Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography

Abstract

Background. Oxygen-15-Iabeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. Methods and Results. The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and γ-Iabeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (γ=0.36+l.0x, r=0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88±0.08 ml/g/min and 3.52±1.12 ml/g/min, respectively; p<0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03±0.23 and 0.93±0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86±0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32±0.27 ml/g/min (p≤0.001). Conclusions. PET with C15O2, inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients.