the selected volume of tissue. The voltage pulses in certain embodiments can be delivered to generate an electric field strength of 0.25 kV/cm with a pulse duration of up to 100 microseconds, and with a time between pulses being 0.15 seconds or longer. In other embodiments the voltage pulses can be delivered to generate an electric field strength of up to 2.5 kV/cm. In yet other embodiments the electric field strength can be between 2.5-3.0 kV/cm. The pulses can be delivered in a nonthermal method. In one embodiment the pulses are delivered so as to ensure that the temperature of the tissue did not exceed 50° C.
A more complete understanding of the present invention can be derived by referring to the detailed description when considered in connection with the following illustrative figures. In the figures, like reference numbers refer to like elements or acts throughout the figures. Throughout the specification, the term “distal” is consistently used in reference to the device or portion of the device farthest from the user and “proximal” refers to the end closest to the user of the device.
Elements and acts in the figures are illustrated for simplicity and have not necessarily been rendered according to any particular sequence or embodiment.
In the following description, and for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the various aspects of the invention. It will be understood, however, by those skilled in the relevant arts, that the present invention can be practiced without these specific details. In other instances, known structures and devices are shown or discussed more generally in order to avoid obscuring the invention. In many cases, a description of the operation is sufficient to enable one to implement the various forms of the invention. It should be noted that there are many different and alternative configurations, devices and technologies to which the disclosed inventions can be applied. The full scope of the inventions is not limited to the examples that are described below.
Probe 10 can include at least two voltage delivery regions 12 and 14, which can be electrically insulated from each other and disposed along the length of the body portion of probe 10. Probe 10 can further include at least one electrically insulating region 13 that separates the at least two voltage delivery regions 12 and 14 in a manner sufficient (such as having a length sufficient) to prevent electrical shorting as well as to prevent arcing between voltage delivery regions 12 and 14. Electrically insulating region 13 can have a diameter substantially the same as or smaller or larger than those of voltage delivery regions 12 and 14. Other features along the body portion of probe 10 can include indexing methods 18, such as depth markings.
The plurality of voltage delivery regions can be independently or inter-dependently configured to be energized with a predetermined polarity, as long as at least two of the voltage delivery regions are configured to be energized with opposite polarities. It has been observed that when voltage delivery regions 12 is configured to be positively (cathodically) energized while voltage delivery region 14 is configured to be negatively (anodically) energized, electrical arcing at tip 11 occurred less than if the polarity is reversed (i.e., with region 12 being negative (anodic) while region 14 being positive (cathodic).
Voltage delivery member 20 can include a distal portion 21 for voltage delivery that includes voltage delivery region 12 and tip 11 (which can be part of voltage delivery region 12), and a proximal portion 25 that can be electrically conducting for electrically coupling voltage delivery region 12 to a power supply (not shown). Portion 21 can extend to edge 22, having a uniform diameter along a majority of its length (excluding tip 11). The uniform diameter can be substantially the same as the outermost diameters shown in
Electrically insulating member 26 can be coaxially disposed about portion 25 of voltage delivery member 20. Electrically insulating member 26 can be coextensive distally with portion 25, and extend from edge 24 into handle 50. Electrically insulating member 26 can include one or more layers of the same or different electrically non-conductive materials. Electrically insulating member 26 can electrically insulate portion 25 to prevent electrical shorting as well as to prevent arcing thereof, which can adversely affect treatment efficiency as well as efficacy. Use of multiple layers as well as coatings to form electrically insulating member 26 reduces or eliminates the occurrence of pin holes and damage occurring during the manufacturing process. When assembling probe 10, electrically insulating member 26 can be applied onto portion 25, among other methods, by sliding on and shrink-wrapping one or more tubular structures (such as sleeves as well as tubing) of thermoplastics, as well as by forming one or more surface coatings (such as vapor deposition, spraying, dipping, as well as molding). Suitable electrically non-conductive materials can have a dielectric strength of 10 MV/m or greater, such as 15 MV/m or greater, or 20 MV/m or greater. Electrically non-conductive materials for electrically insulating member 26 include polyethylene terephthalate, polyimides, polyamides, polyamide-imides, singly and in combinations of two or more. Electrically insulating member 26 can have a uniform outer diameter. Thickness of electrically insulating member 26 can be 0.05 inches or less. In alternative embodiments, member 26 is 0.03 inches or less in diameter.
