FIELD OF THE INVENTION

The present invention is related to medical therapies involving the administering of electrical treatment energy. More particularly, embodiments of the present invention provide systems and methods for modeling and providing a graphical representation of tissue heating and electric field for a medical treatment device that applies electrical treatment energy through a plurality of electrodes defining a target treatment area. Embodiments of the present invention also provide systems and methods providing a graphical representation of a target ablation zone based on one or more electrical conductivity parameters that are specific for the tissue to be treated.

DESCRIPTION OF RELATED ART

Electroporation-based therapies (EBTs) are clinical procedures that utilize pulsed electric fields to induce nanoscale defects in cell membranes. Typically, pulses are applied through minimally invasive needle electrodes inserted directly into the target tissue, and the pulse parameters are tuned to create either reversible or irreversible defects. Reversible electroporation facilitates the transport of molecules into cells without directly compromising cell viability. This has shown great promise for treating cancer when used in combination with chemotherapeutic agents or plasmid DNA (M. Marty et al., “Electrochemotherapy—An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study,” European Journal of Cancer Supplements, 4, 3-13, 2006; A. I. Daud et al., “Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma,” Journal of Clinical Oncology, 26, 5896-5903, Dec. 20, 2008). Alternatively, irreversible electroporation (IRE) has been recognized as a non-thermal tissue ablation modality that produces a tissue lesion, which is visible in real-time on multiple imaging platforms (R. V. Davalos, L. M. Mir, and B. Rubinsky, “Tissue ablation with irreversible electroporation,” Ann Biomed Eng, 33, 223-31, February 2005; R. V. Davalos, D. M. Otten, L. M. Mir, and B. Rubinsky, “Electrical impedance tomography for imaging tissue electroporation,” IEEE Transactions on Biomedical Engineering, 51, 761-767, 2004; L. Appelbaum, E. Ben-David, J. Sosna, Y. Nissenbaum, and S. N. Goldberg, “US Findings after Irreversible Electroporation Ablation: Radiologic-Pathologic Correlation,” Radiology, 262, 117-125, Jan. 1, 2012). Because the mechanism of cell death does not rely on thermal processes, IRE spares major nerve and blood vessel architecture and is not subject to local heat sink effects when using a specific protocol that does not exceed the thermal damage threshold. (B. Al-Sakere, F. Andre, C. Bernat, E. Connault, P. Opolon, R. V. Davalos, B. Rubinsky, and L. M. Mir, “Tumor ablation with irreversible electroporation,” PLoS ONE, 2, e1135, 2007). These unique benefits have translated to the successful treatment of several surgically “inoperable” tumors (K. R. Thomson et al., “Investigation of the safety of irreversible electroporation in humans,” J Vasc Intery Radiol, 22, 611-21, May 2011; R. E. Neal II et al., “A Case Report on the Successful Treatment of a Large Soft-Tissue Sarcoma with Irreversible Electroporation,” Journal of Clinical Oncology, 29, 1-6, 2011; P. A. Garcia et al., “Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient,” Technol Cancer Res Treat, 10, 73-83, 2011).

In EBTs, the electric field distribution is the primary factor for dictating defect formation and the resulting volume of treated tissue (J. F. Edd and R. V. Davalos, “Mathematical modeling of irreversible electroporation for treatment planning,” Technology in Cancer Research and Treatment, 6, 275-286, 2007 (“Edd and Davalos, 2007”); D. Miklavcic, D. Semrov, H. Mekid, and L. M. Mir, “A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy,” Biochimica et Biophysica Acta, 1523, 73-83, 2000). The electric field is influenced by both the geometry and positioning of the electrodes as well as the dielectric tissue properties. Because the pulse duration is typically much longer than the pulse rise/fall time, static solutions of the Laplace's equation incorporating only electric conductivity are sufficient for predicting the electric field distribution. In tissues with uniform conductivity, solutions can be obtained analytically for various needle electrode configurations if the exposure length is much larger than the separation distance (S. Corovic, M. Pavlin, and D. Miklavcic, “Analytical and numerical quantification and comparison of the local electric field in the tissue for different electrode configurations,” Biomed Eng Online, 6, 2007; R. Neal II et al., “Experimental Characterization and Numerical Modeling of Tissue Electrical Conductivity during Pulsed Electric Fields for Irreversible Electroporation Treatment Planning,” Biomedical Engineering, IEEE Transactions on, PP, 1-1, 2012 (“Neal et al., 2012”)). This is not often the case in clinical applications where aberrant masses with a diameter on the order of 1 cm are treated with an electrode exposure length of similar dimensions. Additionally, altered membrane permeability due to electroporation influences the tissue conductivity in a non-linear manner. Therefore numerical techniques may be used to account for any electrode configuration and incorporate a tissue-specific function relating the electrical conductivity to the electric field distribution (i.e. extent of electroporation).

Conventional devices for delivering therapeutic energy such as electrical pulses to tissue include a handle and one or more electrodes coupled to the handle. Each electrode is connected to an electrical power source. The power source allows the electrodes to deliver the therapeutic energy to a targeted tissue, thereby causing ablation of the tissue.

Once a target treatment area is located within a patient, the electrodes of the device are placed in such a way as to create a treatment zone that surrounds the treatment target area. In some cases, each electrode is placed by hand into a patient to create a treatment zone that surrounds a lesion. The medical professional who is placing the electrodes typically watches an imaging monitor while placing the electrodes to approximate the most efficient and accurate placement.

