Patent Description:
The present disclosure generally relates to systems and methods for providing a therapy to a patient. More particularly, the present disclosure relates to apparatuses, systems, and methods assessing electroporation.

Electroporation may permeate cell membranes through exposure to certain electric pulses. Irreversible electroporation may be alternative for the ablation of undesired tissue. Electroporation without thermal effect to ablate tissue may avoid thermal damage to target tissue or other tissue surrounding the target tissue and/or ablates cells without damaging the blood vessel structure.

Atrial fibrillation is an irregular and often rapid heart rate that commonly causes poor blood flow to the body. Ablation procedures, including ablation of thoracic veins such as the pulmonary vein, may be a treatment for atrial fibrillation. During pulmonary vein ablation, for example, catheters are inserted into the atrium and energy is delivered to the tissue of the pulmonary vein and/or near the ostia of the pulmonary veins in the left atrium. Ablative energy, by electroporation, may be used in other areas of the heart, other veins, or blood vessels.

Analysis and/or tracking of the electroporated tissue may be useful in effectively and accurately ablating tissue using electroporation. Presently, it may take days or months to assess the irreversible nature of the procedure.

<CIT> relates to systems and methods for planning of catheter ablation procedures, and in particular for planning of the placement of lesions and/or parameters used in ablation. In some embodiments, planning is based on thermal and/or dielectric simulation of lesions, individualized to the anatomy of the particular patient. Optionally, a plan comprises planning of a path along which an ablation lesion is to be formed, the ablation lesion optionally comprising one or more sub-lesions.

<CIT> relates to a computerized method of tracking a position of an intra-body catheter, comprising: physically tracking coordinates of the position of a distal portion of a physical catheter within the physical body portion of the patient according to physically applied plurality of electrical fields within the body portion and measurements of the plurality of electrical fields performed by a plurality of physical electrodes at a distal portion of the physical catheter; registering the physically tracked coordinates with simulated coordinates generated according to a simulation of a simulated catheter within a simulation of the body of the patient, to identify differences between physically tracked location coordinates and the simulation coordinates; correcting the physically tracked location coordinates according to the registered simulation coordinates; and providing the corrected physically tracked location coordinates for presentation.

The present disclosure provides also further examples useful for better understanding of the invention. In particular, the disclosed methods are not claimed and do not form part of the invention.

While the invention is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.

<FIG> shows an example electroporation device <NUM> at a target tissue region within patient's heart <NUM> in accordance with embodiments of the disclosure. The heart <NUM> shown in <FIG> may be undergoing a pulmonary vein ablation procedure using a electroporation device <NUM> in accordance with various aspects discussed herein. The electroporation device <NUM> may be used in other blood vessels or arteries or other portions of the heart such as the left atrial appendage. The electroporation device <NUM> may include a catheter having an elongate body <NUM> that is connected to a balloon structure <NUM>. The electroporation device <NUM> may be connected to an ablation energy source and controller (e.g., radiofrequency (RF) or direct current (DC) system not shown) and one or more liquid sources (not shown), both of which are located external to the patient. The balloon structure <NUM> may be located near the distal end of elongate body <NUM>. One or more interior chambers of the balloon structure <NUM> may be in fluid communication with a liquid delivery lumen arranged within the elongate body <NUM>. The liquid delivery lumen is used to convey the one or more liquids from the source external to the patient into the balloon structure <NUM>. The elongate body <NUM> and the balloon structure <NUM> may be delivered to a tissue region to which ablation energy may be applied.

As shown in <FIG>, the elongate body <NUM> may be positioned in the left atrium <NUM> of the patient's heart <NUM>. More specifically and in certain instances, the electroporation device <NUM> may enter the right atrium <NUM> of heart <NUM> through a femoral vein and the inferior vena cava (not shown). The electroporation device <NUM> may be passed through a puncture in an atrial septum <NUM> to access left atrium <NUM>. From the left atrium <NUM>, the balloon catheter electroporation device <NUM> may be positioned through any of the pulmonary vein ostia <NUM>, <NUM>, <NUM>, or <NUM> to enter a pulmonary vein such as pulmonary vein <NUM>. In certain instances, the electroporation device <NUM> may be an over-the-wire device that is delivered over or on a pre-placed guidewire or a delivery catheter/sheath and/or be self steerable or rapid exchange catheter may be used to assist in the insertion and placement of the electroporation device <NUM>.

