? Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and non-invasively measuring neuronal and vascular signals in the brain cortex. However, while the optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the fast signal) is just emerging and requires further optimization and validation. Our hypothesis is that the current limitations of optical techniques for noninvasive measurement of the neuronal fast signal are not determined by intrinsic features of the optical effect of neuron activation, but rather are the result of a less-than-optimal experimental approach. We will increase the robustness of our measure of the fast signal by improving the instrumentation, the stimulation protocols, and the signal processing, and then assess its efficiency, reproducibility, and reliability with noninvasive measurement in animals (rats and monkeys) and adult human subjects (Aim 1). Once the optical technique is optimized: (1) We will test the hypothesis of a scattering origin of the fast signal (Aim 2) by determining its spatial and spectral features. (2) We will validate the fast optical signal as a measure of neuronal activity by correlating the fast signal with invasive electrophysiology measures in rats and EEG/MEG measures in humans (Aim 3). Finally, (3) we will explore the macroscopic neuro-vascular relationship between fast and hemodynamic evoked responses (Aim 4). The validation study of the fast signal with concurrent electrophysiology, and EEG/MEG measurements will lead to the investigation of how different phenomena that underlie the electromagnetic and the fast signals correlate temporally, spatially, and in amplitude. The simultaneous and co-localized optical measurement of quantities sensitive to fast (neuronal) and slow (hemodynamic) phenomena will advance our understanding of brain physiology by revealing amplitude/spatial/temporal features of neuro-vascular coupling not currently accessible with existing imaging techniques. The long-term objective of this project is to apply DOI to the study of normal brain development in infants, and to the diagnosis and follow-up of cerebrovascular diseases and psychiatric syndromes in adults and children. ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Zhang, Yantian
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Baek, Kwangyeol; Shim, Woo Hyun; Jeong, Jaeseung et al. (2016) Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies. Brain Struct Funct 221:2801-15
Buckley, Erin M; Miller, Benjamin F; Golinski, Julianne M et al. (2015) Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice. J Cereb Blood Flow Metab 35:1995-2000
Buckley, Erin M; Patel, Shyama D; Miller, Benjamin F et al. (2015) In vivo Monitoring of Cerebral Hemodynamics in the Immature Rat: Effects of Hypoxia-Ischemia and Hypothermia. Dev Neurosci 37:407-16
Selb, Juliette; Boas, David A; Chan, Suk-Tak et al. (2014) Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia. Neurophotonics 1:
Chan, Aaron C; Srinivasan, Vivek J; Lam, Edmund Y (2014) Maximum likelihood Doppler frequency estimation under decorrelation noise for quantifying flow in optical coherence tomography. IEEE Trans Med Imaging 33:1313-23
Roche-Labarbe, Nadege; Fenoglio, Angela; Radhakrishnan, Harsha et al. (2014) Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates. Neuroimage 85 Pt 1:279-86
Buckley, Erin M; Parthasarathy, Ashwin B; Grant, P Ellen et al. (2014) Diffuse correlation spectroscopy for measurement of cerebral blood flow: future prospects. Neurophotonics 1:
Radhakrishnan, Harsha; Srinivasan, Vivek J (2013) Multiparametric optical coherence tomography imaging of the inner retinal hemodynamic response to visual stimulation. J Biomed Opt 18:86010
Srinivasan, Vivek J; Radhakrishnan, Harsha (2013) Total average blood flow and angiography in the rat retina. J Biomed Opt 18:76025
Chan, Aaron C; Lam, Edmund Y; Srinivasan, Vivek J (2013) Comparison of Kasai autocorrelation and maximum likelihood estimators for Doppler optical coherence tomography. IEEE Trans Med Imaging 32:1033-42

Showing the most recent 10 out of 36 publications