“…SIME of the input function achieves less-invasive quantification by fitting the proper tissue compartment model to multiple brain regions’ TACs simultaneously. This allows the free parameters of the model, that is the parameters requiring estimation, to be estimated simultaneously, under the usual assumption that the AIF is the input function common to all regions ( Guo et al, 2007 ; Wong et al, 2002 ; Wong et al, 2001 ; Ogden et al, 2010 ; Bohorquez, 2020 ; Riabkov and Di Bella, 2002 ; Feng et al, 1997 ; Sari, 2018 ; Zanderigo, 2018 ; Maroy et al, 2020 ). In SIME of the input function, the model free parameters are both those describing the tracer kinetics in the tissue (e.g., for an irreversible tracer, the micro-parameters K 1 , k 2 , and k 3 for each brain region) and those describing the AIF (e.g., the parameters of the model often used for the AIF, which is the sum of three decreasing exponentials).…”