Gated Diffuse Correlation Spectroscopy for functional imaging of the human brain

门控弥散相关光谱用于人脑功能成像

MARIA FRANCESCHINI Show email (2017-09-25 to 2019-07-31) $1,014,294

Project ID: R01EB025145 (NIBIB)

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Abstract

With this grant application we aim to dramatically improve over the capabilities of functional near-infrared spectroscopy (fNIRS) by developing a completely novel approach to measure human brain function. This is in line with the Brain Initiative FOA which aims to support early stage development of entirely new and novel noninvasive human brain imaging technologies and methods that will lead to transformative advances in our understanding of the human brain. To substantially improve optical imaging of human brain function, we plan to develop a wearable time- gated, small-separation, diffuse correlation spectroscopy (DCS) system. We will illuminate the scalp with pulsed long-coherence lasers and detect photons with a time-gated photon counting detector positioned at a very short distance from the source. The detector will be turned on at a specific time delay with respect to the laser pulses to discard the early arriving photons, which have travelled only in the surface, and detect only photons which have travelled longer paths through the brain. Each detected photon will be time-stamped with the number of the corresponding laser pulse. Detected photons will be averaged over ~200 ms providing both intensity and temporal autocorrelation function temporal changes to quantify cerebral blood flow, oxygenation, and oxygen metabolic changes. This strategy will: 1) Move from the traditional large source-detector pair geometry with the ?banana? shaped spatial sensitivity profile to a sub-cm source-detector separation with much improved spatial localization; 2) Improve sensitivity to brain and reduce scalp contamination by collecting only the photons that have travelled long paths through the brain; 3) Add the measurement of cerebral blood flow to conventional fNIRS hemoglobin concentration measures; 4) Recover functional cerebral oxygen metabolism changes from the combined hemodynamic measures; 5) Cover the whole head with a dense array of small wearable optodes to produce high resolution images of functional hemodynamic and metabolic changes that at the same time permits measurements with more natural behaviors than presently permitted with fNIRS and other imaging methods. In this phase we will develop the first time-gated fDCS prototype using commercially available components and custom circuits, test the wearable optode in human subjects and determine optimal design specification for the final system to be developed with subsequent funding mechanisms. Once the prototype optode has been tested, the technology has been demonstrated and the best strategy for mass production has been determined, we can move to full production of low-cost time gated fDCS optodes. The development of this NIRS technology will provide an unprecedented tool to characterize brain function in humans.

通过这项资助申请，我们旨在通过开发一种全新的人脑功能测量方法，大幅提高功能性近红外光谱（fNIRS）的功能。这符合大脑倡议FOA，旨在支持全新的和新颖的无创人脑成像技术和方法的早期发展，这将导致我们对人类大脑的理解的变革性进展。为了大幅改善人脑功能的光学成像，我们计划开发一种可穿戴时间门控，小分离，漫反射相关光谱（DCS）系统。我们将使用脉冲长相干激光照射头皮，并使用时间门控光子计数探测器探测光子，该探测器位于离光源非常短的距离处。探测器将在相对于激光脉冲的特定时间延迟打开，以丢弃仅在表面中行进的早期到达光子，并且仅检测已经穿过大脑的较长路径的光子。每个检测到的光子将被加上相应激光脉冲数的时间戳。检测到的光子将在~200ms内平均，提供强度和时间自相关函数的时间变化，以量化脑血流量，氧合作用和氧代谢变化。这个策略将：1）从传统的大型源 - 探测器对几何与'香蕉？形状空间灵敏度分布到亚厘米源 - 探测器分离，具有大大改善的空间定位; 2）通过仅收集穿过大脑的长路径的光子，提高对大脑的敏感性并减少头皮污染; 3）将脑血流量的测量值加到常规fNIRS血红蛋白浓度测量值上; 4）从血流动力学综合措施中恢复功能性脑氧代谢变化; 5）用一系列密集的小型可穿戴光极覆盖整个头部，以产生功能性血液动力学和代谢变化的高分辨率图像，同时允许测量具有比fNIRS和其他成像方法目前允许的更自然的行为。在此阶段，我们将使用商用组件和定制电路开发第一个时间门控fDCS原型，测试人类受试者的可穿戴光极，并确定最终系统的最佳设计规范，以及随后的资助机制。一旦测试了原型光极，就已经证明了该技术并确定了大规模生产的最佳策略，我们可以完全生产低成本时间门控fDCS光极。这种NIRS技术的发展将提供一种前所未有的工具来表征人类的大脑功能。