# Fast volumetric imaging of oxygen delivery in the mouse brain at single red blood cell resolution

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $420,175

## Abstract

PROJECT SUMMARY/ABSTRACT
 The human brain represents 2% of the weight of the body, but consumes ~20% of the total energy at rest.
All that energy – mostly in the form of glucose and oxygen - has to be delivered to the brain cells through an
intricate network of microvessels, the majority of which are capillaries. Although it is well-known that increased
neuronal activity in a region of the brain is associated with an increase in cerebral blood flow (functional
hyperemia), the role of capillaries in blood flow regulation and oxygen delivery remains controversial.
Nevertheless, capillary dysfunction has been suggested to play a crucial role in a wide variety of brain diseases
and conditions, especially Alzheimer’s disease. To better understand capillary function and how it meets the
widely varying energy demand of neurons, it is crucial to be able to measure oxygen delivery at high spatial and
temporal resolution. Unfortunately, current technologies for imaging oxygen delivery, including intrinsic optical
imaging, optical coherence tomography, and photoacoustic microscopy, have either limited spatial resolution or
are incompatible with existing neuronal activity imaging. These limitations prevent a detailed understanding of
the interaction between capillaries and neurons and how capillary dysfunction impacts brain function. To address
this critical technological gap, we aim to develop a novel transient absorption microscopy technique that is
capable of oxygen saturation (sO2) imaging at single red blood cell (RBC) resolution using intrinsic hemoglobin
contrasts. This technique exploits a fundamentally different contrast mechanism from other optical approaches.
It uses the transient absorption of endogenous hemoglobin molecules to image RBCs, and replies on excited-
state dynamics difference between oxyhemoglobin and deoxyhemoglobin to determine sO2. Compared to the
existing two-photon oxygen probe, our new technique potentially offers 3-4 orders of magnitude improvement in
sO2 imaging speed. More importantly, it can be readily integrated with other high-throughput microvessel and
neuron measurements. In Aim 1, we will develop and validate a high sensitivity transient absorption microscope
for in vivo sO2 imaging of the brain cortex. A new dual-wavelength laser will be used to maximize sO2 sensitivity
and imaging depth. Accuracy of sO2 imaging will be determined by comparison with an improved phosphorescent
oxygen probe Oxyphor2. In Aim 2, we will create a high-throughput volumetric imaging microscope by combining
TAM imaging with Bessel beam excitation and a novel interlaced scanning method. The new microscope will be
optimized for simultaneous volumetric imaging of capillary sO2, vessel diameter, blood flow, flux, and neuronal
activity. This breakthrough capability will enable real-time assessment of oxygen delivery through each capillary
in the microvessel network at an unprecedented spatial and temporal resolution. We anticipate broad
applicatio...

## Key facts

- **NIH application ID:** 10525881
- **Project number:** 1R21NS123764-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Dan Fu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $420,175
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525881

## Citation

> US National Institutes of Health, RePORTER application 10525881, Fast volumetric imaging of oxygen delivery in the mouse brain at single red blood cell resolution (1R21NS123764-01A1). Retrieved via AI Analytics 2026-07-17 from https://api.ai-analytics.org/grant/nih/10525881. Licensed CC0.

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