Instrumentation and Bioengineering Development and Application

仪器仪表与生物工程开发与应用

• 批准号: 7593815
• 负责人: Paul Smith
• 金额: $ 5.38万
• 依托单位: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593815
• 关键词: Accounting; Algorithms; Amplifiers; Animals; Area; Bacteriorhodopsins; Behavior; Binding; Biomedical Engineering; Biomedical Research; Calibration; Carbon Monoxide; Carcinogen Metabolism; Carcinogens; Clinic; Collaborations; Color; Computer Systems; Computer software; Computers; Cytochrome P450; Data; Databases; Defect; Detection; Development; Discipline; Dyes; Electroencephalography; Engineering; Equilibrium; Event; Eye; Eye Movements; Floor; Frequencies; Future; Glare; Goals; Head; Image; Image Analysis; Image Enhancement; Individual; Infant; Institutes; Intramural Research Program; Kinetics; Laboratories; Language; Lasers; Light; Lighting; Liver Microsomes; Machine Learning; Measures; Mechanics; Methods; Mission; Modification; Monitor; Movement; Noise; Optics; Patients; Pattern; Persons; Pharmaceutical Preparations; Phase; Physiologic pulse; Placement; Polycyclic Hydrocarbons; Positioning Attribute; Pulse taking; Range; Rattus; Reaction; Reaction Time; Recording of previous events; Reflex action; Resolution; Role; Scheme; Scientist; Seizures; Severities; Shapes; Signal Transduction; Speed; Staining method; Stains; Standards of Weights and Measures; Stimulus; System; Techniques; Technology; Testing; Time; United States National Institutes of Health; Update; Video Recording; analog; digital; eye dryness; flash photolysis; foot; improved; instrument; instrumentation; lens; movie; novel strategies; object motion; physical science; size; sound; success; theories

Development of unique instrumentation using novel approaches is, in many instances, necessary to the success of biomedical research. Areas of emphasis within our group are summarized below. A digital video, EEG imaging system with seizure detection for multiple small animals, being developed in collaboration with Drs. Michael Rogawski and Maciej Gasior NINDS, will detect and record seizures of small animals by monitoring their EEGs together with documenting the animals' accompanying behavior via video recording. The instrumentation consists of animal cages, swivel connectors connected to the head of each animal, EEG analog amplifiers, computer control with movie maker and graphics hardware, and software detection of spikes and seizure patterns. The system has been assembled and will visually display and record EEG data along with video of multiple small animals. The instrument has been tested on small animals and modifications have been made to the mechanical apparatus to allow for more flexible animal movement. The system will continue to be updated as the latest software changes become available. A laser flash photolysis apparatus was developed in collaboration with Dr. Fred Friedman, NCI, to measure the kinetics of carbon monoxide (CO) binding to cytochromes P450 in liver microsomes from rats treated with various drugs and carcinogens. Since numerous forms of P450 contribute to the overall reaction, a difference kinetic method was used to distinguish the kinetic behavior of individual P450s. This method entails analysis of the difference between the kinetic profiles in the absence and presence of a specific P450 effector, and successfully yielded kinetic parameters for individual P450s involved in drug and carcinogen metabolism. Specifically, various polycyclic hydrocarbons differentially accelerated CO binding to the P450 1A1, which metabolizes these carcinogens in a size- and shape-dependent manner. Wavelet analysis allows selection of critical short time scale regions where high frequency information predominates and provides information on the early events associated with the cytochrome P450 binding kinetics. In collaboration with Dr. Brian Brooks, CC, an eye movement system is being developed for use with patients who are unable to understand commands, such as infants, or patients with below-average verbalization or language barriers. Stimuli, such as sound, light, or motion of objects cause eye movements toward the stimuli. The unit has been installed, tested and used on patients in an ophthalmic testing laboratory. In collaboration with Dr. Steven Stanhope and Shih-Chiao Tseng, CC, a time reaction reflex movement system is being developed to test a person's reaction time in attempting to follow a laser beam directed at the floor. Signals generated in a computer system change the position of the light and indicate when a particular light stimulus is activated and deactivated. The computer correlates signals from force plates in the floor with foot placement. The system has been completed and is ready for initial patient testing. In collaboration with Dr. Richard Hendler, NHLBI, a modified version of a high speed optical multichannel spectrometer, developed previously, has been enhanced in terms of temporal and signal amplitude resolution. The kinetics of the bacteriorhodopsin photocycle, initiated with a synchronized laser pulse (532nm, 7ns), is being studied using an optical system that follows the spectral changes associated with the transient intermediates of the photocycle. Complete spectra from approximately 400nm to 700nm are collected with less than 10 microsecond resolution, permitting extraction, though single value decomposition analysis, of the role of the intermediates. To adapt to the next phase of this project, which entails collecting infrared data, a collaboration has been established with the National Institute of Standards and Technology. The optical system has been realigned to incorporate both the high-speed multichannel analyzer and the infrared spectrometer. In collaboration with Dr. Janine Smith, NEI, an ocular imaging system for measuring dry eye severity is being developed. The method uses the Oxford Scheme for grading ocular staining in dry eyes using various dyes. The software for ocular image analysis is complete and will be tested in the clinic in conjuction with a slit biomicroscope. The image analysis uses a support vector machine (SVM) algorithm from statistical learning theory. An ocular instrument will be developed for improving image capture, image enhancement, and the correction of imaging defects. It is intended that the system will enhance image quality by minimizing the potential effects of eye movement, glare, vignetting, lens distortion, noise, and non-uniform eye lighting. System and monitor calibration techniques for color management and white balance will be developed. Instillation and timing of dye administration will be controlled to account for time dilution of dye staining. A database will be developed for storing patient information and history, and to save patient images. Both the instrument and software will be initiated using a semi-automated system with the goal of future development as a fully automatic system.