After positioning of the electroporation device <NUM> at the tissue region (within the pulmonary vein <NUM> as shown in <FIG>), the balloon structure <NUM> may be expanded. The balloon structure <NUM> may be inflated using a liquid (e.g., saline, a pharmacological agent, or a combination thereof) as the inflation medium. In instances where the balloon structure <NUM> is positioned within a vessel such as the pulmonary vein <NUM>, the inflation of balloon structure <NUM> may cause the outer surface of balloon structure <NUM> to contact an inner wall of vessel such as the pulmonary vein <NUM>. In certain instances, ablation energy may be applied through one or more electrodes (not shown) arranged within the balloon structure <NUM> to initiate the modulation of target neural fibers. In addition, one or more portions of the balloon structure <NUM> may have a permeability such that a liquid may exude, elute, weep, or otherwise be transmitted from therethrough. In certain instances, the liquid may be an anti-stenotic pharmaceutical agent that may contact the inner wall of pulmonary vein <NUM>.

The ablation energy may be applied through one or more portions of the balloon structure <NUM> by an electric field generated by the external source/controller and transferred through wires within one or more lumens of the elongate body <NUM> to electrodes (not shown) arranged with the balloon structure <NUM>. The electric energy can be transmitted to the inner wall of pulmonary vein <NUM> directly from the electrodes on the surface of balloon structure <NUM> or from the electrodes within the balloon structure <NUM>. The electric field may at least partially cause apoptotic cell death and/or non-thermal necrosis to the tissue receiving the ablation energy.

In certain instances, the electric field may be generated by applying direct current to the one or more electrodes arranged within the balloon structure <NUM>. In addition, the use of direct current may cause apoptotic cell death and/or non-thermal necrosis to the tissue receiving the ablation energy. The direct current may form pores in the cells of the wall of the pulmonary vein <NUM> that are irreversible (e.g., the pores do not close). The balloon structure <NUM> being in contact with the wall of the pulmonary vein <NUM> may provide controlled and direct ablation of a target area while mitigating against down-stream proliferation of the ablation energy.

<FIG> shows an example electroporation device <NUM> and electromagnetic field <NUM> in accordance with embodiments of the disclosure. electroporation device <NUM> includes a distal electrode <NUM> and a proximal electrode <NUM>. Current may be applied to the distal electrode <NUM> and the proximal electrode <NUM> to create the electromagnetic field <NUM> between the distal electrode <NUM> and the proximal electrode <NUM>. In certain instances, direct current may be pulsed from one of the distal electrode <NUM> and the proximal electrode <NUM> to the other of the distal electrode <NUM> and the proximal electrode <NUM> to create the electromagnetic field <NUM>. The distal electrode <NUM> and the proximal electrode <NUM> may be opposite charged to create the electromagnetic field <NUM>. In certain instances, the distal electrode <NUM> and the proximal electrode <NUM> are electrically separated or isolated in order to oppositely charge the distal electrode <NUM> and the proximal electrode <NUM> to create the electromagnetic field <NUM>.

The electromagnetic field <NUM> may utilized to verify that the electroporation therapy applied by the electroporation device <NUM> is delivered at a desired location and/or at a desired effectiveness. Tissue affected by the electromagnetic field <NUM> may change (e.g., in density) as compared to unaffected tissue.

<FIG> shows the electroporation device <NUM>, as shown in <FIG>, at a target tissue region <NUM> prior to application of electroporation energy in accordance with embodiments of the disclosure. As shown in <FIG>, a group of cells <NUM> are highlighted in the target tissue region <NUM>. The group of cells <NUM> have not been affected (e.g., voided or a ions have not evacuated the group of cells <NUM>) as energy has not been applied to the electroporation device <NUM> at this point.

