Potential errors in interpreting hibernation due to FDG scaling?

Abstract

Metabolic imaging of the myocardium using positron emission tomography (PET) provides a rational basis to select patients for revascularization by distinguishing between hibernating and infarcted tissues. As in many areas, however, the devil lies in the details. The manuscript by Degtiarova and colleagues in this issue provides a timely opportunity to revisit fundamental aspects of fluorodeoxyglucose F-18 (FDG) image interpretation. After an initial 1978 investigation in humans to image myocardial glucose metabolism, FDG emerged in 1983 as a tool to distinguish metabolic versus perfusion patterns in patients with prior infarction. This foundational work from Michael Phelps and Heinrich Schelbert at the University of California in Los Angeles paved the way for a wide, subsequent literature leading to specific United States Food and Drug Administration (FDA) approval in 1999 of FDG for myocardial viability imaging. FDG provides an excellent surrogate marker of glucose uptake since it competes with glucose for intracellular transport, becomes trapped after phosphorylation by hexokinase, and does not proceed further along metabolic pathways, hence remaining fixed for myocardial imaging. A key practical aspect of FDG imaging involves metabolic preparation. American societal guidelines recommend glucose loading after a fasting period to induce a natural insulin response and promote tracer uptake. In diabetic patients, the guidelines recognize the need for exogenous insulin administration and suggest either the gold standard but time-consuming euglycemic-hyperinsulinemic clamp or an abbreviated protocol using serial, intravenous, bolus insulin after a glucose load. Our laboratory, for example, has produced excellent results using a customized version of this latter protocol that requires achieving falling blood glucose regardless of diabetic status. After acquisition of perfusion images (using any of the standard PET tracers and typically performed immediately before FDG imaging due to a much shorter half-life), the perfusion and metabolic patterns must be compared against each other to classify the result into four options: matched normal (normal myocardium with intact perfusion and glucose metabolism), matched abnormal (infarcted myocardium with perfusion defect and reduced/absent glucose metabolism), mismatch (hibernating myocardium with perfusion defect but intact glucose metabolism), and reverse mismatch (viable myocardium with normal perfusion but reduced/ absent glucose metabolism). While commonly interpreted visually, how exactly should these two images be compared quantitatively? Addressing this basic question reveals potential errors of both interpretation and quantification inconsistent with known myocardial physiology.