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.

Public Health Relevance

With this project we will develop a novel near-infrared spectroscopy system based on time-gated diffuse correlation spectroscopy (fDCS). The gated fDCS system will allow to use sources and detectors mounted close to each other (<1cm) in wearable optodes. This approach will provide fundamental improvements on depth and spatial sensitivity and will add blood flow functional measures to the conventional hemoglobin changes. The realization of time-gated fDCS optodes will result in a transformative impact in human neuroscience.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
3R01EB025145-01S1
Application #
9607408
Study Section
Program Officer
Wang, Shumin
Project Start
2017-09-25
Project End
2019-07-31
Budget Start
2018-05-15
Budget End
2018-07-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Cheng, Xiaojun; Tamborini, Davide; Carp, Stefan A et al. (2018) Time domain diffuse correlation spectroscopy: modeling the effects of laser coherence length and instrument response function. Opt Lett 43:2756-2759