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

项目总结/摘要 功能性近红外光谱（fNIRS）是一种成熟的神经成像方法， 神经科学家通过无创监测大脑皮层的血液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，fNIRS的使用显著增加， 随着用户和出版物的增长，以及现有商业文书的数量不断增加，尽管 这些成功，fNIRS作为一种神经成像方法的影响可以通过解决 几个技术限制。 根据BRAIN Initiative RFA EB-17-004“开发下一代人脑成像工具” ”我们建议开发一种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），这将大大提高对 FNIRS的功能。DCS是一种先进的光学模式，通过以下方式量化相对血流变化（rCBF）： 通过移动红光测量由光的动态散射产生的光强度时间波动， 血细胞几年前，我们展示了在时域中操作DCS的能力，并得到了 前身早期RFA EB-17-001开发了第一个便携式时间选通fDCS系统。与此设备 我们可以区分晚到达的光子和早到达的光子，仅从具有以下特征的光子获得血流测量： 深入组织，进一步增加了大脑的敏感性。 我们成立的团队，包括来自马萨诸塞州马萨诸塞州总医院的研究人员 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 该技术的目标是提供一种成像系统，该系统覆盖整个成人头部，同时产生高质量的 功能性血流变化的分辨率图像，对比噪声比提高2- 3倍，大脑 对脑外生理学串扰的敏感性和抗性。这一目标将通过以下方式实现：i）使用较长的 波长，特别是1064 nm，其中多个因素联合收割机组合以提供10倍的光通量增加， 以及更低的散射，以增加穿透深度和空间分辨率; ii）开发新的激光器， 具有最佳规格的时间选通fDCS探测器，克服了当前商业上 三）扩大新的组成部分，以建立一个多渠道系统和高密度的 具有96个光源和192个探测器的光纤帽，以六边形模式分布，间距约为13 mm， 总共576个通道，以产生功能性血流变化的高分辨率图像。小说时间- 门控fDCS系统将在组织样体模中进行表征，并在健康志愿者中进行验证。 标准的功能性任务，与连续波NIRS，DCS和fMRI进行对比。 这项技术的发展将为描述人类大脑功能提供前所未有的工具。

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.