# Quantitative Ultrasound Imaging of the Neonatal Brain

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $218,265

## Abstract

Abstract
Brain injuries affect millions of infants each year and may cause irreversible cell death. Visualizing cell death in
their brains is challenging. There is a need for non-invasive and easy-to-implement bedside imaging methods
which can be performed safely, and repeatedly and have the ability to detect cell death in the brain.
Cell death in infant brains can occur after hypoxia/ischemia, stroke, trauma, or exposure to sedative/anesthetic
or antiseizure medications and presents in different forms (necrosis, apoptosis, autophagy). Structural features
of cell death modify the acoustic scattering properties of tissue, therefore reflecting ultrasound differently from
viable cells. Quantitative ultrasound (QUS) has been used to detect the unique scattering properties of apoptotic
cells in cancer and necrotic cells in cultures. Low cost, portability, lack of need for contrast agents, and rapid
image acquisition and processing make QUS appealing for the in vivo detection of cell death in infants.
Our group has applied these techniques to study cell death in the brains of newborn non-human primates (NHPs)
exposed to sevoflurane anesthesia. Within the thalamus, a region that undergoes apoptosis after prolonged
sevoflurane administration in infancy, we detected changes in the “effective scatterer size” (ESS) and confirmed
histologically that apoptosis was present in this brain region. Notably, a strong correlation between changes in
ESS and the severity of histologically detected apoptosis was confirmed.
Furthermore, we performed pilot studies in four typically developing human neonates, whose fontanels are
excellent sonographic windows, and produced high-quality ultrasound brain images and QUS measurements
with consistent values.
Here we want to apply knowledge gained from the NHP work and develop QUS technology that will enable
capturing cell death in neonatal human brains. First, we will optimize QUS acquisition and analysis of echo data
in typically developing human neonatal brains and obtain normative data for key QUS features in selected brain
regions in the basal ganglia. These regions are the caudate nucleus (CN), globus pallidus (GP), putamen (Put),
and thalamus (Th). Then, we will apply QUS in neonates with brain injury caused by perinatal asphyxia. In
these brains, hypoxic/ischemic cell death can occur in the CN, GP, Put, and Th, and is accompanied by diffusion
restriction on magnetic resonance imaging (MRI). We expect that QUS features obtained from the CN, GP, Put,
and Th in neonates with perinatal asphyxia, who demonstrate diffusion restriction and altered apparent diffusion
coefficient (ADC) and fractional anisotropy (FA) maps in the basal ganglia on MRIs, will differ from those in
typically developing human neonates.
The translational significance of this research is immense. QUS may enable the study of when and where cell
death occurs in infants’ brains and follow its time evolution. It may provide invaluable means of neuromonitoring...

## Key facts

- **NIH application ID:** 10789695
- **Project number:** 1R21HD114041-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Hrissanthi Ikonomidou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,265
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789695

## Citation

> US National Institutes of Health, RePORTER application 10789695, Quantitative Ultrasound Imaging of the Neonatal Brain (1R21HD114041-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10789695. Licensed CC0.

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