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41. 发明授权

US08145316B2 Methods and apparatus for renal neuromodulation 有权
标题翻译：肾脏神经调节的方法和装置
公开(公告)号：US08145316B2
公开(公告)日：2012-03-27
申请号：US11189563
申请日：2005-07-25
申请人： Mark Deem , Denise Demarais , Douglas Sutton , Hanson Gifford, III , Howard R. Levin , Mark Gelfand , Benjamin J. Clark
发明人： Mark Deem , Denise Demarais , Douglas Sutton , Hanson Gifford, III , Howard R. Levin , Mark Gelfand , Benjamin J. Clark
IPC分类号： A61N1/00 , A61N1/30
CPC分类号： A61N1/36117 , A61B18/1492 , A61B2018/00267 , A61B2018/00404 , A61B2018/00434 , A61B2018/00511 , A61B2018/00577 , A61B2018/00613 , A61B2018/00702 , A61B2018/00779 , A61B2018/00791 , A61B2018/00875 , A61B2018/00982 , A61B2018/1435 , A61N1/0551 , A61N1/32 , A61N1/327 , A61N1/36007 , A61N1/36017 , A61N1/36128 , A61N5/00
摘要： Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for extravascular delivery of pulsed electric fields to achieve such neuromodulation.
摘要翻译：提供使用脉冲电场进行肾神经调节以实现电穿孔或电融合的方法和装置。预期肾脏神经调节（例如去神经支配）可以减少急性心肌梗塞的扩张，减少或预防与充血性心力衰竭有关的形态学变化的发生，和/或有效治疗晚期肾脏疾病。本发明的实施例被配置为用于实现这种神经调节的脉冲电场的血管外递送。

42. 发明申请

US20110166499A1 METHODS AND APPARATUS FOR INDUCING CONTROLLED RENAL NEUROMODULATION 审中-公开
标题翻译：诱导控制性肾脏神经调节的方法和装置
公开(公告)号：US20110166499A1
公开(公告)日：2011-07-07
申请号：US13042341
申请日：2011-03-07
申请人： Denise Demarais , Nicolas Zadno
发明人： Denise Demarais , Nicolas Zadno
IPC分类号： A61N1/36 , A61M37/00
CPC分类号： A61N1/327 , A61N1/0514 , A61N1/08 , A61N1/36007
摘要： Methods and apparatus are provided for inducing, monitoring and controlling renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. In some embodiments, tissue impedance, conductance or conductivity may be monitored to determine the effects of pulsed electric field therapy, e.g., to determine an extent of electroporation and its degree of irreversibility. Pulsed electric field electroporation of tissue causes a decrease in tissue impedance and an increase in tissue conductivity. If induced electroporation is reversible, upon cessation of the pulsed electric field, tissue impedance and conductivity should approximate baseline levels; however, if electroporation is irreversible, impedance and conductivity changes should persist. Thus, monitoring of impedance or conductivity may be utilized to determine the onset of electroporation and to determine the type or extent of electroporation. Furthermore, monitoring data may be used in one or more manual or automatic feedback loops to control the electroporation.
摘要翻译：提供了使用脉冲电场诱导，监测和控制肾神经调节以实现电穿孔或电融合的方法和装置。在一些实施例中，可以监测组织阻抗，电导或电导率以确定脉冲电场治疗的效果，例如确定电穿孔的程度及其不可逆程度。组织的脉冲电场电穿孔导致组织阻抗的减少和组织传导性的增加。如果诱导电穿孔是可逆的，则在脉冲电场停止时，组织阻抗和电导率应近似基线水平; 然而，如果电穿孔是不可逆的，阻抗和电导率的变化应该持续。因此，可以使用阻抗或电导率的监测来确定电穿孔的发作并确定电穿孔的类型或程度。此外，监测数据可用于一个或多个手动或自动反馈回路中以控制电穿孔。

