Time-Gated Diffuse Correlation Spectroscopy for functional imaging of the human brain

项目摘要/摘要 功能近红外光谱(FNIRS)是一种成熟的神经成像方法，它能够 神经学家通过非侵入性监测大脑皮层的血流动力学变化来研究大脑活动。 在过去的十年中，随着社会的形成，fNIR的使用显著增加，并呈指数级增长 随着用户和出版物的增长，现有商业文书的数量也在增加。尽管 在这些成功的案例中，fNIRS作为一种神经成像方法的影响可以通过以下方式大大增强 几个技术上的限制。 配合RFA EB-17-004《新一代人脑成像工具的开发》 和技术“我们建议开发全新的方法来测量人脑功能， 时间门控功能扩散相关光谱(FDCS)，它将大大改进 FNIR的功能。Dcs是一种尖端的光学设备，通过以下方式量化相对血流量变化(RCBF) 测量运动红光动态散射产生的光强时间涨落 血细胞。几年前，我们展示了在时间域中操作分布式控制系统的能力，并得到了 母公司早期RFA EB-17-001开发了第一个便携式时间门控FDDC系统。有了这个设备 我们可以区分晚到和早到的光子，只有从具有 深入组织，进一步提高了对大脑的敏感度。 我们现有的团队，其中包括来自马萨诸塞州马萨诸塞州综合医院的调查人员 麻省理工学院林肯实验室和波士顿大学现在准备在这方面取得飞跃 技术的目标是提供一种覆盖整个成人头部的成像系统，同时产生高 与噪声比相比，脑功能血流的分辨率图像变化了2-3倍 对脑外生理学串扰的敏感性和抵抗力。这一目标将通过以下方式实现：i)使用更长的 波长，特别是1064 nm，其中多种因素结合在一起以提供10倍的光吞吐量增加， 以及更低的散射，以增加穿透深度和空间分辨率；ii)开发新的激光和 具有最佳技术指标的时间门控FDC探测器，克服了商用电流的限制 可用部件；三)扩大新部件，以建立多通道系统和高密度 具有96个光源和192个探测器的光纤帽以~13 mm的间隔呈六角形分布， 用于总共576个通道，以产生高分辨率的功能性血流变化图像。小说中的时间- 门控FDDC系统将在组织样模体中进行表征，并在健康志愿者中进行验证 标准功能任务，对抗连续波近红外光谱、分布式控制系统和功能磁共振成像。 这项技术的发展将为表征人脑功能提供一个前所未有的工具。

Project Summary/Abstract Functional near-infrared spectroscopy (fNIRS) is a well-established neuroimaging method which enables neuroscientists to study brain activity by non-invasively monitoring hemodynamic changes in the cerebral cortex. In the last decade, the use of fNIRS has increased significantly with the formation of a society, with an exponential growth of users and publications, and with an increasing number of available commercial instruments. Despite these successes, the impact of fNIRS as a neuroimaging method could be greatly enhanced by addressing several technological limitations. In line with the BRAIN Initiative RFA EB-17-004 “Development of Next Generation Human Brain Imaging Tools and Technologies” we propose to develop completely novel methodology to measure human brain function, time-gated functional diffuse correlation spectroscopy (fDCS), which will dramatically improve upon the capabilities of fNIRS. DCS, a cutting-edge optical modality, quantifies relative blood flow changes (rCBF) by measuring the light intensity temporal fluctuations generated by the dynamic scattering of light by moving red blood cells. A few years ago, we demonstrated the ability to operate DCS in the time-domain, and supported by the parent early stage RFA EB-17-001, developed the first portable time-gated fDCS system. With this device we can discriminate late from early arriving photon, obtaining blood flow measures only from photons which have travelled deeper into the tissue, further increasing sensitivity to brain. Our established team, which includes investigators from Massachusetts General Hospital, Massachusetts Institute of Technology Lincoln Laboratory, and Boston University, is now ready to make a leap forward in this technology with the goal to offer an imaging system that covers the whole adult head while producing high resolution images of functional blood flow changes with 2-3x improvements in contrast to noise ratio, brain sensitivity and resistance to extracerebral physiology cross-talk. This goal will be achieved by: i) using a longer wavelength, specifically 1064 nm, where a multitude of factors combine to offer a 10x increase in light throughput, as well as lower scattering for increased penetration depth and spatial resolution; ii) developing new laser and detectors with optimal specifications for time-gated fDCS, overcoming limitations of current commercially available components; iii) scaling-up the new components to build a multichannel system and an high density fiber optic cap with 96 sources and 192 detectors distributed in a hexagonal pattern with an ~13mm separation, for a total of 576 channels, to produce high resolution images of functional blood flow changes. The novel time- gated fDCS system will be characterized in tissue-like phantoms, and validated in healthy volunteers during standard functional tasks, against continuous-wave NIRS, DCS and fMRI. The development of this technology will provide an unprecedented tool to characterize human brain function.