A local increase in cortical blood flow is widely accepted to report the presence and location of neuronal activity in the brain. This hemodynamic response is the basis of functional brain imaging methods such as functional Magnetic Resonance Imaging (fMRI). Yet the way that the brain controls these blood flow changes, and even the underlying purpose of the hemodynamic response are still unknown. There is growing evidence that impairments in regulation of the hemodynamic response may underlie age-related neurodegeneration, and can be linked to the progression of diseases such as Alzheimer's. A comprehensive model of the mechanisms underlying the coupling between neuronal and hemodynamic responses in the brain is urgently needed. The lack of a conclusive model to date is due, in part, to the difficulties faced in imaging the normal, functioning, intact brain in-vivo. In-vitro studies which investigate potential mechanisms in isolation are uniformly difficult to compare with other in-vitro results, and to reconcile with in-vivo observations. However, it is highly challenging to develop in-vivo imaging paradigms capable of achieving sufficient resolution, sensitivity and contrast to gain a complete picture of the neuronal, metabolic and vascular processes which together generate the hemodynamic response to activation. We have developed a suite of advanced optical imaging and microscopy tools for in-vivo examination of neurovascular coupling. We plan to exploit a wide range of optical contrasts including oxy- and deoxyhemoglobin, calcium sensitive dyes, cell-specific dyes, transgenic mice expressing fluorescent proteins, and intrinsically fluorescent substrates of energy metabolism such as NADH and FAD. We propose to refine and apply our imaging tools to address the following two fundamentally important questions: 'How is the cortical vasculature physically modulated?'and 'Why does the hemodynamic response happen?'Our multi-scale and multi-parametric imaging approaches offer the chance to both fully characterize the physical mechanisms which modulate and control the hemodynamic response, and to investigate the metabolic basis of the response and its relation to energy supply and demand at a cellular level. We believe that these studies will lead to a comprehensive model of neurovascular coupling. We also anticipate that the imaging techniques that we develop, and our careful characterization of the healthy brain, will clear the way for future in-vivo research into the cellular, metabolic and neurovascular underpinnings of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS063226-05
Application #
8252173
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Babcock, Debra J
Project Start
2008-05-15
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$335,737
Indirect Cost
$121,362
Name
Columbia University (N.Y.)
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Ma, Ying; Shaik, Mohammed A; Kim, Sharon H et al. (2016) Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches. Philos Trans R Soc Lond B Biol Sci 371:
Ma, Ying; Shaik, Mohammed A; Kozberg, Mariel G et al. (2016) Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons. Proc Natl Acad Sci U S A :
Kozberg, M; Hillman, E (2016) Neurovascular coupling and energy metabolism in the developing brain. Prog Brain Res 225:213-42
Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A et al. (2016) Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling. J Neurosci 36:6704-17
Akassoglou, Katerina; Agalliu, Dritan; Chang, Christopher J et al. (2016) Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Front Neurosci 10:46
Chow, Daniel S; Horenstein, Craig I; Canoll, Peter et al. (2016) Glioblastoma Induces Vascular Dysregulation in Nonenhancing Peritumoral Regions in Humans. AJR Am J Roentgenol 206:1073-81
Bouchard, Matthew B; Voleti, Venkatakaushik; Mendes, César S et al. (2015) Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics 9:113-119
Galwaduge, P T; Kim, S H; Grosberg, L E et al. (2015) Simple wavefront correction framework for two-photon microscopy of in-vivo brain. Biomed Opt Express 6:2997-3013
Lacroix, Alexandre; Toussay, Xavier; Anenberg, Eitan et al. (2015) COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex. J Neurosci 35:11791-810
Cayce, Jonathan Matthew; Bouchard, Matthew B; Chernov, Mykyta M et al. (2014) Calcium imaging of infrared-stimulated activity in rodent brain. Cell Calcium 55:183-90

Showing the most recent 10 out of 37 publications