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Reference tissue input compartment models for regional analysis of irreversible binding and metabolism

Background

Two reference tissue compartment models are available for quantitation of irreversible binding or metabolism (k3): the (reduced) reference tissue compartment model with constraint k4=0 (RRTM), and the transport limited reference tissue model (TRTM). The advantage of all reference tissue models is that blood sampling and plasma metabolite analysis are not needed. Thus the errors caused by the uncertainties in the measured plasma metabolite fractions are avoided. In RRTM the plasma input is replaced with reference tissue showing non-existent (or very low) specific binding (k3'=0). As an alternative, if a region exists, where the irreversible binding or metabolism is very rapid (k3'>>k2'), it can be used as the reference region in TRTM. One assumption common to all of reference tissue models is that K1/k2 is similar in all studies regions.

RRTM and TRTM include three parameters: R1 (ratio of the K1 values of regions of interest and reference tissue), k2, and k3 can be estimated with nonlinear fitting.

The parameter R1 is unitless. The unit of k2 and k3 is min-1.

Model fit programs

The parameters of RRTM and TRTM can be estimated using programs fit_rrtm and fit_trtm.

Steps of calculation:

Any or all of of the following steps can be done in Solaris terminal window or MS Windows command prompt window on either SUN or PC platform.

1. Preparation of regional tissue TAC data

This is explained in detail elsewhere. In short: draw ROIs and calculate regional TACs from dynamic images, and calculate averages over planes and regions if required. If you have regional TACs in old format (*.roi.kbq), convert those to DFT format using program nci2dft.

2. Adding weights to regional tissue TAC data

3. Computing the k3

Depending on the suitable model, run one of the programs fit_rrtm and fit_trtm with at least the following command line parameters:

  1. regional tissue TAC file (DFT datafile)
  2. name of the reference region in the TAC file
  3. length of study to be used in the fitting (usually a large number to allow fitting to the end of data)
  4. name for result file; note that results are appended to an existing result file

In addition, the fitted TACs can be saved for later use by specifying a filename for it.

For example, the command could be like this:

fit_rrtm ua0268.dft cer 999 ua0268.res

or:

fit_trtm ua0268.dft 'put avg' 999 ua0268.res ua0268srtmfit.dat

The initial values and constraints for the model parameters can be entered to the programs fit_rrtm and fit_trtm with option -i. You should use the same parameter settings file for your whole study material.


Cunningham VJ, Hume SP, Price GR, Ahier RG, Cremer JE, Jones AKP. Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro. J Cereb Blood Flow Metab 1991;11:1-9.

Herholz K, Lercher M, Wienhard K, Bauer B, Lenz O, Heiss W-D. PET measurement of cerebral acetylcholine esterase activity without blood sampling. Eur J Nucl Med 2001;28:472-477.



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