CAREER: Functional Optical Coherence Tomography for Neural Imaging

光学相干断层扫描（OCT）是一种新兴的高分辨率生物医学成像方式，在广泛的医学和生物学专业中具有潜在的应用前景。迄今为止的研究主要将OCT用于非侵入性图像形态学。多普勒和偏振敏感OCT已被用于评估组织的功能特性，但最常分别用于血流和组织损伤。然而，OCT的功能远远超出了显微解剖成像。正如功能性磁共振成像对我们对大脑认知过程的理解产生了重大影响一样，功能性OCT （fOCT）技术也有可能在细胞和分子水平上研究神经活动和通讯模式。在本次职业发展奖项中，将开发fct方法，不仅可以可视化解剖微观结构，还可以可视化神经元和神经组织中的生理功能。新的光学方法将被开发出来，以非侵入性地表征电学和分子功能。为了研究和证明这些成像方法的能力，将在三个代表性的细胞培养和小动物模型中使用fct。功能性OCT检测散射和双折射变化将用于非侵入性检测培养神经元群体中的电神经活动，而不需要添加外源荧光团，也不需要多个电极阵列和电子设备。在胸膜鳃（海蛞蝓）的腹部神经节中，神经通路将通过实时fct成像绘制出来，并与已知网络进行比较。使用光谱和非线性OCT方法表征正常和脆性X小鼠模型大脑中功能分子（氧、乙酰胆碱、脆性X智力迟钝蛋白[FMRP]）的差异。该项目将开发包含集成成像系统的新型fct方法。该系统将建立fct和这些方法作为强大的神经成像工具，用于广泛的调查。这项研究将与教育计划相结合，以吸引具有高度多样化背景的K-12、本科生和研究生以及博士后。将为当地科学博物馆设计和建造两个以K-12观众为对象的展览，一个是“生物光子学”，另一个是“自然光学”。研究成果将整合到现有的光学成像和生物医学仪器的本科课程中，并将加大力度发展光学轨道和开设生物光子学的新课程。将安排研究生与同事实验室进行国际交流，并启动生物光子学研究生水平系列研讨会。

0347747BoppartOptical coherence tomography (OCT) is an emerging high-resolution biomedical imaging modality with potential applications in a wide range of medical and biological specialties. Studies to date have used OCT primarily to non-invasively image morphology. Doppler and polarization-sensitive OCT have been used to assess functional properties of tissue, but most commonly in blood flow and tissue injury, respectively. The capabilities of OCT, however, extend far beyond microanatomical imaging. Just as functional magnetic resonance imaging has had a significant impact on our understanding of cognitive processes in the brain, functional OCT (fOCT) techniques have the potential for investigating neural activity and communication patterns at the cellular and molecular level. For this CAREER Development Award, fOCT methods will be developed to visualize not only anatomical microstructure but also physiological function in neurons and in neural tissue. Novel optical methods will be developed to non-invasively characterize electrical and molecular function. To investigate and demonstrate the capabilities of these imaging methods, fOCT will be used in three representative cell culture and small animal models. Functional OCT detecting scattering and birefringence changes will be used to non-invasively detect electrical neural activity in cultured neuron populations without the addition of exogenous fluorophores and without the need for multiple electrode arrays and electronics. In the abdominal ganglion of Pleurobranchaea (sea slug), neural pathways will be mapped out using real-time fOCT imaging and compared to known networks. Differences in functional molecules (oxygen, acetylcholine, Fragile X mental retardation protein [FMRP]) in the brains of normal and Fragile X mouse models will be characterized using spectroscopic and nonlinear OCT methods. This project will develop novel fOCT methods that comprise an integrated imaging system. This system will establish fOCT and these methods as powerful neural imaging tools for a wide-range of investigations.The research will be integrated with educational plans to engage K-12, undergraduate and graduate students and post-doctoral fellows of highly diverse backgrounds. Two exhibits will be designed and constructed for the local Science Museum targeted toward the K-12 audience, one on "Biophotonics" and the other on "Nature's Optics." Research results will be integrated into existing undergraduate courses in Optical Imaging and Biomedical Instrumentation and efforts will intensify to develop an optics track and initiate a new course in Biophotonics. An international graduate student exchange with colleagues' laboratory will be arranged and a graduate-level seminar series on Biophotonics will be initiated.