# MRI-Based Regional Assessment of Cerebral Metabolism Via 3D Quantitative BOLD

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $243,750

## Abstract

PROJECT SUMMARY
Quantitative assessment of brain oxygen metabolism, usually expressed in terms of cerebral metabolic rate of
oxygen (CMRO2), can provide important information on many neurological disorders as well as normal cerebral
physiology. MRI permits noninvasive, nonradiative measurement of the two key parameters – cerebral blood flow
and oxygen extraction fraction (OEF) – that determine the rate of oxygen consumption, thus CMRO2. Currently,
robust regional quantification of CMRO2 in the brain is not possible, primarily as techniques for OEF mapping are
still at an early stage of development.
 MRI-based OEF mapping methods are commonly based on signal modulations resulting from the paramag-
netism of blood deoxyhemoglobin (dHb). Current techniques either calibrate the effect of dHb’s magnetic suscepti-
bility in a separate procedure, or derive the parameter by estimating the RF-reversible transverse relaxation rate
constant R2¢ (class of methods termed ‘quantitative BOLD (qBOLD)’). Alternatively, a model accounting for several
sources in voxel susceptibility has been invoked based on quantitative susceptibility mapping (QSM). Among these
approaches, qBOLD is unique in that it requires no intervention, and thus is essentially calibration-free.
 One major challenge in qBOLD is to separate dHb’s contribution to R2¢ from other sources, typically non-
heme iron stored, for instance, in the form of ferritin in the basal ganglia. While a recent approach combining qBOLD
and QSM (termed ‘qBOLD+QSM’) mitigates the issue, the method is still prone to errors because acquired signals
are entangled by the effects from the RF-irreversible transverse relaxation rate constant R2, as well as macroscopic
magnetic field variations, in addition to those arising from R2¢. In addition, current techniques for direct R2¢ mapping
are impractically slow for 3D encoding. Furthermore, extracting OEF from the estimate of heme-originated R2¢ is
challenging because of limited sensitivity in the qBOLD model. The proponents’ recent work has addressed the
issue by deriving prior information for the unknown qBOLD parameters.
 Aim 1 of this project seeks to develop a rapid R2¢-sensitive 3D pulse sequence, and implement a data
processing pipeline that addresses the above-mentioned confounders via prior information guided qBOLD. The
newly developed 3D MRI oximetry protocol will be validated at 3T field strength in a group of healthy test subjects
at various physiologic states in comparison to qBOLD+QSM and in terms of reproducibility (Aim 2). Finally, the
protocol’s feasibility towards clinical translation will be examined. To this end, Aim 3 evaluates patients with unilateral
carotid steno-occlusive disease to address the hypothesis that parenchymal hypoxia is manifested ipsilaterally by
greater OEF and lower CMRO2, and these parameters’ association with cerebrovascular reactivity.
 Successful completion of the proposed project will yield a robust, reliable, and clinically prac...

## Key facts

- **NIH application ID:** 10373235
- **Project number:** 1R21EB031364-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Felix W Wehrli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,750
- **Award type:** 1
- **Project period:** 2022-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373235

## Citation

> US National Institutes of Health, RePORTER application 10373235, MRI-Based Regional Assessment of Cerebral Metabolism Via 3D Quantitative BOLD (1R21EB031364-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10373235. Licensed CC0.

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