Noninvasive monitoring of physiological parameters in mice

描述(由申请人提供)：动物模型的使用一直是几乎所有生物医学领域科学和医学知识进步的主要因素。遗传学的最新进展为更好的模型提供了可能性，特别是在基因改变的小鼠和大鼠身上。为了充分开发这些模型的潜力，需要对动物的生理、行为和基因进行评估。不幸的是，一些啮齿动物的大小使得使用一些既定的方法记录生理信号变得困难，这些方法涉及侵入性程序和电极植入。此外，虽然这些技术已经产生了关于机制的有价值的信息，但将它们应用于行为问题有许多限制。这些因素包括手术或束缚给动物带来的潜在压力，以及记录技术可能会影响正在测量的参数或动物的行为。目前需要手术的技术还可能涉及准备和护理长期植入的动物的相当大的劳动力。这些限制表明需要能够记录生理参数的非侵入性技术。我们的目标是开发非侵入性、非接触性监测啮齿动物模型的生理和行为的方法，并评估它们在确定唤醒状态(觉醒和睡眠)方面的有效性。为了实现这些目标，我们将开发传感器应用程序和软件，用于非侵入性地收集啮齿动物的心率、呼吸频率、体表温度和活动。我们将评估用于获取心率、呼吸频率和活动的脉冲多普勒雷达和/或超声波传感器，并将开发用于获取体温的红外热成像应用程序。然后，我们将用现有技术同时收集的数据来验证非侵入性收集的心率、呼吸频率、体温和活动数据。我们将把我们开发的传感器应用程序获得的数据与现有方法(例如，呼吸频率的远程测量记录心率、全身体积图和横隔膜记录、远程测量温度和活动的光束测量)获得的数据进行比较。最后，我们将通过将状态识别与非侵入性获得的信号与基于EEG的唤醒状态评分进行比较，来确定这些信号是否可以可靠地确定三种唤醒状态(清醒、NREM和REM)。该项目对公共卫生具有重要意义，因为它可以为使用动物模型进行研究提供改进的技术。建议的应用对行为和睡眠的研究具有特别重要的意义。

DESCRIPTION (provided by applicant): The use of animal models has been a major factor in the advancement of scientific and medical knowledge in virtually every biomedical field. Recent advances in genetics have provided the potential for even better models, particularly in gene-altered mice and rats. To fully exploit the potential of these models, the animals need to be evaluated on physiology as well as behavior and genotype. Unfortunately, the size of some rodents makes it difficult to use some established methods of recording physiological signals that involve invasive procedures and the implantation of electrodes. In addition, while these techniques have yielded valuable information regarding mechanisms, there are a number of limitations with applying them to behavioral questions. These include potential stress on the animal from surgery or restraint and the possibility that the recording technique can affect the parameter being measured, or the animals behavior. Current techniques that require surgery also may involve considerable labor in preparing and caring for chronically implanted animals. These limitations indicate the need for non-invasive techniques that can record physiological parameters. Our goal is to develop methodologies for non-invasive, non-contact monitoring of physiology and behavior in rodent animal models, and to assess their utility in determining arousal state (wakefulness and sleep). To accomplish these goals we will develop sensor applications and software for the non-invasive collection of heart rate, respiratory rate, body surface temperature and activity in rodents. We will assess pulse Doppler radar and/or ultrasonic sensors for acquiring heart rate, respiratory rate and activity, and we will develop infrared thermal imaging applications for acquiring body temperature. We will then validate non-invasively collected data for heart rate, respiratory rate, temperature and activity with data concurrently collected with established techniques. We will compare the data obtained with the sensor applications we develop with that obtained with established methodologies (e.g., telemetrically recorded heart rate, whole body plethysmography and diaphragm recordings for respiratory rate, telemetrically recorded temperature, and photobeam measurement of activity). Finally, we will determine if these signals can be used to reliably determine three arousal states (wakefulness, NREM and REM) by comparing state discrimination with non- invasively obtained signals to EEG based scoring of arousal states. This project has significance for public health because it can provide improved techniques for studies using animal models. The proposed applications have particular significance for studies of behavior and sleep.