Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 Department of Structural Biology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
3 Department of Neurosurgery, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
4 Department of Radiology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
5 Department of Electrical Engineering and Computer Sciences, University of California, Berkeley 94720, USA
6 School of Optics and Photonics, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian, Beijing 100081, China
7 Biophysics Program, Molecular Imaging Program, and Bio-X Program at Stanford University, Stanford, CA 94305, USA
8 Chan Zuckerberg Biohub, San Francisco, CA 94110, USA
9 Institute of Medical Equipment Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
Optical imaging techniques provide low-cost, non-radiative images with high spatiotemporal resolution, making them advantageous for long-term dynamic observation of blood perfusion in stroke research and other brain studies compared to non-optical methods. However, high-resolution imaging in optical microscopy fundamentally requires a tight optical focus, and thus a limited depth of field (DOF). Consequently, large-scale, non-stitched, high-resolution images of curved surfaces, like brains, are difficult to acquire without z-axis scanning. To overcome this limitation, we developed a needle-shaped beam optical coherence tomography angiography (NB-OCTA) system, and for the first time, achieved a volumetric resolution of less than 8 μm in a non-stitched volume space of 6.4 mm × 4 mm × 620 μm in vivo. This system captures the distribution of blood vessels at 3.4-times larger depths than normal OCTA equipped with a Gaussian beam (GB-OCTA). We then employed NB-OCTA to perform long-term observation of cortical blood perfusion after stroke in vivo, and quantitatively analyzed the vessel area density (VAD) and the diameters of representative vessels in different regions over 10 days, revealing different spatiotemporal dynamics in the acute, sub-acute and chronic phase of post-ischemic revascularization. Benefiting from our NB-OCTA, we revealed that the recovery process is not only the result of spontaneous reperfusion, but also the formation of new vessels. This study provides visual and mechanistic insights into strokes and helps to deepen our understanding of the spontaneous response of brain after stroke.
PhotoniX
2024, 5(1): 7
Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 School of Life Sciences, Tsinghua University, Beijing 100084, China
3 Senior Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100853, China
4 IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China
Biodynamical processes, especially in system biology, that occur far apart in space may be highly correlated. To study such biodynamics, simultaneous imaging over a large span at high spatio-temporal resolutions is highly desired. For example, large-scale recording of neural network activities over various brain regions is indispensable in neuroscience. However, limited by the field-of-view (FoV) of conventional microscopes, simultaneous recording of laterally distant regions at high spatio-temporal resolutions is highly challenging. Here, we propose to extend the distance of simultaneous recording regions with a custom micro-mirror unit, taking advantage of the long working distance of the objective and spatio-temporal multiplexing. We demonstrate simultaneous dual-region two-photon imaging, spanning as large as 9 mm, which is 4 times larger than the nominal FoV of the objective. We verify the system performance in in vivo imaging of neural activities and vascular dilations, simultaneously, at two regions in mouse brains as well as in spinal cords, respectively. The adoption of our proposed scheme will promote the study of systematic biology, such as system neuroscience and system immunology.
Photonics Research
2024, 12(3): 456
Cheng Jin 1†Chi Liu 1†Lingjie Kong 1,2,*
Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China
Two-photon optogenetics has become an indispensable technology in neuroscience, due to its capability in precise and specific manipulation of neural activities. A scanless holographic approach is generally adopted to meet the requirement of stimulating neural ensembles simultaneously. However, the commonly used disk patterns fail in achieving single-neuron resolution, especially in axial dimension, and their inherent speckles decrease stimulation efficiency. Here, we propose a novel speckle-free, beaded-ring pattern for high-axial-resolution optical stimulation of neurons in vivo. Using a dye pool and a fluorescent thin film as samples, we verify that, compared to those with disk patterns, higher axial resolution and better localization ability can be achieved with beaded-ring patterns. Furthermore, we perform two-photon based all-optical physiology with neurons in mouse S1 cortex in vivo, and demonstrate that the axial resolution obtained by beaded-ring patterns can be improved by 24% when stimulating multiple neurons, compared to that of disk patterns.
Photonics Research
2022, 10(6): 06001367
Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China
Fourier light field microscopy (FLFM) shows great potential in high-speed volumetric imaging of biodynamics. However, due to the inherent disadvantage of wide-field illumination, it suffers from intense background, arising from out of the depth-of-field signal and tissue scattered noise. The background will not only deteriorate the image contrast, making quantitative measurement difficult, but also introduce artifacts, especially in functional imaging of the neuronal network activity in vivo. Here, we propose the robust Fourier light field microscopy (RFLFM), which suppresses the background in FLFM by introducing structured illumination and computational reconstruction based on HiLo. The superior performance of RFLFM is verified by volumetric imaging of biological dynamics in larval zebrafish and mouse in vivo, at a volumetric imaging rate up to 33.3 Hz. The statistical results show that the fluorescence background can be significantly depressed, with the signal-to-background ratio improved by orders of magnitude and the whole image contrast improved by as much as 10.4 times. Moreover, we stress that, in functional imaging of neuronal network activity in turbid brain tissues, our system can avoid artifacts resulting from background fluctuations, while conventional light field microscopy fails. As a simple but powerful tool, we anticipate our technique to be widely adopted in robust, high-contrast, high-speed volumetric imaging.
