Objectives: We propose a method of quantitatively measuring drug-induced microvascular volume changes, as well as drug-induced changes in blood oxygenation using calibrated blood oxygen level-dependent magnetic resonance imaging (MRI). We postulate that for MRI signals there is a contribution to R2* relaxation rates from static susceptibility effects of the intravascular blood that scales with the blood volume/magnetic field and depends on the oxygenation state of the blood. These may be compared with the effects of an intravascular contrast agent. With 4 R2* measurements, microvascular blood volume (MBV) and tissue oxygenation changes can be quantified with the administration of a vasoactive drug.
Materials and methods: The protocol examined 12 healthy rats in a prospective observational study. R2* maps were acquired with and without infusion of adenosine, which increases microvascular blood flow, or dobutamine, which increases myocardial oxygen consumption. In addition, R2* maps were acquired after the intravenous administration of a monocrystalline iron oxide nanoparticle, with and without adenosine or dobutamine.
Results: Total microvascular volume was shown to increase by 10.8% with adenosine and by 25.6% with dobutamine ( P < 0.05). When comparing endocardium versus epicardium, both adenosine and dobutamine demonstrated significant differences between endocardial and epicardial MBV changes ( P < 0.05). Total myocardial oxygenation saturation increased by 6.59% with adenosine and by 1.64% with dobutamine ( P = 0.27). The difference between epicardial and endocardial oxygenation changes were significant with each drug (adenosine P < 0.05, dobutamine P < 0.05).
Conclusions: Our results demonstrate the ability to quantify microvascular volume and oxygenation changes using calibrated blood oxygen level-dependent MRI, and we demonstrate different responses of adenosine and dobutamine. This method has clinical potential in examining microvascular disease in various disease states without the administration of radiopharmaceuticals or gadolinium-based contrast agents.
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