# Development of Super-resolution Ultrasound Localization Microscopy for Imaging Vascular Biomarkers of Alzheimer Disease

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $361,174

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer disease (AD) is the leading cause of dementia, which is expected to impact the lives of hundreds of
millions of people worldwide by 2050. AD causes synaptic and neuronal losses that manifest in symptoms such
as cognitive impairment, behavior changes, and eventually loss of motor coordination, which create
overwhelming physical, emotional, and financial burdens to the patients and their families. At present, there is
no substantially effective therapeutics or preventions for AD. Since aging is the leading risk factor of AD, a rapidly
aging world population will continue to drive up the overall societal burden of dementia for years to come. To
facilitate the development of successful AD therapies, discovery and refinement of noninvasive biomarkers will
continue to play an essential role in understanding the therapeutic effects of existing treatments and investigating
alternative therapeutic targets. In particular, vascular biomarkers that reflect the health and integrity of the
cerebral vasculature – which permeate almost all aspects of AD – will remain a crucial tool for understanding
and treating AD. However, despite the strong clinical evidence of significant impact on AD, vascular biomarkers
remain poorly explored and are often overlooked in both preclinical and clinical studies of AD. One reason is that
currently there is lack of a noninvasive, in vivo imaging method that provides both structural (e.g., static vascular
morphology, microhemorrhages) and functional (e.g, blood brain barrier leakage, vessel hemodynamics,
microhemorrhages) vascular biomarkers with high spatial resolution deep into the brain. To this end, we propose
to develop a new ultrasound-based super-resolution microvascular imaging technique based on both contrast
enhanced microbubbles (MBs) and phase-changing nanodrops (NDs) for AD brain imaging. The study seeks to
address several AD-specific technical challenges for conventional ultrasound localization microscopy (ULM),
including low imaging repeatability, high computational cost associated with data acquisition and beamforming,
and the lack of extravascular imaging capability that precludes conventional ULM from measuring important AD
vascular biomarkers such as vessel integrity. Our approach includes the development of a new 3D ULM imaging
platform and an adaptive MB injection method to maximize ULM imaging repeatability between different imaging
sessions across different days; development of a GPU-based computing platform for ultrafast ultrasound data
acquisition and beamforming for AD applications of ULM; and develop a new ND-based extravascular super-
resolution ULM imaging method for assessing AD-induced loss of vascular integrity. Successful completion of
the study will lead to a new noninvasive AD brain imaging technique that provides whole brain structural and
functional vascular imaging at a microscopic spatial resolution.

## Key facts

- **NIH application ID:** 10497551
- **Project number:** 3R21EB030072-01S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Pengfei Song
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $361,174
- **Award type:** 3
- **Project period:** 2020-09-15 → 2023-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497551

## Citation

> US National Institutes of Health, RePORTER application 10497551, Development of Super-resolution Ultrasound Localization Microscopy for Imaging Vascular Biomarkers of Alzheimer Disease (3R21EB030072-01S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10497551. Licensed CC0.

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