Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction

Summary

The assessment of microvascular function by oxygenation-sensitive cardiac magnetic resonance imaging in combination with vasoactive breathing maneuvers is unique in its ability to assess rapid dynamic changes in myocardial oxygenation in vivo and, thus, may serve as a critically important diagnostic technique for coronary vascular function.

Abstract

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents.

OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4-min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided.

As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

Introduction

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of MR contrast^1,2,3. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation as a marker for vascular function, thereby circumventing the need for any extrinsic, intravenous contrast or pharmacologic stress agents ^4,5,

Protocol

All MRI scans utilizing OS-CMR with vasoactive breathing maneuvers should be performed in compliance with local institutional guidelines. The protocol outlined below has been used in studies approved by several institutional human research ethics committee. Written consent was obtained for all the human participant data and results described in this protocol and manuscript.

1. Broad overview

1. Vary the inclusion and exclusion criteria depending on the study population of interest. Use the following general, common exclusion criteria for an OS-CMR with vasoactive breathing maneuvers protocol: general MRI contraindi....

Results

Interpreting B-MORE
In previously published studies utilizing OS-CMR with vasoactive breathing maneuvers, the global or regional B-MORE was calculated by comparing the first end-systolic image of the breath-hold to the end-systolic image closest to 15 s, 30 s, 45 s, etc. of the breath-hold. The end-systolic phase of the cardiac cycle was chosen for several reasons. The end-systolic image is the most consistent phase identified among and between readers: it contains the greatest number of pixels in th.......

Discussion

x`The addition of an OS-CMR acquisition with standardized, vasoactive breathing maneuvers to an already established research or clinical MRI protocol adds little time to the overall scan. With this short addition, information about underlying macro- and microvascular function can be obtained (Figure 2). An important consequence of endothelial dysfunction is the inability of the vasculature to respond to physiologic stimuli, as initially demonstrated through abnormal flow-mediated relaxation .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
balanced SSFP MRI sequence	Any		To modify to create the OS-CMR sequence
DICOM/ Imaging Viewer	Any		Best if the viewer has the ability for quantitative measurements (i.e., Area19 prototype software)
Magnetic Resonance Imaging scanner	Any		3 Tesla or 1.5 Tesla
Metronome	Any		Set to 30 breaths per minute. To use if manually communicating breathing maneuver instructions to participants.
Speaker system	Any		To communicate breathing maneuver instrucitons to participants through
Stopwatch	Any		To use if manually communicating breathing maneuver instructions to participants