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1. 发明申请

WO2013166019A1 ULTRASOUND TRANSDUCER MANUFACTURING USING RAPID-PROTOTYPING METHOD 审中-公开
标题翻译：超声波传感器制造使用快速原型方法
公开(公告)号：WO2013166019A1
公开(公告)日：2013-11-07
申请号：PCT/US2013/038873
申请日：2013-04-30
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： HALL, Timothy L. , MAXWELL, Adam , CAIN, Charles A. , KIM, Yohan , XU, Zhen
IPC分类号： A61N7/00
CPC分类号： A61N7/02 , A61B17/225 , A61B17/320068 , A61B2017/00526 , A61N2007/0039 , A61N2007/006 , A61N2007/0065 , A61N2007/0091 , A61N2007/0095 , B06B1/0607 , B33Y10/00 , B33Y80/00 , G01N29/223 , G01N29/225 , G01N29/226 , G01N29/2437 , G01N29/245 , G10K11/004 , H01L41/04 , H01L41/053 , H01L41/1876 , H01L41/23 , H01L41/25 , Y10T29/42 , Y10T29/49005 , Y10T29/49007
摘要： An ultrasound therapy system is provided that can include any number of features. In some embodiments, the custom transducer housings can be manufactured using a rapid- prototyping method to arrange a plurality of single-element, substantially flat transducers to share a common focal point. The rapid-prototyping method can include, for example, fused- deposition modeling, 3D printing, and stereolithography. In some embodiments, the therapy system can include a plurality of transducer modules insertable into the openings of the transducer housing. Each transducer module can include an acoustic lens, a substantially flat, single-element transducer, and a matching layer disposed between the lens and the transducer. Methods of use and manufacture are also described.
摘要翻译：提供了可以包括任何数量的特征的超声治疗系统。在一些实施例中，定制换能器壳体可以使用快速原型方法制造，以布置多个单元件，基本上平坦的换能器以共享公共焦点。快速原型方法可以包括例如熔融沉积建模，3D印刷和立体光刻。在一些实施例中，治疗系统可以包括可插入换能器壳体的开口中的多个换能器模块。每个换能器模块可以包括声透镜，基本平坦的单元件换能器以及设置在透镜和换能器之间的匹配层。还描述了使用和制造方法。

2. 发明申请

WO2011028609A2 DEVICES AND METHODS FOR USING CONTROLLED BUBBLE CLOUD CAVITATION IN FRACTIONATING URINARY STONES 审中-公开
标题翻译：使用控制的泡状云空腔分割尿石的装置和方法
公开(公告)号：WO2011028609A2
公开(公告)日：2011-03-10
申请号：PCT/US2010/046810
申请日：2010-08-26
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , CAIN, Charles A. , HALL, Timothy L. , ROBERTS, William R. , XU, Zhen , FOWLKES, J. Brian , DAVISON, Thomas W.
发明人： CAIN, Charles A. , HALL, Timothy L. , ROBERTS, William R. , XU, Zhen , FOWLKES, J. Brian , DAVISON, Thomas W.
IPC分类号： A61B17/225 , A61B18/26 , A61B6/12 , A61B8/00
CPC分类号： A61N7/00 , A61B8/00 , A61B17/225 , A61B17/2256 , A61B2017/00172 , A61B2017/22008 , A61B2090/378
摘要： A medical imaging and therapy device is provided that may include any of a number of features. One feature of the device is that it can deliver Lithotripsy therapy to a patient, so as to fractionate urinary stones. Another feature of the device is that it can deliver Histotripsy therapy to a patient, so as to erode urinary stones. In some embodiments, the medical imaging and therapy device is configured to target and track urinary stones in the patient during therapy. Methods associated with use of the medical imaging and therapy device are also covered.
摘要翻译：提供了一种医学成像和治疗设备，其可以包括许多特征中的任何特征。该装置的一个特点是它可以为患者提供碎石治疗，以便分泌尿道结石。该装置的另一个特点是它可以为病人提供组织治疗疗法，从而消除泌尿系结石。在一些实施例中，医疗成像和治疗装置被配置为在治疗期间靶向和追踪患者的泌尿结石。还包括与使用医疗成像和治疗设备相关的方法。

