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1. 发明授权

US10918298B2 High-speed, high-resolution electrophysiology in-vivo using conformal electronics 有权
公开(公告)号：US10918298B2
公开(公告)日：2021-02-16
申请号：US12968637
申请日：2010-12-15
申请人： John A. Rogers , Dae Hyeong Kim , Joshua D. Moss , David J. Callans , Brian Litt , Jonathan Viventi
发明人： John A. Rogers , Dae Hyeong Kim , Joshua D. Moss , David J. Callans , Brian Litt , Jonathan Viventi
IPC分类号： A61B5/042 , A61N1/05 , H01L23/31 , A61B5/07 , H05K1/02 , A61B5/00 , A61N1/04 , H01L23/00 , H05K3/32 , H01L29/786 , H05K1/14 , H01L21/683 , H01L27/12 , A61N1/36
摘要： Provided herein are biomedical devices and methods of making and using biomedical devices for sensing and actuation applications. For example, flexible and/or stretchable biomedical devices are provided including electronic devices useful for establishing in situ conformal contact with a tissue in a biological environment. The invention includes implantable electronic devices and devices administered to the surfaces(s) of a target tissue, for example, for obtaining electrophysiology data from a tissue such as cardiac, brain tissue or skin.

2. 发明申请

US20130072775A1 Conformable Actively Multiplexed High-Density Surface Electrode Array for Brain Interfacing 有权
公开(公告)号：US20130072775A1
公开(公告)日：2013-03-21
申请号：US13486726
申请日：2012-06-01
申请人： John ROGERS , Dae-Hyeong KIM , Brian LITT , Jonathan VIVENTI
发明人： John ROGERS , Dae-Hyeong KIM , Brian LITT , Jonathan VIVENTI
IPC分类号： A61B5/0478 , A61F2/72 , A61N5/06 , A61N1/36 , A61M5/20
CPC分类号： A61B5/0478 , A61B5/04001 , A61B5/4094 , A61B5/4836 , A61B5/6868 , A61B5/7246 , A61B5/7267 , A61B5/7282 , A61B2562/046 , A61B2562/125 , A61B2562/164 , A61F2/72 , A61M5/20 , A61M5/31 , A61N1/0529 , A61N1/0531 , A61N1/36017 , A61N1/36025 , A61N1/3606 , A61N5/0601 , A61N2005/063
摘要： Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

3. 发明申请

US20070043402A1 Active control of epileptic seizures and diagnosis based on critical systems-like behavior 有权
标题翻译：主动控制癫痫发作和基于关键系统的行为诊断
公开(公告)号：US20070043402A1
公开(公告)日：2007-02-22
申请号：US11505906
申请日：2006-08-18
申请人： Javier Echauz , Gregory Worrell , Brian Litt
发明人： Javier Echauz , Gregory Worrell , Brian Litt
IPC分类号： A61N1/00
CPC分类号： A61F7/12 , A61B5/4094 , A61N1/36025 , A61N1/36064 , A61N1/36135
摘要： Developing a measure of critical systems-like behavior in an epilepsy patient in order to map epileptic networks, either passively or evoking responses through subthreshold stimulation, and to apply “therapeutic” stimulations to the patient that cause smaller, but more frequent dissipations of “energy,” a transcription product, subclinical electrophysiological activity or seizures in order to raise the clinical seizure initiation threshold, through releasing accumulated interictal energy in a seizure onset zone or elsewhere in the epileptic network, thereby preventing occurrence of larger more debilitating seizures.
摘要翻译：开发癫痫患者关键系统样行为的度量，以便通过亚阈值刺激来对癫痫网络进行被动或唤醒反应，并对患者施加“治疗”刺激，从而导致更小但更频繁的“能量消耗” “转录产物，亚临床电生理活动或癫痫发作，以提高临床癫痫发作阈值，通过释放癫痫发作区或癫痫网络其他地方的累积间歇能量，从而防止发生更大程度的虚弱癫痫发作。

