Model Configuration and Assumptions
The Simplified Reference Tissue Model (SRTM) of Lammertsma and Hume [1] is used for the analysis of studies with reversibly binding neuroreceptor tracers. A reference tissue devoid of receptors is required which can be modeled by a single-tissue compartment model.
The assumptions of the model are:
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 non-displaceable compartment; ie. the tissue TAC can be fitted by a 1-tissue compartment model with an uptake rate constant k2a = k2/(1+BPND). Note that this assumption may not be valid for all tracers, and in this case SRTM calculates biased BPND estimates.
The model is a further development of the 4 Parameter Reference Tissue method. It has been shown to be less dependent on the initial parameter values, more stable in the presence of noise, and provide more consistent estimates of relative tracer delivery R1.
Operational Model Curve
Defining the ratio of tracer delivery R1 as K1/K1' and the binding potential BPND as k3/k4, the following operational equation can be derived for the measured tissue TAC in a receptor-rich region:
For convolution with the exponentials, the reference tissue TAC C'(t) is resampled on a regular grid, which can be specified by the Resampling parameter.
Parameter Fitting
The operational equation includes four unknowns: R1, k2, and BPnd , which can be fitted using nonlinear fitting techniques. k2', the transfer of tracer from the reference tissue back to the plasma, is provided as a derived parameter, as well as k2a.
Note: The reference methods MRTM2 and SRTM2 require k2' as an input parameter. The k2' resulting from the SRTM method is a suitable estimate. Therefore, when switching in PKIN from the SRTM model to the SRTM2 or MRTM2, k2' is automatically copied from SRTM, in case the Model conversion option in the Extras panel is enabled.
Reference
1. Lammertsma AA, Hume SP: Simplified reference tissue model for PET receptor studies. Neuroimage 1996, 4(3 Pt 1):153-158. DOI