Estimating Input Function with Incomplete Blood Samples for Quantification of Nonhuman Primate Dynamic F-18-FDG PET/CT Using a Patlak Plot-based Optimization Method

Purpose: FDG uptake rate constant K_i is a main physiology parameter measured by dynamic PET study. A model-independent graphical analysis using Patlak plot with plasma input function is a standard approach used to estimate K_i. The plasma input function is the FDG time activity curve in plasma obtained by arterial blood sampling. The purpose of the study is to evaluate a Patlak plot-based optimization approach for noninvasive quantification of dynamic FDG PET.

Methods: Eight 60-min monkey dynamic FDG PET studies with arterial blood samples were collected. The measured plasma input function (mPIF) was determined by arterial blood samples. Time activity curves of seven cerebral regions of interest were generated from each study. With a given number of blood samples, the estimated PIF (ePIF) was determined by either interpolation or extrapolation method using scale calibrated population mean of normalized PIF. The optimal time points for those blood samples to estimate PIF (ePIF) was determined by maximizing the correlations between the K_i estimated ePIF and ones estimated mPIF. A leave-two-out cross-validation method was used for evaluation.

Results: The linear correlations between the K_i estimates from ePIF with optimal sampling schemes and those from measured PIF were: Ki (ePIF 1 sample) = 1.09 Ki (mPIF) - 0.00, R² =0.95±0.08; Ki (ePIF 2 samples) = 1.09 K_i (mPIF) - 0.00, R² =0.95±0.07; K_i (ePIF 3 samples) = 1.04 Ki (mPIF) - 0.00, R² =0.96±0.05; and K_i (ePIF 4 samples) = 1.02 K_i (mPIF)-0.00, R² =0.97±0.04. As sample size became greater or equal 4, the K_i estimates from ePIF with optimal protocol were almost identical to those from mPIF.

Conclusions: The Patlak plot-based optimization approach is a robust method to estimate plasma input function for noninvasive quantification of non-human primate dynamic FDG PET. KEYWORDS FDG PET; Patlak plot; plasma input function; quantification