4. 发明授权

US07146218B2 Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control 有权
公开(公告)号：US07146218B2
公开(公告)日：2006-12-05
申请号：US10358039
申请日：2003-02-04
申请人： Rosana Esteller , Javier Ramón Echauz , Brian Litt , George John Vachtsevanos
发明人： Rosana Esteller , Javier Ramón Echauz , Brian Litt , George John Vachtsevanos
IPC分类号： A61N1/18 , A61B5/02
CPC分类号： A61B5/076 , A61B5/0476 , A61B5/0482 , A61B5/4094 , A61B5/486 , A61B5/7203 , A61B5/726 , A61B5/7264 , A61B5/7267 , A61B5/7275 , A61N1/08 , A61N1/36082 , G06F19/00 , G06K9/00523
摘要： A method and apparatus for forecasting and controlling neurological abnormalities in humans such as seizures or other brain disturbances. The system is based on a multi-level control strategy. Using as inputs one or more types of physiological measures such as brain electrical, chemical or magnetic activity, heart rate, pupil dilation, eye movement, temperature, chemical concentration of certain substances, a feature set is selected off-line from a pre-programmed feature library contained in a high level controller within a supervisory control architecture. This high level controller stores the feature library within a notebook or external PC. The supervisory control also contains a knowledge base that is continuously updated at discrete steps with the feedback information coming from an implantable device where the selected feature set (feature vector) is implemented. This high level controller also establishes the initial system settings (off-line) and subsequent settings (on-line) or tunings through an outer control loop by an intelligent procedure that incorporates knowledge as it arises. The subsequent adaptive settings for the system are determined in conjunction with a low-level controller that resides within the implantable device. The device has the capabilities of forecasting brain disturbances, controlling the disturbances, or both. Forecasting is achieved by indicating the probability of an oncoming seizure within one or more time frames, which is accomplished through an inner-loop control law and a feedback necessary to prevent or control the neurological event by either electrical, chemical, cognitive, sensory, and/or magnetic stimulation.

5. 发明授权

US06678548B1 Unified probabilistic framework for predicting and detecting seizure onsets in the brain and multitherapeutic device 有权
标题翻译：用于预测和检测大脑和多治疗装置中的癫痫发作的统一概率框架
公开(公告)号：US06678548B1
公开(公告)日：2004-01-13
申请号：US09693423
申请日：2000-10-20
申请人： Javier Ramón Echauz , Rosana Esteller , Brian Litt , George John Vachtsevanos
发明人： Javier Ramón Echauz , Rosana Esteller , Brian Litt , George John Vachtsevanos
IPC分类号： A61B504
CPC分类号： A61B5/7267 , A61B5/0476 , A61B5/076 , A61B5/4094 , A61B5/7275 , A61N1/08 , A61N1/36017 , A61N1/36064 , A61N1/36082 , A61N1/36135 , G06F19/00 , G06F19/3456 , G06F19/3481 , G06K9/6262 , G06K9/627 , G06K9/6278 , G16H50/20 , G16H50/50
摘要： A method and an apparatus for predicting and detecting epileptic seizure onsets within a unified multiresolution probabilistic framework, enabling a portion of the device to automatically deliver a progression of multiple therapies, ranging from benign to aggressive as the probabilities of seizure warrant. Based on novel computational intelligence algorithms, a realistic posterior probability function P(St|x) representing the probability of one or more seizures starting within the next T minutes, given observations x derived from IEEG or other signals, is periodically synthesized for a plurality of prediction time horizons. When coupled with optimally determined thresholds for alarm or therapy activation, probabilities defined in this manner provide anticipatory time-localization of events in a synergistic logarithmic-like array of time resolutions, thus effectively circumventing the performance vs. prediction-horizon tradeoff of single-resolution systems. The longer and shorter prediction time scales are made to correspond to benign and aggressive therapies respectively. The imminence of seizure events serves to modulate the dosage and other parameters of treatment during open-loop or feedback control of seizures once activation is triggered. Fast seizure onset detection is unified within the framework as a degenerate form of prediction at the shortest, or even negative, time horizon. The device is required to learn in order to find the probabilistic prediction and control strategies that will increase the patient's quality of life over time. A quality-of-life index (QOLI) is used as an overall guide in the optimization of patient-specific signal features, the multitherapy activation decision logic, and to document if patients are actually improving.
摘要翻译：一种用于在统一的多分辨率概率框架内预测和检测癫痫发作的方法和装置，使得该装置的一部分能够自动地递送多种治疗的进展，从良性到侵略性，随着癫痫发作的可能性。基于新颖的计算智能算法，给出表示在下一个T分钟内开始的一次或多次癫痫发作的概率的现实后验概率函数P（St | x），给定从IEEG导出的观察值x或其他信号，预测时间范围。当与警报或治疗激活的最佳确定的阈值相结合时，以这种方式定义的概率提供事件在时间分辨率协同对数阵列中的预期时间定位，从而有效地规避了单分辨率的性能与预测 - 视距折衷系统。较长和较短的预测时间尺度分别对应于良性和侵略性疗法。癫痫事件的紧急事件有助于在触发激活后，在开环或反馈控制缉获期间调节治疗的剂量和其他参数。快速发作发作检测在框架内被统一为在最短或甚至负的时间范围内的退化形式的预测。该设备需要学习才能找到随着时间的推移增加患者生活质量的概率预测和控制策略。使用生活质量指数（QOLI）作为优化患者特异性信号特征，多功能激活决策逻辑的总体指导，并记录患者是否在实际改善。