As indicated,
Electrically insulating member 26 and spacing member 40 in combination physically separates and electrically insulates voltage delivery member 20 from other voltage delivery members (including voltage delivery member 30 as described herein) of probe 10. In certain examples, electrically insulating member 26 (or a layer thereof) and spacing member 40 (or a layer thereof), comprised of the same or different electrically non-conductive materials, can be fabricated as a single-piece tubular structure rather than separate pieces to simplify the assembly of probe 10. The single-piece, electrically insulating member can have a distal cylindrical portion that is greater in outer diameter and wall thickness than a proximal cylindrical portion. A central lumen passing through the distal and proximal portions of the single-piece electrically insulating member can have a substantially uniform diameter that is equal to or greater than the outer diameter of portion 25 of voltage delivery member 20. Non-limiting methods of making a single electrically insulating piece that includes electrically insulating member 26 and spacing member 40 include extrusion (including co-extrusion), molding (including co-injection molding), and others known to one skilled in the art. In other examples, the optional spacing member 40 can be omitted from probe 10.
As shown in
Electrically insulating member 36 can be coaxially disposed about portion 35 of voltage delivery member 30. Electrically insulating member 36 can be coextensive distally with portion 35, and extend from edge 34 into handle 50. Electrically insulating member 36 can include one or more layers of the same or different electrically non-conductive materials. Electrically insulating member 36 can electrically insulate portion 35 to prevent electrical shorting as well as to prevent arcing thereof, which can adversely affect treatment efficiency as well as efficacy. Use of multiple layers as well as coatings to form electrically insulating member 36 reduces or eliminates the occurrence of pin holes and damages therein during the manufacturing process. When assembling probe 10, electrically insulating member 36 can be applied onto-portion 35, among other methods, by sliding on and shrink-wrapping one or more tubular structures (including sleeves as well as tubing) of thermoplastics, as well as by forming one or more surface coatings (including but not limited to vapor deposition, spraying, dipping, as well as molding). Suitable electrically non-conductive materials can have a dielectric strength of 10 MV/m or greater, such as 15 MV/m or greater, or 20 MV/m or greater. Electrically non-conductive materials for electrically insulating member 36 include polyethylene terephthalate, polyimides, polyamides, polyamide-imides, and combinations of two or more thereof. Electrically insulating member 36 can have a uniform outer diameter (as depicted in
Optionally, one or more of voltage delivery regions 12 and 14 can be rendered more echogenic than other regions (including the electrically insulating region 13, outer surface of electrically insulating member 36) along probe 10. Certain embodiments include non-limiting methods for echogenicity enhancement including particle blasting, echogenic coating. perforating, chemical etching, and laser etching. In certain embodiments, microabrasive blasting is applied to voltage delivery regions 12 and 14 to achieve a depth of 70 microns.
Each of voltage delivery regions 12, 14 and 16 can be independently or inter-dependently configured to be energized with a predetermined polarity, as long as at least two of the voltage delivery regions are configured to be energized with opposite polarities. In certain embodiments each of voltage delivery regions 12, 14 and 16 are electrically coupled to one of three cables and one of three separate connectors, to be independently energized as well as polarized. In additional embodiments, voltage delivery region 12 is oppositely energized with respect to one or both of voltage delivery regions 14 and 16. In other embodiments, voltage delivery region 14 is oppositely energized with respect to one or both of voltage delivered regions 12 and 16. In other embodiments, voltage delivery region 16 can be oppositely energized with respect to one or both of voltage delivery regions 12 and 14. In additional embodiments, only two of voltage delivery regions 12, 14 and 16 are oppositely energized at any given time, while the others are not energized. In certain embodiments, voltage delivery region 12 is cathodically energized, and in other embodiments region 12 is not energized. Certain embodiments include at least one of the following pattern of charge (polarization) for voltage delivery regions 12, 14 an 16: (+, −, −), (+, −, +), (+, +, −), (−, +, +), (−, +, −), (−, −, +), (+, −, X), (+, X, −), (−, +, X), (−, X, +), (X, +, −) and (X, −, +) where X represents no polarization. Any one of such patterns can be chosen exclusively throughout a procedure. Alternatively, a combination of two or more of these patterns can be chosen in a predetermined series, randomly, or manually for any one or more portions of a procedure. In various embodiments of
The tissue treatment devices illustrated as well as described herein are configured for delivery of pulsed electric field gradients to tissue surrounding the two or more voltage delivery regions. The pulsed electric field gradients can emanate away from the energized voltage delivery regions as substantially uniformly gradients of decreasing field strengths. Shapes and sizes of pulsed electric field gradients can depend in part on specific combinations of the following: 1) amplitude of the supplied voltage pulses, 2) dimensions (including lengths as well as diameters) of each of the voltage deliver regions, and 3) dimensions (including lengths as well as diameters) of each of the electrically insulating regions separating the voltage delivery regions. Shapes and sizes of the pulsed electric field gradients can be identified using non-limiting algorithms and software such as Finite Element Analysis (FEA) (COMSOL® Version 3.3, Comsol, Inc., Burlington, Mass.).
