BPnd (Wu SRTM2 Ref): Simplified Reference Tissue Model with fixed k2'

Wu and Carson [35] aimed at making the SRTM basis function approach even more robust and called it Simplified Reference Tissue Model 2 (SRTM2). They noted that with SRTM k₂' is calculated with each pixel TAC, although the same reference TAC is used for all pixels. Therefore they implemented a two-step approach:

1. Calculate k₂' using SRTM in all pixels.
2. Fix k₂' : Average k₂' in all brain pixels outside the reference region. Use this fixed value for the pixel-wise SRTM calculations, reducing the number of fitted parameters from 3 to 2.

The operational equation of the SRTM was re-written to allow for fixing of k₂'

The three parameters R₁, k_2a and k₂' are estimated in step 1. In step 2 k₂' is fixed, and only R₁ and k_2a are estimated. k_2a is the apparent k₂ (k_2a = k₂ /(1+BP)).

The binding potential can then be calculated as

SRTM2 is based on the same assumptions as SRTM:

1. The distribution volume is the same for the tissue of interest and the reference tissue: K₁/k₂=K₁'/k₂'.
2. The kinetics in the receptor-rich tissue of interest is such, that it is difficult to distinguish between the specific and the free/non-specific compartment; i.e. the TAC can be fitted by a 1-tissue compartment model. This assumption may not be valid for all tracers.

Note: As with the SRTM method, BP estimates from SRTM2 tend to be biased if the 1-tissue compartment model assumption does not apply. The magnitude of the bias is even larger for the SRTM2 estimates, most likely because the fixed k₂' can not compensate a part of the model inadequacy [35].