# Magnetic Resonance Imaging Methods to Improve Spatial Measures of Oxygen Extraction Fraction in Cerebrovascular Disease Patients

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $30,747

## Abstract

Project Summary
Patients with sickle cell anemia (SCA) have reduced oxygen carrying capacity, elevated cerebral blood flow
and oxygen extraction fraction (OEF), and increased rate of stroke and vasculopathy. Half of adults with SCA
will display a cerebral infarct by age 30; however, despite the prevalence of disability-inducing injury, no
mechanism for primary stroke prevention has been established in adults with SCA. Difficulty in designing
treatment protocols in these patients is partially due to difficulties associated with measuring cerebral hemo-
metabolism. Recent work suggests that elevation in OEF is correlated with clinical indicators of disease,
including cerebral vasculopathy and stroke history, however widespread implementation of OEF measures to
clinical practice has been impeded due to technical difficulties associated with 15-O positron emission
tomography measurements, which have historically been used to measure OEF. OEF can be measured non-
invasively in magnetic resonance imaging (MRI) with the T2-relaxation-under-spin-tagging (TRUST) pulse
sequence, however this method does not provide regional measures of OEF, so does not report regional
impairment and stroke risk, which is common in patients with SCA associated cerebral vasculopathy. To
address these gaps in treatment, the proposed research will focus on improving the TRUST pulse sequence to
report regional TRUST (rTRUST) measures of OEF. A limited-functionality rTRUST pulse sequence is already
operational in our lab, however this method is limited to unilateral, hemispheric measurements of OEF. In the
first aim of this work, we will refine rTRUST to improve labeling efficiency and increase spatial information
content further, using customized spin labeling approaches with radiofrequency developments that allow for 3D
volumes to be excited with improved specificity. The refined rTRUST pulse sequence will be validated in ex
vivo blood phantoms and optimized in healthy controls. In the second aim, rTRUST will be demonstrated in
vivo whereby participants will be recruited from a cohort of more than 91 known, well-characterized, SCA
patients for a translational component of this research. The SCA cohort with lateralizing vasculopathy will be
scanned at a 3 Tesla MRI scanner, and using spatially specific rTRUST OEF measurements, we will validate
that regions with vasculopathy and reduced CBF have elevated OEF, consistent with known relationships
between CBF, OEF, and CMRO2. Development of rTRUST, and validation of MRI methods for acquiring
spatial OEF information will help to introduce OEF measurement into clinical practice, improving our ability to
design treatment protocols for aggressive surgical revascularization, transfusion, or medical management for
patients with cerebral vasculopathy and sickle cell anemia. These methods will be generalizable to other
diseases that cause hemo-metabolic dysfunction and stroke, particularly other cerebrovascular disease, such
as atheroscler...

## Key facts

- **NIH application ID:** 10137790
- **Project number:** 5F31NS113510-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Spencer Leon Waddle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,747
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137790

## Citation

> US National Institutes of Health, RePORTER application 10137790, Magnetic Resonance Imaging Methods to Improve Spatial Measures of Oxygen Extraction Fraction in Cerebrovascular Disease Patients (5F31NS113510-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10137790. Licensed CC0.

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