Pulsed voltage ablation thresholds, electric field strengths to which cells in a target tissue are exposed substantially damage, destroy, render dead or otherwise metabolically inactivate the cells, can be identified for any tissue type. For example, a pulsed voltage ablation threshold of 0.25 kV/cm has been demonstrated for destruction of certain cancer cells in vitro. This has been discussed in the following publication, which is hereby incorporated by reference: Miller L., Leor J., Rubinsky B. “Cancer Cell[ ] Ablation with Irreversible Electroporation.” Technology in Cancer Research and Treatment, Vol. 4(6), 699-705, 2005. As such, pulsed voltage ablation volumes of any given configuration of voltage delivery regions can be identified, for example, as the FEA-calculated electric field gradient outlined by a predetermined pulsed voltage ablation threshold (in kV/cm).
In certain embodiments, configurations of the voltage deliverer regions and the electrically insulating regions can: increase or maximize a ratio of diameter to length of tie pulsed voltage ablation volume (with the pattern being wide and short, or being or approaching substantially spherical), and can minimize the occurrence of electrical arcing between different voltage deliver), regions. This can have broad clinical applications. In certain embodiments the ratio of diameter to length of the pulsed voltage ablation volume can be 1:2 or greater, and in other embodiments can be 4:7 or greater, and in other embodiments can be 3:5 or greater. In other examples, this ratio of the pulsed voltage ablation volume can be 1:4 or greater, and in other embodiments can have a ratio that is at least one of: 2:7 or greater, 1:3 or greater, as well as 3:7 or greater.
The tissue treatment devices illustrated as well as described herein can be configured to have suitable as well as sufficient probe rigidity to reduce occurrence of kinks and breakages. In certain examples, probes 10 and 110 can have a gauge size of 22 or greater, while other embodiments include sizes 16 or greater. Certain embodiments have a probe or probes with a transverse area moment of inertia (MOI) of 3×10−7 in4 or greater, with other embodiments having probes with an MOI of 4×10−7 in4 or greater. Yet other embodiments have probes with a stress ratio of 9×105 in3 or less, and certain embodiments have probes with a stress ratio of 7×105 in3 or less. Additional embodiments have probes with a deflection factor of 9 lb·in2 or greater, with certain embodiments having probes with a deflection factor of 13 lb·in2 or greater.
The devices of the present application can include a single probe capable of containing two or more voltage delivery regions. The single-probe devices can be sufficient for certain pulsed voltage ablation procedures. Alternatively, the devices of the present application can include two or more probes constructed as illustrated as well as described herein, each carrying two or more voltage delivery regions. In other alternatives, multiple single-probe devices can be used in combination in other treatment procedures. When two or more probes are present in a device, or two or more probes of multiple devices are used in combination, the voltage delivery regions of different probes can in certain embodiments be aligned in parallel and in other embodiments will not be in parallel. Parallel probes can be configured to be sufficiently apart to reduce or eliminate occurrence of electrical shorting as well as arcing. Any two parallel voltage delivery regions of adjacent probes can be energized with the same polarity or opposite polarities. The combined electric field gradients resulting from energizing parallel probes can be calculated using FEA as described herein. Total treatment volumes (including total ablation volumes) can be identified within the combined electric field gradients, as described herein. In certain embodiments where multiple probes are utilized together, independently energizing and independently polarizing can be used to ensure current flows from any voltage delivery region on one probe to any voltage delivery region on another probe, at any point along the length of the voltage deliver, member containing a voltage delivery region.
The tissue treatment devices as illustrated as well as described herein can be suitable for treatment of conditions for various tissues, volumes, sizes and locations, including small to medium sized tissue volumes, and tissue volumes that are in close proximity to other non-targeted structures (that can include but are not limited to neuronal structures, vascular structures, duct structures, collagen-rich structures). Non-limiting examples of tissue masses to which the devices of the present application are applicable include benign tissue masses such as benign prostate hyperplasia (BPH) and uterine fibroids, as well as benign as well as malignant masses such as cancers and tumors of various tissue types (including but not limited to prostate, uterine, lung, liver, kidney, brain, head/neck, bone, stomach, colon, pancreas).
