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

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
Research Transition Award (R00)
Project #
5R00NS067050-05
Application #
8394931
Study Section
Special Emphasis Panel (NSS)
Program Officer
Ludwig, Kip A
Project Start
2011-12-15
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$240,285
Indirect Cost
$79,603
Name
University of California Davis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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
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
Radhakrishnan, Harsha; Srinivasan, Vivek J (2013) Compartment-resolved imaging of cortical functional hyperemia with OCT angiography. Biomed Opt Express 4:1255-68
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
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
Srinivasan, Vivek J; Radhakrishnan, Harsha (2013) Total average blood flow and angiography in the rat retina. J Biomed Opt 18:76025
Srinivasan, Vivek J; Mandeville, Emiri T; Can, Anil et al. (2013) Multiparametric, longitudinal optical coherence tomography imaging reveals acute injury and chronic recovery in experimental ischemic stroke. PLoS One 8:e71478
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