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）：理解行为与潜在大脑功能之间的关系是当今最复杂的智力挑战之一。功能神经影像是应对这一挑战的一项重要技术。在大鼠和小鼠中建立的大量人类大脑疾病动物模型使这些物种成为脑图谱绘制的理想候选者。然而，在传统的神经成像技术中，一个中心困境是，为避免运动伪影所必需的受试者的固定会消除除了最简单的行为之外的所有行为。结果是，人们对攻击、交配、进食和恐惧等核心动物行为的大脑功能仍然知之甚少。为了解决固定问题，我们最近开发了一种微型、独立、完全植入式输液泵，在自由活动的动物中允许通过远程激活对成像放射性示踪剂进行静脉推注。现在，随着原理证明的证明和正在使用的泵的工作模型，要在科学界广泛应用和使用该技术，仍然需要许多关键的里程碑。我们现在提出了一种新型微量输注泵（MIP），该泵将使该工具在广泛的实验环境中具有更大的灵活性。对于小型桌面实验范例中的应用，我们建议通过经皮射频电源连接到由新型 E 类发射器驱动的外部谐振感应线圈来为 MIP 供电。这将允许 MIP 远程供电和触发，并使设备独立于有限的电池电量。对于在开放式笼子范例中使用 MIP，我们建议使用电池，该电池可在动物的笼子中使用射频电源链路进行充电，使 MIP 在动物自由漫游时也能独立运行。该设计中的频率选通光学控制器将允许从几米的距离经皮触发 MIP，且对环境光不敏感。为了使 MIP 小型化以供小鼠使用，我们建议设计微型加压液体储存器和药物喷射室，并开发和验证微型电热阀。 MIP 在自由活动的大鼠和小鼠的大脑绘图中的应用将在小型桌面实验范例（条件恐惧反应）以及开放式笼子研究（莫里斯水迷宫）中进行测试。将使用[14C]-碘安替比林注射然后进行放射自显影来评估与脑血流相关的示踪剂分布。由跨学科团队进行的研究开发了一种工具，该工具不仅可以应用于正常和异常行为的基本神经元回路的大脑绘图，还可以应用于小动物模型的行为药理学和体内生理学研究。