The tissue treatment devices as illustrated as well as described herein fixedly couple the two or more voltage delivery regions at predetermined distances from each other, reducing the demand on probe alignment and on the skill level of the operator, making the related procedures quick, easy, and widely adaptable, with reproducible and reliable outcomes (including the size and shape of the ablation volumes). The devices are configured such that the probe can be placed within or adjacent to the target tissue, enabling safe usage in situations where the tissue targeted for ablation is adjacent to critical as well as vital non-targeted structures (such as the urethra or neurovascular bundles). This feature can further broaden the applicability and adaptability of the related treatment procedures.
The tissue treatment devices as illustrated as well as described herein can enable safe delivery of pulsed voltage (including 1 kV or greater) treatment without endangering the patient or causing device malfunctions (such as shorting or arcing). The devices can further reduce tissue trauma and associated discomfort of the patient during the treatment procedures as compared to other devices using separate tissue-piercing needles containing each voltage delivery region. As such, duration and cost of subsequent recovery can be reduced following the treatment (including percutaneous) procedures. As described herein, the unique features as well as combinations thereof can reduce as well as eliminate device malfunctions such as electrical shorting as well as arcing, and can enhance patient safety as well as procedure efficiency and efficacy.
While the devices of the present application can be used for pulsed voltage ablation as described to engender irreversible electroporation, the can also be used to produce reversible electroporation (in certain embodiments to facilitate transportation of macromolecules across membranes), with appropriate modifications in operating parameters.
More specifically, in referring to
Opening 52, disposed on distal edge 51, can be configured for receiving probe 10, which can extend proximally into cavity 56 and terminate in a distal-facing recess 59 of plug 58. As such, at least opening 52 and plug 58 fixedly couple probe 10 with handle 50. Adhesives or other non-limiting bonding techniques can be used to render probe 10 immovable relative to handle 50. Additional embodiments (not shown in
Opening 54, optionally disposed on a tapering surface of distal portion 53, can be configured with various shapes known in the art including but not limited to elliptic or crescent shaped, and can be configured for receiving cables 60, which can extend proximally into cavity 56. One of the depicted cables 60 can be electrically coupled to proximal portion 25 (thus also to voltage deliver, region 12) through lead wire 80 and coupling methods 83, while another of cables 60 can be electrically coupled to proximal portion 35 (shown with electrically insulating member 36 shown disposed about portion 35) through lead wire 81 and coupling methods 82. Non-limiting examples of coupling methods 82 and 83 include soldering, lead wire wounding, electrically conductor lugs, and combinations thereof. The bonding joints are placed within body portion 55 during assembly. Note that electrically insulating region 13 and voltage delivery region 14 are shown for completeness in
Cavity 56 can be filled with a flowable material (including but not limited to a liquid, semi-liquid, as well as a gel) and with a hardening material (in certain embodiments including at least one of a cross-linkable, polymerizable, or otherwise curable material) that is electrically insulating (such as epoxy) to secure and in certain embodiments to immobilize the various components within body portion 55, as well as provide electrical insulation among the various components and between the components and a device operator. Cavity 56 can be partially filled, or not filled, as long as components within body portion 55 (such as cables 60, lead wires 80 and 81, as well as in certain embodiments ends of proximal portions 25 and 35) are immobilized relative to handle 50. Alternatively, sealing (including making air-tight an in certain embodiments liquid-proof) of openings 52 and 54 for prevention of fluid ingression into handle 50 can be sufficient to achieve the immobilization of components within body portion 55. Plug 58 can be fixedly coupled to body 55 to cap off cavity 56.
The handle designs of the present application allow cables as well as tubing to exit handle 50 distally (from the handle) at less than a 90 degree angle (including at an angle of zero degree or substantially parallel) to the longitudinal axis of handle 50 as well as probes 10. As such, the anchoring point for cables as well as tubing at handle 50 is much closer to distal end of device 100, thereby moving the center of gravity of device 100 closer to its distal end. In certain embodiments the described angles of tubing in relation to handle and described anchoring points can be applied to device 200 from
Such handle designs can minimize the possibility of cables as well as tubing entanglements. Such handle designs can also minimize adverse effects to probe placement as well as positioning caused by unintended forces. Such handle designs can further enable multiple devices to be positioned adjacent to each other so that the ablation volumes of the devices can merge into a combined ablation volume without voids.
Furthermore, devices incorporating distally exiting cables as well as tubing can reduce and can minimize the overall profile (including length as well as width) of the devices, as compared to other devices having proximally exiting cables. The reduced as well as minimized device profiles as disclosed herein can enable multiple devices with distally exiting cables as well as tubing to be used in a restricted operating space (including a biological imaging gantry). As such, the designs of the presently disclosed devices can enhance their applicability in treatment procedures involving, for example, biological imaging guidance (including CT-guidance). An advantage of a device with cables existing distally from the handle is that a center of gravity for the device is closer to the distal portion of the probe (closer to the tip than if the cables exit from the proximal portion of the handle); this adds stability and the probe will not be deflected as much (whether in use at a horizontal or vertical angle or between) during use.