在许多情况下，使用新方法开发独特的仪器对生物医学研究的成功是必要的。 我们小组内的重点领域概述如下。 与Michael Rogawski博士和Maciej Gasior NINDS博士合作开发的数字视频EEG成像系统可检测多只小动物的癫痫发作，将通过监测小动物的EEG来检测和记录小动物的癫痫发作，并通过视频记录记录动物的伴随行为。 仪器包括动物笼、连接到每只动物头部的旋转连接器、EEG模拟放大器、具有电影制作器和图形硬件的计算机控制以及棘波和癫痫发作模式的软件检测。 该系统已经组装好，将直观地显示和记录脑电图数据沿着多个小动物的视频。 该仪器已在小动物身上进行了测试，并对机械装置进行了修改，以允许更灵活的动物运动。 随着最新的软件变更可用，系统将继续更新。 与NCI的Fred Friedman博士合作开发了一种激光闪光光解装置，用于测量用各种药物和致癌物处理的大鼠肝微粒体中一氧化碳（CO）与细胞色素P450结合的动力学。 由于许多形式的P450有助于整个反应，使用差异动力学方法来区分单个P450的动力学行为。 这种方法需要分析的动力学曲线之间的差异，在一个特定的P450效应的存在和不存在，并成功地产生了个别P450参与药物和致癌物质代谢的动力学参数。 具体而言，各种多环烃差异加速CO结合到P450 1A1，代谢这些致癌物质的大小和形状依赖的方式。 小波分析允许选择关键的短时间尺度区域，其中高频信息占主导地位，并提供与细胞色素P450结合动力学相关的早期事件的信息。 与Brian布鲁克斯博士合作，正在开发一种眼动系统，用于无法理解命令的患者，如婴儿，或语言表达或语言障碍低于平均水平的患者。 刺激，如声音、光或物体的运动，会导致眼睛朝向刺激运动。该装置已在眼科检测实验室的患者身上安装、测试和使用。 与Steven斯坦霍普博士和Shih-Chiao Tseng，CC合作，正在开发一种时间反应反射运动系统，以测试一个人试图跟随指向地板的激光束的反应时间。 在计算机系统中产生的信号改变光的位置，并指示何时激活和停用特定的光刺激。 计算机将来自地板上的测力板的信号与脚的位置相关联。 该系统已经完成，并准备进行初步的患者测试。 与Richard Hendler博士合作，NHLBI是以前开发的高速光学多通道光谱仪的修改版本，在时间和信号幅度分辨率方面得到了增强。 细菌视紫红质光循环的动力学，开始与同步激光脉冲（532 nm，7 ns），正在研究使用的光学系统，以下的光谱变化与瞬态中间体的光循环。 从大约400 nm到700 nm的完整光谱以小于10微秒的分辨率收集，允许通过单值分解分析提取中间体的作用。 为了适应该项目下一阶段的工作，即收集红外数据，与国家标准和技术研究所建立了合作关系。 光学系统已重新调整，以纳入高速多通道分析仪和红外光谱仪。 与NEI的Janine Smith博士合作，正在开发用于测量干眼症严重程度的眼部成像系统。 该方法使用Oxford方案，使用各种染料对干眼的眼染色进行分级。 用于眼部图像分析的软件已完成，并将在临床上结合狭缝生物显微镜进行测试。 图像分析使用来自统计学习理论的支持向量机（SVM）算法。 将开发一种目镜仪器，用于改善图像捕获、图像增强和图像缺陷的校正。 预期该系统将通过最小化眼球运动、眩光、渐晕、透镜失真、噪声和眼睛照明不均匀的潜在影响来提高图像质量。 将开发用于色彩管理和白色平衡的系统和监视器校准技术。 将控制染料滴注和给药时间，以考虑染料染色的时间稀释。 将开发一个数据库，用于存储患者信息和历史，并保存患者图像。 仪器和软件都将使用半自动化系统启动，目标是未来发展为全自动系统。