Assessing microvascular function with breathing maneuvers : an oxygenation-sensitive CMR study

This project encompasses five studies, which focus on developing a new cardiovascular diagnostic approach for assessing myocardial oxygenation and microvascular function. In combination with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging, breathing maneuvers and altered arterial blood gases can be used as a non-invasive method for inducing a vasoactive response to test the oxygenation reserve, a key measurement in vascular function.  The number of prescribed cardiac diagnostic tests and interventions is rapidly growing. In particular, imaging and other non-invasive tests are frequently performed prior to invasive procedures. One of the most common uses of cardiac imaging is for the diagnosis of significant coronary artery stenosis, a critical cost factor in today’s health care system.  Non-invasive imaging techniques provide the most reliable information for the presence and location of perfusion or oxygenation deficits in patients with symptoms suggestive of myocardial ischemia, yet many current techniques suffer from the need for radiation, contrast agents or tracers, and pharmacological or physical stress protocols. CMR imaging can identify significant coronary artery stenosis without radiation and new trends in CMR research aim to develop diagnostic techniques that do not require any pharmacological stressors or contrast agents.  For this project, the primary aim was to develop and test a new diagnostic technique to assess coronary vascular function using OS-CMR in combination with breathing maneuvers as the vasoactive stimulus. Secondary aims then used OS-CMR to assess myocardial oxygenation and the coronary response in the presence of altered arterial blood gases.  An animal model was used to validate the vascular response to breathing maneuvers before translating the technique to human subjects into both healthy volunteers, and a patient population with cardiac disease.    In the animal models, breathing maneuvers could induce a significant change in invasively measured coronary blood flow and it was demonstrated that in the presence of a haemodynamically significant coronary stenosis, OS-CMR could detect a myocardial oxygen deficit. This technique was then applied in a human model, with healthy participants. In a direct comparison to the infusion of the coronary vasodilator adenosine, which is considered a standard agent for inducing vasodilation in cardiac imaging, breathing maneuvers induced a stronger response in oxygenation of healthy myocardium. The final study then implemented the breathing maneuvers in a patient population with coronary artery disease; in which myocardium compromised by a coronary stenosis had a compromised oxygenation response. Furthermore, the observed effects of arterial blood gases on myocardial oxygenation were assessed.  This demonstrated that the coronary response to breath-hold stimuli is attenuated during hyperoxia, and this causes an overall reduction in coronary blood flow, and consequently an oxygenation deficit in a coronary stenosis animal model when supplemental oxygen is provided.  In conclusion, this work has improved our understanding of potential new diagnostic techniques for cardiovascular imaging. In particular, it demonstrated that combining breathing maneuvers with oxygenation-sensitive CMR can provide a non-invasive and cost-effective method for assessing global and regional coronary vascular function.

Keyphrases: BOLD (Blood Oxygen Level-Dependent), Vasoconstriction, Oxygenation-Sensitive, CMR (Cardiovascular Magnetic Resonance), Adenosine, Vasodilation, Hyperoxia