Conventional handle designs have cables exiting a handle at its proximal end at an anile of 0 to 90 degrees relative to the longitudinal axis of the handle and the probe. While conventional handle designs do not provide the features of the above-described handle designs, they can be suitable for use with any of the probe designs described herein.
Specifically regarding
Also referring to
Referring specifically to
In various embodiments of
The blunt tip embodiment provides distinct advantages over the current state of the art. A blunt tip provides advantages of accuracy, precision, and exactness due to the non-cutting structure that will allow targeting of tissue without piercing of surrounding structures. A minimization of collateral damage occurs as nontarget tissue remains undamaged and minimally affected, providing the user increased degrees of freedom of action due to the non-piercing actions occurring with use of the blunt tip. In certain embodiments the blunt tip can be used to touch and even provide pressure to, change the shape of, or move a target structure or surrounding structure through the exertion of non-cutting and non-piercing pressure that will not pierce tissue or organ membranes and will not produce holes, tears, or punctures, thereby keeping the target structure intact.
In other embodiments the blunt tip will encounter nontarget tissue and will roll of the tissue, moving along the surface by partly revolving or turning. In various embodiments the blunt tip is utilized near nerve cells, parts of nerve cells, or nerve bundles, and can be used where nerve structural damage needs to be minimized or prevented. In various embodiments the blunt tip is used in regions where myelin sheath damage needs to be minimized or prevented. In additional embodiments the blunt tip can be used near or at biological structures of a conduit appearance, including but not limited to vessels or ureters to minimize or prevent damage. In yet other embodiments the blunt tip can be used at or near biological membranes to minimize or prevent damage.
The blunt tip can be utilized in certain embodiments in microsurgery, in areas where the tissues are delicate, thin, or otherwise prone to damage with current devices utilized in the art. In various embodiments the blunt tip is utilized in therapies, procedures, and surgeries of as well as surrounding the brain, where structures are delicate and where small openings are in many cases utilized for entry. In therapies surrounding the brain, the blunt tip provides the distinct advantage of providing leeway to users that have a buffer so as to prevent piercing of vital tissues. The blunt tip embodiments offer advantages in surgeries involving various brain structures, including but not limited to the parietal, occipital, temporal, and frontal lobes of the brain, the brainstem, the cerebellum, the ducts, glands, ventricles, as well as deep brain structures. In additional embodiments the blunt tip can be used, for example, in delicate surgeries involving dense vessel structures. Additional anatomical regions for therapies, procedures, and surgeries where the blunt tip can be utilized include physiologically homeostatic or pathological (including but not limited to tumors or cancers, benign or metastatic) portions of tissue of or surrounding adipose tissue, breast tissue, lymph (including lymph nodes and conduits), and ovarian tissue.
Yet other embodiments of blunt tip use include work involving tumor as well as cancer removal or treatment, either directly on cells as well as on surrounding cells and vasculature. Various embodiments of the blunt tip may also be utilized in therapies, procedures, and surgeries involving the abdomen as well as the bowels. These areas contain multiple regions of membranes and muscle groupings and are known as regions where ally piercings and tears can lead to medical disruptions requiring exploratory surgeries and which are difficult to find. The blunt tip would provide distinct advantages for work in these regions.
Various blunt tip embodiments also provide advantages to therapies, procedures, and surgeries of as well as around the lung, including the pleural space and pleural sac. Use of sharp instruments in this area is more prone to lead to a pneumothorax, and the result of accumulated gases and secondary responses and exposures can lead to additional infections and complications of lung collapse and other lung failures. The blunt tip embodiments remove this problem from work in these regions. The blunt tip can be utilized in other embodiments with or coupled to coatings or other devices increasing the ease of movement, entry, conductivity of energy, or otherwise increase the efficiency of the use of the device.
