# Novel Optical Imaging Approach to Study Neurovascular Coupling System

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $434,500

## Abstract

Understanding the relationship between neural activity and Blood-brain barrier (BBB) permeability
is important to integrate our knowledge of neurovascular coupling system. Although much effort
is focused in understanding the underlying mechanisms that regulate blood flow in response to
neural activity5, little is known about how neural activity regulates tissue perfusion. Direct in vivo
measurements of Ca2+ dynamics in cerebral blood vessel cells and quantification of BBB
permeability have been difficult largely due to technical limitation. Researchers have been using
bulky fluorescence-labeled solutes for conventional studies on BBB permeability. However, bulky
fluorescence labeling perturbs the structural and functional properties of the biomolecules and
suffered from photo bleaching. For these reasons, tiny Raman tagged molecules combined with
SRS imaging is ideal for studying BBB permeability in vivo. Here we propose a novel optical
imaging approach to determine the relationship between neural activity and BBB permeability in
vivo. The main thrust of this proposal is to use a combination of bioorthogonal probed stimulated
Raman scattering (SRS), multi-photon fluorescence, and mouse genetics to obtain simultaneous
measurements of Ca2+ activity and BBB permeability. Vascular endothelial cells will be labeled
with a genetically encoded calcium indicator while bioorthogonal-tagged molecules with specific
vibrational modes will be injected into the brain vasculature to measure the BBB permeability,
and the relationship between calcium dynamics and permeability of the BBB will be studied.
Successful completion of the aims described in this proposal will enable a novel framework for
future mechanistic studies of in vivo BBB permeability in animal models for blood vessel
development and vasculature diseases.

## Key facts

- **NIH application ID:** 10528336
- **Project number:** 1R21NS125395-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Lingyan Shi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $434,500
- **Award type:** 1
- **Project period:** 2022-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528336

## Citation

> US National Institutes of Health, RePORTER application 10528336, Novel Optical Imaging Approach to Study Neurovascular Coupling System (1R21NS125395-01A1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10528336. Licensed CC0.

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