BACKGROUND:Myocardial perfusion measurement with a low-dose first-pass analysis (FPA) dynamic computed tomography (CT) perfusion technique depends upon acquisition of two whole-heart volume scans at the base and peak of the aortic enhancement. Hence, the objective of this study was to validate an optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement. METHODS:Contrast-enhanced CT of 28 Yorkshire swine (weight, 55 ± 24 kg, mean ± standard deviation) was performed under rest and stress conditions over 20-30 s to capture the aortic enhancement curves. From these curves, an optimal timing protocol was simulated, where one volume scan was acquired at the base of the aortic enhancement while a second volume scan was acquired at the peak of the aortic enhancement. Low-dose FPA perfusion measurements (PFPA) were then derived and quantitatively compared to the previously validated retrospective FPA perfusion measurements as a reference standard (PREF). The 32-cm diameter volume CT dose index, [Formula: see text] and size-specific dose estimate (SSDE) of the low-dose FPA perfusion protocol were also determined. RESULTS:PFPA were related to the reference standard by PFPA = 0.95 · PREF + 0.07 (r = 0.94, root-mean-square error = 0.27 mL/min/g, root-mean-square deviation = 0.04 mL/min/g). The [Formula: see text] and SSDE of the low-dose FPA perfusion protocol were 9.2 mGy and 14.6 mGy, respectively. CONCLUSIONS:An optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement was retrospectively validated and has the potential to be used to implement an accurate, low-dose, FPA perfusion technique.