Additional advantages of the blunt tip embodiments surround the fact that released energy is not focalized. In certain embodiments the tip is part of the voltage delivery region or capable of conducting or releasing energy. In certain embodiments precision and accuracy and exactness are increased due to the fact the released energy is not concentrated into it very sharp tip which circumvents problems associated with nonequal energy release along the delivery region including the tip. The blunt tip provides for equal release of energy and prevents disruption of nontarget tissue as well as preventing unequal damage during therapies and within and around treatment areas. The blunt tip overcomes certain problems associated with the edge effect where high current densities occur in edges. This has been discussed in the following article, hereby incorporated by reference: Tungjitkusolmun S., Woo E., Cao H, Tsai J., Vorperian V., Webster J. “Finite Element Analysis of Uniform Current Density Electrodes for Radio-Frequency Cardiac Ablation.” IEEE Transactions on Biomedical Engineering, Vol. 47(1): 32-40 (2000). The blunt tip embodiments provide the advantage of decreasing arcing by minimizing aberrations of high current densities that can occur on material edges, and this decrease in arcing occurs regardless of whether the tip is charged anodically or even cathodically.
The size of the IRE device, with as well as without the blunt tip, can be that known in the art for treatment involving vessels and tissue of as well as within the prostate, uterus, lung, liver, kidney, brain, head, neck, bone, stomach, colon, pancreas, vascular, and duct. Treatment can include at least one of benign prostate hyperplasia (BHP), uterine fibroids, malignant masses. cancers, tumors, and benign tissues. Treatment can utilize at least one of percutaneous, laparoscopic, endoscopic, and natural orifice entry.
The blunt tip embodiment also provides advantages in treatments, therapies, and surgeries located in regions of the prostate, where delicate and precise ablations must be performed without damaging surrounding structures such as nerves that could lead to biological disruptions and dysfunctions. In certain embodiments the blunt tip device can be utilized in removal of or ablation of part or all of the prostate or tissues adjacent to or structurally supportive of the prostate.
In certain non-limiting examples, device 100 (or 200 from
The methods of the present application can involve imaging (including but not limited to ultrasound, CT, MRI) of the target tissue volume to be ablated. The imaging can include but is not limited to one, two, or more two-dimensional or three-dimensional biological imaging modalities, such as ultrasonography (ultrasound), fluoroscopy, contrast-enhanced imaging, magnetic resonance imaging, tomographic imaging, ionizing radiation imaging, non-ionizing radiation imaging, gamma radiation imaging (using radioactive isotopes), positron emission tomography, projection radiography (including X-ray, using radiopaque contrast agent), photoacoustic imaging, tomography (including linear tomography, poly tomography, zonography, orthopantomography, computed tomography with or without enhancement using contrast agent), diffused optical imaging (using infrared wavelengths), elastography (using ultrasound, MRI, or CT), electrical impedance tomography, as well as optoacoustic imaging. The imaging can be carried out prior to, during, as well as after the tissue treatment using the devices. The imaging can provide constant feedback (including real-time feedback) for any portion of, or throughout, the image-guided treatment. The imaging can be used in part to identify the location of the target tissue volume, determine the desired ablation volume for selection of appropriate tissue treatment devices disclosed herein, as well as to identify appropriate point of entry (including puncture) for the probes thereof.
The methods of the present application can involve providing one or a combination of two or more tissue treatment devices disclosed herein that are suitable for ablating at least a portion of the desired ablation volume or its entirety. Criteria for selection of the appropriate tissue treatment devices include but are not limited to the configuration of the probe, voltage delivery parameters (such as predetermined voltage that in certain embodiments can be 2.5-3 kV), and predetermined electric field strength (including 0.25 kV/cm, 0.425 kV/cm, as well as 0.6 kV/cm).
The methods of the present application can involve coupling the tissue treatment device to a therapeutic energy source, such as a voltage pulse generator (including a high voltage pulse generator). Commercial providers for the therapeutic energy source include AngioDynamics Inc., (Queensbury, N.Y.). In one example, the tissue treatment device can be coupled to the therapeutic energy source such that voltage delivery region 12 can be cathodically energized and voltage delivery region 14 can be anodically energized to minimize arcing.
The methods of the present application can involve inserting a probe of the device at or about the predetermined point of entry into the subject. The insertion of the probe can be percutaneous, laparoscopic, endoscopic, as well as through natural orifices (including insertions related to orifice translumenal endoscopic surgery).
The methods of the present application can involve positioning any one, two, or more than two of the voltage delivery regions along the probe within or adjacent to the target tissue. The positioning can be carried out under image guidance using one or more of the biological imaging modalities disclosed herein. The design of the treatment devices disclosed herein maximizes stability of the positioned probe, minimizes inadvertent movements of the probe, enhances stability of the probe, and can minimize device failure due to kinks as well as breakage.
The methods of the present application can involve imaging the target tissue with the probe positioned for treatment or adjacent to the site to be treated. This imaging can be used to confirm the correct positioning of the probe, particularly the positioning of the one, two, or more than two voltage delivery regions. Repositioning and reimaging can be carried out until the desired positioning of the probe is achieved.
