Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13 N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies

Circ Cardiovasc Imaging. 2020 Jan;13(1):e009407. doi: 10.1161/CIRCIMAGING.119.009407. Epub 2020 Jan 21.


Background: We previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3.

Methods: Nine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images.

Results: In the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained.

Conclusions: This study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

Keywords: infarction; myocardial perfusion imaging; pharmacokinetics; positron-emission tomography; regional blood flow; validation study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adenosine / administration & dosage
  • Ammonia
  • Animals
  • Coronary Circulation
  • Coronary Vessels / diagnostic imaging*
  • Image Processing, Computer-Assisted
  • Microspheres
  • Myocardial Perfusion Imaging / methods*
  • Nitrogen Isotopes
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Regional Blood Flow
  • Reproducibility of Results
  • Swine


  • Nitrogen Isotopes
  • Radiopharmaceuticals
  • Ammonia
  • Adenosine