# Cerebral Oxygen Metabolism and Functional Network Architecture in Pediatric Sickle Cell Disease

> **NIH NIH K23** · WASHINGTON UNIVERSITY · 2020 · $160,449

## Abstract

PROJECT SUMMARY
Research: Children with sickle cell disease (SCD) face progressive cognitive decline compared to their healthy
peers, evidenced by declining IQ, failure to achieve academic milestones, and deficits in executive function.
However, the pathophysiological mechanisms underlying cognitive decline are poorly understood, providing a
barrier to the development of predictive biomarkers and preventative treatments. Dr. Fields' long-term goal is to
understand the pathophysiology of cognitive decline in SCD. Her preliminary studies have shown that oxygen
extraction is elevated in children with SCD, suggesting ongoing cerebral metabolic stress. Her central
hypothesis is that regional metabolic stress in the deep white matter results in disruption of functional
connectivity within specific networks with consequent decline in corresponding cognitive domains. In order to
test her hypothesis, she will obtain longitudinal measures of cerebral oxygen metabolism, resting-state
functional connectivity and neurocognitive testing to complete the following specific aims: 1) To compare inter-
and intra-network connectivity between age-matched children with SCD and healthy siblings unaffected by
SCD, 2) To determine if metabolic stress predicts change in functional network architecture in SCD, and 3) To
evaluate metabolic stress and disruption of connectivity as predictors of cognitive decline. Completion of these
aims will provide insight into the effects of SCD on cognitive development via innovative MRI methods, and
develop neuroimaging biomarkers that can risk stratify patients in future clinical trials testing interventions
aimed to ameliorate the cognitive effects of sickle cell disease. Candidate: Dr. Fields is a pediatric
hematologist whose long-term goal is to become an independent physician-scientist in pediatric hematology
focused on studying the debilitating cognitive and neurologic complications suffered by children with sickle cell
disease. Her career development plan encompasses formal coursework, institutional and national conferences
to facilitate collaboration and one-on-one mentorship and instruction from Dr. Jin-Moo Lee in cerebral
metabolism, Dr. Bradley Schlaggar in acquisition, processing and application of BOLD imaging, Dr. Allison
King in neuropsychology and the cognitive implications of sickle cell disease and Dr. Amber Salter in
biostatistics. This training plan will enable Dr. Fields to use novel imaging modalities to understand the
pathophysiology of cognitive decline in SCD. Environment: Washington University (WU) is world-renowned
for neuroimaging research and resources. The specialized MR sequence used to measure oxygen extraction
fraction in this proposal was developed at WU by Dr. Hongyu An, a consultant for this proposal. Positron
emission tomography imaging was developed at WU, and many of the canonical resting state networks were
discovered at WU. In addition to WU leading the Human Connectome Project, directed by Drs. ...

## Key facts

- **NIH application ID:** 9960563
- **Project number:** 5K23HL136904-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Melanie Erin Fields
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,449
- **Award type:** 5
- **Project period:** 2017-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960563

## Citation

> US National Institutes of Health, RePORTER application 9960563, Cerebral Oxygen Metabolism and Functional Network Architecture in Pediatric Sickle Cell Disease (5K23HL136904-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960563. Licensed CC0.

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