The methods of the present application can involve activating a therapeutic energy source. A therapeutic energy source can be configured to deliver therapeutic energy including high voltage pulses, and can be configured to optionally deliver testing energy, including low voltage pulses or high voltage pulses or with pulses that are each of a duration shorter than the duration of each therapeutic voltage pulse.
The methods of the present application can involve delivering a sufficient number of voltage ablation pulses from the therapeutic energy source through the probe to the target tissue. Each of the pulses can have the same or different duration, which can be on the order of 20 microseconds to 200 microseconds, and in certain embodiments can be from 30 microseconds to 100 microseconds. Each of the pulses can have the same or different voltage, which can be of various levels (including but not limited to 1 kV or greater, 2 kV or greater, 2.7 kV or greater, or 2.5 kV to 3 kV). Each of the pulses can have the same or different waveforms, such as square, triangle, sawtooth, sine, pulse, composite waveforms, and can be in the form of a Fourier series. Any two consecutive pulses can be separated by an inter-pulse duration of 0.15 seconds or greater (including but not limited to 0.2 seconds to 1 second or 0.25 seconds to 0.5 seconds). The pulses can be delivered together or separated into subsets of the same or different number of pulses (including but not limited to subsets of 1 to 10 pulses each). The pulses can be the same or different in pulse duration, waveform, as well as voltage as well as amplitude within each subset as well as between different subsets. The ablation treatment that is sufficient to ablate the predetermined ablation volume can require just one pulse or a few pulses if the ablation volume is small, and 10 or more pulses for medium to large ablation volumes (in certain embodiments being 20 or more, 50 or more, 90 or more, 100 or more, 150 or more, 500 or less, 300 or less, or optionally 200 or less). A “train” is a term used to state a series of sequential electrical pulses. The ablation treatment that is sufficient to ablate the predetermined ablation volume can be delivered within 6 minutes (in certain embodiments being 5 minutes or less, or 2 minutes or less, or 1 minute or less). A non-limiting voltage ablation regimen can include multiple trains (in one embodiment 9 trains) of multiple pulses (in one embodiment 10 pulses) each, with pulse duration being 100 μs or shorter, pulse waveform being square, duration between consecutive pulses being 0.25 seconds, and duration between consecutive trains being 3 seconds. Control of parameters such as pulse durations, inter-pulse durations, voltage, amplitude, pulse waveform, and number of pulses can be handled by the therapeutic energy source. Such control can be carried out automatically according to preset values, based on the sensor (including information from the sensor including but not limited to impedance, current, voltage, chemical concentrations, pH, as well as ionic strength) feedbacks, as well as through manual input by the device operator. In certain embodiments, the application of the pulsed electric fields includes pulses of 1.5 kV/cm in 3 trains of 10 pulses each to ablate tissue.
The methods of the present application can involve exposing cells within the predetermined ablation volume to pulsed high intensity electric fields delivered from the probe. The electric fields can cause irreversible electroporation and subsequent cell death of the predetermined ablation volume. The effects of the ablation can be substantially immediately detectable (as well as detectable almost immediately referring to a very slight delay) following the pulsed voltage ablation delivery.
The methods of the present application can involve terminating the delivery of voltage ablation pulses based on predetermined criteria as well as based on feedback signals. Feedback signals can include sensor feedback signals, visual confirmation of predetermined desirable changes by the operator, or combinations thereof.
The methods of the present application can involve repeating the steps of probe positioning and therapeutic voltage pulse delivery to treat other selected treatment volumes. The other treatment volumes can overlap, partially overlap, or alternatively not overlap with the prior ablation volume.
The methods of the present application can involve retracting the probes partially or fully from the subject once all selected treatment volumes are treated. The probe track can be cauterized as understood by one of ordinary skill in the art, if desired.
Operating parameters suitable for use with the voltage delivery devices of the present application to ablate selected volumes of tissues (such as those depicted in
Duration of each pulse can be 100 microseconds or shorter (including but not limited to 50 microseconds or shorter or alternatively 20 microseconds or shorter). Certain embodiments include short pulses that would be more than sufficient to achieve any clinically relevant ablation, such as a total voltage exposure duration of one second (such as 10,000 pulses of 100 microseconds each).
It is noted that the tissue in the ablation volume subjected to pulsed electric field ablation of the present application is in its entirety exposed to ablative electric fields at the same time, albeit at different field strengths. Utilizing the electric field application effectively can lead to shortened procedures that can be 6 minutes or shorter.