3. 发明申请

WO2022056394A1 TRANSCRANIAL MR-GUIDED HISTOTRIPSY SYSTEMS AND METHODS 审中-公开
公开(公告)号：WO2022056394A1
公开(公告)日：2022-03-17
申请号：PCT/US2021/050088
申请日：2021-09-13
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： XU, Zhen , NOLL, Douglas , HALL, Timothy, L.
IPC分类号： A61N7/02 , A61B5/055 , A61B90/00 , G01R33/48
摘要： A transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system is provided. Using electronic steering only, the tcMRgHt system is configured to create lesions of 25.5 mm in the transverse plane and 50 mm in the axial plane through the skull of a patient. This disclosure provides the design, fabrication, acoustic characterization, and MR compatibility assessment of tcMRgHt systems for histotripsy.

4. 发明申请

WO2015027164A1 HISTOTRIPSY USING VERY SHORT ULTRASOUND PULSES 审中-公开
标题翻译：使用非常短的超声波脉冲的感觉
公开(公告)号：WO2015027164A1
公开(公告)日：2015-02-26
申请号：PCT/US2014/052310
申请日：2014-08-22
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： CAIN, Charles, A. , MAXWELL, Adam , XU, Zhen , LIN, Kuang-Wei
IPC分类号： A61N7/00
CPC分类号： A61N7/00 , A61N2007/0039 , A61N2007/0065
摘要： Apparatus and methods are provided for applying ultrasound pulses into tissue or a medium in which the peak negative pressure (P-) of one or more negative half cycle(s) of the ultrasound pulses exceed(s) an intrinsic threshold of the tissue or medium, to directly form a dense bubble cloud in the tissue or medium without shock-scattering. In one embodiment, a microtripsy method of Histotripsy therapy comprises delivering an ultrasound pulse from an ultrasound therapy transducer into tissue, the ultrasound pulse having at least a portion of a peak negative pressure half-cycle that exceeds an intrinsic threshold in the tissue to produce a bubble cloud of at least one bubble in the tissue, and generating a lesion in the tissue with the bubble cloud.. The intrinsic threshold can vary depending on the type of tissue to be treated. In some embodiments, the intrinsic threshold in tissue can range from 15-30 MPa.
摘要翻译：提供了用于将超声脉冲施加到组织或介质中的装置和方法，其中超声脉冲的一个或多个负半周的峰值负压（P-）超过组织或介质的固有阈值直接在组织或介质中形成致密的气泡云而不产生冲击散射。在一个实施例中，组织切除术治疗的微切术方法包括将超声波脉冲从超声治疗换能器输送到组织中，所述超声脉冲具有超过组织中的固有阈值的至少一部分峰值负压半周期以产生组织中至少有一个气泡的气泡云，并且在气泡云中产生组织中的病变。本征阈值可以根据待治疗组织的类型而变化。在一些实施方案中，组织中的固有阈值可以在15-30MPa的范围内。

5. 发明申请

WO2007038160A2 PULSED CAVITATIONAL ULTRASOUND THERAPY 审中-公开
标题翻译：脉冲超声治疗
公开(公告)号：WO2007038160A2
公开(公告)日：2007-04-05
申请号：PCT/US2006/036721
申请日：2006-09-20
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , CAIN, Charles A. , FOWLKES, J. Brian , XU, Zhen , HALL, Timothy L.
发明人： CAIN, Charles A. , FOWLKES, J. Brian , XU, Zhen , HALL, Timothy L.
IPC分类号： A61B8/00
CPC分类号： A61M37/0092 , A61B8/00 , A61B8/485 , A61B17/22004 , A61B2017/22088 , A61B2017/22089
摘要： Therapy methods using pulsed cavitational ultrasound therapy can include the subprocesses of initiation, maintenance, therapy, and feedback of the histotripsy process, which involves the creation and maintenance of ensembles of microbubbles and the use of feedback in order to optimize the process based on observed spatial- temporal bubble cloud dynamics. The methods provide for the subdivision or erosion of tissue, liquification of tissue, and the enhanced delivery of therapeutic agents. Various feedback mechanisms allow variation of ultrasound parameters and provide control over the pulsed cavitational process, permitting the process to be tuned for a number of applications. Such applications can include specific tissue erosion, bulk tissue homogenization, and delivery of therapeutic agents across barriers.
摘要翻译：使用脉冲空化超声治疗的治疗方法可以包括组织过程的起始，维持，治疗和反馈的子过程，其涉及创建和维护微泡组合以及反馈的使用，以便基于观察到的空间来优化过程 - 时间泡沫云动态。该方法提供了组织的细分或侵蚀，组织的液化以及增强的治疗剂的递送。各种反馈机制允许超声参数的变化并且提供对脉冲空化过程的控制，允许该过程针对多个应用进行调整。这样的应用可以包括特定的组织侵蚀，本体组织均质化和跨越障碍物的治疗剂的递送。

