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

 描述（由申请人提供）：本申请是为了响应总统的大脑研究通过推进创新神经技术（脑）倡议。BRAIN Initiative的核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，并引起感觉，思想，情绪和行动。现有的技术不足以实现这一目标，必须进行重大改进或引入新的工具来分析大脑中的特定回路过程，从而在我们对大脑功能和行为的理解方面取得变革性进展。RFA-EY-15-001寻求最早开发阶段的技术，可以帮助记录和/或操纵人类和动物实验中的神经回路活动。提出的工作的具体目标是介绍和验证一种新的电压敏感的上转换光声成像（VSUPAI）技术。它基于电压敏感染料（VSD）成像，其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活动。VSD在脑深部成像中的使用有限，因为它们需要在可见光范围内激发。该提案通过光声断层扫描（PAT）、生物相容性上转换（UC）纳米颗粒和VSD的融合解决了VSD成像的当前限制。在所提出的方法中，我们利用染料吸光度的电压敏感性变化来产生光声信号的变化，而不是基于荧光的探测与传统的VSD。在我们的提议中，PAT技术将涉及NIR激发和超声检测，而UCNP将作为纳米变压器，将穿透颅骨的NIR光转换为维斯光，该光将被局部施用的VSD吸收，使我们能够监测由动作电位变化引起的吸收变化，并相应地绘制更深层的脑神经元活动。

 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.