Compartmental model ODEs

Compartmental models for PET data can be described in terms of a set of linear, first-order, constant-coefficient, ordinary differential equations (ODEs). Change of tracer concentration in one of the tissue compartments is a linear function of the concentrations in all other compartments:

From the linearity follows that kinetic measurements are the convolution of the tracer input function and the response function of the system.

Convolution:

For example, for two-tissue compartment model with tissue compartments C1 and C2, input function C0(t), and rate constants K1, k2, k3, and k4, can be described mathematically with a system of two ODEs:

The simulated tissue TACs are used to

Analytic solutions using Laplace transformation

Analytic solutions for linear first-order differential equations can be derived using Laplace transformation. For this 2TCM example the solution is (Phelps et al., 1979):

, where ⊗ denotes the operation of convolution. For one-tissue compartmental model the solution is a lot simpler:

For simplified reference tissue model the solution is:

Alternative solutions for discrete-time data

Alternative solution (Kuwabara et al., 1993) avoids the computationally slow convolution operation. Solutions for the most common compartmental models are shown in TPC modelling reports.

As an example, the solution of the one-tissue compartmental model ODE,

starts by integrating the equation, assuming that at time zero all concentrations are zero:

Definite integral of nth compartment is implicitly estimated with the 2nd order Adams-Moulton method, based on Euler integration:

In this example we have just one compartment (n=1). Integrals are calculated using trapezoidal method.

After substitution and rearrangement:

For simplified reference tissue model the solution is:

Using this method the TACs from compartmental models can be easily simulated even in spreadsheet software. For an example, you can download an Excel file where PET tissue data can be simulated using two-tissue compartmental model from measured plasma data and user definable rate constants. Excel files for simulating tissue data with three-tissue compartmental models are also available (compartments in parallel and in series).

Comparison of solution methods

The convolution method provides precise results only if the sampling time interval is very short (relative to the rate constants). The alternative method is computationally faster, and produces correct results (as far as it is possible from discrete data) without any interpolation; the convolution method only approaches the correct result with shorter interpolated sampling intervals. As an example, convolution and the alternative Adams-Moulton method are compared in a simulation of one-tissue compartmental model.

With data sampled at discrete times some errors in simulation will always be present. The longer the sampling time frame durations are, the more important it is to appropriately account for the frame durations in calculating AUC (integral).


See also:



References:

Budinger TF, Huesman RH, Knittel B, Friedland RP, Derenzo SE (1985): Physiological modeling of dynamic measurements of metabolism using positron emission tomography. In: The Metabolism of the Human Brain Studied with Positron Emission Tomography. (Eds: Greitz T et al.) Raven Press, New York, 165-183.

Gunn RN, Gunn RS, Cunningham VJ. Positron emission tomography compartmental models. J Cereb Blood Flow Metab. 2001; 21: 635-652.

Huang SC, Phelps ME (1986): Principles of tracer kinetic modeling in positron emission tomography and autoradiography. In: Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart. (Eds: Phelps,M; Mazziotta,J; Schelbert,H) Raven Press, New York, 287-346.

Kuwabara H, Cumming P, Reith J, Léger G, Diksic M, Evans AC, Gjedde A. Human striatal L-DOPA decarboxylase activity estimated in vivo using 6-[18F]fluoro-DOPA and positron emission tomography: error analysis and application to normal subjects. J Cereb Blood Flow Metab. 1993; 13: 43-56.

Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol. 1979; 6: 371-388.



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Created at: 2004-06-03
Updated at: 2018-03-11
Written by: Vesa Oikonen