# Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced cognitive decline

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $386,208

## Abstract

PROJECT SUMMARY/ABSTRACT
 This supplemental proposal is an extension of our parent R01 to identify the mediators of radiation-induced
vision loss and to develop effective mechanism-based therapies. In the parent project, we are investigating the
time course, mechanism and mitigation of retinal microvasculopathy as a driver of radiation-induced neural
degeneration and functional loss to facilitate earlier detection, prevention and treatment of radiation-associated
retinal damage. Here, we propose that radiation therapy (RT)-induced dementia is driven by the same
microvascular processes and molecular mechanisms as within the retina and that retinal laser speckle
flowgraphy (LSFG) can be used as an early detection strategy. Importantly, Vascular Cognitive
Impairment/Dementia is listed under “Related Dementias” under the “NIH Coding definitions for Alzheimer's
disease and its related Dementias”. Thus, the research proposed herein is directly relevant to NOT-AG-20-034.
 Radiation-induced cognitive impairment occurs in up to 90% of adult survivors of brain tumors. Many
adverse side effects of RT have been attributed to damage of microvascular endothelium that is initiated by
excessive production of reactive oxygen species and mitochondrial injury during RT and leads to endothelial
dysfunction and loss of capillaries over a period of years. However, similar to vision loss after RT, the concept
that microangiopathy is a driver of radiation-related dementia has not been conclusively established. This is in
part because early indicators of microvascular endothelial dysfunction that predict later cognitive decline have
yet to be established. In our parent R01, we are using laser speckle flowgraphy (LSFG) as a novel non-
invasive modality to detect early RT-induced microangiopathy. Here, we propose to deploy the experimental
approaches and genetic models of our parent R01 to analyze cerebral structure and function.
 The objectives of the proposed project are to facilitate earlier detection and treatment of RT-associated
dementia. Specifically, we expect to develop non-invasive tests in mice for the early detection of RT-induced
injury based on altered blood flow and determine whether early endothelial dysfunction is predictive of a
subsequent reduction in capillary density and neuronal dysfunction. We also anticipate identifying the
molecular mechanism of radiation-induced endothelial dysfunction and its impact on cognitive impairment.
 As in the parent R01, the application of LSFG will enable us to identify early “radiation endotheliopathy”
before capillary loss, and to test molecular mechanisms to ultimately develop novel therapies. Our central
hypothesis is that post-radiation endothelial dysfunction is driven by mitochondrial oxidative stress and
is predictive of the severity of subsequent capillary dropout and neuronal damage. Capitalizing on our
imaging protocols, we will (1) establish whether early impairment of the microvascular endothelial function
...

## Key facts

- **NIH application ID:** 10282945
- **Project number:** 3R01EY031544-01S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Isabella Maria Grumbach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,208
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10282945

## Citation

> US National Institutes of Health, RePORTER application 10282945, Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced cognitive decline (3R01EY031544-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10282945. Licensed CC0.

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