43. 发明授权

US07937143B2 Methods and apparatus for inducing controlled renal neuromodulation 有权
标题翻译：诱导受控肾神经调节的方法和装置
公开(公告)号：US07937143B2
公开(公告)日：2011-05-03
申请号：US11252462
申请日：2005-10-18
申请人： Denise Demarais , Nicolas Zadno
发明人： Denise Demarais , Nicolas Zadno
IPC分类号： A61N1/30
CPC分类号： A61N1/327 , A61N1/0514 , A61N1/08 , A61N1/36007
摘要： Methods and apparatus are provided for inducing, monitoring and controlling renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. In some embodiments, tissue impedance, conductance or conductivity may be monitored to determine the effects of pulsed electric field therapy, e.g., to determine an extent of electroporation and its degree of irreversibility. Pulsed electric field electroporation of tissue causes a decrease in tissue impedance and an increase in tissue conductivity. If induced electroporation is reversible, upon cessation of the pulsed electric field, tissue impedance and conductivity should approximate baseline levels; however, if electroporation is irreversible, impedance and conductivity changes should persist. Thus, monitoring of impedance or conductivity may be utilized to determine the onset of electroporation and to determine the type or extent of electroporation. Furthermore, monitoring data may be used in one or more manual or automatic feedback loops to control the electroporation.
摘要翻译：提供了使用脉冲电场诱导，监测和控制肾神经调节以实现电穿孔或电融合的方法和装置。在一些实施例中，可以监测组织阻抗，电导或电导率以确定脉冲电场治疗的效果，例如确定电穿孔的程度及其不可逆程度。组织的脉冲电场电穿孔导致组织阻抗的减少和组织传导性的增加。如果诱导电穿孔是可逆的，则在脉冲电场停止时，组织阻抗和电导率应近似基线水平; 然而，如果电穿孔是不可逆的，阻抗和电导率的变化应该持续。因此，可以使用阻抗或电导率的监测来确定电穿孔的发作并确定电穿孔的类型或程度。此外，监测数据可用于一个或多个手动或自动反馈回路中以控制电穿孔。

44. 发明申请

US20100191112A1 ULTRASOUND APPARATUSES FOR THERMALLY-INDUCED RENAL NEUROMODULATION 有权
标题翻译：用于热诱导的肾脏神经调节的超声波设备
公开(公告)号：US20100191112A1
公开(公告)日：2010-07-29
申请号：US12754337
申请日：2010-04-05
申请人： Denise Demarais , Nicolas Zadno , Benjamin J. Clark , Erik Thai , Howard R. Levin , Mark Gelfand
发明人： Denise Demarais , Nicolas Zadno , Benjamin J. Clark , Erik Thai , Howard R. Levin , Mark Gelfand
IPC分类号： A61N7/02 , A61B8/12
CPC分类号： A61N7/022 , A61B18/02 , A61B18/04 , A61B18/12 , A61B18/1492 , A61B2018/0022 , A61B2018/00434 , A61B2018/00511 , A61B2018/00577 , A61F7/007 , A61F7/12 , A61F7/123 , A61F2007/126 , A61M5/44 , A61M2210/1082 , A61N1/28 , A61N1/36007 , A61N1/403 , A61N5/00 , A61N5/025 , A61N5/045 , A61N5/0603 , A61N7/00 , A61N7/02 , A61N2007/003 , A61N2007/0078
摘要： Methods and apparatus are provided for thermally-induced renal neuromodulation. Thermally-induced renal neuromodulation may be achieved via direct and/or via indirect application of thermal energy to heat or cool neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers. In some embodiments, parameters of the neural fibers, of non-target tissue, or of the thermal energy delivery element, may be monitored via one or more sensors for controlling the thermally-induced neuromodulation. In some embodiments, protective elements may be provided to reduce a degree of thermal damage induced in the non-target tissues.
摘要翻译：提供了用于热诱导的肾神经调节的方法和装置。热诱导的肾神经调节可以通过直接和/或通过间接施加热能来加热或冷却有助于肾功能的神经纤维或者供给或灌注神经纤维的血管结构来实现。在一些实施例中，神经纤维，非目标组织或热能递送元件的参数可以经由一个或多个传感器来监测，以控制热诱导的神经调节。在一些实施方案中，可以提供保护元件以减少在非靶组织中诱导的热损伤程度。

