Multimodality Optical Imaging Tools for Cocaine Studies

描述（由申请人提供）：本申请标题为“用于脑卒中研究的多模态光学成像工具”，将解决广泛的挑战领域（06：使能技术）和特定的挑战主题（06-DA-102：神经科学工具开发）。该提案的中心目标是开发新的成像工具，为慢性可卡因暴露导致的级联事件提供新的见解，特别是对皮质和皮质下大脑区域的毒性作用，包括神经血管变化。当成像啮齿动物大脑对药物的反应时，最大的挑战之一（即，可卡因）已经区分了血管和神经元效应。我们最近开发并测试了一种新的双波长激光散斑成像（DWLSI）工具，该工具首次能够同时测量脑血流量（CBF），血容量和组织血红蛋白氧合，其作为高时空分辨率（30 μ m，10 Hz）和相对较大视场（FOV，4x 5 mm 2）下组织活动的标记。此外，通过与数字频率斜坡光学相干断层扫描（DOCT）共配准，我们可以获得CBF网络的活体定量3D图像。与此同时，我们还开发了细胞内钙成像Rhod 2-荧光技术，作为神经元活动的标志物。在这个挑战补助金，我们建议开发一个多模态同时成像平台，结合DWLSI，DOCT和钙荧光成像研究急性和慢性可卡因暴露对啮齿动物大脑的影响。通过进一步将这项技术与我们的微型中继透镜（F300 <$mx24 mm）相结合，我们将能够首次扩展我们的多模态成像能力，以研究可卡因在体内脑深部区域的作用。具体目标是：（1）开发多模态成像平台，研究可卡因对大脑皮层的影响;（2）开发基于微探针的多模态成像平台，用于皮层下脑成像。成功开发和验证的建议多模态光学技术将允许同时成像的血管和细胞功能和实时响应可卡因的挑战在皮质和皮质下的大脑在体内，从而使区分和详细研究神经元和血管的变化。这些拟议的技术发展将对生物医学成像，神经科学和药物滥用以及转化研究社区产生重大影响。此外，该项目的挑战赠款资金将为1名博士后研究员和2名研究生创造3个研究职位，这将加快新成像技术开发的步伐，并加强下一代生物医学工程和物理学的学术教育，将神经科学仪器开发与药物滥用和成瘾的转化研究联系起来。 公共卫生相关性：本申请题为“用于脑卒中研究的多模态光学成像工具”，将解决广泛的挑战领域（06：使能技术）和特定的挑战主题（06-DA-102：神经科学工具开发）。该提案的中心目标是开发新的成像工具，为慢性可卡因暴露导致的级联事件提供新的见解，特别是对皮质和皮质下大脑区域的毒性作用，包括神经血管变化。在这个挑战补助金，我们建议开发一个多模态同时成像平台，结合DWLSI，DOCT和钙荧光成像研究急性和慢性可卡因暴露对啮齿动物大脑的影响。此外，通过将这种技术与我们的微中继透镜相结合，我们将能够扩展我们的成像能力，以研究可卡因在体内脑深部区域的影响。所提出的技术的成功开发和验证将允许同时成像的血管和细胞功能和实时响应可卡因的挑战在皮质和皮质下的大脑在体内，从而使区分和详细的研究神经元和血管的变化。拟议的技术发展将对生物医学成像、神经科学、药物滥用和转化研究界产生重大影响。此外，该项目的挑战赠款资金将为博士后研究员和研究生创造3个研究职位，这将加强下一代生物医学工程和物理学的学术教育，将神经科学仪器开发与药物滥用和成瘾的转化研究联系起来。

DESCRIPTION (provided by applicant): This application entitled "Multimodality Optical Imaging Tools for Cocaine Studies" will address the broad Challenge Area (06: Enabling Technologies) and Specific Challenge topic (06-DA-102: Tool Development for the Neurosciences). The central goal of this proposal is to develop novel imaging tools that will provide new insights into the cascading events resulting from chronic cocaine exposure, in particular, the toxic effects on cortical and subcortical brain regions and including neurovascular changes. One of the big challenges when imaging the responses of the rodent brain to drugs (i.e., cocaine) has been to distinguish vascular from neuronal effects. We recently developed and tested a novel dual wavelength laser speckle imaging (DWLSI) tool that enables, for the first time, simultaneous measurements of cerebral blood flow (CBF), blood volume and tissue hemoglobin oxygenation, which serves as marker of tissue activity at high spatiotemporal resolutions (30¿m, 10Hz) and over a relatively large field of view (FOV, 4x5mm2). Moreover, by co-registering with digital-frequency-ramping optical coherence tomography (DOCT) we can obtain an in vivo quantitative 3D image of the CBF network. In parallel we also developed intracellular calcium imaging using Rhod2-fluorescence technique, which serves as a marker of neuronal activity. In this Challenge Grant, we propose to develop a multimodality simultaneous imaging platform by combining DWLSI, DOCT and calcium fluorescence imaging to study the effects of acute and chronic cocaine exposures on rodent brain. By further integrating this technique with our micro relay lens (F300¿mx24mm), we will be able, for the first time, to expand our multimodality imaging capabilities to study cocaine effects in deep brain regions in vivo. The Specific Aims are: (1) to develop multimodality imaging platform to study cocaine effects on cortical brain; (2) to develop microprobe-based multimodality imaging platform for subcortical brain imaging. Successful development and validation of the proposed multimodality optical techniques will permit simultaneous imaging of vascular and cellular functions and their real-time responses to cocaine challenge in cortical and subcortical brain in vivo, thus enabling distinction and detailed study of neuronal and vascular changes. These proposed technological developments will have significantly impact on the biomedical imaging, neuroscience and drug abuse and translational research communities. In addition, Challenge grant funds for this project will create 3 research positions for 1 postdoctoral fellow and 2 graduate student, which will accelerate the pace of new imaging technology development and enhance the academic education for next generation on biomedical engineering and physics to bridge instrumentation development for neuroscience to translational research on drug abuse and addiction. PUBLIC HEALTH RELEVANCE: This application entitled "Multimodality Optical Imaging Tools for Cocaine Studies" will address the broad Challenge Area (06: Enabling Technologies) and specific Challenge topic (06-DA-102: Tool Development for the Neurosciences). The central goal of this proposal is to develop novel imaging tools that will provide new insights into the cascading events resulting from chronic cocaine exposure, in particular, the toxic effects on cortical and subcortical brain regions and including neurovascular changes. In this Challenge Grant, we propose to develop a multimodality simultaneous imaging platform by combining DWLSI, DOCT and calcium fluorescence imaging to study the effects of acute and chronic cocaine exposures to the rodent brain. In addition, by integrating this technique with our micro relay lens we will be able to expand our imaging capabilities to study cocaine effects in deep brain regions in vivo. Successful development and validation of the proposed techniques will permit simultaneous imaging of vascular and cellular functions and their real-time responses to cocaine challenge in cortical and subcortical brain in vivo, thus enabling distinction and detailed study of neuronal and vascular changes. The proposed technological developments will have significantly impact on the biomedical imaging, neuroscience and drug abuse and translational research communities. In addition, Challenge grant funds for this project will create 3 research positions for post-doctor fellow and graduate students, which will enhance the academic education for next generation on Biomedical Engineering and Physics to bridge instrumentation development for neuroscience to translational research on drug abuse and addiction.