Determination of Regional Flow by Use of Intravascular PET Tracers: Microvascular Theory and Experimental Validation for Pig Livers

Abstract

Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared with the standard model in a pig liver study. Methods: Eight pigs underwent a 5-min dynamic PET study after ¹⁵O-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual-inlet concentration was calculated as the flow-weighted inlet concentration. Dynamic PET data were analyzed with a traditional single-compartment model and 2 microvascular models. Results: Microvascular models provided a better fit of the tissue activity of an intravascular tracer than did the compartment model. In particular, the early dynamic phase after a tracer bolus injection was much improved. The regional hepatic blood flow estimates provided by the microvascular models (1.3 ± 0.3 mL min⁻¹ mL⁻¹ for the single-capillary model and 1.14 ± 0.14 min⁻¹ mL⁻¹ for the multiple-capillary model) (mean ± SEM mL of blood min⁻¹ mL of liver tissue⁻¹) were in agreement with the total blood flow measured by flow meters and normalized to liver weight (1.03 ± 0.12 mL min⁻¹ mL⁻¹). Conclusion: Compared with the standard compartment model, the 2 microvascular models provide a superior description of tissue activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional flow estimates in agreement with flow measurements.