# High-resolution cerebral microvascular imaging for characterizing vascular dysfunction in Alzheimer's disease mouse model

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $574,742

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) is the most common cause of dementia and impacts the lives of 6 million Americans.
With a worldwide aging population and absence of effective therapies, a global epidemic of AD is looming. At
present, a key challenge for developing effective AD therapies is the complex pathophysiological processes
inherent to AD. In particular, emerging evidence points to vascular dysfunction as an early and ubiquitous feature
of AD. However, despite the importance of vascular contributions to AD, there currently exists a large gap in
understanding the exact mechanisms underlying the vascular-Abeta interactions. This knowledge gap
fundamentally limits our capabilities to understand key mechanisms underlying AD pathogenesis and ultimately
develop effective AD therapies. To fill this knowledge gap, it is essential to conduct mechanistic in vivo studies
that are hypothesis-driven, providing detailed understanding of the relationship between cerebrovascular
impairments and AD pathophysiologies. To that end, cerebrovascular imaging will play an essential and
increasingly important role. However, existing cerebrovascular imaging technologies fall short of providing
adequate imaging spatial resolution and depth of penetration to provide measurements of vascular biomarkers
in deep brain regions that contain AD microvascular pathologies. This significant technical gap limits our ability
to answer important questions about neurovascular pathology in AD. Therefore, the goal of this proposal is to
develop an ultrasound-based, high-resolution cerebral microvascular imaging (HCMI) technique to fill this
important technical gap and ultimately provide a viable, noninvasive imaging tool to answer hypothesis-driven
questions about AD vascular dysfunction and pathologies. If successfully developed, HCMI will achieve whole-
brain, micron-scale, and dynamic microvascular mapping for AD mouse models. In Aim 1, we will develop
innovative solutions for HCMI to enable fast and robust whole-brain microvascular imaging through intact skull
for longitudinal AD studies. We will focus on developing viable solutions that allow reliable longitudinal monitoring
of whole-brain microvasculature through intact skull. We will also extend HCMI from 2D to 3D imaging based on
ultrafast 3D ultrasound. In Aim 2, we will accelerate HCMI with FPGA- and GPU-based parallel computing
techniques. We will develop an FPGA-based ultrafast beamformer for continuous, high-speed ultrasound data
acquisition to support 3D HCMI. We will also develop GPU-based parallel computing method to maximize HCMI
post-processing speed. In Aim 3, we will validate the in vivo performance of HCMI on AD mouse models. We
will use brain histology and cognitive behavioral testing to validate HCMI performance in measuring
microvascular alterations associated with AD. Based on recent evidence indicating the feasibility of in vivo
transcranial microvascular imaging in humans with ultrasound,...

## Key facts

- **NIH application ID:** 10848559
- **Project number:** 1R56NS131516-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** DANIEL A LLANO
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $574,742
- **Award type:** 1
- **Project period:** 2023-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848559

## Citation

> US National Institutes of Health, RePORTER application 10848559, High-resolution cerebral microvascular imaging for characterizing vascular dysfunction in Alzheimer's disease mouse model (1R56NS131516-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10848559. Licensed CC0.

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