In one embodiment, 30 trains of 10 pulses each can be used, with a pulse duration of 100 microseconds, a duration between consecutive pulses of 1 second, and a duration between consecutive trains of 3 seconds. In another embodiment, 300 pulses can be used, with a pulse duration of 100 microseconds and a duration between consecutive pulses of 1 second. In a further embodiment, 9 trains of 10 pulses each can be used, with a pulse duration of 100 microseconds, a duration between consecutive pulses of 0.25 seconds, and a duration between consecutive trains of 3 seconds.
The disclosed pulsed electric field ablation, when carried out under certain parameters and operating conditions, can selectively spare (including without damaging, destroying or denaturing) certain tissues and structures present within the ablation volume. Non-limiting tissues that can be selectably spared by the pulsed electric field ablation include nervous, vascular, duct, as well as collagen-rich tissues.
The total number of voltage pulses necessary to ablate a particular cell within a target tissue can depend on aspects such as cell shape and size within the target tissue, strength of the electric field the cell is subjected to, and duration of each pulse. In a qualitative but not necessarily quantitative example for illustration only, a cell requiring a certain number of pulses (such as 100) each of a certain duration (such as 100 microseconds) at a certain field strength (such as 0.4 kV/cm) to be successfully be ablated can also be ablated when subjected to a smaller number of pulses (such as 60-70) each of substantially the same or shorter duration (such as 20-100 microseconds) at a higher field strength (such as 0.6 kV/cm), or to substantially the same number of pulses (such as 100) each of a shorter duration (such as 20-50 microseconds) at substantially the same field strength (such as 0.4 kV/cm).
In another qualitative but not necessarily quantitative example for illustration only, probe 10 of
Duration between consecutive pulses can be equal to or longer than duration of muscle contractions (typically 50-160 milliseconds) to allow muscle cells to substantially recover following each voltage pulse, and to allow substantial dissipation of thermal buildup, it any, as a result of the voltage pulse. Duration between consecutive pulses can be substantially longer than duration of each pulse, such as 2,000-fold or greater. Duration between consecutive pulses can be 0.15 seconds or longer, or in alternative embodiments can be 0.2 seconds or longer (equivalent to a pulse frequency of lower than 5 Hz), or 0.25 seconds or longer (equivalent to a pulse frequency of 4 Hz or lower), or 1 second or longer.
Unless otherwise defined herein, scientific and technical terminologies employed in the present disclosure shall have the meanings that arc commonly understood and used by one of ordinary skill in the art. Unless otherwise required by context, it will be understood that singular terms shall include plural forms of the same and plural terms shall include the singular. Specifically, as used herein and in the claims, the singular forms “a” and “an” include the plural reference unless the context clearly indicates otherwise. Also, as used herein and in the claims. the terms “at least one” and “one or more” have the same meaning and include one, two, three or more.
Other than in the operating examples, or unless otherwise expressly specified, all of the numerical ranges, amounts, values and percentages such as those for quantities of materials, durations of times, temperatures, operating conditions, ratios of amounts, and the likes thereof disclosed herein should be understood as modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth can be varied.
Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains limitations as to testing measurements. Furthermore, when numerical ranges of varying scope are set forth herein, it is contemplated that any combination of these values inclusive of the recited values can be used.
Examples provided herein, including those following “such as” are considered as illustrative only of various aspects and features of the present disclosure and embodiments thereof, without limiting the scope of any of the referenced terms or phrases either within the context or outside the context of such descriptions. Any suitable equivalents, alternatives, and modifications thereof (including materials, substances, constructions, compositions, formulations, methods, as well as conditions) known as well as available to one skilled in the art can be used or carried out in place of or in combination with those disclosed herein, and are considered to fall within the scope of the present disclosure. All these alternatives and variations are intended to be included within the scope of the claims where the terms “comprising”, “formed from” and “formed of” all denote open claim language. Those familiar with the art can recognize other equivalents to the specific embodiments described herein which equivalents are also intended to be encompassed by the claims.
Throughout the present disclosure in its entirety, any and all of the one, two, or two or more features and aspects disclosed herein, explicitly or implicitly, following terms “example”, “examples”, “such as,” and the likes thereof can be practiced in any combinations of two, three, or more thereof (including their equivalents, alternatives, and modifications), whenever and wherever appropriate as understood by one of ordinary skill in the art. Some of these examples are themselves sufficient for practice singly (including their equivalents, alternatives, and modifications) without being combined with any other features, as understood by one of ordinary skill in the art. Therefore, specific details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ aspects and features of the present disclosure in any appropriate manner.
This application claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application No. 61/051,832, filed May 9, 2008, which is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 61051832 | May 2008 | US |
