Model Configuration and Assumptions

The **Full Reference Tissue** method (or *4 Parameter Reference Tissue Method*) of Lammertsma et al. 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. Tissues of interest which include the target receptor are modeled by a 2-tissue compartment model.

In the model equations C_{T}'(t) represents the tissue TAC from the reference region (k_{3}=0 in the 2-tissue compartment model), and C_{T}(t) the tissue TAC from a receptor-rich region (k_{3}>0). It is assumed that the distribution volume of the non-displaceable compartment is the same for tissues of interest and the reference tissue: K_{1}/k_{2}=K_{1}'/k_{2}'. Furthermore the reference tissue should not affected by the pathology investigated under study.

Operational Model Curve

Defining the ratio of tracer delivery R_{1} as K_{1}/K_{1}' and the binding potential BP_{ND} as k_{3}/k_{4}, the following operational equation can be derived for the measured tissue TAC in a receptor-rich region:

The equation parameters and their relation to the model are given by:

For convolution with the exponentials, the reference tissue TAC C_{T}'(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**, **k3**, and **BPnd **(after substitution of BP_{ND}=k_{3}/k_{4}), which can be fitted using nonlinear fitting techniques.

Reference

Lammertsma AA, Bench CJ, Hume SP, Osman S, Gunn K, Brooks DJ, Frackowiak RS: Comparison of methods for analysis of clinical [11C]raclopride studies. J Cereb Blood Flow Metab 1996, 16(1):42-52. DOI