6. 发明申请

WO2021155026A1 SYSTEMS AND METHODS FOR HISTOTRIPSY IMMUNOSENSITIZATION 审中-公开
公开(公告)号：WO2021155026A1
公开(公告)日：2021-08-05
申请号：PCT/US2021/015532
申请日：2021-01-28
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERAN AFFAIRS
发明人： XU, Zhen , CHO, Clifford, Suhyun
IPC分类号： A61N7/02 , A61B17/00 , A61P35/00 , A61P35/04
摘要： Systems and methods for histotripsy and immunotherapy are provided. In some embodiments, histotripsy can be applied to a target tissue volume to lyse and solubilize the target tissue volume to release tumor antigens. In some embodiments, an immune response of the treatment can be evaluated. In other embodiments, an immune therapy can be applied after applying the histotripsy. In one embodiment, the lysed and solubilized cells can be extracted from the tissue. The extracted cells can be used to create immune therapies, including vaccines.

7. 发明申请

WO2011028603A3 MICROMANIPULATOR CONTROL ARM FOR THERAPEUTIC AND IMAGING ULTRASOUND TRANSDUCERS 审中-公开
公开(公告)号：WO2011028603A3
公开(公告)日：2011-03-10
申请号：PCT/US2010/046794
申请日：2010-08-26
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , ROBERTS, William, W. , HALL, Timothy, L. , CAIN, Charles, A. , FOWLKES, J., Brian , XU, Zhen , KUSNER, Michael, Thomas, Jr. , TEOFILOVIC, Dejan
发明人： ROBERTS, William, W. , HALL, Timothy, L. , CAIN, Charles, A. , FOWLKES, J., Brian , XU, Zhen , KUSNER, Michael, Thomas, Jr. , TEOFILOVIC, Dejan
IPC分类号： A61N7/00 , A61B8/00 , A61B8/13 , B25J7/00
摘要： A medical imaging and therapy device is provided that may include any of a number of features. One feature of the device is that it can image a target tissue volume and apply ultrasound energy to the target tissue volume. In some embodiments, the medical imaging and therapy device is configured controllably apply ultrasound energy into the prostate by maintaining a cavitational bubble cloud generated by an ultrasound therapy system within an image of the prostate generated by an imaging system. The medical imaging and therapy device can be used in therapeutic applications such as Histotripsy, Lithotripsy, and HIFU, for example. Methods associated with use of the medical imaging and therapy device are also covered.

8. 发明申请

WO2009094554A2 HISTOTRIPSY FOR THROMBOLYSIS 审中-公开
标题翻译：血液透析病因
公开(公告)号：WO2009094554A2
公开(公告)日：2009-07-30
申请号：PCT/US2009/031857
申请日：2009-01-23
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , MAXWELL, Adam , XU, Zhen , GURM, Hitinder S. , CAIN, Charles A.
发明人： MAXWELL, Adam , XU, Zhen , GURM, Hitinder S. , CAIN, Charles A.
IPC分类号： A61N7/00 , A61B18/18
CPC分类号： A61N7/02 , A61B2017/22001
摘要： Methods for performing non-invasive thrombolysis with ultrasound using, in some embodiments, one or more ultrasound transducers to focus or place a high intensity ultrasound beam onto a blood clot (thrombus) or other vascular inclusion or occlusion (e.g., clot in the dialysis graft, deep vein thrombosis, superficial vein thrombosis, arterial embolus, bypass graft thrombosis or embolization, pulmonary embolus) which would be ablated (eroded, mechanically fractionated, liquefied, or dissolved) by ultrasound energy. The process can employ one or more mechanisms, such as of cavitational, sonochemical, mechanical fractionation, or thermal processes depending on the acoustic parameters selected. This general process, including the examples of application set forth herein, is henceforth referred to as 'Thrombolysis.'
摘要翻译：在一些实施例中，使用一个或多个超声换能器进行非侵入性溶栓治疗的方法，以将高强度超声波束聚焦或放置在血块（血栓）或其它血管夹层或闭塞（例如，透析移植物中的凝块），深静脉血栓形成，浅静脉血栓形成，动脉栓塞，旁路移植物血栓形成或栓塞，肺栓塞），其将被超声能量消融（侵蚀，机械分级，液化或溶解）。根据所选择的声学参数，该方法可采用一种或多种机制，例如空化，声化学，机械分级或热过程。这个通用方法，包括本文所述的应用实例，以下称为“溶栓”。

