Quantification of myocardial oxygen extraction fraction: A proof-of-concept study

Abstract

Purpose: To demonstrate a proof of concept for the measurement of myocardial oxygen extraction fraction (mOEF) by a cardiovascular magnetic resonance technique.

Methods: The mOEF measurement was performed using an electrocardiogram-triggered double-echo asymmetric spin-echo sequence with EPI readout. Seven healthy volunteers (22-37 years old, 5 females) were recruited and underwent the same imaging scans at rest on 2 different days for reproducibility assessment. Another 5 subjects (23-37 years old, 4 females) underwent cardiovascular magnetic resonance studies at rest and during a handgrip isometric exercise with a 25% of maximal voluntary contraction. Both mOEF and myocardial blood volume values were obtained in septal regions from respective maps.

Results: The reproducibility was excellent for the measurements of mOEF in septal myocardium (coefficient of variation: 3.37%) and moderate for myocardial blood volume (coefficient of variation: 19.7%). The average mOEF and myocardial blood volume of 7 subjects at rest were 0.61 ± 0.05 and 11.0 ± 4.3%, respectively. The mOEF agreed well with literature values that were measured by PET in healthy volunteers. In the exercise study, there was no significant change in mOEF (0.61 ± 0.06 vs 0.62 ± 0.07) or myocardial blood volume (12 ± 6% vs 13 ± 4%) from rest to exercise, as expected.

Conclusion: The implemented cardiovascular magnetic resonance method shows potential for the quantitative assessment of mOEF in vivo. Future technical work is needed to improve image quality and to further validate mOEF measurements.

Keywords: cardiovascular magnetic resonance; contrast-free; handgrip exercise; myocardial blood volume; oxygen extraction fraction.

FIGURE 1

Schematic display of the cardiac asymmetric spin-echo sequence with double-echo EPI (ASE-EPI) data acquisitions. The dotted 180° pulses are the refocusing pulses of the spin-echo sequences (time difference TE₁/2 from 90° pulses). The diffusion gradients, “Diff,” are used to minimize ventricle blood signals. The trigger delay (TD) is to ensure that ASE-EPI data acquisition will occur in middiastole, to minimize cardiac motion. The two echoes $\text{T}{\text{E}}_1$ and $\text{T}{\text{E}}_2$ are constants, while the 180° pulse shift $\text{τ}$ (eg, ${\text{τ}}_1$, ${\text{τ}}_2$) varies with cardiac cycle. Abbreviation: ECG, electrocardiogram

FIGURE 2

A, Examples of curve-fitting processes in the plot of Ln(S) versus time to obtain oxygen extraction fraction (OEF) and myocardial blood flow (MBV). In this case, the critical time ${\text{t}}_{\text{c}}$ is 0.0065 seconds (outlined by the gray vertical line). Equations (1) and (2) in the main text were used to fit to the points at time ${\text{<t}}_{\text{c}}$ and time $>{\text{t}}_{\text{c}}$, respectively. The ${\text{R}}_2$ and $R_2^{\prime }$ can be obtained through the regression fitting of Equation (2) (gray lines). B, Illustration of the handgrip exercise within the MR bore. The photo insert shows what the subject viewed inside the scanner. The Blue curve shows the exercise level from baseline to the prescribed exercise strength, and the two red dotted lines indicate the tolerance range during the exercise (usually 10% of baseline strength)

FIGURE 3

Bland-Altman plots for the cardiovascular MR (CMR)–measured resting mOEF (A) and MBV (B) at two time points (time 1 and time 2). Both are expressed without units

FIGURE 4

Sample myocardial OEF and MBV maps from 1 participant at time 1 (A,B) and time 2 (C,D). The maps are overlaid on anatomic images. The white region-of-interest regions indicate the septal areas to obtain respective mean values