45. 发明授权

US07763010B2 Apparatus and methods for clot dissolution 有权
标题翻译：用于凝块溶解的装置和方法
公开(公告)号：US07763010B2
公开(公告)日：2010-07-27
申请号：US10142005
申请日：2002-05-08
申请人： Michael A. Evans , Denise Demarais , Dino De Cicco , Kelvin Ning , Alexander Khairkhahan , Tyler Jon Strang
发明人： Michael A. Evans , Denise Demarais , Dino De Cicco , Kelvin Ning , Alexander Khairkhahan , Tyler Jon Strang
IPC分类号： A61M31/00
CPC分类号： A61M25/0021 , A61B17/22 , A61B17/320725 , A61B17/320758 , A61B2017/22067 , A61B2017/22084 , A61M25/007 , A61M25/0105
摘要： Clot disruption and dissolution are achieved using a catheter having the ability to infuse a thrombolytic agent, aspirate clot and fluid, and allow passage of a guidewire. Optionally, the catheter may also include a mechanical agitator for further disrupt clot in the presence of the thrombolytic agent. A flow resistor in the catheter provides for infusion and/or aspiration to be concentrated primarily at a clot treatment area in a blood vessel while also providing optional infusion and/or aspiration distal to the treatment area. In some embodiments, infusion, aspiration and guidewire passage occur through a common lumen. The thrombolytic agent, such as tPA, streptokinase, or urokinase, is directly released into the clot at the point where the agitator is engaging the clot. In this way, the thrombolytic activity of the agent is enhanced and the dissolution of the clot is improved.
摘要翻译：使用具有注入溶栓剂，抽吸凝块和流体并允许导丝通过的能力的导管实现凝块破裂和溶解。任选地，导管还可以包括用于在溶栓剂存在下进一步破坏凝块的机械搅拌器。导管中的流阻器提供输注和/或抽吸主要集中在血管中的凝块治疗区域，同时还提供可选的输液和/或远离治疗区域的抽吸。在一些实施例中，输注，抽吸和导丝通过共同内腔。血栓溶解剂如tPA，链激酶或尿激酶在搅拌器与凝块接合的位置处直接释放到凝块中。以这种方式，药剂的溶栓活性增强，并且凝块的溶解得到改善。

46. 发明申请

US20070129761A1 Methods for treating heart arrhythmia 审中-公开
标题翻译：治疗心律失常的方法
公开(公告)号：US20070129761A1
公开(公告)日：2007-06-07
申请号：US11599882
申请日：2006-11-14
申请人： Denise Demarais , Hanson Gifford
发明人： Denise Demarais , Hanson Gifford
IPC分类号： A61N1/00
CPC分类号： A61M25/0084 , A61B17/3478 , A61B18/04 , A61B18/1492 , A61B2018/0022 , A61B2018/00434 , A61B2018/00511 , A61B2018/00577 , A61F7/007 , A61K38/4893 , A61M5/00 , A61M2025/0085 , A61M2202/0007 , A61M2210/1082 , A61N1/05 , A61N1/0551 , A61N1/32 , A61N1/36017 , A61N1/36114 , A61N7/02 , C12Y304/24069
摘要： Methods and apparatus are provided for treatment of heart arrhythmia via renal neuromodulation. Such neuromodulation may effectuate irreversible electroporation or electrofusion, ablation, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential attenuation or blockade, changes in cytokine up-regulation and other conditions in target neural fibers. In some embodiments, such neuromodulation is achieved through application of an electric field. In some embodiments, such neuromodulation is achieved through application of neuromodulatory agents, of thermal energy and/or of high intensity focused ultrasound. In some embodiments, such neuromodulation is performed in a bilateral fashion.
摘要翻译：提供了通过肾脏神经调节治疗心律失常的方法和装置。这种神经调节可以实现不可逆的电穿孔或电融合，消融，坏死和/或诱导凋亡，基因表达的改变，动作电位衰减或阻断，细胞因子上调的变化和靶神经纤维中的其它条件。在一些实施例中，通过施加电场来实现这种神经调节。在一些实施方案中，通过应用神经调节剂，热能和/或高强度聚焦超声来实现这种神经调节。在一些实施方案中，这种神经调节以双向方式进行。

