Microinfusion Pump For Animal Functional Brain Mapping

用于动物功能脑图谱的微输液泵

• 批准号: 7033854
• 负责人: DANIEL PHILIPP HOLSCHNEIDER
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033854
• 关键词: autoradiography; behavior test; behavioral /social science research tag; bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomedical device power system; biomedical equipment development; brain circulation; drug delivery systems; ethology; functional magnetic resonance imaging; implant; laboratory mouse; laboratory rat; medical implant science; microinjections; miniature biomedical equipment; neuropsychology; portable biomedical equipment; radiotracer; radiowave radiation; telemetry

DESCRIPTION (provided by applicant): Understanding the relationship between behavior and underlying brain function constitutes one of the most complex intellectual challenges today. Functional neuroimaging represents an essential technology toward meeting this challenge. The large number of animal models of human brain disorders that have been established in rats and mice makes these species ideal candidates for brain mapping. A central dilemma, however, in conventional neuroimaging techniques is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. The result is that brain function of such core animal behaviors as aggression, mating, feeding, and fear, remains poorly understood. To address the problem of immobilization, we have recently developed a miniature, self-contained, fully implantable infusion pump that in freely-moving animals allows intravenous bolus administration of imaging radiotracers by remote activation. Now with proof of principle demonstrated and a working model of the pump in use, a number of critical milestones remain necessary for widespread application and use of this technology in the scientific community. We now propose a novel microbolus infusion pump (MIP) that will allow greater flexibility of this tool in a broad range of experimental environments. For applications in small table-top experimental paradigms, we propose to power the MIP by a transcutaneous radiofrequency power link to an external resonating inductive coil driven by a novel Class E transmitter. This will allow the MIP to be powered and triggered remotely, and will make the device independent of finite battery power. For use of the MIP in open cage paradigms, we propose the use of a battery, rechargeable in the animal's homecage using the radiofrequency power link that enables the MIP to also operate independently when the animal is roaming free. A frequency-gated, optical controller in this design will allow transcutaneous triggering of the MIP from several meters distance, insensitive to ambient light. To miniaturize the MIP for use in mice, we propose to design a miniature, pressurized liquid reservoir and drug ejection chamber, and to develop and validate a miniature electrothermal valve. Application of the MIP to brain mapping in freely moving rats, as well as mice will be tested in a small table-top experimental paradigm (Conditioned Fear Response), as well as in an open cage study (Morris Water Maze). Cerebral blood flow related tracer distribution will be assessed using [14C]-iodoantipyrine injections followed by autoradiography. Research is conducted by an interdisciplinary team to develop a tool that can be applied not only to the brain mapping of basic neuronal circuits underlying normal and abnormal behavior, but also to behavioral pharmacology and in-vivo physiologic studies in small animal models.

描述（由申请人提供）：了解行为与潜在的大脑功能之间的关系构成了当今最复杂的智力挑战之一。功能神经影像代表了应对这一挑战的重要技术。在大鼠和小鼠中已经建立的人类脑疾病的大量动物模型使这些物种理想地用于脑图。然而，在常规的神经影像技术中，一个中心的困境是，避免运动伪像的受试者的固定化，熄灭了最简单的行为。结果是，这种核心动物行为的大脑功能如侵略，交配，喂养和恐惧，仍然知之甚少。为了解决固定化问题，我们最近开发了一种微型，具有独立的，完全可植入的输液泵，在自由移动的动物中可以通过远程激活对成像放射性示例静脉内给药。现在，有了证明原理的证明和使用的泵的工作模型，在科学界的广泛应用和使用该技术仍然需要许多关键的里程碑。现在，我们提出了一种新型的微生物输液泵（MIP），该泵将在广泛的实验环境中更具灵活性。对于在小台式实验范式中的应用，我们建议通过经皮射频功率链接链接到由新型E类发射器驱动的外部共振电感线圈来为MIP供电。这将使MIP能够远程启动和触发，并将设备独立于有限的电池电源。为了在开放式笼子范式中使用MIP，我们建议使用电池，可在动物的归乡中使用辐射电源链路充电，这使MIP在动物自由漫游时也可以独立运行。该设计中的频率门控光控制器将允许从几米距离的MIP触发MIP，对环境光不敏感。为了将MIP用于小鼠使用，我们建议设计一个微型，加压液体储层和药物喷射室，并开发和验证微型电热阀。在自由移动的大鼠中，将MIP应用于大脑映射，以及小鼠将在小型桌面实验范式（条件恐惧反应）以及开放式笼子研究（Morris Water Maze）中进行测试。脑血流相关的示踪剂分布将使用[14C] - 碘胺注射，然后进行放射自显影评估。研究是由跨学科团队进行的，以开发一种工具，该工具不仅可以应用于正常行为和异常行为的基本神经元电路的大脑映射，还可以应用于小动物模型中的行为药理学和维科生理学研究。