# Photoacoustic Microscopy of the Awake Mouse Brain

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $344,349

## Abstract

PROJECT SUMMARY
A long-standing technical challenge in neuroscience is high-resolution functional and molecular imaging of the
awake mouse brain. The need is evident and pressing, because anesthesia can significantly reduce the overall
brain activity and alter multiple forms of brain dynamics. The profound effects of anesthesia may confound the
readouts of conventional microscopies, which require preparations of anesthetized animals, and thus impose
significant limitations on the interpretation and translation of basic neuroscience findings. Moreover, incapable
of imaging the awake brain for direct comparison with the anesthetized counterpart, conventional microscopies
are of very limited utility in examining the important yet elusive roles of general anesthesia in the progression of
multiple life-threatening brain disorders (e.g., ischemic stroke and Alzheimer's disease, which are the leading
causes of death and disability in the United States). In addressing this challenge, recent efforts have extended
the scope of fluorescence microscopy to the awake brain. While this molecular imaging technology advances
and rapidly expands our understanding of the neural activities underlying behavior, high-resolution functional
imaging of the coevolving hemodynamics falls far behind. This project aims to bridge the increasing technology
gap by developing a first-of-a-kind photoacoustic microscopy (PAM) instrumentation for functional imaging of
cerebral hemodynamics and metabolism at high spatiotemporal resolution in awake mice. The unprecedented
speed of the proposed awake-brain PAM (1 MHz A-line rate), enabled by the innovative designs of wide-field
optical-mechanical hybrid scan and MHz-repetition-rate dual-wavelength Raman laser, will exceed that of the
existing multi-parametric PAM by two orders of magnitude and will enable spatiotemporal visualization of the
functional and metabolic responses of the brain to neural stimulations and disease onsets without the influence
of anesthesia. The complementary algorithms for statistical, spectral and correlation analysis of the same PAM
dataset will further push the technology envelope by enabling simultaneous and comprehensive quantification
of the total concentration and oxygen saturation of hemoglobin, blood flow and perfusion, and metabolic supply
and demand at the microscopic level. This technology innovation will open up new and exciting opportunities in
basic and translational neuroscience, including the mechanistic study of anesthetic neuroprotection in ischemic
stroke proposed in this project. In turn, this stroke study will provide an ideal setting to assess the potential of
awake-brain MHz-PAM in the context of a clinically important brain disease and pave the way for future studies
of neurovascular coupling and neuromodulation in the awake brain. These efforts, together, hold the potential
to establish PAM as a new enabling technology in brain research.

## Key facts

- **NIH application ID:** 9914138
- **Project number:** 5R01NS099261-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Song Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,349
- **Award type:** 5
- **Project period:** 2020-02-14 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914138

## Citation

> US National Institutes of Health, RePORTER application 9914138, Photoacoustic Microscopy of the Awake Mouse Brain (5R01NS099261-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9914138. Licensed CC0.

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