However, if the electrodes are placed by hand in this fashion, it is very difficult to predict whether the locations selected will ablate the entire treatment target area because the treatment region defined by the electrodes vary greatly depending on such parameters as the electric field density, the voltage level of the pulses being applied, size of the electrode and the type of tissue being treated. Further, it is often difficult or sometimes not possible to place the electrodes in the correct location of the tissue to be ablated because the placement involves human error and avoidance of obstructions such as nerves, blood vessels and the like.

Conventionally, to assist the medical professional in visualizing a treatment region defined by the electrodes, an estimated treatment region is generated using a numerical model analysis such as complex finite element analysis. One problem with such a method is that even a modest two dimensional treatment region may take at least 30 minutes to several hours to complete even in a relatively fast personal computer. This means that it would be virtually impossible to try to obtain on a real time basis different treatment regions based on different electrode positions.

In IRE treatments, the electric field distribution is the primary factor for dictating defect formation and the resulting volume of treated tissue (See J. F. Edd and R. V. Davalos, “Mathematical modeling of irreversible electroporation for treatment planning,” Technol Cancer Res Treat, vol. 6, pp. 275-286, 2007; D. Sel, et al., “Sequential finite element model of tissue electropermeabilization,” IEEE Trans Biomed Eng, vol. 52, pp. 816-27, May 2005). The electric field is influenced by both the geometry and positioning of the electrodes as well as the dielectric tissue properties. The application of an electric field across any conductive media will result in some degree of resistive losses in which energy is dissipated as heat. Though cell death in IRE is attributed to non-thermal mechanisms, it is possible to inadvertently elevate tissue temperatures above thermal damage thresholds if parameters are not chosen carefully. Since a major advantage of IRE is the ablation of tissue without deleterious thermal effects and the therapy is often applied in regions which cannot clinically sustain thermal injury, it is important to identify safe operating parameters. Transient heating of tissue in proximity to the electrode can result in the denaturing of the extracellular matrix, scar formation, or damage to local blood vessels and nerves. To avoid these effects, it is important to understand the extent and geometry of tissue heating.

Therefore, it would be desirable to provide an improved system and method to predict a treatment region that avoids electrical and thermal overexposure and damage in order to determine safe and effective pulse protocols for administering electrical energy based therapies, such IRE.

SUMMARY OF THE INVENTION

In one embodiment, the invention provides a system for treating a tissue, which system applies electrical treatment energy through one or more electrodes, such as a plurality of electrodes, defining a target treatment area of the tissue. The system comprises a memory, a display device, a processor coupled to the memory and the display device, and a treatment planning module stored in the memory and executable by the processor. In one embodiment, the treatment planning module is adapted to generate an estimated heat distribution and/or electrical field distribution in the display device based on one or more parameters for an electrical energy based protocol, such as an irreversible electroporation (IRE) protocol. In another embodiment, the treatment planning module is adapted to generate an estimated target ablation zone based on a combination of one or more parameters for an electrical energy based protocol, such as an IRE-based protocol, and one or more tissue-specific conductivity parameters.

In another embodiment, the invention provides a method of treating a tissue with a medical treatment device that applies electrical treatment energy through a one or more or a plurality of electrodes defining a target treatment area of the tissue and comprises a display device. The method may be executed partially or completely using the system of the invention. In a specific embodiment, one or more steps are executed through the treatment planning module.

In embodiments, the treatment planning module can be used to determine a temperature distribution to determine tissue heating at or around a target ablation zone prior to or during treatment. The treatment planning module can be used to graphically display contour lines which represent a specific temperature of tissue heating. In one embodiment, the treatment planning module estimates the temperature rise within tissue due to Joule heating effects, and plots a contour line according to a temperature specified by a user. Further, the treatment planning module may further plot a contour line representing an electric field intensity such that temperature and electric field intensity can be correlated. The treatment planning module may plot the temperature distribution and electric field distribution for a bipolar and single needle electrodes. This capability may allow a user (e.g. treating physician) to determine heating to surrounding tissues during treatment planning and adjust parameters to prevent thermal damage to critical surrounding structures such as nerves and blood vessels. In one embodiment, the contour lines are Cassini oval approximations performed according to the equations and procedure in Example 7.

In embodiments, the treatment planning module can be used to provide the electric field distributions using different configurations of bipolar probes and include the dynamic change in electrical conductivity from the non-electroporated baseline tissue electrical conductivity. The treatment planning module may plot contour lines representing electric field distributions based on a specific combination of electrode length, separation distance, and applied voltage. The treatment planning module may incorporate the dynamic change in electrical conductivity from the baseline during treatment to account for treatment-related changes in conductivity for particular tissues such as liver, kidney, brain, etc. This capability may allow the treating physician to determine electric field distributions and zones of ablation based on the capacity for a specific target tissue to change in conductivity during treatment. In one embodiment, the contour lines are Cassini oval approximations performed according to the equations and procedure in Example 7.

In embodiments, the treatment planning module can be based on a parametric study of the dynamic conductivity curve so that variables related to the dynamic conductivity could be used to fit tissue specific behavior. In embodiments, the treatment planning module may provide input for one or more electrical conductivity parameters such as the baseline (e.g., non-electroporated) conductivity, change in conductivity, the transition zone (how rapidly the conductivity increases), the electric field at which the change in conductivity occurs, and the electric field at which irreversible electroporation occurs. These parameters may be experimentally derived for different tissues and stored in a database. This capability may allow the treating physician to account for different conductivity parameters as they apply to different target tissues when designing a treatment protocol. Thus, when considering a specific tissue, the treating physician may optimize the calculation of an ablation zone for that tissue by inputting one or more of the tissue-specific conductivity parameters for the tissue of interest.