6. 发明授权

US06658287B1 Method and apparatus for predicting the onset of seizures based on features derived from signals indicative of brain activity 失效
标题翻译：基于从指示脑活动的信号导出的特征来预测癫痫发作的方法和装置
公开(公告)号：US06658287B1
公开(公告)日：2003-12-02
申请号：US09762455
申请日：2001-05-18
申请人： Brian Litt , George Vachtsevanos , Javier Echauz , Rosana Esteller
发明人： Brian Litt , George Vachtsevanos , Javier Echauz , Rosana Esteller
IPC分类号： A61B504
CPC分类号： A61B5/048 , A61B5/0476 , A61B5/4094 , A61B5/726 , G06F19/00 , G06F19/3418 , G06F19/3481 , G16H15/00 , G16H40/63 , G16H50/20 , G16H50/50
摘要： This invention is a method, and system for predicting the onset of a seizure prior to electrograph onset in an individual. During an “off-line” mode, signals representing brain activity of an individual (either stored or real time) are collected, and features are extracted from those signals. A subset of features, which comprise a feature vector, are selected by a predetermined process to most efficiently predict (and detect) a seizure in that individual. An intelligent prediction subsystem is also trained “off-line” based on the feature vector derived from those signals. During “on-line” operation, features are continuously extracted from real time brain activity signals to form a feacture vector, and the feature vector is continuously analyzed with the intelligent prediction subsystem to predict seizure onset in a patient. The system, and method are preferably implemented in an implanted device (102) that is capable of warning externally an individual of the probability of a seizure, and/or automatically taking preventative actions to abort the seizure. In addition, methods are provided for applying intervention measures to an animal to abort or modulat a seizure by adjusting the modality of an intervention measure; and/or parameters of an intervention measure based upon a probability measure indicative of a likelihood of seizure occurrence; and/or a predicted time to seizure onset.
摘要翻译：本发明是一种预测个体发作前发作发作的方法和系统。在“离线”模式中，收集表示个体（存储或实时）的大脑活动的信号，并从那些信号中提取特征。包括特征向量的特征子集通过预定过程进行选择，以最有效地预测（和检测）该个体中的癫痫发作。基于从这些信号导出的特征向量，智能预测子系统也被“离线”训练。在“在线”操作中，从实时脑活动信号中连续提取特征，形成发情矢量，并通过智能预测子系统不断分析特征向量，预测病人发作发作。系统和方法优选地实施在植入装置（102）中，所述植入装置能够从外部警告个体发作的可能性，和/或自动采取预防措施来中止缉获。此外，还提供了通过调整干预措施的方式对动物施加干预措施来中止或调节癫痫发作的方法; 和/或基于指示发作发生可能性的概率测量的干预措施的参数; 和/或预测发作时间。