47. 发明申请

US20050261672A1 Systems and methods for selective denervation of heart dysrhythmias 审中-公开
标题翻译：选择性去神经心脏心律失常的系统和方法
公开(公告)号：US20050261672A1
公开(公告)日：2005-11-24
申请号：US11133088
申请日：2005-05-18
申请人： Mark Deem , Hanson Gifford , Denise Demarais
发明人： Mark Deem , Hanson Gifford , Denise Demarais
IPC分类号： A61B18/14
CPC分类号： A61B18/1492 , A61B2018/00351 , A61B2018/00357 , A61B2018/00613
摘要： Methods and apparatus are provided for selective denervation of conduction pathways in the heart for the treatment of dysrhythmias, including one or more ablation or electroporation catheters having electrodes for stimulating, targeting, and ablating fat pad tissue and other cardiac tissue to selectively denervate heart tissue.
摘要翻译：提供了用于选择性去神经支配心脏传导途径用于治疗心律失常的方法和装置，包括一个或多个消融或电穿孔导管，其具有用于刺激，靶向和消融脂肪垫组织和其它心脏组织以选择性去神经细胞组织的电极。

48. 发明授权

US06929633B2 Apparatus and methods for clot dissolution 有权
标题翻译：用于凝块溶解的装置和方法
公开(公告)号：US06929633B2
公开(公告)日：2005-08-16
申请号：US10278735
申请日：2002-10-21
申请人： Michael A. Evans , Denise Demarais , Dino De Cicco , Kelvin Ning , Alexander Khairkhahan , Tyler Jon Strang , Jody Maria Cimbalo , Stephen Leeflang
发明人： Michael A. Evans , Denise Demarais , Dino De Cicco , Kelvin Ning , Alexander Khairkhahan , Tyler Jon Strang , Jody Maria Cimbalo , Stephen Leeflang
IPC分类号： A61B17/22 , A61M25/00 , A61M25/01 , A61M39/22 , A61M31/00
CPC分类号： A61B17/320758 , A61B17/22 , A61B17/22004 , A61B2017/00685 , A61B2017/22054 , A61B2017/22067 , A61B2017/22084 , A61B2017/320716 , A61B2017/320766 , A61M25/0021 , A61M25/007 , A61M25/0075 , A61M25/0105 , A61M39/22 , A61M2025/1052
摘要： Clot disruption and dissolution are achieved using a catheter having the ability to infuse a thrombolytic agent, agitate the clot and agent, and aspirate broken-up clot from the blood vessel. A flow resistor in the catheter provides for infusion and/or aspiration to be concentrated primarily at a clot treatment area in a blood vessel while also providing optional infusion and/or aspiration distal to the treatment area. In some embodiments, infusion, aspiration and guidewire passage occur through a common lumen. The thrombolytic agent, such as tPA, streptokinase, or urokinase, is directly released into the clot at the point where the agitator is engaging the clot. In this way, the thrombolytic activity of the agent is enhanced and the dissolution of the clot is improved.
摘要翻译：使用具有注入溶栓剂，搅动凝块和药剂的能力的导管，以及从血管中抽出破碎的凝块来实现凝块破裂和溶解。导管中的流阻器提供输注和/或抽吸主要集中在血管中的凝块治疗区域，同时还提供可选的输液和/或远离治疗区域的抽吸。在一些实施例中，输注，抽吸和导丝通过共同内腔。血栓溶解剂如tPA，链激酶或尿激酶在搅拌器与凝块接合的位置处直接释放到凝块中。以这种方式，药剂的溶栓活性增强，并且凝块的溶解得到改善。

