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PURPOSE Parametric imaging using the Patlak model has been shown to provide improved lesion detectability and specificity. The Patlak model requires both tissue time-activity-curves (TACs) after equilibrium and knowledge of the input function from the start of injection. Therefore, the conventional dynamic scanning protocol typically starts from the radiotracer injection all the way to equilibrium. In this paper, we propose the use of hybrid population-based and model-based input function estimation and evaluate its use for whole-body Patlak analysis, in order to reduce the total scan time and simplify clinical Patlak parametric imaging protocols. Possible quantitative errors caused by the simplified scanning protocol was also analyzed both theoretically and with the use of clinical data. MATERIALS AND METHODS Clinical data from twenty-four patients referred for tumor staging were included in this study. The patients underwent a whole-body dynamic PET study, 20 minutes after FDG injection (0.13 mCi/kg). The proposed whole-body scanning protocol includes 6 passes with 4-5 bed positions, depending on the size of the patient, with 2 minutes for each bed position. An input function from the literature was selected as the shape of the population-based input function. The descending aorta from the corresponding CT image was segmented and applied on the reconstructed dynamic PET images to acquire an image-based input function, which was later fitted using an exponential model. Due to the late scan time, only the later portion of the input function was available, which was used to scale the population-based input function. The hybrid input function was used to derive the whole-body Patlak images. Assuming a given error in the population-based input function, its influence on the final Patlak images were also derived theoretically and verified using the clinical data sets. Finally, the image quality of the reconstructed Patlak slope image was evaluated by an experienced radiologist in four different aspects: image artifacts, image noise, lesion sharpness, and lesion detectability. RESULTS It was found that errors in the population-based input function only affect the absolute scale of the Patlak slope image. The induced error is proportional to the percentage area-under-curve (AUC) error in the input function. These findings were also confirmed by numerical analysis. The predicted global scale was in good agreement with results from both image-based Patlak and direct Patlak approach. The fractions of the AUC from the early-portion population-based input function were also found to be around 18% of the total AUC of the input function, further limiting the propagation of quantitation error from population-based input function to the final Patlak slope image. The reconstructed Patlak images were also found by the radiologist to provide excellent confidence in lesion detection tasks. CONCLUSIONS We have proposed a simplified whole-body scanning protocol that utilizes both population-based input function and model-based input function. The error from the population-based function was found to only affect the global scale and the overall quantitative impact can be predicted using our proposed formulas.