The technology to characterize microvascular network dynamics and assess its impact on tissue oxygen delivery is only now emerging. We have recently demonstrated the unprecedented ability to map oxygen in the microvasculature and cerebral tissue with two-photon microscopy (TPM) [Sakadzic2010] and are proposing to complement this with our novel statistical intensity variation optical coherence tomography (OCT), enabling quantitative dynamic maps of microvessel flow, red blood cell flux, and vessel diameter. Combined, these technologies will provide unprecedented spatio-temporal resolution imaging of oxygen delivery to brain tissue. These technologies will have a broad impact in health science in preclinical models of neuro-degenerative diseases and cancer, and, as we elaborate in Aim 4, help guide the identification of clinically relevant imaging biomarkers. To demonstrate the technologies' utility, we will address fundamental questions about cerebral vascular physiology: How do microvascular flow properties impact tissue oxygenation, and how do age-related vascular alterations compromise tissue oxygenation? We will then relate these findings to clinically relevant imaging biomarkers.

Public Health Relevance

We develop novel imaging technologies for quantifying tissue oxygen delivery with unprecedented microvascular resolution. These technologies will have a broad impact in health science in preclinical models of neuro-degenerative diseases and cancer, in which oxygen delivery is compromised, and help guide the identification of clinically relevant imaging biomarkers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB021018-04
Application #
9554921
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Shabestari, Behrouz
Project Start
2017-09-01
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Boston University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
Kura, Sreekanth; Xie, Hongyu; Fu, Buyin et al. (2018) Intrinsic optical signal imaging of the blood volume changes is sufficient for mapping the resting state functional connectivity in the rodent cortex. J Neural Eng 15:035003
Tang, Jianbo; Erdener, Sefik Evren; Li, Baoqiang et al. (2018) Shear-induced diffusion of red blood cells measured with dynamic light scattering-optical coherence tomography. J Biophotonics 11:
Gómez, Carlos A; Sutin, Jason; Wu, Weicheng et al. (2018) Phasor analysis of NADH FLIM identifies pharmacological disruptions to mitochondrial metabolic processes in the rodent cerebral cortex. PLoS One 13:e0194578
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Rasmussen, Peter M; Smith, Amy F; Sakadži?, Sava et al. (2017) Model-based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach. Microcirculation 24:
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Yaseen, Mohammad A; Sutin, Jason; Wu, Weicheng et al. (2017) Fluorescence lifetime microscopy of NADH distinguishes alterations in cerebral metabolism in vivo. Biomed Opt Express 8:2368-2385
Li, Baoqiang; Wang, Hui; Fu, Buyin et al. (2017) Impact of temporal resolution on estimating capillary RBC-flux with optical coherence tomography. J Biomed Opt 22:16014
Tang, Jianbo; Erdener, Sefik Evren; Fu, Buyin et al. (2017) Capillary red blood cell velocimetry by phase-resolved optical coherence tomography. Opt Lett 42:3976-3979
Sakadži?, Sava; Yaseen, Mohammad A; Jaswal, Rajeshwer et al. (2016) Two-photon microscopy measurement of cerebral metabolic rate of oxygen using periarteriolar oxygen concentration gradients. Neurophotonics 3:045005

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