# Monitoring Oxidative Capacity in Peripheral Artery Disease Patients using MR Imaging

> **NIH NIH R03** · UNIVERSITY OF PENNSYLVANIA · 2021 · $81,250

## Abstract

ABSTRACT
An estimated 8.5 million Americans suffer from peripheral artery disease (PAD) and it not only interferes with
one’s active lifestyle; but also increases the risks for heart attacks and strokes. Most PAD patients are
asymptomatic, present with atypical pain, and a minority face serious consequence of a threatened limb. Once
diagnosed with PAD, a range of evidence-based therapeutic and interventional options are available, which
includes supervised exercise, antithrombotic medications, and restoring circulation through catheter and surgical
interventions are available. These have potentials to improve the functional status of the patient and reduce the
mortality. Oxidative phosphorylation (OXPHOS) capacity in skeletal muscle are known to get compromised in
PAD and hence, tools (imaging or otherwise) are needed for aiding in the early identification of patients with PAD
and to monitor the effect of supervised exercise and revascularization. Phosphorus (31P) magnetic resonance
spectroscopy (31PMRS) has traditionally been used as a noninvasive tool to evaluate the OXPHOS capacity and
the change in intracellular pH of exercised skeletal muscle. However, it suffers from low coverage, poor spatial
resolution and a very high coefficient of variation (COV) (~20-30%) with respect to half-life of phosphocreatine
recovery (τPCr). Our team previously developed a novel 2D MRI method, named creatine chemical exchange
saturation transfer (CrCEST) imaging, as an alternative with improved spatial resolution (~1x1 mm2) and a
temporal resolution (τRes) of ~30s. Recently, we further improved on this method to enable the 3D coverage
while maintaining the same τRes of 30s. The estimation of creatine recovery half-time (τCr) on a voxel-wise basis
is currently not feasible due to the coarse temporal resolution (30s) combined with the low effective signal to
noise ratio (eSNR) (<20) of 3D-CrCEST time-series. Rather, we performed muscle-group-specific fit, where the
useful information in form of a voxel-wise inherent anatomic/physiological variation were sacrificed in return for
increased SNR. In another important development, we developed a spatial regularized reconstruction approach
and showed the feasibility of a noise robust reconstruction, provided τCr ≳4τRes. Given that the typical τCr of
healthy control is ~45-80s for our plantar flexion exercise protocol, there is a need to improve on τRes ~10-12s.
In this proposal, we aim to improve on the temporal resolution: τRes of CrCEST by implementing keyhole
imaging in combination with the alteration in frequency offset (FO) schemes. By aiming to improve τRes by a factor
of ~2-3x, the information content present in CrCEST time series would be sufficiently increased to enable a noise
robust reconstruction of τCr-map. To reduce the component of variability with physiological origins, we plan to
adjust the exercise load to avoid unpredictable and drastic changes in perfusion profile. For the validation, we
will compar...

## Key facts

- **NIH application ID:** 10303649
- **Project number:** 1R03EB030663-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Dushyant Kumar
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $81,250
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10303649

## Citation

> US National Institutes of Health, RePORTER application 10303649, Monitoring Oxidative Capacity in Peripheral Artery Disease Patients using MR Imaging (1R03EB030663-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10303649. Licensed CC0.

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