9. 发明申请

WO2008143998A1 PULSED CAVITATIONAL ULTRASOUND THERAPY 审中-公开
标题翻译：脉冲超声治疗
公开(公告)号：WO2008143998A1
公开(公告)日：2008-11-27
申请号：PCT/US2008/006327
申请日：2008-05-16
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , CAIN, Charles, A. , XU, Zhen , FOWLKES, J., Brian , HALL, Timothy, L. , ROBERTS, William, W.
发明人： CAIN, Charles, A. , XU, Zhen , FOWLKES, J., Brian , HALL, Timothy, L. , ROBERTS, William, W.
IPC分类号： A61B8/00 , A61B17/22
CPC分类号： A61B17/22004 , A61B5/0536 , A61B5/055 , A61B8/00 , A61B8/08 , A61B8/4272 , A61B8/485 , A61B17/225 , A61B2017/00154 , A61B2017/00172 , A61B2017/22008 , A61B2017/22088 , A61B2017/22089 , A61B2090/378 , A61M37/0092
摘要： Therapy methods using pulsed cavitational ultrasound therapy can include the subprocesses of initiation, maintenance, therapy, and feedback of the histotripsy process, which involves the creation and maintenance of ensembles of microbubbles and the use of feedback in order to optimize the process based on observed spatial-temporal bubble cloud dynamics. The methods provide for the subdivision or erosion of tissue, liquification of tissue, and/or the enhanced delivery of therapeutic agents. Various feedback mechanisms allow variation of ultrasound parameters and provide control over the pulsed cavitational process, permitting the process to be tuned for a number of applications. Such applications can include specific tissue erosion, bulk tissue homogenization, and delivery of therapeutic agents across barriers.
摘要翻译：使用脉冲空化超声治疗的治疗方法可以包括组织过程的起始，维持，治疗和反馈的子过程，其涉及创建和维护微泡组合以及反馈的使用，以便基于观察到的空间来优化过程 - 时空泡云动力学。这些方法提供组织的细分或侵蚀，组织液化和/或治疗剂的增强递送。各种反馈机制允许超声参数的变化并且提供对脉冲空化过程的控制，允许该过程针对多个应用进行调整。这样的应用可以包括特定的组织侵蚀，本体组织均质化和跨越障碍物的治疗剂的递送。

10. 发明申请

WO2022260747A1 ALL-IN-ONE ULTRASOUND SYSTEMS AND METHODS INCLUDING HISTOTRIPSY 审中-公开
公开(公告)号：WO2022260747A1
公开(公告)日：2022-12-15
申请号：PCT/US2022/023786
申请日：2022-04-07
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： XU, Zhen , HALL, Timothy, Lewis , SUKOVICH, Jonathan
IPC分类号： A61B17/22 , A61B17/225 , A61B8/00 , A61N7/02
摘要： An all-in-one ultrasound therapy system configured for the treatment of tissue is provided, which may include any number of features. Provided herein are systems and methods that provide efficacious non-invasive and minimally invasive therapeutic, diagnostic and research procedures. In particular, provided herein are optimized systems and methods that provide targeted, efficacious ultrasound therapy in a variety of different regions and under a variety of different conditions without causing undesired tissue damage to intervening/non-target tissues or structures. The ultrasound therapy can include modalities such as histotripsy, hyperthermia/radio-sensitization, HIFU microbubble-enhanced drug delivery, immunotherapy, sonodynamic therapy, and/or neuromodulation.

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