Noninvasive Quantification of Regional Myocardial Metabolic Rate for Oxygen by Use of 15 O 2 Inhalation and Positron Emission Tomography

Abstract

Background A method has been developed to measure the regional myocardial metabolic rate of oxygen consumption (rMMR o 2 ) and oxygen extraction fraction (rOEF) quantitatively and noninvasively in humans by use of 15 O 2 inhalation and positron emission tomography. This article describes the theory, an error analysis of the technique, and procedures of the method used in a human feasibility study. Methods and Results Inhaled 15 O 2 is transported to peripheral tissues, where it is converted to 15 O-labeled water of metabolism, which exchanges with the relatively large extravascular tissue space. Quantification of this buildup of radioactivity allows the calculation of rMMR o 2 and rOEF. However, a correction for the spillover of the pulmonary gas radioactivity signal into myocardial regions is required and has been made by use of a gas volume distribution estimated from the transmission scan. This was validated by comparative measurements using the inert gas [ 11 C]CH 4 in four greyhounds. Spillover of the cardiac chamber radioactivity has been corrected for with an inhaled [ 15 O]CO (blood volume) scan. The underestimation of myocardial radioactivity due to wall motion and thickness has been corrected for by use of values of tissue fraction obtained from the flow measurement [ 15 O](CO 2 scan). Values of rOEF were similar (within 4%) whether obtained from gas volume measurements determined from the transmission or [ 11 C]CH 4 scan data. 15 O 2 scan information from six healthy volunteers showed a clear distribution of myocardial radioactivity after the vascular and pulmonary gas 15 O background was subtracted. Subsequent compartmental analysis resulted in values for rOEF and rMMR o 2 of 0.60±0.11 and 0.10±0.03 mL·min −1 ·g −1 in the human myocardium at rest. Conclusions The results of this study are in good agreement with established values. This is the first known approach to allow the direct quantitative determination of rOEF and oxygen metabolism to be made noninvasively on a regional basis.