<FIG> shows the electroporation device <NUM>, as shown in <FIG>, at a target tissue region <NUM> after application of electroporation energy in accordance with embodiments of the disclosure. The same group of cells <NUM> shown in <FIG> are shown as affected as a result of the energy applied to the electroporation device <NUM>. The group of cells <NUM> may swell or void after electroporation which would change the density of the group of cells <NUM>. The electromagnetic field <NUM>, shown in <FIG>, voids or swells the group of cells <NUM>. In comparing the group of cells <NUM> in <FIG> (unaffected cells) and the group of cells <NUM> in <FIG> (affected cells), a difference in density is present therebetween. Local magnetic field variations, or magnetic field gradients, may introduced due to the "voiding" or "swelling" of the impacted cells <NUM> (shown in <FIG>). The localized gradients can be utilized to define a successful application of electroporation energy by the electroporation device <NUM> within the target tissue region <NUM>.

<FIG> shows a partial cross-sectional illustration of an example electroporation device <NUM> in accordance with embodiments of the disclosure. The electroporation device <NUM> may include a catheter <NUM> sized and shaped for vascular access that has an elongate body <NUM> extending between a proximal end and a distal end of the catheter <NUM>. A distal portion of the catheter <NUM> and the elongate body <NUM> is shown in <FIG>. The electroporation device <NUM> may also include a balloon structure <NUM> arranged near the distal end of the elongate body <NUM>. The balloon structure <NUM> may be configured to inflate in response to a liquid or inflation medium being provided thereto.

The electroporation device <NUM> may also include one or more electrodes arranged on or within the balloon structure <NUM>. As shown in <FIG>, the apparatus includes a proximal electrode <NUM> arranged near a proximal end and on or within the balloon structure <NUM> and a distal electrode <NUM> arranged near a distal end and on or within the balloon structure <NUM>. The proximal electrode <NUM> and the distal electrode <NUM> may be configured to deliver energy to a tissue region. In certain instances, the proximal electrode <NUM> and the distal electrode <NUM> may be configured to delivery energy in response to a direct current applied thereto. As a result of the direct current applied to the proximal electrode <NUM> and the distal electrode <NUM>, an electromagnetic field develops to delivery electroporation energy to the tissue region. The direct current may be applied in pulse bursts applied that results in electroporation energy delivered by the electroporation device <NUM>.

As shown in <FIG>, the proximal electrode <NUM> includes portions <NUM> that extend toward the distal electrode <NUM> and the distal electrode <NUM> includes portions <NUM> that extend toward the proximal electrode <NUM>. These portions <NUM>, <NUM> may control a shape of the electromagnetic field that develops as a result of the pulse bursts applied to the proximal electrode <NUM> and the distal electrode <NUM>. In addition, the proximal electrode <NUM> are spaced apart by between <NUM> and <NUM>.

The balloon structure <NUM> may anchor the electroporation device <NUM> at a target location within a patient. In certain instances, the target location may be a vein or artery in a patient such as the pulmonary vein. Blood moving through the target location and/or pulsing of the patient's heart may affect movement of the electroporation device <NUM> and hinder the ability of the electroporation device <NUM> to accurate delivery electroporation energy. The electroporation device <NUM> may be used in connection with an array of sensors and an output device as shown in <FIG> and discussed in further detail below. The array of sensors and the output device may be configured to verify location of the electroporation device <NUM> and also may be configured to verify effectiveness of the electroporation energy applied by the electroporation device <NUM>.

<FIG> shows an electroporation system <NUM> at a target tissue region <NUM> within patient's heart <NUM> in accordance with embodiments of the disclosure. The electroporation system <NUM> includes an electroporation device <NUM>, an array of sensors <NUM>, and an output device <NUM>.

