Preclinical validation of a single-scan rest/stress imaging technique for ¹³NH₃ cardiac perfusion studies

Objectives: Due to the 10 min half-life of ¹³N, two separate syntheses of ¹³NH₃ are required for rest/stress imaging, which is performed in two scans that are separated by 50 min. This work validates a single-scan, two-injection method which takes less than 15 min and requires one radiosynthesis. The new method is based on previous work with ¹⁸F-Flurpiridaz (Alpert et al. 2012, Guehl et al. 2017a) and a more computationally efficient algorithm for the generation of rest and stress kinetic parameters (Guehl et al. 2017b). In this work we validated our methods for ¹³NH₃ myocardial perfusion imaging (MPI) using experimental data acquired in a pig model. We compared our single-scan technique with separate rest and stress PET acquisitions, and with microsphere flow measurements. Methods: 9 studies were performed in 6 pigs for a total of 27 scans. 5 studies were done in the control state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 scans (Supplemental Figure, A): a two-injection rest/rest single-scan (scan 1), a two-injection rest/stress single-scan (scan 2), and a conventional one-injection stress scan (scan 3). Variable doses of adenosine (140-300 μg/min/kg) combined with dobutamine (0-15 μg/min/kg) were administered to cover a wide range of myocardial blood flow (MBF). In 4 studies, ¹³NH₃ injections were paired with microsphere injections. The two-injection single-scan measurements were fitted with our non-stationary kinetic model (MGH2). MBF estimates were compared to those obtained with the standard method that analyzes rest ans stress separately with a stationary kinetic model (Hutchins et al. 1990) and with microsphere flows. We used a model-based method to generate rest and stress perfusion images, as if these images were acquired separately: the rest and stress kinetic parameter maps, computed with our rapid algorithm, were used, with the resting part of the input function, to solve the equations describing a stationary kinetic model.

Results: MBF was investigated over the range 0.1 to ~8 mL/min/cc. For all datasets, the MGH2 kinetic model fitted the dynamic ¹³NH₃ data in detail (Supplemental Figure, B). In the absence of stressor administration (scan 1), the estimated MBF values were nearly the same for the two radiotracer injections (mean difference: 0.067±0.070 ml/min/cc), demonstrating the basic repeatability of the method. Our simultaneous rest-stress method (scan 2) was in very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 ml/min/cc; slope= 0.922±0.009; intercept= 0.024±0.007; R²= 0.97) and stress (mean difference: -0.011±0.291 ml/min/cc; slope= 1.050±0.025; intercept= -0.121±0.060; R²= 0.93) MBF measurements, which led in turn to very good agreement in myocardial flow reserve (MFR) values (mean difference: 0.123±0.498 ml/min/cc; slope= 1.110±0.036; intercept= -0.175±0.105; R²= 0.88). PET and microsphere MBF measurements correlated closely (slope= 1.111±0.071; intercept= -0.255±0.097; R²=0.94). In addition, our model-based method provided very good quality rest and stress perfusion images (Figure). Summed rest score (SRS) and summed stress score (SSS) were concordant with those obtained with the conventional method. Conclusions: ¹³NH₃ rest/stress MPI procedure, that is normally acquired as two separate scans, can be compressed into a single ~15 min PET scan session while still obtaining accurate rest ans stress MBF measurements and good quality model-based perfusion images. Our method could significantly reduce ¹³NH₃ MPI imaging cost through optimization of camera time and cyclotron usage, as only one ¹³N production is required. Support: 2017 Bradley-Alavi Student Fellowship; R01HL137230

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