7. 发明申请

US20120143568A1 SELF-ADAPTIVE BIO-SIGNAL AND MODULATION DEVICE 有权
标题翻译：自适应生物信号和调制装置
公开(公告)号：US20120143568A1
公开(公告)日：2012-06-07
申请号：US13321339
申请日：2010-05-20
申请人： Cherie Kagan , Brian Litt , Jonathan Viventi
发明人： Cherie Kagan , Brian Litt , Jonathan Viventi
IPC分类号： G06F17/00 , H01L27/32 , H01L51/10
CPC分类号： A61N1/0529 , A61N1/36082
摘要： A sensor-effector system includes an array of sensor-effector transducers providing a plurality of sensed signals and applying a plurality of effector signals. The array provides signals to input signal conditioning circuitry which digitizes and filters the plurality of sensed signals. A processor receives the digitized signals, and processes them to generate multiple feature vectors. It also analyzes the feature vectors to identify patterns and classify the identified patterns and generates at least one response vector resulting from the recognized pattern. The response vector is applied to output signal conditioning circuitry, coupled which converts the response vector to at least one analog signal which is applied as an effector signal to the array of sensor-effector transducers.
摘要翻译：传感器 - 效应器系统包括提供多个感测信号并施加多个效应器信号的传感器 - 效应器换能器阵列。阵列向输入信号调理电路提供信号，数字化和滤波多个感测信号。处理器接收数字化信号，并处理它们以产生多个特征向量。它还分析特征向量以识别模式并对所识别的模式进行分类，并生成由识别的模式产生的至少一个响应向量。响应矢量被应用于输出信号调节电路，其耦合，其将响应矢量转换为至少一个作为效应器信号施加到传感器 - 效应器换能器阵列的模拟信号。

8. 发明授权

US08150522B2 Active control of epileptic seizures and diagnosis based on critical systems-like behavior 有权
标题翻译：主动控制癫痫发作和基于关键系统的行为诊断
公开(公告)号：US08150522B2
公开(公告)日：2012-04-03
申请号：US11505906
申请日：2006-08-18
申请人： Javier R. Echauz , Gregory A. Worrell , Brian Litt
发明人： Javier R. Echauz , Gregory A. Worrell , Brian Litt
IPC分类号： A61N1/18
CPC分类号： A61F7/12 , A61B5/4094 , A61N1/36025 , A61N1/36064 , A61N1/36135
摘要： Developing a measure of critical systems-like behavior in an epilepsy patient in order to map epileptic networks, either passively or evoking responses through subthreshold stimulation, and to apply “therapeutic” stimulations to the patient that cause smaller, but more frequent dissipations of “energy,” a transcription product, subclinical electrophysiological activity or seizures in order to raise the clinical seizure initiation threshold, through releasing accumulated interictal energy in a seizure onset zone or elsewhere in the epileptic network, thereby preventing occurrence of larger more debilitating seizures.
摘要翻译：开发癫痫患者关键系统样行为的度量，以便通过亚阈值刺激来对癫痫网络进行被动或唤醒反应，并对患者施加“治疗”刺激，从而导致更小但更频繁的“能量消耗” “转录产物，亚临床电生理活动或癫痫发作，以提高临床癫痫发作阈值，通过释放癫痫发作区或癫痫网络其他地方的累积间歇能量，从而防止发生更大程度的虚弱癫痫发作。

