Two-Tissue Compartment Model with Iterative Fitting

The 2-Tissue Compartment, K1/k2 model implements fitting a two-tissue compartment model in each image pixel. However, because of the high noise level in pixel-wise TACs the fitting of a full 2-tissue compartment model is often not successful. One way to alleviate this problem is to reduce the number of fitted parameters, for instance by fixing the values of k₄ and/or K₁/k₂ at a value which can be reasonably assumed as constant across all tissues. As an example, with PMP, Koeppe et al. [26] fixed k₄ at a value of zero and the distribution volume of the non-displacable compartment K₁/k₂ at a value determined beforehand with a regional TAC analysis.

Processing is done in the following way:

During Preprocessing a TAC is read from a file or averaged in a specified VOI. The TAC is then iteratively fitted to a 2-tissue compartment model which is described by the parameters K₁, K₁/k₂, k₃, k₄. Each of the parameters can be estimated or, alternatively, fixed at a value which is known a priori. With PMP, for example, k₄ was fixed at a value of zero. K₁/k₂ represents the distribution volume of non-specific binding. It is used as a fit parameter instead of k₂ because often K₁/k₂ can be assumed to be identical in tissues with and without specific binding.

During model-processing, the same 2-tissue compartment model is fitted to the TAC in each individual image pixel. The parameters resulting from the Preprocessing fit are used per default as the starting values of the pixel-wise iterative fits. These values, however, can be modified in the model parameters dialog, as well as the fitting flags. The default behaviour is suitable for a tracer such as PMP: K₁, and k₃ are fit-enabled, while K₁/k₂, is fixed.

Note that iterative fitting in all image pixels is a computationally intensive process and may well take many hours. For efficiently working with this model it is recommended:

• To apply a mask to the image data and set all background areas to zero beforehand. This can easily be done in the PVIEW tool.
• To first test the model configuration by processing only the current slice (enable the 1S flag, see screen capture below).
• During model processing lower the priority of the java process, so that interactive working is still possible on the computer if needed.
• Or to set up a batch and run the fitting over night.

Note: By fixing k₃ and k₄ at a value of 0 the 2-Tissue Compartment, DV model can be used to fit a 1-tissue compartment model.