49. 发明授权

US08768470B2 Methods for monitoring renal neuromodulation 有权
标题翻译：监测肾脏神经调节的方法
公开(公告)号：US08768470B2
公开(公告)日：2014-07-01
申请号：US12777892
申请日：2010-05-11
申请人： Mark Deem , Hanson Gifford, III , Denise Demarais , Douglas Sutton , Erik Thai , Mark Gelfand , Howard R. Levin
发明人： Mark Deem , Hanson Gifford, III , Denise Demarais , Douglas Sutton , Erik Thai , Mark Gelfand , Howard R. Levin
IPC分类号： A61N1/00 , A61B18/18 , A61N1/05 , A61N1/36 , A61B18/14 , A61N5/00 , A61N1/04 , A61B18/00 , A61N7/00 , A61N1/32
CPC分类号： A61N1/36007 , A61B8/0891 , A61B8/12 , A61B18/1206 , A61B18/1233 , A61B18/1492 , A61B18/18 , A61B2018/00071 , A61B2018/00214 , A61B2018/0022 , A61B2018/00267 , A61B2018/00404 , A61B2018/00434 , A61B2018/00505 , A61B2018/00511 , A61B2018/00577 , A61B2018/00613 , A61B2018/00642 , A61B2018/00904 , A61B2018/126 , A61B2018/1467 , A61M5/14 , A61M25/0023 , A61N1/0412 , A61N1/05 , A61N1/0551 , A61N1/18 , A61N1/205 , A61N1/326 , A61N1/327 , A61N1/36017 , A61N1/36057 , A61N1/3606 , A61N1/36103 , A61N1/36114 , A61N1/36117 , A61N1/36139 , A61N5/00 , A61N7/00 , A61N2007/0021 , A61N2007/003
摘要： Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for percutaneous intravascular delivery of pulsed electric fields to achieve such neuromodulation.
摘要翻译：提供使用脉冲电场进行肾神经调节以实现电穿孔或电融合的方法和装置。预期肾脏神经调节（例如去神经支配）可以减少急性心肌梗塞的扩张，减少或预防与充血性心力衰竭有关的形态学变化的发生，和/或有效治疗晚期肾脏疾病。本发明的实施例被配置用于经皮血管内递送脉冲电场以实现这种神经调节。

50. 发明申请

US20140018879A1 Apparatuses for Renal Neuromodulation 有权
标题翻译：肾脏神经调节装置
公开(公告)号：US20140018879A1
公开(公告)日：2014-01-16
申请号：US13942223
申请日：2013-07-15
申请人： Mark Deem , Denise Demarais , Douglas Sutton , Hanson Gifford, III , Howard R. Levin , Mark Gelfand , Benjamin J. Clark
发明人： Mark Deem , Denise Demarais , Douglas Sutton , Hanson Gifford, III , Howard R. Levin , Mark Gelfand , Benjamin J. Clark
IPC分类号： A61N1/36
CPC分类号： A61N1/36117 , A61B18/1492 , A61B2018/00267 , A61B2018/00404 , A61B2018/00434 , A61B2018/00511 , A61B2018/00577 , A61B2018/00613 , A61B2018/00702 , A61B2018/00779 , A61B2018/00791 , A61B2018/00875 , A61B2018/00982 , A61B2018/1435 , A61N1/0551 , A61N1/32 , A61N1/327 , A61N1/36007 , A61N1/36017 , A61N1/36128 , A61N5/00
摘要： Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for extravascular delivery of pulsed electric fields to achieve such neuromodulation.
摘要翻译：提供使用脉冲电场进行肾神经调节以实现电穿孔或电融合的方法和装置。预期肾脏神经调节（例如去神经支配）可以减少急性心肌梗塞的扩张，减少或预防与充血性心力衰竭有关的形态学变化的发生，和/或有效治疗晚期肾脏疾病。本发明的实施例被配置为用于实现这种神经调节的脉冲电场的血管外递送。

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