The array of sensors <NUM> are configured to sense an application of electroporation energy by the electroporation device <NUM> to determine a location of the electroporation device <NUM> within the patient. In certain instances, the array of sensors <NUM> are configured to sense an electromagnetic field generated by the electroporation device <NUM> (e.g., as discussed above with reference to <FIG>) resulting from pulse bursts applied by the electroporation device <NUM>. The array of sensors <NUM> may be a two-dimensional or three-dimensional array of magnoresistive sensors. The array of sensors <NUM> may be arranged alone one or more sides of the patient. In certain instances, the array of sensors <NUM> may be arranged beneath a patients back during the electroporation procedure. In addition, the array of sensors <NUM>, when three-dimensional, may extend up at least a portion of the patient's side or sides.

The array of sensors <NUM> may be magnoresistive sensors such as Magneto-Resistance (AMR) sensors, Giant Magneto-Resistance (GMR) sensors, Magnetic Tunneling Junction (MTJ) sensors, Tunnel Magneto-Resistance (TMR) sensors, inductive sensors, fluxgate sensors, GMI (giant magnetoimpedance) sensors, hall sensors or other similarly configured sensors. In addition, the array of sensors <NUM> may be configured to measure an output magnetic field density emitted by the electroporation device <NUM> over a grid of the array of sensors <NUM>.

The array of sensors <NUM> communicates, wirelessly or via a direct connection, with the output device <NUM>. The output device <NUM> includes circuitry configured to measure the electromagnetic field generated by the electroporation device <NUM> and sensed by the array of sensors <NUM>. In certain instances, the output device <NUM> is configured to measure a difference between in the electromagnetic field generated by the electroporation device <NUM> prior to application of pulse bursts and the electromagnetic field generated by the electroporation device <NUM> after to application of the pulse bursts. The difference measured by the output device <NUM> measures affected cells to determine the location of the electroporation device <NUM> within the patient. More specifically, the output device <NUM> is configured to measure the difference based on a change in cell density at the target tissue region <NUM>.

Electroporated cells have a different density that cells that have not been electroporated, and the output device <NUM> may determine the difference in the electric fields, sensed by the array of sensors <NUM>, of the affected and unaffected cells. Thus, the output device <NUM> may also be configured to verify effectiveness of the application of electroporation by the electroporation device <NUM> at the tissue region <NUM>. In certain instances, the output device <NUM> is configured to measure the change in cell density to locate impacted and non-impacted cells in the tissue region. In addition, the output device <NUM> may be configured to display an indication of the impacted and non-impacted cells during application of the application of electroporation energy. In this manner, the output device <NUM> may provide a real-time display of the effectiveness of the electroporation device <NUM> during application of electroporation by the electroporation device <NUM> at the tissue region <NUM>.

The electroporation device <NUM> may also include a balloon structure <NUM> configured to anchor the electroporation device <NUM> at the tissue region <NUM> within the patient. Blood moving through the tissue region and/or pulsing of the patient's heart <NUM> may affect movement of the electroporation device <NUM> and hinder the ability of the electroporation device <NUM> to accurate delivery electroporation energy. The balloon structure <NUM> may also facilitate application of the electroporation energy to the tissue region <NUM> by providing a contact area between the electroporation device <NUM> and the tissue region <NUM>.

In addition, the array of sensors <NUM> and the output device <NUM> may provide real-time feedback to an operating physician using the electroporation device <NUM>. The ability of the output device <NUM> to indicate location of the electroporation device <NUM> and effectiveness of the electroporation device <NUM> during use of the electroporation device <NUM> increases the effectives of the electroporation device <NUM>.

Claim 1:
An apparatus for assessing electroporation therapy applied to a tissue region (<NUM>, <NUM>) of a patient, the apparatus comprising:
an electroporation device (<NUM>, <NUM>, <NUM>, <NUM>) comprising:
a catheter (<NUM>) sized and shaped for vascular access and including an elongate body (<NUM>, <NUM>) extending between a proximal end and a distal end,
a balloon structure (<NUM>, <NUM>) arranged near the distal end of the elongate body, and
one or more electrodes (<NUM>, <NUM>, <NUM>, <NUM>) arranged on or within the balloon structure and configured to deliver electroporation energy to the tissue region; and
an array of sensors (<NUM>) configured to be positioned on the patient and to sense an application of the electroporation energy by the electroporation device to determine a location of the electroporation device within the patient.