Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve

Abstract

Background: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs.

Methods: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively.

Results: Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant.

Conclusions: Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.

Keywords: Myocardial perfusion imaging; PET flow; [N-13]-ammonia extraction fraction.

Figure 1.

Plots of MFR vs CFR agreement (top row, n = 37) and of RFR vs FFR agreement (bottom row, n = 91) for each compartment model using the proposed optimization model and EF computed from eqn 3 and optimized PS constants from this work reported in Table 3. Note that RFR vs FFR moderate agreement almost reaches good agreement for model 3 (CCC ≥ .7). (PS = the permeability and capillary surface area product; CCC = Concordance correlation coefficient).

Figure 2.

Plots of MFR vs CFR agreement (top row, n = 37) and of RFR vs FFR agreement (bottom row, n = 91) for each compartment model using published PS constants (Table 3) and EF computed from eqn. 3. (PS, the permeability and capillary surface area product; CCC, Concordance correlation coefficient).