# A Novel Wavelet Neurovascular Bundle for Real Time Detection of Injury in Neonatal Encephalopathy

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $538,062

## Abstract

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of newborn death and disability
worldwide and presents clinically as neonatal encephalopathy that is difficult to classify within a
short window after birth to inform neuroprotective interventions. Therapeutic hypothermia (TH)
has dramatically improved outcomes in moderate to severe HIE when initiated within six hours of
life (HOL), yet trials have not included mild HIE. The difficulties to discern the clinical severity
shortly after birth and to analyze the dynamic circulation in sick newborns represent important
challenges. As new trials are now considered to target unstudied mild HIE, neurophysiological
and neuroimaging biomarkers are critically needed 1) to guide real-time patient selection within a
short therapeutic window and 2) to provide insight into timing of the metabolic energy failure and
effect on structural and functional brain outcomes. Our team pioneered a “wavelet neurovascular
bundle” analytical system to measure neurovascular coupling (NVC) under dynamic conditions
and in real time, and to measure regional oxygen consumption one step further into the core of
brain energy homeostasis. The parent grant initially focused on infants with moderate to severe
HIE during the 72 hours of treatment and resulted in twenty six new publications. The overarching
goal of this renewal is to harness our novel physiological biomarkers to focus on untreated mild
HIE to identify those who need treatment. Our objective is to test dynamic biomarkers that can
predict structural and functional outcomes chosen with input from stakeholders, and inform
physiological and metabolic disturbances specific to mild HIE. We plan to enroll a new cohort of
100 neonates with mild HIE (35 per year over 3 years) and to follow up for two years infants for
developmental outcomes. Our infrastructure ensures the success of this proposal and includes a
multidisciplinary team of experts in hemodynamics and electrophysiology signals (Chalak,
Zhang), bioengineering (Liu), and neuroimaging (Liu P, Wisnowski). The high-volume, supportive
research environment at Parkland Hospital, including a 3T Siemens Skyra located inside the
NICU, permits imaging of sick newborns as early as the first day of life. New knowledge will
specifically provide: 1) Development and optimization of neuroimaging and neurophysiological
assessments of mild HIE; and 2) improved HIE stratification via multi-modal assessments.
Impact. The ability to monitor global neurovascular functions in real time could lead to a paradigm
shift by providing the field with sensitive physiological biomarkers to detect the evolution of deficits
in mild HIE and allow targeted interventions in this unstudied population. Engaging community
stakeholders ensures that the NIH mission remains aligned with the priorities of affected families.

## Key facts

- **NIH application ID:** 10814834
- **Project number:** 5R01NS102617-07
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** LINA F CHALAK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,062
- **Award type:** 5
- **Project period:** 2017-07-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814834

## Citation

> US National Institutes of Health, RePORTER application 10814834, A Novel Wavelet Neurovascular Bundle for Real Time Detection of Injury in Neonatal Encephalopathy (5R01NS102617-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10814834. Licensed CC0.

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