Optical coherence tomography (OCT) is an optical imaging modality that can perform micron scale, tomographic cross-sectional imaging of microstructure in biological tissues in situ and in real time. Due to the high axial resolution, OCT is ideally suited for imaging tissues with a laminar structure, such as the retina. Recent advances in OCT technology over the past 5 years have enabled dramatic advances in OCT imaging speed and sensitivity. Importantly, high-speed OCT enables rapid volumetric imaging, and facilitates new sources of contrast such as Doppler and spectroscopic OCT. A central goal of this proposal is that the advances in OCT technology will enable depth-resolved, quantitative hemodynamic and metabolic measurements during functional activation in the brain with high spatiotemporal resolution. This proposal will develop novel technologies and methods to enhance the capability of OCT to quantitatively measure blood flow, blood volume, hematocrit, oxygen saturation, and capillary dilation. These technologies and methods will be applied to study neurovascular coupling and oxygen consumption during somatosensory activation.
The specific aims of this program are: 1. Develop high-speed OCT microscope platforms for brain imaging. Two spectral / Fourier domain OCT microscope platforms, one operating at near-infrared wavelengths and the other operating at visible wavelengths, will be developed. 2. Develop and validate methods of measuring of blood flow, blood volume, hematocrit, oxygen saturation and capillary dilation with OCT. Methods of quantitatively measuring cortical hemodynamics will be developed. These methods will be validated in vitro in circulating whole blood samples, and in vivo by comparison with two photon microscopy and optical intrinsic signal imaging (OISI).
This aim will characterize the performance of OCT relative to other imaging technologies used for measuring cortical hemodynamics. 3. Characterize the laminar response and quantify oxygen consumption during functional activation. The methods developed in Aim 2 will be used to characterize the cortical hemodynamic response according to vascular compartment and cortical layer, and to quantitatively measure oxygen consumption during somatosensory activation. The results of this program will answer fundamental questions about the hemodynamic and metabolic responses at the microscopic level, which will aid interpretation of macroscopic measurements such as BOLD fMRI and improve understanding of cerebrovascular physiology and pathology.

Public Health Relevance

PROJECT NARRATIVE The hypothesis of this proposal is that optical coherence tomography (OCT) enables depth-resolved, quantitative measurements of blood flow, blood volume, hematocrit, oxygen saturation, and capillary dilation which can be used to study neurovascular coupling. This program will develop high-speed OCT microscopy technologies for depth-resolved in vivo brain imaging and develop and validate methods of measuring cortical hemodynamic using these technologies. These technologies and methods will be applied to characterize the laminar hemodynamic response and oxygen metabolism during somatosensory activation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Career Transition Award (K99)
Project #
5K99NS067050-02
Application #
7941756
Study Section
NST-2 Subcommittee (NST)
Program Officer
Ludwig, Kip A
Project Start
2009-09-28
Project End
2011-11-30
Budget Start
2010-09-01
Budget End
2011-11-30
Support Year
2
Fiscal Year
2010
Total Cost
$90,000
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Srinivasan, Vivek J; Yu, Esther; Radhakrishnan, Harsha et al. (2015) Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography. J Cereb Blood Flow Metab 35:1552-60
Srinivasan, Vivek J; Radhakrishnan, Harsha (2014) Optical Coherence Tomography angiography reveals laminar microvascular hemodynamics in the rat somatosensory cortex during activation. Neuroimage 102 Pt 2:393-406
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
Yuzawa, Izumi; Sakadzic, Sava; Srinivasan, Vivek J et al. (2012) Cortical spreading depression impairs oxygen delivery and metabolism in mice. J Cereb Blood Flow Metab 32:376-86
Srinivasan, Vivek J; Radhakrishnan, Harsha; Jiang, James Y et al. (2012) Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast. Opt Express 20:2220-39
Goergen, Craig J; Radhakrishnan, Harsha; Sakadži?, Sava et al. (2012) Optical coherence tractography using intrinsic contrast. Opt Lett 37:3882-4
Devor, Anna; Sakadzic, Sava; Srinivasan, Vivek J et al. (2012) Frontiers in optical imaging of cerebral blood flow and metabolism. J Cereb Blood Flow Metab 32:1259-76
Srinivasan, Vivek J; Atochin, Dmitriy N; Radhakrishnan, Harsha et al. (2011) Optical coherence tomography for the quantitative study of cerebrovascular physiology. J Cereb Blood Flow Metab 31:1339-45
Lee, Jonghwan; Srinivasan, Vivek; Radhakrishnan, Harsha et al. (2011) Motion correction for phase-resolved dynamic optical coherence tomography imaging of rodent cerebral cortex. Opt Express 19:21258-70
Carp, Stefan A; Roche-Labarbe, Nadàege; Franceschini, Maria-Angela et al. (2011) Due to intravascular multiple sequential scattering, Diffuse Correlation Spectroscopy of tissue primarily measures relative red blood cell motion within vessels. Biomed Opt Express 2:2047-54

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