Multimodality Optical Imaging Tools for Cocaine Studies

描述(由申请人提供)：这项题为“用于可卡因研究的多模式光学成像工具”的申请将涉及广泛的挑战领域(06：使能技术)和特定的挑战主题(06-DA-102：用于神经科学的工具开发)。这项提议的中心目标是开发新的成像工具，为长期接触可卡因引起的级联事件提供新的见解，特别是对皮质和皮质下脑区的毒性影响，包括神经血管变化。在对啮齿动物大脑对药物(即可卡因)的反应进行成像时，最大的挑战之一是区分血管和神经的影响。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，作为高时空分辨率(30？m，10赫兹)和相对较大视野(FOV，4x5 mm2)下组织活动的标志。此外，通过与数字频率斜坡光学相干断层成像(DOCT)的共同配准，我们可以获得CBF网络的在体定量3D图像。与此同时，我们还利用Rhod2荧光技术开发了细胞内钙成像，作为神经元活动的标志。在这项挑战赠款中，我们建议开发一个结合DWLSI、DOCT和钙荧光成像的多模式同时成像平台，以研究急性和慢性可卡因暴露对啮齿类动物大脑的影响。通过进一步将这项技术与我们的微型中继镜(F300？mx24 mm)相结合，我们将首次能够扩展我们的多模式成像能力，以研究体内大脑深层区域的可卡因效应。具体目标是：(1)开发研究可卡因对大脑皮层影响的多模式成像平台；(2)开发基于微探头的皮质下脑成像多模式成像平台。建议的多模式光学技术的成功开发和验证将允许在活体皮质和皮质下大脑中同时成像血管和细胞功能及其对可卡因挑战的实时反应，从而能够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性研究领域产生重大影响。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，将神经科学的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：这项题为“用于可卡因研究的多模式光学成像工具”的申请将涉及广泛的挑战领域(06：使能技术)和具体的挑战主题(06-DA-102：神经科学的工具开发)。这项提议的中心目标是开发新的成像工具，为长期接触可卡因引起的级联事件提供新的见解，特别是对皮质和皮质下脑区的毒性影响，包括神经血管变化。在这项挑战赠款中，我们建议开发一个结合DWLSI、DOCT和钙荧光成像的多模式同时成像平台，以研究急性和慢性可卡因暴露对啮齿类动物大脑的影响。此外，通过将这项技术与我们的微型继电器透镜相结合，我们将能够扩展我们的成像能力，以研究体内大脑深层区域的可卡因效应。拟议技术的成功开发和验证将允许在活体皮质和皮质下大脑中同时成像血管和细胞功能及其对可卡因挑战的实时反应，从而能够区分和详细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、神经科学和药物滥用以及转化性研究领域产生重大影响。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，将神经科学的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.