Searching for alternatives to full kinetic analysis in 18F-FDG PET: an extension of the simplified kinetic analysis method

The most accurate way to estimate the glucose metabolic rate (or its influx constant) from (18)F-FDG PET is to perform a full kinetic analysis (or its simplified Patlak version), requiring dynamic imaging and the knowledge of arterial activity as a function of time. To avoid invasive arterial blood sampling, a simplified kinetic analysis (SKA) has been proposed, based on blood curves measured from a control group. Here, we extend the SKA by allowing for a greater variety of arterial input function (A(t)) curves among patients than in the original SKA and by accounting for unmetabolized (18)F-FDG in the tumor. Ten A(t)s measured in patients were analyzed using a principal-component analysis to derive 2 principal components describing most of the variability of the A(t). The mean distribution volume of (18)F-FDG in tumors for these patients was used to estimate the corresponding quantity in other patients. In subsequent patient studies, the A(t) was described as a linear combination of the 2 principal components, for which the 2 scaling factors were obtained from an early and a late venous sample drawn for the patient. The original and extended SKA (ESKA) were assessed using fifty-seven (18)F-FDG PET scans with various tumor types and locations and using different injection and acquisition protocols, with the K(i) derived from Patlak analysis as a reference. ESKA improved the accuracy or precision of the input function (area under the blood curve) for all protocols examined. The mean errors (±SD) in K(i) estimates were -12% ± 33% for SKA and -7% ± 22% for ESKA for a 20-s injection protocol with a 55-min postinjection PET scan, 20% ± 42% for SKA and 1% ± 29% for ESKA (P < 0.05) for a 120-s injection protocol with a 55-min postinjection PET scan, and -37% ± 19% for SKA and -4% ± 6% for ESKA (P < 0.05) for a 20-s injection protocol with a 120-min postinjection PET scan. Changes in K(i) between the 2 PET scans in the same patients also tended to be estimated more accurately and more precisely with ESKA than with SKA. ESKA, compared with SKA, significantly improved the accuracy and precision of K(i) estimates in (18)F-FDG PET. ESKA is more robust than SKA with respect to various injection and acquisition protocols.