# Probing silent cerebral infarct pathogenesis in sickle cell disease with cerebrovascular MRI

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $22,131

## Abstract

PROJECT SUMMARY
Children with sickle cell disease are at increased risk for serious cerebrovascular complications. The most
prevalent of these complications are silent cerebral infarcts, focal areas of ischemic tissue damage in the brain
associated with cognitive impairment and poor school performance. Despite the significant consequences of
silent cerebral infarcts, they are often detected after ischemic damage has occurred. Clinical protocols to triage
sickle cell patients utilize ultrasound measurements of blood velocity in large cerebral arteries, with high blood
velocity indicating increased risk for stroke. However, there is conflicting evidence whether high blood velocity is
a risk factor for silent cerebral infarcts. Additionally, therapies prescribed to high-risk patients may not protect
against silent cerebral infarcts. We need improved understanding of the vascular impairments associated with
silent cerebral infarcts in sickle cell disease to better prevent and treat this source of neurological injury.
This work proposes MRI measurements of cerebrovascular reactivity as a novel source of hemodynamic
information related to silent cerebral infarct formation. Cerebrovascular reactivity is the blood flow response to a
dilatory stressor and is measured in smaller vessels in the cortex, making it a more local metric of vascular health
than blood velocity. Previous studies have demonstrated impaired cerebrovascular reactivity in adults and
children with sickle cell disease, indicating reduced ability to increase blood flow to meet oxygen demands and
increased likelihood for ischemia. The aims of this proposal are to: 1) evaluate the relationship between blood
velocity in large cerebral arteries and cerebrovascular reactivity in the cortex, and 2) determine if cerebrovascular
reactivity is altered in brain regions close to silent cerebral infarcts. Aim 1 is a step forward from previous work,
contextualizing cerebrovascular reactivity against the clinical standard for cerebrovascular risk assessment in
sickle cell disease. Aim 2 determines whether this additional information improves our understanding of the
spatial distribution of silent infarcts.
The proposed study will provide a comprehensive assessment of cerebral hemodynamics in children with sickle
cell disease and offer preliminary evidence for cerebrovascular reactivity as a hemodynamic biomarker for silent
cerebral infarct occurrence. A hemodynamic biomarker that is coupled to silent cerebral infarcts could inform the
treatment of sickle cell disease and aid in the development of new preventative therapies. In the long term, the
imaging techniques developed in this proposal could serve as an alternative or complementary MRI screening
tool to stratify for silent cerebral infarct risk more effectively.

## Key facts

- **NIH application ID:** 10903928
- **Project number:** 5F31HL166079-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kristina M Zvolanek
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $22,131
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903928

## Citation

> US National Institutes of Health, RePORTER application 10903928, Probing silent cerebral infarct pathogenesis in sickle cell disease with cerebrovascular MRI (5F31HL166079-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10903928. Licensed CC0.

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