# Development of real-time, non-invasive photoacoustic imaging to rapidly detect and track perinatal focal stroke at birth

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $517,633

## Abstract

Perinatal arterial ischemic stroke is estimated to occur in 1/2300–1/5000 live births and can result in long-term
deficits in motor, cognitive, attention, and executive functions and persistent seizures. Rapid diagnosis of focal
ischemic stroke in newborns, the timing of the stroke, and differentiation of perinatal stroke from global
hypoxia-ischemia allow more efficient and directed interventions/prognosticacions. In the proposed work, we
will develop miniaturized noninvasive photoacoustic imaging for use on the scalp of human fetuses and
newborns to dynamically track changes in oxygenation in sagittal sinus venous blood and regional cortical
tissue both during and after labor. Using a newborn animal with a large gyrencephalic brain, we will validate
the oxygenation measurements against directly measured sagittal sinus O2 saturation during hypoxia-ischemia
and against pimonidazole-based measurements of regional tissue hypoxia during focal stroke. Based on these
data, we will then develop algorithms for detecting graded progressive ischemia based on tissue hemoglobin
content and O2 saturation. We will test the sensitivity and specificity of these algorithms with different size and
locations of photothrombotic-induced stroke. Furthermore, secondary injury cascades that transpire in the
immature brain after arterial thrombotic stroke may differ from those that transpire in mature brain and likely
depend on maturation of connectivity and energy metabolism in specific brain regions. After photothrombosis
of the middle cerebral artery, we will contrast dynamic changes in tissue hemoglobin content and O2 saturation
in 1) the metabolically active primary sensorimotor cortex, known to be selectively vulnerable to hypoxia-
ischemia, 2) the metabolically quiescent secondary sensorimotor cortex known to be resistant to hypoxia-
ischemia, and 3) the watershed penumbra. In addition, we will use noninvasive imaging to track tissue uptake
of photoacoustically sensitive dyes conjugated to different size molecules and relate regional differences in
size-dependent blood brain-barrier permeability to markers of energy metabolism. Finally, we will investigate
whether stabilizing anti-inflammatory, anti-epileptic, anti-platelet, pro-vasodilatory, and pro-angiogenic
epoxyeicosatrienoic acids with an inhibitor of soluble epoxide hydrolase (sEH) is protective. Though
pretreatment with such inhibitors is protective in adult rodent models of transient cerebral ischemia, post-
treatment efficacy has not been determined with prolonged ischemia or in immature brain. We will test the
concept that a multi-potent sEH inhibitor will attenuate neuroinflammation, blood-brain barrier permeability,
perivascular loss of aquaporin-4 channels, ischemia-induced increase in Sur1-TrpM4 channels known to
contribute to malignant edema, and the loss of peri-ischemic neurons, while promoting VEGF expression; we
will also determine whether an inhibitor of EET synthesis will exert the opposite ...

## Key facts

- **NIH application ID:** 9841306
- **Project number:** 5R01HL139543-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Emad M Boctor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,633
- **Award type:** 5
- **Project period:** 2017-12-18 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841306

## Citation

> US National Institutes of Health, RePORTER application 9841306, Development of real-time, non-invasive photoacoustic imaging to rapidly detect and track perinatal focal stroke at birth (5R01HL139543-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841306. Licensed CC0.

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