Card. NH3 (2 Compartments)

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 ¹³NH₃ ammonia bolus injection. The compartment model has the following structure

where C₁ is free tracer in tissue, and C₂ is metabolically trapped tracer in the form of ¹³N glutamine. Because ammonia is considered in this model as freely diffusible across the capillary wall, the unidirectional uptake parameter K₁ 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 t₀=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, K₁/k₂)

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 K₁/k₂ (distribution volume of the first compartment) as a fit parameter instead of k₂. In this configuration physiological restrictions can be imposed on K₁/k₂ , or K₁/k₂ 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