9. 发明授权

US08086294B2 Unified probabilistic framework for predicting and detecting seizure onsets in the brain and multitherapeutic device 有权
标题翻译：用于预测和检测大脑和多治疗装置中的癫痫发作的统一概率框架
公开(公告)号：US08086294B2
公开(公告)日：2011-12-27
申请号：US11837814
申请日：2007-08-13
申请人： Javier Ramón Echauz , Brian Litt , Rosana Esteller , George John Vachtsevanos
发明人： Javier Ramón Echauz , Brian Litt , Rosana Esteller , George John Vachtsevanos
IPC分类号： A61B5/04 , G01N33/48 , G01N31/00
CPC分类号： A61B5/7267 , A61B5/0476 , A61B5/076 , A61B5/4094 , A61B5/7275 , A61N1/08 , A61N1/36017 , A61N1/36064 , A61N1/36082 , A61N1/36135 , G06F19/00 , G06F19/3456 , G06F19/3481 , G06K9/6262 , G06K9/627 , G06K9/6278 , G16H50/20 , G16H50/50
摘要： A method and system for assessing a quality of life index to adjust an implanted device to optimize patient-specific feature signals and treatment therapies. Accumulated energy of intracranial electroencephalogram (IEEG) signals is calculated over multiple data channels during seizures over a fixed time period. Accumulated energy of a treatment control is calculated over the multiple data channels over all times of activation of the implanted device over the fixed time period. The accumulated energy of both the IEEG signals and treatment control are weighted by seizure and treatment factors to determine a quality value for the fixed time period. A quality of life index is determined as a weighted average of current and previous quality values for a plurality of fixed time periods.
摘要翻译：一种用于评估生活质量指数以调整植入装置以优化患者特异性特征信号和治疗疗法的方法和系统。在固定时间段内癫痫发作期间，通过多个数据通道计算颅内脑电图（IEEG）信号的累积能量。在固定时间段内在植入装置的所有激活时间内，通过多个数据通道计算处理控制的累积能量。 IEEG信号和治疗控制的累积能量通过扣押和处理因子加权，以确定固定时间段的质量值。生活质量指数被确定为多个固定时间段的当前和先前质量值的加权平均值。

10. 发明申请

US20110054583A1 Flexible and Scalable Sensor Arrays for Recording and Modulating Physiologic Activity 有权
标题翻译：灵活和可扩展的传感器阵列用于记录和调节生理活动
公开(公告)号：US20110054583A1
公开(公告)日：2011-03-03
申请号：US12921808
申请日：2009-03-12
申请人： Brian Litt , Jonathan Viventi
发明人： Brian Litt , Jonathan Viventi
IPC分类号： A61N1/05 , A61B5/04
CPC分类号： A61B5/04001 , A61B5/0031 , A61B5/0084 , A61B5/0261 , A61B5/04 , A61B5/0478 , A61B5/14503 , A61B5/14552 , A61B5/6852 , A61B2562/02 , A61B2562/0209 , A61B2562/0233 , A61B2562/028 , A61B2562/046 , A61B2562/125 , A61B2562/164 , A61N1/05 , A61N1/0531 , A61N1/0534 , A61N1/0553 , A61N5/0601 , H01L21/2686 , H01L21/28 , H01L21/56
摘要： An implantable sensor array incorporates active electronic elements to greatly increase the number of sensors and their density that can be simultaneously recorded and activated. The sensors can be of various configurations and types, for example: optical, chemical, temperature, pressure or other sensors including effectors for applying signals to surrounding tissues. The sensors/effectors are arranged on a flexible and stretchable substrate with incorporated active components that allow the effective size, configuration, number and pattern of sensors/effectors to be dynamically changed, as needed, through a wired or wireless means of communication. Active processing allows many channels to be combined either through analog or digital means such that the number of wires exiting the array can be substantially reduced compared to the number of sensors/effectors on the array.
摘要翻译：可植入传感器阵列包含有源电子元件，可大大增加可同时记录和激活的传感器数量及其密度。传感器可以具有各种配置和类型，例如：光学，化学，温度，压力或其它传感器，包括用于向周围组织施加信号的效应器。传感器/效应器布置在柔性和可拉伸的基板上，并具有结合的有源部件，其允许根据需要通过有线或无线通信方式动态地改变传感器/效应器的有效尺寸，配置，数量和图案。有源处理允许通过模拟或数字装置组合许多通道，使得与阵列上的传感器/效应器的数量相比，离开阵列的导线的数量可以显着减少。

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