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Miniature, Integrated Fluorescence Microscopes for In Vivo Brain Imaging

用于体内脑成像的微型集成荧光显微镜

基本信息

批准号：
8516112
负责人：
Kunal Ghosh
金额：
$ 36.65万
依托单位：
INSCOPIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516112
关键词：
Adult American Animal Behavior Animals Area Autistic Disorder Behavior Boxing Brain Brain Diseases Brain imaging Cells Chronic Communities Computer software Core Facility Corpus striatum structure Custom Data Data Set Devices Disease Electronics Elements Exhibits Extravasation Feedback Fluorescence Microscopy Foundations Goals Head Hippocampus (Brain)Home environment Housing Human Image Imagery Imaging technology Individual Intellectual Property Knowledge Letters Licensing Life Light Location Magnetism Marketing Medicine Mental Depression Methods Microcirculation Microscope Monitor Mus National Institute of Mental Health Nature Neurons Neurosciences Neurosciences Research Neurotransmitters Optics Pathologic Pathway interactions Pattern Performance Peripheral Phase Preparation Problem Solving Production Publishing Rattus Research Personnel Resolution Rodent Role Schizophrenia Scientist Sea Shapes Small Business Innovation Research Grant Solutions Source Speed Staging Stream Technology Testing Therapeutic Time Universities Validation awake base brain research commercialization computerized data processing cost data acquisition design digital disease phenotype electronic data flexibility fluorescence microscope graphical user interface image registration improved in vivo innovation interest lens member miniaturize mouse model neural circuit neural patterning neurochemistry neuropsychiatry news novel therapeutics prototype relating to nervous system research study seal sensor spatiotemporal technological innovation theories user-friendly

项目摘要

DESCRIPTION (provided by applicant): There is a rising emphasis today on the role of neural circuitry in neuropsychiatric disease. However we still lack crucial knowledge of both normal patterns of neural activity and how these patterns go awry in disease. Although brain researchers have already created mouse models of many human brain diseases, presently there is no technology that can visualize the activity of large numbers of individual, neurons of genetically identified types in the brains of behaving mice - ideally in multiple mice in parallel. The capacity to obtain such large-scale data sets is important towards identifying neurophysiologic signatures of brain disease and is a prerequisite for developing therapeutic means of re-tuning aberrant activity patterns. Fluorescence microscopy has key advantages for tracking neural activity. However, while conventional fluorescence microscopes offer the spatiotemporal resolution needed for imaging the brain's cellular dynamics, they neither permit studies in freely behaving mice nor are scalable for studies of large numbers of animal subjects. If fluorescence microscopes could be made small, portable, and cheap, then in principle large numbers of behaving mice could be studied in parallel. Inscopix, Inc. has spun-out of Stanford University to commercialize miniature, integrated fluorescence microscopes - imaging technology that helps neuroscientists visualize neural circuit dynamics in awake behaving mice and rats. Prototype microscopes at Stanford are already enabling imaging of cerebellar microcirculation and permitting visualization of Ca2+ dynamics within hundreds of individual neurons (over weeks in some experiments) as the animal behaves freely in a naturalistic manner. The core miniature, integrated microscope technological innovation and its promise for studying the brain and its diseases was recently featured in Nature, MIT Technology Review, and several media outlets. In Phase I Inscopix aims to develop and test a new set of prototype microscopes that are significantly higher-performing, robust and part of a user-friendly end-to-end solution for in vivo brain imaging in freely behaving rodents. Specifically, we will: (1) Desig and create a new version of our miniaturized, integrated microscope. We will further develop the core technology and incorporate several improvements to significantly enhance imaging performance and extend the capabilities for in vivo brain imaging, including: (a) Attaining spatial resolution finer than 1 ¿m over fields-of-view up to 1 mm2; (b) Developing a digital, high-speed rotary commutator enabling unsupervised, imaging studies of brain activity; (c) Creating a robust and reliable microscope housing suitable for low-cost manufacturing in large volumes. (2) Develop accompanying hardware and software for data acquisition and processing. We will create a compact and user-friendly USB-compatible box for image acquisition and microscope control along with an easy-to-use Graphical User Interface (GUI). (3) Fabricate and test 10 new miniature microscopes with accompanying peripherals. We will fabricate and internally test our new designs before distributing 10 prototypes to carefully chosen beta labs for in vivo testing and validation. By the end of Phase I we expect to have received considerable in vivo usage feedback from beta labs, laying the foundation for volume production and roll-out of a market-ready product in Phase II.

描述（由申请人提供）：今天越来越强调神经回路在神经精神疾病中的作用。然而，我们仍然缺乏神经活动的正常模式以及这些模式在疾病中如何出错的关键知识。虽然大脑研究人员已经创建了许多人类大脑疾病的小鼠模型，但目前还没有技术可以可视化行为小鼠大脑中大量个体神经元的活动，这些神经元的遗传识别类型-理想情况下是多只小鼠平行。获得这种大规模数据集的能力对于识别脑疾病的神经生理学特征是重要的，并且是开发重新调整异常活动模式的治疗手段的先决条件。荧光显微镜在跟踪神经活动方面具有关键优势。然而，虽然传统的荧光显微镜提供了成像大脑的细胞动力学所需的时空分辨率，它们既不允许在自由行为的小鼠的研究，也不是可扩展的大量动物受试者的研究。如果荧光显微镜可以做得小巧、轻便、便宜，那么原则上就可以对大量行为正常的老鼠进行平行研究。 Insopix，Inc.从斯坦福大学分离出来，将微型集成荧光显微镜商业化，这种成像技术可以帮助神经科学家可视化清醒行为小鼠和大鼠的神经回路动力学。斯坦福大学的原型显微镜已经能够对小脑微循环进行成像，并允许在动物以自然的方式自由行为时可视化数百个单个神经元内的Ca 2+动力学（在某些实验中长达数周）。核心的微型集成显微镜技术创新及其对研究大脑及其疾病的承诺最近在《自然》、《麻省理工学院技术评论》和几家媒体上发表。在第一阶段，Insopix的目标是开发和测试一套新的原型显微镜，这些显微镜具有更高的性能，更强大，并且是用户友好的端到端解决方案的一部分，用于在自由行为的啮齿动物体内进行脑成像。具体来说，我们将：（1）设计和创建一个新版本的小型化，集成显微镜。我们将进一步开发核心技术，并结合几项改进，以显着提高成像性能，并扩展体内脑成像的能力，包括：分辨率小于1？（B）开发一种数字化高速旋转换向器，能够对大脑活动进行无人监督的成像研究;（c）创建一种坚固可靠的显微镜外壳，适合于大批量低成本制造。(2)开发用于数据采集和处理的配套硬件和软件。我们将创建一个紧凑和用户友好的USB兼容盒，用于图像采集和显微镜控制沿着易于使用的图形用户界面（GUI）。(3)制造和测试10台新的微型显微镜及其附带的外围设备。我们将制造和内部测试我们的新设计，然后将10个原型分发给精心挑选的beta实验室进行体内测试和验证。到第一阶段结束时，我们预计将收到来自beta实验室的大量体内使用反馈，为第二阶段的批量生产和市场准备产品的推出奠定基础。