Photonics Research
2022, 10(5): 05001255
Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China
Localized wavefront aberrations would introduce artifacts in biomedical imaging, which, however, are often neglected, as their compensations are at the cost of the field-of-view. Here, we show rarely reported local artifacts in two-photon imaging of dendrites beneath blood vessels in a mouse brain in vivo and interpret the phenomena via numerical simulations. The artifacts of divided parallel structures are found to be induced by coma and astigmatism, resulting from sample tilting and the cylinder shape of vasculatures, respectively. Different from that in single-photon microscopy, such artifacts in nonlinear microscopy show unique characteristics and should be recognized for proper interpretation of the images.
biomedical imaging two-photon microscopy wavefront aberration artifacts of dendrites mouse cortex 
Chinese Optics Letters
2021, 19(12): 121701
作者单位
摘要
1 清华大学精密仪器系精密测试技术与仪器国家重点实验室, 北京 100084
2 清华⁃IDG/麦戈文脑科学研究院, 北京 100084
相比传统电生理方法,基于光遗传学的神经调控技术具有低侵入性、可结合基因工程实现特定神经元选择性激发等优势,近年来在脑科学研究领域得到广泛应用。对基于光遗传学的神经调控方法进行了系统回顾,详细介绍了双光子光遗传技术及其在在体高空间分辨率神经调控方面的研究进展,包括串行螺旋扫描激发、串行扩展光斑扫描激发以及基于广义相衬和计算机生成全息图的并行激发技术等。此外,还讨论了目前双光子光遗传技术在激发精度及激发视场等方面存在的问题及解决方案,并指出将双光子成像与双光子光遗传结合的全光电生理技术可实现神经活动的同步观测与调控,进而极大地推动神经环路解析等神经科学研究。
材料 光遗传学 光敏蛋白 双光子激发 计算全息算法 全光电生理系统 
中国激光
2021, 48(15): 1507003
Author Affiliations
Abstract
1 State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
2 e-mail: guojj018@tsinghua.edu.cn
Dopamine (DA), as a neurotransmitter in human brain, plays a crucial role in reward motivation and motor control. An improper level of DA can be associated with neurological disorders such as schizophrenia and Parkinson’s disease. To quantify DA, optical DA sensors have emerged as an attractive platform due to their capability of high-precision and label-free measurement, and immunity to electromagnetic interference. However, the lack of selectivity, limited biocompatibility, and complex fabrication processes are challenges that hinder their clinical applications. Here, we report a soft and biocompatible luminescent hydrogel optical sensor capable of recognizing and quantifying DA with a simple and compact interrogation setup. The sensor is made of a hydrogel optical fiber (HOF) incorporated with upconversion nanoparticles (UCNPs). DA molecules are detected through the luminescence energy transfer (LET) between the UCNPs and the oxidation products of DA, while the light-guiding HOF enables both excitation and emission collection of the UCNPs. The hydrogel sensor provides an optical readout that shows a linear response up to 200 μmol/L with a detection limit as low as 83.6 nmol/L. Our results show that the UCNP-based hydrogel sensor holds great promise of serving as a soft and biocompatible probe for monitoring DA in situ.
Photonics Research
2020, 8(11): 11001800
作者单位
摘要
菏泽学院物理与电子工程系, 山东 菏泽 274015
借鉴阻尼谐振子正则量子化的方法,实现了对耗散介观RLC串并联电路的量子化,并 在此基础上,研究了真空态下电路中电荷和自感磁通链、电压和电流的量子涨落。结果表明,电路 中电荷和自感磁通链、电压和电流在真空态下都具有各自的量子涨落,且量子涨落及量子涨落积的 大小皆与电路中的器件参数有关,并随时间按指数规律衰减。
量子光学 耗散介观RLC串并联电路 量子化 真空态 量子涨落 quantum optics dissipative mesoscopic RLC series and parallel cir quantization vacuum state quantum fluctuation 
量子电子学报
2015, 32(3): 341
作者单位
摘要
吉林大学通信工程学院光通信系, 吉林 长春 130012
随着短距离通信网的不断发展,多模光纤(MMF)已经成为实现高速大容量信息传输的理想介质,但多模光纤严重的模式色散限制了其传输能力。为了提高多模光纤的传输能力,设计了基于自适应调制(AM)的正交频分复用(OFDM)多模光纤通信系统。提出了适用于该系统的自适应比特分配算法,并通过仿真证明了该算法的有效性。在此基础上重点分析了自适应调制对系统性能的影响,对比了自适应前后不同传输速率、不同信道情况下的误码特性。结果表明,自适应调制能较好地克服深衰落点对系统性能的影响,有效降低了系统误码率(BER)。
光通信 自适应调制 正交频分复用 多模光纤 
中国激光
2008, 35(4): 582

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