Global Compartmental Pharmacokinetic Models for Spatiotemporal SPECT and PET Imaging

A new mathematical framework is introduced for combining the linear compartmental models used in pharmacokinetics with the spatiotemporal distributions of activity that are measured in single photon emission computed tomography (SPECT) and PET imaging. This approach is global in the sense that the compartmental differential equations involve only the overall spatially integrated activity in each compartment. The kinetics for the local compartmental activities are not specified by the model and would be determined from data. It is shown that an increase in information about the spatial distribution of the local compartmental activities leads to an increase in the number of identifiable quantities associated with the compartmental matrix. These identifiable quantities, which are important kinetic parameters in applications, are determined by computing the invariants of a symmetry group. This group generates the space of compartmental matrices that are compatible with a given activity distribution, input function, and set of support constraints. An example is provided where all of the compartmental spatial supports have been separated, except that of the vascular compartment. The question of estimating the identifiable parameters from SPECT and PET data is also discussed.