# Two-photon Imaging of Oxygen and Blood Flow in Retinal and Cerebral Vasculature

> **NIH NIH RF1** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $1,897,240

## Abstract

PROJECT SUMMARY/ABSTRACT
High-resolution imaging techniques are essential for investigation of the pathogenesis and development of
therapeutic and screening strategies for cerebral small vessel disease (SVD), including Alzheimer Disease (AD)
and AD-related dementias. Previous studies have demonstrated a link between retinal and cerebral
microvascular changes. Moreover, the accessibility of the retinal tissue for noninvasive imaging offers an
advantage for identifying microvascular dysfunction due to SVD. However, a significant gap remains in our
understanding how changes in the capillary networks in cortex and retina mirror each other during both normal
ageing and SVD progression. Filling the gap requires innovative technologies to measure absolute microvascular
oxygenation, perfusion, and morphology at subcapillary scale in both retina and cortex, applied to animal models
that recapitulate the clinical and histopathological features of microvasculopathy.
We propose to develop novel methods to investigate retinal O2 delivery and consumption with unprecedented
spatial resolution and to correlate changes that occur in parallel in retinal and cortical microvasculature during
normal ageing and AD. Aim 1 will develop and validate a multimodal two-photon fluorescence imaging method
for combined measurements of absolute oxygen tension (pO2) and blood flow in major retinal vessels and derive
global measurements of O2 metabolic rate. We will then investigate how normal aging affects microvascular
structure and function in cortical and retinal tissue. Aim 2 will develop and validate an adaptive optics two-photon
microscopy imaging method for pO2 in the retinal capillaries, coupled with imaging of capillary red blood cell
(RBC) flux using the previously established RBC passage method. High-resolution retinal tissue pO2 imaging
will also be developed, as well as a deep Differential Aberration imaging of pO2 in vasculature and tissue. Aim 3
will test the hypothesis that microvascular hemodynamic and tissue metabolic changes during early stages of
AD occur in parallel in retina and cerebral cortex. We will compare retinal and cortical microvascular oxygenation,
blood flow, and O2 metabolic rate in experimental mouse model of AD.
Development of novel methods to investigate retinal O2 delivery and consumption will advance our understanding
of the concurrent microvascular dysfunction in cortex and retina during both normal ageing and SVD progression,
provide broad utility in assessing retinal microvascular domains in animal models of eye disorders, and augment
knowledge of vascular mechanisms of progressive neurodegeneration and cognitive impairment in common
forms of SVD as well as in AD and related dementias.

## Key facts

- **NIH application ID:** 10184187
- **Project number:** 1RF1NS121095-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Sava Sakadzic
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,897,240
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10184187

## Citation

> US National Institutes of Health, RePORTER application 10184187, Two-photon Imaging of Oxygen and Blood Flow in Retinal and Cerebral Vasculature (1RF1NS121095-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10184187. Licensed CC0.

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