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41.发明授权公开(公告)号：US11382681B2
公开(公告)日：2022-07-12
申请号：US16372520
申请日：2019-04-02
摘要： The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.
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公开(公告)号：US20220161027A1
公开(公告)日：2022-05-26
申请号：US17535742
申请日：2021-11-26
摘要： High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay-negative phase-interpulse delay pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively. The present invention provides methods of pulse delivery, including delays, that mitigate bubble formation and/or minimize the risk of arcing, such as due to the presence of bubbles, and/or minimize muscle stimulation are described herein.
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公开(公告)号：US20220151688A1
公开(公告)日：2022-05-19
申请号：US17591992
申请日：2022-02-03
摘要： Systems and methods are provided for modeling and for providing a graphical representation of tissue heating and electric field distributions for medical treatment devices that apply electrical treatment energy through one or a plurality of electrodes. In embodiments, methods comprise: providing one or more parameters of a treatment protocol for delivering one or more electrical pulses to tissue through a plurality of electrodes; modeling electric and heat distribution in the tissue based on the parameters; and displaying a graphical representation of the modeled electric and heat distribution. In another embodiment, a treatment planning module is adapted to generate an estimated target ablation zone based on a combination of one or more parameters for an irreversible electroporation protocol and one or more tissue-specific conductivity parameters.
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公开(公告)号：US11254926B2
公开(公告)日：2022-02-22
申请号：US16404392
申请日：2019-05-06
发明人： Robert E. Neal, II , Paulo A. Garcia , Rafael V. Davalos , John H. Rossmeisl , John L. Robertson
摘要： The present invention provides systems, methods, and devices for electroporation-based therapies (EBTs). Embodiments provide patient-specific treatment protocols derived by the numerical modeling of 3D reconstructions of target tissue from images taken of the tissue, and optionally accounting for one or more of physical constraints or dynamic tissue properties. The present invention further relates to systems, methods, and devices for delivering bipolar electric pulses for irreversible electroporation exhibiting reduced or no damage to tissue typically associated with an EBT-induced excessive charge delivered to the tissue.
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公开(公告)号：US10959772B2
公开(公告)日：2021-03-30
申请号：US16275429
申请日：2019-02-14
发明人： Rafael V. Davalos , Paulo A. Garcia , John L. Robertson , John H. Rossmeisl , Robert E. Neal, II
摘要： The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. Included is a method of treating tissue with electrical energy, the method comprising: delivering electrical energy to tissue using one or more electroporation devices comprising one or more electrodes; and cooling the tissue, surrounding tissue, one or more of the electrodes, or one or more of the electroporation devices to minimize heating. In embodiments, the invention can be used to treat solid tumors, such as brain tumors, and in some embodiments, exemplary methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors.
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46.发明申请公开(公告)号：US20210052882A1
公开(公告)日：2021-02-25
申请号：US17000049
申请日：2020-08-21
发明人： Elisa M. Wasson , Rafael V. Davalos
摘要： High-frequency irreversible electroporation (H-FIRE) is an electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short pulses in a series of bursts. Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages are typically applied to generate ablations comparable in size. Administration of adjuvant calcium enhances ablation area in vitro for H-FIRE treatments of several pulse durations. Furthermore, H-FIRE treatment delivered with CaCl2 results in cell death thresholds higher than that of H-FIRE without calcium and comparable to IRE thresholds without calcium. Quantifying the reversible electroporation threshold revealed that CaCl2 enhances the permeabilization of cells compared to a NaCl control. H-FIRE treatment with calcium enhances the IRE to thermal cell death ratio, thereby also enhancing the positive immune response from treatment.
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公开(公告)号：US20210023362A1
公开(公告)日：2021-01-28
申请号：US16938778
申请日：2020-07-24
发明人： Melvin F. Lorenzo , Christopher B. Arena , Suyashree Bhonsle , Natalie White , Lucy Epshteyn , Rafael V. Davalos
摘要： Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue, resulting in changes in passive electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time (˜10 s); this timeframe is much larger than pulse periods used with EBTs (˜1 s). Fourier Analysis SpecTroscopy (FAST) is introduced as a methodology for monitoring tissue inter-burst impedance (diagnostic FAST) and intra-burst impedance (therapeutic FAST) during EBTs. FAST is a rapid-capture (
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公开(公告)号：US20210022795A1
公开(公告)日：2021-01-28
申请号：US17069359
申请日：2020-10-13
摘要： Methods for treating tissue with irreversible electroporation and immunotherapy are described. The methods include placing a probe in tissue within a human body, wherein the probe has at least a first electrode, applying a plurality of electrical pulses through the first electrode and a second electrode, causing irreversible electroporation (IRE) of the tissue within a target ablation zone, and administering one or more exogenous agents into the tissue within the target ablation zone or to the human, thereby stimulating or otherwise modulating an immune system response within the body.
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公开(公告)号：US10828086B2
公开(公告)日：2020-11-10
申请号：US16232962
申请日：2018-12-26
摘要： Methods for treating tissue with irreversible electroporation and immunotherapy are described. The methods include placing a probe in tissue within a human body, wherein the probe has at least a first electrode, applying a plurality of electrical pulses through the first electrode and a second electrode, causing irreversible electroporation (IRE) of the tissue within a target ablation zone, and administering one or more exogenous agents into the tissue within the target ablation zone or to the human, thereby stimulating or otherwise modulating an immune system response within the body.
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50.发明申请公开(公告)号：US20200046432A1
公开(公告)日：2020-02-13
申请号：US16655845
申请日：2019-10-17
发明人： Paulo A. Garcia , Rafael V. Davalos
摘要： The invention provides for a system for estimating a 3-dimensional treatment volume for a device that applies treatment energy through a plurality of electrodes defining a treatment area, the system comprising 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 first 3-dimensional treatment volume for display in the display device based on the ratio of a maximum conductivity of the treatment area to a baseline conductivity of the treatment area. The invention also provides for a method for estimating 3-dimensional treatment volume, the steps of which are executable through the processor. In embodiments, the system and method are based on a numerical model which may be implemented in computer readable code which is executable through a processor.
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