Potentiometric photoacoustic imaging of brain activity enabled by near infrared to visible light converting nanoparticles

通过近红外到可见光转换纳米颗粒实现大脑活动的电位光声成像

• 批准号: 9056047
• 负责人: PARAS N. PRASAD
• 金额: $ 29.46万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9056047
• 关键词: Action Potentials; Address; Anatomy; Animal Experiments; Area; Attenuated; BRAIN initiative; Behavior; Binding; Biochemical; Biocompatible; Brain; Brain imaging; Cell membrane; Cellular Membrane; Chemicals; Code; Communities; Complex; Contrast Media; Detection; Development; Dyes; Electrodes; Electrons; Emotions; Engineering; Esthesia; Fluorescence; Goals; Human; Hybrids; Image; Imaging Techniques; Imaging technology; In Situ; In Vitro; Ions; Knowledge; Lanthanoid Series Elements; Lasers; Light; Location; Magnetic Resonance Imaging; Maps; Membrane; Membrane Potentials; Methods; Microelectrodes; Monitor; Morphologic artifacts; Mus; Nature; Needles; Neurons; Neurosciences; Optical Methods; Optics; Pathway interactions; Photons; Physiologic pulse; Process; Property; Quantum Dots; Research; Resolution; Shapes; Signal Transduction; Solutions; Specificity; Speed; Staging; Surface; System; Techniques; Technology; Testing; Thalamic structure; Thinking; Time; Tissues; Transducers; Ultrasonics; Ultrasonography; Ultraviolet Rays; Validation; Variant; Vibrissae; Visible Radiation; Work; absorption; aerobic respiration control protein; barrel cortex; base; brain research; contrast imaging; cost; cranium; fluorescence imaging; imaging modality; improved; in vivo; in vivo imaging; innovation; interest; membrane synthesis; nanocrystal; nanoparticle; neural circuit; neurotechnology; non-invasive imaging; novel; optical imaging; photoacoustic imaging; public health relevance; quantum; relating to nervous system; response; temporal measurement; tomography; tool; ultraviolet; voltage

 DESCRIPTION (provided by applicant): This application is in response to the President's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. Existing technologies are not sufficient to accomplish this goal and have to be significantly improved or novel tools should be introduced to analyze circuit-specific processes in the brain, leading to transformative advances in our understanding of the brain function and behavior. RFA-EY-15-001 seeks technology at the very earliest stage of development, which can assist recording and/or manipulating neural circuit activity in human and animal experiments. The specific goal of the proposed work is to introduce and validate a new voltage-sensitive upconverting photoacoustic imaging (VSUPAI) technique. It is based on voltage-sensitive dye (VSD) imaging, which exploits change of optical properties of dye associated with a cell membrane with variation of a membrane potential, allowing for real-time probing of the neuronal activity via non-invasive optical methods. VSDs have limited use in deep brain imaging, because they require excitation in the visible range. This proposal addresses the current limitation of VSD imaging through the convergence of photoacoustic tomography (PAT), biocompatible upconversion (UC) nanoparticles, and VSDs. In the proposed method, we exploit the voltage-sensitive change in dye absorbance to produce a change in the photoacoustic signal, as opposed to fluorescence-based probing with conventional VSDs. In our proposal, the PAT technique will involve NIR excitation and ultrasound detection, while UCNPs will serve as nanotransformers that convert skull penetrating NIR light to VIS light, which will be absorbed by the locally administered VSDs, allowing us to monitor changes in their absorption, induced by changes in action potentials, and, correspondingly, map the deeper brain neuronal activity.

 描述(申请人提供)：此申请是对总统通过推进创新神经技术(Brain)倡议进行的大脑研究的回应。大脑计划的一个中心目标是了解电信号和化学信号如何在神经回路中编码信息，并产生感觉、思想、情感和行动。现有的技术不足以实现这一目标，必须显著改进或引入新的工具来分析大脑中特定于电路的过程，从而在我们对大脑功能和行为的理解方面取得革命性的进展。RFA-EY-15-001寻求最早开发阶段的技术，该技术可以帮助记录和/或操作人类和动物实验中的神经回路活动。这项工作的具体目标是引入和验证一种新的电压敏感上转换光声成像(VSUPAI)技术。它基于电压敏感染料(VSD)成像，它利用与细胞膜相关的染料的光学性质随着膜电位的变化而变化，从而允许通过非侵入性光学方法实时探测神经元的活动。VSD在脑深部成像中的应用有限，因为它们需要在可见光范围内进行激发。这一建议通过融合光声断层成像(PAT)、生物兼容上转换(UC)纳米颗粒和VSD来解决当前VSD成像的局限性。在提出的方法中，我们利用染料吸光度的电压敏感变化来产生光声信号的变化，而不是传统的VSD基于荧光的探测。在我们的提议中，PAT技术将涉及近红外激发和超声波检测，而UCNPs将作为纳米转换器，将穿透颅骨的近红外光转换为可见光，后者将被局部注射的VSD吸收，使我们能够监测其吸收的变化，由动作电位的变化引起，并相应地绘制更深层次的大脑神经元活动图。