The **Card NH3 (2-Tissue)** model developed by Hutchins et al. [1] is an implementation of the irreversible 2-tissue-compartment model for cardiac PET studies using ^{13}NH_{3 }ammonia bolus injection. The compartment model has the following structure

where C_{1} is free tracer in tissue, and C_{2 }is metabolically trapped tracer in the form of ^{13}N glutamine. Because ammonia is considered in this model as freely diffusible across the capillary wall, the unidirectional uptake parameter K_{1} equals the myocardial perfusion.

Operational Model Curve

The system of differential equations is

To allow the fitting of data over an extended period, the model includes the exponential metabolite correction described by van den Hoff et al. [2]

with a delay t_{0}=0.48 min and half-time T_{1/2}=6.69 min. C_{LV}(t) is the total tracer concentration measured in the left ventricular cavity, including metabolites.

Additionally, the model incorporates a cardiac dual spillover correction by the operational equation

where

V_{LV} = spill-over fraction of the blood activity in the left ventricle C_{LV}(t),

V_{RV} = spill-over fraction of the blood activity in the right ventricle C_{RV}(t) .

Implementation Notes:

When using the model from the PCARD module, the data are transferred appropriately. When using it in PKIN the blood data have to be loaded as follows:

- The left ventricle curve must be loaded as the
**Plasma activity**curve. No metabolite correction needs to be enabled on the**Blood**panel of PKIN because it is included in the tissue model. - The right ventricle curve must be loaded as the
**Whole blood**curve.

The following automatic adjustments are performed within the model:

- The spill-over fraction from the right ventricle V
_{RV}is automatically fixed to zero if the string "Sep" is*not*contained in the name a region. The assumption is that such a TAC is not from septal tissue and should thus be modeled with spill-over from the left ventricle only. - The
**valid**flag for all data samples after 2 minutes is set to false, and they are consequently not considered in the fit.

Parameter Fitting

The model includes the five fitable parameters **F**, **vLV**, **vRV**, **k2**, **k3**. Please inspect the **%SE** standard error to get information about the reliability of their estimates. The input parameters **MC T0** (0.48) and **MC T12** (6.69) are related to the metabolite correction as described above and can be adjusted if needed.

Alternate Model Card NH3 (2-Tissue, K_{1}/k_{2})

Due to the increased number of fit parameters it has been found, that the **Card NH3 (2-Tissue)** may suffer from identifiability problems. Therefore, the variant **Card NH3 (2-Tissue, K1/k2)** has been developed using the parameter K_{1}/k_{2} (distribution volume of the first compartment) as a fit parameter instead of k_{2}. In this configuration physiological restrictions can be imposed on K_{1}/k_{2} , or K_{1}/k_{2} can be used as a common parameter in a coupled fit.

References

1. Hutchins GD, Schwaiger M, Rosenspire KC, Krivokapich J, Schelbert H, Kuhl DE: Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging. J Am Coll Cardiol 1990, 15(5):1032-1042.

2. van den Hoff J, Burchert W, Borner AR, Fricke H, Kuhnel G, Meyer GJ, Otto D, Weckesser E, Wolpers HG, Knapp WH: [1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med 2001, 42(8):1174-1182. PDF