Card. NH3 (2 Compartments)

The Card NH3 (2-Tissue) model developed by Hutchins et al. [45] 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.

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. [46]

with 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 ventricle, 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) .

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 (DV, distribution volume of free tracer is used as a fit parameter instead of k₂, and k₂ is derived from the estimated K₁ and K₁/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.

Implementation Notes:

• The right ventricle curve is only used for spillover correction of septal TACs. It must be loaded as the Total blood curve.
• The left ventricle curve serves two purposes: (1) corrected for metabolites it serves as the input curve, (2) it is used for spillover correction of all myocardial TACs. It must be loaded as the Input curve.
• The delay and half-time of the metabolite correction are input parameters of the kinetic 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 reason for this automatism is usage of the model in the PCARD tool.
• To set V_rv = 0 in all regional models proceed as follows: in one region, set V_rv =0 and disable the fit checkbox; fit the region; configure the button below Copy to all regions to Model and Par. and activate it.

Abstract [45]

"Evaluation of regional myocardial blood flow by conventional scintigraphic techniques is limited to the qualitative assessment of regional tracer distribution. Dynamic imaging with positron emission tomography allows the quantitative delineation of myocardial tracer kinetics and, hence, the measurement of physiologic processes such as myocardial blood flow. To test this hypothesis, positron emission tomographic imaging in combination with N-13 ammonia was performed at rest and after pharmacologically induced vasodilation in seven healthy volunteers. Myocardial and blood time-activity curves derived from regions of interest over the heart and ventricular chamber were fitted using a three compartment model for N-13 ammonia, yielding rate constants for tracer uptake and retention. Myocardial blood flow (K1) averaged 88 +/- 17 ml/min per 100 g at rest and increased to 417 +/- 112 ml/min per 100 g after dipyridamole infusion (0.56 mg/kg) and handgrip exercise. The coronary reserve averaged 4.8 +/- 1.3 and was not significantly different in the septal, anterior and lateral walls of the left ventricle. Blood flow values showed only a minor dependence on the correction for blood metabolites of N-13 ammonia. These data demonstrate that quantification of regional myocardial blood flow is feasible by dynamic positron emission tomographic imaging. The observed coronary flow reserve after dipyridamole is in close agreement with the results obtained by invasive techniques, indicating accurate flow estimates over a wide range. Thus, positron emission tomography may provide accurate and noninvasive definition of the functional significance of coronary artery disease and may allow the improved selection of patients for revascularization."